Predictive values of haematological parameters in Plasmodium falciparum infection in immunocompetent adults at an urban hospital in Douala

Predictive values of haematological parameters in Plasmodium falciparum infection in immunocompetent adults at an urban hospital in Douala | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictive values of haematological parameters in Plasmodium falciparum infection in immunocompetent adults at an urban hospital in Douala Yembu Ngwengi, Alan Geater, Stephane Nguembu, Martine Nida This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9177783/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background The haematological profile of children and at-risk groups of malaria patients in endemic areas has been extensively studied, but those parameters have not been thoroughly evaluated in immunocompetent adults with malaria. Method This was a cross-sectional study at Marie O Polyclinic which included all patients over 15 years who were symptomatic and had Plasmodium falciparum infection confirmed on microscopy. Consenting patients received complete clinical examinations, then venous blood samples were collected and analysed for Complete Blood Counts and C-Reactive Protein. Results Samples of 349 adults were retained. 147/349 had anaemia, 221/349 had thrombocytopaenia and 261/349 had at least one alteration of their leukogram profile. The most frequent alteration of the white blood cells was lymphopenia (240/349). All but three patients with malaria had positive CRP values, that is, CRP > 5mg/L. Parasitaemia (in trophozoites of Plasmodium falciparum /µl -TPF/µl) ranged from 5,020 to 84,040. Multivariable logistic regression showed that the presence of moderate thrombocytopenia, moderate leukopenia and CRP levels above 100 mg/L were the best predictors of severe malaria. A scoring system was developed using these variables, in which scores less than 5 (level 1) were associated with a low probability for severe malaria, scores of 6–9 (level 2) with an intermediate probability, and scores of 10 or more (level 3) with a high probability for severe malaria. A predictor graph based on the patient sample in which 43% of patients had severe malaria and a ROC curve were constructed. The AUROC with this prediction model was 94%. Using a cut-point between level 2 and 3 on the predictor graph gave sensitivity of 66%, specificity of 99%, a positive predictive value of 0.98, and a negative predictive value of 0.79 for severe malaria. Conclusion Complete blood counts and CRP values can predict severe malaria accurately independently of currently established clinical and paraclinical criteria. Figures Figure 1 Figure 2 Figure 4 Figure 5 Strengths and Limitations This was a hospital-based, one-centre limited study and thus is not truly representative of the entire population of Douala, especially since MOP is a tertiary care centre which is not accessible to a large proportion of the population. We did not exclude with certainty other possible causes of anaemia like haemoglobinopathies or helminthic infections- however, apart from the acute febrile illness they presented with, these were all reasonably healthy adults with no known past medical history. We excluded with almost complete certainty any mixed infections by ensuring only febrile patients with confirmed malaria and whose symptoms resolved completely after only antimalarial treatment were retained. Sampling was random and consecutive, as all adult febrile patients over a 13-month period were screened for eligibility, which considerably reduced selection bias. Building on previous work with CRP and malaria, we included CRP values in the haematological parameters studied- a valuable insight, as nearly all febrile patients in lower-resource settings receive CRP testing as part of their initial triage, but interpretation of results when malaria is confirmed has been widely debated. Introduction Malaria is an infection of humans caused by protozoa of the genus Plasmodium [ 1 ]. Despite enormous advances in prevention, diagnosis and treatment in recent years, it still remains the most important parasitic infection of humans [ 1 , 2 ], with an estimated 247 million malaria cases and 619000 deaths in 84 malaria endemic countries in 2021, and with Africa accounting for 95% of cases and 96% of deaths [ 2 ]. Five species of Plasmodium can infect humans, though most human cases are caused by Plasmodium vivax and Plasmodium falciparum , and most deaths are caused by P. falciparum [ 1 , 3 ]. Malaria is, essentially, a haematological disease, and circulating falciparum parasites have significant effects on all three haematological cell lines [ 4 , 5 ]. Anaemia is the most common haematological anomaly found in malaria patients, with all five species of Plasmodium known to cause it [ 1 , 3 ]. Anaemia refers to a decrease in blood haemoglobin concentration below normal values when compared to age, gender and regional-specific controls [ 6 , 7 ]. While high-risk groups, especially children under five and pregnant women, are particularly prone to this condition [ 3 , 4 , 6 ], anaemia results in significant morbidity at both an individual and societal level even for immunocompetent adults [ 5 , 7 ]. The pathogenesis of anaemia in Plasmodium infection is multifactorial, with the main contributors being intravascular haemolysis, hypersplenism with decreased survival rates of both parasitized and non-parasitized erythrocytes, and bone marrow dyserythropoiesis [ 1 , 3 , 8 , 9 ]. The association between malaria and anaemia has been thoroughly established in high-risk groups in endemic areas; it is frequently found in children [ 10 – 13 ], pregnant women [ 14 – 16 ] and immunocompromised individuals [ 17 ] with malaria. However, very few data exist on the association between anaemia and malaria in immunocompetent adults. A recent study among asymptomatic adults in malaria endemic areas found that malaria positivity was not associated with decreased haemoglobin levels [ 18 ], but few studies on the prevalence of anaemia in immunocompetent adults with symptomatic and/or severe disease are available. Thrombocytopenia is a very frequent haematological alteration in Plasmodium infection [ 1 , 4 , 5 ]. Although historically considered to be a harbinger of severe malaria, recent evidence suggests that it is present in most cases of acute malaria [ 5 , 19 , 20 ], even without severe disease, and in some cases even in asymptomatic individuals [ 21 ]. Thrombocytopenia refers to a decreased number of platelets in circulating blood (platelet count less than 150000 platelets/µl), and has been recognized as an important part of the innate immune response in many diseases, including malaria, where platelets have been found to bind to and kill intraerythrocytic parasites of all the Plasmodium species, particularly P.vivax and P. falciparum [ 20 , 22 ]. Not surprisingly, perhaps, P. falciparum and P. vivax have been found to cause the most significant drop in platelet levels [ 20 , 23 ], with severe thrombocytopenia (platelet count less than 50000 platelets/µl) found to be a significant predictor of morbidity and mortality in patients with malaria [ 23 , 24 ]. A recent study on a mixed population of both symptomatic and asymptomatic outpatient attendees in Ghana found that platelet levels were inversely correlated with malaria positivity, and thus low platelet counts could possibly be a predictive factor for malaria in both adults and children [ 5 ]. Findings in a paediatric study on asymptomatic children in Nigeria were similar [ 25 ]. There is thus a paucity of data available on the association between malaria and thrombocytopenia in the sub-Saharan African region, especially in severely ill immunocompetent adults. The leukogram profile in Plasmodium infection is a confusing issue. Some studies have found no difference in leucocyte counts or differentials among infected and non-malaria groups [ 5 , 26 ], while others have found leucocytosis [ 17 ], monocytosis [ 4 , 25 ], leukopenia and lymphopenia [ 27 , 28 ]. A recent systematic review found that there was a significant association between lymphopenia and malaria [ 28 ]; however, a concern when interpreting these results is the frequent association of malaria and other diagnoses like viral and bacterial infections. Nevertheless, P. falciparum monoinfection has been shown to significantly activate inflammatory pathways [ 1 , 4 , 29 ], suggesting a possible direct link between malaria and leukogram alterations, and highlighting the role of CRP in diagnosing and predicting malaria [ 29 ]. More research, especially in areas of heavy falciparum infection, is needed to further clarify the relationship between leukogram alterations, CRP and malaria. There is thus a relatively small amount of data available on the haematological alterations of immunocompetent adults with malaria in sub-Saharan Africa, especially in symptomatic and severely ill individuals. This study aims to investigate the haematological indices of P. falciparum infected adults in a tertiary care setting in Cameroon. Methods Study Characteristics This was a hospital based, cross-sectional analytic study, carried out from March 1st 2023 to March 31st 2024, for a duration of thirteen months. This study was carried out at the Marie O Polyclinic (MOP) in Douala. Douala is the capital city of the Littoral Region of Cameroon, a country in sub-Saharan Africa. It is the largest city and the economic capital of the country, with a population of more than 3.5 million inhabitants [ 30 ]. MOP is a private tertiary care centre in Douala with a 24-hour laboratory service, a 24-hour outpatient service and a 30-bed capacity for adult inpatients. It has a regular staff of about twenty doctors, most of whom work in the outpatient unit, fifty nurses and ten laboratory technicians. Most cases of malaria self-present to MOP and are treated following the national and WHO guidelines [ 31 ]. Study Population and Sampling The study targeted immunocompetent adults with confirmed malaria at the Medical Ward (MW) and Out Patient Department (OPD) of MOP Douala. Sampling was consecutive. All adults who presented with acute febrile illness or suspected malaria were screened for eligibility. Included were all symptomatic adults above 15 years in whom malaria had been confirmed (positive thick smears or positive malaria rapid diagnostic tests - RDTs). The cohort retained is considered demographically representative, as no specific adult group was excluded. To make sure only malaria monoinfection was considered in the analysis, only patients whose symptoms resolved after treatment with nothing but antimalarials were retained. We excluded patients with suspected or confirmed viral or bacterial infection, patients who required antibiotics for symptom resolution even in the absence of confirmed bacterial infection, patients with neoplasm, haematological disorders, confirmed HIV infection (whether on treatment or not and regardless of CD4 count and viral load), chronic inflammatory conditions, pregnancy at any gestational age and up to six weeks postpartum and patients with malnourishment, chronic liver disease or any other form of immunodeficiency subsequently discovered. The required sample size was calculated based on the assumption that around 40% of patients would have severe malaria [ 29 ]. To identify differences in haematological characteristics, such as lymphopenia, between severe and uncomplicated patients of say, 60% and 40% respectively, with a power of 90% and alpha of 0.05 requires a sample of 290 malaria-positive adults, though we eventually accumulated a larger sample. Ethical Considerations The study was conducted only after ethical and administrative clearance had been obtained from both the University of Douala (No.3610 IEC-UD/04/2024/M) and the Review Board of MOP. All participants signed a consent form explaining the details of the study, including risks and benefits, before being included in the study, in accordance with the Declaration of Helsinki. Autonomy was respected, as participants had the right to withdraw from the study at any time. Risks to participants were minimized to the best of our ability. The confidentiality of patients was maintained by using serial numbers rather than names on questionnaires. Privacy was maintained at all times. Samples were obtained following recommended guidelines and coded to ensure anonymity. Patient/Public Involvement Neither patients nor the public were involved with the design, conduct, evaluation or dissemination of this study. Study Procedure and Laboratory Analysis Patients were approached at presentation in the OPD or in the MW. After obtaining informed consent, patients were interviewed by the principal investigator and blood samples collected. Clinical interview identified sociodemographic characteristics (age and sex), characterized the fever (degree and duration), and investigated past history for exclusion criteria. Topographical examination was done to search for infectious foci and classify malaria as uncomplicated or severe, as based on current WHO definitions [ 31 ]. The final diagnosis was based on both clinical findings and the results of investigations. Findings were documented in a structured questionnaire developed from this study [ 32 ]. Specimen collection is described in detail in the full study protocol, available on request from the authors and in the library of MOP. About 10ml of venous blood was collected in sterile syringes and distributed as thus: about 5ml was inserted into plastic EDTA tubes, to be used for thick smears and automated Complete Blood Counts (CBCs), while about 5ml was inserted into plastic dry tubes, to be used for immunoturbidimetric CRP analysis with Cobas C111® as a control for infection and to predict malaria severity. Thick smears were performed by the principal investigator with the aid of laboratory technicians at MOP, using the WHO recommendation for thick smears [ 33 ]. Blood for thick smears was stained with a 3% Giemsa stain on glass slides, dried for 60 mins and examined under an electrically-powered optical microscope (Optika ®) at 100x magnification. Parasite counts were performed on thick film/200 WBCs, with results of two primary readers averaged. The parasite densities were calculated as parasite/µl of blood by using parasites/WBCs counted x total WBCs in a µl of blood. Blood counts were done using an automated complete blood count (CBC) analyser (ABX Micros 60®), within one hour of collection. Samples for CRP analysis were analysed within two hours of collection, so no freezing was required. Samples were centrifuged in the BIOBASE ® centrifuge at a g-force of 1006 for five minutes, then plasma was used for immunoturbidimetric analysis with the Cobas C111®. All CBC analyses, thick smears and CRP assays were read independently by two operators, both blinded to the final diagnosis (the diagnosis of uncomplicated or severe malaria was made by the investigators only after all the clinical and laboratory variables were available). Quality Control and Assessment Laboratory investigations were carried out at the Marie O Polyclinic, Douala, Cameroon. Quality control was performed daily for each parameter before analysis of patient samples. All procedures were performed according to standard guidelines and instructions from product manufacturers. Statistical Analysis and Definitions Data were entered into Epi Info Version 7, transferred to Microsoft Excel 2019 and analysed using STATA release 18. Out of the 400 admissions, 349 had complete laboratory and clinical data. Data normality of continuous variables was checked using histogram, quantile-normal plot and Shapiro-Wilk normality test and summarized as mean (standard deviation) or median (interquartile range) as appropriate; categorical variables, and variables dichotomised or discretised based on predetermined or calculated cut-offs, were presented as frequency and percentage. Standard definitions were used for anaemia [ 6 , 7 ], thrombocytopenia [ 20 , 23 ], leukopenia, neutropenia, lymphopenia and leucocytosis [ 25 , 26 ]. The outcome variable here was the final diagnosis - that is, uncomplicated or severe malaria, as defined by the WHO criteria [ 33 ]. Comparison of haematological parameters between uncomplicated and severe malaria cases was made using two-sample t-test, rank-sum test or chi-square test as appropriate. Multivariable logistic regression models were then constructed to find the most suitable predictors of uncomplicated and severe malaria. Haematological count variables, as well as C-reactive protein (CRP) level and parasitaemia level, were each heavily right skewed and were therefore transformed to natural logarithms, rendering a more symmetrical distribution, before entering into logistic regression models. Subsequently, the variables significantly contributing to the fit of the model were discretised and the model refit. As per the STARD guidelines, the discriminant ability of each constructed logistic regression model was evaluated based on the Area Under the Curve (AUC) of the Receiver Operating Curve (ROC). Owing to some patients having repeat admissions, mixed effects logistic models were initially constructed in which patient study identification number (id) was considered as the random element. However, to obtain ROC curves, logistic models were subsequently used in which adjustment was made for the repeated admissions using the sandwich robust variance estimator based on clustering on patient study id. The two types of model were compared for any inconsistency. A multivariable Firth logistic model was used to estimate odds ratios of significant variables when used as predictors of severe malaria. A feasible set of criteria that could be applied in practice for discriminating severe and uncomplicated malaria among populations similar to that in the current study was then inferred from the modelling. Statistical significance was set at p < 0.05. Results Demographic and Clinical Characteristics A total of 400 patient admissions aged over 15 years and with fever were enrolled in the study. Fifty-one (12.75%) were excluded: thirty-four (8.5%) due to incomplete laboratory data, fifteen (3.75%) who subsequently required antibiotics for symptoms to resolve, and two (0.5%) who were found to be pregnant. The remaining 349 patient admissions (87.25%) had complete clinical and laboratory data, were malaria-positive and recovered completely after antimalarials alone, confirming malaria monoinfection. Forty-one patients were admitted on more than one occasion, one of whom had 3 admissions. Among overall admissions, the mean age was 33 years (range 16–89 years) and women accounted for 50.1%. The most frequent highest febrile peak was 38.7 o C, while the median duration of fever was three days. Patients presented in all thirteen months of the study (year-round), but the months with the lowest and highest numbers of malaria patients were March 2023 and March 2024 (10 and 14 cases respectively) and September and December 2023 and January 2024 (43, 40, and 40 cases respectively). More than half (65.0%) of the patients arrived at the hospital having already taken antimalarials. A significant portion of patients had severe malaria (43.3%). Males accounted for a higher proportion of severe cases, but there were no significant differences across groups in age, duration of fever, highest febrile peak, antimalarials having been taken, haemoglobin, haematocrit, mean corpuscular haemoglobin concentration (MCHC) or mean corpuscular volume (MCV), or in anaemia. Significant differences were evident in white blood cell and platelet counts, parasitaemia, C-reactive protein value and mean corpuscular haemoglobin (MCH), as indicated in Table 1 . Table 1 Baseline variables of malaria cases Variable Level or unit Total N = 349 Number (%) Uncomplicated N = 198 Severe N = 151 P value Sex Male 174 (49.9) 87 (43.9) 87 (57.6) .011 Age (mean) years 33.1 (12.7) 33.3 (12.4) 32.9 (13.1) .781 Age group 16–25 26–35 36–45 46–55 Over 56 105 (30.1) 98 (28.1) 90 25.8) 39 (17.2) 17 (4.9) 52 (26.3) 63 (31.8) 50 (25.3) 26 (13.1) 7 (3.5) 53 (35.1) 35 (23.2) 40 (26.5) 13 (8.6) 10 (6.6) .099 Duration of fever (mean) Days 3.0 (1.4) 3.0 (1.5) 3.0 (1.4) .745 Duration group ≤ 2 days > 2 days 148 (42.4) 201 (57.6) 85 (42.9) 113 (57.1) 63 41.7) 88 (58.3) .821 Highest febrile peak (mean) o C 39.0 (0.7) 38.9 (0.8) 39.0 (0.7)) .088 Antimalarials received prior to admission Yes 227 (65.0) 135 (68.2) 92 (60.9) .159 Haemoglobin g/dl 12.7 (1.8) 12.6 (1.7) 12.8 (1.9) .524 Haematocrit % 38.2 (5.5) 38.1 (5.3) 38.3 (5.9) .765 MCH pg/cell 28.1 (2.4) 27.9 (2.6) 28.5 (2.3) .031 MCHC g/dl 33.2 (2.5) 33.1 (2.5) 33.3 (2.4) .481 MCV fl/cell 85.4 (8.7) 84.7 (9.2) 86.2 (8.1) .124 Leucocytes cells/µl 4390 [3450, 5390] 4725 [4020, 5530] 3720 [2890, 5000] < .001 Neutrophils cells/µl 2910 [2020, 3790] 3055 [2400, 3930] 2330 [1650, 3440] < .001 Lymphocytes cells/µl 780 [550, 1090] 850 [610, 1190] 680 [480, 970] < .001 Monocytes cells/µl 480 [290, 670] 500 [330, 650] 410 [240, 720] .041 Platelets platelets/µl 135000 [107000, (169000] 154000 [128000, 194000] 103000 [86000, 135000] < .001 Parasitaemia TPF/mm 3, 16200 [11300, 18620] 13950 [10030, 17340] 18370 [15060, 21300] < .001 CRP value mg/l 54.6 [28.7, 97.4] 38.2 [19.8, 65.1] 96.0 [54.8, 156.8] < .001 Anaemia Yes 147 (42.1) 83 (41.9) 64 (42.4) .931 Leukopenia Yes 92 (26.4) 23 (11.6) 69 (45.7) < .001 Leucocytosis Yes 3 (0.9) 2 (1.0) 1 (0.7) .126 Neutropenia Yes 38 (10.9) 7 (3.5) 31 (20.5) < .001 Neutrophilia Yes 3 (0.9) 2 (1.0) 1 (0.7) .122 Lymphopenia Yes 240 (68.8) 123 (62.1) 117 (77,5) .002 Thrombocytopenia Yes 221 (63.3) 93 (47.0) 128 (84.8) < .001 Leucocyte level leukopenia normal leucocytosis 92 (26.4) 254 (72.8) 3 (0.7) 23 (11.6) 173 (89.4) 2 (1.0) 69 (45.7) 81 (53.6) 1 (0.7) < .001 Neutrophil level neutropenia normal neutrophilia 38 (10.9) 308 (88.2) 3 (0.9) 7 (3.5) 189 (95.5) 2 (1.0) 31 (20.5) 119 (78.8) 1 (0.7) < .001 Values expressed as mean (SD), median [IQR] or number (column %). P-values from t-test, rank-sum test, and chi-square test, respectively. Haemoglobin Anaemia was defined as haemoglobin (Hb) level < 12g/dl for women and < 13g/dl for men and further classified as severe if <7g/dl. As per the WHO criteria for severity, patients with Hb <7g/dl and confirmed parasitaemia were classified as severe malaria. Overall, 49.86% of patients had anaemia; of those, 91/147 were female and 56/147 were male. Hb counts tended to increase with age. Mean Hb values were similar in the uncomplicated and severe malaria group (12.6 and 12.8g/dl, respectively). Almost all cases of anaemia were mild, in both uncomplicated and severe malaria; and in both groups, a larger proportion of men were anaemic than women (Table 2 ). Only one patient was found with severe anaemia, and they also had severe malaria. Table 2 Severity of anaemia according to final diagnosis Anaemia severity Total (%) Uncomplicated Malaria Severe malaria Male N = 174 Female N = 175 Male N = 87 Female N = 111 Male N = 87 Female N = 64 No anaemia 118/174 (67.8) 84/175 (48.0) 60/87 (69.0) 55/111 (49.5) 58/87 (66.7) 29/64 (45.3) Mild anaemia 143/349 (41.0) 83/198 (41.9) 60/151 (39.7) Moderate anaemia 4/349 (0.01) 1/198 (0.5) 3/151 (2.0) Severe anaemia 1/349 (0.003) - 1/151 (0.7) Haemoglobin levels (g/dl): No anaemia ≥ 13 in men, ≥ 12 in women; mild anaemia ≥ 9, <13 in men, Hb ≥ 9, <12 women); moderate anaemia ≥ 7, <9; severe anaemia < 7. Platelets Thrombocytopenia was defined as platelet count less than 150,000 cells/µl and further classified as severe if the platelet count was less than 50,000 cells/µl. The median platelet count in the severe malaria group was significantly lower than the uncomplicated malaria group (103,000 vs 154,000; p < 0.001). Thrombocytopenia was found in 84.8% of patients with severe malaria as opposed to 47.0% of those with uncomplicated malaria. Thrombocytopaenia was mild in all cases of uncomplicated malaria. Most cases of low platelets with severe malaria were moderate, with only 1/221 having severe thrombocytopaenia (Table 3 ). Table 3 Distribution of thrombocyte counts according to final diagnosis Thrombocytopenia severity Total (%) N = 349 Uncomplicated malaria N = 198 Severe malaria N = 151 No thrombocytopenia 128 (36.7) 105 (53.0) 23 (15.2) Mild thrombocytopenia 153 (43.8) 93 (47.0) 60 (39.7) Moderate thrombocytopenia 67 (19.2) - 67 (44.4) Severe thrombocytopenia 1 (0.3) - 1 (0.7) Platelet counts (cells/ µl): No thrombocytopenia ≥ 150,000: Mild thrombocytopenia ≥ 100,000 < 150,000; Moderate thrombocytopenia ≥ 50,000 < 100,000; Severe thrombocytopenia < 50,000. White blood cells There were alterations in the leukogram profile in terms of total white blood cell count, neutrophil and lymphocyte counts. Eosinophil, basophil and monocyte counts were largely within normal levels, and so were not included in the analysis. Leucocytosis was defined as a total leukocyte count greater than 10,000 cells/µl, neutrophilia as absolute neutrophil counts greater than 8000 cells/µl, leukopenia as leukocyte counts less than 3500 cells/µl, neutropenia as absolute neutrophil counts less than 1500 cells/µl and lymphopenia as lymphocyte counts less than 1000 cells/µl. Median leukocyte levels were significantly lower in the severe malaria group than the uncomplicated malaria group (3720 vs 4725 cells/µl; p < 0.001), though both medians were within the normal leukocyte range for adults. Most (72.8%) adults with malaria had normal leukocyte counts, with leukopenia being the more common alteration (26.4%), and leucocytosis being extremely rare (0.7%). Leukopenia was significantly more frequent among the severe malaria group than the uncomplicated malaria group (45.7% vs 11.6%; p < 0.001). Leukopenia was further classified as mild if ≥ 2500 and < 3500; moderate if ≥ 1500 and < 2500; and severe if < 1500 (Table 4 ). Neutrophil counts displayed a similar trend, with median values significantly lower in the severe malaria group (2330 vs 3055 cells/µl; p < 0.001), but with medians both within normal ranges. The majority of patients (310/349) had normal neutrophil counts. Neutropenia was found in 38/349, while neutrophilia was present in 3/349. A significant majority of those with neutropenia had severe malaria (31/38 vs 7/38; p < 0.001), (supplemental Fig. 1). The median lymphocyte count was lower than the normal adult range in both the severe and uncomplicated malaria groups, though it was significantly lower in the group with severe malaria (680 vs 850 cells/µl; p < 0.001). A large proportion of all malaria patients had lymphopenia (68.8%), regardless of whether it was uncomplicated or severe (123/198 vs 117/151; p = 0.002), (supplemental Fig. 1). Table 4 Distribution of leukocyte counts according to final diagnosis Leukopenia severity Total (%) N = 349 Uncomplicated malaria N = 198 Severe malaria N = 151 No leukopenia 257 (73.6) 175 (88.4) 82 (54.3) Mild leukopenia 77 (22.1) 23 (11.6) 54 (35.8) Moderate leukopenia 13 (3.7) - 13 (8.6) Severe leukopenia 2 (0.6) - 2 (1.3) Leukopenia (in cells/µl): >3500 normal; ≥2500 and < 3500 mild; ≥1500 and < 2500 moderate; 5mg/L. The median values of CRP were significantly higher in severe malaria than in uncomplicated malaria (96.0 vs 38.2mg/L; p < 0.001). The distribution of CRP levels following the ranges most frequently used in clinical settings and stratified by outcome is indicated in Table 5 . Table 5 Distribution of CRP levels according to final diagnosis CRP (mg/l) Total N = 349 Uncomplicated malaria N = 198 Severe malaria N = 151 100 78 (22.3) 11 (5.6) 67 (44.4) Parasite Density Parasitaemia (in trophozoites of Plasmodium falciparum /µl -TPF/µl) ranged from 5,020 to 84,040. Parasite count medians were significantly higher in the group with severe malaria than in the uncomplicated malaria group (18,370 vs 13,950 TPF/µl), though both were well below the WHO threshold for severe malaria. Parasite densities were unaffected by age (correlation coefficient − 0.0543, p = 0.312) and gender (p = 0.460). Parasitaemia was positively correlated with the highest febrile peak (correlation coefficient 0.1909, p < 0.001), but not with the duration of fever (correlation coefficient 0.0703, p = 0.190) or not having taken antimalarials before presenting to the hospital (p = 0.796). There was no significant relationship between parasite counts and haemoglobin levels (correlation coefficient − 0.0173, p = 0.740). Parasite density was negatively correlated with platelet counts (correlation coefficient − 0.3282, p < 0.001). There was no significant correlation between parasite densities and leukocyte count (correlation coefficient 0.0306, p = 0.569), absolute neutrophil count (correlation coefficient 0.0913, p = 0.088) or lymphocyte count (correlation coefficient − 0.1020, p = 0.057). There was a positive correlation between CRP levels and parasitaemia (correlation coefficient 0.4084, p < 0.001). The relationship between parasitaemia and the various haematological parameters is illustrated in supplemental Fig. 2 and supplemental Fig. 3. Diagnostic values of haematological parameters The haematological parameters which emerged as having the most significant effect on patient outcomes were leukocyte counts, neutrophil counts, lymphocyte counts, platelet counts and CRP levels. As leukocyte count, platelet count and CRP levels could be stratified by grade (Tables 3 , 4 and 5 ), they were fitted into a multivariable Firth logistic model to estimate their odds ratios (OR) when used as predictors of severe malaria (Table 6 ). Patients with moderate leukopenia had 150 times, with moderate thrombocytopaenia 600 times, and with CRP levels above 100mg/L 170 times (OR) higher odds of having severe malaria. Logarithmic transformation of these odds ratios yielded numerical coefficients. Scores were then allocated to the various levels of each predictor in approximately the same ratio as their coefficients (scores for thrombocytopenia grades were 0, 1 and 10; for leukopenia 0, 4 and 8; and for CRP levels 0, 3, 5 and 8). For each patient, the scores were summed to give a predictor score. A logistic regression model was used to examine the predictive ability of this score, following which a ROC curve (supplemental Fig. 4) and a predictor graph based on the patient sample in which 43% of patients had severe malaria (supplemental Fig. 5) were constructed. The AUROC with this prediction model was 94.02%. Suitable cut-offs at approximate tertiles are illustrated in supplemental Fig. 5, whereby scores less than 5 (level 1) are associated with a low probability for severe malaria, scores of 6–9 (level 2) with an intermediate probability, and scores of 10 or more (level 3) with a high probability for severe malaria. Using a cut-point between level 2 and 3 gives a sensitivity of 66%, specificity of 99%, a positive predictive value of 0.98, and a negative predictive value of 0.79 (Table 7 ). Table 6 Odds ratios, coefficients and score values of haematological parameters as predictors of severe malaria. Variable Level Crude OR 95% CI Adjusted OR 95% CI Wald P -value LR P-value Coefficient Score Thrombocytopenia no 1 - 1 - <.001 0 0 mild 2.90 1.67, 5.04 1.89 0.92, 3.89 .084 0.635 1 moderate* 615.0 36.7, 10293 612.4 28.8, 13028 < .001 6.417 10 Leukopenia no 1 - 1 - <.001 0 0 mild 4.93 2.85, 8.55 15.7 6.45, 38.3 < .001 2.755 4 moderate# 65.9 3.90, 1115 150.5 6.86, 3304 < .001 5.014 8 CRP level (mg/l) ≤ 20 1 - 1 - 20, ≤ 40 2.52 0.89, 7.16 5.58 1.12, 27.9 .036 1.720 3 > 40, ≤ 100 7.27 2.84, 18.6 19.6 4.37, 87.8 100 53.9 18.3, 158.6 172.8 33.1, 902.6 < .001 5.152 8 Note: * 1 case is severe thrombocytopenia; # 2 cases are severe leukopenia. Table 7 Performance of predictive score derived from the logistic model with two cut-points. Level Predictive score Uncomplicated malaria Severe malaria Total (col %) Likelihood ratio Probability of severe malaria * (95% CI) 3 10 or over 2 100 102 (29.2) 65.6 0.98 (0.95, 1.00) 2 6–9 97 45 142 (40.7) 0.61 0.32 (0.24, 0.39) 1 5 or less 99 6 105 (30.1) 0.08 0.06 (0.01, 0.10) Prior 198 151 349 1 0.43 * Given a prior probability of 0.43 Discussion This study described various haematological parameters among malaria-positive immunocompetent adults at a tertiary hospital in urban Cameroon, and confirms that all the currently known haematological abnormalities of Plasmodium infection reported in at-risk groups are prevalent in immunocompetent adults, both in uncomplicated and severe disease. The abnormalities previously cited include changes in haemoglobin levels [ 4 – 6 , 15 – 18 ], leucocyte counts [ 4 , 5 , 25 – 28 ], platelet counts [ 4 , 5 , 19 – 23 ] and CRP levels [ 29 , 34 , 35 ]. Erythrocytes are the primary targets of Plasmodium merozoites in active disease, and thus unsurprisingly, anaemia is one of the most commonly reported complications of malaria [ 3 ]. A myriad of pathophysiological processes have been implicated: intravascular and tissular haemolysis, splenic sequestration and dysregulations of bone marrow erythropoiesis [ 3 , 8 , 9 ]. Reported prevalence of anaemia in at-risk groups ranges from around 40–60% in pregnant women [ 14 , 15 ] to 60%-65% in children [ 4 , 13 ], with the anaemia being severe in up to 5% of cases. By contrast, haemoglobin values in this study were normal for the majority (68.7%) of study participants. Nearly all (143/147) of the anaemic adults had mild anaemia, and only one patient (0.7%) had severe anaemia. The underlying issue in reporting anaemia prevalence with malaria in endemic areas is the presence of several confounding variables like haemoglobinopathies [ 4 ], poor nutritional status [ 12 ] and other asymptomatic infections, notably helminthic infestations, that can cause microcytic anaemia [ 12 , 13 ]. This might explain why the prevalence of anaemia was much lower in a study focusing on immunocompetent adults, as most of these conditions do not significantly affect haemoglobin levels in healthy adults [ 10 ]. Also, this study was conducted within a tertiary hospital in an urban region where nutritional and socioeconomic concerns were minimal. This might suggest that in endemic zones, malaria is a relatively infrequent cause of anaemia by itself; and findings of moderate or severe anaemia in a febrile adult should prompt investigation for other causes like immunodeficiency, haemoglobinopathies or poor nutritional status. Anomalies in both platelet count and function are known features of malarial disease. This study focused on platelet count derangements. Thrombocytopenia was found in 63.3% of malaria patients overall, and was the only parameter that was significantly inversely correlated with parasite density (Fig. 2). In addition, the percentage of adults with severe malaria that had thrombocytopenia was 84.8%, as opposed to 47.0% with uncomplicated malaria. However, only one patient presented with severe thrombocytopenia, and all cases of thrombocytopenia in uncomplicated malaria were mild. These findings would seem to suggest that platelet counts might be predictors of disease burden and severity, and corroborate findings in previous studies [ 4 , 23 , 24 ]. The mechanisms of platelet count reduction in malaria are varied: splenic sequestration [ 3 ], consumption in abnormal bleeding processes like Disseminated Intravascular Coagulation [ 3 , 4 ] and most importantly, peripheral destruction as agents of defence against plasmodial parasites [ 20 , 22 ]. These would support the observation of decreasing platelet counts as parasitaemia increased in our study. An interesting phenomenon is that parasite densities in this study were all below the threshold of severity as defined by the WHO (100,000TPF/µl, or > 10% parasitized erythrocytes) [ 33 ], which could either mean that adults in falciparum -endemic zones have extremely efficient platelets that destroy parasites before they can reach high densities, or that other immune mechanisms of healthy adults in endemic zones prevent high parasitaemia, and thus limit the amount of severe thrombocytopenia (and perhaps severe disease) that would otherwise be seen. The findings of a 63.3% prevalence of thrombocytopenia with a 0.7% occurrence of severe thrombocytopenia are at odds with those in a study of malaria patients (both adult and paediatric) in Sri Lanka [ 19 ], where the prevalence of thrombocytopenia was found to be 86%, and severe thrombocytopenia was found in 18.2% of patients. This increased risk of severe thrombocytopenia might be related to the inclusion of paediatric patients in the study, as platelet count reports were not stratified by age; however, in a large study in Papua, severe thrombocytopenia was found among nearly 6% of malaria patients, especially those with falciparum malaria, even when adjusting for age [ 23 ]. However, this study was reported in a zone where mixed infections were frequent, and thus endemicity to falciparum malaria cannot be assumed. In all these comparable studies, there is also the fact that steps were not taken to eliminate mixed infections- malaria is frequently found in association with other viral and bacterial illnesses in tropical settings [ 29 ], many of which are known to cause thrombocytopenia. Leukocyte counts in this study were normal for the vast majority of patients (72.8%), with leukopenia being the more common alteration (26.4%) and leucocytosis found very rarely (0.7%). These values are similar to those of a study involving both adults and children in Colombia [ 27 ], where leukopenia was found in 18% of malaria patients while leucocytosis emerged in only 4%. The higher value of leucocytosis is likely related to the inclusion of children in the study, as leucocytosis is frequent in febrile children and the possibility of co-infection was not excluded. Leukopenia is especially associated with falciparum malaria- an experimental study found a 12% prevalence of leukopenia and a 9% prevalence of severe leukopenia in volunteers inoculated with P. falciparum in England [ 36 ], compared to the 0.6% prevalence in our study. The difference in the prevalence of severe leukopenia is likely explained by the fact that the volunteers in the experimental study lacked the natural immunity present in adults in endemic zones. The occurrence of leukopenia in Plasmodium infection has many proposed mechanisms, with splenic sequestration being the most favoured explanation, especially given the rapid recovery that usually occurs [ 1 , 3 , 27 ]. However, there is a lot of recent evidence pointing to plasmodial ability to significantly activate inflammatory pathways [ 4 , 27 , 29 , 34 , 35 ], which would lead to white cell activation and consumption. This is especially significant in severe disease- 75.0% of those with leukopenia had severe malaria in this study, and patients with leukopenia were up to 150 times (OR) more likely to have severe malaria. With the white cell differentials, neutrophil counts displayed a similar trend- most patients (88.8%) had normal counts while neutropenia was more common (10.3%) and neutrophilia was rare (0.9%). Most (83.3%) of the neutropenic patients had severe malaria. These findings are consistent with similar studies [ 4 , 27 ] and are explained by the same mechanisms of splenic pooling and inflammatory cascade that have been proposed for leukopenia. Lymphopenia, on the other hand, was the most frequent leukogram alteration overall, with nearly 70% of all malaria patients being lymphopenic regardless of severity, and with the median lymphocyte count well below the normal range for adults (850 cells/µl in uncomplicated malaria and 680 cells//µl in severe malaria). This is similar to findings in other studies- it was the most frequent alteration in a Colombian study, with a prevalence of 54% [ 27 ]; with falciparum malaria, in particular, it was found in 63% of cases of imported malaria in the United Kingdom and was the most common alteration found [ 37 ]. The origin of lymphopenia in such an acute disease is still being elucidated; however, proposed mechanisms include splenic sequestration [ 3 ], redistribution into more active tissues [ 28 ] and dysleucopoiesis [ 3 , 4 , 27 , 28 ]. Lymphopenia in many clinical contexts raises concern for transient immunodeficiency and thus more severe disease and complications; in our study, lymphocytes counts were significantly lower in severe malaria than uncomplicated infection (p < 0.001), and it was found to be a significant predictor in univariable analysis. This was similar to findings in the Colombian study, where lymphopenia was associated with severity of disease [ 27 ]. However, including lymphopenia in the model already consisting of thrombocytopenia, leukopenia and CRP levels did not appreciably improve the predictive ability. This study demonstrates that moderate thrombocytopenia (OR = 612.4), moderate leukopenia (OR = 150.5), and CRP levels greater than 100mg/L (OR = 172.8) are the most reliable haematological predictors of malaria outcome in healthy adults in endemic settings. The scoring system proposed in this study has an AUROC of 0.94, with a sensitivity of 66% and a specificity of nearly 100% when a cut-off between level 2 (intermediate probability) and level 3 (high probability) is used. Comparable studies [ 4 , 19 , 20 , 27 ] have mainly evaluated the predictive power of the haematological variables for distinguishing non-infected from malarial patients. However, malaria remains a leading cause of significant morbidity and mortality even among healthy adults in endemic regions- with the proportion of malaria deaths in children under five decreasing between 2010 and 2021 [ 2 ], implying that more older children and adults are succumbing to severe disease. The main challenge in diagnosing severe malaria in adults is that many of the WHO criteria for severity like severe anaemia and severe thrombocytopaenia are very late findings in older people, as shown in this study. Therefore, in a malaria endemic region, adults (febrile or not) who are at risk of malaria and whose haematological parameters indicate an intermediate or high probability of severe malaria using the proposed scoring system in this study should be re-evaluated for malaria (and possibly receive parenteral antimalarials) even if initial thick smears or RDTs are negative, unless there is a confirmed alternative diagnosis that explains the haematological alterations. Abbreviations AUC – Area Under the Curve AUROC – Area Under the Receiver Operating Characteristic Curve CBC – Complete Blood Count(s) CI – Confidence Interval CRP – C‑Reactive Protein EDTA – Ethylenediaminetetraacetic Acid Hb – Haemoglobin HIV – Human Immunodeficiency Virus IQR – Interquartile Range MCV – Mean Corpuscular Volume MCH – Mean Corpuscular Haemoglobin MCHC – Mean Corpuscular Haemoglobin Concentration MOP – Marie O Polyclinic MW – Medical Ward OPD – Out Patient Department OR – Odds Ratio RDT – Rapid Diagnostic Test ROC – Receiver Operating Characteristic (curve) SD – Standard Deviation STARD – Standards for Reporting Diagnostic Accuracy Studies TPF/μl – Trophozoites of Plasmodium falciparum per microlitre WBC – White Blood Cell(s) WHO – World Health Organization Declarations Ethics Approval and Consent to Participate The study was conducted only after ethical and administrative clearance had been obtained from both the University of Douala (No.3610 IEC-UD/04/2024/M) and the Review Board of MOP. All participants signed a consent form explaining the details of the study, including risks and benefits, before being included in the study, in accordance with the Declaration of Helsinki. Autonomy was respected, as participants had the right to withdraw from the study at any time. Risks to participants were minimized to the best of our ability. The confidentiality of patients was maintained by using serial numbers rather than names on questionnaires. Privacy was maintained at all times. Samples were obtained following recommended guidelines and coded to ensure anonymity. Consent for Publication Not applicable. This study did not include any individual‑level identifiable data, images, or case details. All data were analysed and reported in aggregate form, and written informed consent to participate was obtained from all participants prior to enrolment, in accordance with ethical approval. Availability of Data and Materials The dataset and materials used for this study are freely available from the corresponding author upon reasonable request. Competing Interests The authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work. Funding The funding from this study was derived completely from the authors. All the researchers are completely independent from funders. Authors’ Contributions YN was the principal investigator, assisted with study conceptualisation and design, helped with data collection and prepared the initial and final drafts of the manuscript. AG assisted with study design, performed most of the data analysis and helped revise the manuscript. SG assisted with data collection and referencing, and helped revise the manuscript. MN conceptualised the study and helped design it, and also helped revise the manuscript. Acknowledgments The authors would like to acknowledge the contributions of the laboratory staff of Marie O Polyclinic, including Tchio Emmanuel Chrispo, Nyemb Teclaire, Legnida Hilaire, Dimo Towa Clovis and Kalat Tchio Chantal, for their help with the laboratory aspects of this study. Special thanks to Dr Ngoulla Roger and Dr Sylvie Ngoubeyou of Marie O Polyclinic for their advice and assistance. References White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malar Lancet. 2014;383:723–35. WHO. World malaria report 2022. Geneva: World Health Organization; 2022. White NJ. Anaemia and malaria. Malar J. 2018;17(1):371. 10.1186/s12936-018-2509-9 . PMID: 30340592; PMCID: PMC6194647. Maina RN, Walsh D, Gaddy C, Hongo G, Waitumbi J, Otieno L, Jones D, Ogutu BR. Impact of Plasmodium falciparum infection on haematological parameters in children living in Western Kenya. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9177783","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":639025445,"identity":"8d7dd6a5-817a-4426-a555-31188c9a9555","order_by":0,"name":"Yembu Ngwengi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYNCCHzbM/CA6oYBYHYw9aeySDSAtBkTbwnaY3+AAiEGMFoPj3cmfeXiYpY3Pr0788MCAQZ5f7AABLWfObpPmsWAzNrvxdrME0GGGM2cnENByI3cbMw8PT7LZjbMbQFoSDG4T0nL/7ebPPGwS9ZtnnN38gzgtN3g3SPOwGTAb8PduI84WyTO52yTn9iQwS9zg3WaRYCBB2C98x89u/vDmx39m/v6zm2/+qLCR55cmoEXhAAMDEw+IJQFWKYFfOQjINwAj/weIxX+AsOpRMApGwSgYmQAA+0ZGG6WsJm8AAAAASUVORK5CYII=","orcid":"","institution":"University of Douala","correspondingAuthor":true,"prefix":"","firstName":"Yembu","middleName":"","lastName":"Ngwengi","suffix":""},{"id":639025446,"identity":"769ae23c-aa13-41e3-9014-418609771b95","order_by":1,"name":"Alan Geater","email":"","orcid":"","institution":"Prince of Songkla University","correspondingAuthor":false,"prefix":"","firstName":"Alan","middleName":"","lastName":"Geater","suffix":""},{"id":639025447,"identity":"30b45a63-57ac-402f-b21f-523a9d0db46c","order_by":2,"name":"Stephane Nguembu","email":"","orcid":"","institution":"University of Douala","correspondingAuthor":false,"prefix":"","firstName":"Stephane","middleName":"","lastName":"Nguembu","suffix":""},{"id":639025448,"identity":"1a42dfe4-170b-4f22-aaee-662148623903","order_by":3,"name":"Martine Nida","email":"","orcid":"","institution":"University of Douala","correspondingAuthor":false,"prefix":"","firstName":"Martine","middleName":"","lastName":"Nida","suffix":""}],"badges":[],"createdAt":"2026-03-20 10:23:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9177783/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9177783/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109263727,"identity":"3ee307b6-5bf8-4cb0-b2b8-1ba1bdad87d4","added_by":"auto","created_at":"2026-05-14 12:07:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56553,"visible":true,"origin":"","legend":"\u003cp\u003eBox plots showing the distribution in uncomplicated (0) and severe malaria (1) of ln[leucocytes (cells/μl)], ln[lymphocytes (cells/μl)], and ln[lymphocytes (cells/μl)]. Horizontal dashed lines indicate cut points used for leukopenia, lymphopenia, and neutropenia. The counts have been logarithm-transformed to render the distributions more symmetrical.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9177783/v1/221af215ee915f4c578208cf.png"},{"id":109263729,"identity":"82b1449e-c898-4ca5-9c15-6d6987725df3","added_by":"auto","created_at":"2026-05-14 12:07:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":149781,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot matrix corresponding to the correlation matrix showing the relationships among the haematological parameters and parasite level. The variables are logarithm of parasite count, haemoglobin, haematocrit, platelet count, leucocyte count, neutrophil count, lymphocyte count and C-reactive protein level. Parasite count, white blood cell counts and C-reactive protein level are logarithm-transformed.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9177783/v1/31b9dcbe15892371ac01e269.png"},{"id":109263730,"identity":"95a6d2bf-36de-436a-aedf-599202bebcae","added_by":"auto","created_at":"2026-05-14 12:07:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":59143,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve with leukopenia, thrombocytopaenia and CRP for predicting severe malaria.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9177783/v1/bbb7164489c0f9744abcb5cf.png"},{"id":109263732,"identity":"cf1de48e-fd5c-4b68-b82d-235faafd21db","added_by":"auto","created_at":"2026-05-14 12:07:17","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":59081,"visible":true,"origin":"","legend":"\u003cp\u003eThe graph shows the predicted probability of having severe malaria according to the prediction score in a patient group with 43% severe malaria. Vertical bars indicate 95% confidence intervals.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-9177783/v1/44b786fbae0acd7d1394cc00.png"},{"id":109296065,"identity":"94a57a3d-135a-4e14-bfc9-7a1aa9f18dd3","added_by":"auto","created_at":"2026-05-15 08:45:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":720447,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9177783/v1/8b6b94da-9cf0-410f-a3f9-046e30f10626.pdf"},{"id":109263728,"identity":"1cdd5ffa-f83b-4f15-83b3-52f22c659925","added_by":"auto","created_at":"2026-05-14 12:07:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":143450,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9177783/v1/c4fc939ad301f259a82e4c62.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive values of haematological parameters in Plasmodium falciparum infection in immunocompetent adults at an urban hospital in Douala","fulltext":[{"header":"Strengths and Limitations","content":"\u003cul\u003e\n \u003cli\u003eThis was a hospital-based, one-centre limited study and thus is not truly representative of the entire population of Douala, especially since MOP is a tertiary care centre which is not accessible to a large proportion of the population.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWe did not exclude with certainty other possible causes of anaemia like haemoglobinopathies or helminthic infections- however, apart from the acute febrile illness they presented with, these were all reasonably healthy adults with no known past medical history.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWe excluded with almost complete certainty any mixed infections by ensuring only febrile patients with confirmed malaria and whose symptoms resolved completely after only antimalarial treatment were retained.\u003c/li\u003e\n \u003cli\u003eSampling was random and consecutive, as all adult febrile patients over a 13-month period were screened for eligibility, which considerably reduced selection bias.\u003c/li\u003e\n \u003cli\u003eBuilding on previous work with CRP and malaria, we included CRP values in the haematological parameters studied- a valuable insight, as nearly all febrile patients in lower-resource settings receive CRP testing as part of their initial triage, but interpretation of results when malaria is confirmed has been widely debated.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eMalaria is an infection of humans caused by protozoa of the genus \u003cem\u003ePlasmodium\u003c/em\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite enormous advances in prevention, diagnosis and treatment in recent years, it still remains the most important parasitic infection of humans [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], with an estimated 247\u0026nbsp;million malaria cases and 619000 deaths in 84 malaria endemic countries in 2021, and with Africa accounting for 95% of cases and 96% of deaths [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Five species of \u003cem\u003ePlasmodium\u003c/em\u003e can infect humans, though most human cases are caused by \u003cem\u003ePlasmodium vivax\u003c/em\u003e and \u003cem\u003ePlasmodium falciparum\u003c/em\u003e, and most deaths are caused by \u003cem\u003eP. falciparum\u003c/em\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Malaria is, essentially, a haematological disease, and circulating \u003cem\u003efalciparum\u003c/em\u003e parasites have significant effects on all three haematological cell lines [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnaemia is the most common haematological anomaly found in malaria patients, with all five species of \u003cem\u003ePlasmodium\u003c/em\u003e known to cause it [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Anaemia refers to a decrease in blood haemoglobin concentration below normal values when compared to age, gender and regional-specific controls [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. While high-risk groups, especially children under five and pregnant women, are particularly prone to this condition [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], anaemia results in significant morbidity at both an individual and societal level even for immunocompetent adults [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The pathogenesis of anaemia in \u003cem\u003ePlasmodium\u003c/em\u003e infection is multifactorial, with the main contributors being intravascular haemolysis, hypersplenism with decreased survival rates of both parasitized and non-parasitized erythrocytes, and bone marrow dyserythropoiesis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The association between malaria and anaemia has been thoroughly established in high-risk groups in endemic areas; it is frequently found in children [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], pregnant women [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and immunocompromised individuals [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] with malaria. However, very few data exist on the association between anaemia and malaria in immunocompetent adults. A recent study among asymptomatic adults in malaria endemic areas found that malaria positivity was not associated with decreased haemoglobin levels [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], but few studies on the prevalence of anaemia in immunocompetent adults with symptomatic and/or severe disease are available.\u003c/p\u003e \u003cp\u003eThrombocytopenia is a very frequent haematological alteration in \u003cem\u003ePlasmodium\u003c/em\u003e infection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Although historically considered to be a harbinger of severe malaria, recent evidence suggests that it is present in most cases of acute malaria [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], even without severe disease, and in some cases even in asymptomatic individuals [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Thrombocytopenia refers to a decreased number of platelets in circulating blood (platelet count less than 150000 platelets/\u0026micro;l), and has been recognized as an important part of the innate immune response in many diseases, including malaria, where platelets have been found to bind to and kill intraerythrocytic parasites of all the \u003cem\u003ePlasmodium\u003c/em\u003e species, particularly \u003cem\u003eP.vivax\u003c/em\u003e and \u003cem\u003eP. falciparum\u003c/em\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Not surprisingly, perhaps, \u003cem\u003eP. falciparum\u003c/em\u003e and \u003cem\u003eP. vivax\u003c/em\u003e have been found to cause the most significant drop in platelet levels [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], with severe thrombocytopenia (platelet count less than 50000 platelets/\u0026micro;l) found to be a significant predictor of morbidity and mortality in patients with malaria [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A recent study on a mixed population of both symptomatic and asymptomatic outpatient attendees in Ghana found that platelet levels were inversely correlated with malaria positivity, and thus low platelet counts could possibly be a predictive factor for malaria in both adults and children [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Findings in a paediatric study on asymptomatic children in Nigeria were similar [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. There is thus a paucity of data available on the association between malaria and thrombocytopenia in the sub-Saharan African region, especially in severely ill immunocompetent adults.\u003c/p\u003e \u003cp\u003eThe leukogram profile in \u003cem\u003ePlasmodium\u003c/em\u003e infection is a confusing issue. Some studies have found no difference in leucocyte counts or differentials among infected and non-malaria groups [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], while others have found leucocytosis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], monocytosis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], leukopenia and lymphopenia [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. A recent systematic review found that there was a significant association between lymphopenia and malaria [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]; however, a concern when interpreting these results is the frequent association of malaria and other diagnoses like viral and bacterial infections. Nevertheless, \u003cem\u003eP. falciparum\u003c/em\u003e monoinfection has been shown to significantly activate inflammatory pathways [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], suggesting a possible direct link between malaria and leukogram alterations, and highlighting the role of CRP in diagnosing and predicting malaria [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. More research, especially in areas of heavy \u003cem\u003efalciparum\u003c/em\u003e infection, is needed to further clarify the relationship between leukogram alterations, CRP and malaria.\u003c/p\u003e \u003cp\u003eThere is thus a relatively small amount of data available on the haematological alterations of immunocompetent adults with malaria in sub-Saharan Africa, especially in symptomatic and severely ill individuals. This study aims to investigate the haematological indices of \u003cem\u003eP. falciparum\u003c/em\u003e infected adults in a tertiary care setting in Cameroon.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Characteristics\u003c/h2\u003e \u003cp\u003eThis was a hospital based, cross-sectional analytic study, carried out from March 1st 2023 to March 31st 2024, for a duration of thirteen months. This study was carried out at the Marie O Polyclinic (MOP) in Douala. Douala is the capital city of the Littoral Region of Cameroon, a country in sub-Saharan Africa. It is the largest city and the economic capital of the country, with a population of more than 3.5\u0026nbsp;million inhabitants [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. MOP is a private tertiary care centre in Douala with a 24-hour laboratory service, a 24-hour outpatient service and a 30-bed capacity for adult inpatients. It has a regular staff of about twenty doctors, most of whom work in the outpatient unit, fifty nurses and ten laboratory technicians. Most cases of malaria self-present to MOP and are treated following the national and WHO guidelines [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population and Sampling\u003c/h3\u003e\n\u003cp\u003eThe study targeted immunocompetent adults with confirmed malaria at the Medical Ward (MW) and Out Patient Department (OPD) of MOP Douala. Sampling was consecutive. All adults who presented with acute febrile illness or suspected malaria were screened for eligibility. Included were all symptomatic adults above 15 years in whom malaria had been confirmed (positive thick smears or positive malaria rapid diagnostic tests - RDTs). The cohort retained is considered demographically representative, as no specific adult group was excluded. To make sure only malaria monoinfection was considered in the analysis, only patients whose symptoms resolved after treatment with nothing but antimalarials were retained. We excluded patients with suspected or confirmed viral or bacterial infection, patients who required antibiotics for symptom resolution even in the absence of confirmed bacterial infection, patients with neoplasm, haematological disorders, confirmed HIV infection (whether on treatment or not and regardless of CD4 count and viral load), chronic inflammatory conditions, pregnancy at any gestational age and up to six weeks postpartum and patients with malnourishment, chronic liver disease or any other form of immunodeficiency subsequently discovered.\u003c/p\u003e \u003cp\u003eThe required sample size was calculated based on the assumption that around 40% of patients would have severe malaria [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. To identify differences in haematological characteristics, such as lymphopenia, between severe and uncomplicated patients of say, 60% and 40% respectively, with a power of 90% and alpha of 0.05 requires a sample of 290 malaria-positive adults, though we eventually accumulated a larger sample.\u003c/p\u003e\n\u003ch3\u003eEthical Considerations\u003c/h3\u003e\n\u003cp\u003e The study was conducted only after ethical and administrative clearance had been obtained from both the University of Douala (No.3610 IEC-UD/04/2024/M) and the Review Board of MOP. All participants signed a consent form explaining the details of the study, including risks and benefits, before being included in the study, in accordance with the Declaration of Helsinki. Autonomy was respected, as participants had the right to withdraw from the study at any time. Risks to participants were minimized to the best of our ability. The confidentiality of patients was maintained by using serial numbers rather than names on questionnaires. Privacy was maintained at all times. Samples were obtained following recommended guidelines and coded to ensure anonymity.\u003c/p\u003e\n\u003ch3\u003ePatient/Public Involvement\u003c/h3\u003e\n\u003cp\u003eNeither patients nor the public were involved with the design, conduct, evaluation or dissemination of this study.\u003c/p\u003e\n\u003ch3\u003eStudy Procedure and Laboratory Analysis\u003c/h3\u003e\n\u003cp\u003ePatients were approached at presentation in the OPD or in the MW. After obtaining informed consent, patients were interviewed by the principal investigator and blood samples collected. Clinical interview identified sociodemographic characteristics (age and sex), characterized the fever (degree and duration), and investigated past history for exclusion criteria. Topographical examination was done to search for infectious foci and classify malaria as uncomplicated or severe, as based on current WHO definitions [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The final diagnosis was based on both clinical findings and the results of investigations. Findings were documented in a structured questionnaire developed from this study [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSpecimen collection is described in detail in the full study protocol, available on request from the authors and in the library of MOP. About 10ml of venous blood was collected in sterile syringes and distributed as thus: about 5ml was inserted into plastic EDTA tubes, to be used for thick smears and automated Complete Blood Counts (CBCs), while about 5ml was inserted into plastic dry tubes, to be used for immunoturbidimetric CRP analysis with Cobas C111\u0026reg; as a control for infection and to predict malaria severity.\u003c/p\u003e \u003cp\u003eThick smears were performed by the principal investigator with the aid of laboratory technicians at MOP, using the WHO recommendation for thick smears [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Blood for thick smears was stained with a 3% Giemsa stain on glass slides, dried for 60 mins and examined under an electrically-powered optical microscope (Optika \u0026reg;) at 100x magnification. Parasite counts were performed on thick film/200 WBCs, with results of two primary readers averaged. The parasite densities were calculated as parasite/\u0026micro;l of blood by using parasites/WBCs counted x total WBCs in a \u0026micro;l of blood.\u003c/p\u003e \u003cp\u003eBlood counts were done using an automated complete blood count (CBC) analyser (ABX Micros 60\u0026reg;), within one hour of collection. Samples for CRP analysis were analysed within two hours of collection, so no freezing was required. Samples were centrifuged in the BIOBASE \u0026reg; centrifuge at a g-force of 1006 for five minutes, then plasma was used for immunoturbidimetric analysis with the Cobas C111\u0026reg;.\u003c/p\u003e \u003cp\u003eAll CBC analyses, thick smears and CRP assays were read independently by two operators, both blinded to the final diagnosis (the diagnosis of uncomplicated or severe malaria was made by the investigators only after all the clinical and laboratory variables were available).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eQuality Control and Assessment\u003c/h2\u003e \u003cp\u003eLaboratory investigations were carried out at the Marie O Polyclinic, Douala, Cameroon. Quality control was performed daily for each parameter before analysis of patient samples. All procedures were performed according to standard guidelines and instructions from product manufacturers.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistical Analysis and Definitions\u003c/h3\u003e\n\u003cp\u003eData were entered into Epi Info Version 7, transferred to Microsoft Excel 2019 and analysed using STATA release 18. Out of the 400 admissions, 349 had complete laboratory and clinical data. Data normality of continuous variables was checked using histogram, quantile-normal plot and Shapiro-Wilk normality test and summarized as mean (standard deviation) or median (interquartile range) as appropriate; categorical variables, and variables dichotomised or discretised based on predetermined or calculated cut-offs, were presented as frequency and percentage. Standard definitions were used for anaemia [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], thrombocytopenia [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], leukopenia, neutropenia, lymphopenia and leucocytosis [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The outcome variable here was the final diagnosis - that is, uncomplicated or severe malaria, as defined by the WHO criteria [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Comparison of haematological parameters between uncomplicated and severe malaria cases was made using two-sample t-test, rank-sum test or chi-square test as appropriate.\u003c/p\u003e \u003cp\u003eMultivariable logistic regression models were then constructed to find the most suitable predictors of uncomplicated and severe malaria. Haematological count variables, as well as C-reactive protein (CRP) level and parasitaemia level, were each heavily right skewed and were therefore transformed to natural logarithms, rendering a more symmetrical distribution, before entering into logistic regression models. Subsequently, the variables significantly contributing to the fit of the model were discretised and the model refit. As per the STARD guidelines, the discriminant ability of each constructed logistic regression model was evaluated based on the Area Under the Curve (AUC) of the Receiver Operating Curve (ROC). Owing to some patients having repeat admissions, mixed effects logistic models were initially constructed in which patient study identification number (id) was considered as the random element. However, to obtain ROC curves, logistic models were subsequently used in which adjustment was made for the repeated admissions using the sandwich robust variance estimator based on clustering on patient study id. The two types of model were compared for any inconsistency. A multivariable Firth logistic model was used to estimate odds ratios of significant variables when used as predictors of severe malaria. A feasible set of criteria that could be applied in practice for discriminating severe and uncomplicated malaria among populations similar to that in the current study was then inferred from the modelling.\u003c/p\u003e \u003cp\u003eStatistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and Clinical Characteristics\u003c/h2\u003e \u003cp\u003eA total of 400 patient admissions aged over 15 years and with fever were enrolled in the study. Fifty-one (12.75%) were excluded: thirty-four (8.5%) due to incomplete laboratory data, fifteen (3.75%) who subsequently required antibiotics for symptoms to resolve, and two (0.5%) who were found to be pregnant. The remaining 349 patient admissions (87.25%) had complete clinical and laboratory data, were malaria-positive and recovered completely after antimalarials alone, confirming malaria monoinfection. Forty-one patients were admitted on more than one occasion, one of whom had 3 admissions. Among overall admissions, the mean age was 33 years (range 16\u0026ndash;89 years) and women accounted for 50.1%. The most frequent highest febrile peak was 38.7\u003csup\u003eo\u003c/sup\u003eC, while the median duration of fever was three days. Patients presented in all thirteen months of the study (year-round), but the months with the lowest and highest numbers of malaria patients were March 2023 and March 2024 (10 and 14 cases respectively) and September and December 2023 and January 2024 (43, 40, and 40 cases respectively). More than half (65.0%) of the patients arrived at the hospital having already taken antimalarials. A significant portion of patients had severe malaria (43.3%). Males accounted for a higher proportion of severe cases, but there were no significant differences across groups in age, duration of fever, highest febrile peak, antimalarials having been taken, haemoglobin, haematocrit, mean corpuscular haemoglobin concentration (MCHC) or mean corpuscular volume (MCV), or in anaemia. Significant differences were evident in white blood cell and platelet counts, parasitaemia, C-reactive protein value and mean corpuscular haemoglobin (MCH), as indicated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline variables of malaria cases\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevel or unit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;349\u003c/p\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUncomplicated\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;198\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;151\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e174 (49.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87 (43.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e87 (57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyears\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.1 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.3 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.9 (13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.781\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u0026ndash;25\u003c/p\u003e \u003cp\u003e26\u0026ndash;35\u003c/p\u003e \u003cp\u003e36\u0026ndash;45\u003c/p\u003e \u003cp\u003e46\u0026ndash;55\u003c/p\u003e \u003cp\u003eOver 56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (30.1)\u003c/p\u003e \u003cp\u003e98 (28.1)\u003c/p\u003e \u003cp\u003e90 25.8)\u003c/p\u003e \u003cp\u003e39 (17.2)\u003c/p\u003e \u003cp\u003e17 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52 (26.3)\u003c/p\u003e \u003cp\u003e63 (31.8)\u003c/p\u003e \u003cp\u003e50 (25.3)\u003c/p\u003e \u003cp\u003e26 (13.1)\u003c/p\u003e \u003cp\u003e7 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53 (35.1)\u003c/p\u003e \u003cp\u003e35 (23.2)\u003c/p\u003e \u003cp\u003e40 (26.5)\u003c/p\u003e \u003cp\u003e13 (8.6)\u003c/p\u003e \u003cp\u003e10 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of fever (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDays\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.0 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.745\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2 days\u003c/p\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e148 (42.4)\u003c/p\u003e \u003cp\u003e201 (57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85 (42.9)\u003c/p\u003e \u003cp\u003e113 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63 41.7)\u003c/p\u003e \u003cp\u003e88 (58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.821\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHighest febrile peak (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003csup\u003eo\u003c/sup\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.0 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.9 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.0 (0.7))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntimalarials received prior to admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e227 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e135 (68.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92 (60.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.159\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eg/dl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.7 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.6 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.8 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematocrit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.2 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.1 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.3 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epg/cell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.1 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.9 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.5 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eg/dl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.2 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.1 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.3 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.481\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efl/cell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85.4 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.7 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86.2 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeucocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecells/\u0026micro;l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4390\u003c/p\u003e \u003cp\u003e[3450, 5390]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4725\u003c/p\u003e \u003cp\u003e[4020, 5530]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3720\u003c/p\u003e \u003cp\u003e[2890, 5000]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecells/\u0026micro;l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2910 [2020, 3790]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3055 [2400, 3930]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2330 [1650, 3440]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecells/\u0026micro;l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e780 [550, 1090]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e850 [610, 1190]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e680 [480, 970]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecells/\u0026micro;l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e480 [290, 670]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e500 [330, 650]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e410 [240, 720]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eplatelets/\u0026micro;l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e135000 [107000,\u003c/p\u003e \u003cp\u003e(169000]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e154000 [128000, 194000]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103000 [86000, 135000]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParasitaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTPF/mm\u003csup\u003e3,\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16200 [11300, 18620]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13950 [10030, 17340]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18370 [15060, 21300]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emg/l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.6 [28.7, 97.4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.2 [19.8, 65.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e96.0 [54.8, 156.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e147 (42.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.931\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (26.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69 (45.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeucocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.126\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophilia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e240 (68.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e123 (62.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e117 (77,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e221 (63.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93 (47.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e128 (84.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeucocyte level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eleukopenia\u003c/p\u003e \u003cp\u003enormal\u003c/p\u003e \u003cp\u003eleucocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (26.4)\u003c/p\u003e \u003cp\u003e254 (72.8)\u003c/p\u003e \u003cp\u003e3 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (11.6)\u003c/p\u003e \u003cp\u003e173 (89.4)\u003c/p\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69 (45.7)\u003c/p\u003e \u003cp\u003e81 (53.6)\u003c/p\u003e \u003cp\u003e1 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eneutropenia\u003c/p\u003e \u003cp\u003enormal\u003c/p\u003e \u003cp\u003eneutrophilia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (10.9)\u003c/p\u003e \u003cp\u003e308 (88.2)\u003c/p\u003e \u003cp\u003e3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (3.5)\u003c/p\u003e \u003cp\u003e189 (95.5)\u003c/p\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (20.5)\u003c/p\u003e \u003cp\u003e119 (78.8)\u003c/p\u003e \u003cp\u003e1 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eValues expressed as mean (SD), median [IQR] or number (column %). P-values from t-test, rank-sum test, and chi-square test, respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eHaemoglobin\u003c/h2\u003e \u003cp\u003eAnaemia was defined as haemoglobin (Hb) level\u0026thinsp;\u0026lt;\u0026thinsp;12g/dl for women and \u0026lt;\u0026thinsp;13g/dl for men and further classified as severe if \u0026lt;7g/dl. As per the WHO criteria for severity, patients with Hb \u0026lt;7g/dl and confirmed parasitaemia were classified as severe malaria. Overall, 49.86% of patients had anaemia; of those, 91/147 were female and 56/147 were male. Hb counts tended to increase with age. Mean Hb values were similar in the uncomplicated and severe malaria group (12.6 and 12.8g/dl, respectively). Almost all cases of anaemia were mild, in both uncomplicated and severe malaria; and in both groups, a larger proportion of men were anaemic than women (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Only one patient was found with severe anaemia, and they also had severe malaria.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSeverity of anaemia according to final diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAnaemia severity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eUncomplicated\u003c/p\u003e \u003cp\u003eMalaria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eSevere malaria\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;174\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;175\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;87\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;111\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;87\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;64\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo anaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118/174 (67.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84/175 (48.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60/87 (69.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55/111\u003c/p\u003e \u003cp\u003e(49.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e58/87 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29/64 (45.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild anaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e143/349 (41.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e83/198 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e60/151 (39.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate anaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e4/349 (0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1/198 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e3/151 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere anaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1/349 (0.003)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1/151 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHaemoglobin levels (g/dl): No anaemia\u0026thinsp;\u0026ge;\u0026thinsp;13 in men, \u0026ge;\u0026thinsp;12 in women; mild anaemia\u0026thinsp;\u0026ge;\u0026thinsp;9, \u0026lt;13 in men, Hb\u0026thinsp;\u0026ge;\u0026thinsp;9, \u0026lt;12 women); moderate anaemia\u0026thinsp;\u0026ge;\u0026thinsp;7, \u0026lt;9; severe anaemia\u0026thinsp;\u0026lt;\u0026thinsp;7.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePlatelets\u003c/h2\u003e \u003cp\u003eThrombocytopenia was defined as platelet count less than 150,000 cells/\u0026micro;l and further classified as severe if the platelet count was less than 50,000 cells/\u0026micro;l. The median platelet count in the severe malaria group was significantly lower than the uncomplicated malaria group (103,000 vs 154,000; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Thrombocytopenia was found in 84.8% of patients with severe malaria as opposed to 47.0% of those with uncomplicated malaria. Thrombocytopaenia was mild in all cases of uncomplicated malaria. Most cases of low platelets with severe malaria were moderate, with only 1/221 having severe thrombocytopaenia (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of thrombocyte counts according to final diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia severity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (%)\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;349\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUncomplicated malaria\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;198\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere malaria\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;151\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (36.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (53.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (15.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93 (47.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (39.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePlatelet counts (cells/ \u0026micro;l): No thrombocytopenia\u0026thinsp;\u0026ge;\u0026thinsp;150,000: Mild thrombocytopenia\u0026thinsp;\u0026ge;\u0026thinsp;100,000\u0026thinsp;\u0026lt;\u0026thinsp;150,000; Moderate thrombocytopenia\u0026thinsp;\u0026ge;\u0026thinsp;50,000\u0026thinsp;\u0026lt;\u0026thinsp;100,000; Severe thrombocytopenia\u0026thinsp;\u0026lt;\u0026thinsp;50,000.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eWhite blood cells\u003c/h2\u003e \u003cp\u003eThere were alterations in the leukogram profile in terms of total white blood cell count, neutrophil and lymphocyte counts. Eosinophil, basophil and monocyte counts were largely within normal levels, and so were not included in the analysis. Leucocytosis was defined as a total leukocyte count greater than 10,000 cells/\u0026micro;l, neutrophilia as absolute neutrophil counts greater than 8000 cells/\u0026micro;l, leukopenia as leukocyte counts less than 3500 cells/\u0026micro;l, neutropenia as absolute neutrophil counts less than 1500 cells/\u0026micro;l and lymphopenia as lymphocyte counts less than 1000 cells/\u0026micro;l.\u003c/p\u003e \u003cp\u003eMedian leukocyte levels were significantly lower in the severe malaria group than the uncomplicated malaria group (3720 vs 4725 cells/\u0026micro;l; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), though both medians were within the normal leukocyte range for adults. Most (72.8%) adults with malaria had normal leukocyte counts, with leukopenia being the more common alteration (26.4%), and leucocytosis being extremely rare (0.7%). Leukopenia was significantly more frequent among the severe malaria group than the uncomplicated malaria group (45.7% vs 11.6%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Leukopenia was further classified as mild if\u0026thinsp;\u0026ge;\u0026thinsp;2500 and \u0026lt;\u0026thinsp;3500; moderate if\u0026thinsp;\u0026ge;\u0026thinsp;1500 and \u0026lt;\u0026thinsp;2500; and severe if\u0026thinsp;\u0026lt;\u0026thinsp;1500 (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNeutrophil counts displayed a similar trend, with median values significantly lower in the severe malaria group (2330 vs 3055 cells/\u0026micro;l; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but with medians both within normal ranges. The majority of patients (310/349) had normal neutrophil counts. Neutropenia was found in 38/349, while neutrophilia was present in 3/349. A significant majority of those with neutropenia had severe malaria (31/38 vs 7/38; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), (supplemental Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe median lymphocyte count was lower than the normal adult range in both the severe and uncomplicated malaria groups, though it was significantly lower in the group with severe malaria (680 vs 850 cells/\u0026micro;l; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). A large proportion of all malaria patients had lymphopenia (68.8%), regardless of whether it was uncomplicated or severe (123/198 vs 117/151; p\u0026thinsp;=\u0026thinsp;0.002), (supplemental Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of leukocyte counts according to final diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukopenia severity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (%)\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;349\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUncomplicated malaria\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;198\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere malaria\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;151\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo leukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e257 (73.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175 (88.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82 (54.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild leukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (22.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 (35.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate leukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (8.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere leukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eLeukopenia (in cells/\u0026micro;l): \u0026gt;3500 normal; \u0026ge;2500 and \u0026lt;\u0026thinsp;3500 mild; \u0026ge;1500 and \u0026lt;\u0026thinsp;2500 moderate; \u0026lt;1500 severe\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eCRP Levels\u003c/h2\u003e \u003cp\u003eNearly all malaria patients (346/349) had \u0026lsquo;positive\u0026rsquo; CRP levels; that is, CRP\u0026gt;5mg/L. The median values of CRP were significantly higher in severe malaria than in uncomplicated malaria (96.0 vs 38.2mg/L; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The distribution of CRP levels following the ranges most frequently used in clinical settings and stratified by outcome is indicated in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of CRP levels according to final diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;349\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUncomplicated malaria N\u0026thinsp;=\u0026thinsp;198\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere malaria\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;151\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (9.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e41\u0026ndash;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145 (41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (40.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64 (42.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (22.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eParasite Density\u003c/h2\u003e \u003cp\u003eParasitaemia (in trophozoites of \u003cem\u003ePlasmodium falciparum\u003c/em\u003e/\u0026micro;l -TPF/\u0026micro;l) ranged from 5,020 to 84,040. Parasite count medians were significantly higher in the group with severe malaria than in the uncomplicated malaria group (18,370 vs 13,950 TPF/\u0026micro;l), though both were well below the WHO threshold for severe malaria. Parasite densities were unaffected by age (correlation coefficient\u0026thinsp;\u0026minus;\u0026thinsp;0.0543, p\u0026thinsp;=\u0026thinsp;0.312) and gender (p\u0026thinsp;=\u0026thinsp;0.460). Parasitaemia was positively correlated with the highest febrile peak (correlation coefficient 0.1909, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but not with the duration of fever (correlation coefficient 0.0703, p\u0026thinsp;=\u0026thinsp;0.190) or not having taken antimalarials before presenting to the hospital (p\u0026thinsp;=\u0026thinsp;0.796).\u003c/p\u003e \u003cp\u003eThere was no significant relationship between parasite counts and haemoglobin levels (correlation coefficient\u0026thinsp;\u0026minus;\u0026thinsp;0.0173, p\u0026thinsp;=\u0026thinsp;0.740). Parasite density was negatively correlated with platelet counts (correlation coefficient\u0026thinsp;\u0026minus;\u0026thinsp;0.3282, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no significant correlation between parasite densities and leukocyte count (correlation coefficient 0.0306, p\u0026thinsp;=\u0026thinsp;0.569), absolute neutrophil count (correlation coefficient 0.0913, p\u0026thinsp;=\u0026thinsp;0.088) or lymphocyte count (correlation coefficient\u0026thinsp;\u0026minus;\u0026thinsp;0.1020, p\u0026thinsp;=\u0026thinsp;0.057). There was a positive correlation between CRP levels and parasitaemia (correlation coefficient 0.4084, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The relationship between parasitaemia and the various haematological parameters is illustrated in supplemental Fig.\u0026nbsp;2 and supplemental Fig.\u0026nbsp;3.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eDiagnostic values of haematological parameters\u003c/h2\u003e \u003cp\u003eThe haematological parameters which emerged as having the most significant effect on patient outcomes were leukocyte counts, neutrophil counts, lymphocyte counts, platelet counts and CRP levels. As leukocyte count, platelet count and CRP levels could be stratified by grade (Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), they were fitted into a multivariable Firth logistic model to estimate their odds ratios (OR) when used as predictors of severe malaria (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Patients with moderate leukopenia had 150 times, with moderate thrombocytopaenia 600 times, and with CRP levels above 100mg/L 170 times (OR) higher odds of having severe malaria. Logarithmic transformation of these odds ratios yielded numerical coefficients. Scores were then allocated to the various levels of each predictor in approximately the same ratio as their coefficients (scores for thrombocytopenia grades were 0, 1 and 10; for leukopenia 0, 4 and 8; and for CRP levels 0, 3, 5 and 8). For each patient, the scores were summed to give a predictor score. A logistic regression model was used to examine the predictive ability of this score, following which a ROC curve (supplemental Fig.\u0026nbsp;4) and a predictor graph based on the patient sample in which 43% of patients had severe malaria (supplemental Fig.\u0026nbsp;5) were constructed. The AUROC with this prediction model was 94.02%. Suitable cut-offs at approximate tertiles are illustrated in supplemental Fig.\u0026nbsp;5, whereby scores less than 5 (level 1) are associated with a low probability for severe malaria, scores of 6\u0026ndash;9 (level 2) with an intermediate probability, and scores of 10 or more (level 3) with a high probability for severe malaria. Using a cut-point between level 2 and 3 gives a sensitivity of 66%, specificity of 99%, a positive predictive value of 0.98, and a negative predictive value of 0.79 (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOdds ratios, coefficients and score values of haematological parameters as predictors of severe malaria.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCrude OR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eWald P -value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLR P-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCoefficient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eScore\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.67, 5.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.92, 3.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.084\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.635\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emoderate*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e615.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.7, 10293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e612.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28.8, 13028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e6.417\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.85, 8.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.45, 38.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.755\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emoderate#\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.90, 1115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e150.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.86, 3304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP level (mg/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;20, \u0026le;\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.89, 7.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.12, 27.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.720\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;40, \u0026le;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.84, 18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.37, 87.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.975\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.3, 158.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e172.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33.1, 902.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003eNote: * 1 case is severe thrombocytopenia; # 2 cases are severe leukopenia.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePerformance of predictive score derived from the logistic model with two cut-points.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePredictive score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUncomplicated malaria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere malaria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(col %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLikelihood ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eProbability of severe malaria *\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 or over\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e102 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.98 (0.95, 1.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u0026ndash;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e142 (40.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.32 (0.24, 0.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 or less\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e105 (30.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.06 (0.01, 0.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e349\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e* Given a prior probability of 0.43\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study described various haematological parameters among malaria-positive immunocompetent adults at a tertiary hospital in urban Cameroon, and confirms that all the currently known haematological abnormalities of \u003cem\u003ePlasmodium\u003c/em\u003e infection reported in at-risk groups are prevalent in immunocompetent adults, both in uncomplicated and severe disease. The abnormalities previously cited include changes in haemoglobin levels [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], leucocyte counts [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], platelet counts [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21 CR22\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and CRP levels [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eErythrocytes are the primary targets of \u003cem\u003ePlasmodium\u003c/em\u003e merozoites in active disease, and thus unsurprisingly, anaemia is one of the most commonly reported complications of malaria [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. A myriad of pathophysiological processes have been implicated: intravascular and tissular haemolysis, splenic sequestration and dysregulations of bone marrow erythropoiesis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Reported prevalence of anaemia in at-risk groups ranges from around 40\u0026ndash;60% in pregnant women [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] to 60%-65% in children [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], with the anaemia being severe in up to 5% of cases. By contrast, haemoglobin values in this study were normal for the majority (68.7%) of study participants. Nearly all (143/147) of the anaemic adults had mild anaemia, and only one patient (0.7%) had severe anaemia. The underlying issue in reporting anaemia prevalence with malaria in endemic areas is the presence of several confounding variables like haemoglobinopathies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], poor nutritional status [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] and other asymptomatic infections, notably helminthic infestations, that can cause microcytic anaemia [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This might explain why the prevalence of anaemia was much lower in a study focusing on immunocompetent adults, as most of these conditions do not significantly affect haemoglobin levels in healthy adults [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Also, this study was conducted within a tertiary hospital in an urban region where nutritional and socioeconomic concerns were minimal. This might suggest that in endemic zones, malaria is a relatively infrequent cause of anaemia by itself; and findings of moderate or severe anaemia in a febrile adult should prompt investigation for other causes like immunodeficiency, haemoglobinopathies or poor nutritional status.\u003c/p\u003e \u003cp\u003eAnomalies in both platelet count and function are known features of malarial disease. This study focused on platelet count derangements. Thrombocytopenia was found in 63.3% of malaria patients overall, and was the only parameter that was significantly inversely correlated with parasite density (Fig.\u0026nbsp;2). In addition, the percentage of adults with severe malaria that had thrombocytopenia was 84.8%, as opposed to 47.0% with uncomplicated malaria. However, only one patient presented with severe thrombocytopenia, and all cases of thrombocytopenia in uncomplicated malaria were mild. These findings would seem to suggest that platelet counts might be predictors of disease burden and severity, and corroborate findings in previous studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The mechanisms of platelet count reduction in malaria are varied: splenic sequestration [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], consumption in abnormal bleeding processes like Disseminated Intravascular Coagulation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and most importantly, peripheral destruction as agents of defence against plasmodial parasites [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These would support the observation of decreasing platelet counts as parasitaemia increased in our study. An interesting phenomenon is that parasite densities in this study were all below the threshold of severity as defined by the WHO (100,000TPF/\u0026micro;l, or \u0026gt;\u0026thinsp;10% parasitized erythrocytes) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], which could either mean that adults in \u003cem\u003efalciparum\u003c/em\u003e-endemic zones have extremely efficient platelets that destroy parasites before they can reach high densities, or that other immune mechanisms of healthy adults in endemic zones prevent high parasitaemia, and thus limit the amount of severe thrombocytopenia (and perhaps severe disease) that would otherwise be seen.\u003c/p\u003e \u003cp\u003eThe findings of a 63.3% prevalence of thrombocytopenia with a 0.7% occurrence of severe thrombocytopenia are at odds with those in a study of malaria patients (both adult and paediatric) in Sri Lanka [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], where the prevalence of thrombocytopenia was found to be 86%, and severe thrombocytopenia was found in 18.2% of patients. This increased risk of severe thrombocytopenia might be related to the inclusion of paediatric patients in the study, as platelet count reports were not stratified by age; however, in a large study in Papua, severe thrombocytopenia was found among nearly 6% of malaria patients, especially those with \u003cem\u003efalciparum\u003c/em\u003e malaria, even when adjusting for age [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, this study was reported in a zone where mixed infections were frequent, and thus endemicity to \u003cem\u003efalciparum\u003c/em\u003e malaria cannot be assumed. In all these comparable studies, there is also the fact that steps were not taken to eliminate mixed infections- malaria is frequently found in association with other viral and bacterial illnesses in tropical settings [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], many of which are known to cause thrombocytopenia.\u003c/p\u003e \u003cp\u003eLeukocyte counts in this study were normal for the vast majority of patients (72.8%), with leukopenia being the more common alteration (26.4%) and leucocytosis found very rarely (0.7%). These values are similar to those of a study involving both adults and children in Colombia [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], where leukopenia was found in 18% of malaria patients while leucocytosis emerged in only 4%. The higher value of leucocytosis is likely related to the inclusion of children in the study, as leucocytosis is frequent in febrile children and the possibility of co-infection was not excluded. Leukopenia is especially associated with \u003cem\u003efalciparum\u003c/em\u003e malaria- an experimental study found a 12% prevalence of leukopenia and a 9% prevalence of severe leukopenia in volunteers inoculated with \u003cem\u003eP. falciparum\u003c/em\u003e in England [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], compared to the 0.6% prevalence in our study. The difference in the prevalence of severe leukopenia is likely explained by the fact that the volunteers in the experimental study lacked the natural immunity present in adults in endemic zones. The occurrence of leukopenia in Plasmodium infection has many proposed mechanisms, with splenic sequestration being the most favoured explanation, especially given the rapid recovery that usually occurs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, there is a lot of recent evidence pointing to plasmodial ability to significantly activate inflammatory pathways [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], which would lead to white cell activation and consumption. This is especially significant in severe disease- 75.0% of those with leukopenia had severe malaria in this study, and patients with leukopenia were up to 150 times (OR) more likely to have severe malaria.\u003c/p\u003e \u003cp\u003eWith the white cell differentials, neutrophil counts displayed a similar trend- most patients (88.8%) had normal counts while neutropenia was more common (10.3%) and neutrophilia was rare (0.9%). Most (83.3%) of the neutropenic patients had severe malaria. These findings are consistent with similar studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and are explained by the same mechanisms of splenic pooling and inflammatory cascade that have been proposed for leukopenia. Lymphopenia, on the other hand, was the most frequent leukogram alteration overall, with nearly 70% of all malaria patients being lymphopenic regardless of severity, and with the median lymphocyte count well below the normal range for adults (850 cells/\u0026micro;l in uncomplicated malaria and 680 cells//\u0026micro;l in severe malaria). This is similar to findings in other studies- it was the most frequent alteration in a Colombian study, with a prevalence of 54% [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]; with \u003cem\u003efalciparum\u003c/em\u003e malaria, in particular, it was found in 63% of cases of imported malaria in the United Kingdom and was the most common alteration found [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The origin of lymphopenia in such an acute disease is still being elucidated; however, proposed mechanisms include splenic sequestration [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], redistribution into more active tissues [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and dysleucopoiesis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Lymphopenia in many clinical contexts raises concern for transient immunodeficiency and thus more severe disease and complications; in our study, lymphocytes counts were significantly lower in severe malaria than uncomplicated infection (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and it was found to be a significant predictor in univariable analysis. This was similar to findings in the Colombian study, where lymphopenia was associated with severity of disease [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, including lymphopenia in the model already consisting of thrombocytopenia, leukopenia and CRP levels did not appreciably improve the predictive ability.\u003c/p\u003e \u003cp\u003eThis study demonstrates that moderate thrombocytopenia (OR\u0026thinsp;=\u0026thinsp;612.4), moderate leukopenia (OR\u0026thinsp;=\u0026thinsp;150.5), and CRP levels greater than 100mg/L (OR\u0026thinsp;=\u0026thinsp;172.8) are the most reliable haematological predictors of malaria outcome in healthy adults in endemic settings. The scoring system proposed in this study has an AUROC of 0.94, with a sensitivity of 66% and a specificity of nearly 100% when a cut-off between level 2 (intermediate probability) and level 3 (high probability) is used. Comparable studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] have mainly evaluated the predictive power of the haematological variables for distinguishing non-infected from malarial patients. However, malaria remains a leading cause of significant morbidity and mortality even among healthy adults in endemic regions- with the proportion of malaria deaths in children under five decreasing between 2010 and 2021 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], implying that more older children and adults are succumbing to severe disease. The main challenge in diagnosing severe malaria in adults is that many of the WHO criteria for severity like severe anaemia and severe thrombocytopaenia are very late findings in older people, as shown in this study. Therefore, in a malaria endemic region, adults (febrile or not) who are at risk of malaria and whose haematological parameters indicate an intermediate or high probability of severe malaria using the proposed scoring system in this study should be re-evaluated for malaria (and possibly receive parenteral antimalarials) even if initial thick smears or RDTs are negative, unless there is a confirmed alternative diagnosis that explains the haematological alterations.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e – Area Under the Curve\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eAUROC\u003c/strong\u003e – Area Under the Receiver Operating Characteristic Curve\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eCBC\u003c/strong\u003e – Complete Blood Count(s)\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eCI\u003c/strong\u003e – Confidence Interval\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eCRP\u003c/strong\u003e – C‑Reactive Protein\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eEDTA\u003c/strong\u003e – Ethylenediaminetetraacetic Acid\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eHb\u003c/strong\u003e – Haemoglobin\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eHIV\u003c/strong\u003e – Human Immunodeficiency Virus\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eIQR\u003c/strong\u003e – Interquartile Range\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eMCV\u003c/strong\u003e – Mean Corpuscular Volume\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eMCH\u003c/strong\u003e – Mean Corpuscular Haemoglobin\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eMCHC\u003c/strong\u003e – Mean Corpuscular Haemoglobin Concentration\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eMOP\u003c/strong\u003e – Marie O Polyclinic\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eMW\u003c/strong\u003e – Medical Ward\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eOPD\u003c/strong\u003e – Out Patient Department\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eOR\u003c/strong\u003e – Odds Ratio\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eRDT\u003c/strong\u003e – Rapid Diagnostic Test\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eROC\u003c/strong\u003e – Receiver Operating Characteristic (curve)\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eSD\u003c/strong\u003e – Standard Deviation\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eSTARD\u003c/strong\u003e – Standards for Reporting Diagnostic Accuracy Studies\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eTPF/μl\u003c/strong\u003e – Trophozoites of\u0026nbsp;\u003cem\u003ePlasmodium falciparum\u003c/em\u003e per microlitre\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eWBC\u003c/strong\u003e – White Blood Cell(s)\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eWHO\u003c/strong\u003e – World Health Organization\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe study was conducted only after ethical and administrative clearance had been obtained from both the University of Douala (No.3610 IEC-UD/04/2024/M) and the Review Board of MOP. All participants signed a consent form explaining the details of the study, including risks and benefits, before being included in the study, in accordance with the Declaration of Helsinki. Autonomy was respected, as participants had the right to withdraw from the study at any time. Risks to participants were minimized to the best of our ability. The confidentiality of patients was maintained by using serial numbers rather than names on questionnaires. Privacy was maintained at all times. Samples were obtained following recommended guidelines and coded to ensure anonymity.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eNot applicable. This study did not include any individual‑level identifiable data, images, or case details. All data were analysed and reported in aggregate form, and written informed consent to participate was obtained from all participants prior to enrolment, in accordance with ethical approval.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe dataset and materials used for this study are freely available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe funding from this study was derived completely from the authors. All the researchers are completely independent from funders.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAuthors’ Contributions\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eYN was the principal investigator, assisted with study conceptualisation and design, helped with data collection and prepared the initial and final drafts of the manuscript. AG assisted with study design, performed most of the data analysis and helped revise the manuscript. SG assisted with data collection and referencing, and helped revise the manuscript. MN conceptualised the study and helped design it, and also helped revise the manuscript.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe authors would like to acknowledge the contributions of the laboratory staff of Marie O Polyclinic, including Tchio Emmanuel Chrispo, Nyemb Teclaire, Legnida Hilaire, Dimo Towa Clovis and Kalat Tchio Chantal, for their help with the laboratory aspects of this study. Special thanks to Dr Ngoulla Roger and Dr Sylvie Ngoubeyou of Marie O Polyclinic for their advice and assistance.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWhite NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malar Lancet. 2014;383:723\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWHO. World malaria report 2022. Geneva: World Health Organization; 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhite NJ. 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Am J Trop Med Hyg. 1998;59(6):859.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9177783/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9177783/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe haematological profile of children and at-risk groups of malaria patients in endemic areas has been extensively studied, but those parameters have not been thoroughly evaluated in immunocompetent adults with malaria.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eThis was a cross-sectional study at Marie O Polyclinic which included all patients over 15 years who were symptomatic and had \u003cem\u003ePlasmodium falciparum\u003c/em\u003e infection confirmed on microscopy. Consenting patients received complete clinical examinations, then venous blood samples were collected and analysed for Complete Blood Counts and C-Reactive Protein.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSamples of 349 adults were retained. 147/349 had anaemia, 221/349 had thrombocytopaenia and 261/349 had at least one alteration of their leukogram profile. The most frequent alteration of the white blood cells was lymphopenia (240/349). All but three patients with malaria had positive CRP values, that is, CRP\u0026thinsp;\u0026gt;\u0026thinsp;5mg/L. Parasitaemia (in trophozoites of \u003cem\u003ePlasmodium falciparum\u003c/em\u003e/\u0026micro;l -TPF/\u0026micro;l) ranged from 5,020 to 84,040. Multivariable logistic regression showed that the presence of moderate thrombocytopenia, moderate leukopenia and CRP levels above 100 mg/L were the best predictors of severe malaria. A scoring system was developed using these variables, in which scores less than 5 (level 1) were associated with a low probability for severe malaria, scores of 6\u0026ndash;9 (level 2) with an intermediate probability, and scores of 10 or more (level 3) with a high probability for severe malaria. A predictor graph based on the patient sample in which 43% of patients had severe malaria and a ROC curve were constructed. The AUROC with this prediction model was 94%. Using a cut-point between level 2 and 3 on the predictor graph gave sensitivity of 66%, specificity of 99%, a positive predictive value of 0.98, and a negative predictive value of 0.79 for severe malaria.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eComplete blood counts and CRP values can predict severe malaria accurately independently of currently established clinical and paraclinical criteria.\u003c/p\u003e","manuscriptTitle":"Predictive values of haematological parameters in Plasmodium falciparum infection in immunocompetent adults at an urban hospital in Douala","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-14 12:07:13","doi":"10.21203/rs.3.rs-9177783/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"292056082850831845485571812098965162407","date":"2026-05-12T09:29:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"79358094543697213515859115479670474359","date":"2026-05-07T12:40:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-05T12:12:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-04T10:09:02+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-10T13:53:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-10T13:31:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2026-04-10T12:04:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"de63a5cd-3249-44bb-be2c-d1ea765828ca","owner":[],"postedDate":"May 14th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"292056082850831845485571812098965162407","date":"2026-05-12T09:29:27+00:00","index":68,"fulltext":""},{"type":"reviewerAgreed","content":"79358094543697213515859115479670474359","date":"2026-05-07T12:40:55+00:00","index":48,"fulltext":""},{"type":"reviewersInvited","content":"30","date":"2026-05-05T12:12:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-04T10:09:02+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T12:07:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-14 12:07:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9177783","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9177783","identity":"rs-9177783","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}