Haematological parameters of Plasmodium falciparum infection in immunocompetent adults at a tertiary care centre in Douala

Haematological parameters of Plasmodium falciparum infection in immunocompetent adults at a tertiary care centre 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 Haematological parameters of Plasmodium falciparum infection in immunocompetent adults at a tertiary care centre in Douala Yembu Ngwengi, Alan Geater, Stephane Nguembu, Martine Nida This is a preprint; it has not been peer reviewed by a journal.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-8401521/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted 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 (CRP). 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 Receiver Operating Characteristic (ROC) curve were constructed. The Area under the ROC curve (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. Clinical trial number: not applicable. malaria anaemia leukopenia lymphopenia thrombocytopenia CRP Figures Figure 1 Figure 2 Figure 3 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 six 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. More research, especially in areas of heavy falciparum infection, is needed to further clarify the relationship between leukogram alterations 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]. 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 Human Immunodeficiency Virus- HIV infection (whether on treatment or not and regardless of Cluster of Differentiation 4- 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 [31]. 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. 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 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. The final diagnosis was based on clinical findings and results of investigations. 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 Ethylene Diamine Tetra-Acetate- 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 World Heath Organisation (WHO) recommendation for thick smears [32]. Blood for thick smears was stained with the Giemsa stain on glass slides 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, thrombocytopenia, leukopenia, neutropenia, lymphopenia and leucocytosis. 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 Standards of Reporting for Diagnostic Accuracy (STARD) guidelines, the discriminant ability of each constructed logistic regression model was evaluated based on the Area Under the Receiver Operating Curve (AUROC). 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 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 < 7 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 (see 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), (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), (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 Figs. 2 and 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 (Fig. 4 ) and a predictor graph based on the patient sample in which 43% of patients had severe malaria (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 CRP: C Reactive Protein TPF/μl: Trophozoites of Plasmodium falciparum /μl ROC curve: Receiver Operating Characteristic curve AUROC: Area under the Receiver Operating Characteristic curve P. falciparum: Plasmodium falciparum P. vivax: Plasmodium vivax MOP: Marie O Polyclinic Medical Ward: MW Out Patient Department: OPD RDT: Rapid Diagnostic Test HIV: Human Immunodeficiency Virus CD4: Cluster of Differentiation 4 EDTA: Ethylene Diamine Tetra-Acetate WHO: World Health Organisation CBC: Complete Blood Count STARD: Standards of Reporting for Diagnostic Accuracy MCV: Mean Corpuscular Volume MCH: Mean Corpuscular Haemoglobin MCHC: Mean Corpuscular Haemoglobin Concentration OR: Odds Ratios CI: Confidence Interval 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 (No.0052 IEC-MOP/03/2024/L). All participants signed a consent form explaining the details of the study, including risks and benefits, before being included in the study. 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 Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors declare that they have no competing interests. Funding The funding from this study was derived completely from the authors. All the researchers are completely independent from funders. Authors’ Contributions YN contributed to the study conception and design, was the main author involved in data collection, drafted the original manuscript and revised version of the manuscript. AG supported study design, was the main data analyst, and reviewed the original manuscript. SG contributed to study conception and design, supported data collection and reviewed the original manuscript. MN was the main author involved in study conception and design and reviewed the original 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. Malaria. 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Doherty, “Short report: hematologic changes in acute, imported Plasmodium falciparum malaria,” The American Journal of Tropical Medicine and Hygiene, vol. 59, no. 6, p. 859, 1998. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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01:01:42","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":131674,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8401521/v1/1dc7f56ef613c82996351241.html"},{"id":99192080,"identity":"106eea66-cef5-4a17-99a2-8d78e840880f","added_by":"auto","created_at":"2025-12-30 01:01:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56900,"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-8401521/v1/4a1a284e740d757baafbf8b8.png"},{"id":99319228,"identity":"0cc63301-c403-4f10-a07c-4dc580a8570c","added_by":"auto","created_at":"2025-12-31 16:36:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":205657,"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-8401521/v1/7541863fbba12a020d0497c9.png"},{"id":99317202,"identity":"8b97d05a-8d05-42a4-8a33-9282d96a2e15","added_by":"auto","created_at":"2025-12-31 16:29:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":125149,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between logarithm of parasitemia (in TRF/cu.mm) and logarithm of C-reactive protein (in mg/l). Red dots = severe, blue dots = uncomplicated malaria. The estimated linear regression and 95% confidence band are shown\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8401521/v1/1ab6970c4d646c192978d516.png"},{"id":99192083,"identity":"8af3083e-122a-46c8-949c-ff57fa2ebef1","added_by":"auto","created_at":"2025-12-30 01:01:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":59554,"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-8401521/v1/ce69da80593ae3a953248d30.png"},{"id":99317212,"identity":"a4e8799d-160e-4a6d-b484-9546ef91c6a6","added_by":"auto","created_at":"2025-12-31 16:29:46","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":60413,"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-8401521/v1/a22eb78fe1f18690bcebd215.png"},{"id":104590693,"identity":"12155b23-0d42-44aa-9314-e9faa87f4ed5","added_by":"auto","created_at":"2026-03-13 16:56:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1592371,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8401521/v1/470ebdae-de81-4068-abf9-5c9e8ea45dc8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eHaematological parameters of Plasmodium falciparum infection in immunocompetent adults at a tertiary care centre in Douala\u003c/p\u003e","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 [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\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 [2]. 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 [1,3]. Malaria is, essentially, a haematological disease, and circulating \u003cem\u003efalciparum\u003c/em\u003e parasites have significant effects on all three haematological cell lines [4,5].\u003c/p\u003e \u003cp\u003eAnaemia is the most common haematological anomaly found in malaria patients, with all six species of \u003cem\u003ePlasmodium\u003c/em\u003e 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 \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 [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\u0026ndash;13], pregnant women [14\u0026ndash;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.\u003c/p\u003e \u003cp\u003eThrombocytopenia is a very frequent haematological alteration in \u003cem\u003ePlasmodium\u003c/em\u003e 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/\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 [20, 22]. 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 [20,23], 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 [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.\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 [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, \u003cem\u003eP. falciparum\u003c/em\u003e monoinfection has been shown to significantly activate inflammatory pathways [1,4,29], suggesting a possible direct link between malaria and leukogram alterations. More research, especially in areas of heavy \u003cem\u003efalciparum\u003c/em\u003e infection, is needed to further clarify the relationship between leukogram alterations 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 [30].\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 Human Immunodeficiency Virus- HIV infection (whether on treatment or not and regardless of Cluster of Differentiation 4- 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 [31]. 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\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 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. The final diagnosis was based on clinical findings and results of investigations.\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 Ethylene Diamine Tetra-Acetate- 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 World Heath Organisation (WHO) recommendation for thick smears [32]. Blood for thick smears was stained with the Giemsa stain on glass slides 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\n\u003ch3\u003eQuality Control and Assessment\u003c/h3\u003e\n\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 \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis and Definitions\u003c/h2\u003e \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, thrombocytopenia, leukopenia, neutropenia, lymphopenia and leucocytosis. 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.\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 Standards of Reporting for Diagnostic Accuracy (STARD) guidelines, the discriminant ability of each constructed logistic regression model was evaluated based on the Area Under the Receiver Operating Curve (AUROC). 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 \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" 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\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=\"Sec11\" 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\u0026thinsp;\u0026lt;\u0026thinsp;7g/dl. As per the WHO criteria for severity, patients with Hb\u0026thinsp;\u0026lt;\u0026thinsp;7 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 (see 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=\"Sec12\" 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=\"Sec13\" 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), (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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), (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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 \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" 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\u0026thinsp;\u0026gt;\u0026thinsp;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=\"Sec15\" 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 \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 \u0026minus;\u0026thinsp;0.0173, p\u0026thinsp;=\u0026thinsp;0.740). Parasite density was negatively correlated with platelet counts (correlation coefficient \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 \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 Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" 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 (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) and a predictor graph based on the patient sample in which 43% of patients had severe malaria (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) 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 \u003c/p\u003e \u003cp\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 [4\u0026ndash;6,15\u0026ndash;18], leucocyte counts [4,5,25\u0026ndash;28], platelet counts [4,5, 19\u0026ndash;23] and CRP levels [29, 34, 35].\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 [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\u0026ndash;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.\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;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). 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/\u0026micro;l, or \u0026gt;\u0026thinsp;10% parasitized erythrocytes) [33], 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 [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 \u003cem\u003efalciparum\u003c/em\u003e malaria, even when adjusting for age [23]. 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 [29], 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 [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 \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 [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.\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 [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/\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% [27]; 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 [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\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 [27]. 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 [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.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCRP: C Reactive Protein\u003c/p\u003e\n\u003cp\u003eTPF/μl: Trophozoites of \u003cem\u003ePlasmodium falciparum\u003c/em\u003e/μl\u003c/p\u003e\n\u003cp\u003eROC curve: Receiver Operating Characteristic curve\u003c/p\u003e\n\u003cp\u003eAUROC: Area under the Receiver Operating Characteristic curve\u003c/p\u003e\n\u003cp\u003eP. falciparum: Plasmodium falciparum\u003c/p\u003e\n\u003cp\u003eP. vivax: Plasmodium vivax\u003c/p\u003e\n\u003cp\u003eMOP: Marie O Polyclinic\u003c/p\u003e\n\u003cp\u003eMedical Ward: MW\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOut Patient Department: OPD\u003c/p\u003e\n\u003cp\u003eRDT: Rapid Diagnostic Test\u003c/p\u003e\n\u003cp\u003eHIV: Human Immunodeficiency Virus\u003c/p\u003e\n\u003cp\u003eCD4: Cluster of Differentiation 4\u003c/p\u003e\n\u003cp\u003eEDTA: Ethylene Diamine Tetra-Acetate\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organisation\u003c/p\u003e\n\u003cp\u003eCBC: Complete Blood Count\u003c/p\u003e\n\u003cp\u003eSTARD: Standards of Reporting for Diagnostic Accuracy\u003c/p\u003e\n\u003cp\u003eMCV: Mean Corpuscular Volume\u003c/p\u003e\n\u003cp\u003eMCH: Mean Corpuscular Haemoglobin\u003c/p\u003e\n\u003cp\u003eMCHC: Mean Corpuscular Haemoglobin Concentration\u003c/p\u003e\n\u003cp\u003eOR: Odds Ratios\u003c/p\u003e\n\u003cp\u003eCI: Confidence Interval\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and Consent to participate\u003c/strong\u003e\u003c/p\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 (No.0052 IEC-MOP/03/2024/L). All participants signed a consent form explaining the details of the study, including risks and benefits, before being included in the study. 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 \u0026nbsp;for Publication\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\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 contributed to the study conception and design, was the main author involved in data collection, drafted the original manuscript and revised version of the manuscript.\u003c/p\u003e\n\u003cp\u003eAG supported study design, was the main data analyst, and reviewed the original manuscript.\u003c/p\u003e\n\u003cp\u003eSG contributed to study conception and design, supported data collection and reviewed the original manuscript.\u003c/p\u003e\n\u003cp\u003eMN was the main author involved in study conception and design and reviewed the original 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\n\u003cli\u003eWhite NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet. 2014;383:723\u0026ndash;35.\u003c/li\u003e\n\u003cli\u003eWHO. World malaria report 2022. Geneva: World Health Organization; 2022.\u003c/li\u003e\n\u003cli\u003eWhite NJ. Anaemia and malaria. Malar J. 2018 Oct 19;17(1):371. doi: 10.1186/s12936-018-2509-9. PMID: 30340592; PMCID: PMC6194647.\u003c/li\u003e\n\u003cli\u003eMaina 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. Malar J. 2010 Dec 13;9 Suppl 3(Suppl 3):S4. doi: 10.1186/1475-2875-9-S3-S4. PMID: 21144084; PMCID: PMC3002140.\u003c/li\u003e\n\u003cli\u003eMutala AH, Badu K, Owusu C, Agordzo SK, Tweneboah A, Abbas DA, Addo MG. Impact of malaria on haematological parameters of urban, peri-urban and rural residents in the Ashanti region of Ghana: a cross-sectional study. AAS Open Res. 2020 Jul 9;2:27. doi: 10.12688/aasopenres.12979.3. PMID: 32704620; PMCID: PMC7355218.\u003c/li\u003e\n\u003cli\u003eG. A. Stevens, M. M. Finucane, L. M. De-Regil et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995\u0026ndash;2011: a systematic analysis of population-representative data, Lancet Global Health, vol. 1, no. 1, pp. E16\u0026ndash;E25, 2013.\u003c/li\u003e\n\u003cli\u003eE. McLean, M. Cogswell, I. Egli, D. Wojdyla, B. de Benoist. Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system, 1993\u0026ndash;2005,\u0026rdquo; Public Health Nutrition, vol. 12, no. 4, pp. 444\u0026ndash;454, 2009.\u003c/li\u003e\n\u003cli\u003eLooareesuwan S, Davis TME, Pukrittayakamee S, Supanaranond W, Desakorn V, Silamut K, et al. Erythrocyte survival in severe falciparum malaria. Acta Trop. 1991;48:263\u0026ndash;70.\u003c/li\u003e\n\u003cli\u003eVedovato M, De Paoli Vitali E, Dapporto M, Salvatorelli G. Defective erythropoietin production in the anaemia of malaria. Nephrol Dial Transplant. 1999;14:1043\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eMakenga G, Baraka V, Francis F, Minja DTR, Gesase S, Kyaruzi E, Mtove G, Nakato S, Madebe R, S\u0026oslash;eborg SR, Langhoff KH, Hansson HS, Alifrangis M, Lusingu JPA, Van Geertruyden JP. Attributable risk factors for asymptomatic malaria and anaemia and their association with cognitive and psychomotor functions in schoolchildren of north-eastern Tanzania. PLoS One. 2022 May 26;17(5):e0268654. doi: 10.1371/journal.pone.0268654. PMID: 35617296; PMCID: PMC9135275.\u003c/li\u003e\n\u003cli\u003eRoberts DJ, Zewotir T. Copula geoadditive modelling of anaemia and malaria in young children in Kenya, Malawi, Tanzania and Uganda. J Health Popul Nutr. 2020 Nov 6;39(1):8. doi: 10.1186/s41043-020-00217-8. PMID: 33158460; PMCID: PMC7648409.\u003c/li\u003e\n\u003cli\u003eSakwe N, Bigoga J, Ngondi J, Njeambosay B, Esemu L, Kouambeng C, Nyonglema P, Seumen C, Gouado I, Oben J. Relationship between malaria, anaemia, nutritional and socio-economic status amongst under-ten children, in the North Region of Cameroon: A cross-sectional assessment. PLoS One. 2019 Jun 21;14(6):e0218442. doi: 10.1371/journal.pone.0218442. PMID: 31226133; PMCID: PMC6588222.\u003c/li\u003e\n\u003cli\u003eSama SO, Chiamo SN, Taiwe GS, Njume GE, Ngole Sumbele IU. 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PMID: 32365839; PMCID: PMC7246851.\u003c/li\u003e\n\u003cli\u003eRouamba T, Samadoulougou S, Ou\u0026eacute;draogo M, Hien H, Tinto H, Kirakoya-Samadoulougou F. Asymptomatic malaria and anaemia among pregnant women during high and low malaria transmission seasons in Burkina Faso: household-based cross-sectional surveys in Burkina Faso, 2013 and 2017. Malar J. 2021 May 1;20(1):211. doi: 10.1186/s12936-021-03703-4. PMID: 33933072; PMCID: PMC8088076.\u003c/li\u003e\n\u003cli\u003eJegede FE, Oyeyi TI, Abdulrahman SA, Mbah HA, Badru T, Agbakwuru C, Adedokun O. Effect of HIV and malaria parasites co-infection on immune-haematological profiles among patients attending anti-retroviral treatment (ART) clinic in Infectious Disease Hospital Kano, Nigeria. PLoS One. 2017 Mar 27;12(3):e0174233. doi: 10.1371/journal.pone.0174233. PMID: 28346490; PMCID: PMC5367709.\u003c/li\u003e\n\u003cli\u003eShankar H, Singh MP, Hussain SSA, Phookan S, Singh K, Mishra N. Epidemiology of malaria and anemia in high and low malaria-endemic North-Eastern districts of India. Front Public Health. 2022 Jul 28;10:940898. doi: 10.3389/fpubh.2022.940898. PMID: 35968433; PMCID: PMC9366887.\u003c/li\u003e\n\u003cli\u003eKarunaratna S, Ranaweera D, Vitharana H, Ranaweera P, Mendis K, Fernando D. Thrombocytopenia in Malaria: A Red-Herring for Dengue, Delaying the Diagnosis of Imported Malaria. J Glob Infect Dis. 2021 Nov 9;13(4):172-176. doi: 10.4103/jgid.jgid_9_21. PMID: 35017873; PMCID: PMC8697816.\u003c/li\u003e\n\u003cli\u003eNaing C, Whittaker MA. Severe thrombocytopaenia in patients with vivax malaria compared to falciparum malaria: a systematic review and meta-analysis. Infect Dis Poverty. 2018 Feb 9;7(1):10. doi: 10.1186/s40249-018-0392-9. PMID: 29427995; PMCID: PMC5808388.\u003c/li\u003e\n\u003cli\u003eMurewanhema G, Musiniwa TC, Chimhina MT, Madombi S, Nyakanda MI, Madziyire MG. 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PMID: 25170106; PMCID: PMC4305266.\u003c/li\u003e\n\u003cli\u003eFoko LPK, Narang G, Tamang S, Hawadak J, Jakhan J, Sharma A, Singh V. The spectrum of clinical biomarkers in severe malaria and new avenues for exploration. Virulence. 2022 Dec;13(1):634-653. doi: 10.1080/21505594.2022.2056966. PMID: 36036460; PMCID: PMC9427047.\u003c/li\u003e\n\u003cli\u003eNwaneri D, Oladipo O, Ifebi E, Oviawe O, Asemota O, Ogboghodo B, Israel-Aina Y, Sadoh A. Haematological Parameters and Spleen Rate of Asymptomatic and Malaria Negative Children in Edo South District, Nigeria. Ann Glob Health. 2020 Jun 17;86(1):62. doi: 10.5334/aogh.24 58. PMID: 32587812; PMCID: PMC7304450.\u003c/li\u003e\n\u003cli\u003eKosiyo P, Otieno W, Gitaka J, Munde EO, Ouma C. Haematological abnormalities in children with sickle cell disease and non-severe malaria infection in western Kenya. BMC Infect Dis. 2021 Apr 7;21(1):329. doi: 10.1186/s12879-021-06025-7. PMID: 33827455; PMCID: PMC8028187.\u003c/li\u003e\n\u003cli\u003eTob\u0026oacute;n-Casta\u0026ntilde;o A, Mesa-Echeverry E, Miranda-Arboleda AF. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia. J Trop Med. 2015;2015:796182. doi: 10.1155/2015/796182. Epub 2015 Nov 18. PMID: 26664413; PMCID: PMC4667023.\u003c/li\u003e\n\u003cli\u003eKotepui M, Kotepui KU, Milanez GD, Masangkay FR. Reduction in total leukocytes in malaria patients compared to febrile controls: A systematic review and meta-analysis. PLoS One. 2020 Jun 23;15(6):e0233913. doi: 10.1371/journal.pone.0233913. PMID: 32574170; PMCID: PMC7310711.\u003c/li\u003e\n\u003cli\u003eNgwengi Y, Ngaba GP, Nida M, Enyama D. Evaluation of CRP as a marker for bacterial infection and malaria in febrile children at the Douala Gyneco-Obstetric and Pediatric Hospital. PLoS One. 2023 Jul 21;18(7):e0289012. doi: 10.1371/journal.pone.0289012. PMID: 37478118; PMCID: PMC10361518.\u003c/li\u003e\n\u003cli\u003ehttps://www.macrotrends.net/cities/20362/douala/population#:~:text=The%20metro%20area%20population%20of,a%204.72%25%20increase%20from%202016.\u003c/li\u003e\n\u003cli\u003ehttps://www.statisticshowto.com/probability-and-statistics/find-sample-size \u003c/li\u003e\n\u003cli\u003eOyegoke OO, Maharaj L, Akoniyon OP, Kwoji I, Roux AT, Adewumi TS, et al. Malaria diagnostic methods with the elimination goal in view. Parasitol Res. 2022 Jul;121(7):1867-1885. doi:10.1007/s00436-022-07521-9. Epub 2022 Apr 23. PMID: 35460369; PMCID: PMC9033523\u003c/li\u003e\n\u003cli\u003eWHO Guidelines for malaria, 3 June 2022. Geneva: World Health Organization; 2022 (WHO/UCN/GMP/2022.01 Rev.2). License: CC-BY-NC-SA 3.0 IGO.\u003c/li\u003e\n\u003cli\u003eMahende C, Ngasala B, Lusingu J, M\u0026aring;rtensson T, Lushino P, Lemnge M, et al. 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Doherty, \u0026ldquo;Short report: hematologic changes in acute, imported Plasmodium falciparum malaria,\u0026rdquo; The American Journal of Tropical Medicine and Hygiene, vol. 59, no. 6, p. 859, 1998.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"malaria, anaemia, leukopenia, lymphopenia, thrombocytopenia, CRP","lastPublishedDoi":"10.21203/rs.3.rs-8401521/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8401521/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\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\n\u003cp\u003e\u003cstrong\u003eMethod\u003c/strong\u003e\u003c/p\u003e\n\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 (CRP).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\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 \u0026gt; 5mg/L. Parasitaemia (in trophozoites of \u003cem\u003ePlasmodium falciparum\u003c/em\u003e/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 Receiver Operating Characteristic (ROC) curve were constructed. The Area under the ROC curve (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\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eComplete blood counts and CRP values can predict severe malaria accurately independently of currently established clinical and paraclinical criteria.\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e","manuscriptTitle":"Haematological parameters of Plasmodium falciparum infection in immunocompetent adults at a tertiary care centre in Douala","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-30 01:01:37","doi":"10.21203/rs.3.rs-8401521/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"de63a5cd-3249-44bb-be2c-d1ea765828ca","owner":[],"postedDate":"December 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-13T16:55:39+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-30 01:01:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8401521","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8401521","identity":"rs-8401521","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}