Intracellular adhesion molecule-1 and Vascular adhesion molecule-1 profile in uncomplicated malaria cases in Lagos, Nigeria

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Oyibo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3886351/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 Objectives: High levels of endothelial activation markers have been reported mostly in severe malaria cases and associated with several malaria syndromes following Plasmodium falciparum infected erythrocytes sequestration into blood vessels of deep tissues and organs. Data on their roles in uncomplicated malaria is scarce. This study evaluated levels of vascular endothelial adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in uncomplicated malaria and their relationship with host factors. Results: Mean levels of ICAM-1 (1.03x10 6 ±20689.2 pg/ml) and median level of VCAM-1 (1.11x10 6 pg/ml, range 3,725-6,273,725 pg/ml) were both significantly increased in malaria cases compared to the malaria negative group (p<0.01). The geometric mean parasite density was 11,183 parasites /μl, ICAM-1 and VCAM-1 levels did not correlate with parasite density, p=0.125, p=0.945; r=0.138, r=0.006 respectively. Mean PCV was significantly lower (P=0.042) in malaria positive cases than negative cases. A negative correlation was seen between ICAM-1 and PCV (r = -0.167, p =0.026; VCAM-1) and PCV (r=-0.173, p = 0.021). However, ICAM-1 and VCAM-1 levels were negatively associated with age (r =-0.314, p= 0.000; r = -0.160, p=0.033) respectively. This study showed increased VCAM-1 and ICAM-1 levels in uncomplicated malaria, an indication of endothelial activation, which plays a significant role in malaria pathogenesis. uncomplicated malaria endothelial adhesion molecules ICAM-1 VCAM-1 Figures Figure 1 Figure 2 Introduction Malaria, a persistent affliction throughout human history, continues to pose challenges despite significant advancements in its control. Efforts are underway to adopt new strategies in pursuit of the global goal of a malaria-free world. In 2022, the worldwide number of malaria cases surged to approximately 247 million, marking an increase from 227 million in 2019, with the majority concentrated in countries within the WHO African region [ 1 ]. Notably, Nigeria stood at the forefront among the six nations contributing 55% of all global malaria cases, accounting for approximately 31.3% of this burden [ 1 ]. P. falciparum parasites are renowned for sequestering in the deep vascular beds of various tissues. In response to malaria infection, endothelial activation assumes a pivotal role in the immune response. As the endothelium undergoes activation and dysfunction, cell adhesion molecules, including ICAM-1 and VCAM-1, are expressed on the endothelial cell membrane, facilitating robust adhesion of leukocytes and infected red blood cells (iRBCs) to the endothelium. Cell adhesion has been implicated in mediating cerebral and non-cerebral cytoadherence of P. falciparum -infected red blood cells to the host endothelium [ 2 ]. ICAM-1 and VCAM-1 serve as receptors for ligands such as P. falciparum erythrocyte membrane protein 1 (PfEMP1), a variant surface antigen expressed on knobs on the iRBCs surface and encoded by approximately 60 var genes per parasite genome. Only one Pf EMP1 is expressed on the surface of any individual iRBC [ 3 , 4 ], mediating cytoadherence [ 5 ], a process shown to positively correlate with the extent of ICAM-1 and VCAM-1 expression [ 6 , 7 ]. The expression of ICAM-1 has been associated with severe falciparum malaria [ 8 ], as well as severe infections in children [ 9 ]. Conversely, a Malawian study on childhood malaria reported a negative correlation with the disease [ 10 ]. Studies on uncomplicated P. falciparum infection have demonstrated an increase in concentrations of both ICAM-1 and VCAM-1 [ 11 , 12 ]. This research aims to determine the plasma concentrations of ICAM-1 and VCAM-1 in cases of uncomplicated malaria and evaluate their association with various host factors. Materials and methods Study site This was a cross-sectional study conducted on symptomatic cases at four (4) health facilities situated in Ikorodu Local Government Area (LGA) of Lagos State. Ikorodu LGA spans a total area of 345 square kilometers and is located to the north-east of Lagos city, with coordinates between longitudes 6°31′N and 6°41′N and latitudes 3°26′E and 3°42′E. The region experiences two distinct seasons: dry and rainy, with an average humidity level of 72 percent and a temperature of 26°C. The selected health facilities for the study were Imota Primary Health Centre (longitude E3⁰40'23.6244'', latitude N6⁰39'39.6288''), Bayioku Primary Health Centre (longitude E3032'34.6884'', latitude N6032'47.9004''), Agura Primary Health Centre (longitude E3037'38.3916'', latitude N6034'47.2872''), and Ijede General Hospital (longitude E3035'48.5772'', latitude N6033'51.7068''). Data and sample collection Parents, guardians, and children were informed about the research protocol and provided written consent or assent voluntarily. Three milliliters of venous blood were collected and stored in EDTA tubes for each participant. The collected blood samples were utilized for malaria diagnosis, total WBC count, and PCV. Following a 5-minute centrifugation at 1500 RPM, plasma was separated, stored in aliquots, and subsequently frozen at -80°C for future experimentation. The inclusion criteria involved symptomatic out-patients queried for malaria who had not taken antimalarials before their clinic visit. Control subjects were apparently healthy individuals negative for malaria (by microscopy) and had not experienced recent malaria attacks, treatment, or any recent pathological or physiological manifestations. The inclusion criteria involved symptomatic out-patients queried for malaria who had not taken antimalarials before their clinic visit. Control subjects were apparently healthy individuals negative for malaria (by microscopy) and had not experienced recent malaria attacks, treatment, or any recent pathological or physiological manifestations. Malaria diagnosis by Microscopy Thick and thin blood films were prepared and Giemsa-stained to estimate parasite density by counting the number of parasites per 200 white blood cells on the thick film following the WHO guideline for malaria diagnosis by microscopy [ 13 ]. Determination of Packed cell volume (PCV) The micro method was used to perform PCV. This involved filling plain capillary tubes, 75 mm long with a 1 mm internal diameter, with EDTA blood using capillary action and sealing them with plasticine. The tubes were then centrifuged for 5 minutes at 1200 rpm using a Haematokrit 210, Hettich Zentrifugen model of centrifuge. The resulting PCV values were read using a Microhaematokrit Reader from Hawksley, England. Total White Blood Cell Determination The WBC counts were obtained manually by employing the Neubauer Counting Chamber (Haemocytometer) (New Improved Neubauer). To do so, 20µl of whole blood sample was properly diluted in 380µl (1:20 dilution) of Turk's solution (2% acetic acid tinted with gentian violet). The diluted solution was transferred to the haemocytometer using a capillary tube, and WBCs were observed using a light microscope with a 40x objective. A hand counter was used to calculate the number of cells in four chambers, which were then multiplied by 50 [ 13 ]. The ultimate outcome was designated as the number ofWBCs per litre of blood. Measurement of ICAM-1 and VCAM-1 by Enzyme linked immune sorbent assay (ELISA) Plasma samples were thawed on ice, and ELISA kits purchased from Aviscera Bioscience INC USA were used to quantify ICAM-1 and VCAM-1 plasma levels according to the manufacturer's instructions. The optical density was read at 450 nm within 15 minutes using an ELISA reader (Techan, China). The concentration of ICAM-1 and VCAM-1 were determined by comparing them to a parallel serial dilution of standard and taking the average of duplicate readings for each standard, control, and sample having subtracted them from the average zero standard optical density. The software generated a log-log curve fit was used to create a standard curve. For diluted samples, the concentration read from the standard curve was multiplied by the dilution factor. Statistical Analysis SPSS version 23 statistical software was employed to analyze the data obtained from the study. Chi-square analysis, student t-test, and analysis of variance were applied as appropriate to determine associations and differences. Test of statistical significance was set at P value less than 0.05 at 95% confidence interval. Results A total of 179 individuals participated in the study. Of these, 54 were uninfected controls, and 125 had microscopic parasitaemia. Among the parasitaemia group, 56 (44.8%) were males and 69 (55.2%) were females, with no significant difference in the proportions of males to females (P = 0.936). The age range of participants was 2–63 years, with a mean age of 16.4 ± 13.1 years. Malaria prevalence was highest among those aged 10 years and above, and this difference was statistically significant (p < 0.001) (Table 1 ). Out of the 125 individuals with parasitaemia, 51 presented with an axillary temperature ≥ 37.5°C. The parasitaemia level ranged from 63 to 202,010 parasites/µl, with a geometric mean parasite density of 11,183 parasites/µl (Table 1 ). The mean PCV among the malaria-positive group was 34.5 ± 4.6%, significantly lower than in the malaria-negative group (P = 0.042) (Table 1 ). Table 1: Characteristics of the Study Participants Character Malaria Positive n (%) Healthy Control n (%) Febrile Control n (%) P-value Age (years) Mean ±SD ≤5 6-10 >10 16.4±13.1 17 (13.6) 42 (33.6) 66 (52.8) 29.0±7.5 0 0 29 (100) 19.3±10.9 3 (12.0) 1 (4.0) 21 (84.0) P<0.001 P<0.001 Sex (n=179) M F 56 (44.8) 69 (55.2) 14 (48.3) 15 (51.7) 11 (44.0) 14 (56.0) X 2 = 0.133 P = 0.936 Temperature ( o C) Mean ±SD <37.5 ≥37.5 37.2±1.4 74 (59.2) 51 (40.8) 36.3±0.6 29 (100) 0 37.0±1.3 20 (80.0) 5 (20.0) P = 0.001 P<0.001 PCV Mean ±SD 34.5±4.6 37.1±4.6 34.8±7.1 P = 0.042 WBC (cells/µL) Median Range Grouping 11000 5400 2000-24200 29 (23.2%) 65 (52.0) 26 (20.8%) 5 (4.0%) 4900 3800-8400 6 (20.7%) 18 (62.1) 5 (17.2%) 0 5600 1500-11300 6 (24.0%) 12 (48.0%) 6 (24.0%) 1 (4.0%) P = 0.476 P = 0.846 P = 0.907 Malaria Geometric Mean Parasite Density (GMPD) (parasites/µL) Range Microscopy 11,183 63 – 202,010 125 (100%) 0 0 0 8 (32.0%) Levels of ICAM-1 and VCAM-1 in participants with microscopic parasitaemia The levels of ICAM-1 and VCAM-1 were significantly higher in participants with microscopic parasitaemia compared with uninfected controls (P < 0.001) (Fig. 1 ; A & B). Effect of Parasitaemia on Levels of ICAM-1 and VCAM-1 Additionally, levels of ICAM-1 and VCAM-1 did not correlate with the parasite density, p = 0.125, p = 0.945; r = 0.138, 0.006 respectively (Fig. 2 ; A & B). Level of ICAM-1, VCAM-1 and host characteristics In this study, it was observed that both ICAM-1 and VCAM-1 were not significantly associated with levels of parasitaemia (p = 0.15, p = 0.945 respectively) (Fig. 2 ; A & B). However, ICAM-1 and VCAM-1 levels were negatively associated with age (r = -0.314, p = 0.000; r = -0.160, p = 0.033) respectively in individuals with microscopic parasitaemia. Furthermore, we stratified the ages for the group with microscopic parasitaemia to determine if ICAM-1 and VCAM-1 levels may vary across different age ranges (Figure S1 ; A & B). There was significant difference between the age group > 10 years and ICAM-1 / VCAM-1, there was a trend of decreasing ICAM-1 and VCAM-1 levels with increasing age (> 10 years) (r = -0.285, p = 0.000, r = -0.187, p = 0.012) respectively (Figure S1 ; A & B). There was no correlation between VCAM-1 and body temperature r = 0.070, p = 0.352; while ICAM-1 and body temperature correlated r = 0.181, p = 0.016. The mean PCV (34.5% ±4.6) of the malaria cases in this study was significantly lower than malaria negative cases (37.1% ±4.6) P = 0.042 and, there was a significant negative correlation between ICAM − 1 and PCV r = -0.167, p = 0.026; VCAM-1 and PCV r=-0.173, p = 0.021. Discussion ICAM-1 and VCAM-1 bind malaria parasite infected erythrocytes and their up-regulation by inflammatory cytokines may increase sequestration of parasites to endothelium in the brain, leading to severe malaria outcome [ 14 ]. In this study, the plasma concentrations of endothelial adhesion molecules; ICAM-1 and VCAM-1 were increased in cases with microscopic parasitaemia compared to uninfected controls. This finding aligns with previous studies [ 15 , 16 , 17 ], that reported an increase in ICAM-1 expression during malaria infections, and suggested its heightened binding with parasites displaying the appropriate Pf EMP-1 phenotype, indicating its potential significance in the development of cerebral malaria. It suggests that endothelial cells may react swiftly to the presence of the parasite in infected individuals, particularly when parasitaemia is visible by microscopy [ 15 ]. According to a study conducted by [ 18 ], higher levels of endothelial adhesion molecules were observed in a naïve population that developed sub-microscopic infections during a controlled human malaria infection. This indicates that naturally infected persons may develop some degree of tolerance towards Plasmodium parasites after repeated exposure, leading to little to no significant upregulation of endothelial adhesion molecules at the sub-patent level. In this study, there was no association between parasite density and levels of ICAM-1 and VCAM-1. This is similar with the results of prior studies [ 15 , 16 , 19 , 20 ] which reported significant variances between uninfected controls and children with microscopic parasitaemia, but no significant correlation between parasite levels and these molecules. The mean PCV of the malaria cases in this study was significantly lower than malaria negative cases and, ICAM-1 and VCAM-I correlated negatively with PCV, in contrast, the study by [ 12 ], showed that ICAM-1 was significantly associated with increased risk of severe anaemia and that children with severe malarial anaemia relative to those without, showed significantly elevated levels of the ICAM-1, VCAM-1 and E-selectin. According to a study conducted on animal models by [ 21 ], mice infected with malaria and lacking the ICAM-1 receptor experienced less anaemia and weight loss compared to mice with control infections. Despite developing a higher level of parasites in their peripheral blood, which continued for a longer duration, their reduced tissue cytoadherence was a contributing factor to their improved condition. Severe malaria poses a higher risk for individuals of advanced age, while children residing in malaria-endemic regions acquire immunity against severe malaria more rapidly, although this immunity does not necessarily reduce the number of parasites in their system [ 22 ]. According to the findings of this study, levels of ICAM-1 and VCAM-1 were lower in individuals with microscopic parasitaemia as they grew older, with significant differences observed between various age groups. Conversely, a different study [ 23 ] observed that the binding of infected erythrocytes (IE) to ICAM-1 receptors was more prevalent in older individuals, while no significant change was noted in the adhesion of IE to VCAM-1 receptors over time. ICAM-1 expression has been associated with severe infections in children [ 9 ], while also found to have a negative correlation with malaria in a separate study that focused on Malawian childhood malaria [ 10 ]. This information explains why P. falciparum is accountable for only 2% of clinical malaria cases that result in severe illness in African children [ 24 ], but are responsible for the majority of malaria-related deaths [ 1 ]. The variant surface antigens (VSAs) in field isolates of P. falciparum that lead to severe malaria in children tend to express a subset of surface antigens that are not recognized by the immune systems of infants and young children [ 25 ]. Limitations of this study include our inability to measure plasma level of ICAM-1 and VCAM-1 in severe malaria cases for comparison with uncomplicated and malaria negative cases. Abbreviations ELISA Enzyme linked immune sorbent assay (iRBCs infected red blood cells ICAM-1 Intracellular adhesion molecule-1 LGA Local Government Area PCV packed cell volume VSA variant surface antigens VCAM-1 vascular cell adhesion molecule-1 WBC white blood cell Pf EMP1 P. falciparum erythrocyte membrane protein 1 Declarations Ethics approval and consent to participate The study protocol was approved by Research Grants and Experimentation Ethics Committee, College of Medicine, University of Lagos, Nigeria (CM/COM/08/VOL.XXIV). Informed consent was obtained from the participants, parents or legal guardians for minor participants. Availability of data and materials Data generated or analysed during this study are included in this published article (and its Additional file: 1). Funding None Acknowledgements We express our sincere gratitude to the Lagos State Ministry of Health, which authorized the execution of this study at the various facilities. Our appreciation goes to the patients who actively participated in this study, as well as the management teams of the following health facilities in Ikorodu LGA, Lagos State: Ijede General Hospital, Imota Primary Health Centre, Bayeku Primary Health Centre, Agura Primary Health Centre. Consent for publication Not applicable Competing interests The authors declare that there is no conflict of interest. Authors' contributions All the authors have made substantial contributions to the conception of the article, UTO -contributed significantly to writing and editing of the manuscript for important intellectual content, WAO - approved its final version and agreed to its submission. Authors' information 1 Centre for Infectious Diseases Research, Microbiology Department, Nigerian Institute of Medical Research, 6 Edmund Crescent, Yaba - Lagos, Nigeria. 2 Centre for Transdisciplinary Research in Malaria/ANDI Centre of Excellence for Malaria Diagnosis, College of Medicine, University of Lagos, Lagos, Nigeria. References WHO. World malaria report. 2022. Serghides L, Smith TG, Patel SN, Kain KC. CD36 and malaria: friends or foes. Trends Parasitol. 2003;19:461–9. Scherf A, Lopez-Rubio JJ, Riviere L. Antigenic variation in Plasmodium falciparum . Annu Rev Microbiol. 2008;62(1):445–70. Pasternak ND, Dzikowski R. PfEMP1: an antigen that plays a key role in the pathogenicity and immune evasion of the malaria parasite Plasmodium falciparum. Int J Biochem Cell Biol. 2009;41(7):1463–6. Sherman IW, Eda S, Winograd E. Cytoadherence and sequestration in Plasmodium falciparum : defining the ties that bind. Microbes Infect. 2003;5(10):897–909. Newbold C, Warn P, Black G, Berendt A, Craig A, Snow B, et al. Receptor specific adhesion and clinical disease in Plasmodium falciparum . Am J Trop Med Hyg. 1997;57:389–98. Baruch DI, Rogerson SJ, Cooke BM. Asexual blood stages of malaria antigens: cytoadherence. Chem Immunol. 2002;80:144–62. Turner GD, Morrison H, Jones M, Davis TM, Looareesuwan S, Buley ID, et al. An immune histochemical study of the pathology of fatal malaria: evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994;145:1057–69. Ochola LB, Siddondo BR, Ocholla H, Nkya S, Kimani EN, Williams TN, et al. Specific receptor usage in Plasmodium falciparum cytoadherence is associated with disease outcome. PLoS ONE. 2011;6:e14741. Rogerson SJ, Tembenu R, Dobano C, Plitt S, Taylor TE, Molyneux ME. Cytoadherence characteristics of Plasmodium falciparum -infected erythrocytes from Malawian children with severe and uncomplicated malaria. Am J Trop Med Hyg. 1999;61:467–72. Ohnishi K. Serum levels of thrombomodulin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in the acute phase of Plasmodium vivax malaria. Am J Trop Med Hyg. 1999;60:248–50. PubMed: 10072144. Tchinda VH, Tadem AD, Tako EA, Tene G, Fogako J, Nyonglema P, et al. Severe malaria in Cameroonian children: correlation between plasma levels of three soluble inducible adhesion molecules and TNF-α. Acta Trop. 2007;102(1):20–8. WHO. Basic Laboratory Methods in Medical Parasitology. World Health Organization Geneva 12; 1991. Jakobsen PH, Morris-Jones S, Rønn A, Hviid L, Theander TG, Elhassan IM, et al. Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity. Immunology. 1994;83(4):665. Frimpong A, Amponsah J, Agyemang D, Adjokatseh AS, Eyiah-Ampah S, Ennuson NA, Kusi KA. Elevated Levels of the Endothelial Molecules ICAM-1, VEGF-A, and VEGFR2 in Microscopic Asymptomatic Malaria. Open Forum Infect. Dis. 2021; 8(7): p ofab302). US: Oxford University Press. Park GS, Ireland KF, Opoka RO, John CC. Evidence of endothelial activation in asymptomatic Plasmodium falciparum parasitemia and effect of blood group on levels of von Willebrand factor in malaria. J Pediatr Infect Dis Soc. 2012;1:16–25. Oxford U, De Mast Q, Brouwers J, Syafruddin D, Bousema T, Baidjoe AY, de Groot PG, et al. Is asymptomatic malaria really asymptomatic? Hematological, vascular and inflammatory effects of asymptomatic malaria parasitemia. J Infect. 2015;71:587–96. Mast QD, Groot E, Lenting PJ, de Groot PG, McCall M, Sauerwein RW, et al. Thrombocytopenia and release of activated von Willebrand factor during early Plasmodium falciparum malaria. J Infect Dis. 2007;196:622–8. Yeo TW, Lampah DA, Tjitra E, Piera K, Gitawati R, Kenangalem E, et al. Greater endothelial activation, Weibel-Palade body release and host inflammatory response to Plasmodium vivax , compared with Plasmodium falciparum : a prospective study in Papua. Indonesia J Infect Dis. 2010;202:109–12. Armah H, Dodoo AK, Wiredu EK, Stiles JK, Adjei AA, Gyasi RK, et al. High-level cerebellar expression of cytokines and adhesion molecules in fatal, paediatric, cerebral malaria. Ann Trop Med Parasitol. 2005;99:629–47. Cunningham DA, Lin JW, Brugat T, Jarra W, Tumwine I, Kushinga G, et al. ICAM-1 is a key receptor mediating cytoadherence and pathology in the Plasmodium chabaudi malaria model. Malar J. 2017;16(1):1–11. Goncalves BP, Huang CY, Morrison R, Holte S, Kabyemela E, Prevots DR, et al. Parasite burden and severity of malaria in Tanzanian children. N Engl J Med. 2014;370:1799–808. Mahamar A, Attaher O, Swihart B, Barry A, Diarra BS, Kanoute MB, et al. Host factors that modify Plasmodium falciparum adhesion to endothelial receptors. Sci Rep. 2017;7(1):1–8. Greenwood B, Marsh K, Snow R. Why do some African children develop severe malaria? Parasitol Today. 1991;7:277–81. Bull PC, Lowe BS, Kortok M, Marsh K. Antibody recognition of Plasmodium falciparum erythrocyte surface antigens in Kenya: evidence for rare and prevalent variants. Infect Immun. 1999;67:733–9. Additional Declarations No competing interests reported. Supplementary Files SupplimentaryMaterialfile.docx 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3886351","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":269004368,"identity":"e63ea645-5d07-430c-b59e-4a131c4d965f","order_by":0,"name":"Uche Thecla Igbasi","email":"","orcid":"","institution":"Nigerian Institute of Medical Research","correspondingAuthor":false,"prefix":"","firstName":"Uche","middleName":"Thecla","lastName":"Igbasi","suffix":""},{"id":269004369,"identity":"d5e5369a-4a7c-449a-bab8-b6835f061614","order_by":1,"name":"Wellington A. 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The boxes include the 25\u003csup\u003eth\u003c/sup\u003e and 75\u003csup\u003eth\u003c/sup\u003e percentiles. The horizontal line in the box represents the mean and the whiskers represent the 10\u003csup\u003eth\u003c/sup\u003e and 90\u003csup\u003eth\u003c/sup\u003e percentiles of the ICAM-1 and VCAM-1 responses, excluding outliers.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3886351/v1/59844663b0ab5888ce9f64de.jpeg"},{"id":50227352,"identity":"d2e45674-820a-4f63-a048-e2579b0f3910","added_by":"auto","created_at":"2024-01-26 18:25:31","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":122390,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelation between ICAM -1, VCAM-1 and parasite density among study participants with microscopic parasitaemia\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eA) ICAM -1 profile in parasitaemic individuals did not correlate with the parasite density, p = 0.125, correlation coefficient =0.138\u003c/p\u003e\n\u003cp\u003eB) VCAM -1 profile in parasitaemic individuals did not correlate with the parasite density, p = 0.945, correlation coefficient = 0.006\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3886351/v1/8a6e408008fd10fc09e934b0.jpeg"},{"id":60140100,"identity":"efbc3c91-8af8-4dc8-b447-c58de44ae4a8","added_by":"auto","created_at":"2024-07-12 08:48:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":890192,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3886351/v1/53d3be9a-5cb9-4856-8d61-88b0fe81aecd.pdf"},{"id":50227693,"identity":"9fd7a01e-c53d-4e87-ae1a-4d89a24f8071","added_by":"auto","created_at":"2024-01-26 18:33:31","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":95556,"visible":true,"origin":"","legend":"","description":"","filename":"SupplimentaryMaterialfile.docx","url":"https://assets-eu.researchsquare.com/files/rs-3886351/v1/4a20172641b7dbf89760f34b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Intracellular adhesion molecule-1 and Vascular adhesion molecule-1 profile in uncomplicated malaria cases in Lagos, Nigeria","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMalaria, a persistent affliction throughout human history, continues to pose challenges despite significant advancements in its control. Efforts are underway to adopt new strategies in pursuit of the global goal of a malaria-free world. In 2022, the worldwide number of malaria cases surged to approximately 247\u0026nbsp;million, marking an increase from 227\u0026nbsp;million in 2019, with the majority concentrated in countries within the WHO African region [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Notably, Nigeria stood at the forefront among the six nations contributing 55% of all global malaria cases, accounting for approximately 31.3% of this burden [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eP. falciparum\u003c/em\u003e parasites are renowned for sequestering in the deep vascular beds of various tissues. In response to malaria infection, endothelial activation assumes a pivotal role in the immune response. As the endothelium undergoes activation and dysfunction, cell adhesion molecules, including ICAM-1 and VCAM-1, are expressed on the endothelial cell membrane, facilitating robust adhesion of leukocytes and infected red blood cells (iRBCs) to the endothelium.\u003c/p\u003e \u003cp\u003eCell adhesion has been implicated in mediating cerebral and non-cerebral cytoadherence of \u003cem\u003eP. falciparum\u003c/em\u003e-infected red blood cells to the host endothelium [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. ICAM-1 and VCAM-1 serve as receptors for ligands such as \u003cem\u003eP. falciparum\u003c/em\u003e erythrocyte membrane protein 1 (PfEMP1), a variant surface antigen expressed on knobs on the iRBCs surface and encoded by approximately 60 var genes per parasite genome. Only one \u003cem\u003ePf\u003c/em\u003eEMP1 is expressed on the surface of any individual iRBC [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], mediating cytoadherence [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], a process shown to positively correlate with the extent of ICAM-1 and VCAM-1 expression [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe expression of ICAM-1 has been associated with severe falciparum malaria [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], as well as severe infections in children [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Conversely, a Malawian study on childhood malaria reported a negative correlation with the disease [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Studies on uncomplicated \u003cem\u003eP. falciparum\u003c/em\u003e infection have demonstrated an increase in concentrations of both ICAM-1 and VCAM-1 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This research aims to determine the plasma concentrations of ICAM-1 and VCAM-1 in cases of uncomplicated malaria and evaluate their association with various host factors.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy site\u003c/h2\u003e \u003cp\u003eThis was a cross-sectional study conducted on symptomatic cases at four (4) health facilities situated in Ikorodu Local Government Area (LGA) of Lagos State. Ikorodu LGA spans a total area of 345 square kilometers and is located to the north-east of Lagos city, with coordinates between longitudes 6\u0026deg;31\u0026prime;N and 6\u0026deg;41\u0026prime;N and latitudes 3\u0026deg;26\u0026prime;E and 3\u0026deg;42\u0026prime;E. The region experiences two distinct seasons: dry and rainy, with an average humidity level of 72 percent and a temperature of 26\u0026deg;C. The selected health facilities for the study were Imota Primary Health Centre (longitude E3⁰40'23.6244'', latitude N6⁰39'39.6288''), Bayioku Primary Health Centre (longitude E3032'34.6884'', latitude N6032'47.9004''), Agura Primary Health Centre (longitude E3037'38.3916'', latitude N6034'47.2872''), and Ijede General Hospital (longitude E3035'48.5772'', latitude N6033'51.7068'').\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData and sample collection\u003c/h2\u003e \u003cp\u003e Parents, guardians, and children were informed about the research protocol and provided written consent or assent voluntarily. Three milliliters of venous blood were collected and stored in EDTA tubes for each participant. The collected blood samples were utilized for malaria diagnosis, total WBC count, and PCV. Following a 5-minute centrifugation at 1500 RPM, plasma was separated, stored in aliquots, and subsequently frozen at -80\u0026deg;C for future experimentation.\u003c/p\u003e \u003cp\u003eThe inclusion criteria involved symptomatic out-patients queried for malaria who had not taken antimalarials before their clinic visit. Control subjects were apparently healthy individuals negative for malaria (by microscopy) and had not experienced recent malaria attacks, treatment, or any recent pathological or physiological manifestations.\u003c/p\u003e \u003cp\u003eThe inclusion criteria involved symptomatic out-patients queried for malaria who had not taken antimalarials before their clinic visit. Control subjects were apparently healthy individuals negative for malaria (by microscopy) and had not experienced recent malaria attacks, treatment, or any recent pathological or physiological manifestations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eMalaria diagnosis by Microscopy\u003c/h2\u003e \u003cp\u003eThick and thin blood films were prepared and Giemsa-stained to estimate parasite density by counting the number of parasites per 200 white blood cells on the thick film following the WHO guideline for malaria diagnosis by microscopy [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDetermination of Packed cell volume (PCV)\u003c/h2\u003e \u003cp\u003eThe micro method was used to perform PCV. This involved filling plain capillary tubes, 75 mm long with a 1 mm internal diameter, with EDTA blood using capillary action and sealing them with plasticine. The tubes were then centrifuged for 5 minutes at 1200 rpm using a Haematokrit 210, Hettich Zentrifugen model of centrifuge. The resulting PCV values were read using a Microhaematokrit Reader from Hawksley, England.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTotal White Blood Cell Determination\u003c/h2\u003e \u003cp\u003eThe WBC counts were obtained manually by employing the Neubauer Counting Chamber (Haemocytometer) (New Improved Neubauer). To do so, 20\u0026micro;l of whole blood sample was properly diluted in 380\u0026micro;l (1:20 dilution) of Turk's solution (2% acetic acid tinted with gentian violet). The diluted solution was transferred to the haemocytometer using a capillary tube, and WBCs were observed using a light microscope with a 40x objective. A hand counter was used to calculate the number of cells in four chambers, which were then multiplied by 50 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The ultimate outcome was designated as the number ofWBCs per litre of blood.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of ICAM-1 and VCAM-1 by Enzyme linked immune sorbent assay (ELISA)\u003c/h2\u003e \u003cp\u003ePlasma samples were thawed on ice, and ELISA kits purchased from Aviscera Bioscience INC USA were used to quantify ICAM-1 and VCAM-1 plasma levels according to the manufacturer's instructions. The optical density was read at 450 nm within 15 minutes using an ELISA reader (Techan, China). The concentration of ICAM-1 and VCAM-1 were determined by comparing them to a parallel serial dilution of standard and taking the average of duplicate readings for each standard, control, and sample having subtracted them from the average zero standard optical density. The software generated a log-log curve fit was used to create a standard curve. For diluted samples, the concentration read from the standard curve was multiplied by the dilution factor.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003e SPSS version 23 statistical software was employed to analyze the data obtained from the study. Chi-square analysis, student t-test, and analysis of variance were applied as appropriate to determine associations and differences. Test of statistical significance was set at P value less than 0.05 at 95% confidence interval.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 179 individuals participated in the study. Of these, 54 were uninfected controls, and 125 had microscopic parasitaemia. Among the parasitaemia group, 56 (44.8%) were males and 69 (55.2%) were females, with no significant difference in the proportions of males to females (P\u0026thinsp;=\u0026thinsp;0.936). The age range of participants was 2\u0026ndash;63 years, with a mean age of 16.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1 years. Malaria prevalence was highest among those aged 10 years and above, and this difference was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Out of the 125 individuals with parasitaemia, 51 presented with an axillary temperature\u0026thinsp;\u0026ge;\u0026thinsp;37.5\u0026deg;C. The parasitaemia level ranged from 63 to 202,010 parasites/\u0026micro;l, with a geometric mean parasite density of 11,183 parasites/\u0026micro;l (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean PCV among the malaria-positive group was 34.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6%, significantly lower than in the malaria-negative group (P\u0026thinsp;=\u0026thinsp;0.042) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1: Characteristics of the Study Participants\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.201298701298704%\" valign=\"top\"\u003e\n \u003cp\u003eCharacter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.506493506493506%\" valign=\"top\"\u003e\n \u003cp\u003eMalaria Positive\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.61038961038961%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy Control\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.558441558441558%\" valign=\"top\"\u003e\n \u003cp\u003eFebrile Control\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.123376623376624%\" valign=\"top\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.201298701298704%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026le;5\u003c/p\u003e\n \u003cp\u003e6-10\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026gt;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.506493506493506%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e16.4\u0026plusmn;13.1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e17 (13.6)\u003c/p\u003e\n \u003cp\u003e42 (33.6)\u003c/p\u003e\n \u003cp\u003e66 (52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.61038961038961%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e29.0\u0026plusmn;7.5\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e29 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.558441558441558%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e19.3\u0026plusmn;10.9\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e3 (12.0)\u003c/p\u003e\n \u003cp\u003e1 (4.0)\u003c/p\u003e\n \u003cp\u003e21 (84.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.123376623376624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eP\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eP\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.201298701298704%\" valign=\"top\"\u003e\n \u003cp\u003eSex (n=179)\u003c/p\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.506493506493506%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56 (44.8)\u003c/p\u003e\n \u003cp\u003e69 (55.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.61038961038961%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (48.3)\u003c/p\u003e\n \u003cp\u003e15 (51.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.558441558441558%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (44.0)\u003c/p\u003e\n \u003cp\u003e14 (56.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.123376623376624%\" valign=\"top\"\u003e\n \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e = 0.133\u003c/p\u003e\n \u003cp\u003eP = 0.936\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.201298701298704%\" valign=\"top\"\u003e\n \u003cp\u003eTemperature (\u003csup\u003eo\u003c/sup\u003eC)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;37.5\u003c/p\u003e\n \u003cp\u003e\u0026ge;37.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.506493506493506%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e37.2\u0026plusmn;1.4\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e74 (59.2)\u003c/p\u003e\n \u003cp\u003e51 (40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.61038961038961%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e36.3\u0026plusmn;0.6\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e29 (100)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.558441558441558%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e37.0\u0026plusmn;1.3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e20 (80.0)\u003c/p\u003e\n \u003cp\u003e5 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.123376623376624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eP = 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eP\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.201298701298704%\" valign=\"top\"\u003e\n \u003cp\u003ePCV\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.506493506493506%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e34.5\u0026plusmn;4.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.61038961038961%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e37.1\u0026plusmn;4.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.558441558441558%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e34.8\u0026plusmn;7.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.123376623376624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eP = 0.042\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.201298701298704%\" valign=\"top\"\u003e\n \u003cp\u003eWBC (cells/\u0026micro;L)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGrouping\u003c/p\u003e\n \u003cp\u003e\u0026lt;4000\u003c/p\u003e\n \u003cp\u003e4000-7000\u003c/p\u003e\n \u003cp\u003e7001 \u0026ndash; 11000\u003c/p\u003e\n \u003cp\u003e\u0026gt;11000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.506493506493506%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5400\u003c/p\u003e\n \u003cp\u003e2000-24200\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (23.2%)\u003c/p\u003e\n \u003cp\u003e65 (52.0)\u003c/p\u003e\n \u003cp\u003e26 (20.8%)\u003c/p\u003e\n \u003cp\u003e5 (4.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.61038961038961%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4900\u003c/p\u003e\n \u003cp\u003e3800-8400\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (20.7%)\u003c/p\u003e\n \u003cp\u003e18 (62.1)\u003c/p\u003e\n \u003cp\u003e5 (17.2%)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.558441558441558%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5600\u003c/p\u003e\n \u003cp\u003e1500-11300\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (24.0%)\u003c/p\u003e\n \u003cp\u003e12 (48.0%)\u003c/p\u003e\n \u003cp\u003e6 (24.0%)\u003c/p\u003e\n \u003cp\u003e1 (4.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.123376623376624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eP = 0.476\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eP = 0.846\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eP = 0.907\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.201298701298704%\" valign=\"top\"\u003e\n \u003cp\u003eMalaria Geometric Mean Parasite Density (GMPD) (parasites/\u0026micro;L)\u003c/p\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003cp\u003eMicroscopy\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.506493506493506%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11,183\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63 \u0026ndash; 202,010\u003c/p\u003e\n \u003cp\u003e125 (100%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.61038961038961%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.558441558441558%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e8 (32.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.123376623376624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eLevels of ICAM-1 and VCAM-1 in participants with microscopic parasitaemia\u003c/h2\u003e\n \u003cp\u003eThe levels of ICAM-1 and VCAM-1 were significantly higher in participants with microscopic parasitaemia compared with uninfected controls (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e; A \u0026amp; B).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eEffect of Parasitaemia on Levels of ICAM-1 and VCAM-1\u003c/h2\u003e\n \u003cp\u003eAdditionally, levels of ICAM-1 and VCAM-1 did not correlate with the parasite density, p\u0026thinsp;=\u0026thinsp;0.125, p\u0026thinsp;=\u0026thinsp;0.945; r\u0026thinsp;=\u0026thinsp;0.138, 0.006 respectively (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e; A \u0026amp; B).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eLevel of ICAM-1, VCAM-1 and host characteristics\u003c/h2\u003e\n \u003cp\u003eIn this study, it was observed that both ICAM-1 and VCAM-1 were not significantly associated with levels of parasitaemia (p\u0026thinsp;=\u0026thinsp;0.15, p\u0026thinsp;=\u0026thinsp;0.945 respectively) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e; A \u0026amp; B). However, ICAM-1 and VCAM-1 levels were negatively associated with age (r = -0.314, p\u0026thinsp;=\u0026thinsp;0.000; r = -0.160, p\u0026thinsp;=\u0026thinsp;0.033) respectively in individuals with microscopic parasitaemia. Furthermore, we stratified the ages for the group with microscopic parasitaemia to determine if ICAM-1 and VCAM-1 levels may vary across different age ranges (Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e; A \u0026amp; B). There was significant difference between the age group\u0026thinsp;\u0026gt;\u0026thinsp;10 years and ICAM-1 / VCAM-1, there was a trend of decreasing ICAM-1 and VCAM-1 levels with increasing age (\u0026gt;\u0026thinsp;10 years) (r = -0.285, p\u0026thinsp;=\u0026thinsp;0.000, r = -0.187, p\u0026thinsp;=\u0026thinsp;0.012) respectively (Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e; A \u0026amp; B).\u003c/p\u003e\n \u003cp\u003eThere was no correlation between VCAM-1 and body temperature r\u0026thinsp;=\u0026thinsp;0.070, p\u0026thinsp;=\u0026thinsp;0.352; while ICAM-1 and body temperature correlated r\u0026thinsp;=\u0026thinsp;0.181, p\u0026thinsp;=\u0026thinsp;0.016. The mean PCV (34.5% \u0026plusmn;4.6) of the malaria cases in this study was significantly lower than malaria negative cases (37.1% \u0026plusmn;4.6) P\u0026thinsp;=\u0026thinsp;0.042 and, there was a significant negative correlation between ICAM \u0026minus;\u0026thinsp;1 and PCV r = -0.167, p\u0026thinsp;=\u0026thinsp;0.026; VCAM-1 and PCV r=-0.173, p\u0026thinsp;=\u0026thinsp;0.021.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eICAM-1 and VCAM-1 bind malaria parasite infected erythrocytes and their up-regulation by inflammatory cytokines may increase sequestration of parasites to endothelium in the brain, leading to severe malaria outcome [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In this study, the plasma concentrations of endothelial adhesion molecules; ICAM-1 and VCAM-1 were increased in cases with microscopic parasitaemia compared to uninfected controls. This finding aligns with previous studies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], that reported an increase in ICAM-1 expression during malaria infections, and suggested its heightened binding with parasites displaying the appropriate \u003cem\u003ePf\u003c/em\u003e EMP-1 phenotype, indicating its potential significance in the development of cerebral malaria. It suggests that endothelial cells may react swiftly to the presence of the parasite in infected individuals, particularly when parasitaemia is visible by microscopy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to a study conducted by [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], higher levels of endothelial adhesion molecules were observed in a na\u0026iuml;ve population that developed sub-microscopic infections during a controlled human malaria infection. This indicates that naturally infected persons may develop some degree of tolerance towards Plasmodium parasites after repeated exposure, leading to little to no significant upregulation of endothelial adhesion molecules at the sub-patent level.\u003c/p\u003e \u003cp\u003eIn this study, there was no association between parasite density and levels of ICAM-1 and VCAM-1. This is similar with the results of prior studies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] which reported significant variances between uninfected controls and children with microscopic parasitaemia, but no significant correlation between parasite levels and these molecules.\u003c/p\u003e \u003cp\u003eThe mean PCV of the malaria cases in this study was significantly lower than malaria negative cases and, ICAM-1 and VCAM-I correlated negatively with PCV, in contrast, the study by [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], showed that ICAM-1 was significantly associated with increased risk of severe anaemia and that children with severe malarial anaemia relative to those without, showed significantly elevated levels of the ICAM-1, VCAM-1 and E-selectin.\u003c/p\u003e \u003cp\u003eAccording to a study conducted on animal models by [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], mice infected with malaria and lacking the ICAM-1 receptor experienced less anaemia and weight loss compared to mice with control infections. Despite developing a higher level of parasites in their peripheral blood, which continued for a longer duration, their reduced tissue cytoadherence was a contributing factor to their improved condition.\u003c/p\u003e \u003cp\u003eSevere malaria poses a higher risk for individuals of advanced age, while children residing in malaria-endemic regions acquire immunity against severe malaria more rapidly, although this immunity does not necessarily reduce the number of parasites in their system [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. According to the findings of this study, levels of ICAM-1 and VCAM-1 were lower in individuals with microscopic parasitaemia as they grew older, with significant differences observed between various age groups. Conversely, a different study [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] observed that the binding of infected erythrocytes (IE) to ICAM-1 receptors was more prevalent in older individuals, while no significant change was noted in the adhesion of IE to VCAM-1 receptors over time. ICAM-1 expression has been associated with severe infections in children [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], while also found to have a negative correlation with malaria in a separate study that focused on Malawian childhood malaria [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This information explains why \u003cem\u003eP. falciparum\u003c/em\u003e is accountable for only 2% of clinical malaria cases that result in severe illness in African children [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], but are responsible for the majority of malaria-related deaths [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The variant surface antigens (VSAs) in field isolates of \u003cem\u003eP. falciparum\u003c/em\u003e that lead to severe malaria in children tend to express a subset of surface antigens that are not recognized by the immune systems of infants and young children [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eLimitations\u003c/b\u003e of this study include our inability to measure plasma level of ICAM-1 and VCAM-1 in severe malaria cases for comparison with uncomplicated and malaria negative cases.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eELISA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEnzyme linked immune sorbent assay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e(iRBCs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einfected red blood cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICAM-1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntracellular adhesion molecule-1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLocal Government Area\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epacked cell volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVSA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evariant surface antigens\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVCAM-1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evascular cell adhesion molecule-1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewhite blood cell\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cem\u003ePf\u003c/em\u003eEMP1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e \u003cem\u003eP. falciparum\u003c/em\u003e erythrocyte membrane protein 1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by Research Grants and Experimentation Ethics Committee, College of Medicine, University of Lagos, Nigeria (CM/COM/08/VOL.XXIV). Informed consent was obtained from the participants, parents or legal guardians for minor participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData generated or analysed during this study are included in this published article (and its Additional file: 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe express our sincere gratitude to the Lagos State Ministry of Health, which authorized the execution of this study at the various facilities. Our appreciation goes to the patients who actively participated in this study, as well as the management teams of the following health facilities in Ikorodu LGA, Lagos State: Ijede General Hospital, Imota Primary Health Centre, Bayeku Primary Health Centre, Agura Primary Health Centre.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll the authors have made substantial contributions to the conception of the article, UTO -contributed significantly to writing and editing of the manuscript for important intellectual content, WAO - approved its final version and agreed to its submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eCentre for Infectious Diseases Research, Microbiology Department, Nigerian Institute of Medical Research, 6 Edmund Crescent, Yaba - Lagos, Nigeria. \u003csup\u003e2\u003c/sup\u003eCentre for Transdisciplinary Research in Malaria/ANDI Centre of Excellence for Malaria Diagnosis, College of Medicine, University of Lagos, Lagos, Nigeria.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWHO. 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Microbes Infect. 2003;5(10):897\u0026ndash;909.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNewbold C, Warn P, Black G, Berendt A, Craig A, Snow B, et al. Receptor specific adhesion and clinical disease in \u003cem\u003ePlasmodium falciparum\u003c/em\u003e. Am J Trop Med Hyg. 1997;57:389\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaruch DI, Rogerson SJ, Cooke BM. Asexual blood stages of malaria antigens: cytoadherence. Chem Immunol. 2002;80:144\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurner GD, Morrison H, Jones M, Davis TM, Looareesuwan S, Buley ID, et al. An immune histochemical study of the pathology of fatal malaria: evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. 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PubMed: 10072144.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTchinda VH, Tadem AD, Tako EA, Tene G, Fogako J, Nyonglema P, et al. Severe malaria in Cameroonian children: correlation between plasma levels of three soluble inducible adhesion molecules and TNF-α. Acta Trop. 2007;102(1):20\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWHO. Basic Laboratory Methods in Medical Parasitology. World Health Organization Geneva 12; 1991.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJakobsen PH, Morris-Jones S, R\u0026oslash;nn A, Hviid L, Theander TG, Elhassan IM, et al. Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity. Immunology. 1994;83(4):665.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrimpong A, Amponsah J, Agyemang D, Adjokatseh AS, Eyiah-Ampah S, Ennuson NA, Kusi KA. 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Infect Immun. 1999;67:733\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\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":"uncomplicated malaria, endothelial adhesion molecules, ICAM-1, VCAM-1","lastPublishedDoi":"10.21203/rs.3.rs-3886351/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3886351/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e High levels of endothelial activation markers have been reported mostly in severe malaria cases and associated with several malaria syndromes following \u003cem\u003ePlasmodium falciparum\u003c/em\u003e infected erythrocytes sequestration into blood vessels of deep tissues and organs. Data on their roles in uncomplicated malaria is scarce. This study evaluated levels of vascular endothelial adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in uncomplicated malaria and their relationship with host factors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Mean levels of ICAM-1 (1.03x10\u003csup\u003e6\u003c/sup\u003e±20689.2 pg/ml) and median level of VCAM-1 (1.11x10\u003csup\u003e6\u003c/sup\u003e pg/ml, range 3,725-6,273,725 pg/ml) were both significantly increased in malaria cases compared to the malaria negative group (p\u0026lt;0.01). The geometric mean parasite density was 11,183 parasites /μl, ICAM-1 and VCAM-1 levels did not correlate with parasite density, p=0.125, p=0.945; r=0.138, r=0.006 respectively. Mean PCV was significantly lower (P=0.042) in malaria positive cases than negative cases. A negative correlation was seen between ICAM-1 and PCV (r = -0.167, p =0.026; VCAM-1) and PCV (r=-0.173, p = 0.021). However, ICAM-1 and VCAM-1 levels were negatively associated with age (r =-0.314, p= 0.000; r = -0.160, p=0.033) respectively. This study showed increased VCAM-1 and ICAM-1 levels in uncomplicated malaria, an indication of endothelial activation, which plays a significant role in malaria pathogenesis.\u003c/p\u003e","manuscriptTitle":"Intracellular adhesion molecule-1 and Vascular adhesion molecule-1 profile in uncomplicated malaria cases in Lagos, Nigeria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-26 18:25:27","doi":"10.21203/rs.3.rs-3886351/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":"d698af1c-10b0-4026-b7ff-626a30f858f7","owner":[],"postedDate":"January 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-12T08:40:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-26 18:25:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3886351","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3886351","identity":"rs-3886351","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}