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Objective: To investigate the carriage of HBs antigen (Ag) and hepatitis C virus in people with human immunodeficiency virus (HIV) at Grand-Yoff General Hospital. Materials and Methods: Sera from patients living with HIV and monitored at Grand-Yoff General Hospital have benefited from research for HBs Ag, HBe Ag, anti-H[8] Be antibodies and on these co-infected patients, a test for hepatitis C virus was also carried out. Results: This study included 147 HIV-infected patients and including 95 women (64.63%) and 52 men (35, 37%) with a median age of 46 years (16-78 years). The gender ratio is M/W was 0.54 and the age group most represented at inclusion was 30-39 years old with 31.97% of patients. 12, 25% of patients were co-infected HIV and hepatitis B including 11 women (61.11%) and 7 men (38.89%). The median age was 39.5 years (33-60 years), women were the affected by co-infection and 44.44% of them were married. Chronic hepatitis B and hepatitis C markers were tested for in HIV/HBV coinfected patients using a microparticulate chemiluminescence immunoassay technic. Investigation of hepatitis B chronicity markers indicated that all patient, except one, underwent anti-HBe seroconversion (94.4%) and no case of co-infection with HCV had been noted. During follow-up, all patients were under antiretroviral therapy with mainly tenofovir (TDF) which was the most used molecule with 83.33%, followed by lamivudine (3TC) 16.67%. Conclusion: HIV infection is a major public health problem when it is associated with hepatitis B and C virus.

Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria, whether IL-17A gene polymorphisms are involved in severe malaria susceptibility and the polymorphism’s influence on the IL-17A serum levels. 125 malaria patients and 48 free malaria controls were enrolled in this research. Malaria patients were classified into severe malaria (SM) and uncomplicated malaria (UM). IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum level and malaria outcome. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P

BackgroundThe first discovery of Plasmodium vivax infections in Senegal used archived patients’ sera in place of blood pellet, the preferred specimen for the molecular diagnosis of Plasmodium species. The present study assessed the reliability of detecting P. vivax DNA in plasma in comparison to blood pellet from the same patient’s samples.MethodsA total of 616 blood samples obtained from febrile patients living in Kolda (2015 and 2020), Tambacounda (2017 and 2020), and Kedougou (2020) regions in Senegal, were first screened for Plasmodium species composition by 18S ssrRNA-based nested PCR. Paired blood pellets and plasma samples were selected from a subset of 50 P. vivax-positive patients matched by age and sex with 50 P. vivax-negative patients, and subjected to a cytochrome b-based qPCR to compare the detection and quantification of P. vivax genomic DNA between the two specimen types.Results and discussionThe study reports 1.8% and 14.77% of single and mixed P. vivax infections in the study population, and a high concordance (84%) between the qPCR detection of P. vivax genomic DNA from paired blood pellets and plasma samples. Importantly, all P. vivax negative samples from the blood pellets were also confirmed plasma-negative, and parasitaemia in blood pellets was higher compared to plasma samples. The results support investigations of P. vivax infections in archived sera or plasma collections with a high degree of confidence to generate additional data on the neglected P. vivax malaria, and ultimately guide strategies to control the disease.

Galectin-3 is a member of the lectin family encoded by the LGALS3 gene on chromosome 14. It is secreted by a wide range of immune cells and mammary tumor cells. Through its activity on the tumor microenvironment, in particular on tumor-infiltrating leukocytes, galectin-3 improves the proliferation, survival, and colonizing ability of mammary neoplastic cells. Consequently, galectin-3 expression in the tumor microenvironment could worsen therapeutic outcomes of breast neoplasms and become a biomarker and a therapeutic target in combined immunotherapy in breast neoplasms. There is a limited amount of information that is available on galectin-3 in breast cancer in Africa. In this review, we analyze how galectin-3 influences the tumor microenvironment and its potential as a biomarker and therapeutic target in breast neoplasms. We aim to emphasize the significance of investigating galectin-3 in breast neoplasms in Africa based on the results of studies conducted elsewhere.

Genome-wide association studies for severe malaria (SM) have identified 30 genetic variants mostly located in non-coding regions. Here, we aimed to identify potential causal genetic variants located in these loci and demonstrate their functional activity. We systematically investigated the regulatory effect of the SNPs in linkage disequilibrium (LD) with the malaria-associated genetic variants. Annotating and prioritizing genetic variants led to the identification of a regulatory region containing five

BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p.Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing ~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred ~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.

Founder mutations have been reported in BRCA1 and BCRA2 in different ethnic groups with inherited breast cancer. Testing of targeted mutations in specific populations is important for cancer prevention in mutation carriers. In Sub-Saharan Africa, only a few studies have reported specific founder mutations in inherited breast cancer. The pathogenic variant c.815_824dup of BRCA1 has been reported as the most frequent among African American populations with inherited breast cancer and was supposed to have a West African origin. Recent report from Senegal identified this variant in women with inherited breast cancer at the highest frequency ever reported. The variant was linked to a common haplotype confirming its founder effect in West Africa. In this article, we review the mutation history of c.815_824dup and discuss how it spread out of Africa through the transatlantic slave trade.

Summary Merozoite surface proteins (MSPs) are critical for parasite invasion; they represent attractive targets for antibody-based protection against clinical malaria. To identify protection-associated target MSPs, the present study analysed antibody responses to whole merozoite extract (ME) and to defined MSP recombinant antigens in hospitalized patients from a low endemic urban area as a function of disease severity (mild versus cerebral malaria). Sera from 110 patients with confirmed severe cerebral malaria (CM) and 91 patients with mild malaria (MM) were analysed (mean age = 29 years) for total and subclass immunoglobulin (Ig)G to ME and total IgG to MSP1p19, MSP2, MSP3, MSP4 and MSP5 by enzyme-linked immunosorbent assay (ELISA). Functional antibody responses were evaluated using the antibody-dependent respiratory burst (ADRB) assay in a subset of sera. There was a trend towards higher IgG1 and IgG4 levels to ME in CM compared to MM; only ME IgM responses differed significantly between fatal and surviving CM patients. Increased prevalence of IgG to individual MSPs was found in the CM compared to the MM group, including significantly higher levels of IgG to MSP4 and MSP5 in the former. Sera from fatal (24·5%) versus surviving cases showed significantly lower IgG to MSP1p19 and MSP3 (P < 0·05). ADRB assay readouts correlated with high levels of anti-MSP IgG, and trended higher in sera from patients with surviving compared to fatal CM outcome (P = 0·07). These results document strong differential antibody responses to MSP antigens as targets of protective immunity against CM and in particular MSP1p19 and MSP3 as prognostic indicators.

Background and Objectives: Cervical cancer is a leading cause of cancer death in female populations. It is a virally induced carcinoma resulting from sexually transmitted high risk Human Papillomavirus infections (e.g. HPV-16, HPV-18). Previous studies have shown associations between IL-17A levels in cancer micro-environments and metastasis of tumor cells. In Africa, chemotherapy (CT) is the standard first-line treatment for cervical cancer and the prognosis remains poor for metastatic and recurrent cases. The impact of CT as a treatment option is still unclear. We investigated the prognostic relevance of IL-17A profiles in Cervical cancer patients (CP) patients treated with cisplatin in combination with 5-fluouracil (5FU) for three cycles. Methods: The study included 57 CP and 59 women with no history of malignancy as healthy controls (HC). IL-17A plasma levels were evaluated by ELISA. For each CP, three blood samples were collected at three-week intervals before initiation of the chemotherapy protocol. Results: Before chemotherapy CP showed higher serum levels of IL-17A compared to HCs (p = 0.035). No relation was detected between age and IL-17A levels. We observed a significant increase in serum IL-17A during treatment of the CP group (p < 0.05). Depending on chemotherapy’s efficacy, CP were divided into 1) non responders, 2) partial responders and 3) good responders. Non-responders patients showed significantly higher serum levels of IL-17A during the follow-up compared to partial and good responder groups both following the first CT cycle (p < 0.05) and the second CT cycle (p < 0.03). Conclusion: Our results suggest that high serum levels of IL-17A are associated with poor responses to classical chemotherapy. However, considering these results to design CC biomarkers, we need further investigations particularly about the relevant prognostic indicator following chemotherapy.

Plasmodium resistance to Artemisinin Combination-based Therapies (ACT) in Southeast Asia is a major public health concern that is sporadically appearing in Africa. Senegal has shifted from malaria control to elimination plans. Given notable progresses obtained through robust strategic plans, it is still crucial to assess genetic variability of the Plasmodium falciparum artemisinin resistance gene marker Kelch13 (PfKelch13) in circulating field isolates. We here report an analysis of PfKelch13-propeller polymorphism in clinical isolates collected nine years after ACT introduction in five Senegalese regions with different malaria transmission settings. Sequencing of PfKelch13-propeller domain from 280 clinical isolates reveals that 16% (45/280) of the parasite population harbored variants. Dynamics of PfKelch13 variants reveals emerging, persistent but also disappearing mutations over time. In addition to the malaria epidemiology, our survey also shows the dynamics of PfKelch13 variants in different malaria transmission settings in Senegal. Despite the absence of PfKelch13 associated artemisinin resistance mutations, a shift from 86% to 68% of PfKelch13WT was observed when comparing parasites collected prior vs. post ACT intensive usage in Dakar a low malaria transmission area. All together, our data confirms the need to closely monitor PfKelch13 polymorphism to anticipate and or prevent emergence of P. falciparum resistance in Senegal.

International audience; Genome-wide association studies for severe malaria (SM) have identified 30 genetic variants mostly located in non-coding regions. Here, we aimed to identify potential causal genetic variants located in these loci and demonstrate their functional activity. We systematically investigated the regulatory effect of the SNPs in linkage disequilibrium (LD) with the malaria-associated genetic variants. Annotating and prioritizing genetic variants led to the identification of a regulatory region containing five ATP2B4 SNPs in LD with rs10900585. We found significant associations between SM and rs10900585 and our candidate SNPs (rs11240734, rs1541252, rs1541253, rs1541254, and rs1541255) in a Senegalese population. Then, we demonstrated that both individual SNPs and the combination of SNPs had regulatory effects. Moreover, CRISPR/Cas9-mediated deletion of this region decreased ATP2B4 transcript and protein levels and increased Ca2+ intracellular concentration in the K562 cell line. Our data demonstrate that severe malaria-associated genetic variants alter the expression of ATP2B4 encoding a plasma membrane calcium-transporting ATPase 4 (PMCA4) expressed on red blood cells. Altering the activity of this regulatory element affects the risk of SM, likely through calcium concentration effect on parasitaemia.

The COVID-19 pandemic is shining a spotlight on the field of immunology like never before. To appreciate the diverse ways in which immunologists have contributed, Nature Reviews Immunology invited the president of the International Union of Immunological Societies and the presidents of 15 other national immunology societies to discuss how they and their members responded following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., For this Viewpoint, Nature Reviews Immunology asked the presidents of 16 immunology societies from around the world to discuss how their society and its members responded to the COVID-19 pandemic. Their answers highlight the incredible contributions that immunologists around the globe have made following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Background Ongoing efforts to fight Plasmodium falciparum malaria has reduced malaria in many areas, but new tools are needed to monitor further progress, including indicators of decreasing exposure to parasite infection. Sero-surveillance is considered promising to monitor exposure, transmission and immunity. Methods IgG responses to three antigen biomarkers were evaluated in a retrospective study involving: (i) surveys of 798 asymptomatic villagers from 2 Senegalese endemic settings conducted before 2002 and after the 2013 intensification of control measures, and (ii) in 105 symptomatic individuals from different settings in Côte d’Ivoire. Response to up to eight P. falciparum antigens, including recombinant MSP1p9 antigen and LSA141 peptide, were analysed using multiplex technology and responses to whole P. falciparum schizont extract (SE, local strain adapted to culture) were measured by ELISA. Results MSP1p9 and LSA141 IgG responses were shown to be relevant indicators monitoring immune status in the different study sites both from Côte d’Ivoire and Senegal. Between 2002 and 2013, individuals participating in both studies showed higher decline of sero-positivity in young ( 15 years: no decline to 15%) individuals from Dielmo and Ndiop. A mathematical sero-catalytic model from the complete Dielmo/Ndiop survey was used to reconstruct declining levels of sero-positivity in more detail, demonstrating that anti-SE seroprevalence levels most accurately reflected malaria exposure in the two villages. Conclusion For standard screening of population immune status at sites envisaging elimination, the use of ELISA-based assays targeting selected antigens can contribute to provide important epidemiologic surveillance data to aid malaria control programmes.

Background Several genetic polymorphisms were reported to be prevalent among populations living in tropical endemic regions and induce protection against malaria. In this study, we investigated the prevalence of key malaria-protective polymorphisms in G6PD and HBB genes in a Senegalese population. Methods We performed a retrospective study in 323 samples from patients recruited in hospitals located in three different endemic areas where malaria episodes were confirmed. Patients enrolled were classified in two groups: severe (153 patients) and uncomplicated malaria (170 patients). PCR and DNA sequencing assessed host genetic polymorphisms in HBB and G6PD. Using a multivariate regression and additive model, estimates the impact of human HBB and G6PD polymorphisms on malaria incidence were performed. Results We identified 12 SNPs in HBB gene. Among them, 6 SNPs (rs7946748, rs7480526, rs10768683, rs35209591, HbS (rs334) and rs713040) were detected with high frequencies in global population. The MAF of the sickle cell HbS polymorphism was estimated to 0.026, 0.069 and 0.035; and HbC polymorphism was estimated to be 0, 0.009, 0.029, in SM, UM and CTR group respectively. The MAF of G6PD deficiency polymorphisms such as G6PD-202 G>A were 0.022, 0.032 and 0.018 in SM, UM and CTR, respectively. Analysis of selected HbS polymorphism showed significant association with protection against severe malaria with a significant p-value = 0.033 (OR 0.38, 95%CI: 0.16–0.91). Surprisingly, HbC polymorphism is not a protective variant in our population. Finally, we found that the selected SNPs were associated to biological parameters such as PNE, PNB and lymphocytes. Conclusion Our data report at the first time the prevalence of HBB and G6PD mutations in senegalese population. These deficiencies are very common in West Africa endemic regions such as Gambia, Mali and Burkina Faso. Our findings show the important role of genetic factors in malaria outcome and these genetic markers could be good tools for malaria diagnosis and prognosis. Keywords : severe malaria, HBB, G6PD, Polymorphisms, Senegal, severe malaria.

Additional file 1: Table S1. Estimates from sero-catalytic models. Statistical inference was implemented in a Bayesian framework with uniform priors. Parameters are presented as median and 95% credible intervals of the estimated posterior distributions.

Background: The loss of function in TP53 gene is an early event of carcinogenesis and is now considered as a full etiological factor in oral squamous cell carcinoma (OSCC). The most common polymorphism in this gene that is associated to OSCC and has been extensively studied as a potential risk factor for the development of malignancies is the single nucleotide polymorphism (SNP) encoding either proline or arginine at residue 72. Today, despite the multiplicity of publications and approaches used, the contradiction of the results have not remove the ambiguity of the possible impact of this polymorphism in OSCC. So we aimed this meta-analysis to investigate the distribution of TP53 codon 72 genotypes and alleles in patients with OSCC and healthy matched controls, by using an ethnicity subgroups analysis. Method: A literature search was conducted to identify studies concerning TP53 codon 72 polymorphism and OSCC risk. Retrieved publications from 2000 to 2014 were classified by ethnicity, according to the sampling collection continent. Allelic frequencies were estimated by using genotypic data and Hardy-Weinberg Equilibrium and distributions were checked with Chi-2 test. Statistical tests for contrast models of association were performed with Proline allele as reference stratum. Results: Arg allele distribution was almost similar in both cases and controls for African and Caucasian populations whereas Arg frequency was significantly greater in cases than in controls for Asians (p=0.011). After stratified statistical analyses, we’ve found again a significant association between Arginine allele and OSCC risk in the Asian subgroup (OR=1.31; 95% CI=1.09-1.58; P=0.004). Conclusion: This current study revealed that allelic distribution of TP53 Arg72Pro polymorphism may depend on ethnicity and latitude, and highlighted that Arginine carrier in Asian populations may be considered to be predisposed to OSCC.

Introduction: Precordial pain is a common reason for admission in cardiology, and has many causes. Acute myocarditis in its pseudo-infarctoid form is sometimes difficult to differentiate from myocardial infarction. Cardiac magnetic resonance imaging (MRI) helps to differentiate these two disease entities. We report the respective cases of two young patients, one presenting with myocarditis whilst the other with myocardial infarction. Case Report: We present the cases of two patients. The first who had a recent history of febrile syndrome is a 23-year-old who stopped smoking 3 months prior to presentation whilst the second is a 22-year-old professional footballer with a history of stress with no other cardiovascular risk factors. They were respectively admitted in our emergency department for a constrictive, intense chest pain. Physical examination was normal. The chest pain in both patients was associated with elevated cardiac markers, primary repolarisation abnormalities on ECG, wall motion abnormalities as well as left ventricular systolic dysfunction on transthoracic echocardiography. Coronary angiograms were normal in both patients. In the first patient, MRI concluded with an acute myocarditis with apical akinesia extending to the anterior wall, a T2 hypersignal indicative of myocardial edema, and uptake of a nodular heterogeneous contrast without affecting the sub-endocardial layers on the late enhancement sequences. In the second patient, MRI showed an appearance consistent with acute extensive infarction in the antero-apical region with severe hypokinesia and late quasi-transmural enhancement, impairment of the anterior papillary muscle of the mitral valve and a reduced left ventricular ejection fraction at 33%. In addition to analgesics, the first patient was treated with perindopril and bisoprolol, and the second patient received antithrombotic and anticoagulant treatment. There was clinical improvement in both patients. Conclusion: Cardiac MRI is a useful diagnostic tool for the precise diagnosis of precordial pain with elevated cardiac enzymes, especially in young patients.

Identification of parasite antigens targeted by immune effector mechanisms that confer protection against malaria is important for the design of a multi-component malaria vaccine. Here, the association of antibodies reacting with the Plasmodium falciparum merozoite surface protein-4 (MSP4) with protection against clinical malaria was investigated in a Senegalese community living in an area of moderate, seasonal malaria transmission. Blood samples were collected at the end of an 8-month long dry season without any recorded parasite transmission from 206 residents enrolled in a prospective follow-up study. Active daily clinical monitoring was implemented during the subsequent five months. Entomologic monitoring documented parasite transmission during the first three months of follow-up. Serum IgG levels were determined by ELISA against three MSP4 baculovirus-encoded recombinant protein constructs, namely the full-length MSP4p40, MSP4p30 devoid of a highly polymorphic sequence stretch and the conserved C-terminal EGF-containing MSP4p20, as well as against a merozoite crude extract. Community seroprevalence against all three constructs was quite high, the lowest being against MSP4p30. Seroprevalence and antibody levels against the three MSP4 constructs were age-dependent. IgG1 dominated the anti-MSP4p20 responses, while both IgG1 and IgG3 were observed against MSP4p40. Anti-MSP4 antibodies were associated with the antibody-dependent respiratory burst (ADRB) activity in a functional assay of merozoite phagocytosis by polymorphonuclear cells. Importantly, high antibody levels against each of the three MSP4 constructs at the end of the dry season were associated with reduced morbidity during the subsequent transmission season in an age-adjusted Poisson regression model (IRR = 0.65 [0.50-0.83], P < 0.001 for responses over the median values). These data are consistent with a protective role for the naturally acquired anti-MSP4 antibodies and support further development of MSP4 as a candidate component of malaria vaccine.

Objective: Evaluate the immunological status to hepatitis B virus of Senegalese pregnant women by screening HBs antigen. Material and methods: The selection criteria of women were presence at the laboratory for biological exams of pregnancy follow-up. All volunteers for the study were screened for HBs antigen (HBs Ag). Investigation of chronic hepatitis B markers (HBe Ag, anti-HBe, viral quantification) was performed in HBs Ag positive participants. The concentration of anti-HBs antibodies was assessed in HBs Ag negative women. Results: One hundred and fifteen (115) pregnant women were included in the study from July to October 2014. The mean age was 29 ± 6 years, ranging from 16 to 47. The seroprevalence of HBs Ag was 12% and the majority of women (90%) were not vaccinated. Any of the 14 HBs Ag-positive subjects did not express serum HBe Ag, (marker of active viral replication) and all were positive for anti-HBe antibodies. Their viral load (HBV DNA) was undetectable and serum transaminases were normal. The anti-HBs antibodies titrated in HBs-Ag negative women serum revealed that only 46 had protective levels against HBV whilst 55 of them were unprotected.

Background Pathogenic variants associated with hereditary breast cancer have been reported for BRCA1 and BRCA2 (BRCA1/2) genes in patients from multiple ethnicities, but limited information is available from sub-Saharan African populations. We report a BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. Methods An index case from a consanguineous family and nineteen healthy female relatives were recruited after informed consent. Along with this family, 14 other index cases with family history of breast cancer were also recruited. For the control populations we recruited 48 healthy women with no cancer diagnosis and 48 women diagnosed with sporadic breast cancer without family history. Genomic DNA was extracted from peripheral blood. All BRCA2 exons were amplified by PCR and sequenced. Sequences were compared to the BRCA2 GenBank reference sequence (NM_000059.3) using Alamut Software. Results We identified a novel nonsense pathogenic variant c.5219 T > G; p.(Leu1740Ter) in exon 11 of BRCA2 in the index case. The pathogenic variant was also identified in three sisters and one daughter, but was absent in the controls and unrelated cases. Conclusions This is the first report of a novel BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. This result confirms the diversity of hereditary breast cancer pathogenic variants across populations and extends our knowledge of genetic susceptibility to breast cancer in Africa. Electronic supplementary material The online version of this article (10.1186/s12881-019-0814-y) contains supplementary material, which is available to authorized users.

Ndiaye R BRCA2 Supplementary Material. Table S1 Primers used for BRCA1 coding exons PCR amplification. Table S2 Primers used for BRCA2 coding exons PCR amplification. (DOCX 26 kb)

Background Host factors, including host genetic variation, have been shown to influence the outcome of Plasmodium falciparum infection. Genome-wide linkage studies have mapped mild malaria resistance genes on chromosome 6p21, whereas NCR3-412 polymorphism (rs2736191) lying within this region was found to be associated with mild malaria. Methods Blood samples were taken from 188 Plasmodium falciparum malaria patients (76 mild malaria patients, 85 cerebral malaria patients, and 27 severe non-cerebral malaria patients). NCR3-412 (rs2736191) was analysed by sequencing, and haematological parameters were measured. Finally, their association with clinical phenotypes was assessed. Results We evidenced an association of thrombocytopenia with both cerebral malaria and severe non-cerebral malaria, and of an association of high leukocyte count with cerebral malaria. Additionally, we found no association of NCR3-412 with either cerebral malaria, severe non-cerebral malaria, or severe malaria after grouping cerebral malaria and severe non-cerebral malaria patients. Conclusions Our results suggest that NCR3 genetic variation has no effect, or only a small effect on the occurrence of severe malaria, although it has been strongly associated with mild malaria. We discuss the biological meaning of these results. Besides, we confirmed the association of thrombocytopenia and high leukocyte count with severe malaria phenotypes.

Malaria remains a major health problem in sub- Saharan African countries despite substantial decreases in morbidity and mortality due to sustained control programs. Vaccines candidates were mainly tested in rural endemic setting; however increasing proportion of the population is living in urban area. Evaluation of the qualitative or quantitative immune responses to key targets of anti-Plasmodium immunity requires further investigation in urban area. In a cohort of 144 patients with mild malaria living in Dakar, we analyzed IgG responses against target antigens of P. falciparum: CSP, LSA-3NR2 and GLURP by ELISA. A mean age of 15 yrs (4-65 yrs) was found and patients were separated in 59 adults (

Background. Management of clinical malaria requires the development of reliable diagnostic methods and efficient biomarkers for follow-up of patients. Protection is partly based on IgG responses to parasite antigens exposed at the surface of infected erythrocytes (iRBCs). These IgG responses appeared low during clinical infection, particularly in severe disease.Methods. We analyzed the IgG binding capacity to the surface of live erythrocytes infected by knob positive FCR3 strain. Sera from 69 cerebral malaria (CM) and 72 mild malaria (MM) cases were analyzed by ELISA for IgG responses to five antigens from iRBC and by flow cytometry for IgG binding as expressed in labeling index ratio (LIR). The relationship between IgG levels, LIR, parasitemia, age, and the clinical outcomes was evaluated.Results. We found a significant decrease of LIR in adult CM fatal cases compared to surviving patients (p=0.019). In MM, LIRs were correlated to IgG anti-iRBC and anti-PfEMP3/5 levels. In CM, no correlation was found between LIR, IgG levels, and parasitemia.Conclusion. The IgG binding assay was able to discriminate outcome of cerebral malaria cases and it deserves further development as a potential functional-associated assay for symptomatic malaria analysis.

International audience; Background: Serological markers are potentially useful tools for monitoring the progress of malaria control programs , but a better understanding of antibody response dynamics is necessary. The use of a magnetic bead-based immunoassay (MBA) is advantageous compared to ELISA, due to its multiplexing capacity, but limited information is available on the standardization and validation of this assay. Methods: Several parameters for multiplex testing of antibodies to Plasmodium antigens were analysed using a set of 4 antigens and 98 sera from Senegalese rural asymptomatic and urban symptomatic individuals. The 4 antigens included Plasmodium falciparum CSP and PfAMA1 peptides, recombinant P. falciparum MSP4p20 and a Plasmodium malariae CSP (PmCSP) peptide. Comparisons with ELISA were done using MSP4p20 and whole schizont extract (SE) antigens.Results: The use of fewer beads (1000 beads per well instead of 2000) and 5 µg of antigen per 10 6 bead were validated as lower amounts. The use of a carrier protein (BSA) was shown to be critical when using peptides and the effect of a 24 h delayed measures was evaluated (5-25% signal decrease). Analysis of Ab responses showed almost equally high levels and prevalence in all transmission settings. Clear distinctions between rural and urban malaria were noted using PmCSP and SE antigens.Conclusions: This study underlines the importance of further optimization of the MBA technique and highlights the interest of using multistage/multispecies antigens for surveillance of malaria in endemic settings.