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Meurs L.,Institute of Tropical Medicine | Mbow M.,Institute of Tropical Medicine | Mbow M.,Laboratory of Bacteriology and Virology | Mbow M.,Leiden University | And 11 more authors.
PLoS Neglected Tropical Diseases | Year: 2014

Background: In Africa, many areas are co-endemic for the two major Schistosoma species, S. mansoni and S. haematobium. Epidemiological studies have suggested that host immunological factors may play an important role in co-endemic areas. As yet, little is known about differences in host immune responses and possible immunological interactions between S. mansoni and S. haematobium in humans. The aim of this study was to analyze host cytokine responses to antigens from either species in a population from a co-endemic focus, and relate these to S. mansoni and S. haematobium infection. Methodology: Whole blood cytokine responses were investigated in a population in the north of Senegal (n = 200). Blood was stimulated for 72 h with schistosomal egg and adult worm antigens of either Schistosoma species. IL-10, IL-5, IFN-γ, TNF-α, and IL-2 production was determined in culture supernatants. A multivariate (i.e. multi-response) approach was used to allow a joint analysis of all cytokines in relation to Schistosoma infection. Principal Findings: Schistosoma haematobium egg and worm antigens induced higher cytokine production, suggesting that S. haematobium may be more immunogenic than S. mansoni. However, both infections were strongly associated with similar, modified Th2 cytokine profiles. Conclusions/Significance: This study is the first to compare S. mansoni and S. haematobium cytokine responses in one population residing in a co-endemic area. These findings are in line with previous epidemiological studies that also suggested S. haematobium egg and worm stages to be more immunogenic than those of S. mansoni. © 2014 Meurs et al. Source

Meurs L.,Leiden University | Meurs L.,Institute of Tropical Medicine | Brienen E.,Leiden University | Mbow M.,Laboratory of Bacteriology and Virology | And 6 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Background The current reference test for the detection of S. mansoni in endemic areas is stool microscopy based on one or more Kato-Katz stool smears. However, stool microscopy has several shortcomings that greatly affect the efficacy of current schistosomiasis control programs. A highly specific multiplex real-time polymerase chain reaction (PCR) targeting the Schistosoma internal transcriber-spacer-2 sequence (ITS2) was developed by our group a few years ago, but so far this PCR has been applied mostly on urine samples. Here, we performed more in-depth evaluation of the ITS2 PCR as an alternative method to standard microscopy for the detection and quantification of Schistosoma spp. in stool samples. Methodology/Principal findings Microscopy and PCR were performed in a Senegalese community (n = 197) in an area with high S. mansoni transmission and co-occurrence of S. haematobium, and in Kenyan schoolchildren (n = 760) from an area with comparatively low S. mansoni transmission. Despite the differences in Schistosoma endemicity the PCR performed very similarly in both areas; 13–15% more infections were detected by PCR when comparing to microscopy of a single stool sample. Even when 2–3 stool samples were used for microscopy, PCR on one stool sample detected more infections, especially in people with light-intensity infections and in children from low-risk schools. The low prevalence of soil-transmitted helminthiasis in both populations was confirmed by an additional multiplex PCR. Conclusions/Significance The ITS2-based PCR was more sensitive than standard microscopy in detecting Schistosoma spp. This would be particularly useful for S. mansoni detection in low transmission areas, and post-control settings, and as such improve schistosomiasis control programs, epidemiological research, and quality control of microscopy. Moreover, it can be complemented with other (multiplex real-time) PCRs to detect a wider range of helminths and thus enhance effectiveness of current integrated control and elimination strategies for neglected tropical diseases. © 2015, PLOS Neglected Tropical Diseases. All rights reserved. Source

Ahouidi A.D.,Laboratory of Bacteriology and Virology | Ahouidi A.D.,Harvard University | Bei A.K.,Harvard University | Neafsey D.E.,The Broad Institute of MIT and Harvard | And 9 more authors.
Infection, Genetics and Evolution | Year: 2010

Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed as potential vaccine candidates. Members of the multi-gene PfRh family are surface antigens that have been shown to play a central role in directing merozoites to alternative erythrocyte receptors for invasion. Recently, we identified a large structural polymorphism, a 0.58 Kb deletion, in the C-terminal region of the PfRh2b gene, present at a high frequency in parasite populations from Senegal. We hypothesize that this region is a target of humoral immunity. Here, by analyzing 371 P. falciparum isolates we show that this major allele is present at varying frequencies in different populations within Senegal, Africa, and throughout the world. For allelic dimorphisms in the asexual stage antigens, Msp-2 and EBA-175, we find minimal geographic differentiation among parasite populations from Senegal and other African localities, suggesting extensive gene flow among these populations and/or immune-mediated frequency-dependent balancing selection. In contrast, we observe a higher level of inter-population divergence (as measured by Fst) for the PfRh2b deletion, similar to that observed for SNPs from the sexual stage Pfs45/48 loci, which is postulated to be under directional selection. We confirm that the region containing the PfRh2b polymorphism is a target of humoral immune responses by demonstrating antibody reactivity of endemic sera. Our analysis of inter-population divergence suggests that in contrast to the large allelic dimorphisms in EBA-175 and Msp-2, the presence or absence of the large PfRh2b deletion may not elicit frequency-dependent immune selection, but may be under positive immune selection, having important implications for the development of these proteins as vaccine candidates. © 2009 Elsevier B.V. All rights reserved. Source

Patel S.D.,Harvard University | Patel S.D.,Howard Hughes Medical Institute | Ahouidi A.D.,Harvard University | Ahouidi A.D.,Laboratory of Bacteriology and Virology | And 10 more authors.
Journal of Infectious Diseases | Year: 2013

Plasmodium falciparum is an intracellular protozoan parasite that infects erythrocytes and hepatocytes. The blood stage of its life cycle causes substantial morbidity and mortality associated with millions of infections each year, motivating an intensive search for potential components of a multi-subunit vaccine. In this study, we present data showing that antibodies from natural infections can recognize a recombinant form of the relatively conserved merozoite surface antigen, PfRH5. Furthermore, we performed invasion inhibition assays on clinical isolates and laboratory strains of P. falciparum in the presence of affinity purified antibodies to RH5 and show that these antibodies can inhibit invasion in vitro. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. Source

Mbaye E.H.S.,International Agency for Research on Cancer IARC WHO | Mbaye E.H.S.,Laboratory of Bacteriology and Virology | Mbaye E.H.S.,Cancer Institute | Mbaye E.H.S.,Laboratoire Of Bacteriologie Et Virologie | And 8 more authors.
Journal of Medical Virology | Year: 2014

Cervical cancer is the most frequent cancer among women in Senegal. However, there are few data concerning the human papillomavirus (HPV) types inducing neoplasia and cervical cancers and their prevalence in the general population of Senegal. The aim of this study is to determine the prevalence of HPV infection in Senegalese women aged 18 years and older in Dakar Region and three other regions. Cervical samples were collected from 498 women aged 18-80 years (mean, 42.1 years) in Dakar Region. Also, 438 samples were collected from three other regions: Thiès, Saint-Louis, and Louga. The samples were screened for 21 HPV genotypes using an HPV type-specific E7 PCR bead-based multiplex genotyping assay (TS-MPG). The prevalence of high risk (HR)-HPV in Dakar Region was 17.4%. HPV 52 (3.2%) was the most prevalent HPV type, followed by HPV 31 (3.0%) and HPV 16, 45, and 53 (all 2.8%). In the Thiès, Saint-Louis, and Louga Regions, the prevalence of HR-HPV was 23.2%, 13.1%, and 19.4%, respectively. The study revealed the specificity of HPV prevalence in Dakar Region and other regions of Senegal. The observed patterns show some differences compared with other regions of the world. These findings raise the possibility that, in addition to HPV 16 and HPV 18, other HPV types should be considered for a vaccination program in Senegal. However, additional studies to determine the HPV type distribution in cervical cancer specimens in Senegal are required to further corroborate this hypothesis. © 2013 Wiley Periodicals, Inc. Source

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