Title Participants Abstract "Acute schistosomiasis with a Schistosoma mattheei x Schistosoma haematobium hybrid species in a cluster of 34 travelers infected in South Africa" "Lieselotte Cnops, Tine Huyse, Ula Maniewski-Kelner, Patrick Soentjens, Emmanuel Bottieau, Marjan Van Esbroeck, Joannes Clerinx" "BACKGROUND: Diagnosis of schistosomiasis remains elusive soon after infection. We evaluated several diagnostic methods in a cluster of travelers with simultaneous freshwater exposure in South Africa.METHODS: Eosinophil count, schistosome antibody tests, stool and urine microscopy, and serum Dra1 PCR assays were performed at weeks 4-5 (early symptomatic phase), 7-8 (praziquantel treatment), and 13-14 (after treatment). Sequencing was done on serum samples from 3 patients to identify the species.RESULTS: Of the 34 travelers (16 adults and 18 children), 32 developed symptoms 2-6 weeks after exposure. A raised eosinophil count (>750/µL) was seen in 12 of 33 at weeks 4-5, and in 22 of 34 at weeks 7-8. Schistosoma antibodies were detected in 3 of 33 at weeks 4-5 and in 12 of 34 at weeks 7-8 and weeks 13-14. The Dra1 PCR result was positive in 24 of 33 travelers at weeks 4-5, in 31 of 34 at weeks 7-8, in 25 of 34 at weeks 13-14, and at least once in all. Ova were absent in all urine and stool samples obtained. Sequencing identified Schistosoma mattheei nuclear and Schistosoma haematobium mitochondrial DNA, indicative of a hybrid species.CONCLUSIONS: The Dra1 PCR confirmed the diagnosis in all exposed travelers at a much earlier stage than conventional tests. The causative species is probably an S. mattheei × S. haematobium hybrid." "Epidemiology of mixed Schistosoma mansoni and Schistosoma haematobium infections in northern Senegal" "Lynn Meurs, M. Mbow, Kim Vereecken, Joris Menten, Souleymane Mboup, Katja Polman" "Due to the large overlap of Schistosoma mansoni- and Schistosoma haematobium-endemic regions in Africa, many people are at risk of co-infection, with potential adverse effects on schistosomiasis morbidity and control. Nonetheless, studies on the distribution and determinants of mixed Schistosoma infections have to date been rare. We conducted a cross-sectional survey in two communities in northern Senegal (n=857) to obtain further insight into the epidemiology of mixed infections and ectopic egg elimination. Overall prevalences of S. mansoni and S. haematobium infection were 61% and 50%, respectively, in these communities. Among infected subjects, 53% had mixed infections and 8% demonstrated ectopic egg elimination. Risk factors for mixed infection - i.e. gender, community of residence and age - were not different from what is generally seen in Schistosoma-endemic areas. Similar to overall S. mansoni and S. haematobium infections, age-related patterns of mixed infections showed the characteristic convex-shaped curve for schistosomiasis, with a rapid increase in children, a peak in adolescents and a decline in adults. Looking at the data in more detail however, the decline in overall S. haematobium infection prevalences and intensities appeared to be steeper than for S. mansoni, resulting in a decrease in mixed infections and a relative increase in single S. mansoni infections with age. Moreover, individuals with mixed infections had higher infection intensities of both S. mansoni and S. haematobium than those with single infections, especially those with ectopic egg elimination (P" "The epidemiology of a recent focus of mixed Schistosoma haematobium and Schistosoma mansoni infections around the 'Lac de Guiers' in the Senegal river basin, Senegal" "D De Clercq, J. Vercruysse, M Picquet, DJ Shaw, M Diop, A Ly, Bruno Gryseels" "Schistosoma mansoni and Schistosoma haematobium infection and morbidity in a co-endemic focus" "Lynn Meurs" "The aim of this thesis was to get a detailed insight into the epidemiological patterns of Schistosoma infection and associated morbidity on a micro-geographical scale in Schistosoma mansoni and S. haematobium co-endemic areas. A S. mansoni and S. haematobium co-endemic focus in the north of Senegal was selected as the primary study site. The small scale of this study allowed a detailed, multidisciplinary analysis of complex infection and morbidity patterns. Moreover, it enabled us to take the well-known focality of schistosomiasis into account (Chapter 1).We observed prevalences of 61% and 50% for S. mansoni and S. haematobium infection, respectively. Most of these infections were mixed S. mansoni and S. haematobium infections (53%). In comparison to single infections, mixed infections were of higher intensity. Eight percent of the infected people also showed ectopic excretion of Schistosoma eggs (mainly S. mansoni in urine; Chapter 2). While elevated S. haematobium infection intensities predisposed for S. haematobium-specific urinary tract morbidity, the presence of S. mansoni in co-infections tended to protect against this. The latter effect was most pronounced in people with ectopic S. mansoni egg excretion. On the other hand, no association was found between S. mansoni-specific hepatic fibrosis and Schistosoma infection. This is likely due to a slower disease onset in S. mansoni as compared to S. haematobium infection. Indeed, the delay between the age peak for S. mansoni infection and morbidity was >10 years, while such a delay could not be observed for S. haematobium (Chapter 3). We were the first to look into the micro-geographical distribution of chronic Schistosoma morbidity. In contrast to classical epidemiological analyses (see Chapter 3), spatial analysis did reveal a clear association between S. mansoni infection and morbidity. It was shown that adults living adjacent to the main Schistosoma transmission site were more than six times more likely to develop severe S. mansoni-specific hepatic fibrosis than their counterparts living farther away. Children living in the same spot were also more at risk of heavy S. mansoni infection, indicating that cumulative exposure to Schistosoma eggs is likely to be the main driver of chronic morbidity in schistosomiasis (Chapter 4). We explored immune responses in the two Schistosoma infections in this population by means of whole blood cytokine responses. Cytokine responses to adult worm antigens were used as a proxy for host responses to living adult worms, and thus infection. Cytokine responses to soluble Schistosoma egg antigens were used as a proxy for the egg-induced responses that may have contributed to the observed morbidity patterns. It was found that S. haematobium antigens induce higher cytokine levels than those of S. mansoni. This supports the idea that the first species may be more immunogenic. This hypothesis corresponds with our epidemiological findings: 1) in line with previous studies, we found the S. haematobium age curve to decline more steeply after adolescence than that of S. mansoni; and 2) we observed more S. haematobium- than S. mansoni-specific morbidity (83% versus 27%). Our investigations did not reveal any interspecies differences in the immunological phenotypes that were induced. Both Schistosoma species were associated with a modified Th2 response in a dose-dependent manner. Such a response is characteristic for Schistosoma infection (Chapter 5). Subsequently, the innate immune responses that generally precede and shape these adaptive cytokine responses were investigated. This study was performed in children from a S. haematobium mono-endemic area in Lambaréné, Gabon. While children infected with S. haematobium produced more of the anti-inflammatory cytokine IL-10 than uninfected children in response to adaptive stimuli (egg and worm antigens), their innate immune response to TLR ligands was more pro-inflammatory (TNF-α) than that of uninfected children. Hence, schistosomal infection suppresses the host’s adaptive immune system but does not appear to affect innate stimulation with single TLR ligands. This indicates that schistosomiasis does not induce a general suppression of the host immune system (Chapter 6).This thesis provides a novel, holistic approach to understanding schistosomiasis. It has led to important new insights into demographic and geographic patterns of S. mansoni and S. haematobium on a micro scale, and provides new leads for further research on disease etiology and underlying mechanisms. Further studies are necessary to investigate to which extent these results can be extrapolated over time and to other populations. Such knowledge is key to rationalizing and optimizing current schistosomiasis control strategies, particularly in co-endemic areas. An improved understanding of this complex disease would furthermore greatly aid in developing successful elimination strategies in the future (Chapter 7)." "Barcoding hybrids: heterogeneous distribution of Schistosoma haematobium × Schistosoma bovis hybrids across the Senegal River Basin" "Nele Boon, Frederik Van den Broeck, Djiby Faye, Filip A M Volckaert, Souleymane Mboup, Katja Polman, Tine Huyse" "ABSTRACTHybridization events between Schistosoma species (Digenea, Platyhelminthes) are reported with increasing frequency, largely due to improved access to molecular tools. Nevertheless, little is known about the distribution and frequency of hybrid schistosomes in nature. Screening for hybrids on a large scale is complicated by the need for nuclear and mitochondrial sequence information, precluding a 'simple' barcoding approach. Here we aimed to determine and understand the spatiotemporal distribution of Schistosoma haematobium × Schistosoma bovis hybrids in the Senegal River Basin. From ten villages, distributed over the four main water basins, we genotyped a total of 1236 schistosome larvae collected from human urine samples using a partial mitochondrial cox1 fragment; a subset of 268 parasites was also genotyped using ITS rDNA. Hybrid schistosomes were unevenly distributed, with substantially higher numbers in villages bordering Lac de Guiers than in villages from the Lampsar River and the Middle Valley of the Senegal River. The frequency of hybrids per village was not linked with the prevalence of urinary schistosomiasis in that village. However, we did find a significant positive association between the frequency of hybrids per village and the prevalence of Schistosoma mansoni. We discuss the potential consequences of adopting a barcoding approach when studying hybrids in nature." "Cytokine responses to Schistosoma mansoni and Schistosoma haematobium in relation to infection in a co-endemic focus in northern Senegal" "Lynn Meurs, Moustapha Mbow, Nele Boon, Kim Vereecken, Abena Serwaa Amoah, Lucja A Labuda, Tandakha Ndiaye Dieye, Souleymane Mboup, Maria Yazdanbakhsh, Katja Polman" "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." "Cytokine Responses to Schistosoma mansoni and Schistosoma haematobium in Relation to Infection in a Co-endemic Focus in Northern Senegal" "Lynn Meurs, Moustapha Mbow, Nele Boon, Kim Vereecken, Abena Serwaa Amoah, Lucja A Labuda, Tandakha Ndiaye Dièye, Souleymane Mboup, Maria Yazdanbakhsh, Katja Polman" "BackgroundIn 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.MethodologyWhole 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 FindingsSchistosoma 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/SignificanceThis 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." "Diagnosis and clinical management of Schistosoma haematobium-Schistosoma bovis hybrid infection in a cluster of travelers returning from Mali" "Patrick Soentjens, Lieselotte Cnops, Tine Huyse, Cedric Yansouni, Daniel De Vos, Emmanuel Bottieau, Joannes Clerinx, Marjan Van Esbroeck" "Ten Belgian travelers returned from Mali with a Schistosoma haematobium-Schistosoma bovis hybrid infection, confirmed by DNA sequencing from eggs. Clinical symptoms and laboratory findings resembled those of classic acute schistosomiasis, but the detected eggs were morphologically unusual." "Bladder morbidity and hepatic fibrosis in mixed Schistosoma haematobium and S. mansoni infections: a population-wide study in northern Senegal" "Lynn Meurs, M. Mbow, Kim Vereecken, Joris Menten, Souleymane Mboup, Katja Polman" "BACKGROUND: The global distribution map of schistosomiasis shows a large overlap of Schistosoma haematobium- and S. mansoni-endemic areas in Africa. Yet, little is known about the consequences of mixed Schistosoma infections for the human host. A recent study in two neighboring co-endemic communities in Senegal indicated that infection intensities of both species were higher in mixed than in single infections. Here, we investigated the relationship between mixed Schistosoma infections and morbidity in the same population. So far, this has only been studied in children. METHODS: Schistosoma infection was assessed by microscopy. Schistosoma-specific morbidity was assessed by ultrasound according to WHO guidelines. Multivariable logistic regression models were used to identify independent risk factors for morbidity. PRINCIPAL FINDINGS: Complete parasitological and morbidity data were obtained from 403 individuals. Schistosoma haematobium-specific bladder morbidity was observed in 83% and S. mansoni-specific hepatic fibrosis in 27% of the participants. Bladder morbidity was positively associated with S. haematobium infection intensity (OR = 1.9 (95% CI 1.3-2.9) for a 10-fold increase in intensity). Moreover, people with mixed infections tended to have less bladder morbidity than those with single S. haematobium infections (OR = 0.3 (95% CI 0.1-1.1)). This effect appeared to be related to ectopic S. mansoni egg elimination in urine. Hepatic fibrosis on the other hand was not related to S. mansoni infection intensity (OR = 0.9 (95% CI 0.6-1.3)), nor to mixed infections (OR = 1.0 (95% CI 0.7-1.7)). CONCLUSIONS/SIGNIFICANCE: This is the first population-wide study on the relationship between mixed Schistosoma infections and morbidity. Mixed infections did not increase the risk of S. mansoni-associated morbidity. They even tended to reduce the risk of S. haematobium-associated morbidity, suggesting a protective effect of S. mansoni infection on bladder morbidity. These unexpected results may have important consequences for schistosomiasis control in co-endemic areas and warrant further investigation." "A praziquantel treatment study of immune and transcriptome profiles in Schistosoma haematobium-infected Gabonese schoolchildren" "Lucja A Labuda, Ayola A Adegnika, Bruce A. Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D. Manurung, Jeannot F. Zinsou, Hermelijn H. Smits, Peter G. Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh" "Background. Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.Methods. Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.Results. Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were negatively associated with CD4(+)CD25(+)FOXP3(+) T-cells and accompanied by increased frequency of effector memory T-cells. Innate responses to Toll like receptor (TLR) ligation decreased with treatment and showed positive association with CD4(+)CD25(+)FOXP3(+) T-cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, whereas parasite removal was associated with a more quiescent profile. Further analysis indicated that alteration in cellular energy metabolism was associated with S haematobium infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), transcription factors that negatively regulate T-cell activation, may play a role in adaptive immune hyporesponsiveness.Conclusions. Using a longitudinal study design, we found contrasting effects of schistosome infection on innate and adaptive immune responses. Whereas the innate immune system appears more activated, the adaptive immunity is in a hyporesponsive state reflected in alterations in CD4(+)CD25(+)FOXP3(+) T-cells, cellular metabolism, and transcription factors involved in anergy."