Prevalence of urogenital and intestinal schistosomiasis among school children in South-west Nigeria

BackgroundThe risk of co-infection with Schistosoma haematobium and S. mansoni and the potential harmful effect on morbidity and control is enhanced by the overlapping distribution of both species in sub-Saharan Africa. Despite the reported high endemicity of both species in Nigeria, studies on the spread and effect of their mixed infection are limited. Therefore, a cross-sectional survey was conducted among school children in two communities in South-west Nigeria to investigate the prevalence of mixed human schistosome infection, intensity, and possible ectopic egg elimination.MethodsUrine and stool samples were collected from consenting school children in Ilie and Ore communities of Osun State, Nigeria. Schistosoma haematobium eggs were detected in urine using the urine filtration technique, while S. mansoni eggs were detected in stool using the Kato–Katz thick smear technique.ResultsThe study enrolled 466 primary and secondary school children (211; 45.3% males vs. 255; 54.7% females; mean age 11.6 ± 3.16 years). The overall prevalence of schistosomiasis was 40% (185/466), with 19% (89/466) recording single S. haematobium infection while 9% (41/465) had a single S. mansoni infection. The geometric mean egg count for S. haematobium was 189.4 egg/10ml urine; 95% CI: range 115.9–262.9, while for S. mansoni, it was 115.7 epg; 95% CI: range 78.4–152.9. The prevalence of ectopic S mansoni (S. mansoni eggs in urine) was 4.7%, while no ectopic S. haematobium (S. haematobium eggs in stool) was recorded. Mixed infection of S. haematobium/S. mansoni had a prevalence of 9.5% (44/466). More females (54.5%) presented with S. haematobium/S. mansoni co-infection. For both parasites, males had higher infection intensity, with a significant difference observed with S. haematobium (p = 0.0004). Hematuria was significant in individuals with single S. haematobium infection (p = 0.002), mixed ectopic S. haematobium/S. mansoni (p = 0.009) and mixed S. haematobium/S. mansoni/ectopic S. mansoni (p = 0.0003).ConclusionsThese findings suggest the probability of interspecific interactions between S. haematobium and S. mansoni. Scaling up of mass administration of praziquantel and control measures in the study areas is highly desirable.     

Identifying and Evaluating Field Indicators of Urogenital Schistosomiasis-Related Morbidity in Preschool-Aged Children

BackgroundSeveral studies have been conducted quantifying the impact of schistosome infections on health and development in school-aged children. In contrast, relatively little is known about morbidity levels in preschool-aged children (≤5 years) who have been neglected in terms of schistosome research and control. The aim of this study was to compare the utility of available point-of-care (POC) morbidity diagnostic tools in preschool versus primary school-aged children (6–10 years) and determine markers which can be used in the field to identify and quantify Schistosoma haematobium-related morbidity.Conclusions/SignificancePreschool-aged children in endemic areas can be effectively screened for schistosome-related morbidity using the same currently available diagnostic tools applicable to older children. UACR for detecting albuminuria is recommended as the best choice for rapid assessment of morbidity attributed to S. haematobium infection in children in the field. The use of dipstick microhaematuria and proteinuria as additional indicators of schistosome-related morbidity would improve the estimation of disease burden in young children.     

Prevalence and risk factors of schistosomiasis among primary school children in four selected regions of The Gambia

BackgroundThe Gambia initiated a control programme for schistosomiasis in 2015. In light of this, recent and comprehensive data on schistosomiasis is required to effectively guide the control programme. This study aimed to evaluate the prevalence and associated risk factors of schistosomiasis among primary school children in The Gambia.MethodsWe utilised data from a previous study conducted in 2015 in 4 regions of The Gambia: North Bank Region (NBR), Lower River Region (LRR), Central River Region (CRR) and Upper River Region (URR). In the parent study, ten schools were selected randomly from each region. Urine and stool samples collected from 25 boys and 25 girls (7–14 years) in each school were examined for urinary schistosomiasis (Schistosoma haematobium infection) and intestinal schistosomiasis (Schistosoma mansoni infection) using urine filtration, dipstick and Kato-Katz methods.Principal findingsUrinary schistosomiasis had an overall prevalence of 10.2% while intestinal schistosomiasis had a prevalence of 0.3% among the sampled school children. Prevalence of urinary schistosomiasis was significantly different among regions (χ 2 = 279.958, df = 3, p < 0.001), with CRR (27.6%) being the most endemic region, followed by URR (12.0%), then LRR (0.6%), and NBR (0.0%). Prevalence of intestinal schistosomiasis was also significantly variable among regions, with 4 of the 5 positive cases detected in CRR and 1 case in URR. Every school sampled in CRR had at least one student infected with S. haematobium, 50% of schools in URR had S. haematobium infection, and just one school in LRR had S. haematobium infection. While S. haematobium infection was significantly higher in boys (χ 2 = 4.440, df = 1, p = 0.035), no significant difference in infection rate was observed among age groups (χ 2 = 0.882, df = 2, p = 0.643). Two of the 5 students infected with S. mansoni were boys and 3 were girls. Four of these 5 students were in the 10–12 years age group and 1 was in the 7–9 years age group. Macrohaematuria and microhaematuria were found to be statistically associated with presence of S. haematobium eggs in urine. Being a male was a risk factor of S. haematobium infection. Bathing, playing and swimming in water bodies were found to pose less risk for S. haematobium infection, indicating that the true water contact behaviour of children was possibly underrepresented.ConclusionThe findings of this study provide invaluable information on the prevalence of schistosomiasis in The Gambia. This was useful for the schistosomiasis control efforts of the country, as it guided mass drug administration campaigns in eligible districts in the study area. More studies on S. mansoni and its intermediate snail hosts are required to establish its true status in The Gambia. As children sometimes tend to provide responses that potentially please the research or their teacher, data collection frameworks and approaches that ensure true responses in studies involving children should be devised and used.     

Urinary Estrogen Metabolites and Self-Reported Infertility in Women Infected with Schistosoma haematobium

Background

Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens.

Methodology/Principal Findings

A cross-sectional study was undertaken of female residents of a region in Bengo province, Angola, endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two (parents interviewed) to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosome infection, and for liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn) to investigate estrogen metabolites in the urine. Novel estrogen-like metabolites, potentially of schistosome origin, were detected in the urine of participants who were positive for eggs of S. haematobium, but not detected in urines negative for S. haematobium eggs. The catechol-estrogens/ DNA adducts were significantly associated with schistosomiasis (OR 3.35; 95% CI 2.32–4.84; P≤0.001). In addition, presence of these metabolites was positively associated with infertility (OR 4.33; 95% CI 1.13–16.70; P≤0.05).

Conclusions/Significance

Estrogen metabolites occur widely in diverse metabolic pathways. In view of the statistically significant association between catechol-estrogens/ DNA adducts and self-reported infertility, we propose that an estrogen-DNA adduct mediated pathway in S. haematobium-induced ovarian hormonal deregulation could be involved. In addition, the catechol-estrogens/ DNA adducts described here represent potential biomarkers for schistosomiasis haematobia.     

Algorithm for diagnosis of early Schistosoma haematobium using prodromal signs and symptoms in pre-school age children in an endemic district in Zimbabwe

IntroductionPrompt diagnosis of acute schistosomiasis benefits the individual and provides opportunities for early public health intervention. In endemic areas schistosomiasis is usually contracted during the first 5 years of life, thus it is critical to look at how the infection manifests in this age group. The aim of this study was to describe the prodromal signs and symptoms of early schistosomiasis infection, correlate these with early disease progression and risk score to develop an easy to use clinical algorithm to identify early Schistosoma haematobium infection cases in resource limited settings.MethodologyTwo hundred and four, preschool age children who were lifelong residence of a schistosomiasis endemic district and at high risk of acquiring schistosomiasis were followed up from July 2019 to December 2019, during high transmission season. The children received interval and standard full clinical evaluations and laboratory investigations for schistosomiasis by clinicians blinded from their schistosomiasis infection status. Diagnosis of S. haematobium was by urine filtration collected over three consecutive days. Signs and symptoms of schistosomiasis at first examination visit were compared to follow-up visits. Signs and symptoms common on the last schistosomiasis negative visit (before a subsequent positive) were assigned as early schistosomiasis infection (ESI), after possible alternative causes were ruled out. Logistic regression identified clinical predictors. A model based score was assigned to each predictor to create a risk for every child. An algorithm was created based on the predictor risk scores and validated on a separate cohort of 537 preschool age children.ResultsTwenty-one percent (42) of the participants were negative for S. haematobium infection at baseline but turned positive at follow-up. The ESI participants at the preceding S. haematobium negative visit had the following prodromal signs and symptoms in comparison to non-ESI participants; pruritic rash adjusted odds ratio (AOR) = 21.52 (95% CI 6.38–72.66), fever AOR = 82 (95% CI 10.98–612), abdominal pain AOR = 2.6 (95% CI 1.25–5.43), pallor AOR = 4 (95% CI 1.44–11.12) and a history of facial/body swelling within the previous month AOR = 7.31 (95% CI 3.49–15.33). Furthermore 16% of the ESI group had mild normocytic anaemia, whilst 2% had moderate normocytic anaemia. A risk score model was created using a rounded integer from the relative risks ratios. The diagnostic algorithm created had a sensitivity of 81% and a specificity of 96.9%, Positive predictive value = 87.2% and NPV was 95.2%. The area under the curve for the algorithm was 0.93 (0.90–0.97) in comparison with the urine dipstick AUC = 0.58 (0.48–0.69). There was a similar appearance in the validation cohort as in the derivative cohort.ConclusionThis study demonstrates for the first time prodromal signs and symptoms associated with early S. haematobium infection in pre-school age children. These prodromal signs and symptoms pave way for early intervention and management, thus decreasing the harm of late diagnosis. Our algorithm has the potential to assist in risk-stratifying pre-school age children for early S. haematobium infection. Independent validation of the algorithm on another cohort is needed to assess the utility further.     

Cervicovaginal bacterial communities in reproductive-aged Tanzanian women with Schistosoma mansoni,Schistosoma haematobium,or without schistosome infection

Schistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV acquisition and have not been studied in schistosome infection. We collected cervical swabs from Tanzanian women with and without S. mansoni and S. haematobium to determine effects on cervicovaginal microbiota. Infected women were treated, and follow-up swabs were collected after 3 months. 16S rRNA sequencing was performed on DNA extracted from swabs. We compared 39 women with S. mansoni with 52 uninfected controls, and 16 with S. haematobium with 27 controls. S. mansoni-infected women had increased abundance of Peptostreptococcus (p = 0.026) and presence of Prevotella timonesis (p = 0.048) compared to controls. High-intensity S. haematobium infection was associated with more diverse cervicovaginal bacterial communities than uninfected controls (p = 0.0159). High-intensity S. mansoni infection showed a similar trend (p = 0.154). At follow-up, we observed increased alpha diversity in S. mansoni (2.53 vs. 1.72, p = 0.022) and S. haematobium (2.05 vs. 1.12, p = 0.066) infection groups compared to controls. Modifications in cervicovaginal microbiota, particularly increased diversity and abundance of taxa associated with bacterial vaginosis and HIV (Peptostreptococcus, Prevotella), were associated with schistosome infection.     

Age-Related Patterns in Human Myeloid Dendritic Cell Populations in People Exposed to Schistosoma haematobium Infection

Background

Urogenital schistosomiasis is caused by the helminth parasite Schistosoma haematobium. In high transmission areas, children acquire schistosome infection early in life with infection levels peaking in early childhood and subsequently declining in late childhood. This age-related infection profile is thought to result from the gradual development of protective acquired immunity. Age-related differences in schistosome-specific humoral and cellular responses have been reported from several field studies. However there has not yet been a systematic study of the age-related changes in human dendritic cells, the drivers of T cell polarisation.

Methods

Peripheral blood mononuclear cells were obtained from a cohort of 61 Zimbabwean aged 5–45 years with a S. haematobium prevalence of 47.5%. Two subsets of dendritic cells, myeloid and plasmacytoid dentritic cells (mDCs and pDCs), were analyzed by flow cytometry.

Findings

In this population, schistosome infection levels peaked in the youngest age group (5–9 years), and declined in late childhood and adulthood (10+ years). The proportions of both mDCs and pDCs varied with age. However, for mDCs the age profile depended on host infection status. In the youngest age group infected people had enhanced proportions of mDCs as well as lower levels of HLA-DR on mDCs than un-infected people. In the older age groups (10–13 and 14–45 years) infected people had lower proportions of mDCs compared to un-infected individuals, but no infection status-related differences were observed in their levels of HLA-DR. Moreover mDC proportions correlated with levels of schistosome-specific IgG, which can be associated with protective immunity. In contrast proportions of pDCs varied with host age, but not with infection status.

Conclusions

Our results show that dendritic cell proportions and activation in a human population living in schistosome-endemic areas vary with host age reflecting differences in cumulative history of exposure to schistosome infection.     

Co-endemicity of Plasmodium falciparum and Intestinal Helminths Infection in School Age Children in Rural Communities of Kwara State Nigeria

Background

Malaria and intestinal helminths co-infection are major public health problems particularly among school age children in Nigeria. However the magnitude and possible interactions of these infections remain poorly understood. This study determined the prevalence, impact and possible interaction of Plasmodium falciparum and intestinal helminths co-infection among school children in rural communities of Kwara State, Nigeria.

Methods

Blood, urine and stool samples were collected from 1017 primary school pupils of ages 4–15 years. Stool samples were processed using both Kato-Katz and formol-ether concentration techniques and microscopically examined for intestinal helminths infection. Urine samples were analyzed using sedimentation method for Schistosoma haematobium. Plasmodium falciparum was confirmed by microscopy using thick and thin blood films methods and packed cell volume (PCV) was determined using hematocrit reader. Univariate analysis and chi-square statistical tests were used to analyze the data.

Results

Overall, 61.2% of all school children had at least an infection of either P. falciparum, S. haematobium, or intestinal helminth. S. haematobium accounted for the largest proportion (44.4%) of a single infection followed by P. falciparum (20.6%). The prevalence of malaria and helminth co-infection in the study was 14.4%. Four species of intestinal helminths were recovered from the stool samples and these were hookworm (22.5%), Hymenolepis species (9.8%), Schistosoma mansoni (2.9%) and Enterobius vermicularis (0.6%). The mean densities of P. falciparum in children co-infected with S. haematobium and hookworm were higher compared to those infected with P. falciparum only though not statistically significant (p = 0.062). The age distribution of both S. haematobium (p = 0.049) and hookworm (p = 0.034) infected children were statistically significant with the older age group (10–15 years) recording the highest prevalence of 47.2% and 25% respectively. Children who were infected with S. haematobium (RR = 1.3) and hookworm (RR = 1.4) have equal chances of being infected with P. falciparum as children with no worm infection. On the other hand children infected with Hymenolepis spp. (p<0.0001) are more likely to be infected with P. falciparum than Hymenolepis spp. uninfected children (RR = 2.0)

Conclusions

These findings suggest that multiple parasitic infections are common in school age children in rural communities of Kwara State Nigeria. The Hymenolepis spp. induced increase susceptibility to P. falciparum could have important consequences on how concurrent infections affect the expression or pathogenesis of these infections.     

Differences in the Faecal Microbiome in Schistosoma haematobium Infected Children vs. Uninfected Children

BackgroundSeveral infectious diseases and therapeutic interventions cause gut microbe dysbiosis and associated pathology. We characterised the gut microbiome of children exposed to the helminth Schistosoma haematobium pre- and post-treatment with the drug praziquantel (PZQ), with the aim to compare the gut microbiome structure (abundance and diversity) in schistosome infected vs. uninfected children.MethodsStool DNA from 139 children aged six months to 13 years old; with S. haematobium infection prevalence of 27.34% was extracted at baseline. 12 weeks following antihelminthic treatment with praziqunatel, stool DNA was collected from 62 of the 139 children. The 16S rRNA genes were sequenced from the baseline and post-treatment samples and the sequence data, clustered into operational taxonomic units (OTUs). The OTU data were analysed using multivariate analyses and paired T- test.ResultsPre-treatment, the most abundant phyla were Bacteroidetes, followed by Firmicutes and Proteobacteria respectively. The relative abundance of taxa among bacterial classes showed limited variation by age group or sex and the bacterial communities had similar overall compositions. Although there were no overall differences in the microbiome structure across the whole age range, the abundance of 21 OTUs varied significantly with age (FDR<0.05). Some OTUs including Veillonella, Streptococcus, Bacteroides and Helicobacter were more abundant in children ≤ 1 year old compared to older children. Furthermore, the gut microbiome differed in schistosome infected vs. uninfected children with 27 OTU occurring in infected but not uninfected children, for 5 of these all Prevotella, the difference was statistically significant (p <0.05) with FDR <0.05. PZQ treatment did not alter the microbiome structure in infected or uninfected children from that observed at baseline.ConclusionsThere are significant differences in the gut microbiome structure of infected vs. uninfected children and the differences were refractory to PZQ treatment.     

CD16 Expression on Monocytes in Healthy Individuals but Not Schistosome-Infected Patients Is Positively Associated with Levels of Parasite-Specific IgG and IgG1

Human IgG1 antibody responses are associated with protection against Schistosoma haematobium infection and are now a target for schistosome vaccine development. This study aimed to investigate the relationship between total IgG and the IgG subclasses and the monocyte IgG receptor, known as FcγRIIIa or CD16, in schistosome exposed people. Systemic levels of schistosome-specific anti-adult worm total IgG and IgG subclass titres were measured by ELISA in 100 individuals from an S. haematobium endemic area in Zimbabwe and, using parametric statistical methods and regression analysis, related to the levels of CD16 expression on individuals'' circulating monocytes, determined via flow cytometry. Monocyte CD16 expression rose with parasite-specific total IgG and IgG1 in healthy participants, but not in schistosome infected patients. Similar to parasite-specific IgG and IgG1, CD16 expression in healthy individuals is associated with protection against schistosome infection. This relationship indicates a mechanistic link between the innate and adaptive immune responses to helminth infection in protection against infection. Further understanding the elements of a protective immune response in schistosomiasis may aid in efforts to develop a protective vaccine against this disease.     

Exposure,hazard, and vulnerability all contribute to Schistosoma haematobium re-infection in northern Senegal

BackgroundInfectious disease risk is driven by three interrelated components: exposure, hazard, and vulnerability. For schistosomiasis, exposure occurs through contact with water, which is often tied to daily activities. Water contact, however, does not imply risk unless the environmental hazard of snails and parasites is also present in the water. By increasing reliance on hazardous activities and environments, socio-economic vulnerability can hinder reductions in exposure to a hazard. We aimed to quantify the contributions of exposure, hazard, and vulnerability to the presence and intensity of Schistosoma haematobium re-infection.Methodology/Principal findingsIn 13 villages along the Senegal River, we collected parasitological data from 821 school-aged children, survey data from 411 households where those children resided, and ecological data from all 24 village water access sites. We fit mixed-effects logistic and negative binomial regressions with indices of exposure, hazard, and vulnerability as explanatory variables of Schistosoma haematobium presence and intensity, respectively, controlling for demographic variables. Using multi-model inference to calculate the relative importance of each component of risk, we found that hazard (Ʃw_{i =} 0.95) was the most important component of S. haematobium presence, followed by vulnerability (Ʃw_i = 0.91). Exposure (Ʃw_i = 1.00) was the most important component of S. haematobium intensity, followed by hazard (Ʃw_i = 0.77). Model averaging quantified associations between each infection outcome and indices of exposure, hazard, and vulnerability, revealing a positive association between hazard and infection presence (OR = 1.49, 95% CI 1.12, 1.97), and a positive association between exposure and infection intensity (RR 2.59–3.86, depending on the category; all 95% CIs above 1)Conclusions/SignificanceOur findings underscore the linkages between social (exposure and vulnerability) and environmental (hazard) processes in the acquisition and accumulation of S. haematobium infection. This approach highlights the importance of implementing both social and environmental interventions to complement mass drug administration.     

Prevalence of Schistosoma haematobium Infection among School-Age Children in Afar Area,Northeastern Ethiopia

In this study, the prevalence and intensity of Schistosoma haematobium infection was determined among school-age children living in the Middle and Lower Awash Valley, Afar Regional State of Ethiopia. Between February and May 2014, urine samples were collected from 885 school-age children (5–16 years of age) from the Middle (n = 632; 4 villages) and Lower (n = 253; 3 villages) Awash Valley. All samples were processed using urine filtration to detect and quantify S. haematobium eggs. In addition, a subset of the urine samples was tested for hematuria using a urine dipstick (n = 556). The overall prevalence was 20.8% (95% Confidence Interval (CI) = 18.1%, 23.5%), based on urine filtration but the prevalence considerably varied across villages both in the Middle (from 12.5% to 37.0%) and Lower Awash Valley (from 0 to 5.3%). The overall mean urine egg count (UEC) among the infected children was 4.0 eggs/10 ml of urine (95% CI = 2.43, 5.52). The infection intensity varied from 0.4 eggs/10 ml of urine to 7.7 eggs/10 ml of urine in the Middle Awash Valley, and from 0 to 1.1 eggs/10 ml of urine in Lower Awash Valley. Age and sex were not associated with S. haematobium infection based on the multivariable logistic regression model. The prevalence of hematuria was 56.3% (95% CI = 52.2%, 60.4%) among a subset of the study participants (556) examined using the urine dipstick. The prevalence of hematuria also varies with villages from 8.3% to 93.2%. In conclusion, the prevalence of S. haematobium infection in the Middle Awash Valley was high and it varies across villages. Hence, children living in the present study villages of the Middle Awash Valley need to be treated with praziquantel to reduce morbidity and disrupt transmission.     

Malaria and Helminth Co-Infections in School and Preschool Children: A Cross-Sectional Study in Magu District,North-Western Tanzania

Background

Malaria, schistosomiasis and soil transmitted helminth infections (STH) are important parasitic infections in Sub-Saharan Africa where a significant proportion of people are exposed to co-infections of more than one parasite. In Tanzania, these infections are a major public health problem particularly in school and pre-school children. The current study investigated malaria and helminth co-infections and anaemia in school and pre-school children in Magu district, Tanzania.

Methodology

School and pre-school children were enrolled in a cross-sectional study. Stool samples were examined for Schistosoma mansoni and STH infections using Kato Katz technique. Urine samples were examined for Schistosoma haematobium using the urine filtration method. Blood samples were examined for malaria parasites and haemoglobin concentrations using the Giemsa stain and Haemoque methods, respectively.

Principal Findings

Out of 1,546 children examined, 1,079 (69.8%) were infected with one or more parasites. Malaria-helminth co-infections were observed in 276 children (60% of all children with P. falciparum infection). Malaria parasites were significantly more prevalent in hookworm infected children than in hookworm free children (p = 0.046). However, this association was non-significant on multivariate logistic regression analysis (OR = 1.320, p = 0.064). Malaria parasite density decreased with increasing infection intensity of S. mansoni and with increasing number of co-infecting helminth species. Anaemia prevalence was 34.4% and was significantly associated with malaria infection, S. haematobium infection and with multiple parasite infections. Whereas S. mansoni infection was a significant predictor of malaria parasite density, P. falciparum and S. haematobium infections were significant predictors of anaemia.

Conclusions/Significance

These findings suggest that multiple parasite infections are common in school and pre-school children in Magu district. Concurrent P. falciparum, S. mansoni and S. haematobium infections increase the risk of lower Hb levels and anaemia, which in turn calls for integrated disease control interventions. The associations between malaria and helminth infections detected in this study need further investigation.     

Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study

Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21–1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15–1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27–2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22–2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D’ = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.     

Cytokine Responses to the Anti-schistosome Vaccine Candidate Antigen Glutathione-S-transferase Vary with Host Age and Are Boosted by Praziquantel Treatment

Background

Improved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ), which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST) is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment.

Methodology

Blood samples from inhabitants of a Schistosoma haematobium-endemic area were incubated for 48 hours with or without GST before (n = 195) and six weeks after PZQ treatment (n = 107). Concentrations of cytokines associated with innate inflammatory (TNFα, IL-6, IL-8), type 1 (Th1; IFNγ, IL-2, IL-12p70), type 2 (IL-4, IL-5, IL-13), type 17 (IL-17A, IL-21, IL-23p19) and regulatory (IL-10) responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA). Factor analysis and multidimensional scaling were used to analyse multiple cytokines simultaneously.

Principal Findings

A combination of GST-specific type 2 (IL-5 and IL-13) and regulatory (IL-10) cytokines was significantly lower in 10–12 year olds, the age group at which S. haematobium infection intensity and prevalence peak, than in 4–9 or 13+ year olds. Following PZQ treatment there was an increase in the number of participants producing detectable levels of GST-specific cytokines (TNFα, IL-6, IL-8, IFNγ, IL-12p70, IL-13 and IL-23p19) and also a shift in the GST-specific cytokine response towards a more pro-inflammatory phenotype than that observed before treatment. Participant age and pre-treatment infection status significantly influenced post-treatment cytokine profiles.

Conclusions/Significance

In areas where schistosomiasis is endemic host age, schistosome infection status and PZQ treatment affect the cellular cytokine response to GST. Thus the efficacy of a GST-based vaccine may also be shaped by the demographic and epidemiological characteristics of targeted populations.     

Interaction of the extracellular domain of the epidermal growth factor receptor with gangliosides.

Ganglioside GM3 inhibits epidermal growth factor (EGF)-dependent cell proliferation in a variety of cell lines. Both in vitro and in vivo, this glycosphingolipid inhibits the kinase activity of the EGF receptor (EGFR). Furthermore, membrane preparations containing EGFR can bind to GM3-coated surfaces. These data suggest that GM3 may interact directly with the EGFR. In this study, the interaction of gangliosides with the extracellular domain (ECD) of the EGFR was investigated. The purified human recombinant ECD from insect cells bound directly to ganglioside GM3. The ganglioside interaction site appears to be distinct from the EGF-binding site. In agreement with previous reports on the effects of specific gangliosides on EGFR kinase activity, the ECD preferentially interacted with GM3. The order of relative binding of other gangliosides investigated was as follows: GM3 GM2, GD3, GM4 > GM1, GD1a, GD1b, GT1b, GD2, GQ1b > lactosylceramide. These data suggest that NeuAc-lactose is essential for binding and that any sugar substitution reduces binding. In agreement with the specificity of soluble ECD binding to gangliosides, GM3 specifically inhibited EGFR autophosphorylation. Identification of a ganglioside interaction site on the ECD of the EGFR is consistent with the hypothesis that endogenous GM3 may function as a direct modulator of EGFR activity.     

Housing environment and early childhood development in sub-Saharan Africa: A cross-sectional analysis

BackgroundThe influence of the safety and security of environments on early childhood development (ECD) has been under-explored. Although housing might be linked to ECD by affecting a child’s health and a parent’s ability to provide adequate care, only a few studies have examined this factor. We hypothesized that housing environment is associated with ECD in sub-Saharan Africa (SSA).Methods and findingsFrom 92,433 children aged 36 to 59 months who participated in Multiple Indicator Cluster Survey (MICS) in 20 SSA countries, 88,271 were tested for cognitive and social–emotional development using the Early Childhood Development Index (ECDI) questionnaire and were thus included in this cross-sectional analysis. Children’s mean age was 47.2 months, and 49.8% were girls. Children were considered developmentally on track in a certain domain if they failed no more than 1 ECDI item in that domain. In each country, we used conditional logistic regression models to estimate the association between improved housing (housing with finished building materials, improved drinking water, improved sanitation facilities, and sufficient living area) and children’s cognitive and social–emotional development, accounting for contextual effects and socioeconomic factors. Estimates from each country were pooled using random-effects meta-analyses. Subgroup analyses were conducted by the child’s gender, maternal education, and household wealth quintiles. On-track cognitive development was associated with improved housing (odds ratio [OR] = 1.15, 95% CI 1.06 to 1.24, p < 0.001), improved drinking water (OR = 1.07, 95% CI 1.00 to 1.14, p = 0.046), improved sanitation facilities (OR = 1.15, 95% CI 1.03 to 1.28, p = 0.014), and sufficient living area (OR = 1.06, 95% CI 1.01 to 1.10, p = 0.018). On-track social–emotional development was associated with improved housing only in girls (OR = 1.14, 95% CI 1.04 to 1.25, p = 0.006). The main limitations of this study included the cross-sectional nature of the datasets and the use of the ECDI, which lacks sensitivity to measure ECD outcomes.ConclusionsIn this study, we observed that improved housing was associated with on-track cognitive development and with on-track social–emotional development in girls. These findings suggest that housing improvement in SSA may be associated not only with benefits for children’s physical health but also with broader aspects of healthy child development.

In a cross-sectional analysis of nationally representative survey data from 20 countries, Yaqing Gao and colleagues investigate associations between housing environment and cognitive and social development in children.     

Associations between infection intensity categories and morbidity prevalence in school-age children are much stronger for Schistosoma haematobium than for S. mansoni

BackgroundWorld Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children.MethodologyA total of 22,488 children aged 6–15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003–2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data.Principal findingsS. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed.Conclusions/significanceCurrent status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual’s intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program.     

Micro-Geographical Heterogeneity in Schistosoma mansoni and S. haematobium Infection and Morbidity in a Co-Endemic Community in Northern Senegal

Background

Schistosoma mansoni and S. haematobium are co-endemic in many areas in Africa. Yet, little is known about the micro-geographical distribution of these two infections or associated disease within such foci. Such knowledge could give important insights into the drivers of infection and disease and as such better tailor schistosomiasis control and elimination efforts.

Methodology

In a co-endemic farming community in northern Senegal (346 children (0–19 y) and 253 adults (20–85 y); n = 599 in total), we studied the spatial distribution of S. mansoni and S. haematobium single and mixed infections (by microscopy), S. mansoni-specific hepatic fibrosis, S. haematobium-specific urinary tract morbidity (by ultrasound) and water contact behavior (by questionnaire). The Kulldorff''s scan statistic was used to detect spatial clusters of infection and morbidity, adjusted for the spatial distribution of gender and age.

Principal Findings

Schistosoma mansoni and S. haematobium infection densities clustered in different sections of the community (p = 0.002 and p = 0.023, respectively), possibly related to heterogeneities in the use of different water contact sites. While the distribution of urinary tract morbidity was homogeneous, a strong geospatial cluster was found for severe hepatic fibrosis (p = 0.001). Particularly those people living adjacent to the most frequently used water contact site were more at risk for more advanced morbidity (RR = 6.3; p = 0.043).

Conclusions/Significance

Schistosoma infection and associated disease showed important micro-geographical heterogeneities with divergent patterns for S. mansoni and S. haematobium in this Senegalese community. Further in depth investigations are needed to confirm and explain our observations. The present study indicates that local geospatial patterns should be taken into account in both research and control of schistosomiasis. The observed extreme focality of schistosomiasis even at community level, suggests that current strategies may not suffice to move from morbidity control to elimination of schistosomiasis, and calls for less uniform measures at a finer scale.     

Increased ShTAL1 IgE responses post-Praziquantel treatment may be associated with a reduced risk to re-infection in a Ghanaian S. haematobium-endemic community

BackgroundEvidence from recent studies in Schistosoma mansoni-endemic areas show an age-associated immunity that is positively correlated with IgE titres to Schistosoma mansoni-specific tegumental allergen-like protein 1 (SmTAL1). The structural homology between SmTAL1 and the S. haematobium-specific TAL1 (ShTAL1) has been verified, yet it remains unclear whether similar age- and immune-associated trends characterize ShTAL1. This community-based intervention study was conducted to assess whether ShTAL1IgE responses post-treatment with praziquantel (PZQ) might be associated with a reduced risk to re-infection with S. haematobium.Methodology/Principal findingsThis study was conducted at Agona Abodom, Central Region, Ghana, and involved 114 participants aged 6 to 55 years. EDTA blood samples were collected at baseline and 7 weeks after PZQ treatment (Follow-up). Baseline and Follow-up titres of specific IgG1, IgG4, and IgE antibodies to the S. haematobium-specific adult worm antigen (ShAWA), the Sh-specific soluble egg antigen (ShSEA), and the Sh-specific tegumental-allergen-like 1 protein (ShTAL1) in plasma samples were measured using sandwich ELISA. Participants at both time points also provided stool and urine for helminth egg detection by microscopy. Prevalence of S. haematobium at baseline was 22.80%, and decreased to 3.50% at Follow-up. The egg reduction rate (ERR) was 99.87%. Overall plasma levels of ShTAL1-IgE increased 7 weeks post-PZQ treatment, and with increasing age; whiles S. haematobium infection prevalence and intensity decreased. For S. haematobium-infected participants who were egg-negative at Follow-up (N = 23), minimal median levels of ShTAL1-IgE were observed for all age groups prior to treatment, whilst median levels increased considerably among participants aged 12 years and older at Follow-up; and remained minimal among participants aged 11 years or less. In the univariate analysis, being aged 12 years or older implied an increased likelihood for ShTAL1-IgE positivity [12–14 years (cOR = 9.64, 95% CI = 2.09–44.51; p = 0.004); 15+ years (cOR = 14.26, 95% CI = 3.10–65.51; p = 0.001)], and this remained significant after adjusting for confounders [12–14 years (aOR = 22.34, 95% CI = 2.77–180.14; p = 0.004); ≥15 years (aOR = 51.82, 95% CI = 6.44–417.17; p < 0.001)]. Conversely, median ShTAL1-IgG4 titres were hardly detectible at Follow-up.Conclusions/SignificanceThese findings demonstrate that increased IgE levels to ShTAL1 7 weeks after PZQ treatment could be associated with a reduced risk to re-infection, and adds to the large body of evidence suggesting a protective role of the treatment-induced ShTAL1 antigen in schistosomiasis infections. It was also quite clear from this work that apart from being persistently S. haematobium-positive, elevated ShTAL1-IgG4 levels at Follow-up could be indicative of susceptibility to re-infection. These outcomes have important implications in vaccine development, and in shifting the paradigm in mass chemotherapy programmes from a ‘one-size-fits-all’ approach to more sub-group-/participant-specific strategies in endemic areas.