Cytokine Kinetics during Progression of COVID-19 in Rwanda Patients: Could IL-9/IFNγ Ratio Predict Disease Severity?

For effective treatments and preventive measures against severe COVID-19, it is essential to determine early markers of disease severity in different populations. We analysed the cytokine kinetics of 129 COVID-19 patients with mild symptoms, 68 severe cases, and 20 healthy controls for the first time in Rwanda. Pro-inflammatory (IFNγ, IL-6, TNFα), Treg (IL-10, TGFß1, TGFß3), Th9 (IL-9), Th17 (IL-17), and Th2 (IL-4, IL-13) cytokines, total IgM and IgG, as well as gene expressions of FoxP3, STAT5+, IFNγ-R1, and ROR alpha+, were measured at day 1, day 7, day 14, day 21, and day 28 post-infection. Severe cases showed a significantly stronger increase than mild patients in levels of all cytokines (except IL-9) and all gene expression on day 1 of infection. Some cytokine levels dropped to levels comparable to mild cases at later time points. Further analysis identified IFNγ as a marker of severity throughout the disease course, while TGFß1, IL-6, and IL-17 were markers of severity only at an early phase. Importantly, this study revealed a striking low IL-9 level and high IFNγ/IL-9 ratio in the plasma of patients who later died compared to mild and severe cases who recovered, suggesting that this could be an important biomarker for predicting the severity of COVID-19 and post-COVID-19 syndrome.

Malacological Survey and Spatial Distribution of Intermediate Host Snails in Schistosomiasis Endemic Districts of Rwanda.

BACKGROUND: Schistosomiasis, due to S. mansoni, is prevalent in Rwanda. However, there is a paucity of information related to the abundance, species, distribution, and infectivity of Schistosoma intermediate host snails. METHODS: Snails were collected from 71 sites, including lakeshores and wetlands. Snails obtained were morphologically identified, and cercariae were shed using standard procedures. Cercariae were molecularly characterized using PCR. GPS coordinates were used to generate geospatial maps of snail distribution that were overlaid with geospatial distribution of schistosomiasis among pre-school children in the same areas. RESULTS: Overall, 3653 snails were morphologically classified as Bulinus spp. and 1449 as Biomphalaria spp. A total of 306 snails shed cercariae, 130 of which were confirmed as S. mansoni cercaria by PCR. There was no significant difference in the proportion of S. mansoni cercariae in wetlands compared to lakeshores. CONCLUSION: Rwandan water bodies harbor an important number of snails that shed S. mansoni cercariae. Furthermore, a strong spatial correlation was observed between the distribution of schistosomiasis in children and the spatial distribution of snail infectivity with S. mansoni. The presence of Bulinus spp. Suggests a potential risk of S. haematobium, although molecular analysis did not show any current transmission of this parasite.

Interprofessional ArclightTM eye health workshop: impact on students' clinical identification and ophthalmic skills.

Visual impairment and blindness affect an estimated 2.2 billion people worldwide. Accessible low-cost diagnostic tools and interprofessional education and collaborative practice are part of ongoing strategies to improve eye care services. This study evaluated the impact of an interprofessional Arclight workshop on undergraduate healthcare students' clinical identification skills related to eye health, and self-reported confidence in ophthalmic skills. Undergraduate students from clinical medical officer, ophthalmic clinical officer, Bachelors and Diploma nursing, and medical programs at the University of Rwanda participated in a pilot interprofessional eye health workshop. The Arclight device, a low-cost ophthalmoscope and simulation eyes were used to enable students to practice ophthalmic skills and thereafter equip them. Clinical identification skills related to common eye conditions, and self-reported confidence in ophthalmic skills were assessed pre and post workshop. Overall, students' ability to identify common eye conditions, and self-reported confidence in relation to all skills statistically improved post workshop, with some differences between professional groups in relation to eye health skills. This IPE experience used the Arclight package as a vehicle for IPE, enabling healthcare students to share and acquire new skills and confidence in relation to recognizing common eye conditions and assessing eye health.

Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-ß1, ß3, and IL-9 in Mild Clinical Presentation.

The proper control of Plasmodium infection requires a finely balanced immune response. Here, we evaluated the implication of TGF-ß1 and TGF-ß3 in this process using novel monoclonal antibodies to measure their plasma concentrations in comparison with other cytokines and the expression of FOXP3 mRNA. Plasma cytokine levels were measured in 80 patients with severe anaemic malaria and 186 with a mild presentation using ELISA, and rtPCR was used to measure FOXP3 mRNA expression. While no mature TGF-ß isoforms were detected in the plasma, the latent TGF-ß1 and TGF-ß3 were strongly upregulated in patients with mild malaria and nearly undetected in patients with severe disease. Similar selective upregulation in mild patients was observed for IL-9 and FOXP3 mRNA, while IL-7, IL-10, IL-17, and IL-27, although higher in mild cases, were also detected in severe disease. In contrast, a clearly skewed trend of severe cases towards higher pro-inflammatory (IL-6, IL-13, TNF-α) and Th1 (IFN-γ) responses was observed, which was associated with a higher level of parasitaemia as well as lower IgG and higher IgM responses. Together, these results suggest that the stimulation of regulatory T cells through TGF-ß1/TGF-ß3 and IL-9 is paramount to an effective and balanced protective immunity in natural human malaria infection.

Using Routinely Collected Health Records to Identify the Fine-Resolution Spatial Patterns of Soil-Transmitted Helminth Infections in Rwanda.

Background. Soil-transmitted helminths (STH) are parasitic diseases with significant public health impact. Analysis is generally based on cross-sectional prevalence surveys; outcomes are mostly aggregated to larger spatial units. However, recent research demonstrates that infection levels and spatial patterns differ between STH species and tend to be localized. Methods. Incidence data of STHs including roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura) and hookworms per primary health facility for 2008 were linked to spatially delineated primary health center service areas. Prevalence data per district for individual and combined STH infections from the 2008 nationwide survey in Rwanda were also obtained. Results. A comparison of reported prevalence and incidence data indicated significant positive correlations for roundworm (R2 = 0.63) and hookworm (R2 = 0.27). Weak positive correlations were observed for whipworm (R2 = 0.02) and the three STHs combined (R2 = 0.10). Incidence of roundworm and whipworm were found to be focalized with significant spatial autocorrelation (Moran's I > 0: 0.05−0.38 and p ≤ 0.03), with (very) high incidence rates in some focal areas. In contrast, hookworm incidence is ubiquitous and randomly distributed (Moran's I > 0: 0.006 and p = 0.74) with very low incidence rates. Furthermore, an exploratory regression analysis identified relationships between helminth infection cases and potential environmental and socio-economic risk factors. Conclusions. Findings show that the spatial distribution of STH incidence is significantly associated with soil properties (sand proportion and pH), rainfall, wetlands and their uses, population density and proportion of rural residents. Identified spatial patterns are important for guiding STH prevention and control programs.

Prevalence Mapping of Schistosoma mansoni Among Pre-school Age Children in Rwanda.

Schistosoma mansoni is endemic in Rwanda, and control programs have been implemented with a special focus on school-age children (SAC), ignoring pre-school age children (pre-SAC) for which the actual prevalence of the disease is not well established. This study consisted of a cross-sectional quantitative mapping of the distribution of Schistosoma mansoni and identification of associated risk factors among pre-SAC throughout the country. The study covered all the 17 districts of Rwanda endemic for Schistosoma mansoni, with a total sample of 4,675 children enrolled from 80 purposively selected villages. The parasitological assessment of children's urine and stool samples was conducted using CCA and Kato Katz methods, respectively, for infection detection. A standard questionnaire was used to collect data on the risk factors, and geospatial assessment was performed using tablets and GPS to record geographic coordinates for plotting locations on maps using ArcGIS software. The overall prevalence of S. mansoni infection across the surveyed areas was 24 and 0.8% by CCA and Kato-Katz, respectively. Infection was significantly associated with bathing children in open water bodies. Furthermore, pre-SAC looked after by siblings (sisters) were two times as much likely to be infected compared to those looked after by mothers. Schistosomiasis control interventions are needed for pre-SAC to limit their exposure to open water bodies with expectations of adapted chemotherapy to be availed. Community-based deworming campaigns may be the best way to ensure good treatment coverage of pre-SAC in Rwanda.

Possible Interactions between Malaria, Helminthiases and the Gut Microbiota: A Short Review.

Malaria, caused by the Plasmodium species, is an infectious disease responsible for more than 600 thousand deaths and more than 200 million morbidity cases annually. With above 90% of those deaths and cases, sub-Saharan Africa is affected disproportionately. Malaria clinical manifestations range from asymptomatic to simple, mild, and severe disease. External factors such as the gut microbiota and helminthiases have been shown to affect malaria clinical manifestations. However, little is known about whether the gut microbiota has the potential to influence malaria clinical manifestations in humans. Similarly, many previous studies have shown divergent results on the effects of helminths on malaria clinical manifestations. To date, a few studies, mainly murine, have shown the gut microbiota's capacity to modulate malaria's prospective risk of infection, transmission, and severity. This short review seeks to summarize recent literature about possible interactions between malaria, helminthiases, and the gut microbiota. The knowledge from this exercise will inform innovation possibilities for future tools, technologies, approaches, and policies around the prevention and management of malaria in endemic countries.

Genomic sequencing of SARS-CoV-2 in Rwanda reveals the importance of incoming travelers on lineage diversity.

COVID-19 transmission rates are often linked to locally circulating strains of SARS-CoV-2. Here we describe 203 SARS-CoV-2 whole genome sequences analyzed from strains circulating in Rwanda from May 2020 to February 2021. In particular, we report a shift in variant distribution towards the emerging sub-lineage A.23.1 that is currently dominating. Furthermore, we report the detection of the first Rwandan cases of the B.1.1.7 and B.1.351 variants of concern among incoming travelers tested at Kigali International Airport. To assess the importance of viral introductions from neighboring countries and local transmission, we exploit available individual travel history metadata to inform spatio-temporal phylogeographic inference, enabling us to take into account infections from unsampled locations. We uncover an important role of neighboring countries in seeding introductions into Rwanda, including those from which no genomic sequences were available. Our results highlight the importance of systematic genomic surveillance and regional collaborations for a durable response towards combating COVID-19.

Using a Value Chain Approach to Map the Pig Production System in Rwanda, Its Governance, and Sanitary Risks.

Rwanda has a fast growing pig production sector projected to continue expansion, due to rising local and regional demand. We undertook a value chain analysis to establish the flows of pigs and pork in Rwanda and the roles of various actors involved, and to understand governance and sanitary risks in the value chain. Cross-sectional qualitative data were collected through focus group discussions and key informant interviews with farmers, brokers, butchers, abattoir managers, and veterinarians. Data were collected on pig production methods and inputs, the source and destination of live and slaughtered pigs, value-adding infrastructures (abattoirs and processing factories), the people involved and interactions between them, governance, and challenges. Pig production in Rwanda is dominated by smallholders, mainly as a source of supplementary income and secondarily for manure. Emerging medium-sized and large pig farms were also identified, located mainly around urban areas. Live pig markets are the main mechanism allowing various actors to buy/sell pigs. Brokers have an important role in pig transactions: they are key in setting prices at markets, examining pigs for disease, organising the supply of pigs for abattoirs and for export. Only a few formal pig abattoirs were identified, which mainly supply to pork processing factories based in Kigali and/or export to customers. Local consumers rely on informal slaughtering at farm or bar/restaurant backyards, with irregular veterinary inspection. Formal abattoirs were attended by a veterinary inspector, however a lack of record keeping was noted. Sanitary risks identified were a lack of biosecurity throughout the chain and poor hygiene at slaughter places. Lingual palpation was practised in pig markets to identify cysticercosis infection, however cyst-positive pigs were not destroyed, but were sold for reduced prices in the same market or later informally sold by the owner. There are few veterinarians attending farms, with most services provided by less qualified technicians or self-treatment of pigs by farmers. Overall, this production system is characterised by a high degree of informality at all nodes, combined with the rapid growth trajectory in the sector. These findings provide a basis to plan interventions tailored to vulnerabilities identified in the Rwanda pig value chain.

A pooled testing strategy for identifying SARS-CoV-2 at low prevalence.

Suppressing infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will probably require the rapid identification and isolation of individuals infected with the virus on an ongoing basis. Reverse-transcription polymerase chain reaction (RT-PCR) tests are accurate but costly, which makes the regular testing of every individual expensive. These costs are a challenge for all countries around the world, but particularly for low-to-middle-income countries. Cost reductions can be achieved by pooling (or combining) subsamples and testing them in groups1-7. A balance must be struck between increasing the group size and retaining test sensitivity, as sample dilution increases the likelihood of false-negative test results for individuals with a low viral load in the sampled region at the time of the test8. Similarly, minimizing the number of tests to reduce costs must be balanced against minimizing the time that testing takes, to reduce the spread of the infection. Here we propose an algorithm for pooling subsamples based on the geometry of a hypercube that, at low prevalence, accurately identifies individuals infected with SARS-CoV-2 in a small number of tests and few rounds of testing. We discuss the optimal group size and explain why, given the highly infectious nature of the disease, largely parallel searches are preferred. We report proof-of-concept experiments in which a positive subsample was detected even when diluted 100-fold with negative subsamples (compared with 30-48-fold dilutions described in previous studies9-11). We quantify the loss of sensitivity due to dilution and discuss how it may be mitigated by the frequent re-testing of groups, for example. With the use of these methods, the cost of mass testing could be reduced by a large factor. At low prevalence, the costs decrease in rough proportion to the prevalence. Field trials of our approach are under way in Rwanda and South Africa. The use of group testing on a massive scale to monitor infection rates closely and continually in a population, along with the rapid and effective isolation of people with SARS-CoV-2 infections, provides a promising pathway towards the long-term control of coronavirus disease 2019 (COVID-19).

Evaluation of a pilot interprofessional Arclight™ workshop for healthcare students in Rwanda: promoting collaborative practice in eye health.

Preventable and treatable visual impairment affects more than 1 billion people worldwide. Rwanda has an estimated visual impairment prevalence of 3.7% amongst the 12 million inhabitants. Around one third of this demand could be addressed through a more integrated and collaborative approach, particularly in primary eye care services. Healthcare students, therefore, need to be prepared for collaborative practice in eye health through interprofessional learning. Interprofessional workshops were piloted with ophthalmic clinical officer, medical clinical officer, nursing and medical students from the University of Rwanda. The aim was to promote collaborative practice by teaching students how to assess and recognize common eye conditions using the Arclight; a low cost, solar powered, portable ophthalmoscope designed for use in low resource settings. Students reported that the workshop content was relevant to all professional groups. They valued the opportunity to learn interprofessionally, share their knowledge and perspectives, and acquire new knowledge and skills together. This pilot helped to identify the most relevant skills and knowledge for future interprofessional eye health training. It enabled the facilitators to reflect on how best to maintain a balance between a quality interprofessional experience and the more specific eye health related learning objectives.

Prevalence and risk factors of intestinal parasites among children under two years of age in a rural area of Rutsiro district, Rwanda - a cross-sectional study.

INTRODUCTION: This study aimed to assess the prevalence and associated risk factors of intestinal parasite infections among children less than two years of age in Rutsiro, Rwanda. METHODS: A cross-sectional parasitological survey was conducted in Rutsiro in June 2016. Fresh stool samples were collected from 353 children and examined using microscopy to detect parasite. A questionnaire was administered to collect data on hygiene, sanitation, socio-demographic and economic characteristics. RESULTS: Approximately one in two children (44.8%) were found to be infected with at least one intestinal parasite. Ascaris (28.5%) was the most prevalent infection followed by Entamoeba histolytica (25.95%) and Giardia lamblia (19.6%). Infection with more than one pathogen was noted e.g. presence of Ascaris and yeasts (8.9%), and amoeba with Trichocephale (4.4%), respectively. Children from non-farming families were less likely to be at risk of intestinal parasite infections (AOR = 0.41, p = 0.028) compared to children from farming families. Children from households with access to treated drinking water were less likely to contract intestinal parasite infections (AOR = 0.44, p = 0.021) compared with those who used untreated water. Children from families with improved sources of water were twice as likely to be diagnosed with intestinal parasitoses compared to those who did not. We postulate that the majority of families (50.1%) who have access to improved water sources do not treat water before consumption. CONCLUSION: The high prevalence of intestinal parasitoses in children warrants strict control measures for improved sanitation, while treatment of drinking water should be considered.

Pre-school aged children are exposed to Schistosoma through Lake Kivu in Rwanda.

Background: Schistosomiasis is prevalent in many sub-Saharan African countries and transmission is through waters contaminated by infected snails. In Rwanda, although schistosomiasis is endemic, very few epidemiological studies exist; of these, schoolchildren have been the focus, neglecting pre-school-aged children (PSAC). Furthermore, malacological surveys to indicate the potential for transmission are scarce in the country. The aim of this study was to determine the prevalence of schistosomiasis among PSAC living on Nkombo Island in Lake Kivu and to map the distribution and infectivity of snails in the area. Methods: Stool and urine samples were collected from children aged 1 to 4 years and tested for schistosomiasis using the Kato Katz and the point-of-care circulating cathodic antigen (POC-CCA) diagnostic techniques respectively. Snails were collected along the shores at five different locations with human-water contact activities and cercaria shedding was microscopically examined. GPS receivers were used to collect geographical coordinates and snail distribution maps were generated using ArcGIS. A questionnaire was used to assess water contact activities and frequency.     Results: A total of 278 PSAC were recruited. Overall, 9.5% (excluding traces) of the tested children reacted positively to the POC-CCA, although there were no ova detected in their stool via Kato Katz. The questionnaire revealed that 48.2% of parents/guardians use Lake Kivu's water for household activities while 42.4% children are taken to the Lake shores daily. Overall, 13.5% of collected snails shed cercariae. Conclusions: PSAC of Nkombo Island are exposed to Schistosoma parasites through contact with Lake Kivu, which hosts a number of snails shedding cercaria. Exposure is through recreational activities but also through bathing as safe water is scarce in the area. Health education of parents/guardians of these young children should be promoted and the national schistosomiasis control program should be integrated into water supply projects.

Schistosomiasis and soil-transmitted helminthiasis in Rwanda: an update on their epidemiology and control.

Even though Rwanda lies within a region that has a high prevalence of schistosomiasis and soil-transmitted helminth (STH) infections, epidemiological information regarding these infections in the country remains scarce. The present review attempts to compile the available data on schistosomiasis and STHs, from 1940 to 2014, to provide an insight on the epidemiological profile of these infections. This information will, in turn, support the design and implementation of sustainable control measures. The available records indicate that only Schistosoma mansoni and all the major species of STHs are endemic in Rwanda. In 2008, the national prevalence of S. mansoni was reported to be 2.7%, ranging from 0 to 69.5%, and that of STH infections was 65.8% (diagnosed using the Kato-Katz technique). The prevalence of these infections varies from one district to another, with schoolchildren remaining a highly affected group. The main control approach is mass drug administration using albendazole and praziquantel, mostly targeting school-aged children in school environments. In 2008, adult individuals living in areas with a prevalence of S. mansoni ≥30% were also included in the mass drug administration programme. However, despite Rwanda achieving an almost 100% coverage of this programme in 2008-2010, the transmission of S. mansoni and STHs continues to take place, as illustrated by the most recent surveys. If Rwanda is to achieve sustainable control and elimination of schistosomiasis and STHs, there is a need to revise the country's control strategy and adopt an integrated control approach that involves a combination of measures.

Decline in Child Hospitalization and Mortality After the Introduction of the 7-Valent Pneumococcal Conjugative Vaccine in Rwanda.

Pneumonia is a public health problem in the tropics, and the 7-valent pneumococcal conjugative vaccine (PCV-7) has been introduced in an effort to prevent the disease and therefore reduce childhood mortality. In Rwanda, PCV-7 was introduced in 2009, and we aimed to determine its impact on the rate of child hospitalization/mortality due to pneumonia. A retrospective survey was conducted on hospitalization rates and pediatric deaths between two periods, that is, before the introduction of PCV-7 (2007-2009) and after the introduction of PCV-7 (2010-2013) in Kabutare District Hospital. There was a 53% reduction in hospitalization, with a significant decline in in-hospital deaths between the two periods. There was also a significant correlation between vaccination coverage and decline in hospitalization rates between 2009 and 2013. We conclude that PCV-7 vaccine is associated with significant reduction in the rate of child hospitalization and mortality but more mechanistic studies are warranted to determine the immunological impact, especially in the context of coinfections and malnutrition.

Prevalence of Brucellosis among Women Presenting with Abortion/Stillbirth in Huye, Rwanda.

The incidence of human brucellosis is not documented in Rwanda despite several reports on the disease in cattle. Because brucellosis has been associated with abortion, the aim of this study was to investigate the prevalence of positive serology in women presenting with abortion and/or stillbirth. The study was done in Huye District, in the Southern Province of Rwanda, and the patients were recruited from both the University Teaching Hospital of Butare (CHUB) and Kabutare District Hospital. Serum samples were collected and the Rose Bengal plate test (RBPT) was performed on each sample. A questionnaire was also used to investigate potential contacts with animals and/or consumption of raw milk. A total of 60 women were recruited and 15 (i.e., 25%) were Brucella seropositive. The questionnaire showed that those with seropositivity either were in contact with domestic animals (cattle, goat, or sheep) or were consuming raw cow's milk. Human brucellosis appears to be of public health importance in Rwanda and more attention should be drawn on the disease. The current study provides a basis for larger studies to establish the incidence of human brucellosis in Rwanda. More mechanistic studies will also demonstrate the pathogenicity of Brucella in human placentas.

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.

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.