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The intestinal nematodes Enterobius vermicularis, Trichuris trichiura, Capillaria philippinensis, and Trichostrongylus spp. are endemic worldwide, although the true prevalence is not known, as many infections are undiagnosed and some are difficult to diagnose. T. trichiura is estimated to infect as many as 500 million people worldwide. Each of these nematodes has distinctive life cycles, varying degrees of pathology, and different epidemiologic features. However, they all infect the gut as larvae and adults, producing eggs that are excreted in the stool. Most of the intestinal nematodes are susceptible to anti-helminthic drugs, with trichuriasis requiring additional rounds of treatment for maximum efficacy. Prevention is through handwashing, sanitary disposal of human excreta, prevention of fecal contamination of topsoil, and improved food hygiene.

Ascariasis is the most prevalent human helminth infection, with an estimated 819 million infections worldwide. Transmission primarily occurs in warm, tropical climates that lack water and sanitation facilities and have poor hygiene. Worms inhabit the small intestine, and morbidity is related to worm burden. A small proportion of the infected population harbors the majority of worms, with intense infection most common in school-age children, and intensity and prevalence declining to a low level throughout adulthood. School-age children are therefore the targets for school-based community control efforts in large-scale treatment campaigns. Light infections can affect growth and development, whereas, due to the size of the worms, heavier worm burdens can result in intestinal obstruction, particularly in young children. Treatment with mebendazole or albendazole is efficacious, with cure rates of >90% commonly achieved.

School health and nutrition (SHN) programmes are recognized as a significant contributor to both health and education sector goals. The school system offers an ideal platform from which to deliver basic health interventions that target the most common health conditions affecting school-age children (SAC) in low-income countries, leading to improved participation and learning outcomes. However, governments require evidence to cost, design, and implement these programmes. In Ethiopia, prevalent health conditions affecting SAC's education participation and learning outcomes include infection with soil-transmitted helminths (STHs), hunger, and malnutrition. In recognition of the multiple issues affecting the health and education of SAC, the government has taken a proactive approach, coordinating an integrated SHN programme designed to be implemented in partnership and monitored and financed through a single, integrated mechanism. The programme, known as the Enhanced School Health Initiative (ESHI), integrates three complimentary health interventions: deworming; school feeding; and provision of a water, sanitation, and hygiene (WASH) package in schools, which in delivery aim to maximize the benefits of each of the individual components. Operational research surrounding the ESHI programme includes both qualitative and quantitative analyses. Here, we present an overview of the ESHI programme and its genesis. We also introduce three additional supporting papers that provide in-depth analyses of key findings, including the baseline situational analysis, the costs, and community perceptions of the programme. The findings from ESHI provide initial evidence to develop an understanding of the related costs and synergies of integrating multiple health interventions onto a single platform. The work has translated into strengthened institutional capacity and improved cross-sectoral coordination. The government is now committed to supporting 25 million school children in Ethiopia through SHN. The ESHI model serves as a reference point for other countries looking to scale up targeted SHN interventions.

For more than 100 years, countries have used mass drug administration as a public health response to soil-transmitted helminth infection. The series of analyses published as Disease Control Priorities is the World Bank's vehicle for exploring the cost-effectiveness and value for money of public health interventions. The first edition was published in 1993 as a technical supplement to the World Bank's World Development Report Investing in Health where deworming was used as an illustrative example of value for money in treating diseases with relatively low morbidity but high prevalence. Over the second (2006) and now third (2017) editions deworming has been an increasingly persuasive example to use for this argument. The latest analyses recognize the negative impact of intestinal worm infection on human capital in poor communities and document a continuing decline in worm infection as a result of the combination of high levels of mass treatment and ongoing economic development trends in poor communities.

The realisation of human potential for development requires age-specific investment throughout the 8000 days of childhood and adolescence. Focus on the first 1000 days is an essential but insufficient investment. Intervention is also required in three later phases: the middle childhood growth and consolidation phase (5-9 years), when infection and malnutrition constrain growth, and mortality is higher than previously recognised; the adolescent growth spurt (10-14 years), when substantial changes place commensurate demands on good diet and health; and the adolescent phase of growth and consolidation (15-19 years), when new responses are needed to support brain maturation, intense social engagement, and emotional control. Two cost-efficient packages, one delivered through schools and one focusing on later adolescence, would provide phase-specific support across the life cycle, securing the gains of investment in the first 1000 days, enabling substantial catch-up from early growth failure, and leveraging improved learning from concomitant education investments. Refereed/Peer-reviewed

For more than 100 years, countries have used Mass Drug Administration (MDA) as a public health response to Soil Transmitted Helminth (STH) infection. The series of analyses published as Disease Control Priorities is the World Bank’s vehicle for exploring the cost-effectiveness and value for money of public health interventions. The first edition was published in 1993 as a technical supplement to the World Bank’s World Development Report Investing in Health where deworming was used as an illustrative example of value for money in treating diseases with relatively low morbidity but high prevalence. Over the second (2006) and now third (2017) editions deworming has been an increasingly persuasive example to use for this argument. The latest analyses recognize the negative impact of intestinal worm infection on human capital in poor communities, and document a continuing decline in worm infection as a result of the combination of high levels of mass treatment and ongoing economic development trends in poor communities.

Globally, more than 600 million school-age children are at risk of infection with soil-transmitted helminths (STH) and require treatment [1]. These infected children frequently carry the largest burden of disease in a community and are at greater risk of malnutrition and anaemia [2–5], with detrimental effects on educational access and learning as well as mental and physical performance [4,6–10]. Many of these detrimental effects of helminth infection, however, are reversible with antihelminthic drugs [9–11]; thus, the World Health Organization (WHO) advocates reaching a minimum target of regular administration of antihelminthics to at least 75%, and up to 100%, of school-age children at risk of morbidity from STH infection by 2020 [1,12]. The high levels of safety and efficacy of antihelminthic tablets make them ideal for mass drug administration (MDA), and recommended control efforts consist of antihelminthic treatment, administered through MDA, once a year for school-age children in whom STH infection prevalence is between 20% and 49% and twice a year for all school-age children in whom prevalence is at least 50% [13]. By providing easy access to large numbers of children in a structured setting, the school-based deworming model has been successfully used to administer these antihelminthics in multiple settings [14–16]. Thus, school-based deworming, in which the point of care for children is the school and the teachers are administers of the drugs, with critical oversight by health care staff, is recommended in order to cost-effectively and efficiently reach large numbers of children [14–17]. Despite the availability of cheap and efficacious drugs, WHO goals of reaching 75% of at-risk children by 2020 is not on target [18]. Clearly, in order to achieve WHO goals of reaching 75% by 2020, an effort needs to be taken to increase the scale and coverage of deworming programmes to regional and national levels. Box 1 highlights the key elements of a deworming programme implemented in Bihar, which presents a scalable and sustainable school-based model, using the tools available and harnessing existing structures to create a successful, structured deworming programme. Box 1. Key Elements for Success of the Deworming Programme in Bihar Institutional Framework ◆ Ownership of the programme by the government led to increased programme sustainability and continued financial and governmental support. ◆ Additionally, the existence of a multi-sectoral coordination committee (the State School Health Coordination Committee [SSHCC]) provided the necessary supervision, flexibility, and direction to address challenges arising during the programme while ensuring the sustained high profile of the programme. Evidence-Based Design and Implementation ◆ The catalytic role of development partners helped build a strong, evidence-based programme and resulted in overall reduced costs as well as additional high-level government support. Collaboration, Communication, and Coordination ◆ Throughout the design and implementation of the programme, close communication and collaboration among different state government bodies, in particular the health and education sectors, enabled the leveraging of their respective physical infrastructures and human resources and maximized coverage while reducing the overall cost of the programme. ◆ High levels of acceptability of the deworming programme by the community was a result of context-relevant community awareness campaigns that built local ownership of the programme, prevented a purely “top-down” approach to the programme, and increased participation on the deworming day. India is estimated to account for more than a quarter of all children requiring treatment for STH globally [1,19], and in 2009 the State Government of Bihar, in the eastern region of India, planned to initiate a state-wide, evidence-based deworming programme run out of state-schools and with technical support from Deworm the World (DtW). From inception, DtW was technically and administratively supported by Partnership for Child Development (PCD) and Innovations for Poverty Action (IPA) and led by PCD’s Executive Director Dr Lesley Drake, who was seconded to DtW to lead the campaign. This joint initiative is reflected in this paper with the term DtW/PCD. Bihar is one of India’s poorest states, with 8.5% of India’s population and only 1.6% of its gross domestic product (GDP) [20]. The population of Bihar was estimated to be over 104 million in the 2011 census [21] with approximately 28% between 6–14 years of age [21]. Surveys conducted in 2010–2011 found a high prevalence of STH throughout Bihar state [22], and subsequent predictive mapping indicated that at least annual, and in some cases biannual, MDA treatment would be required [17]. This paper outlines the political environment, development, and implementation of all stages of this pioneering and sustainable large-scale deworming programme, which led to the treatment of over 17 million school-age children in Bihar state. In addition, the synergistic support provided by all partners ensured a rapid rollout of the programme, which went from conception to implementation to treatment in less than 12 months, and deworming was rolled out across the state over three months.

SUMMARYDespite the overlapping distribution ofSchistosoma haematobiumandPlasmodium falciparuminfections, few studies have investigated early immune responses to both parasites in young children resident in areas co-endemic for the parasites. This study measures infection levels of both parasites and relates them to exposure and immune responses in young children. Levels of IgM, IgE, IgG4 directed against schistosome cercariae, egg and adult worm and IgM, IgG directed againstP. falciparumschizonts and the merozoite surface proteins 1 and 2 together with the cytokines IFN-γ, IL-4, IL-5, IL-10 and TNF-αwere measured by ELISA in 95 Zimbabwean children aged 1–5 years. Schistosome infection prevalence was 14·7% and that ofPlasmodiuminfection was 0% in the children. 43. 4% of the children showed immunological evidence of exposure to schistosome parasites and 13% showed immunological evidence of exposure toPlasmodiumparasites. Schistosome–specific responses, indicative of exposure to parasite antigens, were positively associated with cercariae-specific IgE responses, whilePlasmodium-specific responses, indicative of exposure to parasite antigens, were negatively associated with responses associated with protective immunity againstPlasmodium. There was no significant association between schistosome-specific andPlasmodium-specific responses. Systemic cytokine levels rose with age as well as with schistosome infection and exposure. Overall the results show that (1) significantly more children are exposed to schistosome andPlasmodiuminfection than those currently infected and; (2) the development of protective acquired immunity commences in early childhood, although its effects on infection levels and pathology may take many years to become apparent.

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., Author Summary Schistosomiasis is caused by infection with Schistosoma spp. parasites, for which the main treatment is the drug praziquantel (PZQ). Since PZQ does not prevent reinfection, an anti-schistosome vaccine based on the Schistosoma haematobium enzyme glutathione-S-transferase (GST) is being developed. In this study we investigated the GST-specific immune responses of people naturally exposed to schistosomes and the affect that PZQ has on these responses. We cultured blood samples from a schistosome-exposed community with GST before and six weeks after PZQ treatment and measured a range of soluble proteins (cytokines) in culture supernatants as indicators of blood cell activation and phenotype. Before treatment, GST-specific cytokine responses varied with host age, particularly in children with high intensity schistosome infections. Following treatment, GST activated blood samples from more individuals to produce a broader range of cytokines and the combination of GST-specific cytokine responses reflected a more pro-inflammatory immune phenotype than that observed pre-treatment. Post-treatment responses varied according to host age and pre-treatment infection status. Taken together, our study suggests that current and future GST-based vaccine trials should take host age, schistosome infection status and PZQ treatment history into account since these factors influence GST-specific immune activation.

Highlights • Variation in monocyte phenotype is explored using the markers CD14, CD16, HLA-DR, CX3CR1 and CCR2. • The CD14++CD16+ monocytes exhibit a spectrum of markers dependent on location within the gate. • Monocyte phenotype varies dependent on genetic background and history of exposure to infection. • Processing technique for PBMC purification does not lead to changes in monocyte subsets. • Processing technique for purification can alter intensity but not pattern of marker expression., Human monocytes are commonly defined and discriminated by the extent of their cell surface expression of CD14 and CD16, with associated differences in function and phenotype related to the intensity of expression of these markers. With increasing interest into the function and behaviour of monocytes, it is important to have a clear understanding of how differing strategies of analysis can affect results and how different protocols and population backgrounds can affect this highly morphogenic cell type. Using PBMCs from populations with differing ethnicities and histories of parasite exposure we have characterized monocyte phenotype based on intensity of CD14 and CD16 expression. Using the surface markers HLA-DR, CCR2 and CX3CR1, we compared monocyte phenotype between populations and further assessed changes in monocytes with freezing and thawing of PBMCs. Our results reveal that there is a progression of surface marker expression based on intensity of CD14 or CD16 expression, stressing the importance of careful gating of monocyte subtypes. Freezing and thawing of the PBMCs has no effect generally on the monocytes, although it does lead to a decrease in CD16 and CX3CR1 expression. We show that there are differences in the monocyte populations based on ethnicity and history of exposure to the common parasites Plasmodium falciparum and Schistosoma haematobium. This study highlights that blood monocytes consist of a continuous population of cells, within which the dominant phenotype may vary dependent on the background of the study population. Comparing results from monocyte studies therefore needs to be done with great care, as ethnic background of donor population, gating strategy and processing of PBMCs may all have an effect on outcome of monocyte phenotype.

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., Author Summary A characteristic feature of most helminth infections is the convex age infection profile, where infection levels rise to peak in early childhood and decline in adulthood, a pattern thought to result from the development of protective acquired immunity. Thus, several investigations characterizing protective responses to inform vaccine research have focused on responses present in older people, who despite continued exposure to infection carry little or no infection. To date, such studies have identified key responses which are correlates of resistance. However, there is a paucity of information on cell types that are mediators rather than effectors of the immune responses. One such group where there are limited studies in human schistosome infections is dendritic cells which are important for the polarizations of CD4+ T cell responses. Therefore, we characterized the age profile of dendritic cells in Zimbabweans exposed to Schistosoma haematobium infection. We found an age-related pattern in the proportions of myeloid dendritic cells (a subset of dendritic cells) in this population. Furthermore, in the case myeloid dendritic cells, the age profile differed between schistosome infected and un-infected people. Thus our study suggests that activation and migration of myeloid dendritic cells also develop in an age-related pattern consistent with the cumulative history of exposure to schistosome parasites.

Characterisation of protective helminth acquired immunity in humans or experimental models has focused on effector responses with little work conducted on memory responses. Here we show for the first time, that human helminth infection is associated with altered proportions of the CD4+ memory T cells, with an associated alteration of T(H)1 responses. The reduced CD4+ memory T cell proportions are associated with a significantly lower ratio of schistosome-specific IgE/IgG4 (marker for resistance to infection/re-infection) in uninfected older people. Helminth infection does not affect the CD8+ memory T cell pool. Furthermore, we show for the first time in a helminth infection that the CD4+ memory T cell proportions decline following curative anti-helminthic treatment despite increased CD4+ memory cell replication. Reduced accumulation of the CD4+ memory T cells in schistosome-infected people has implications for the development of natural or vaccine induced schistosome-specific protective immunity as well as for unrelated pathogens.

Urogenital schistosomiasis is a debilitating disease caused by the parasitic trematode Schistosoma haematobium, which currently infects >100 million people [1]. Humans are exposed to infective larvae (cercariae), which invade via percutaneous penetration; adult male and female worms, which mate in the urogenital tract; and eggs, which are transmitted to the environment in urine. Repeated passage of eggs across the bladder and urogenital tract leads to characteristic immune-mediated morbidities [2, 3]. The World Health Organization advocates schistosomiasis control via treatment with the antihelminthic drug praziquantel (PZQ) [4] due to its efficacy at clearing infection [5, 6] and reducing the prevalence of schistosome-associated morbidities [7]. Praziquantel treatment also alters schistosome-specific immune responses, and removal of infection and/or exposure to antigens released from parasites damaged by treatment may influence responses to subsequent infection [8–10]. Studies showing a decline in the proportion of circulating T regulatory (Treg) cells [11] and increased effector responses to parasite [12, 13] and nonparasite antigens [14, 15] post-treatment indicate that immunoregulatory mechanisms established during infection are alleviated when infection is removed. Furthermore, PZQ-induced changes in antibody levels, CD23+ B cells [16], and cellular proliferation [13] have been associated with reduced Schistosoma mansoni reinfection rates, suggesting that treatment may have longer-term benefits in addition to transient infection clearance. Taken together, these observations suggest that treatment alters not only the magnitude of the host immune response but also the phenotype of schistosome-specific responses. However, although previous human studies have inferred relative changes in the phenotype of the schistosome-specific cytokine response from changes in individual responses [12, 17], this hypothesis has not been directly assessed. Importantly, experimental models of helminth infection suggest that innate cells and CD4+ T helper (Th) cells (Th1, Th2, Treg, and Th17) cross-regulate one another during infection [18, 19], and the interaction between these responses rather than levels of individual cytokines alone may influence resistance to reinfection [20]. No studies to date have investigated schistosome-specific, Th17-associated cytokine responses in humans despite the role of Th17 in schistosome egg-mediated immunopathologies in mice [21–23] and detectable levels of Th17-type cytokines in plasma samples from S. haematobium–exposed humans [24]. This study addresses 4 key hypotheses relating to the effect of PZQ on schistosome-specific immune responses: (1) treatment influences levels of schistosome-specific, Th17-associated cytokines in addition to the previously assayed cytokines; (2) the cytokine environment (comprising markers associated with innate inflammatory, Th1, Th2, Th17, and regulatory responses) of treated individuals is fundamentally altered relative to pretreatment responses; (3) the effects of treatment on schistosome-specific cytokines differ between responses to cercariae, adult worms and eggs; and (4) cytokine responses elicited 6 weeks post-treatment influence reinfection rates. Our results yield insights into the immunological effects of antihelminthic treatment and how these relate to parasite life history and the development of protective immunity.

Background Morbidity due to schistosomiasis is currently controlled by treatment of schistosome infected people with the antihelminthic drug praziquantel (PZQ). Children aged up to 5 years are currently excluded from schistosome control programmes largely due to the lack of PZQ safety data in this age group. This study investigated the safety and efficacy of PZQ treatment in such children. Methods Zimbabwean children aged 1–5 years (n = 104) were treated with PZQ tablets and side effects were assessed by questionnaire administered to their caregivers within 24 hours of taking PZQ. Treatment efficacy was determined 6 weeks after PZQ administration through schistosome egg counts in urine. The change in infection levels in the children 1–5 years old (n = 100) was compared to that in 6–10 year old children (n = 435). Principal Findings Pre-treatment S. haematobium infection intensity in 1–5 year olds was 14.6 eggs/10 ml urine and prevalence was 21%. Of the 104 children, 3.8% reported side effects within 24 hours of taking PZQ treatment. These were stomach ache, loss of appetite, lethargy and inflammation of the face and body. PZQ treatment significantly reduced schistosome infection levels in 1–5 year olds with an egg reduction rate (ERR) of 99% and cure rate (CR) of 92%. This was comparable to the efficacy of praziquantel in 6–10 year olds where ERR was 96% and CR was 67%. Interpretation/Significance PZQ treatment is as safe and efficacious in children aged 1–5 years as it is in older children aged 6–10 years in whom PZQ is the drug of choice for control of schistosome infections., Author Summary Urogenital schistosomiasis is an important, but neglected, infectious disease affecting over 100 million people, mainly in Africa. Children carry the heaviest burden of infection with children as young as 1 year old showing signs of infection. Children aged 5 years and below are currently excluded from schistosome control programmes for several reasons, including operational difficulties associated with accessing preschool children, misconceptions about their level of exposure to infective water and lack of safety data on the drug of choice for schistosome control, praziquantel, in children aged 5 years and below. This study was one of a small number of studies recently funded by the World Health Organization to investigate the need for praziquantel treatment in preschool children (aged 1–5 years) and to subsequently assess the safety and efficacy of the drug praziquantel in this age group. This study confirmed that preschool children carry significant levels of schistosome infection, exceeding those carried by their parents/guardians, highlighting the urgent need for their immediate inclusion in schistosome control programmes. The study also showed that praziquantel treatment is as safe and efficacious in children aged 1–5 years as it is in older children aged 6–10 years who are currently the target for mass drug administration.

Background Currently there are few studies characterising the nature and aetiology of human schistosome-related inflammatory processes. The aim of this study was to determine the relationship between Chitinase 3-like 1 (CHI3L1), also known as YKL-40, a molecule associated with inflammatory processes, and schistosome infection, morbidity and systemic cytokine levels. Methods Serological levels of CHI3L1 and a panel of cytokines (IFN-y, IL-4/5/6/9/10/13 and 17) were measured in two Zimbabwean populations resident in a high and low schistosome infection area. CHI3L1 levels were related to schistosome infection, haematuria status and cytokine levels after allowing for confounding variables. The effect of antihelminthic treatment with praziquantel on CHI3L1 levels was determined in 246 participants 6 weeks post-treatment. Results CHI3L1 levels increased with age in both areas but were significantly higher in the high infection areas compared to the low infection area. CHI3L1 levels were also higher in infected compared to uninfected individuals with this difference being significant in the youngest age group. Curative antihelminthic treatment resulted in a significant decrease in CHI3L1 levels. Of the cytokines, only IL-10 and IL-17 had a significant association with CHI3L1 levels, and this association was negative. Conclusions Serum CHI3L1 levels differ between infected and uninfected people before and after antihelminthic treatment. The greatest difference occurs in the youngest age group, in keeping with the period when schistosome-related pathological processes are initiated. Following from previous studies in non-infectious diseases showing that CHI3L1 is a biomarker for the inflammatory process, this study suggests that the potential for CHI3L1 as a biomarker for schistosome-related pathology should be explored further., Author Summary Over 100 million people, mainly living in sub-Saharan Africa, are infected with the blood fluke Schistosoma haematobium. Morbidity includes anaemia, malnutrition, impaired cognition and physical growth as well as pathology of the urogenital tract. Urogenital morbidity is initiated by eggs laid at the site of infection causing mechanical damage and leading to haematuria, or blood in the urine. Eggs also secrete antigens, triggering a protective granuloma to form around the eggs which can lead to fibrosis and organ failure. Currently there are few non invasive markers of schistosome-related pathology hampering diagnosis and evaluation of control programmes. Chitinase 3-like 1 (CHI3L1) has been associated with several inflammatory disorders involving tissue remodelling. In this study we assessed the levels of CHI3L1 in a group of individuals from a schistosomiasis endemic area in Zimbabwe. We showed that CHI3L1 is elevated in schistosomiasis infected individuals over uninfected individuals, with the strongest association seen in the youngest age group who have a shorter history of schistosome infection. Treating individuals with a drug that eliminates the adult worm leads to a decrease in CHI3L1 in infected individuals. These results suggest that the potential for CHI3L1 as a biomarker for schistosomerelated pathology should be explored further in different human populations.