Infection History and Current Coinfection With Schistosoma mansoni Decreases Plasmodium Species Intensities in Preschool Children in Uganda.

Malaria-schistosomiasis coinfections are common in sub-Saharan Africa but studies present equivocal results regarding the interspecific relationships between these parasites. Through mixed-model analyses of a dataset of Ugandan preschool children, we explore how current coinfection and prior infection with either Schistosoma mansoni or Plasmodium species alter subsequent Plasmodium intensity, Plasmodium risk, and S mansoni risk. Coinfection and prior infections with S mansoni were associated with reduced Plasmodium intensity, moderated by prior Plasmodium infections, wealth, and host age. Future work should assess whether these interactions impact host health and parasite control efficacy in this vulnerable age group.

Diarrhoeal outcomes in young children depend on diarrhoeal cases of other household members: a cross-sectional study of 16,025 people in rural Uganda.

BACKGROUND: There is a limited understanding of how diarrhoeal cases across other household members influence the likelihood of diarrhoea in young children (aged 1-4 years). METHODS: We surveyed 16,025 individuals from 3421 households in 17 villages in Uganda. Using logistic regressions with standard errors clustered by household, diarrhoeal cases within households were used to predict diarrhoeal outcomes in young children. Regressions were adjusted for socio-demographic, water, sanitation, and hygiene (WASH), and ecological covariates. Selection bias for households with (1632/3421) and without (1789/3421) young children was examined. RESULTS: Diarrhoeal prevalence was 13.7% (2118/16,025) across all study participants and 18.5% (439/2368) in young children. Young children in households with any other diarrhoeal cases were 5.71 times more likely to have diarrhoea than young children in households without any other diarrhoeal cases (95% CI: 4.48-7.26), increasing to over 29 times more likely when the other diarrhoeal case was in another young child (95% CI: 16.29-54.80). Diarrhoeal cases in older household members (aged ≥ 5 years) and their influence on the likelihood of diarrhoea in young children attenuated with age. School-aged children (5-14 years) had a greater influence on diarrhoeal cases in young children (Odds Ratio 2.70, 95% CI: 2.03-3.56) than adults of reproductive age (15-49 years; Odds Ratio 1.96, 95% CI: 1.47-2.59). Diarrhoeal cases in individuals aged ≥ 50 years were not significantly associated with diarrhoeal outcomes in young children (P > 0.05). These age-related differences in diarrhoeal exposures were not driven by sex. The magnitude and significance of the odds ratios remained similar when odds ratios were compared by sex within each age group. WASH factors did not influence the likelihood of diarrhoea in young children, despite influencing the likelihood of diarrhoea in school-aged children and adults. Households with young children differed from households without young children by diarrhoeal prevalence, household size, and village WASH infrastructure and ecology. CONCLUSIONS: Other diarrhoeal cases within households strongly influence the likelihood of diarrhoea in young children, and when controlled, removed the influence of WASH factors. Future research on childhood diarrhoea should consider effects of diarrhoeal cases within households and explore pathogen transmission between household members.

Social network fragmentation and community health.

Community health interventions often seek to intentionally destroy paths between individuals to prevent the spread of infectious diseases. Immunizing individuals through direct vaccination or the provision of health education prevents pathogen transmission and the propagation of misinformation concerning medical treatments. However, it remains an open question whether network-based strategies should be used in place of conventional field approaches to target individuals for medical treatment in low-income countries. We collected complete friendship and health advice networks in 17 rural villages of Mayuge District, Uganda. Here we show that acquaintance algorithms, i.e., selecting neighbors of randomly selected nodes, were systematically more efficient in fragmenting all networks than targeting well-established community roles, i.e., health workers, village government members, and schoolteachers. Additionally, community roles were not good proxy indicators of physical proximity to other households or connections to many sick people. We also show that acquaintance algorithms were effective in offsetting potential noncompliance with deworming treatments for 16,357 individuals during mass drug administration (MDA). Health advice networks were destroyed more easily than friendship networks. Only an average of 32% of nodes were removed from health advice networks to reduce the percentage of nodes at risk for refusing treatment in MDA to below 25%. Treatment compliance of at least 75% is needed in MDA to control human morbidity attributable to parasitic worms and progress toward elimination. Our findings point toward the potential use of network-based approaches as an alternative to role-based strategies for targeting individuals in rural health interventions.

Profiling the best-performing community medicine distributors for mass drug administration: a comprehensive, data-driven analysis of treatment for schistosomiasis, lymphatic filariasis, and soil-transmitted helminths in Uganda.

BACKGROUND: The most prevalent neglected tropical diseases are treated through blanket drug distribution that is reliant on lay community medicine distributors (CMDs). Yet, treatment rates achieved by CMDs vary widely and it is not known which CMDs treat the most people. METHODS: In Mayuge District, Uganda, we tracked 6779 individuals (aged 1+ years) in 1238 households across 31 villages. Routine, community-based mass drug administration (MDA) was implemented for schistosomiasis, lymphatic filariasis, and soil-transmitted helminths. For each CMD, the percentage of eligible individuals treated (offered and ingested medicines) with at least one drug of praziquantel, albendazole, or ivermectin was examined. CMD attributes (more than 25) were measured, ranging from altruistic tendencies to socioeconomic characteristics to MDA-specific variables. The predictors of treatment rates achieved by CMDs were selected with least absolute shrinkage and selection operators and then analyzed in ordinary least squares regression with standard errors clustered by village. The influences of participant compliance and the ordering of drugs offered also were examined for the treatment rates achieved by CMDs. RESULTS: Overall, only 44.89% (3043/6779) of eligible individuals were treated with at least one drug. Treatment rates varied amongst CMDs from 0% to 84.25%. Treatment rate increases were associated (p value< 0.05) with CMDs who displayed altruistic biases towards their friends (13.88%), had friends who helped with MDA (8.43%), were male (11.96%), worked as fishermen/fishmongers (14.93%), and used protected drinking water sources (13.43%). Only 0.24% (16/6779) of all eligible individuals were noncompliant by refusing to ingest all offered drugs. Distributing praziquantel first was strongly, positively correlated (p value < 0.0001) with treatment rates for albendazole and ivermectin. CONCLUSIONS: These findings profile CMDs who treat the most people during routine MDA. Criteria currently used to select CMDs-community-wide meetings, educational attainment, age, years as a CMD, etc.-were uninformative. Participant noncompliance and the provision of praziquantel before albendazole and ivermectin did not negatively impact treatment rates achieved by CMDs. Engaging CMD friend groups with MDA, selecting CMDs who practise good preventative health behaviours, and including CMDs with high-risk occupations for endemic infections may improve MDA treatment rates. Evidence-based guidelines are needed to improve the monitoring, selection, and replacement of CMDs during MDA.

Non-invasive surveillance of Plasmodium infection by real-time PCR analysis of ethanol preserved faeces from Ugandan school children with intestinal schistosomiasis.

BACKGROUND: As part of ongoing co-surveillance of intestinal schistosomiasis and malaria in Ugandan school children, a non-invasive detection method for amplification of Plasmodium DNA using real-time (rt)PCR analysis of ethanol preserved faeces (EPF) was assessed. For diagnostic tabulations, results were compared to rtPCR analysis of dried blood spots (DBS) and field-based point-of-care (POC) rapid diagnostic tests (RDTs). METHODS: A total of 247 school children from 5 primary schools along the shoreline of Lake Albert were examined with matched EPF and DBS obtained. Mean prevalence and prevalence by school was calculated by detection of Plasmodium DNA by rtPCR using a 18S rDNA Taqman® probe. Diagnostic sensitivity, specificity, positive and negative predictive values were tabulated and compared against RDTs. RESULTS: By rtPCR of EPF and DBS, 158 (63.9%; 95% CI 57.8-69.7) and 198 (80.1%, 95% CI 74.7-84.6) children were positive for Plasmodium spp. By RDT, 138 (55.8%; 95% CI 49.6-61.9) and 45 (18.2%; 95% CI 13.9-23.5) children were positive for Plasmodium falciparum, and with non-P. falciparum co-infections, respectively. Using RDT results as a convenient field-based reference, the sensitivity of rtPCR of EPF and DBS was 73.1% (95% CI 65.2-79.8) and 94.2% (95% CI 88.9-97.0) while specificity was 47.7% (95% CI 38.5-57.0) and 37.6% (95% CI 29.0-46.9), respectively. With one exception, school prevalence estimated by analysis of EPF was higher than that by RDT. Positive and negative predictive values were compared and discussed. CONCLUSIONS: In this high transmission setting, EPF sampling with rtPCR analysis has satisfactory diagnostic performance in estimation of mean prevalence and prevalence by school upon direct comparison with POC-RDTs. Although analysis of EPF was judged inferior to that of DBS, it permits an alternative non-invasive sampling regime that could be implemented alongside general monitoring and surveillance for other faecal parasites. EPF analysis may also have future value in passive surveillance of low transmission settings.

Emergence of Nonfalciparum Plasmodium Infection Despite Regular Artemisinin Combination Therapy in an 18-Month Longitudinal Study of Ugandan Children and Their Mothers.

As part of a longitudinal cohort investigation of intestinal schistosomiasis and malaria in Ugandan children and their mothers on the shorelines of Lakes Victoria and Albert, we documented risk factors and morbidity associated with nonfalciparum Plasmodium infections and the longitudinal dynamics of Plasmodium species in children. Host age, household location, and Plasmodium falciparum infection were strongly associated with nonfalciparum Plasmodium infections, and Plasmodium malariae infection was associated with splenomegaly. Despite regular artemisinin combination therapy treatment, there was a 3-fold rise in P. malariae prevalence, which was not accountable for by increasing age of the child. Worryingly, our findings reveal the consistent emergence of nonfalciparum infections in children, highlighting the complex dynamics underlying multispecies infections here. Given the growing body of evidence that nonfalciparum malaria infections cause significant morbidity, we encourage better surveillance for nonfalciparum Plasmodium infections, particularly in children, with more sensitive DNA detection methods and improved field-based diagnostics.

Surveillance of intestinal schistosomiasis during control: a comparison of four diagnostic tests across five Ugandan primary schools in the Lake Albert region.

Programmatic surveillance of intestinal schistosomiasis during control can typically use four diagnostic tests, either singularly or in combination, but these have yet to be cross-compared directly. Our study assembled a complete diagnostic dataset, inclusive of infection intensities, from 258 children from five Ugandan primary schools. The schools were purposely selected as typical of the endemic landscape near Lake Albert and reflective of high- and low-transmission settings. Overall prevalence was: 44.1% (95% CI 38.0-50.2) by microscopy of duplicate Kato-Katz smears from two consecutive stools, 56.9% (95% CI 50.8-63.0) by urine-circulating cathodic antigen (CCA) dipstick, 67.4% (95% CI 61.6-73.1) by DNA-TaqMan® and 75.1% (95% CI 69.8-80.4) by soluble egg antigen enzyme-linked immunosorbent assay (SEA-ELISA). A cross-comparison of diagnostic sensitivities, specificities, positive and negative predictive values was undertaken, inclusive of a latent class analysis (LCA) with a LCA-model estimate of prevalence by each school. The latter ranged from 9.6% to 100.0%, and prevalence by school for each diagnostic test followed a static ascending order or monotonic series of Kato-Katz, urine-CCA dipstick, DNA-TaqMan® and SEA-ELISA. We confirm that Kato-Katz remains a satisfactory diagnostic standalone in high-transmission settings but in low-transmission settings should be augmented or replaced by urine-CCA dipsticks. DNA-TaqMan® appears suitable in both endemic settings though is only implementable if resources permit. In low-transmission settings, SEA-ELISA remains the method of choice to evidence an absence infection. We discuss the pros and cons of each method concluding that future surveillance of intestinal schistosomiasis would benefit from a flexible, context-specific approach both in choice and application of each diagnostic method, rather than a single one-size fits all approach.

One hundred years of neglect in paediatric schistosomiasis.

Early in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel - PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts.

A centenary of Robert T. Leiper's lasting legacy on schistosomiasis and a COUNTDOWN on control of neglected tropical diseases.

Part of Robert T. Leiper's (1881-1969) lasting legacy in medical helminthology is grounded on his pioneering work on schistosomiasis (Bilharzia). Having undertaken many expeditions to the tropics, his fascination with parasite life cycles typically allowed him to devise simple preventive measures that curtailed transmission. Building on his formative work with others in Africa and Asia, and again in Egypt in 1915, he elucidated the life cycles of African schistosomes. His mandate, then commissioned by the British War Office, was to prevent and break transmission of this disease in British troops. This he did by raising standing orders based on simple water hygiene measures. Whilst feasible in military camp settings, today their routine implementation is sadly out of reach for millions of Africans living in poverty. Whilst we celebrate the centenary of Leiper's research we draw attention to some of his lesser known colleagues, then focus on schistosomiasis in Uganda discussing why expanded access to treatment with praziquantel is needed now. Looking to WHO 2020 targets for neglected tropical diseases, we introduce COUNTDOWN, an implementation research consortium funded by DFID, UK, which fosters the scale-up of interventions and confirm the current relevance of Leiper's original research.

Profiling Nonrecipients of Mass Drug Administration for Schistosomiasis and Hookworm Infections: A Comprehensive Analysis of Praziquantel and Albendazole Coverage in Community-Directed Treatment in Uganda.

BACKGROUND: Repeated mass drug administration (MDA) with preventive chemotherapies is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths, yet the World Health Organization recently reported that less than one-third of individuals who required preventive chemotherapies received treatment. METHODS: Coverage of community-directed treatment with praziquantel (PZQ) and albendazole (ALB) was analyzed in 17 villages of Mayuge District, Uganda. National drug registers, household questionnaires, and parasitological surveys were collected to track 935 individuals before and after MDA. Multilevel logistic regressions, including household and village effects, were specified with a comprehensive set of socioeconomic and parasitological variables. The factors predicting who did not receive PZQ and ALB from community medicine distributors were identified. RESULTS: Drug receipt was correlated among members within a household, and nonrecipients of PZQ or ALB were profiled by household-level socioeconomic factors. Individuals were less likely to receive either PZQ or ALB if they had a Muslim household head or low home quality, belonged to the minority tribe, or had settled for more years in their village. Untreated individuals were also more likely to belong to households that did not purify drinking water, had no home latrine, and had no members who were part of the village government. CONCLUSIONS: The findings demonstrate how to locate and target individuals who are not treated in MDA. Infection risk factors were not informative. In particular, age, gender, and occupation were unable to identify non-recipients, although World Health Organization guidelines rely on these factors. Individuals of low socioeconomic status, minority religions, and minority tribes can be targeted to expand MDA coverage.

Reduced Efficacy of Praziquantel Against Schistosoma mansoni Is Associated With Multiple Rounds of Mass Drug Administration.

BACKGROUND: Mass drug administration (MDA) with praziquantel is the cornerstone of schistosomiasis control in sub-Saharan Africa. The effectiveness of this strategy is dependent on the continued high efficacy of praziquantel; however, drug efficacy is rarely monitored using appropriate statistical approaches that can detect early signs of wane. METHODS: We conducted a repeated cross-sectional study, examining children infected with Schistosoma mansoni from 6 schools in Uganda that had previously received between 1 and 9 rounds of MDA with praziquantel. We collected up to 12 S. mansoni egg counts from 414 children aged 6-12 years before and 25-27 days after treatment with praziquantel. We estimated individual patient egg reduction rates (ERRs) using a statistical model to explore the influence of covariates, including the number of prior MDA rounds. RESULTS: The average ERR among children within schools that had received 8 or 9 previous rounds of MDA (95% Bayesian credible interval [BCI], 88.23%-93.64%) was statistically significantly lower than the average in schools that had received 5 rounds (95% BCI, 96.13%-99.08%) or 1 round (95% BCI, 95.51%-98.96%) of MDA. We estimate that 5.11%, 4.55%, and 16.42% of children from schools that had received 1, 5, and 8-9 rounds of MDA, respectively, had ERRs below the 90% threshold of optimal praziquantel efficacy set by the World Health Organization. CONCLUSIONS: The reduced efficacy of praziquantel in schools with a higher exposure to MDA may pose a threat to the effectiveness of schistosomiasis control programs. We call for the efficacy of anthelmintic drugs used in MDA to be closely monitored.

Microbial and chemical contamination of water, sediment and soil in the Nakivubo wetland area in Kampala, Uganda.

The reuse of domestic and industrial wastewater in urban settings of the developing world may harm the health of people through direct contact or via contaminated urban agricultural products and drinking water. We assessed chemical and microbial pollutants in 23 sentinel sites along the wastewater and faecal sludge management and reuse chain of Kampala, Uganda. Water samples were examined for bacteria (thermotolerant coliforms (TTCs), Escherichia coli and Salmonella spp.) and helminth eggs. Physico-chemical parameters were determined. Water, sediment and soil samples and edible plants (yams and sugar cane) were tested for heavy metals. Water samples derived from the Nakivubo wetland showed mean concentrations of TTCs of 2.9 × 10(5) colony-forming units (CFU)/100 mL. Mean E. coli was 9.9 × 10(4) CFU/100 mL. Hookworm eggs were found in 13.5% of the water samples. Mean concentrations of iron (Fe), copper (Cu) and cadmium (Cd) were 21.5, 3.3 and 0.14 mg/L, respectively. In soil samples, we found a mean lead (Pb) concentration of 132.7 mg/L. In yams, concentrations of Cd, chromium (Cr) and Pb were 4.4, 4.0 and 0.2 mg/L, while the respective concentrations in sugar cane were 8.4, 4.3 and 0.2 mg/L. TTCs and E. coli in the water, Pb in soil, and Cd, Cr and Pb in the plants were above national thresholds. We conclude that there is considerable environmental pollution in the Nakivubo wetland and the Lake Victoria ecosystem in Kampala. Our findings have important public health implications, and we suggest that a system of sentinel surveillance is being implemented that, in turn, can guide adequate responses.

Suppression of basophil histamine release and other IgE-dependent responses in childhood Schistosoma mansoni/hookworm coinfection.

BACKGROUND: The poor correlation between allergen-specific immunoglobulin E (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm. METHODS: Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Nonspecific (anti-IgE), helminth-specific, and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment. RESULTS: Nonspecific- and helminth-specific-HR, and associations between helminth-specific IgE and helminth-specific HR increased post-treatment. Hookworm infection appeared to modify the relationship between circulating levels of HDM-IgE and HR: a significant positive association was observed among children without detectable hookworm infection, but no association was observed among infected children. In addition, hookworm infection was associated with a significantly reduced risk of wheeze, and IgG4 to somatic adult hookworm antigen with a reduced risk of HDM-SPT sensitivity. There was no evidence for S. mansoni infection having a similar suppressive effect on HDM-HR or symptoms of allergy. CONCLUSIONS: Basophil responsiveness appears suppressed during chronic helminth infection; at least in hookworm infection, this suppression may protect against allergy.

A latent Markov modelling approach to the evaluation of circulating cathodic antigen strips for schistosomiasis diagnosis pre- and post-praziquantel treatment in Uganda.

Regular treatment with praziquantel (PZQ) is the strategy for human schistosomiasis control aiming to prevent morbidity in later life. With the recent resolution on schistosomiasis elimination by the 65th World Health Assembly, appropriate diagnostic tools to inform interventions are keys to their success. We present a discrete Markov chains modelling framework that deals with the longitudinal study design and the measurement error in the diagnostic methods under study. A longitudinal detailed dataset from Uganda, in which one or two doses of PZQ treatment were provided, was analyzed through Latent Markov Models (LMMs). The aim was to evaluate the diagnostic accuracy of Circulating Cathodic Antigen (CCA) and of double Kato-Katz (KK) faecal slides over three consecutive days for Schistosoma mansoni infection simultaneously by age group at baseline and at two follow-up times post treatment. Diagnostic test sensitivities and specificities and the true underlying infection prevalence over time as well as the probabilities of transitions between infected and uninfected states are provided. The estimated transition probability matrices provide parsimonious yet important insights into the re-infection and cure rates in the two age groups. We show that the CCA diagnostic performance remained constant after PZQ treatment and that this test was overall more sensitive but less specific than single-day double KK for the diagnosis of S. mansoni infection. The probability of clearing infection from baseline to 9 weeks was higher among those who received two PZQ doses compared to one PZQ dose for both age groups, with much higher re-infection rates among children compared to adolescents and adults. We recommend LMMs as a useful methodology for monitoring and evaluation and treatment decision research as well as CCA for mapping surveys of S. mansoni infection, although additional diagnostic tools should be incorporated in schistosomiasis elimination programs.

Towards malaria microscopy at the point-of-contact: an assessment of the diagnostic performance of the Newton Nm1 microscope in Uganda.

Malaria microscopy in sub-Saharan Africa is often restricted by access to light microscopes. To address this gap, a novel portable inverted monocular microscope, the Newton Nm1, was designed and is now commercially available. Its diagnostic performance was assessed in a blinded-slide trial at ×1000 (oil) of Giemsa-stained thick blood films against a conventional microscope as undertaken by four Ugandan Ministry of Health technicians. With the Newton Nm1, diagnostic performance was: sensitivity 93.5% (95% confidence interval (CI) 78.6-99.2%), specificity 100.0% (95% CI 82.4-100.0%), positive predictive value 100.0% (95% CI 88.1-100.0%) and negative predictive value 90.5% (95% CI 69.6-98.8%). Discordance was due to a systematic error underestimating parasitaemia by ~45%; when counting Plasmodium parasites against 200 white blood cells, blood films with low parasitaemia (i.e. <100 µL(-1) of blood) could be overlooked and misclassified. By contrast, specificity was excellent with no false positives encountered. Whilst proven useful, especially in resource-poor environments, it is still unclear how we can ensure the uptake of the Newton Nm1 within sub-Saharan Africa.

Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment.

During a longitudinal study investigating the dynamics of malaria in Ugandan lakeshore communities, a consistently high malaria prevalence was observed in young children despite regular treatment. To explore the short-term performance of artemether-lumefantrine (AL), a pilot investigation into parasite carriage after treatment(s) was conducted in Bukoba village. A total of 163 children (aged 2-7 years) with a positive blood film and rapid antigen test were treated with AL; only 8.7% of these had elevated axillary temperatures. On day 7 and then on day 17, 40 children (26.3%) and 33 (22.3%) were positive by microscopy, respectively. Real-time PCR analysis demonstrated that multi-species Plasmodium infections were common at baseline, with 41.1% of children positive for Plasmodium falciparum/Plasmodium malariae, 9.2% for P. falciparum/ Plasmodium ovale spp. and 8.0% for all three species. Moreover, on day 17, 39.9% of children infected with falciparum malaria at baseline were again positive for the same species, and 9.2% of those infected with P. malariae at baseline were positive for P. malariae. Here, chronic multi-species malaria infections persisted in children after AL treatment(s). Better point-of-care diagnostics for non-falciparum infections are needed, as well as further investigation of AL performance in asymptomatic individuals.

Schistosoma mansoni infection in preschool-aged children: development of immunoglobulin E and immunoglobulin G4 responses to parasite allergen-like proteins.

Specific immunoglobulin E (IgE) responses are upregulated during chronic schistosome infection and during allergy. These responses are tightly regulated during schistosomiasis. We have previously shown that IgE regulation depends on the extent and length of exposure to individual parasite allergen-like proteins. Here we compare the development of IgE and immunoglobulin G4 (IgG(4)) responses to the differentially expressed allergen-like proteins SmTAL1 and SmTAL2 among preschool-aged children from 2 villages with different levels of Schistosoma mansoni transmission. We found a lack of SmTAL1 responsiveness among all children, but evidence for IgG(4)-dependent IgE-SmTAL2 desensitization in both villages, occurring earlier among children from the village where the level of transmission was greater. Findings provide insights into the development and regulation of allergic-type immune responses.

Effects of treatment on IgE responses against parasite allergen-like proteins and immunity to reinfection in childhood schistosome and hookworm coinfections.

Naturally occurring human immunity to both schistosomiasis and hookworm infection has been associated with IgE responses against parasite allergen-like proteins. Since the two helminths frequently coinfect the same individuals, there is growing advocacy for their concurrent treatment. However, both helminths are known to exert strong immunomodulatory effects; therefore, coinfected individuals could have immune responses different from those characteristically seen in monoinfected individuals. In this study, we measured changes in IgE, IgG1, and IgG4 responses to schistosome and hookworm antigens, including the allergen-like proteins Schistosoma mansoni tegumental-allergen-like 1 protein (SmTAL1), SmTAL2, and Necator americanus Ancylostoma-secreted protein-2 (Na-ASP-2), following concurrent treatment of schoolchildren coinfected with Schistosoma mansoni and hookworm. Antibody responses to schistosome egg (soluble egg antigen and SmTAL2) or somatic adult hookworm (AHW) antigens either decreased after treatment or were unchanged, whereas those to schistosome worm antigens (soluble worm antigen and SmTAL1) increased. The observed different effects of treatment likely reflect the different modes of drug action and sites of infection for these two helminths. Importantly, there was no evidence that the simultaneous treatment of coinfected children with praziquantel and albendazole affected schistosome- and hookworm-specific humoral responses differently from those characteristic of populations in which only one organism is endemic; schistosome- and hookworm-specific responses were not associated, and there was no evidence for cross-regulation. Posttreatment increases in the levels of IgE to schistosome worm antigens were associated with lower Schistosoma mansoni reinfection intensity, while no associations between humoral responses to AHW antigen and protection from hookworm reinfection were observed in this sample of school-aged children.

Plasmodium-helminth coinfection and its sources of heterogeneity across East Africa.

BACKGROUND: Plasmodium-helminth coinfection can have a number of consequences for infected hosts, yet our knowledge of the epidemiology of coinfection across multiple settings is limited. This study investigates the distribution and heterogeneity of coinfection with Plasmodium falciparum and 3 major helminth species across East Africa. METHODS: Cross-sectional parasite surveys were conducted among 28 050 children in 299 schools across a range of environmental settings in Kenya, Uganda, and Ethiopia. Data on individual, household, and environmental risk factors were collected and a spatially explicit Bayesian modeling framework was used to investigate heterogeneities of species infection and coinfection and their risk factors as well as school- and individual-level associations between species. RESULTS: Broad-scale geographical patterns of Plasmodium-helminth coinfection are strongly influenced by the least common infection and by species-specific environmental factors. At the individual level, there is an enduring positive association between P. falciparum and hookworm but no association between P. falciparum and Schistosoma species. However, the relative importance of such within-individual associations is less than the role of spatial factors in influencing coinfection risks. CONCLUSIONS: Patterns of coinfection seem to be influenced more by the distribution of the least common species and its environmental risk factors, rather than any enduring within-individual associations.

Heterogeneities and consequences of Plasmodium species and hookworm coinfection: a population based study in Uganda.

BACKGROUND: Previous studies have suggested that helminth infection exacerbates malaria, but few existing epidemiological studies adequately control for infection heterogeneities and confounding factors. In this study, we investigate spatial and household heterogeneities, predictors, and consequences of Plasmodium species and hookworm coinfection in rural communities in Uganda. METHODS: A cross-sectional study was conducted among 1770 individuals aged 0-88 years in 4 villages. We recorded demographic, socioeconomic, and microgeographic factors during household surveys. We determined malaria parasitemia and hemoglobin concentration and collected stool samples on 2 consecutive days. For data analysis, we used a hierarchical, spatially explicit Bayesian framework. RESULTS: Prevalence of Plasmodium-hookworm coinfection was 15.5% overall and highest among school-aged children. We found strong evidence of spatial and household clustering of coinfection and an enduring positive association between Plasmodium-species and hookworm infection among preschool-aged children (odds ratio [OR], 2.36; 95% Bayesian credible interval [BCI], 1.26-4.30) and adults (OR, 2.09; 95% BCI, 1.35-3.16) but not among school-aged children. Coinfection was associated with lower hemoglobin level only among school-aged children. CONCLUSIONS: Plasmodium-hookworm coinfection exhibits marked age dependency and significant spatial and household heterogeneity, and among preschool-aged children and adults, occurs more than would be expected by chance. Such heterogeneities provide insight into factors underlying observed patterns and the design of integrated control strategies.