Improved sanitation has been associated with a reduced prevalence of soil-transmitted helminth (STH) infection and has been hypothesized to prevent fecal contamination from spreading throughout the household environment. We evaluated the effect of providing households with a pit latrine with a plastic slab and drophole cover, child feces management tools, and associated behavioral messaging on reducing STH eggs in household soil. We collected soil samples from 2107 households (898 control and 1209 improved sanitation intervention households) that were enrolled in the WASH Benefits cluster randomized controlled trial in rural Kenya and performed a post-intervention analysis after two years of intervention exposure. Following a pre-specified analysis plan, we combined all households that received the sanitation intervention into one group for comparison to control households. The prevalence of STH eggs in soil was 18.9% in control households and 17.0% in intervention households. The unadjusted prevalence ratio of total STH eggs in the intervention groups compared to the control group was 0.94 (95% CI: 0.78-1.13). The geometric mean concentration was 0.05 eggs/g dry soil in control households and intervention households. Unadjusted and adjusted models gave similar results. We found use of a shared latrine, presence of a roof over the sampling area, and the number of dogs owned at baseline was associated with an increased prevalence of STH eggs in soil; the presence of a latrine that was at least 2 years old and a latrine with a covered drophole was associated with a reduction in the prevalence of STH eggs in soil. Soil moisture content was also associated with an increased prevalence of STH eggs in soil. Our results indicate that an intervention designed to increase access to improved latrines and child feces management tools may not be enough to impact environmental occurrence of STH in endemic areas where latrine coverage is already high.

Almost one-quarter of the world's population is infected with soil-transmitted helminths (STH). We conducted a study to determine the prevalence and location of STH-Ascaris, Trichuris, and hookworm spp.-egg contamination in soil within rural household plots in Kenya. Field staff collected soil samples from July to September 2014 from the house entrance and the latrine entrance of households in Kakamega County; additional spatial sampling was conducted at a subset of households (N = 22 samples from 3 households). We analyzed soil samples using a modified version of the US Environmental Protection Agency (EPA) method for enumerating Ascaris in biosolids. We found 26.8% of households had one or more species of STH eggs present in the soil in at least one household location (n = 18 out of 67 households), and Ascaris was the most commonly detected STH (19.4%, n = 13 out of 67 households). Prevalence of STH eggs in soil was equally likely at the house entrance (19.4%, N = 67) as at the latrine entrance (11.3%, N = 62) (p = 0.41). We also detected STH eggs at bathing and food preparation areas in the three houses revisited for additional spatial sampling, indicating STH exposure can occur at multiple sites within a household plot, not just near the latrine. The highest concentration of eggs in one house occurred in the child's play area. Our findings suggest interventions to limit child exposure to household soil could complement other STH control strategies.

Schistosomiasis is among the most common parasitic diseases in the world, with over 142 million people infected in low- and middle-income countries. Measuring population-level transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected using stool microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to S. mansoni soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. We estimated force of infection among children using the seroconversion rate and examined how it varied geographically and by age. At the community level, serological measures of transmission aligned with stool-based measures of infection (ρ = 0.94), and serological measures provided more resolution for between-community differences at lower levels of infection. Force of infection showed a clear gradient of transmission with distance from Lake Victoria, with 94% of infections and 93% of seropositive children in communities <1.5 km from the lake. Force of infection increased through age 3 y, by which time 65% (95% CI: 53%, 75%) of children were SEA positive in high-transmission communities-2 y before they would be reached by school-based deworming programs. Our results show that serologic surveillance platforms represent an important opportunity to guide and monitor schistosomiasis control programs, and that in high-transmission settings preschool-age children represent a key population missed by school-based deworming programs.

Globally, about 1.5 billion people are infected with at least one species of soil-transmitted helminth (STH). Soil is a critical environmental reservoir of STH, yet there is no standard method for detecting STH eggs in soil. We developed a field method for enumerating STH eggs in soil and tested the method in Bangladesh and Kenya. The US Environmental Protection Agency (EPA) method for enumerating Ascaris eggs in biosolids was modified through a series of recovery efficiency experiments; we seeded soil samples with a known number of Ascaris suum eggs and assessed the effect of protocol modifications on egg recovery. We found the use of 1% 7X as a surfactant compared to 0.1% Tween 80 significantly improved recovery efficiency (two-sided t-test, t = 5.03, p = 0.007) while other protocol modifications-including different agitation and flotation methods-did not have a significant impact. Soil texture affected the egg recovery efficiency; sandy samples resulted in higher recovery compared to loamy samples processed using the same method (two-sided t-test, t = 2.56, p = 0.083). We documented a recovery efficiency of 73% for the final improved method using loamy soil in the lab. To field test the improved method, we processed soil samples from 100 households in Bangladesh and 100 households in Kenya from June to November 2015. The prevalence of any STH (Ascaris, Trichuris or hookworm) egg in soil was 78% in Bangladesh and 37% in Kenya. The median concentration of STH eggs in soil in positive samples was 0.59 eggs/g dry soil in Bangladesh and 0.15 eggs/g dry soil in Kenya. The prevalence of STH eggs in soil was significantly higher in Bangladesh than Kenya (chi-square, χ2 = 34.39, p < 0.001) as was the concentration (Mann-Whitney, z = 7.10, p < 0.001). This new method allows for detecting STH eggs in soil in low-resource settings and could be used for standardizing soil STH detection globally.

Accurate and cost-effective identification of areas where co-endemic infections occur would enable public health managers to identify opportunities for implementation of integrated control programs. Dried blood spots collected during cross-sectional lymphatic filariasis surveys in coastal Kenya were used for exploratory integrated detection of IgG antibodies against antigens from several parasitic infections (Wuchereria bancrofti, Schistosoma mansoni, Plasmodium spp., Ascaris lumbricoides, and Strongyloides stercoralis) as well as for detection of responses to immunizing agents used against vaccine-preventable diseases (VPDs) (measles, diphtheria, and tetanus) using a multiplex bead assay (MBA) platform. High heterogeneity was observed in antibody responses by pathogen and antigen across the sentinel sites. Antibody seroprevalence against filarial antigens were generally higher in Ndau Island (P < 0.0001), which also had the highest prevalence of filarial antigenemia compared with other communities. Antibody responses to the Plasmodium species antigens circumsporozoite protein (CSP) and merozoite surface protein-1 (MSP-1)₁₉ were higher in Kilifi and Kwale counties, with Jaribuni community showing higher overall mean seroprevalence (P < 0.0001). Kimorigo community in Taita-Taveta County was the only area where antibody responses against S. mansoni Sm25 recombinant antigen were detected. Seroprevalence rates to Strongyloides antigen NIE ranged between 3% and 26%, and there was high heterogeneity in immune responses against an Ascaris antigen among the study communities. Differences were observed between communities in terms of seroprevalence to VPDs. Seroprotection to tetanus was generally lower in Kwale County than in other counties. This study has demonstrated that MBA holds promise for rapid integrated monitoring of trends of infections of public health importance in endemic areas.

Identifying populations with active transmission and monitoring changes in transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected in stool using microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to schistosomiasis soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. Serological measures of transmission closely aligned with stool-based measures of infection, and serological measures provided better resolution for between-community differences at lower levels of infection. Serology enabled fine- scale measures of heterogeneity in force of infection both geographically and by age. Our results show that serologic surveillance platforms represent an important new opportunity to guide and monitor schistosomiasis control programs.

Accurate, cost-effective measurement of the burden of co-endemic infections would enable public health managers to identify opportunities for implementation of integrated control programs. Dried blood spots (DBS) collected during a cross-sectional lymphatic filariasis sentinel site survey in the Kenyan coastal counties of Lamu, Tana River, Kilifi, Kwale, and Taita-Taveta were used for the integrated detection of serologic IgG antibodies against antigens from several parasitic infections ( Wuchereria bancrofti , Schistosoma mansoni , Plasmodium spp, Ascaris lumbricoides , and Strongyloides stercoralis ) as well as markers for immunity to vaccine-preventable diseases (measles, diphtheria, and tetanus) on a multiplex bead assay (MBA) platform. High heterogeneity was observed in antibody responses by pathogen and antigen across the sentinel sites. Antibody seroprevalence against Wb123, Bm14, and Bm33 recombinant filarial antigens were generally higher in Ndau Island (p<0.0001), which also had the highest prevalence of filarial antigenemia compared to other communities. Antibody responses to the Plasmodium species antigens CSP and MSP-1 19 were higher in Kilifi and Kwale counties, with Jaribuni community showing higher overall mean seroprevalence (p<0.0001). Kimorigo community in Taita-Taveta County was the only area where antibody responses against Schistosoma mansoni Sm25 recombinant antigen were detected. Seroprevalence rates to Strongyloides antigen NIE ranged between 3% and 26%, and there was high heterogeneity in immune responses against an Ascaris antigen among the study communities. Differences were observed between communities in terms of seroprevalence to vaccine-preventable diseases. Seroprotection to tetanus was lower in all 3 communities in Kwale County compared to the rest of the communities. This study has demonstrated that the MBA platform holds promise for rapid integrated monitoring of trends of infections of public health importance in endemic areas, and assessing the effectiveness of control and elimination programs.

Author Summary

Establishment of successful private-public partnerships in the recent past has led to an increase in resources available for control and elimination of malaria and Neglected Tropical Diseases (NTDs). Implementation of control and elimination programs and their subsequent monitoring and evaluation would be greatly facilitated by development of new tools and strategies for rapid identification of areas of transmission so that interventions could be prioritized to regions where they were most needed. Since development of antibody responses in a host depend on exposure to an infectious agent, assessment of such serologic markers provides a sensitive way to measure differences between populations in pathogen exposure. Our study applied a state-of-the-art multiplex bead assay platform to perform integrated measurement of antibody responses to multiple parasitic diseases and immunizing antigens for vaccine-preventable diseases (VPDs) in ten lymphatic filariasis sentinel sites across the Kenyan coastal region. A community-level analysis of age-specific and overall mean seroprevalence fit using a flexible model ensemble provided an improved understanding about the distributions of the various parasitic infections and seroprotection to VPDs. This study provides an important proof of concept for how we could dramatically increase the value of existing surveillance activities using small volumes of blood collected on filter paper and analyzed using a single multiplex laboratory assay and novel data analysis techniques.

Background

The relation between subclinical hemoglobinopathies and concentrations of the iron-regulatory hormone hepcidin is not well characterized.

Objective

We investigated the relation of hepcidin concentration with hemoglobinopathies among young children in Kenya.

Methods

We quantified serum hepcidin and ferritin in 435 Kenyan children aged 14-20 mo in a subsample of the Water, Sanitation, and Handwashing (WASH) Benefits Trial. Blood samples were genotyped for α+-thalassemia and for sickle cell disorder. Hepcidin was compared across sickle cell and α+-thalassemia genotypes separately by using generalized linear models, and children who were normozygous for both conditions were also compared with those who had either of these conditions. In the association between hepcidin and ferritin, we assessed effect modification by genotype.

Results

In this population, we found that 16.2% had sickle cell trait and 0.2% had sickle cell disorder, whereas 40.0% were heterozygous for α+-thalassemia and 8.2% were homozygous. Hepcidin concentration did not differ by genotype, but effect modification was found by genotype in the association between hepcidin and ferritin (P < 0.1). Among normozygous sickle cell children (HbAA), there was an association between hepcidin and ferritin (β = 0.92; 95% CI: 0.72, 1.10). However, among those with sickle cell trait (HbAS), the association was no longer significant (β = 0.31; 95% CI: -0.04, 0.66). Similarly, among children who were normozygous (αα/αα) or heterozygous (-α/αα) for α+-thalassemia, hepcidin and ferritin were significantly associated [β = 0.94 (95% CI: 0.68, 1.20) and β = 0.77 (95% CI: 0.51, 1.03), respectively]; however, in children who were homozygous for α+-thalassemia (-α/-α), there was no longer a significant association (β = 0.45; 95% CI: -0.10, 1.00).

Conclusion

Hepcidin was not associated with hemoglobin genotype, but there may be a difference in the way hepcidin responds to iron status among those with either sickle cell trait or homozygous α+-thalassemia in young Kenyan children. This trial was registered at clinicaltrials.gov as NCT01704105.

Poor nutrition and hand hygiene are risk factors for acute respiratory infections (ARIs). Safe drinking water and sanitation can reduce exposure to pathogens and encourage healthy immune responses, reducing the risk of ARIs. Within a trial assessing impacts of water, sanitation, and handwashing (WASH), and nutritional interventions, we evaluated effects on ARIs. The WASH Benefits cluster-randomized trial enrolled pregnant women from Kenyan villages and evaluated health outcomes in children born to enrolled mothers 1 and 2 years after intervention delivery. Geographically adjacent clusters were block-randomized into a passive control (no promotional visits), a double-sized active control (monthly visits to measure mid-upper arm circumference), and six intervention groups: chlorinated drinking water (W), improved sanitation (S), handwashing with soap (H), combined WSH, improved nutrition (N) through counseling and lipid-based nutrient supplementation (LNS), and combined WSHN. The main outcome was the prevalence of ARI symptoms (cough, panting, wheezing, or difficulty breathing) in children younger than 3 years. Masking participants was not possible. Analyses were intention-to-treat. Between November 2012 and May 2014, 702 clusters were enrolled, including 6,960 (year 1) and 7,088 (year 2) children with ARI data. The cluster-level intra-cluster correlation coefficient for ARIs was 0.026 across both years. Water, sanitation, and handwashing interventions with behavior change messaging did not reduce ARIs. Nutrition counseling and LNS modestly reduced ARI symptoms compared with controls in year 1 [prevalence ratio (PR): 0.87, 95% confidence interval (CI): 0.77-0.99], but no effect in the combined WSHN group weakens this finding.