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Objective To determine if the prevalence of schistosomiasis in children aged 9--12 years is associated with the prevalence in 5--8-year-olds and adults after preventive chemotherapy in schools or the community. Methods We combined data from four community-randomized, preventive chemotherapy trials in treatment-naïve populations in Côte d'Ivoire, Kenya and the United Republic of Tanzania during 2010--2016 according to the number of praziquantel treatments and the delivery method. Schistosoma mansoni infection was sought on two slides prepared from each participant's first stool using the Kato--Katz technique. We assessed associations between S. mansoni prevalence in 9--12-year-olds and 5--8-year-olds and adults in the community before and after treatment using Bayesian regression models. Findings Stool samples from 47 985 5--8-year-olds, 81 077 9--12-year-olds and 20 492 adults were analysed. We found associations between the prevalence in 9--12-year-olds and that in 5--8-year-olds and adults after preventive treatment, even when only school-age children were treated. When the prevalence in 9--12-year-olds was under 10%, the prevalence in 5--8-year-olds was consistently under 10%. When the prevalence in 9--12-year-olds was under 50%, the prevalence in adults after two or four rounds of preventive chemotherapy was 10%--15% lower than before chemotherapy. Post-chemotherapy age-group associations were consistent with pre-chemotherapy associations in this analysis and previous studies. Conclusion The prevalence of S. mansoni infection in 9--12-year-olds was associated with the prevalence in other age groups and could be used to guide community treatment decisions. [ABSTRACT FROM AUTHOR]

WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, palatability, and pharmacokinetics of arpraziquantel (L-praziquantel) orodispersible tablets for preschool-aged children. This open-label, partly randomised, phase 3 study was conducted at two hospitals in Côte d'Ivoire and Kenya. Children with a minimum bodyweight of 5 kg in those aged 3 months to 2 years and 8 kg in those aged 2–6 years were eligible. In cohort 1, participants aged 4–6 years infected with Schistosoma mansoni were randomly assigned (2:1) to receive a single dose of oral arpraziquantel 50 mg/kg (cohort 1a) or oral praziquantel 40 mg/kg (cohort 1b) using a computer-generated randomisation list. Cohorts 2 (aged 2–3 years) and 3 (aged 3 months to 2 years) infected with S mansoni , and the first 30 participants in cohort 4a (aged 3 months to 6 years) infected with Schistosoma haematobium , received a single dose of oral arpraziquantel 50 mg/kg. After follow-up assessments, arpraziquantel was increased to 60 mg/kg (cohort 4b). Laboratory personnel were masked to the treatment group, screening, and baseline values. S mansoni was detected using a point-of-care circulating cathodic antigen urine cassette test and confirmed using the Kato-Katz method. The primary efficacy endpoint was clinical cure rate at 17–21 days after treatment in cohorts 1a and 1b, measured in the modified intention-to-treat population and calculated using the Clopper-Pearson method. This study is registered with ClinicalTrials.gov , NCT03845140. Between Sept 2, 2019, and Aug 7, 2021, 2663 participants were prescreened and 326 were diagnosed with S mansoni or S haematobium. 288 were enrolled (n=100 in cohort 1a, n=50 in cohort 1b, n=30 in cohort 2, n=18 in cohort 3, n=30 in cohort 4a, and n=60 in cohort 4b), but eight participants received antimalarial drugs and were excluded from the efficacy analyses. The median age was 5·1 years (IQR 4·1–6·0) and 132 (47%) of 280 participants were female and 148 (53%) were male. Cure rates with arpraziquantel were similar to those with praziquantel (87·8% [95% CI 79·6–93·5] in cohort 1a vs 81·3% [67·4–91·1] in cohort 1b). No safety concerns were identified during the study. The most common drug-related treatment-emergent adverse events were abdominal pain (41 [14%] of 288 participants), diarrhoea (27 [9%]), vomiting (16 [6%]), and somnolence (21 [7%]). Arpraziquantel, a first-line orodispersible tablet, showed high efficacy and favourable safety in preschool-aged children with schistosomiasis. The Global Health Innovative Technology Fund, the European and Developing Countries Clinical Trials Partnership, and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). [ABSTRACT FROM AUTHOR]

Background: Evidence indicates that whereas repeated rounds of mass drug administration (MDA) programs have reduced schistosomiasis prevalence to appreciable levels in some communities referred to here as responding villages (R). However, prevalence has remained high or less than anticipated in other areas referred to here as persistent hotspot villages (PHS). Using a cross-sectional quantitative approach, this study investigated the factors associated with sustained high Schistosoma mansoni prevalence in some villages despite repeated high annual treatment coverage in western Kenya. Method: Water contact sites selected based on observation of points where people consistently go to collect water, wash clothes, bathe, swim or play (young children), wash cars and harvest sand were mapped using hand-held smart phones on the Commcare platform. Quantitative cross-sectional surveys on behavioral characteristics were conducted using interviewer-based semi-structured questionnaires administered to assess water usage/contact patterns and open defecation. Questionnaires were administered to 15 households per village, 50 pupils per school and 1 head teacher per school. One stool and urine sample was collected from 50 school children aged 9–12 year old and 50 adults from both responding (R) and persistent hotspot (PHS) villages. Stool was analyzed by the Kato-Katz method for eggs of S. mansoni and soil-transmitted helminths. Urine samples were tested using the point-of-care circulating cathodic antigen (POC-CCA) test for detection of S. mansoni antigen. Results: There was higher latrine coverage in R (n = 6) relative to PHS villages (n = 6) with only 33% of schools in the PHS villages meeting the WHO threshold for boy: latrine coverage ratio versus 83.3% in R, while no villages met the girl: latrine ratio requirement. A higher proportion of individuals accessed unprotected water sources for both bathing and drinking (68.5% for children and 89% for adults) in PHS relative to R villages. In addition, frequency of accessing water sources was higher in PHS villages, with swimming being the most frequent activity. As expected based upon selection criteria, both prevalence and intensity of S. mansoni were higher in the PHS relative to R villages (prevalence: 43.7% vs 20.2%; P < 0.001; intensity: 73.8 ± 200.6 vs 22.2 ± 96.0, P < 0.0001), respectively. Conclusion: Unprotected water sources and low latrine coverage are contributing factors to PHS for schistosomiasis in western Kenya. Efforts to increase provision of potable water and improvement in latrine infrastructure is recommended to augment control efforts in the PHS areas. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic inequality including wealth distribution is a barrier to implementation of health policies. Wealth distribution can be measured effectively using household data on durable assets. Compared to other methods of analysing Socio-economic Status (SES) using durable assets, Multiple Correspondence Analysis (MCA) can create more reliable wealth quintiles. We therefore evaluated socioeconomic determinants of Schistosoma mansoni using MCA on household data among adult population in western Kenya. The hypothesis of this study was that MCA would be a useful predictor of S. mansoni prevalence and/or intensity. Methodology: Twelve villages, 6 villages that had showed the greatest decrease in S. mansoni prevalence (Responder villages) and 6 villages that showed relatively lower decrease (Hotspot villages) between the year 2011 and 2015 were randomly selected for this study. This was according to a previous Schistosomiasis Consortium for Operational Research and Elimination (SCORE) report from western Kenya. From each village, convenience sampling was used to identify 50 adults from 50 households for inclusion in this study. An interview with a questionnaire based upon MCA indicators was conducted. One stool sample from each of the 600 adults was examined based on four slides for S. mansoni eggs using Kato Katz technique. Mean Eggs per gram(EPG) was calculated by taking the average of the readings from the four slides. A log binomial regression model was used to identify the influence of the various age-groups(<30 years, 30-60 years and >60 years), household size, wealth class, occupation, education status, main water supply, sex and sub-county of residence on S. mansoni infection. EPG was then compared across variables that were significant based on multivariate log binomial model analysis using a mixed model. Principal findings: Overall prevalence of S. mansoni was 41.3%. Significantly higher prevalence of S. mansoni were associated with males, those aged below 30 years, those who use unsafe water sources (unprotected wells, lakes and rivers), residents of Rachuonyo North, Hotspot villages and those earning livelihood from fishing. Only sex and household size were significant predictors in the multivariate model. Males were associated with significantly higher prevalence compared to the females (aPR = 1.37; 95% CI = 1.14–1.66). In addition, households with at least four persons had higher prevalence compared to those with less than four (aPR = 1.29; 95% CI = 1.03–1.61). However, there was no difference in prevalence between the wealth classes(broadly divided into poor and less poor categories). Intensity of infection (Mean EPG)was also significantly higher among males, younger age group, Rachuonyo North residents and Hotspot Villages. Conclusion: Socioeconomic status based on an MCA model was not a contributing factor to S. mansoni prevalence and/or intensity possibly because the study populations were not sufficiently dissimilar. The use of convenience sampling to identify participants could also have contributed to the lack of significant findings. [ABSTRACT FROM AUTHOR]

Effective future control of female genital schistosomiasis (FGS) requires an integrated and multisectoral approach, bringing together HIV, sexual and reproductive health, and reproductive rights sectors. In this article, an underappreciated but important connection between FGS and menstrual hygiene initiatives in Africa is highlighted. [ABSTRACT FROM AUTHOR]

Neonatal immune development begins in pregnancy and continues into lactation and may be affected by maternal diet. We investigated the possibility that maternal protein deficiency (PD) during a chronic gastrointestinal (GI) nematode infection could impair neonatal immune development. Beginning on d 14 of pregnancy, mice were fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets and were infected weekly with either 0 (sham) or 100 Heligmosomoides bakerilarvae. Pups were killed on d 2, 7, 14, and d 21 and dams on d 20 of lactation. Lymphoid organs were weighed. Cytokine concentration in maternal and pup serum and in milk from pup stomachs and lymphoid cell populations in pup spleen and thymus were determined using luminex and flow cytometry, respectively. GI nematode infection increased Th2 cytokines (IL-4, IL-5, IL-13), IL-2, IL-10, and eotaxin in serum of dams whereas PD reduced IL-4 and IL-13. The lower IL-13 in PD dams was associated with increased fecal egg output and worm burdens. Maternal PD increased vascular endothelial growth factor in pup milk and eotaxin in pup serum. Maternal infection increased eotaxin in pup serum. Evidence of impaired neonatal immune development included reduced lymphoid organ mass in pups associated with both maternal infection and PD and increased percentage of T cells and T:B cell ratio in the spleen associated with maternal PD. Findings suggest that increases in specific proinflammatory cytokines as a result of the combination of infection and dietary PD in dams can impair splenic immune development in offspring. [ABSTRACT FROM AUTHOR]

High levels of environmental contamination, often associated with improper waste and excreta management, are widespread among informal settlements within urban areas in developing countries. We determined the level of faecal contamination in domestic water sources and evaluated the potential contribution of these water sources to intestinal helminthiases in seven informal settlements of Kisumu City, western Kenya. Membrane filtration technique was used for enumeration of total and (aecal (Escherichia coli) coliform bacteria in water samples collected from dams, rivers, springs and wells. Out of the 80 water sources sampled, 76 (95%) were highly contaminated with E. coli. All water samples from unprotected wells (26) and 92.6% of samples from protected wells (25) were positive for E. coli. The highest and lowest E. coil densities were observed in samples from dams (3,800 ± 1,807 coliforms per 100 ml) and boreholes (419 ± 223 coliforms per 100 ml), respectively (p = 0.0321). Distance from pit latrines was negatively associated with E. coli coliform density for wells (r= -0.34, n = 53, p = 0.0142). Untreated well-water may not be suitable for human consumption, and its continued use constitutes a major health risk for the inhabitants of these informal settlements. [ABSTRACT FROM AUTHOR]

Background: Intestinal schistosomiasis continues to be a significant cause of morbidity among communities located around Lake Victoria and on its islands. Although epidemiological surveys have been conducted in other areas bordering the lake in western Kenya, Mbita district and its adjacent islands have never been surveyed, largely due to logistical challenges in accessing these areas. Consequently, there is a paucity of data on prevalence of schistosomiasis and soil-transmitted helminth (STH) infections that are endemic in this region. Methods: This cross-sectional study determined the prevalence, intensity of infection and geographical distribution of schistosome and STH infections among 4,065 children aged 5-19 years in 84 primary schools in Mbita and nearby islands of Lake Victoria (Mfangano, Ringiti, Rusinga and Takawiri), in western Kenya. Single stool samples were collected and examined for eggs of Schistosoma mansoni and STHs (Hookworms, Ascaris lumbricoides and Trichuris trichiura) using the Kato-Katz technique. Primary schools were mapped using geographical information system data on PDAs and prevalence maps generated using ArcView GIS software. Results: Overall, 65.6% (95% CI = 64.2-67.1%) of children were infected with one or more helminth species; 12.4% (95% CI = 11.4-13.4%) of children were infected with one or more STH species. Mean school prevalence of S. mansoni infection was 60.5% (95% CI = 59.0-62.0%), hookworms 8.4% (95% CI = 7.6-9.3%), A. lumbricoides 3.3% (95% CI = 2.7-3.8%), and T. trichiura 1.6% (95% CI = 1.2-2.0%). Interestingly, the mean S. mansoni prevalence was 2-fold higher on the islands (82%) compared to the mainland (41%) (z = 5.8755, P < 0.0001). Similarly, intensity of infection was 54% higher on the islands (217.2 ± 99.3) compared to the mainland (141.3 ± 123.7) (z = 3.9374, P < 0.0001). Schools in closest proximity to Lake Victoria had the highest S. mansoni prevalence while prevalence of STHs was more homogenously distributed. Conclusions: The very high prevalence of schistosomiasis in Mbita and the 4 islands is quite alarming, and indicates an urgent and critical need for control interventions. Findings from this survey indicate the need to implement treatment in remote areas not previously covered by mass drug administration programs. [ABSTRACT FROM AUTHOR]

Using a 2 × 2 factorial design, we investigated the combined impact of protein deficiency (PD) and gastrointestinal nematode infection during late pregnancy and lactation on resting metabolic rate (RMR), body composition and bone mineralization, neonatal growth, and the regulatory hormones Icorticosterone, leptin, and insulin-like growth factor-1 (IGF-1)] and proinflammatory cytokines linterleukin (IL)-1β and IL-6] that may drive these processes. Pregnant CD1 mice, fed either a protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isocaloric diet, were infected 4 times with either 0 (sham) or 100 Heligmosomoides baker/larvae beginning on d 14 of pregnancy. Dams were killed on d 20 postpartum and pups on d 2, 7, 14, and 21. Diet and infection had largely independent effects. The PD diet elevated corticosterone and upregulated leptin concentration in maternal serum, which was associated with reduced food intake leading to lower body mass, RMR, and body temperature. Infection reduced food intake but elevated maternal serum IL-1β and IL-6 and did not affect corticosterone, leptin, RMR, or body temperature. The PD diet decreased maternal bone area and bone mineral content. Infection lowered maternal bone mineral density, consistent with elevated IL-1β and IL-6. The elevated serum IL- 1β and lower IGF-1 in pups of PD dams and lower serum leptin and IGF-1 in pups of infected dams were both consistent with the lower pup body mass and shorter crown-rump length. This mouse model provides a novel framework to study the impact of diet and nematode infection on bone. [ABSTRACT FROM AUTHOR]

Background: Female genital schistosomiasis (FGS) constitutes four different lesions known to be caused by Schistosoma haematobium ova deposited in the genital tract. Schistosoma mansoni ova may also be found in the genital tract. However, it is not known if S. mansoni causes lower genital tract lesions characteristic of FGS. Methodology: This study was conducted in 8 villages along the shores of Lake Victoria, western Kenya. Stool and urine samples collected from women of reproductive age on three consecutive days were analysed for S. mansoni and S. haematobium infection. S. mansoni positive and S. haematobium negative willing participants, aged 18–50 years were invited to answer a questionnaire (demographics, symptoms), undergo a gynaecological examination and cytology specimen collection by an FGS expert. Principal findings: Gynaecologic investigations were conducted in 147 S. mansoni-positive women who had a mean infection intensity of 253.3 epg (95% CI: 194.8–311.9 epg). Nearly 90% of them used Lake Victoria as their main water source. None were found to have cervicovaginal grainy sandy patches or rubbery papules. Homogenous yellow patches were found in 12/147 (8.2%) women. Women with homogenous yellow patches were significantly older (47 years) than the rest (34 years, p = 0.001). No association was found between intensity of S. mansoni infection and homogenous yellow patches (p = 0.70) or abnormal blood vessels (p = 0.14). S. mansoni infection intensity was not associated with genital itch, bloody or malodorous vaginal discharge. Conclusion: S. mansoni infection was neither associated with lower genital tract lesions nor symptoms typically found in women with FGS. Author summary: Women who have fresh water contact in rivers or lakes may get infected with the waterborne parasites, that can cause Bilharzia, also called schistosomiasis. In Africa, Schistosoma (S.) haematobium is associated with HIV acquisition, genital tract lesions, bloody and malodorous discharge. There is also decreased clearance of human papillomavirus (HPV) in women with genital schistosomiasis. There are occasional case reports showing eggs of S. mansoni (intestinal schistosomiasis) in the genitals. However, no study has systematically looked for the genital tract lesions of S. mansoni and the impact on gynaecological health has never been explored. We sought to explore if S. mansoni causes the lower genital tract genital lesions. In women living near Lake Victoria, Kenya, we included 147 women who had S. mansoni but not S. haematobium infection. We found that the few women who had signs of sequelae of schistosomiasis infection in the genitals, so-called homogenous yellow patches had all potentially been exposed to S. haematobium in their youth. In this study population we found no lower genital tract lesions or genital symptoms to be associated with S. mansoni. [ABSTRACT FROM AUTHOR]

Background: The standard diagnosis of Ascaris lumbricoides and other soil-transmitted helminth (STH) infections relies on the detection of worm eggs by copromicroscopy. However, this method is dependent on worm patency and shows only limited accuracy in low-intensity infection settings. We aimed to decipher the diagnostic accuracy of different antibodies using various Ascaris antigens in reference to copromicroscopy and quantitative PCR (qPCR), four months after national STH preventative chemotherapy among school children in western Kenya. Methodology: STH infection status of 390 school children was evaluated via copromicroscopy (Kato-Katz and mini-FLOTAC) and qPCR. In parallel, Ascaris-specific antibody profiles against larval and adult worm lysates, and adult worm excretory-secretory (ES) products were determined by enzyme-linked immunosorbent assay. Antibody cross-reactivity was evaluated using the closely related zoonotic roundworm species Toxocara cati and Toxocara canis. The diagnostic accuracy of each antibody was evaluated using receiver operating curve analysis and the correspondent area under the curve (AUC). Principal findings: Ascaris was the predominant helminth infection with an overall prevalence of 14.9% (58/390). The sensitivity of mini-FLOTAC and Kato-Katz for Ascaris diagnosis reached only 53.5% and 63.8%, respectively compared to qPCR. Although being more sensitive, qPCR values correlated with microscopic egg counts (R = -0.71, P<0.001), in contrast to antibody levels. Strikingly, IgG antibodies recognizing the ES products of adult Ascaris worms reliably diagnosed active Ascaris infection as determined by qPCR and microscopy, with IgG1 displaying the highest accuracy (AUC = 0.83, 95% CI: 0.75–0.91). Conclusion: IgG1 antibody responses against adult Ascaris-ES products hold a promising potential for complementing the standard fecal and molecular techniques employed for monitoring Ascaris infections. This is of particular importance in the context of deworming programs as the antibody diagnostic accuracy was independent of egg counts. Author summary: Ascaris lumbricoides is the most common human intestinal helminth globally, affecting a quarter of the world's population. Microscopic methods are used to diagnose and monitor Ascaris infections. However, these methods are unsatisfactory for diagnosing low-intensity infections, are prone to human error, their accuracy is greatly affected by the heterogeneous distribution of worm eggs and are limited to detecting only patent infections. qPCR offers an attractive alternative with regard to sensitivity and high-throughput capacity but is also limited by worm patency. Here, we compared the diagnostic accuracy of different antibodies using Ascaris antigen lysates as well as Ascaris excretory/secretory (ES) products using copromicroscopy and qPCR as reference. Our data show that IgG1 antibody responses directed against ES antigens of adult Ascaris worms, but not against the infective third-stage larval or adult worm extracts, reliably decipher between Ascaris-infected and Ascaris-negative participants independent of the microscopic egg counts. Our study is the first to report strong IgG1 responses directed against ES products of adult worms and their potential value as markers for an active Ascaris infection. Our results indicate the potential to develop an antibody-based Ascaris-immunoassay utilizing Ascaris-ES antigens to complement the monitoring of reinfections and transmission dynamics. [ABSTRACT FROM AUTHOR]

Background: Control and elimination of schistosomiasis is an arduous task, with current strategies proving inadequate to break transmission. Exploration of genetic approaches to interrupt Schistosoma mansoni transmission, the causative agent for human intestinal schistosomiasis in sub-Saharan Africa and South America, has led to genomic research of the snail vector hosts of the genus Biomphalaria. Few complete genomic resources exist, with African Biomphalaria species being particularly underrepresented despite this being where the majority of S. mansoni infections occur. Here we generate and annotate the first genome assembly of Biomphalaria sudanica sensu lato, a species responsible for S. mansoni transmission in lake and marsh habitats of the African Rift Valley. Supported by whole-genome diversity data among five inbred lines, we describe orthologs of immune-relevant gene regions in the South American vector B. glabrata and present a bioinformatic pipeline to identify candidate novel pathogen recognition receptors (PRRs). Results: De novo genome and transcriptome assembly of inbred B. sudanica originating from the shoreline of Lake Victoria (Kisumu, Kenya) resulted in a haploid genome size of ~ 944.2 Mb (6,728 fragments, N50 = 1.067 Mb), comprising 23,598 genes (BUSCO = 93.6% complete). The B. sudanica genome contains orthologues to all described immune genes/regions tied to protection against S. mansoni in B. glabrata, including the polymorphic transmembrane clusters (PTC1 and PTC2), RADres, and other loci. The B. sudanica PTC2 candidate immune genomic region contained many PRR-like genes across a much wider genomic region than has been shown in B. glabrata, as well as a large inversion between species. High levels of intra-species nucleotide diversity were seen in PTC2, as well as in regions linked to PTC1 and RADres orthologues. Immune related and putative PRR gene families were significantly over-represented in the sub-set of B. sudanica genes determined as hyperdiverse, including high extracellular diversity in transmembrane genes, which could be under pathogen-mediated balancing selection. However, no overall expansion in immunity related genes was seen in African compared to South American lineages. Conclusions: The B. sudanica genome and analyses presented here will facilitate future research in vector immune defense mechanisms against pathogens. This genomic/transcriptomic resource provides necessary data for the future development of molecular snail vector control/surveillance tools, facilitating schistosome transmission interruption mechanisms in Africa. [ABSTRACT FROM AUTHOR]

To examine whether anti-tetanus toxoid (anti-TT) immunoglobulin G (IgG) levels measured in oral fluid and adjusted for collection difficulties and specimen quality are associated with total IgG and anti-TTIgG in oral fluid and assess if statistical adjustment for them improves prediction of anti-TT IgG in serum. 267 children, ages 12 to 15 months, enrolled in the M-SIMU randomized controlled trial participated in this nested cross-sectional analysis. Venous blood and oral fluid (OF) specimens were collected, and OF collection difficulties such as crying or gagging were recorded. OF volume was documented and total IgG was measured in OF specimens and anti-TT IgG was measured in OF and serum by enzyme immunoassay (EIA). Collection difficulties, volume and sociodemographic characteristics were assessed in relation to total IgG and anti-TT IgG in OF via multivariate regression. These models were extended to evaluate the association between anti-TT IgG in OF and in serum. A prediction model was developed to adjust anti-TT IgG in OF estimates as proxy for serum. Blood in the specimen, sores in the mouth and crying were positively associated with total IgG concentration while high oral fluid volume and sucking on the swab were inversely associated. None were significant predictors of anti-TT IgG in OF after adjusting for total IgG (geometric mean [GM] ratio: 1.99; 95% confidence interval: 1.78–2.24) and vaccination history (GM ratio: 2.44; 95% CI: 1.98–3.01). When predicting anti-TT IgG levels in serum with OF, total IgG modified the effect of anti-TT IgG in OF. Anti-TT IgG in OF is a good proxy for levels in serum, after controlling for total IgG in the specimen and other variables. Post hoc adjustments for OF volume and total IgG concentration are an important consideration when conducting serosurveys with oral fluid. [ABSTRACT FROM AUTHOR]

Background: Accurate mapping of schistosomiasis (SCH) and soil transmitted helminths (STH) is a prerequisite for effective implementation of the control and elimination interventions. A precision mapping protocol was developed and implemented in the coastal region of Kenya by applying the current World Health Organization (WHO) mapping guide at a much lower administrative level (ward). Methods: A two-stage cluster survey design was undertaken, with 5 villages in each ward selected. From within each village 50 households were randomly selected, and a single child between the ages of 8 and 14 sampled following appropriate assent. The prevalence and intensity of infection of Schistosoma mansoni and STH were determined using the Kato-Katz method (single stool, duplicate slides) and urine filtration for S. haematobium. Results: Of the 27,850 school age children sampled, 6.9% were infected with at least one Schistosoma species, with S. haematobium being the most common 6.1% (95% CI: 3.1–11.9), and Tana River County having highest prevalence 19.6% (95% CI: 11.6–31.3). Prevalence of any STH infection was 5.8% (95% CI: 3.7–8.9), with Lamu County having the highest prevalence at 11.9% (95% CI: 10.0–14.1). The most prevalent STH species in the region was Trichuris trichiura at 3.1% (95% CI: 2.0–4.8). According to the WHO threshold for MDA implementation, 31 wards (in 15 sub-Counties) had a prevalence of ≥10% for SCH and thus qualify for annual MDA of all age groups from 2 years old. On the other hand, using the stricter Kenya BTS MDA threshold of ≥2%, 72 wards (in 17 sub-Counties) qualified for MDA and were targeted for treatment in 2021. Conclusions: The precision mapping at the ward level demonstrated the variations of schistosomiasis prevalence and endemicity by ward even within the same sub-counties. The data collected will be utilized by the Kenyan Ministry of Health to improve targeting Author summary: Mapping of schistosomiasis (SCH) and soil-transmitted helminths (STH) is a critical step in understanding where at-risk populations live so as to plan and target available resources in order to achieve maximum impact on disease burden. While there has been progress in mapping of SCH across the world, the current mapping design for SCH is limited in addressing the focal nature of SCH in implementation units. As part of the Breaking Transmission Strategy (BTS) developed by the Kenyan Ministry of Health that focuses on elimination of neglected diseases including SCH and STH, an evaluation was conducted to identify the SCH and STH at-risk population to better target control using a precision mapping approach. The findings from this evaluation provided a comprehensive delineation of the distribution and prevalence of SCH and STH that informed the rollout of community-based mass drug administration for control of SCH and STH at the Kenyan coast. [ABSTRACT FROM AUTHOR]

Background: The Community Directed Intervention (CDI) strategy has been used to conduct various health interventions in Africa, including control of Neglected Tropical Diseases (NTDs). Although the CDI approach has shown good results in the control of onchocerciasis and lymphatic filariasis with respect to treatment coverage using community drug distributors, its utility in the control of schistosomiasis among urban poor is yet to be established. Using a longitudinal qualitative study, we explored the experiences, opportunities, challenges as well as recommendations of Community Health Workers (CHWs) after participation in annual mass drug administration (MDA) activities for schistosomiasis using the CDI approach in an urban setting.Methods: Unstructured open-ended group discussions were conducted with CHWs after completion of annual MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussions, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.ti. software, and themes explored using the principle of interpretative phenomenological analysis (IPA).Results: From the perspective of the CHWs, opportunities for implementing CDI in urban settings, included the presence of CHWs, their supervisory structures and their knowledge of intervention areas, and opportunity to integrate MDA with other health interventions. Several challenges were mentioned with regards to implementing MDA using the CDI strategy among them lack of incentives, fear of side effects, misconceptions regarding treatment and mistrust, difficulties working in unsanitary environmental conditions, insecurity, and insufficient time. A key recommendation in promoting more effective MDA using the CDI approach was allocation of more time to the exercise.Conclusion: Findings from this study support the feasibility of using CDI for implementing MDA for schistosomiasis in informal settlements of urban areas. Extensive community sensitization and provision of incentives may help address the aforementioned challenges associated with implementing MDA using the CDI strategy. Opportunities highlighted in this study may be of value to other programmes that may be considering the adoption of the CDI strategy for rolling out interventions in the urban setting. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis studies in western Kenya have mainly focused on the intestinal form, with evidence of urinary schistosomiasis remaining anecdotal. Detailed disease mapping has been carried out predominantly along the shores of Lake Victoria, but there is a paucity of information on intestinal and urinary schistosomiasis in inland sites. Methods: This cross-sectional survey of 3,487 children aged 7–18 years from 95 schools in south Nyanza, western Kenya determined the prevalence, infection intensity, and geographical distribution of Schistosoma haematobium, evaluating its co-endemicity with Schistosoma mansoni and soil-transmitted helminths (STHs). Helminth eggs were analyzed from single urine (for S. haematobium) and stool (for S. mansoni and STHs) samples by centrifugation and Kato-Katz, respectively. Hematuria was used as a proxy indicator for S. haematobium. Schools and water bodies (ponds, water-points, streams, dams and rivers) were mapped using Geographical Information System and prevalence maps obtained using ArcView GIS Software. Results: S. haematobium infections with an overall prevalence of 9.3% (95% CI = 8.4-10.2%) were mostly prevalent in Rachuonyo, 22.4% (95% CI = 19.2-25.9% and 19.7 eggs/10 ml) and Migori, 10.7% (95% CI = 9.2-12.3% and 29.5 eggs/10 ml) districts, particularly around Kayuka pond and Ongoche river respectively. Overall infections correlated with hematuria (r = 0.9, P < 0.0001) and were more likely in boys (P < 0.0001, OR = 0.624). S. mansoni infections with an overall prevalence of 13% (95% CI =11.9-14.1%) were majorly confined along the shores of Lake Victoria. STH infections were homogenously distributed with A. lumbricoides occurring in 5.4% (95% CI = 4.7-6.3%) and T. trichiura in 2.8% (95% CI = 2.3-3.4%) of the children. Although S. mansoni infections were more co-endemic with S. haematobium, only A. lumbricoides infections were positively associated with S. haematobium (P = 0.0295, OR = 0.4585). Overall prevalence of S. haematobium monoinfection was 7.2% (95% CI = 6.4-8%), S. mansoni monoinfection was 12.3% (95% CI = 10.4-12.5%), and S. haematobium-S. mansoni coinfection was 1.2% (95% CI = 0.9-1.6%). There was no significant difference in infection intensity between mono and coinfections. Conclusion: Prevalence distribution maps obtained are important for planning and implementing disease control programs in these areas. [ABSTRACT FROM AUTHOR]

Background: High coverage of insecticide-treated bed nets in Asembo and low coverage in Seme, two adjacent communities in western Nyanza Province, Kenya; followed by expanded coverage of bed nets in Seme, as the Kenya national malaria programme rolled out; provided a natural experiment for quantification of changes in relative abundance of two primary malaria vectors in this holoendemic region. Both belong to the Anopheles gambiae sensu lato (s.l.) species complex, namely A. gambiae sensu stricto (s.s.) and Anopheles arabiensis. Historically, the former species was proportionately dominant in indoor resting collections of females. Methods: Data of the relative abundance of adult A. gambiae s.s. and A. arabiensis sampled from inside houses were obtained from the literature from 1970 to 2002 for sites west of Kisumu, Kenya, to the region of Asembo ca. 50 km from the city. A sampling transect was established from Asembo (where bed net use was high due to presence of a managed bed net distribution programme) eastward to Seme, where no bed net programme was in place. Adults of A. gambiae s.l. were sampled from inside houses along the transect from 2003 to 2009, as were larvae from nearby aquatic habitats, providing data over a nearly 40 year period of the relative abundance of the two species. Relative proportions of A. gambiae s.s. and A. arabiensis were determined for each stage by identifying species by the polymerase chain reaction method. Household bed net ownership was measured with surveys during mosquito collections. Data of blood host choice, parity rate, and infection rate for Plasmodium falciparum in A. gambiae s.s. and A. arabiensis were obtained for a sample from Asembo and Seme from 2005. Results: Anopheles gambiae s.s. adult females from indoor collections predominated from 1970 to 1998 (ca. 85%). Beginning in 1999, A. gambiae s.s decreased proportionately relative to A. arabiensis, then precipitously declined to rarity coincident with increased bed net ownership as national bed net distribution programmes commenced in 2004 and 2006. By 2009, A. gambiae s.s. comprised proportionately ca. 1% of indoor collections and A. arabiensis 99%. In Seme compared to Asembo in 2003, proportionately more larvae were A. gambiae s.s., larval density was higher, and more larval habitats were occupied. As bed net use rose in Seme, the proportion of A. gambiae larvae declined as well. These trends continued to 2009. Parity and malaria infection rates were lower in both species in Asembo (high bed net use) compared to Seme (low bed net use), but host choice did not vary within species in both communities (predominantly cattle for A. arabiensis, humans for A. gambiae s.s.). [ABSTRACT FROM AUTHOR]

The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated. Author summary: Today's diagnosis of infection with the filarial parasite Onchocerca volvulus mainly depends on the microscopic analysis of skin biopsies and serological testing. The work presented here describes the use of multiple mass spectrometry-based screening methods (metabolomics and lipidomics) to search for biomarkers indicative of infection with Onchocerca volvulus. This resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine as biomarker for O. volvulus. Further evaluation of these biomarkers in a geographically distinct non-endemic population however invalidated the use of urine cis-cinnamoylglycine. These findings are of utmost importance as it not only opens new avenues in the development of non-invasive diagnostic tools for filarial infections, but also emphasizes the need for evaluation and validation of newly discovered biomarkers in different populations from different geographies. [ABSTRACT FROM AUTHOR]

Background: Currently, serodiagnosis of infection with the helminth parasite Onchocerca volvulus is limited to the Ov-16 IgG4 test, a test that has limited sensitivity and suboptimal specificity. In previous studies, we identified several linear epitopes that have the potential to supplement the diagnostic toolbox for onchocerciasis. Methods: In this study three peptides, bearing in total six linear epitopes were transferred to a multiplex ELISA platform. This multiplex ELISA was used to assess the clinical utility of the peptide serology markers by analyzing sample sets from both O. volvulus endemic and non-endemic regions. Results: The multiplex platform was shown to be reproducible and data obtained on the multiplex platform were comparable to the singleplex ELISA data. The clinical utility assessment showed that in a population of school-aged children from western Kenya, a virtually O. volvulus-free area, significant cross-reactivity with an as-yet to be determined immunogen was detected. Conclusions: The observations made in this study invalidate the usefulness of the peptide serology markers for onchocerciasis detection. We discuss what could be the origin of this unexpected serological response, but also highlight the need for better characterized biobanks for biomarker discovery activities. [ABSTRACT FROM AUTHOR]

Intestinal worms, or soil-transmitted helminths (STHs), affect hundreds of millions of people in all tropical and subtropical regions of the world. The most prevalent STH is Ascaris lumbricoides. Through large-scale deworming programs, World Health Organization aims to reduce morbidity, caused by moderate-to-heavy intensity infections, below 2%. In order to monitor these control programs, stool samples are examined microscopically for the presence of worm eggs. This procedure requires well-trained personnel and is known to show variability between different operators interpreting the slides. We have investigated whether ABA-1, one of the excretory-secretory products of A. lumbricoides can be used as a coproantigen marker for infection with this parasite. Polyclonal antibodies were generated and a coproantigen ELISA was developed. Using this ELISA, it was found that ABA-1 in stool detected Ascaris infection with a sensitivity of 91.5% and a specificity of 95.3%. Our results also demonstrate that there is a correlation between ABA-1 levels in stool and A. lumbricoides DNA detected in stool. Using a threshold of 18.2 ng/g stool the ABA-1 ELISA correctly assigned 68.4% of infected individuals to the moderate-to-heavy intensity infection group, with a specificity of 97.1%. Furthermore, the levels of ABA-1 in stool were shown to rapidly and strongly decrease upon administration of a standard anthelminthic treatment (single oral dose of 400 mg albendazole). In an Ascaris suum infection model in pigs, it was found that ABA-1 remained undetectable until day 28 and was detected at day 42 or 56, concurrent with the appearance of worm eggs in the stool. This report demonstrates that ABA-1 can be considered an Ascaris -specific coproantigen marker that can be used to monitor infection intensity. It also opens the path for development of point-of-care immunoassay-based tests to determine A. lumbricoides infection in stool at the sample collection site. Author summary: Intestinal worms are one of the most common infections in tropical and subtropical parts of the world. The roundworm Ascaris lumbricoides is the most prevalent and efforts are ongoing to use preventive chemotherapy to reduce both prevalence and intensity of this infection. To monitor these programs, stool-based microscopy is currently used. We have investigated the possibility of using ABA-1, an abundantly secreted protein from the worm, as a biomarker in stool of infected individuals. We have developed an ELISA and using this assay determined that ABA-1 as stool biomarker had a sensitivity of 91.5% and a specificity of 95.3% to detect infection with A. lumbricoides. We also showed that ABA-1 in stool rapidly and strongly decreased upon administration of a standard anthelminthic treatment. The main asset of this novel stool biomarker is its potential to be used in of point-of-care immunoassay-based tests to determine A. lumbricoides infection in stool at the sample collection site. [ABSTRACT FROM AUTHOR]

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 serologicalmeasures 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 hightransmission 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 hightransmission settings preschool-age children represent a key population missed by school-based deworming programs. [ABSTRACT FROM AUTHOR]

Although preventive chemotherapy has been instrumental in reducing schistosomiasis incidence worldwide, serious challenges remain. These problems include the omission of certain groups from campaigns of mass drug administration, the existence of persistent disease hotspots, and the risk of recrudescent infections. Central to these challenges is the fact that the diagnostic tools currently used to establish the burden of infection are not sensitive enough, especially in low-endemic settings, which results in underestimation of the true prevalence of active Schistosoma spp infections. This central issue necessitates that the current schistosomiasis control strategies recommended by WHO are re-evaluated and, possibly, adapted. More targeted interventions and novel approaches have been used to estimate the prevalence of schistosomiasis, such as establishing infection burden by use of precision mapping, which provides high resolution spatial information that delineates variations in prevalence within a defined geographical area. Such information is instrumental in guiding targeted intervention campaigns. However, the need for highly accurate diagnostic tools in such strategies is a crucial factor that is often neglected. The availability of highly sensitive diagnostic tests also opens up the possibility of applying strategies of sample pooling to reduce the cost of control programmes. To interrupt the transmission of, and eventually eliminate, schistosomiasis, better local targeting of preventive chemotherapy, in combination with highly sensitive diagnostic tools, is crucial. [ABSTRACT FROM AUTHOR]

Background: Since 2011, cohorts of schoolchildren in regions bordering Lake Victoria in Kenya and Tanzania have been investigated for morbidity caused by Schistosoma mansoni infection. Despite being neighbouring countries with similar lifestyles and ecological environments, Tanzanian schoolchildren had lower S. mansoni prevalence and intensity and they were taller and heavier, fewer were wasted and anaemic, and more were physical fit compared to their Kenyan peers. The aim of the present study was to evaluate whether diet and school-related markers of socioeconomic status (SES) could explain differences in morbidity beyond the effect of infection levels. Methods and principal findings: Parasitological and morbidity data from surveys in 2013–2014 were compared with information on diet and school-related markers of SES collected in 2015 using questionnaires. A total of 490 schoolchildren (163 Kenyans and 327 Tanzanians) aged 9–11 years provided data. A higher proportion of Tanzanian pupils (69.4%, 95% CI: 64.3–74.5) knew where to wash hands after toilet visits compared to Kenyan pupils (48.5%, 95% CI: 40.9–56.1; P<0.0005). Similar proportions of children in the two countries ate breakfast, lunch and dinner, but the content of the meals differed. At all three meals, a higher proportion (95% CI) of Tanzanian pupils consumed animal proteins (mostly fish proteins) compared to their Kenyan peers (35.0% (28.3–41.7) vs. 0%; P<0.0005 at breakfast; 69.0% (63.9–74.1) vs. 43.6% (35.8–51.4); P<0.0005 at lunch; and 67.2% (62.1–72.3) vs. 53.4% (45.8–61.0); P = 0.003 at dinner). Multivariable analyses investigating risk factors for important morbidity markers among individuals revealed that after controlling for schistosome and malaria infections, eating animal proteins (fish) and knowing where to wash hands after toilet visits were significant predictors for both haemoglobin levels and physical fitness (measured as VO2 max). Conclusions: These results suggest that the differences in morbidity may be affected by factors other than S. mansoni infection alone. Diet and hygiene practice differences were associated with health status of schoolchildren along Lake Victoria in Kenya and Tanzania. Trial registration: Trials Registration numbers: (Kenya), (Tanzania). [ABSTRACT FROM AUTHOR]

The article discusses the user-centered framework in determining circumstances in which population-level diagnostic data can guide the decision of an soil-transmitted helminth (STH) program manager to transition a program to the next phase. Topics mentioned include the development of the framework by key opinion leaders to offer a research pathway or product development resources, the use-cases and companion target product profiles for the program, and the required diagnostics in the program.

Background. Persistent hotspots have been described after mass drug administration (MDA) for the control of schistosomiasis, but they have not been studied during the course of a multiyear MDA program. Methods. In data from a 5-year study of school-based and village-wide preventive chemotherapy strategies for Schistosoma mansoni, spatial scan statistics were used to find infection hotspots in 3 populations: 5- to 8-year-olds, 9- to 12-year-olds, and adults. Negative binomial regression was used to analyze changes from baseline, and receiver operating characteristic analyses were used to predict which villages would reach prevalence and intensity endpoints. Results. We identified a persistent hotspot, not associated with study arm, where S. mansoni infection prevalence and intensity did not decrease as much as in villages outside the hotspot. Significant differences from baseline were realized after 1 year of MDA: we did not identify factors that moderated this relationship. Villages meeting specified endpoints at year 5 were predicted from prior year data with moderately high sensitivity and specificity. Conclusions. The MDA strategies were less effective at reducing prevalence and intensity in the hotspot compared with other villages. Villages that reached year 5 endpoints could be detected earlier, which may provide the opportunity to amend intervention strategies. [ABSTRACT FROM AUTHOR]

Background: School-based deworming is widely implemented in various countries to reduce the burden of soil-transmitted helminths (STHs), however, the frequency of drug administration varies in different settings. In this study, we compared the impact of a single annual treatment and 4-monthly treatment over a follow-up among Kenyan school children, and investigated the factors associated with residual infection. Methods: We performed a secondary analysis of data from a randomized trial investigating whether deworming for STHs alters risk of acquiring malaria. Children received either a single treatment or 4-monthly albendazole treatments were followed longitudinally from February 2014 to October 2014. The relative impact of treatment and factors associated with residual infections were investigated using mixed-effects regression models. Predisposition to infection was assessed based on Spearman's rank and Kendall's Tau correlation coefficients. Results: In the 4-monthly treatment group, the proportion of children infected with hookworm decreased from 59.9 to 5.7%, while Ascaris lumbricoides infections dropped from 55.7 to 6.2%. In the single treatment group, hookworm infections decreased over the same time period from 58.7 to 18.3% (12.6% absolute difference in reduction, 95% CI: 8.9-16.3%), and A. lumbricoides from 56.7 to 23.3% (17.1% absolute difference in reduction, 95% CI: 13.1-21.1%). There was strong evidence for predisposition to both STH types. Residual hookworm infection among children on 4-monthly treatment were associated with male sex and baseline nutritional status, whereas A. lumbricoides infection was associated with individual and school-level infection at baseline, latrine cleanliness at schools. Conclusions: This study found that 4-monthly treatment w more effective than single annual treatment. Repeated treatments led to dramatic reductions in the intensities of STHs, but did not completely clear infections among school children in Kenya, a presumed reflection of reinfection in a setting where there is ongoing transmission. [ABSTRACT FROM AUTHOR]

Background: Private sector medicine outlets are an important provider of health services across the developing world, and are an untapped means of distributing and selling vaccines outside of childhood immunization programs. The present study assessed the viability of medicine outlets (chemists and pharmacies) as potential channels for sale of vaccines. Methods: To evaluate the viability of the medicine outlet model, we partnered with nine outlets across urban and rural communities in western Kenya to sell a nurse-administered typhoid vaccine. Purchasers were surveyed to reveal market demographic characteristics, reasons for vaccine purchase, and sources of information about the program. Key informant interviews and focus group discussions defined acceptability, demand, and additional suggestions for improving this mechanism of selling and distributing vaccines. Results: There was a higher than expected demand for the vaccine that resulted in stock-outs. Previous instance of typhoid, desire to prevent disease, affordable price and convenience were cited by most participants as main reasons for purchase of vaccine at the local outlet. The most common source of information on the vaccine sale was word-of-mouth and referral from friends. Longer vaccine sale duration, adequate stocking of vaccines and extended hours of administration in the evening to allow working individuals to buy vaccines were cited by participants as ways for improved participation in the future. Conclusions: This study demonstrated a high demand for vaccines at community medicine outlets. Important insights on how to improve and sustain such a program included extension of distribution time, education of outlet keepers, and minimizing vaccine stockouts. With improved social marketing, infrastructure mapping, education and pricing schemes, medicine outlets could become a sustainable avenue for selling adult vaccines in emerging markets for both routine and pandemic vaccines. [ABSTRACT FROM AUTHOR]

Background: Identification of populations to be targeted for individual treatment and broad-spectrum therapy in schistosomiasis-endemic areas, assessment of therapy efficacy, morbidity, and evaluation of control strategies need to be based on reliable diagnostic tools. Kato-Katz is routinely used and remains the standard diagnostic technique for schistosomiasis, despite its many challenges. This study was conducted in Nyamanga village, Mbita, western Kenya, and evaluated the diagnostic performance of Kato-Katz, Mini-Parasep and modified Mini-FLOTAC techniques in detection of Schistosoma mansoni and soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and hookworm) ova. Methods: Stool samples from 132 individuals were screened for eggs of S. mansoni by the 3 techniques. Mini-Parasep® faecal parasite concentrator (Apacor Ltd, England), a single-use diagnostic device with a built-in filter for faecal concentration of helminth eggs by sedimentation was employed on stool samples fixed in 10 % formalin. A modified Mini-FLOTAC (University of Naples, Italy) was based on floatation of helminths eggs with two different solutions (FS2 and FS7) using a closed system (Fill-FLOTAC) with 5 % formalin. Kato-Katz was performed following WHO recommendation. Prevalence of S. mansoni and STH, sensitivity and degree of agreement among the 3 techniques were determined. Results: Prevalence of S. mansoni was 47.0 %, 34.1 % and 20.5 % by Mini-Parasep, Kato-Katz and modified Mini-FLOTAC FS7 techniques, respectively. Prevalence of any STH infection was 6.1 %, 3.0 %, 6.1 % and 6.8 % by Mini-Parasep, Kato-Katz, modified Mini-FLOTAC FS2 and modified Mini-FLOTAC FS7 techniques, respectively. Considering the pooled results of the three methods (Mini-Parasep, Kato-Katz and modified Mini-FLOTAC FS7) as diagnostic 'gold' standard, the sensitivity of Mini-Parasep, Kato-Katz and modified Mini-FLOTAC FS7 for S. mansoni was 77.5 %, 56.1 %, and 33.8 %, respectively. Mini-Parasep and modified Mini-FLOTAC FS7 techniques had moderate (κ = 0.46) and fairly good (κ = 0.25) agreements with Kato-Katz for S. mansoni, respectively. Mini-Parasep detected a higher proportion of light intensity S. mansoni infections compared to Kato-Katz, which detected high proportions of heavy infections. Mini-Parasep detected a similar mean number of S. mansoni eggs per gram (EPG) of stool compared to the standard Kato-Katz (62.9 vs 97.3; t(131) = -0.49, P = 0.6265) and significantly higher EPG compared to the modified Mini-FLOTAC FS7 (62.9 vs 34.6; t(131) = 5.39, P < 0.0001). Conclusions: The high sensitivity of Mini-Parasep suggests its promising potential as an alternative tool in enhancing diagnosis and in monitoring schistosomiasis transmission and determining endpoint of intervention programs, especially in low endemicity areas. Mini-Parasep is also easy to operate, safe and also permits work with fresh stool. [ABSTRACT FROM AUTHOR]

Background: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. Methods: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. Results: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15 % for Entamoeba histolytica. The prevalence was <1 % for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98 % for A. lumbricoides and N. americanus, whereas KK sensitivity was 70 % and 32 %, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). Conclusions: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information. [ABSTRACT FROM AUTHOR]

Background: School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria.Methods: We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%.Results: During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys.Conclusions: Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria.Clinical Trials Registration: NCT01658774. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal schistosomiasis is widely distributed around Lake Victoria in Kenya where about 16 million people in 56 districts are at risk of the infection with over 9.1 million infected. Its existence in rural settings has been extensively studied compared to urban settings where there is limited information about the disease coupled with low level of awareness. This study therefore assessed community awareness on existence, signs and symptoms, causes, transmission, control and risk factors for contracting schistosomiasis as well as attitudes, health seeking behaviour and environmental antecedents that affect its control so as to identify knowledge gaps that need to be addressed in order to strengthen schistosomiasis control interventions in informal urban settings. Methods: The study was carried out in an informal urban settlement where the prevalence of intestinal schistosomiasis was previously reported to be the highest (36%) among the eight informal settlements of Kisumu city. The study adopted cross-sectional design and purposive sampling technique. Eight focus group discussions were conducted with adult community members and eight key informant interviews with opinion leaders. Data was audio recorded transcribed, coded and thematically analyzed using ATLAS.ti version 6 software. Results: Most respondents stated having heard about schistosomiasis but very few had the correct knowledge of signs and symptoms, causes, transmission and control of schistosomiasis. However, there was moderate knowledge of risk factors and at high risk groups. Their attitudes towards schistosomiasis and its control were generally indifferent with a general belief that they had no control over their environmental circumstances to reduce transmission. Discussion/Conclusion: Although schistosomiasis was prevalent in the study area, majority of the people in the community had low awareness. This study, therefore, stresses the need for health education to raise community's awareness on schistosomiasis in such settings in order to augment prevention, control and elimination efforts. Author Summary: Bilharzia also known as schistosomiasis is one of the neglected tropical diseases found in western part of Kenya. The major source of infection is Lake Victoria; however, there is evidence of inland transmission especially within the informal settlements of Kisumu city. Schistosomiasis can be controlled using three key approaches which include improved sanitation, health education and mass treatment with praziquantel. Additional interventions for infection prevention include: promotion of hygiene, access to safe water, and sanitation improvement and environmental management. However, the success of control initiatives involving the community depend on the level of the communities' uptake of the program, which is hinged upon understanding the community knowledge and practices towards the disease. This study therefore collected information from the community to assess level of awareness of schistosomiasis. The findings revealed a low level of awareness in spite of a high prevalence of schistosomiasis. These findings are invaluable in the designing of appropriate education messages targeted at raising community awareness on schistosomiasis and relevant behavioural change required for a successful control programme. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal schistosomiasis is widely distributed around Lake Victoria in Kenya where about 16 million people in 56 districts are at risk of the infection with over 9.1 million infected. Its existence in rural settings has been extensively studied compared to urban settings where there is limited information about the disease coupled with low level of awareness. This study therefore assessed community awareness on existence, signs and symptoms, causes, transmission, control and risk factors for contracting schistosomiasis as well as attitudes, health seeking behaviour and environmental antecedents that affect its control so as to identify knowledge gaps that need to be addressed in order to strengthen schistosomiasis control interventions in informal urban settings. Methods: The study was carried out in an informal urban settlement where the prevalence of intestinal schistosomiasis was previously reported to be the highest (36%) among the eight informal settlements of Kisumu city. The study adopted cross-sectional design and purposive sampling technique. Eight focus group discussions were conducted with adult community members and eight key informant interviews with opinion leaders. Data was audio recorded transcribed, coded and thematically analyzed using ATLAS.ti version 6 software. Results: Most respondents stated having heard about schistosomiasis but very few had the correct knowledge of signs and symptoms, causes, transmission and control of schistosomiasis. However, there was moderate knowledge of risk factors and at high risk groups. Their attitudes towards schistosomiasis and its control were generally indifferent with a general belief that they had no control over their environmental circumstances to reduce transmission. Discussion/Conclusion: Although schistosomiasis was prevalent in the study area, majority of the people in the community had low awareness. This study, therefore, stresses the need for health education to raise community's awareness on schistosomiasis in such settings in order to augment prevention, control and elimination efforts. [ABSTRACT FROM AUTHOR]

Infections with intestinal worms, such as Ascaris lumbricoides, affect hundreds of millions of people in all tropical and subtropical regions of the world. Through large-scale deworming programs, World Health Organization aims to reduce moderate-to-heavy intensity infections below 1%. Current diagnosis and monitoring of these control programs are solely based on the detection of worm eggs in stool. Here we describe how metabolome analysis was used to identify the A. lumbricoides-specific urine biomarker 2-methyl pentanoyl carnitine (2-MPC). This biomarker was found to be 85.7% accurate in determining infection and 90.5% accurate in determining a moderate-to-heavy infection. Our results also demonstrate that there is a correlation between 2-MPC levels in urine and A. lumbricoides DNA detected in stool. Furthermore, the levels of 2-MPC in urine were shown to rapidly and strongly decrease upon administration of a standard treatment (single oral dose of 400 mg albendazole). In an Ascaris suum infection model in pigs, it was found that, although 2-MPC levels were much lower compared to humans, there was a significant association between urinary 2-MPC levels and both worm counts (p = 0.023) and the number of eggs per gram (epg) counts (p < 0.001). This report demonstrates that urinary 2-MPC can be considered an A. lumbricoides-specific biomarker that can be used to monitor infection intensity. [ABSTRACT FROM AUTHOR]

Background: Persistent hotspots have been described after mass drug administration (MDA) for the control of schistosomiasis, but they have not been studied during the course of a multiyear MDA program.Methods: In data from a 5-year study of school-based and village-wide preventive chemotherapy strategies for Schistosoma mansoni, spatial scan statistics were used to find infection hotspots in 3 populations: 5- to 8-year-olds, 9- to 12-year-olds, and adults. Negative binomial regression was used to analyze changes from baseline, and receiver operating characteristic analyses were used to predict which villages would reach prevalence and intensity endpoints.Results: We identified a persistent hotspot, not associated with study arm, where S. mansoni infection prevalence and intensity did not decrease as much as in villages outside the hotspot. Significant differences from baseline were realized after 1 year of MDA: we did not identify factors that moderated this relationship. Villages meeting specified endpoints at year 5 were predicted from prior year data with moderately high sensitivity and specificity.Conclusions: The MDA strategies were less effective at reducing prevalence and intensity in the hotspot compared with other villages. Villages that reached year 5 endpoints could be detected earlier, which may provide the opportunity to amend intervention strategies. [ABSTRACT FROM AUTHOR]