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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: 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: 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]

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: 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]

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]

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.

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]