Targeted Amplicon Deep Sequencing for Monitoring Antimalarial Resistance Markers in Western Kenya.

Molecular surveillance of Plasmodium falciparum parasites is important to track emerging and new mutations and trends in established mutations and should serve as an early warning system for antimalarial resistance. Dried blood spots were obtained from a Plasmodium falciparum malaria survey in school children conducted across eight counties in western Kenya in 2019. Real-time PCR identified 500 P. falciparum-positive samples that were amplified at five drug resistance loci for targeted amplicon deep sequencing (TADS). The absence of important kelch 13 mutations was similar to previous findings in Kenya pre-2019, and low-frequency mutations were observed in codons 569 and 578. The chloroquine resistance transporter gene codons 76 and 145 were wild type, indicating that the parasites were chloroquine and piperaquine sensitive, respectively. The multidrug resistance gene 1 haplotypes based on codons 86, 184, and 199 were predominantly present in mixed infections with haplotypes NYT and NFT, driven by the absence of chloroquine pressure and the use of lumefantrine, respectively. The sulfadoxine-pyrimethamine resistance profile was a "superresistant" combination of triple mutations in both Pfdhfr (51I 59R 108N) and Pfdhps (436H 437G 540E), rendering sulfadoxine-pyrimethamine ineffective. TADS highlighted the low-frequency variants, allowing the early identification of new mutations, Pfmdr1 codon 199S and Pfdhfr codon 85I and emerging 164L mutations. The added value of TADS is its accuracy in identifying mixed-genotype infections and for high-throughput monitoring of antimalarial resistance markers.

Patterns and Drivers of Household Sanitation Access and Sustainability in Kwale County, Kenya.

Many sanitation interventions suffer from poor sustainability. Failure to maintain or replace toilet facilities risks exposing communities to environmental pathogens, yet little is known about the factors that drive sustained access beyond project life spans. Using data from a cohort of 1666 households in Kwale County, Kenya, we investigated the factors associated with changes in sanitation access between 2015 and 2017. Sanitation access is defined as access to an improved or unimproved facility within the household compound that is functional and in use. A range of contextual, psychosocial, and technological covariates were included in logistic regression models to estimate their associations with (1) the odds of sustaining sanitation access and (2) the odds of gaining sanitation access. Over two years, 28.3% households sustained sanitation access, 4.7% lost access, 17.7% gained access, and 49.2% remained without access. Factors associated with increased odds of households sustaining sanitation access included not sharing the facility and presence of a solid washable slab. Factors associated with increased odds of households gaining sanitation access included a head with at least secondary school education, level of coarse soil fragments, and higher local sanitation coverage. Results from this study can be used by sanitation programs to improve the rates of initial and sustained adoption of sanitation.

Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial.

BACKGROUND: School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection. METHODS: In this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households in Kenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting 2-14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome was community hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondary outcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmitted helminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02397772. FINDINGS: After 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9-23·2) to 13·8% (10·5-17·0) in the annual school-based treatment group, 17·9% (13·7-22·1) to 8·0% (6·0-10·1) in the annual community-wide treatment group, and 20·6% (15·8-25·5) to 6·2% (4·9-7·5) in the biannual community-wide treatment group. Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI 0·42-0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33-0·63; p<0·001). More modest reductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomic subgroups after 24 months. No adverse events related to albendazole were reported. INTERPRETATION: Community-wide treatment was more effective in reducing hookworm prevalence and intensity than school-based treatment, with little additional benefit of treating every 6 months, and was shown to be remarkably equitable in coverage and effects. FUNDING: Bill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children's Investment Fund Foundation.

Association between Schistosoma mansoni infection and access to improved water and sanitation facilities in Mwea, Kirinyaga County, Kenya.

BACKGROUND: Schistosomiasis remains a public health problem in Central Kenya despite concerted control efforts. Access to improved water and sanitation has been emphasized as important control measures. Few studies have assessed the association between access to improved water sources and sanitation facilities with Schistosoma mansoni infection in different environmental settings. This study assessed the association between S. mansoni infection and household access to improved water sources and sanitation facilities in Mwea, Kirinyaga County, Kenya. METHODS: A cross sectional study was conducted between the months of August and October 2017. A total of 905 household heads from seven villages were interviewed and their stool samples screened for S. mansoni using the Kato Katz technique. Comparisons of demographic factors by S. mansoni infection were tested for significance using the chi-square test (χ2) or the Fisher exact test for categorical variables. Variables associated with S. mansoni infection were analyzed using univariable analysis and the strength of the association measured as odds ratio (OR) using mixed effects logistic regression at 95% CI, with values considered significant at p < 0.05. RESULTS: The overall prevalence of S. mansoni was, 23.1% (95% CI: 20.5-26.0%), with majority of the infections being of light intensity. Rurumi village had the highest prevalence at 33.3%, with Kirogo village having the least prevalence at 7.0%. Majority (84.1%) of the households lacked access to improved water sources but had access to improved sanitation facilities (75%). Households with access to piped water had the lowest S. mansoni infections. However, there was no significant association between S. mansoni infections with either the main source of water in the household (Odds Ratio (OR) =0.782 (95% CI: 0.497-1.229) p = 0.285 or sanitation facilities (OR = 1.018 (95% CI: 0.705-1.469) p = 0.926. CONCLUSION: Our study suggests that S. mansoni is still a public health problem among all age groups in Mwea irrigation scheme, Kirinyaga County, Central Kenya. Majority of the households lacks access to improved water sources but have access to improved sanitation facilities. This study recommends initiatives to ensure adequate provision of improved water sources, and the inclusion of the adult community in preventive chemotherapy programs.

Co-infection of Schistosoma mansoni/hepatitis C virus and their associated factors among adult individuals living in fishing villages, north-western Tanzania.

BACKGROUND: Schistosoma mansoni and Hepatitis C virus (HCV) are co-existence in sub-Saharan Africa and co-infection is common among humans population. The immunological responses characterized with Th2-immune responses for S. mansoni and Th1-immune responses for HCV are responsible for development hepatic morbidities in infected individuals. However, the co-occurrences of S. mansoni and HCV infection, their related ultrasound detectable morbidities and associated risk factors at community levels have not been examined in fishing communities, north-western Tanzania. In this context, the present study covers that gap. METHODS: A cross-sectional study was conducted among 1924 asymptomatic individuals aged 15-55 years in four fishing villages (Igombe, Igalagala, Sangabuye and Kayenze) of Northwestern Tanzania. A single stool sample was collected from each study participants and examined for S. mansoni eggs using Kato Katz technique. Hepatitis C surface antigen (HCVsAg) was determined from a finger prick blood sample using a rapid test. RESULTS: Overall, 51.8% (997/1924; 95%CI: 49.6-54.1) of the study participants were infected with S. mansoni and had a mean intensity of 223.7epg (95%; 202.4-247.1). Of the study participants, 90 (4.7%) were infected with hepatitis C virus (HCV). Overall, 2. 4% (47/1924) of the study participants were co-infected with S. mansoni and hepatitis C virus. Among the co-infected individuals, 42.6%, 70.2% and 19.1% had splenomegaly, hepatomegaly and periportal fibrosis (PPF). Factors associated with S. mansoni/HCV co-infection were being aged 26-35 years (aRR = 2.67, 95%CI: 1.03-6.93, P < 0.04), 46-55 years (aRR = 2.89, 95%CI: 1.10-7.57, P < 0.03) and having marked hepatomegaly (aRR = 2.32, 95%CI: 1.09-4.9, P < 0.03). CONCLUSION: In this setting, S. mansoni and Hepatitis C are co-endemic and a proportion of individuals were co-infected. Hepatosplenic morbidities characterized with hepatomegaly, splenomegaly, hepatosplenomegaly and PPF were observed in co-infected individuals. These results highlight the need for integrated interventions measures against parasitic and viral diseases.

Schistosoma mansoni Infection and Its Related Morbidity among Adults Living in Selected Villages of Mara Region, North-Western Tanzania: A Cross-Sectional Exploratory Study.

Schistosoma mansoni is highly endemic in Tanzania and affects all age groups at different degrees. However, its control approach does not include adult individuals who are equally at risk and infected. To justify the inclusion of adult individuals in MDA programs in Tanzania, the present study focused on determining the prevalence of S. mansoni infection and its related morbidities among adult individuals. This was a cross sectional study conducted among 412 adult individuals aged 18-89 years living in selected villages of Rorya and Butiama districts located along the shoreline of the Lake Victoria. A pretested questionnaire was used to collect socio-demographic and socio-economic information of participants. Ultrasonographic examinations were conducted for all study participants using the Niamey protocol. A single stool sample was obtained from all study participants and examined for S. mansoni using the Kato-Katz technique. The study revealed a high prevalence of S. mansoni (56.3%), and the majority of infected individuals had a light intensity of infection. Ultrasonographic findings revealed that 22.4% of adult individuals had periportal fibrosis (PPF) (grade C-F), with 18.4% having grade C and D and 4% having grade E and F. Males had the highest prevalence of PPF (31.7% vs 10.8%, P<0.001). Organomegaly was common with 28.5% and 29.6% having splenomegaly and hepatomegaly, respectively. S. mansoni infection and its related morbidities included PPF, hepatomegaly, and splenomegaly were common among adult individuals. To reduce the level of transmission of S. mansoni infection, planned mass drug administration campaigns should include adult individuals living in these villages.

Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial.

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.

Plasmodium falciparum parasitaemia and clinical malaria among school children living in a high transmission setting in western Kenya.

BACKGROUND: Malaria among school children is increasingly receiving attention, yet the burden of malaria in this age group is poorly defined. This study presents data on malaria morbidity among school children in Bungoma county, western Kenya. METHOD: This study investigated the burden and risk factors of Plasmodium falciparum infection, clinical malaria, and anaemia among 2346 school children aged 5-15 years, who were enrolled in an individually randomized trial evaluating the effect of anthelmintic treatment on the risks of malaria. At baseline, children were assessed for anaemia and nutritional status and information on household characteristics was collected. Children were followed-up for 13 months to assess the incidence of clinical malaria by active detection, and P. falciparum infection and density evaluated using repeated cross-sectional surveys over 15 months. RESULTS: On average prevalence of P. falciparum infection was 42% and ranged between 32 and 48% during the five cross-sectional surveys. Plasmodium falciparum prevalence was significantly higher among boys than girls. The overall incidence of clinical malaria was 0.26 episodes per person year (95% confidence interval, 0.24-0.29) and was significantly higher among girls (0.23 versus 0.31, episodes per person years). Both infection prevalence and clinical disease varied by season. In multivariable analysis, P. falciparum infection was associated with being male, lower socioeconomic status and stunting. The risk of clinical malaria was associated with being female. CONCLUSION: These findings show that the burden of P. falciparum parasitaemia, clinical malaria and anaemia among school children is not insignificant, and suggest that malaria control programmes should be expanded to include this age group.

Population Pharmacokinetics and Exposure-Response Analysis of a Fixed-Dose Combination of Ivermectin and Albendazole in Children, Adolescents, and Adults.

Trichuris trichiura is a soil-transmitted helminth causing intestinal disease. Albendazole is the standard treatment despite its moderate efficacy, which is improved when co-administered with ivermectin. A fixed-dose combination adds practical advantages mainly for mass drug administration. The aim of this article is to define the population pharmacokinetic models and exposure-response of an innovative albendazole/ivermectin combination. Data were obtained from a phase I clinical trial in healthy adults and from a phase II trial in children and adolescents infected with T. trichiura. Nonlinear mixed-effects models were built for albendazole and ivermectin using NONMEM®. Area under the curve was calculated using the empirical Bayes estimates of the pharmacokinetic parameters of each individual and used for evaluation of exposure-response between cure rate and pharmacokinetic exposure. The pharmacokinetics of albendazole was described using a two-compartmental model with first-order absorption and the pharmacokinetics of ivermectin was described using a two-compartmental model with zero-order followed by first-order absorption. Clearance and volume of distribution increased with body weight for both albendazole and ivermectin. Day 1 area under the curve of albendazole and ivermectin from the children and adolescents treated with the combination regimens were similar to the healthy adults treated with control drugs. A flat exposure-response relationship was observed between the cure rate and drug exposure. Population pharmacokinetic of a combination of albendazole and ivermectin in children, adolescents, and adults, either healthy or infected by T. trichiura was described. The dosage selected in the phase II trial was appropriate for the subsequent phase III.

Exploring factors associated with Trichuris trichiura infection in school children in a high-transmission setting in Kenya.

Objectives: Kenya has implemented a national school-based deworming program, which has led to substantial decline in the prevalence of soil-transmitted helminths (STHs), although some pockets of infections remain. To effectively design an STH control program that leads to significant reductions of Trichuris trichiura, there is a need to understand the drivers of persistent infection despite ongoing treatment programs. Methods: This study was conducted between July and September 2019 at the south coast of Kenya, using a two-stage sampling design. First, a school-based cross-sectional survey was conducted in 2265 randomly selected school children from selected schools in areas known to be endemic for T. trichiura. After this, we conducted a nested case-control study wherein all children positive for T. trichiura (142) were matched to 148 negative controls based on age and village. A household survey was then conducted with all household members of cases and controls. In addition, a subsample of 116 children found to be infected with T. trichiura were followed up to assess the efficacy of albendazole at day 21 post-treatment. The predictors of presence of T. trichiura were investigated through multilevel logistic regression, considering clustering of infection. Results: Overall, 34.4% of the children were infected with at least one STH species; T. trichiura was the most common (28.3%), 89.1% of those with T. trichiura had light-intensity infections. The prevalence of T. trichiura was significantly higher in male children and was positively associated with younger age and number of people infected with T. trichiura in a household. The parasitological cure rate and egg reduction rate of T. trichiura were 35% and 51%, respectively. Other STHs identified were hookworm (9.6%) and Ascaris lumbricoides (5.7%). Conclusions: T. trichiura remains a significant public health challenge in the study area with albendazole treatment efficacy against the parasite, remaining lower than the World Health Organization-recommended thresholds. Because of the observed focal transmission of T. trichiura in the current area, control efforts tailored to local conditions and targeting lower implementation units should be used to achieve optimal results on transmission.

Identifying Potential Determinants of Faecal Contamination on Domestic Floors in Three Settings in Rural Kenya: A Mixed Methods Analysis.

Observational evidence suggests that household floors may be an important domain for the transmission of enteric and parasitic infections. However, little work has been done to investigate how household floors can become contaminated with human and animal faeces. This study uses a mixed methods approach to postulate the proximal and distal determinants of household floor contamination with faeces in groups of rural villages in 3 counties in Kenya (Bungoma, Kwale and Narok). Quantitative data was collected through a household census and analysed descriptively and using mixed effects logistic regression models. Qualitative data was collected through unstructured observations of daily routines and in-depth interviews. These data were analysed thematically with case memos produced for routine activities that were hypothesised to be determinants of floor contamination. Possible proximal determinants of floor contamination included; (1) animal contact with floors; (2) child faeces disposal, and; (3) floor cleaning routines. Distal determinants are suggested to be rooted in the socioeconomic, environmental, and cultural context in which households were located and included; (1) the type and number of animals owned by households; (2) presence/absence of dedicated shelters for housing animals at night, which impacted whether sleeping or cooking areas were exposed to animals; (3) Accessibility of inside spaces to poultry and other roaming animals; (4) ownership of an improved floor; (5) ability of animals to access neighbours compounds; (6) seasonal changes in weather. These results will be of use in identifying the contexts in which faecal contamination of domestic floors may be contributing towards transmission of enteric and parasitic infections and in designing effective interventions to prevent this exposure.

Review of the WHO guideline on preventive chemotherapy for public health control of strongyloidiasis.

Strongyloidiasis is a soil-transmitted helminthiasis that is estimated to affect 300-600 million people across Asia, Africa, South and central America, and the Pacific. This neglected parasitic disease is most known for its ability to persist as a lifelong infection due to autoinfection and its risk of hyperinfection and disseminated disease during immunosuppression, which has a more than 60% case fatality. Despite the large global burden of strongyloidiasis, there have been no large-scale public health programmes or WHO guidelines directed towards its control and elimination. However, over the past decade, key scientific and policy changes along with requests from endemic countries have led to WHO incorporating strongyloidiasis into its 2021-30 roadmap and public health targets for control and elimination of neglected tropical diseases. In 2024, WHO published its first guideline on public health control of strongyloidiasis with a single recommendation: in endemic settings with a Strongyloides stercoralis infection prevalence of 5% or higher (measured either with Baermann or agar plate culture from stool specimens), WHO conditionally recommends mass drug administration with single-dose ivermectin (200 µg/kg; oral therapy) in all age groups from 5 years and older to reduce strongyloidiasis. This Review, written by the 2023-24 strongyloidiasis guidelines development group along with WHO colleagues and international experts, presents a summary of the recently published WHO guideline recommendation for strongyloidiasis, and the supporting evidence, considerations for public health implementation, and future research needs.

Impact of a disability-targeted microentrepreneurship programme in Kenya: study protocol for a randomised controlled trial of the InBusiness programme.

BACKGROUND: There is a lack of evidence on the effectiveness of livelihood interventions amongst people with disabilities. In many countries, self-employment or microentrepreneurship is a dominant source of livelihoods for people with disabilities and their caregivers. However, this group may face heightened barriers to successful microentrepreneurship, including discrimination, exclusion from training or inaccessible transport, infrastructure and communication systems. The InBusiness programme is a livelihoods programme targeted to microentrepeneurs with disabilities or their caregivers delivered by a consortium of non-governmental organisations. The programme focuses on improving the skills, practices and opportunities of microentrepreneurs while linking them with procurement opportunities with private and public institutions. This protocol describes a randomised controlled trial of the InBusiness programme in eight counties of Kenya. METHODS: The randomised controlled trial will involve 495 microentrepreneurs who have been verified as eligible for InBusiness by programme implementers. Individuals will be randomised within counties, either being invited to enrol in InBusiness in March 2023 or allocated to a control group. Participants in the control arm will receive information about compliance with business-related laws and available social protection programmes. The trial will assess the impact of InBusiness on household consumption and individual economic empowerment (primary outcomes) as well as food security, well-being, social attitudes, unmet need for disability-related services and microenterprise profits (secondary outcomes). Baseline was conducted in March 2023, and follow-up will be 24 months from baseline (12 months from completion of the programme). Analysis will be through intention to treat. A process evaluation will explore fidelity, mechanisms of impact and the role of context, and complementary qualitative research with participants will be used to triangulate findings across the trial. DISCUSSION: This study will provide evidence on the impact of a large-scale disability-targeted livelihood programme on household and individual financial security and well-being. Currently, there is a lack of evidence on the effectiveness of livelihood programmes amongst people with disabilities, and so this trial can help inform the design and delivery of InBusiness as well as other livelihood programmes targeted to people with disabilities. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN13693137. Registered on April 24, 2023.

Precision mapping of schistosomiasis and soil-transmitted helminthiasis among school age children at the coastal region, Kenya.

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.

Effects of the COVID-19 pandemic on antenatal care utilisation in Kenya: a cross-sectional study.

OBJECTIVE: The aim of this study was to assess the effects of COVID-19 on antenatal care (ANC) utilisation in Kenya, including women's reports of COVID-related barriers to ANC and correlates at the individual and household levels. DESIGN: Cross-sectional study. SETTING: Six public and private health facilities and associated catchment areas in Nairobi and Kiambu Counties in Kenya. PARTICIPANTS: Data were collected from 1729 women, including 1189 women who delivered in healthcare facilities before the COVID-19 pandemic (from September 2019-January 2020) and 540 women who delivered during the pandemic (from July through November 2020). Women who delivered during COVID-19 were sampled from the same catchment areas as the original sample of women who delivered before to compare ANC utilisation. PRIMARY AND SECONDARY OUTCOME MEASURES: Timing of ANC initiation, number of ANC visits and adequate ANC utilisation were primary outcome measures. Among only women who delivered during COVID-19 only, we explored women's reports of the pandemic having affected their ability to access or attend ANC as a secondary outcome of interest. RESULTS: Women who delivered during COVID-19 had significantly higher odds of delayed ANC initiation (ie, beginning ANC during the second vs first trimester) than women who delivered before (aOR 1.72, 95% CI 1.24 to 2.37), although no significant differences were detected in the odds of attending 4-7 or ≥8 ANC visits versus <4 ANC visits, respectively (aOR 1.12, 95% CI 0.86 to 1.44 and aOR 1.46, 95% CI 0.74 to 2.86). Nearly half (n=255/540; 47%) of women who delivered during COVID-19 reported that the pandemic affected their ability to access ANC. CONCLUSIONS: Strategies are needed to mitigate disruptions to ANC among pregnant women during pandemics and other public health, environmental, or political emergencies.

Precision and geographical prevalence mapping of schistosomiasis and soil-transmitted helminthiasis among school-aged children in selected districts of north-western Tanzania.

BACKGROUND: The identification and mapping of at-risk populations at a lower administrative level than the district are prerequisites for the planning, resource allocation and design of impactful control intervention measures. Thus, the objective of the current study was to conduct sub-district precision mapping of soil-transmitted helminthiasis (STH) and schistosomiasis in 29 districts of north-western Tanzania using the current recommended World Health Organization criteria. METHODS: A cross-sectional survey was conducted in 145 schools between March and May 2021. A urine filtration technique was used for the quantification of Schistosoma haematobium eggs, whereas quantification of Schistosoma mansoni and STH eggs was done using the Kato-Katz technique. Microhaematuria was examined using a urine dipstick. RESULTS: The overall prevalences of any STH and schistosome infections were 9.3% [95% confidence interval (95%CI) 8.6-9.9] and 14.6% (95%CI 13.9-15.4), respectively. The overall prevalence of S. mansoni was 8.7% (95%CI 8.1-9.3), and 36.4%, 41.6%, and 21.9% of the children had low, moderate, and heavy infections, respectively. The overall prevalence of S. haematobium was 6.1% (95%CI 5.5-6.5), and 71.7% and 28.3% of the infected children had light and heavy intensity infections, respectively. The prevalence of microhaematuria was 7.3% (95%CI 6.7-7.8), with males having the highest prevalence (8.4%, P < 0.001). The prevalences of Trichuris trichiura, Ascaris lumbricoides and hookworm were, respectively, 1.3% (95%CI 0.1-1.5), 2.9% (95%CI 2.5-3.3) and 6.2% (95%CI 5.7-6.7). Most of the children infected with STH had light to moderate intensities of infection. The overall prevalence of co-infection with STH and schistosomiasis was 19.1%. The prevalence of schistosomiasis (P < 00.1) and STH (P < 0.001) varied significantly between schools and sub-districts. Schistosoma mansoni and S. haematobium were observed in 60 and 71 schools, respectively, whereas any STH was observed in 49 schools. In schools where schistosomiasis was observed, prevalence was < 10% in 90.8% of them, and ranged from ≥ 10% to < 50% in the other 9.2%. In schools where any STH was observed, the prevalence was < 10% in 87.7% of them. CONCLUSIONS: The data reported here show that schistosomiasis and STH are widely distributed around Lake Victoria. In most of the schools where schistosomiasis and STH occurred the transmission thresholds were low. These data are important and need to be taken into consideration when decisions are made on the implementation of the next round of mass chemotherapies for schistosomiasis and STH in Tanzania.

Ivermectin and albendazole coadministration: opportunities for strongyloidiasis control.

In 2020, WHO recognised the importance of strongyloidiasis alongside soil-transmitted helminths (STH) in their 2021-30 roadmap, which aspires to target Strongyloides stercoralis with preventive chemotherapy by use of ivermectin. Combination treatment with both albendazole, the primary drug used to treat STH, and ivermectin, would improve the efficiency of mass drug administration targeting both STH and S stercoralis. In this Personal View, we discuss the challenges and opportunities towards the development of an efficient control programme for strongyloidiasis, particularly if it is to run concurrently with STH control. We argue the need to define the prevalence threshold to implement preventive chemotherapy for S stercoralis, the target populations and optimal dosing schedules, and discuss the added benefits of a fixed-dose coformulation of ivermectin and albendazole. Implementation of an efficient control programme will require improvements to current diagnostics, and validation of new diagnostics, to target and monitor S stercoralis infections, and consideration of the challenges of multispecies diagnostics for S stercoralis and STH control. Finally, the evolution of ivermectin resistance represents a credible risk to control S stercoralis; we argue that genome-wide approaches, together with improved genome resources, are needed to characterise and prevent the emergence of resistance. Overcoming these challenges will help to reduce strongyloidiasis burden and enhance the feasibility of controlling it worldwide.

An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol.

Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH . Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021).

Comparison of quantitative polymerase chain reaction, Kato-Katz and circulating cathodic antigen rapid test for the diagnosis of Schistosoma mansoni infection: A cross-sectional study in Kirinyaga County, Kenya.

The current standard diagnostic tests for Schistosoma mansoni are the Kato-Katz and circulating cathodic antigen (CCA) techniques. However, these techniques have been documented to have several limitations that have a direct impact on schistosomiasis control programmes. Therefore, there is a need for more sensitive and specific tests for diagnosing schistosomiasis. This study compared the performance of quantitative polymerase chain reaction (qPCR), Kato-Katz, and point-of-care circulating cathodic antigen (POC-CCA) techniques in the diagnosis of S. mansoni infection in the Mwea irrigation scheme, Kirinyaga County in Central Kenya. We carried out a cross-sectional study on 357 individuals residing in four villages in the Mwea irrigation scheme. The participants provided urine and stool samples which were screened for S. mansoni infections using the three techniques. The prevalence of S. mansoni by each technique was calculated and 95% confidence intervals estimated using binomial regression model. Sensitivity and specificity were determined using 2 × 2 contingency tables and compared using the McNemar's chi-square test. Positive and negative predictive values were also determined using the weighted generalized score chi-square test for paired data. The study showed that the prevalence of S. mansoni was 32.8%, 62.5% and 72.8% using Kato-Katz, POC-CCA and qPCR techniques, respectively. Further, when using Kato-Katz as a gold standard, POC-CCA sensitivity was 78.6% and specificity was 45.4%, while qPCR sensitivity was 97.4% and specificity was 39.2%. When using qPCR as the gold standard, Kato-Katz sensitivity was 43.8% and specificity was 96.9%, while POC-CCA sensitivity was 78.1% and specificity was 79.4%. Finally, when using the averaged results from the three techniques as the gold standard, the sensitivity was 41.6%, 79.4% and 92.5% for Kato-Katz, POC-CCA and qPCR, respectively, with a specificity of 100% for all techniques. Kato-Katz technique showed low sensitivity compared to the POC-CCA and qPCR despite it being the most commonly preferred method of choice to diagnose S. mansoni infections. qPCR showed superior sensitivity followed by POC-CCA, hence it can be used as an alternative or to confirm the results obtained by the Kato-Katz technique.

Performance evaluation of Baermann techniques: The quest for developing a microscopy reference standard for the diagnosis of Strongyloides stercoralis.

BACKGROUND: Soil-transmitted helminths (STH) are common in low and middle income countries where there is lack of access to clean water and sanitation. Effective diagnosis and treatment are essential for the control of STH infections. However, among STH parasites, Strongyloides stercoralis is the most neglected species, both in diagnostics and control strategies. Diagnostic methods cover different approaches, each with different sensitivities and specificities, such as serology, molecular techniques and microscopy based techniques. Of the later, the Baermann technique is the most commonly used procedure. In the literature, several ways have been described to perform the Baermann method, which illustrates the overall lack of a '(gold) reference standard' method for the diagnosis of S. stercoralis infection. In this study we have evaluated the performance of three Baermann techniques in order to improve the reference standard for the microscopic diagnosis of S. stercoralis infection thereby facilitating individual case detection, mapping of the disease and proper evaluation of treatment responses. METHODS/PRINCIPAL FINDINGS: A community based cross sectional study was conducted at Zenzelima, Bahir Dar Zuria Ethiopia. A total of 437 stool samples were collected and analyzed by the following procedures: conventional Baermann (CB), modified Baermann (MB), and modified Baermann with charcoal pre-incubation (MBCI). The diagnostic sensitivity and Negative Predictive Value (NPV) of each technique was calculated using the combination of all the three techniques as a composite reference standard. Our result indicated that larvae of S. stercoralis were detected in 151 (34.6%) stool samples. The prevalence of S. stercoralis infection based on the three diagnostic methods was 9.6%, 8.0%, and 31.3% by CB, MB, and MBCI respectively. The sensitivity and NPV for CB, MB, and MBCI were 26.7% and 70.8%, 22.1% and 69.6%, and 87.0% and 93.2%, respectively. The MBCI showed significant difference (P- value = <0.001) in the sensitivity and NPV values when compared with CB and MB values. The agreement between CB, MB, and MBCI with the composite reference standard was 31.8%, 26.7%, 89.6%, respectively. CONCLUSION/SIGNIFICANCE: Our results suggest the superior performance of MBCI. It is relatively easy to implement, simple to perform and comparatively cheaper. The CB is by far the commonly used method in routine diagnostic although this technique significantly underestimates the true burden of the disease and thereby contributing to the exclusion of S. stercoralis from the control strategies. Therefore, MBCI is recommended as a routine microscopy-based diagnostic test for S. stercoralis infection, particularly in settings where molecular procedures are not available.