Rapid appraisal of liver diseases using transient elastography, abdominal ultrasound, and microbiology in Côte d'Ivoire: A single-center study.

BACKGROUND: Liver diseases of infectious and non-infectious etiology cause considerable morbidity and mortality, particularly in low- and middle-income countries (LMICs). However, data on the prevalence of liver diseases and underlying risk factors in LMICs are scarce. The objective of this study was to elucidate the occurrence of infectious diseases among individuals with chronic liver damage in a rural setting of Côte d'Ivoire. METHODOLOGY: In 2021, we screened 696 individuals from four villages in the southern part of Côte d'Ivoire for hepatic fibrosis and steatosis, employing transient elastography (TE) and controlled attenuation parameter (CAP). We classified CAP ≥248 dB/m as steatosis, TE ≥7.2 kPa as fibrosis, and did subgroup analysis for participants with TE ranging from 7.2 kPa to 9.1 kPa. Clinical and microbiologic characteristics were compared to an age- and sex-matched control group (TE <6.0 kPa; n = 109). Stool samples were subjected to duplicate Kato-Katz thick smears for diagnosis of Schistosoma mansoni. Venous blood samples were examined for hepatitis B and hepatitis C virus. Additionally, an abdominal ultrasound examination was performed. PRINCIPAL FINDINGS: Among 684 individuals with valid TE measurements, TE screening identified hepatic pathologies in 149 participants (17% with fibrosis and 6% with steatosis). 419 participants were included for further analyses, of which 261 had complete microbiological analyses available. The prevalence of S. mansoni, hepatitis B, and hepatitis C were 30%, 14%, and 7%, respectively. Logistic regression analysis revealed higher odds for having TE results between 7.2 kPa and 9.1 kPa in individuals with S. mansoni infection (odds ratio [OR] = 3.02, 95% confidence interval [CI] = 1.58-5.76, P = 0.001), while HCV infection (OR = 5.02, 95% CI = 1.72-14.69, P = 0.003) and steatosis (OR = 4.62, 95% CI = 1.60-13.35, P = 0.005) were found to be risk factors for TE ≥9.2 kPa. CONCLUSIONS/SIGNIFICANCE: Besides viral hepatitis, S. mansoni also warrants consideration as a pathogen causing liver fibrosis in Côte d'Ivoire. In-depth diagnostic work-up among individuals with abnormal TE findings might be a cost-effective public health strategy.

Capacities and needs of health care facilities for schistosomiasis diagnosis and management in elimination settings.

BACKGROUND: Schistosomiasis is a debilitating neglected tropical disease endemic in sub-Saharan Africa. The role of health facilities in the prevention, diagnosis, control, and elimination of schistosomiasis is poorly documented. In a setting targeted for schistosomiasis elimination in Zanzibar, we assessed the prevalence of Schistosoma haematobium among patients seeking care in a health facility and investigated schistosomiasis-related knowledge of staff, and health facilities' capacities and needs for schistosomiasis diagnosis and management. METHODS: We conducted a health facility-based mixed-method study on Pemba Island from June to August 2023. Patients aged ≥ 4 years seeking care in four health facilities were screened for S. haematobium infection using urine filtration and reagent strips. Those patients aged ≥ 10 years were additionally interviewed about signs and symptoms. Staff from 23 health facilities responded to a questionnaire assessing knowledge and practices. Ten staff participated in a focus group discussion (FGD) about capacities and needs for schistosomiasis diagnosis and management. RESULTS: The prevalence of S. haematobium infection in patients attending the health facilities, as determined by the presence of eggs in urine, was 1.1% (8/712). Microhaematuria was detected in 13.3% (95/712) of the patients using reagent strips. Among patients responding to the questionnaire, pelvic pain, pain during sex, and painful urination were reported by 38.0% (237/623), 6.3% (39/623), and 3.2% (20/623), respectively. Among the health facility staff, 90.0% (44/49) and 87.8% (43/49) identified blood in urine and pelvic pain, respectively, as symptoms of urogenital schistosomiasis, 81.6% (40/49) and 93.9% (46/49) reported collecting a urine sample and pursuing a reagent strip test, respectively, for diagnosis, and 87.8% (43/49) administered praziquantel for treatment. The most reoccurring themes in the FGD were the need for more staff training about schistosomiasis, requests for diagnostic equipment, and the need to improve community response to schistosomiasis services in health facilities. CONCLUSIONS: The prevalence of S. haematobium infection in patients seeking care in health facilities in Pemba is very low and similar to what has been reported from recent community-based cross-sectional surveys. The health facility staff had good schistosomiasis-related knowledge and practices. However, to integrate schistosomiasis patient management more durably into routine health facility activities, scalable screening pathways need to be identified and capacities need to be improved by regular staff training, and an unbroken supply of accurate point-of-care diagnostics and praziquantel for the treatment of cases.

Prospects and Perspectives of Health Impact Assessment: A Systematic Review of the Peer-Reviewed Literature From June 2007 to January 2023.

Objectives: In 2008, an analysis investigating health impact assessment (HIA) practice found that only 6% of HIA-related peer-reviewed publications had a focus on low- and medium-developed countries, whereas 94% were conducted in countries with a high or very high development state. We aimed to update and deepen these observations. Methods: We conducted a systematic review, searching PubMed and Web of Science for HIA-related papers published in the scientific literature from June 2007 to January 2023. Only applied HIA and papers with HIA as a subject were included. Results: The search yielded 3,036 publications and the final selection consisted of 1,019 publications. The annual number of total publications increased considerably over the past 15 years. Whereas research-driven HIA (n = 460) showed a steep increase, step-by-step HIA (n = 71) did not show a clear trend. Conclusion: The gap between the number of HIA-related peer-reviewed publications focusing on low/medium and high/very high developed countries has diminished from 6/94 to 11/89. There is a growing tendency to apply the terminology HIA for health impact modelling studies and quantitative health risk assessments.

Prevalence and Determinants of Undernutrition in Schoolchildren in the Kilombero District, South-Eastern Tanzania.

Childhood undernutrition is a major issue in low- and middle-income countries, affecting the health, well-being, and educational outcomes of schoolchildren. This study aimed to assess the prevalence and associated factors of stunting, wasting, and underweight among schoolchildren in peri-urban areas in the south-eastern part of Tanzania. A cross-sectional study was conducted involving 930 children aged 6-12 years from four primary schools from July to August 2019. The WHO Anthro Survey Analyzer was employed to estimate the prevalence of stunting, wasting, and underweight, while logistic regression analyses examined sociodemographic background, malaria infection, anaemia, anthropometric measures, and dietary diversity score as potential factors. The prevalence of stunting, wasting, underweight, overweight, and obesity was 11.8%, 4.3%, 3.9%, 11.1%, and 2.0%, respectively. Overall, 1.5% of the children had malaria, as determined by rapid diagnostic tests, and 0.4% had severe anaemia. Univariate analysis indicated higher odds of undernutrition among children aged 9-12 compared to their younger peers. Stunting was more common among children with low and medium dietary diversity. Anaemia was found in 11.2% of schoolchildren, and severe anaemia was associated with wasting. Multivariate analysis revealed that age and low dietary diversity were significantly associated with undernutrition. These findings emphasise the need for school-based health and nutrition programmes targeting children beyond the age of 5 to improve their nutritional status and mitigate potential adverse effects on health, cognition, and academic achievement. Regular assessment of the nutritional status of schoolchildren is warranted.

Multiplex PCR for bacterial, viral and protozoal pathogens in persistent diarrhoea or persistent abdominal pain in Côte d'Ivoire, Mali and Nepal.

In contrast to acute diarrhoea, the aetiology of persistent digestive disorders (≥ 14 days) is poorly understood in low-resource settings and conventional diagnostic approaches lack accuracy. In this multi-country study, we compared multiplex real-time PCR for enteric bacterial, parasitic and viral pathogens in stool samples from symptomatic patients and matched asymptomatic controls in Côte d'Ivoire, Mali and Nepal. Among 1826 stool samples, the prevalence of most pathogens was highest in Mali, being up to threefold higher than in Côte d'Ivoire and up to tenfold higher than in Nepal. In all settings, the most prevalent bacteria were EAEC (13.0-39.9%) and Campylobacter spp. (3.9-35.3%). Giardia intestinalis was the predominant intestinal protozoon (2.9-20.5%), and adenovirus 40/41 was the most frequently observed viral pathogen (6.3-25.1%). Significantly different prevalences between symptomatic and asymptomatic individuals were observed for Campylobacter, EIEC and ETEC in the two African sites, and for norovirus in Nepal. Multiple species pathogen infection was common in Côte d'Ivoire and Mali, but rarely found in Nepal. We observed that molecular testing detected multiple enteric pathogens and showed low discriminatory accuracy to distinguish between symptomatic and asymptomatic individuals. Yet, multiplex PCR allowed for direct comparison between different countries and revealed considerable setting-specificity.

Acceptability and perceived feasibility of the KaziKidz health promotion intervention among educators and caregivers in schools from South Africa: a qualitative descriptive study.

BACKGROUND: Despite the uncontested benefits of physical activity, its promotion lags behind in the public health agenda of low- and middle-income countries (LMICs). School-based interventions are promising strategies to foster health during childhood, but evidence of their effectiveness is limited and inconclusive for LMICs. Thus, further investigation is needed on contextual factors associated with intervention implementation in low-resource settings. We studied the acceptability and feasibility of the KaziKidz health promotion intervention and its implementation and make recommendations to improve future adoption and sustainability. METHODS: KaziKidz was implemented in four primary schools from low-income communities in South Africa in 2019. Semi-structured interviews with four school principals, three focus group interviews with 16 educators, and another three with 16 caregivers were conducted between October and November 2021. Participants were purposively recruited. Interview transcripts were analyzed via thematic analysis using a deductive and reflexive approach. RESULTS: Three main themes influencing intervention implementation and adoption were identified: (1) prioritizing teachers' needs (2), integrating the program into the school structure, and (3) creating opportunities in the community. Supporting recommendations included: (theme 1) adopting intervention approaches that are inclusive of educators' health and providing them with capacity development and external support; (theme 2) fostering a feeling of ownership and belonging among school stakeholders to adapt interventions to specific resources and needs; and (theme 3) raising community awareness to encourage individuals to claim power over and actively engage with the program. CONCLUSIONS: Comprehensive interventions comprising health support, adequate training, and ongoing assistance for educators combined with school-wide and community outreach actions seeking to strengthen program ownership, accountability, and engagement can enhance uptake of school-based interventions and long-term maintenance. TRIAL REGISTRATION: ISRCTN15648510, registered on 17/04/2020.

Genetic characterization of schistosome species from cattle in Côte d'Ivoire.

BACKGROUND: Schistosomiasis is a water-based parasitic disease that affects humans, livestock and wild animals. While considerable resources are dedicated to the surveillance, disease mapping, control and elimination of human schistosomiasis, this is not the case for livestock schistosomiasis. Indeed, there are important data and knowledge gaps concerning the species present, population genetic diversity, infection prevalence, morbidity and economic impact. This study aimed to identify circulating schistosome species in cattle across Côte d'Ivoire and to investigate their population diversity and structuring. METHODS: Overall, 400 adult schistosomes were collected from slaughtered cattle at six sites across Côte d'Ivoire. Additionally, 114 miracidia were collected from live cattle at one site: Ferkessédougou, in the northern part of Côte d'Ivoire. DNA from all specimens was extracted and the cox1 and ITS1/2 regions amplified and analysed to confirm species. The genetic diversity and structuring of the schistosome populations were investigated using 12 microsatellite markers. RESULTS: All adult schistosomes and miracidia presented Schistosoma bovis mitochondrial cox1 profile. Nuclear ITS1/2 data were obtained from 101 adult schistosomes and four miracidia, all of which presented an S. bovis profile. Genetic diversity indices revealed a deficiency of heterozygotes and signals of inbreeding across all sites, while structure analyses displayed little geographic structuring and differentiation. Cattle in Côte d'Ivoire thus appear to be mono-species infected with S. bovis. Hybrids of Schistosoma haematobium × S. bovis have not been identified in this study. Cattle schistosomes appear to be panmictic across the country. CONCLUSIONS: Our results contribute to a deeper understanding of schistosome populations in Ivorian cattle and emphasize a One Health approach of joint human and animal surveillance and prevention and control programmes for schistosomiasis.

Diagnostic tests for human Schistosoma mansoni and Schistosoma haematobium infection: a systematic review and meta-analysis.

BACKGROUND: Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infections, respectively. We aimed to collate all available evidence on the accuracy of other proposed diagnostic techniques. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane Library, and LILACS for studies published from database inception to Dec 31, 2022, investigating the sensitivity and specificity of diagnostic tests for S haematobium and S mansoni infections against Kato-Katz thick smears or urine microscopy (reference tests) involving adults (aged ≥18 years), school-aged children (aged 7 to 18 years), or preschool-aged children (aged 1 month to 7 years). We extracted raw data on true positives, true negatives, false positives, and false negatives for the diagnostic tests and data on the number of participants, study authors, publication year, journal, study design, participants' age and sex, prevalence of Schistosoma infection, and treatment status. To account for imperfect reference tests, we used a hierarchical Bayesian latent class meta-analysis to model test accuracy. FINDINGS: Overall, we included 121 studies, assessing 28 different diagnostic techniques. Most studies (103 [85%] of 121) were done in Africa, 14 (12%) in South America, one (1%) in Asia, and one (1%) in an unknown country. Compared with the reference test, Kato-Katz thick smears, circulating cathodic antigen urine cassette assay version 1 (CCA1, 36 test comparisons) had excellent sensitivity (95% [95% credible interval 88-99]) and reasonable specificity (74% [63-83]) for S mansoni. ELISA-based tests had a performance comparable to circulating cathodic antigen, but there were few available test comparisons. For S haematobium, proteinuria (42 test comparisons, sensitivity 73% [62-82]; specificity 94% [89-98]) and haematuria (75 test comparisons, sensitivity 85% [80-90]; specificity 96% [92-99]) reagent strips showed high specificity, with haematuria reagent strips having better sensitivity. Despite limited data, nucleic acid amplification tests (NAATs; eg, PCR or loop-mediated isothermal amplification [LAMP]) showed promising results with sensitivity estimates above 90%. We found an unclear risk of bias of about 70% in the use of the reference or index tests and of 50% in patient selection. All analyses showed substantial heterogeneity (I2>80%). INTERPRETATION: Although NAATs and immunological diagnostics show promise, the limited information available precludes drawing definitive conclusions. Additional research on diagnostic accuracy and cost-effectiveness is needed before the replacement of conventional tests can be considered. FUNDING: WHO and Luxembourg Institute of Health.

Operational Differences between Product Development Partnership, Pharmaceutical Industry, and Investigator Initiated Clinical Trials.

Medicine development is a lengthy endeavour. Increasing regulatory stringency and trial complexity might lead to reduced efficiency, dwindled output, and elevated costs. However, alternative models are possible. We compared the operational differences between pharmaceutical industry sponsored trials, product development partnership trials, and investigator-initiated trials to identify key drivers of inefficiency in clinical research. We conducted an exploratory mixed-methods study with stakeholders, including clinical trial sponsors, contract research organisations, and investigators. The qualitative component included 40 semi-structured interviews, document reviews of 12 studies and observations through work shadowing in research institutions in Burkina Faso, Mali, and Switzerland. The findings were triangulated with an online survey polling clinical research professionals. The operational differences were grouped under five categories: (i) trial start-up differences including governance and management structure; (ii) study complexity; (iii) site structural and organisational differences; (iv) study conduct, quality approaches, and standard operating procedures; and (v) site capacity strengthening and collaboration. Early involvement of sites in the planning and tailored quality approaches were considered critical for clinical operations performance. Differences between the types of trials reviewed pertained to planning, operational complexities, quality approaches, and support to the sites. Integration of quality-by-design components has the potential to alleviate unnecessary process burden.

Design of a targeted blood transcriptional panel for monitoring immunological changes accompanying pregnancy.

Background: Immunomodulatory processes exert steering functions throughout pregnancy. Detecting diversions from this physiologic immune clock may help identify pregnant women at risk for pregnancy-associated complications. We present results from a data-driven selection process to develop a targeted panel of mRNAs that may prove effective in detecting pregnancies diverting from the norm. Methods: Based on a de novo dataset from a resource-constrained setting and a dataset from a resource-rich area readily available in the public domain, whole blood gene expression profiles of uneventful pregnancies were captured at multiple time points during pregnancy. BloodGen3, a fixed blood transcriptional module repertoire, was employed to analyze and visualize gene expression patterns in the two datasets. Differentially expressed genes were identified by comparing their abundance to non-pregnant postpartum controls. The selection process for a targeted gene panel considered (i) transcript abundance in whole blood; (ii) degree of correlation with the BloodGen3 module; and (iii) pregnancy biology. Results: We identified 176 transcripts that were complemented with eight housekeeping genes. Changes in transcript abundance were seen in the early stages of pregnancy and similar patterns were observed in both datasets. Functional gene annotation suggested significant changes in the lymphoid, prostaglandin and inflammation-associated compartments, when compared to the postpartum controls. Conclusion: The gene panel presented here holds promise for the development of predictive, targeted, transcriptional profiling assays. Such assays might become useful for monitoring of pregnant women, specifically to detect potential adverse events early. Prospective validation of this targeted assay, in-depth investigation of functional annotations of differentially expressed genes, and assessment of common pregnancy-associated complications with the aim to identify these early in pregnancy to improve pregnancy outcomes are the next steps.

Relative effects of climate factors and malaria control interventions on changes of parasitaemia risk in Burkina Faso from 2014 to 2017/2018.

BACKGROUND: In Burkina Faso, the prevalence of malaria has decreased over the past two decades, following the scale-up of control interventions. The successful development of malaria parasites depends on several climatic factors. Intervention gains may be reversed by changes in climatic factors. In this study, we investigated the role of malaria control interventions and climatic factors in influencing changes in the risk of malaria parasitaemia. METHODS: Bayesian logistic geostatistical models were fitted on Malaria Indicator Survey data from Burkina Faso obtained in 2014 and 2017/2018 to estimate the effects of malaria control interventions and climatic factors on the temporal changes of malaria parasite prevalence. Additionally, intervention effects were assessed at regional level, using a spatially varying coefficients model. RESULTS: Temperature showed a statistically important negative association with the geographic distribution of parasitaemia prevalence in both surveys; however, the effects of insecticide-treated nets (ITNs) use was negative and statistically important only in 2017/2018. Overall, the estimated number of infected children under the age of 5 years decreased from 704,202 in 2014 to 290,189 in 2017/2018. The use of ITNs was related to the decline at national and regional level, but coverage with artemisinin-based combination therapy only at regional level. CONCLUSION: Interventions contributed more than climatic factors to the observed change of parasitaemia risk in Burkina Faso during the period of 2014 to 2017/2018. Intervention effects varied in space. Longer time series analyses are warranted to determine the differential effect of a changing climate on malaria parasitaemia risk.

Randomized Trial to Improve Body Composition and Micronutrient Status Among South African Children.

INTRODUCTION: Physical activity (PA) promotion combined with multimicronutrient supplementation (MMNS) among school-age children may reduce fat mass accrual and increase muscle mass through different mechanisms and so benefit child health. This study determined the efficacy of combined interventions on body composition among South African schoolchildren and determined if micronutrients mediate these effects. STUDY DESIGN: Longitudinal cluster randomized controlled trial of children followed from 2019 to 2021. Statistical analyses carried from 2022 to 2023. SETTING/PARTICIPANTS: A total of 1,304 children 6-12 years of age recruited from public schools in Gqeberha, South Africa. INTERVENTION: Children were randomized by classes to either: (a) a physical activity group (PA); (b) a MMNS group; (c) a physical activity + multimicronutrient supplementation group (PA + MMNS); and (d) a placebo control group. MAIN OUTCOME MEASURES: Trajectories of overall and truncal fat free mass (FFM) and fat mass (FM) estimates in modeled at 9 and 21 months using latent growth curve models (LGCM). Changes in micronutrient concentrations at 9 months from baseline. RESULTS: An increased FFM trajectory was found among children in the MMNS arm at 9 months (Beta 0.16, 95% CI = 0.12, 0.31). The PA and MMNS arms both had positive indirect effects on this trajectory at 9 months (Beta 0.66, 95% CI = 0.44, 0.88 and Beta 0.32 95% CI = 0.1 0.5, respectively) and similarly at 21 months when mediated by zinc concentration changes. A reduced FM trajectory was found among children in the PA promotion arm at 9 months when using this collection point as the referent intercept. This arm was inversely associated with the FM trajectory at 9 months when mediated by zinc changes. CONCLUSIONS: PA and MMNS promotion in school-based interventions directly contributed to reductions in FM and increased FFM among South African children and indirectly through changes in micronutrient status. TRIAL REGISTRATION: ISRCTN, ISRCTN29534081. Registered on August 9, 2018 Institutional review board: Ethikkommission Nordwest- und Zentralschweiz" (EKNZ, project number: Req-2018-00608). Date of approval: 2018.

Randomised controlled trial on the effect of social support on disease control, mental health and health-related quality of life in people with diabetes from Côte d'Ivoire: the SoDDiCo study protocol.

INTRODUCTION: Diabetes mellitus (DM) and its severe complications contribute significantly to disability and, hence, burden of disease. Poor mental health, a frequent DM consequence, may hinder successful diabetes control in low-income and middle-income countries (LMICs). Evidence suggests social support as a cost-effective tool to improve diabetes self-management, behaviour and mental health. However, its real-world application in LMICs has rarely been tested. We aim to investigate the effect of a social support intervention on disease control, mental health and health-related quality of life in people with diabetes from Côte d'Ivoire (SoDDiCo) through a randomised controlled trial. METHODS AND ANALYSIS: The trial will take place in the Centre Antidiabétique d'Abidjan, Institut National de Santé Publique, Abidjan, Côte d'Ivoire. We will prospectively randomise up to 1500 people with newly diagnosed diabetes into two parallel arms: intervention (routine care+family supporter accompanying clinical management) and control (routine care), using gender-stratified blocked randomisation with random block sizes of 10, 16, 20 and 24. Participants will undergo baseline, 3-month and 12-month postrandomisation assessments. The primary study outcome will be glycated haemoglobin (HbA1c). Secondary outcomes will include glycaemic control (HbA1c<7.0%), presence at follow-up visits, mental health and quality of life scores. Using intention-to-treat framework, we will assess the impact of the family support intervention on these endpoints over the course of the 1-year follow-up. Effect modification by baseline social capital will be assessed. ETHICS AND DISSEMINATION: The SoDDiCo trial was approved by the Ethikkommission Nordwest- und Zentralschweiz (ref: AO_2021-00041; approved: 12 July 2021) and by Comité National d'Éthique des Sciences de la Vie et de la Santé (ref: 049-22/MSHPCMU/CNESVS-kp; approved: 20 April 2022). The randomised intervention trial will follow good clinical practice guidelines. All results will be made available to the public through abstracts at conferences as well as through peer-reviewed articles. International guidelines for authorship will be respected. TRIAL REGISTRATION NUMBER: ISRCTN10901121, ISRCTN registry.

Strongyloidiasis.

Strongyloidiasis is a neglected tropical disease caused primarily by the roundworm Strongyloides stercoralis. Strongyloidiasis is most prevalent in Southeast Asia and the Western Pacific. Although cases have been documented worldwide, global prevalence is largely unknown due to limited surveillance. Infection of the definitive human host occurs via direct skin penetration of the infective filariform larvae. Parasitic females reside in the small intestine and reproduce via parthenogenesis, where eggs hatch inside the host before rhabditiform larvae are excreted in faeces to begin the single generation free-living life cycle. Rhabditiform larvae can also develop directly into infectious filariform larvae in the gut and cause autoinfection. Although many are asymptomatic, infected individuals may report a range of non-specific gastrointestinal, respiratory or skin symptoms. Autoinfection may cause hyperinfection and disseminated strongyloidiasis in immunocompromised individuals, which is often fatal. Diagnosis requires direct examination of larvae in clinical specimens, positive serology or nucleic acid detection. However, there is a lack of standardization of techniques for all diagnostic types. Ivermectin is the treatment of choice. Control and elimination of strongyloidiasis will require a multifaceted, integrated approach, including highly sensitive and standardized diagnostics, active surveillance, health information, education and communication strategies, improved water, sanitation and hygiene, access to efficacious treatment, vaccine development and better integration and acknowledgement in current helminth control programmes.

Clonorchiasis and opisthorchiasis: epidemiology, transmission, clinical features, morbidity, diagnosis, treatment, and control.

Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both C. sinensis and O. viverrini and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures.

Editorial : Swiss TPH: 30 Years of R&D Towards New Drugs for Tropical Diseases.

The year 2023 marks the 80th anniversary of the Swiss Tropical and Public Health Institute (Swiss TPH). Associated with the University of Basel, Swiss TPH combines research, education and services, working across a value chain from innovation and validation to application to improve people's health and well-being. Around 700 staff and students work in Swiss TPH's new headquarters in an emerging life-science cluster in Allschwil, Switzerland, focusing on infectious and non-communicable diseases, environment, society and health as well as health systems and interventions. In this special issue of Chimia, we highlight 30 years of research and development (R&D) at Swiss TPH, deeply grounded in partnership, towards new drugs for tropical diseases.

Repurposing Know-how for Drug Development: Case Studies from the Swiss Tropical and Public Health Institute.

In pursuing novel therapeutic solutions, drug discovery and development rely on efficiently utilising existing knowledge and resources. Repurposing know-how, a strategy that capitalises on previously acquired information and expertise, has emerged as a powerful approach to accelerate drug discovery and development processes, often at a fraction of the costs of de novo developments. For 80 years, collaborating within a network of partnerships, the Swiss Tropical and Public Health Institute (Swiss TPH) has been working along a value chain from innovation to validation and application to combat poverty-related diseases. This article presents an overview of selected know-how repurposing initiatives conducted at Swiss TPH with a particular emphasis on the exploration of drug development pathways in the context of neglected tropical diseases and other infectious diseases of poverty, such as schistosomiasis, malaria and human African trypanosomiasis.

Key Contributions by the Swiss Tropical and Public Health Institute Towards New and Better Drugs for Tropical Diseases.

Thanks to its expertise in clinical research, epidemiology, infectious diseases, microbiology, parasitology, public health, translational research and tropical medicine, coupled with deeply rooted partnerships with institutions in low- and middle-income countries (LMICs), the Swiss Tropical and Public Health Institute (Swiss TPH) has been a key contributor in many drug research and development consortia involving academia, pharma and product development partnerships. Our know-how of the maintenance of parasites and their life-cycles in the laboratory, plus our strong ties to research centres and disease control programme managers in LMICs with access to field sites and laboratories, have enabled systems for drug efficacy testing in vitro and in vivo, clinical research, and modelling to support the experimental approaches. Thus, Swiss TPH has made fundamental contributions towards the development of new drugs - and the better use of old drugs - for neglected tropical diseases and infectious diseases of poverty, such as Buruli ulcer, Chagas disease, food-borne trematodiasis (e.g. clonorchiasis, fascioliasis and opisthorchiasis), human African trypanosomiasis, leishmaniasis, malaria, schistosomiasis, soil-transmitted helminthiasis and tuberculosis. In this article, we show case the success stories of molecules to which Swiss TPH has made a substantial contribution regarding their use as anti-infective compounds with the ultimate aim to improve people's health and well-being.

Maternal stimulation and early child development in sub-saharan Africa: evidence from Kenya and Zambia.

BACKGROUND: Despite major improvements in child survival over the past decade, many children in low and middle-income countries (LMICs) remain at risk of not reaching their developmental potential due to malnutrition, poor health, and a lack of stimulation. Maternal engagement and stimulation have been identified as some of the most critical inputs for healthy development of children. However, relatively little evidence exists on the links between maternal stimulation and child development exists in sub-Saharan Africa (SSA). This current paper aims to identify the associations between maternal stimulation and child development in Kenya and Zambia, as well as the activities that are most predictive of developmental outcomes in these settings. METHODS: We conducted a descriptive study using data from a prospective study in Kenya and Zambia. The study included three rounds of data collection. Children were on average 10 months old in round one, 25 months old in round two, and 36 months old in round three. The primary exposure variable of interest was maternal stimulation activities, which we grouped into cognitive, language, motor, and socio-emotional activities. The outcome of interest was child development measured through the Third Edition of the Ages and Stages Questionnaire (ASQ-3). Linear regression models were used to estimate the associations between overall maternal stimulation and domain-specific maternal stimulation and child development across the three rounds of the survey. RESULTS: Higher maternal stimulation scores were associated with higher ASQ scores (effect size = 0.25; 95% CI: 0.19, 0.31) after adjusting for other confounders. For domain specific and child development (ASQ scores), the largest effect size (ES) was found for language stimulation (ES = 0.15) while weakest associations were found for socio-emotional domain activities (ES= -0.05). Overall maternal stimulation was most strongly associated with gross motor development (ES = 0.21) and the least associated with problem-solving (ES = 0.16). CONCLUSION: Our study findings suggest a strong positive link between maternal stimulation activities and children's developmental outcomes among communities in poor rural settings. TRIAL REGISTRATION: NA (not a clinical trial).

Distribution and treatment needs of soil-transmitted helminthiasis in Bangladesh: A Bayesian geostatistical analysis of 2017-2020 national survey data.

BACKGROUND: In Bangladesh, preventive chemotherapy targeting soil-transmitted helminth (STH) infections in school-age children has been implemented since 2008. To evaluate the success of this strategy, surveys were conducted between 2017 and 2020 in 10 out of 64 districts. We estimate the geographic distribution of STH infections by species at high spatial resolution, identify risk factors, and estimate treatment needs at different population subgroups. METHODOLOGY: Bayesian geostatistical models were fitted to prevalence data of each STH species. Climatic, environmental, and socioeconomic predictors were extracted from satellite images, open-access, model-based databases, and demographic household surveys, and used to predict the prevalence of infection over a gridded surface at 1 x 1 km spatial resolution across the country, via Bayesian kriging. These estimates were combined with gridded population data to estimate the number of required treatments for different risk groups. PRINCIPAL FINDINGS: The population-adjusted prevalence of Ascaris lumbricoides, Trichuris trichiura, and hookworm across all ages is estimated at 9.9% (95% Bayesian credible interval: 8.0-13.0%), 4.3% (3.0-7.3%), and 0.6% (0.4-0.9%), respectively. There were 24 out of 64 districts with an estimated population-adjusted STH infection prevalence above 20%. The proportion of households with improved sanitation showed a statistically important, protective association for both, A. lumbricoides and T. trichiura prevalence. Precipitation in the driest month of the year was negatively associated with A. lumbricoides prevalence. High organic carbon concentration in the soil's fine earth fraction was related to a high hookworm prevalence. Furthermore, we estimated that 30.5 (27.2; 36.0) million dosages of anthelmintic treatments for school-age children were required per year in Bangladesh. CONCLUSIONS/SIGNIFICANCE: For each of the STH species, the prevalence was reduced by at least 80% since treatment was scaled up more than a decade ago. The current number of deworming dosages could be reduced by up to 61% if the treatment strategy was adapted to the local prevalence.