Systems epidemiology of snail-borne diseases : from methodological to social-ecological considerations in the fight towards elimination

Background: Snail-borne trematode infections, including schistosomiasis and fascioliasis, affect an estimated 250 million and 2.4 million people worldwide, respectively. Health implications range from asymptomatic infections to severe morbidity, developmental and cognitive impairment, thus affecting the current and later life of infected individuals. Nonetheless, snail-borne trematodiasis in general, and fascioliasis in particular, remain among the most neglected of the neglected tropical diseases. The occurrence of these parasitic liver- and blood-fluke infections depend on a myriad of interrelating factors comprising a complex system of disease and health. A key feature pertains to the availability of suitable aquatic snail intermediate hosts from the family of the Lymnaeidae (for schistosomiasis) and Planorbidae (for fascioliasis). The distribution of these intermediate host snails, in turn, depends on ecological and environmental factors of their habitats, whereas these habitats are shaped by humans. The construction of dams, for example, extends the suitable habitats for intermediate host snail species and has been implicated with the spread and intensification of schistosomiasis. Furthermore, socio-economic and cultural factors as well as behaviour largely determine the extent of risky water contact including direct and indirect consumption and thus govern the risk of becoming infected with Schistosoma and Fasciola. Prevailing habits and social believes as well as knowledge and education likewise influence water contact patterns and health seeking behaviour. Individual immunology plays a role in acquiring infections and subsequent development of the disease for individuals exposed to these fluke infections. The nature of the interrelations in snail-borne trematode infections are complex and widespread. In order to eliminate snail-borne trematodiasis, especially schistosomiasis, efforts in the domains from innovation to application need to be increased covering all aspects of the whole system. Goal and specific objectives: The overarching goal of this PhD thesis was to obtain a systems overview of schistosomiasis and – to some extend – fascioliasis in the northern area of Côte d’Ivoire, placing particular emphasis of disease prevalence, social-ecological systems and methodological considerations. Specific objectives include: (i) to evaluate and improve currently existing tools for the assessment of infection within the communities ranging from household sampling to the validation of two rapid-diagnostic test within the setting; (ii) to elucidate prevailing water contact pattern and underlying reasons thereof alongside other factors leading to an increased risk of acquiring snail-borne trematodiasis for the local communities in northern Côte d’Ivoire; and (iii) to assess the distribution and ecological determinants of aquatic snail species serving as intermediate hosts for schistosomiasis and fascioliasis and relating it to the prevalence of infections within the human communities using these water sources. Methods: A literature review was performed to identify suitable household sampling methods for situations where sampling frames are not available. Identified and newly proposed sampling methods were simulated over 250 iterations to identify features or the resulting samplings and assessing the amount of oversampling, systematic household exclusion as well as clustering. For the studies involving fieldwork, a total of forty villages were randomly selected for participation. The study protocols received clearance from the ethics committees of Basel (EKBB, reference no. 64/13) and the national ethics committee in Côte d’Ivoire (reference no. 32-MSLS/CNERdkn). In Chad, research authorization including ethical approval was granted by the District, regional and local authorities, village chiefs, study participants and parents/guardians of individuals aged below 18 years were informed about the purpose, procedures and potential risks and benefits of the study. Written informed consent was obtained from all participants and the parents/guardians of minors. Parasitological examinations as well as questionnaire surveys, focus group discussions and direct observations were performed within the villages, nearby Peulh settlements and surrounding water bodies. Parasitological examinations included reagent strip testing with Hemastix®, (Bayer Diagnostics; Basingstoke, United Kingdom), urine filtration of 10 ml of urine, double Kato-Katz of a single stool sample, Baerman filtration and the point-of-care circulating cathodic antigen test. Snails and water parameters were collected from water sites indicated by the communities as the ones most frequently accessed by the population. Results: Our literature review revealed 21 methods for household sampling and/or the creation or update of sampling frames. Some methods describe variations of cluster sampling, some aiming at the creation/obtaining or improving of existing sampling frames and some pertaining to achieve sampling in the absence of a sampling frame. Three methods pertained to sampling with rather strict requirements in surveys. A preliminary computer simulation of several existing and newly proposed spatial methods for household sampling revealed that all sampling methods based on a spatial approach oversampled houses around the starting point. Additionally many also systematically excluded certain households. One newly proposed method which employs the simple to implement use of a pouch of numbered paper lots is an adaption of the method from the extended programme of immunization (EPI). Equally sized and shaped paper lots containing numbers ranging from 1 to 20 are put into the pouch. An additional 21st lot is included, indicating that a new walking direction will have to be chosen randomly by spinning a bottle. This method delivered the best sample in the simulations, whereas several methods developed to improve the original EPI methods actually had worse outcomes compared to the original EPI method. A decision frame for choosing an adequate household sampling method for researchers and other individuals conducting surveys is proposed in the respective chapter. The prevalence of schistosomiasis in the Tchologo region of northern Côte d’Ivoire was very low; Infections with S. haematobium and S. mansoni infections were found in 2.2% and 1.0%, respectively. No human Fasciola infection was found. With a prevalence of 13%, microhaematuria, as assessed with reagent strips, far surpassed the prevalence of S. haematobium determined with urine filtration in the study region. Our literature review revealed that in many published surveys, microhaematuria-positive test results that were not linked to positive urine filtration results occurred irrespective of the underlying S. haematobium prevalence assessed by urine filtration. These findings indicate either the occurrence of alternative causes for blood in urine in endemic settings or the gross underestimation of the true prevalence of S. haematobium in various settings. All individuals in our study villages had access to, and were using, safe water sources. Nevertheless, accessing and consuming unsafe water was very common and occurred in most instances during work on the fields or at the side of the road where it was unfeasible to transport needed quantities of drinking water and/or where water from the dams, rivers and small water collections was needed for the work. Additionally we could show that 38% of direct physical contact with unsafe water resulted from the fact that people who otherwise reported to only use safe water sources had to cross open water and thus increase the risk of acquiring schistosomiasis, albeit adequate water supply and sanitation facilities. Intermediate host snail species were present in the study area, with fascioliasis intermediate host snails from the family of the Lymnaeidae occurring mostly in the northern part of the region, whereas Schistosoma mansoni transmitting Biomphalaria snails occurred mostly in the southern region, while Bulinus (intermediate host of S. haematobium) were ubiquitous. Human and animal presence at the water sites strongly correlated with snail occurrence. Conclusions: The adoption of a systemic approach for the control and elimination of snail-borne trematodiases can be very helpful, as it allows inclusion and consideration of a myriad of factors, ranging from methodological to social-ecological issues. Furthermore, researchers and intervention programmes could benefit from an even greater collaboration between different scientific fields, including but not limited to epidemiology, parasitology, sociology, anthropology and social psychology. Indeed, understanding the factors which make humans act in a certain desired or undesired way can play a major role in the success of control or elimination efforts. Most notably, the largest potential benefit could arise from working together with social marketers and drawing upon their years of experience in adequately identifying and analysing target populations and designing ways to tailor implement and communicate public health programmes/messages in a way that maximises community interest and incentives to adopt and sustain the programmes

Knowledge and Practices on the Prevention and management of diarrhea in children under-2 years among women dwelling in urban slums of Karachi, Pakistan

Background: Diarrhea is the second leading cause of death especially among children. The age-proportionate mortality of diarrheal disease in infants under 2 years is 72%, among children under 5 years of age. Children living in urban slums are more prone to develop diarrhea. Although the disease can be prevented by many simple cost-effective interventions, i.e. proper sanitation and hygiene, appropriate feeding, and timely vaccination, poverty and lack of basic life amenities often potentiate diarrhea mortality. Gadap town is the largest town of Karachi with a deprived health system. This study aims to assess pediatric diarrhea prevalence and related knowledge-practice gaps in the slums of Gadap Town, Karachi, Pakistan. Method: A community-based cross-sectional study was conducted from November 2016 to May 2017 among mothers of children under 2 years, who were residents of Gadap Town, Karachi, Pakistan. The participants were approached by a multistage sampling method. A validated dichotomous questionnaire, piloted on 40 participants, translated into local language Urdu was used for data collection and the data was analyzed by SPSS® version 20.0. Results: 51.8% (n = 199) of participants were aged between 25 and 34 years. Among all participants, 68% (n = 261) had primary level education or less, compared to 4.7% (n = 18) of women who had graduate-level education. The mean number of children per woman was 2.52 ± 1.62. Self-reported pediatric diarrhea incidence was 72.1% (n = 277). More than half (55.2% n = 149) of participants reported frequent diarrhea episodes during the 2nd year of their child\u27s life. In this survey, we found the knowledge of women regarding diarrhea management and how to reduce diarrhea morbidity to be inadequate (p \u3e 0.05). However, many women reported appropriate practices which can significantly reduce diarrhea morbidity (p \u3c 0.05). Conclusion: While the knowledge among women on preventive measures for pediatric diarrhea was insufficient, the translation of the right knowledge into appropriate practices showed promising outcomes for reducing diarrhea morbidity. An integrated approach for improving feeding, sanitation, and hygiene practices along with continuous health education could curtail the burden of diarrhea among infants living in urban slum

A call for systems epidemiology to tackle the complexity of schistosomiasis, its control, and elimination

Ever since the first known written report of schistosomiasis in the mid-19th century, researchers have aimed to increase knowledge of the parasites, their hosts, and the mechanisms contributing to infection and disease. This knowledge generation has been paramount for the development of improved intervention strategies. Yet, despite a broad knowledge base of direct risk factors for schistosomiasis, there remains a paucity of information related to more complex, interconnected, and often hidden drivers of transmission that hamper intervention successes and sustainability. Such complex, multidirectional, non-linear, and synergistic interdependencies are best understood by looking at the integrated system as a whole. A research approach able to address this complexity and find previously neglected causal mechanisms for transmission, which include a wide variety of influencing factors, is needed. Systems epidemiology, as a holistic research approach, can integrate knowledge from classical epidemiology, with that of biology, ecology, social sciences, and other disciplines, and link this with informal, tacit knowledge from experts and affected populations. It can help to uncover wider-reaching but difficult-to-identify processes that directly or indirectly influence exposure, infection, transmission, and disease development, as well as how these interrelate and impact one another. Drawing on systems epidemiology to address persisting disease hotspots, failed intervention programmes, and systematically neglected population groups in mass drug administration programmes and research studies, can help overcome barriers in the progress towards schistosomiasis elimination. Generating a comprehensive view of the schistosomiasis system as a whole should thus be a priority research agenda towards the strategic goal of morbidity control and transmission elimination

Estimating the prevalence, quality of life, economic and societal impact of arthritis in Tanzania: protocol for a mixed methods study [Protocol]

Introduction: Musculoskeletal (MSK) disorders are one of the major causes of disability globally. A 2010 Global Burden of Disease study reported that MSK diseases account for 20% of all Years Lived with Disability (YLDs) in Low- and Middle-Income countries. This study will use mixed methods to generate new findings on the prevalence, quality of life, economic and societal impact of musculoskeletal disorders (including arthritis) in the Hai district in Tanzania. Methods and analysis: In this mixed-methods study funded by the UK’s National Institute for Health Research (NIHR) Global Health Research Units and Groups (Award no: 17/63/35) we will conduct quantitative, community-based (urban, peri - urban and rural) and hospital based prospective surveys, supported by rapid ethnographic assessments (REAs), in-depth interviews, focus group discussions (FGDs) and clinical diagnostic screening to estimate the prevalence, economic and societal impact of arthritis. A retrospective medical records baseline review at the Kilimanjaro Christian Medical Centre (KCMC) will also be conducted to assess prevailing documentation and management of arthritis. Ethics and dissemination: Ethical approval has been obtained through Kilimanjaro Christian Medical University College (KCMUCo) Research Ethics and Review committee (CRERC) in Moshi, National Health Research Ethics Committee (NatHREC) of the National Institute for Medical research (NIMR) in Tanzania and the Medical Veterinary and Life Sciences (MVLS) Ethics committee at the University of Glasgow, UK (MVLS ethics project number:20018010). We will disseminate the findings in clinical, epidemiological, and economic peer reviewed journals. Other dissemination modalities include professional conferences, short reports, community leaflets, policy briefs and dissemination events to communities and various stakeholders including the Ministry of health in Tanzania

Effect of Schistosomiasis and Soil-Transmitted Helminth Infections on Physical Fitness of School Children in Côte d'Ivoire

The burden of parasitic worm infections is considerable, particularly in developing countries. It is acknowledged that parasitic worm infections negatively impact on children's school performance and physical development. A deeper understanding of these linkages is important for updating burden of disease measures. We investigated the relationship between worm infection status and physical fitness of 156 school children from Côte d'Ivoire and controlled for potential confounding of Plasmodium infection (the causative agent of malaria) and environmental parameters (temperature and humidity). Children were diagnosed for parasitic worm and Plasmodium infections, examined by a physician, and participated in a 20 m shuttle run test to assess their maximal oxygen uptake (VO2 max) as a proxy for physical fitness. Most of the children had parasitic worms and a Plasmodium infection. Nevertheless, their physical fitness was excellent (average VO2 max: 52.7 ml kg−1 min−1). The level of VO2 max was only influenced by sex and age, but not by parasitic worms and Plasmodium infections. In future studies, the dynamics of children's physical performance should be assessed before and after control interventions, including the assessment of blood hemoglobin, hematocrit, and nutritional indicators to determine whether physical fitness in worm- and Plasmodium-infected individuals can be further improved

Evidence for exercise-based interventions across 45 different long-term conditions: an overview of systematic reviews

Background: Almost half of the global population face significant challenges from long-term conditions (LTCs) resulting in substantive health and socioeconomic burden. Exercise is a potentially key intervention in effective LTC management. Methods: In this overview of systematic reviews (SRs), we searched six electronic databases from January 2000 to October 2023 for SRs assessing health outcomes (mortality, hospitalisation, exercise capacity, disability, frailty, health-related quality of life (HRQoL), and physical activity) related to exercise-based interventions in adults (aged >18 years) diagnosed with one of 45 LTCs. Methodological quality was assessed using AMSTAR-2. International Prospective Resister of Systematic Reviews (PROSPERO) ID: CRD42022319214. Findings: Forty-two SRs plus three supplementary RCTs were included, providing 990 RCTs in 936,825 people across 39 LTCs. No evidence was identified for six LTCs. Predominant outcome domains were HRQoL (82% of SRs/RCTs) and exercise capacity (66%); whereas disability, mortality, physical activity, and hospitalisation were less frequently reported (≤25%). Evidence supporting exercise-based interventions was identified in 25 LTCs, was unclear for 13 LTCs, and for one LTC suggested no effect. No SRs considered multimorbidity in the delivery of exercise. Methodological quality varied: critically-low (33%), low (26%), moderate (26%), and high (12%). Interpretation: Exercise-based interventions improve HRQoL and exercise capacity across numerous LTCs. Key evidence gaps included limited mortality and hospitalisation data and consideration of multimorbidity impact on exercise-based interventions

Dynamics of Schistosoma haematobium egg output and associated infection parameters following treatment with praziquantel in school-aged children

BACKGROUND: Praziquantel is the drug of choice in preventive chemotherapy targeting schistosomiasis. Increasing large-scale administration of praziquantel requires monitoring of drug efficacy to detect early signs of development of resistance. Standard protocols for drug efficacy monitoring are necessary. Here, we determined the optimal time point for praziquantel efficacy assessment against Schistosoma haematobium and studied the dynamics of infection parameters following treatment. METHODS: Ninety school-aged children from south Cote d'Ivoire with a parasitologically confirmed S. haematobium infection were treated with a single oral dose of praziquantel (40 mg/kg) and followed up for 62 days post-treatment. Urine samples were collected on 23 schooldays during this period and were subjected to visual examination (macrohaematuria), urine filtration and microscopy (S. haematobium eggs) and reagent strip testing (microhaematuria, proteinuria and leukocyturia). RESULTS: Observed cure and egg reduction rates were highly dependent on the time point post-treatment. Egg reduction rates were high (<97%) in weeks 3--9 post-treatment. Cure rates were highest in weeks 6 (92.9%) and 9 (95.0%) post-treatment. The prevalence of infection-associated parameters decreased after treatment, reaching a minimum of 2.4% in weeks 5 (proteinuria) and 7 (leukocyturia) post-treatment, and 16.3% at the end of week 8 (microhaematuria). Macrohaematuria disappeared between weeks 3 and 6 post-treatment. CONCLUSIONS: For monitoring praziquantel efficacy against S. haematobium, we recommend that the cure rate is assessed at week 6 post-treatment. The egg reduction rate can be evaluated earlier, from day 14 post-treatment onwards. Reagent strips are a useful additional tool for evaluating treatment outcomes in areas with high endemicity, preferably at weeks 5 and 6 post-treatment. The delayed decrease of microhaematuria confirms that lesions in the urinary tract persist longer the egg excretion post-treatment

Dynamics of Schistosoma haematobium egg output and associated infection parameters following treatment with praziquantel in school-aged children

BACKGROUND: Praziquantel is the drug of choice in preventive chemotherapy targeting schistosomiasis. Increasing large-scale administration of praziquantel requires monitoring of drug efficacy to detect early signs of development of resistance. Standard protocols for drug efficacy monitoring are necessary. Here, we determined the optimal time point for praziquantel efficacy assessment against Schistosoma haematobium and studied the dynamics of infection parameters following treatment. METHODS: Ninety school-aged children from south Cote d'Ivoire with a parasitologically confirmed S. haematobium infection were treated with a single oral dose of praziquantel (40 mg/kg) and followed up for 62 days post-treatment. Urine samples were collected on 23 schooldays during this period and were subjected to visual examination (macrohaematuria), urine filtration and microscopy (S. haematobium eggs) and reagent strip testing (microhaematuria, proteinuria and leukocyturia). RESULTS: Observed cure and egg reduction rates were highly dependent on the time point post-treatment. Egg reduction rates were high (<97%) in weeks 3--9 post-treatment. Cure rates were highest in weeks 6 (92.9%) and 9 (95.0%) post-treatment. The prevalence of infection-associated parameters decreased after treatment, reaching a minimum of 2.4% in weeks 5 (proteinuria) and 7 (leukocyturia) post-treatment, and 16.3% at the end of week 8 (microhaematuria). Macrohaematuria disappeared between weeks 3 and 6 post-treatment. CONCLUSIONS: For monitoring praziquantel efficacy against S. haematobium, we recommend that the cure rate is assessed at week 6 post-treatment. The egg reduction rate can be evaluated earlier, from day 14 post-treatment onwards. Reagent strips are a useful additional tool for evaluating treatment outcomes in areas with high endemicity, preferably at weeks 5 and 6 post-treatment. The delayed decrease of microhaematuria confirms that lesions in the urinary tract persist longer the egg excretion post-treatment

Knowledge and practices on the prevention and management of diarrhea in children under-2 years among women dwelling in urban slums of Karachi, Pakistan

Background: Diarrhea is the second leading cause of death especially among children. The age-proportionate mortality of diarrheal disease in infants under 2 years is 72%, among children under 5 years of age. Children living in urban slums are more prone to develop diarrhea. Although the disease can be prevented by many simple cost-effective interventions, i.e. proper sanitation and hygiene, appropriate feeding, and timely vaccination, poverty and lack of basic life amenities often potentiate diarrhea mortality. Gadap town is the largest town of Karachi with a deprived health system. This study aims to assess pediatric diarrhea prevalence and related knowledge-practice gaps in the slums of Gadap Town, Karachi, Pakistan. Method: A community-based cross-sectional study was conducted from November 2016 to May 2017 among mothers of children under 2 years, who were residents of Gadap Town, Karachi, Pakistan. The participants were approached by a multistage sampling method. A validated dichotomous questionnaire, piloted on 40 participants, translated into local language Urdu was used for data collection and the data was analyzed by SPSS® version 20.0. Results: 51.8% (n = 199) of participants were aged between 25 and 34 years. Among all participants, 68% (n = 261) had primary level education or less, compared to 4.7% (n = 18) of women who had graduate-level education. The mean number of children per woman was 2.52 ± 1.62. Self-reported pediatric diarrhea incidence was 72.1% (n = 277). More than half (55.2% n = 149) of participants reported frequent diarrhea episodes during the 2nd year of their child’s life. In this survey, we found the knowledge of women regarding diarrhea management and how to reduce diarrhea morbidity to be inadequate (p &gt; 0.05). However, many women reported appropriate practices which can significantly reduce diarrhea morbidity (p &lt; 0.05). Conclusion: While the knowledge among women on preventive measures for pediatric diarrhea was insufficient, the translation of the right knowledge into appropriate practices showed promising outcomes for reducing diarrhea morbidity. An integrated approach for improving feeding, sanitation, and hygiene practices along with continuous health education could curtail the burden of diarrhea among infants living in urban slums

All that is blood is not schistosomiasis : experiences with reagent strip testing for urogenital schistosomiasis with special consideration to very-low prevalence settings

Reagent strip testing for microhaematuria has long been used for community diagnosis of Schistosoma haematobium. Sensitivities and specificities are reasonable, and hence, microhaematuria can serve as a proxy for S. haematobium infection. However, assessment of test performance in the context of the underlying S. haematobium prevalence is rare and test parameters other than sensitivity and specificity have been neglected.; Data about the association between microhaematuria and urine filtration results from three studies were compared and put into context with findings from a recent Cochrane review. Data were stratified by S. haematobium prevalence to identify prevalence-related differences in test performance. Kappa agreement and regression models were employed to compare data for different S. haematobium prevalence categories.; We found a "background" prevalence of microhaematuria (13 %, on average) which does not seem to be associated with schistosomiasis in most settings, irrespective of the prevalence of S. haematobium. This background level of microhaematuria might be due to cases missed with urine filtration, or alternative causes apart from S. haematobium. Especially in very-low prevalence settings, positive results for microhaematuria likely give an inaccurate picture of the extent of S. haematobium, whereas negative results are a sound indicator for the absence of infection.; Reagent strip testing for microhaematuria remains a good proxy for urogenital schistosomiasis, but implications of test results and scope of application differ depending on the setting in which reagent strips are employed. In very-low prevalence settings, microhaematuria is an unstable proxy for urogenital schistosomiasis and treatment decision should not be based on reagent strip test results alone. Our findings underscore the need for highly accurate diagnostic tools for settings targeted for elimination of urogenital schistosomiasis