Mass Drug Administration and beyond: how can we strengthen health systems to deliver complex interventions to eliminate neglected tropical diseases?

Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs

A School-Based Cross-Sectional Survey of Adverse Events following Co-Administration of Albendazole and Praziquantel for Preventive Chemotherapy against Urogenital Schistosomiasis and Soil-Transmitted Helminthiasis in Kwale County, Kenya

Background Soil-transmitted helminths and schistosomiasis are mostly prevalent in developing countries due to poor sanitation and lack of adequate clean water. School-age children tend to be the target of chemotherapy-based control programmes because they carry the heaviest worm and egg burdens. The present study examines adverse events (AEs) experienced following co-administration of albendazole and praziquantel to school-age children in a rural area in Kwale County, Kenya. Methods Children were treated with single doses of albendazole and praziquantel tablets and then interviewed using a questionnaire for post treatment AEs. Results Overall, 752 children, 47.6% boys, participated in the study. Their median (interquartile range) age was 12.0 (10.0–14.0) years. A total of 190 (25.3%) children reportedly experienced at least one AE. In total, 239 cases of AEs were reported with the most frequent being abdominal pains (46.3%), dizziness (33.2%) and nausea (21.1%). Majority of the reported AEs (80.8%) resolved themselves while 12.1% and 6.3% were countered by, respectively, self-medication and visiting a nearby health facility. More girls (60.5%) than boys (39.5%) reported AEs (P = 0.027). Conclusions The AEs were mild and transient, and were no worse than those expected following monotherapy. The current study adds to the evidence base that dual administration of albendazole and praziquantel in school-based mass drug administration is safe with only mild adverse events noted

Treatment of Uncomplicated Falciparum Malaria with Artesunate-Amodiaquine Combination Therapy (ACT) in a Rural Fishing Community in Sierra Leone

Until recently, Chloroquine was the mainstay for malaria chemotherapy in Africa because it is cheap, safe and practicable for out-patient use. Resistance to this drug has however over the past decade, presented a major public health problem with therapeutic and prophylactic implications. As a response to the emergence of resistance to the commonly used antimalarial drugs, the World Health Organisation (WHO) now recommends the use of artemisinin-based combination therapies (ACTs). We assessed the therapeutic efficacy of oral Artesunate-Amodiaquine hydrochloride combination therapy in the treatment of uncomplicated falciparum malaria in a rural fishing community in Sierra Leone. One hundred and fourteen (114) participants aged 0 – 5 years attending the Outpatient Department of Gbondapi Health Centre were screened for recruitment into the study of which 70 fulfilled the inclusion criteria. Artesunate-Amodiaquine hydrochloride combined drug which passed the general counterfeit test of the Ministry of Health and Sanitation was used in the study. Adequate Clinical and parasitological Response (ACPR) was observed in 97% of the study population. Mean parasite clearance time in the participants with ACPR was found to be 24 hours (range 24 –72 hours). All 3% of the treatment failures were observed to be Early Treatment Failures (ETF). Results from the study indicate that Artesunate-Amodiaquine hydrochloride combination therapy is an effective antimalarial drug in a high transmission zone like Sierra Leone, and in the event that the drug is not effective, the results will be evident within one day of commencement of treatment

Modelling strategies to break transmission of lymphatic filariasis : aggregation, adherence and vector competence greatly alter elimination

Background: With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. Methods: We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control. Results: In all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions. Conclusion: Even moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more individual level data to be analysed to effectively tailor programmes in the drive for elimination

Geographic and ecologic heterogeneity in elimination thresholds for the major vector-borne helminthic disease, lymphatic filariasis

<p>Abstract</p> <p>Background</p> <p>Large-scale intervention programmes to control or eliminate several infectious diseases are currently underway worldwide. However, a major unresolved question remains: what are reasonable stopping points for these programmes? Recent theoretical work has highlighted how the ecological complexity and heterogeneity inherent in the transmission dynamics of macroparasites can result in elimination thresholds that vary between local communities. Here, we examine the empirical evidence for this hypothesis and its implications for the global elimination of the major macroparasitic disease, lymphatic filariasis, by applying a novel Bayesian computer simulation procedure to fit a dynamic model of the transmission of this parasitic disease to field data from nine villages with different ecological and geographical characteristics. Baseline lymphatic filariasis microfilarial age-prevalence data from three geographically distinct endemic regions, across which the major vector populations implicated in parasite transmission also differed, were used to fit and calibrate the relevant vector-specific filariasis transmission models. Ensembles of parasite elimination thresholds, generated using the Bayesian fitting procedure, were then examined in order to evaluate site-specific heterogeneity in the values of these thresholds and investigate the ecological factors that may underlie such variability</p> <p>Results</p> <p>We show that parameters of density-dependent functions relating to immunity, parasite establishment, as well as parasite aggregation, varied significantly between the nine different settings, contributing to locally varying filarial elimination thresholds. Parasite elimination thresholds predicted for the settings in which the mosquito vector is anopheline were, however, found to be higher than those in which the mosquito is culicine, substantiating our previous theoretical findings. The results also indicate that the probability that the parasite will be eliminated following six rounds of Mass Drug Administration with diethylcarbamazine and albendazole decreases markedly but non-linearly as the annual biting rate and parasite reproduction number increases.</p> <p>Conclusions</p> <p>This paper shows that specific ecological conditions in a community can lead to significant local differences in population dynamics and, consequently, elimination threshold estimates for lymphatic filariasis. These findings, and the difficulty of measuring the key local parameters (infection aggregation and acquired immunity) governing differences in transmission thresholds between communities, mean that it is necessary for us to rethink the utility of the current anticipatory approaches for achieving the elimination of filariasis both locally and globally.</p

Attitudes toward home-based malaria testing in rural and urban Sierra Leone

Background The purpose of this study was to examine malaria testing practices and preferences in Bo, Sierra Leone, and to ascertain interest in and willingness to take a home-based rapid diagnostic test administered by a community health volunteer (CHV) or a trained family member rather than travelling to a clinical facility for laboratory-based testing. Methods A population-based, cross-sectional survey of 667 randomly-sampled rural households and 157 urban households was conducted in December 2013 and January 2014. Results Among rural residents, 69% preferred a self/family- or CHV-conducted home-based malaria test and 20% preferred a laboratory-based test (with others indicating no preference). Among urban residents, these numbers were 38% and 44%, respectively. If offered a home-based test, 28% of rural residents would prefer a self/family-conducted test and 68% would prefer a CHV-assisted test. For urban residents, these numbers were 21% and 77%. In total, 36% of rural and 63% of urban residents reported usually taking a diagnostic test to confirm suspected malaria. The most common reasons for not seeking malaria testing were the cost of testing, waiting to see if the fever resolved on its own, and not wanting to travel to a clinical facility for a test. In total, 32% of rural and 27% of urban participants were very confident they could perform a malaria test on themselves or a family member without assistance, 50% of rural and 62% of urban participants were very confident they could perform a test after training, and 56% of rural and 33% of urban participants said they would pay more for a home-based test than a laboratory-based test. Conclusion Expanding community case management of malaria to include home testing by CHVs and family members may increase the proportion of individuals with febrile illnesses who confirm a positive diagnosis prior to initiating treatment

An investigation of the disparity in estimates of microfilaraemia and antigenaemia in lymphatic filariasis surveys

The diagnosis of lymphatic filariasis (LF) is based typically on either microfilaraemia as assessed by microscopy or filarial antigenaemia using an immuno-chromatographic test. While it is known that estimates of antigenaemia are generally higher than estimates of microfilaraemia, the extent of the difference is not known. This dataset was produced as part of a literature review of surveys that estimate microfilaraemia and antigenaemia

Reduction in acute filariasis morbidity during a mass drug administration trial to eliminate lymphatic filariasis in Papua New Guinea.

Background Acute painful swelling of the extremities and scrotum are debilitating clinical manifestations of Wuchereria bancrofti infection. The ongoing global program to eliminate filariasis using mass drug administration is expected to decrease this and other forms of filarial morbidity in the future by preventing establishment of new infections as a consequence of eliminating transmission by the mosquito vector. We examined whether mass treatment with anti-filarial drugs has a more immediate health benefit by monitoring acute filariasis morbidity in Papua New Guinean communities that participated in a 5-year mass drug administration trial. Methodology/Principal Findings Weekly active surveillance for acute filariasis morbidity defined by painful swelling of the extremities, scrotum and breast was performed 1 year before and each year after 4 annual mass administrations of anti-filarial drugs (16,480 person-years of observation). Acute morbidity events lasted <3 weeks in 92% of affected individuals and primarily involved the leg (74–79% of all annual events). The incidence for all communities considered together decreased from 0.39 per person-year in the pre-treatment year to 0.31, 0.15, 0.19 and 0.20 after each of 4 annual treatments (p<0.0001). Residents of communities with high pre-treatment transmission intensities (224–742 infective bites/person/year) experienced a greater reduction in acute morbidity (0.62 episodes per person-year pre-treatment vs. 0.30 in the 4th post-treatment year) than residents of communities with moderate pre-treatment transmission intensities (24–167 infective bites/person/year; 0.28 episodes per person-year pre-treatment vs. 0.16 in the 4th post-treatment year). Conclusions Mass administration of anti-filarial drugs results in immediate health benefit by decreasing the incidence of acute attacks of leg and arm swelling in people with pre-existing infection. Reduction in acute filariasis morbidity parallels decreased transmission intensity, suggesting that continuing exposure to infective mosquitoes is involved in the pathogenesis of acute filariasis morbidity

Cooking as part of a global sustainable food system - a 6 country pilot survey

The cooking of food is a nexus point for multiple issues. Cooking is intertwined with dietary choices, affects the nutrient content and environmental impacts of food, and is linked to time use and gender roles in the home. Due to its intersectionality, changing cooking practices can potentially impact upon multiple Sustainable Development Goals. However, cookery is seldom considered in the wider perspective of a sustainable food system - with only ethnographic studies examining how cooking is performed being the norm. Overall there is a limited evidence base at the population level of how different nations/populations currently cook, and how changing this would result in changes to the environment, consumer health, and economy. The current research aims to create a wider evidence base to demonstrate and quantify why cooking and food practices are important, and how they differ by geography. In this research we piloted a ~40 minute survey using the Qualtrics online survey panel in 6 countries (Nigeria, Ghana, India, Kenya, Brazil, and the UK). Participants were asked a series of questions about their: dietary preferences (e.g. vegetarian, omnivore, etc.), cooking habits (e.g frequency of cooking at home), food preparation (e.g. time taken), cooking methods used (e.g. boil, fry, roast), and perceptions of food waste, food safety, calorie and carbon footprints, as well as food security and demographic questions. 10-15 culturally appropriate/popular foods were accessed through a food frequency questionnaire, containing images of food portion size estimates, from food manuals developed by a research group from the Federal University of Paraná (http://gupea.ufpr.br/?page_id=19; Additional images of bread were sourced from the Food4Me project (DOI: 10.2196/jmir.3105). Figure 1 presents this list of foods. Recruitment used Qualtrics global recruitment services as well the Prolific panel (for the UK). Participants were potentially given financial compensation for taking part by Qualtrics, but this was outside the control of the research team. The surveys were deployed from the 25th of March, 2020. There were slight recruitment issues for some countries due to parts of the survey being carried out in Ramadan and during the COVID-19 lockdown, and so the recruitment window had to be extended until the 1st of June 2020. Participant rates, gender splits (Figure 2) and dietary patterns (figure 3) varied by country. Figure 4 to 10 compare Chicken food habits and perceptions across the 6 countries