Mass Drug Administration Programs Research Articles

Persons 'never treated' in mass drug administration for lymphatic filariasis: identifying programmatic and research needs from a series of research review meetings 2020-2021.

As neglected tropical disease programs rely on participation in rounds of mass drug administration (MDA), there is concern that individuals who have never been treated could contribute to ongoing transmission, posing a barrier to elimination. Previous research has suggested that the size and characteristics of the never-treated population may be important but have not been sufficiently explored. To address this critical knowledge gap, four meetings were held from December 2020 to May 2021 to compile expert knowledge on never treatment in lymphatic filariasis (LF) MDA programs. The meetings explored four questions: the number and proportion of people never treated, their sociodemographic characteristics, their infection status and the reasons why they were not treated. Meeting discussions noted key issues requiring further exploration, including how to standardize measurement of the never treated, adapt and use existing tools to capture never-treated data and ensure representation of never-treated people in data collection. Recognizing that patterns of never treatment are situation specific, participants noted measurement should be quick, inexpensive and focused on local solutions. Furthermore, programs should use existing data to generate mathematical models to understand what levels of never treatment may compromise LF elimination goals or trigger programmatic action.

Perceptions Associated with Noncompliance to Community-Wide Mass Drug Administration for Soil-Transmitted Helminths.

Mass drug administration (MDA) is a key strategy for the control of soil-transmitted helminths (STHs). Within MDA programs, poor and non-random compliance threaten successful control of STHs. A case-control study was conducted comparing perceptions among non-compliant participants with compliant participants during a community-wide MDA (cMDA) with albendazole in southern India. Common reasons cited for non-compliance were that the individual was not infected with STH (97.4%), the perception that he/she was healthy (91%), fear of side-effects (12.8%), and dislike of consuming tablets (10.3%). Noncompliance was associated with poor awareness of intestinal worms (odds ratio [OR]: 9.63, 95% CI: 2.11-43.84), the perception that cMDA was only required for those with worms (OR: 2.14, 95% CI: 1.06-4.36), and the perception that the drug is not safe during pregnancy (OR: 2.19, 95% CI: 1.18-4.07) or when on concomitant medications (OR: 3.14, 95% CI: 1.38-7.15). Understanding of perceptions driving noncompliance can provide valuable insights to optimize participation during MDA for STHs.

Efficacy of Single-Dose Praziquantel for the Treatment of Schistosoma mansoni Infections among School Children in Rwanda.

Preventive chemotherapy with single-dose praziquantel is the WHO-recommended intervention strategy to eliminate schistosomiasis as a public health problem in endemic countries. Surveillance of drugs used in mass drug administration (MDA) programs is recommended to evaluate its effectiveness in reducing transmissions. After a decade-long implementation of a school-based MDA program in Rwanda, we conducted efficacy surveillance of single-dose praziquantel MDA against S. mansoni infection. Two weeks before MDA, stool examinations were performed to screen MDA-eligible school children (n = 4998) for S. mansoni infection using the Kato-Katz technique, and 265 (6.5%) children tested positive for the infection. All children received praziquantel and albendazole as preventive chemotherapy through the MDA campaign. Infected children were enrolled and followed for efficacy monitoring, and stool examination was repeated after three weeks post-MDA (n = 188). Before treatment, 173 (92%) had a light infection, and 15 (8%) had a moderate infection intensity. The primary and secondary outcomes were parasitological cure and egg reduction rates at three weeks post-treatment. The overall cure and egg reduction rates for S. mansoni infection were 97.9% (95% CI = 94.6-99.4) and 97.02%, respectively. Among the 173 children with light infection intensity, 170 (98.3%, 95% CI = 95.0-99.6) were cured, and among the 15 children who had moderate infection intensity, 14 (93.3%) were cured. No significant association between cure rate and pre-treatment infection intensity was observed. We conclude that single-dose praziquantel is efficacious against light-to-moderate S. mansoni infection. Preventive chemotherapy with praziquantel effectively reduces schistosome reservoirs and transmission among school-age children.

Assessment of antigenemia among children in four hotspots of filarial endemic districts of Nepal during post-MDA surveillance

BackgroundSixty-three out of 77 districts reported lymphatic filariasis (LF) endemic in Nepal. Mass drug administration (MDA) with diethylcarbamazine (DEC) and albendazole (ALB) treatment program was continued for 6 to 11 rounds in these districts. Nepal government has stopped the MDA program based on the transmission assessment survey (TAS) report of 2014 and 2018 indicating Wuchereria bancrofti antigenemia prevalence < 2%. But the persistence of low levels of the circulating filarial antigen (CFA) in some foci of four endemic districts of Central Nepal, i.e., 0.4% in Dhading, 0.7% in Mahottari, 0.21% in Lalitpur and 1.2% in Bara district could responsible for enhancing the risk of infection resurgence. Hence the present study was designed to assess antigenic prevalence using Filariasis Test Strip (Alere, Scarborough ME) in children born after MDA in hotspot areas of four endemic districts of Central Nepal.ResultsThe present study covers 70% children of the eligible population. The result revealed significantly high CFA prevalence in hotspots of Mahottari district belonging to the Terai region and Dhading district belonging to the hilly region, i.e., 13% and 10%, respectively, compared to baseline prevalence and TAS report. While in Lalitpur district and Bara district CFA prevalence was still found to be less than 2%. A higher number of MDA rounds covered in hotspots were found significantly associated with the low antigenic prevalence of W. bancrofti. Whereas median treatment coverage and inter-quartile range (IQR) in study districts were not found significantly associated with CFA prevalence. Although the clinical manifestation of hydrocele (1%) was found in all four study districts, it was not due to the W. bancrofti infection.ConclusionsTwo hotspot regions, one each from the Terai (Mahottari) and hilly (Dhading) districts were found highly prevalent with CFA and significantly associated with the number of MDA rounds but were not associated with treatment coverage and IQR. Higher CFA prevalence was observed in hotspots where baseline prevalence was high together indicating that rounds of MDA program need to be extended further in these hotspot regions of endemic districts.

Understanding gender and its intersection with social stratifiers on prevention and care seeking behavior of lymphatic filariasis in Nepal

BackgroundLymphatic filariasis (LF) is a debilitating and painful neglected tropical disease and is one of the leading causes of permanent disability. In many countries, the intersection of gender with various social stratifiers has influenced exposure to LF and ultimately impacting the disease burden and its elimination. This study aimed to explore the influence of gender and its intersection with other social stratifiers for the prevention and care seeking behavior of LF in Nepal.MethodsThis study employed qualitative research methods: in-depth interviews (IDIs) and focus group discussions (FGDs) for data collection in Bardiya, Nepal. A total of 22 IDIs (11 male, 11 female) and 2 FGDs (1 male and 1 female) were conducted with the community people between January and March 2020. The participants were purposively selected to represent different social stratifiers including age, sex, ethnicity, occupation. The data collected were analyzed using a thematic framework approach with use of intersectional gender analysis matrix.ResultsThe study findings revealed that men spend more time outside their household compared to women while fulfilling their roles and responsibilities, largely determined by societal expectations and gender norms. This resulted in limited access to preventive health services for men, as they often missed annual mass drug administration programme in their community and limited access to preventive methods. Further traditional occupation, specific to particular ethnicity, influenced the vulnerability to LF for certain ethnic groups. The ability to prevent exposure varied among individuals. Although women made decisions regarding the use of protective methods, it was influenced by patriarchal and gender norms. They often felt a responsibility to take care and priorities males and other family members when resources are limited. The intersectionality of gender with other social stratifiers such as marital status, ethnicity, and geographical areas influenced individual’s ability to access information related to LF and care seeking.ConclusionsOverall, the findings emphasized how access to resources, division of work, norms and values and decision-making power alone and its interaction with various social stratifiers shaped peoples’ vulnerability to disease, ability to prevent exposure and response to illness.Graphical

Comparative Safety Surveillance of Triple (IDA) Versus Dual Therapy (DA) in Mass Drug Administration for Elimination of Lymphatic Filariasis in Kenya: A Cohort Event Monitoring Study.

Dual diethylcarbamazine and albendazole (DA) therapy is the standard mass drug administration (MDA) regimen for lymphatic filariasis in Kenya. Following the recent World Health Organization recommendation, Kenya piloted triple therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) in MDA. We conducted a community-based, observational, cohort event monitoring study to compare the types, frequency, severity, and predictors of adverse events following dual versus triple therapy in 20,421 eligible residents. Residents in Kilifi (n = 10,010) and Mombasa counties (n = 10,411) received DA and IDA through MDA campaigns, respectively. Adverse events were actively monitored through house-to-house visits on days 1, 2, and 7 after MDA. Any clinical events reported before and after MDA were cross-checked and verified to differentiate pre-existing events from MDA-associated adverse events. Overall, 5807 and 3102 adverse events were reported by 2839 and 1621 individuals in the IDA and DA groups, respectively. The incidence of experiencing one or more adverse events was significantly higher (p < 0.0001) in the IDA group (27.3%; 95% confidence interval [CI] 26.4-28.2) than in the DA group (16.2%; 95% CI 15.5-16.9). Dizziness (15.9% vs 5.9%) and drowsiness (10.1% vs 2.6%) were the most common adverse events and significantly higher in the IDA group compared with the DA group (p < 0.0001). Most adverse events were mild or moderate with a few severe cases (IDA = 0.05%; 95% CI 0.35-0.78, DA = 0.03%; 95% CI 0.14-0.60). Female sex, obesity, taking three or more diethylcarbamazine or ivermectin tablets, and having pre-existing clinical symptoms were significant predictors of adverse events following IDA treatment. Ivermectin, diethylcarbamazine, and albendazole as a combination is as safe and well tolerated as DA to use in MDA campaigns with no serious life-threatening adverse events. Systemic mild-to-moderate adverse events with a few severe cases and transient adverse events are more common with IDA treatment than with DA treatment. Hence, integrating pharmacovigilance into a MDA program is recommended for the timely detection and management of adverse events.

Community perception of school-based mass drug administration program for soil-transmitted helminths and Schistosomiasis in Ogun State, Nigeria.

Neglected tropical diseases, such as soil-transmitted helminths and Schistosomiasis, are prevalent in sub-Saharan Africa, particularly Ogun State, Nigeria. School-based mass drug administration program is the primary control intervention, but the coverage and uptake of this intervention have been inadequate. This study aimed to investigate community perceptions of school-based mass drug administration programs for these infections in Ogun State, Nigeria, and identify the barriers to their uptake and coverage. The study used a qualitative research approach involving focus group discussions and in-depth interviews with community members and stakeholders engaged in neglected tropical disease control programs in Ogun State, Nigeria. A semi-structured questionnaire guided the exploration of ideas, and the data were analyzed using the QRS Nvivo 12 software package. The study found several barriers, such as the influence of parents, lack of sufficient knowledge, and side effects. The study recommended strategies such as improving community sensitization and engagement, drug distribution and performance, and enhancing partner collaboration and coordination to improve the school-based mass drug administration programs. The study revealed correct perceptions of transmission but some misconceptions about disease causation, transmission, and drug safety. Participants expressed a desire for better sensitization campaigns and more assurances of their safety. The study recommends strengthening health education messages and increasing the visibility of on-site medical personnel. The findings have implications for improving the performance of these programs and reducing the burden of intestinal parasitic infections in the community. The study highlights the need for community engagement and education, health system support, and partner collaboration to successfully implement mass drug administration programs.

"Our interventions are still here to support communities during the pandemic": Resuming mass drug administration for neglected tropical diseases after COVID-19 implementation delays.

The COVID-19 pandemic disrupted essential health services, including those provided by national neglected tropical disease (NTD) programs. Most mass drug administration (MDA) programs were postponed for 6-12 months following World Health Organization guidance released in April 2020 to temporarily halt NTD programs and launch necessary COVID-19 precautions. While NTD-endemic countries have since resumed MDA activities, it is critical to understand implementers' perspectives on the key challenges and opportunities for program relaunch, as these insights are critical for maximizing gains towards disease control and elimination during public health emergencies. Using data from using online surveys and focus group discussions, this mixed-methods study sought perspectives from Ministry of Health NTD Program Managers and implementing partners from non-governmental organizations working in sub-Saharan Africa. Data analysis revealed that findings converged around several main themes: disruptions for MDA programs included resource shortages due to prioritization of pandemic response, challenges adhering to COVID-19 safety protocols, and community hesitancy due to coronavirus transmission fears. Identified solutions for restarting MDA programs focused on adapting intervention delivery and packaging to minimize disease transmission, embracing technology to optimize intervention planning and delivery, and identifying opportunities to promote program integration between pandemic response strategies and NTD campaign delivery. Findings identifies key challenges due to disruptions to NTD program delivery and provide strategic recommendations for endemic countries to build resilient programs that can continue to perform during and beyond global pandemics.

GD01 (P25) Considering the burden of scabies alongside a mass drug administration treatment programme in an indigenous community in northern Australia

Abstract Scabies is estimated to affect 455 million people worldwide and is one of 20 neglected tropical diseases recognized by the World Health Organization (WHO). It is caused by a parasitic mite infestation that is hyperendemic in low-resource regions, and the disease burden in northern Australia is believed to be among the highest in the world. However, few recent prevalence assessments have been conducted in northern Australia and it is not known whether historical assessments are still representative of the disease burden. Therefore, it is difficult to advocate for the allocation of government funding and resources without accurate information on the burden of disease. Considering the effectiveness of an ivermectin-based mass drug administration (MDA) treatment programme in northern Australia is important to explore a control strategy, following successful large trials conducted in the Pacific and recommendations from the WHO. The aim was to consider the burden of scabies and other skin conditions in an indigenous community in northern Australia, from undertaking a simplified skin assessment of all consenting community residents. An observational cross-sectional study design was used for this purpose. Five field teams covered different regions in Maningrida. The teams were comprised of a medical practitioner from the investigative team who worked alongside a local healthcare worker and an Aboriginal healthcare worker. All community residents who gave verbal consent were administered ivermectin, or topical permethrin cream if ivermectin was contraindicated, as part of a MDA programme, which was locally developed and implemented by the Mala’la Health Service. Simplified skin examinations (n = 1306) were conducted in Maningrida during Healthy Skin Week from 14 to 18 November 2022, with verbal consent from 99% of community residents approached for recruitment to undergo a simplified skin assessment and administration of ivermectin as part of the MDA treatment programme. The point prevalence for scabies was 25.2% (330 individuals). Ninety-three people (7.1%) were diagnosed with impetigo, and ∼40% of community residents had evidence of skin disease. No study participants were diagnosed with crusted scabies. Scabies is endemic in indigenous communities in northern Australia. This was the first prevalence assessment to be conducted in the Northern Territory since the East Arnhem Healthy Skin Project, which concluded in 2007, and the first MDA treatment programme conducted by an aboriginal medical service as a local health intervention. The consideration of effective rapid mapping and regional control strategies is essential to tailor a public health response that addresses the high burden of skin disease in northern Australia.

P25 Considering the burden of scabies alongside a mass drug administration treatment programme in an indigenous community in northern Australia

Abstract Scabies is estimated to affect 455 million people worldwide and is one of 20 neglected tropical diseases recognized by the World Health Organization (WHO). It is caused by a parasitic mite infestation that is hyperendemic in low-resource regions, and the disease burden in northern Australia is believed to be among the highest in the world. However, few recent prevalence assessments have been conducted in northern Australia and it is not known whether historical assessments are still representative of the disease burden. Therefore, it is difficult to advocate for the allocation of government funding and resources without accurate information on the burden of disease. Considering the effectiveness of an ivermectin-based mass drug administration (MDA) treatment programme in northern Australia is important to explore a control strategy, following successful large trials conducted in the Pacific and recommendations from the WHO. The aim was to consider the burden of scabies and other skin conditions in an indigenous community in northern Australia, from undertaking a simplified skin assessment of all consenting community residents. An observational cross-sectional study design was used for this purpose. Five field teams covered different regions in Maningrida. The teams were comprised of a medical practitioner from the investigative team who worked alongside a local healthcare worker and an Aboriginal healthcare worker. All community residents who gave verbal consent were administered ivermectin, or topical permethrin cream if ivermectin was contraindicated, as part of a MDA programme, which was locally developed and implemented by the Mala’la Health Service. Simplified skin examinations (n = 1306) were conducted in Maningrida during Healthy Skin Week from 14 to 18 November 2022, with verbal consent from 99% of community residents approached for recruitment to undergo a simplified skin assessment and administration of ivermectin as part of the MDA treatment programme. The point prevalence for scabies was 25.2% (330 individuals). Ninety-three people (7.1%) were diagnosed with impetigo, and approximately 40% of community residents had evidence of skin disease. No study participants were diagnosed with crusted scabies. Scabies is endemic in indigenous communities in northern Australia. This was the first prevalence assessment to be conducted in the Northern Territory since the East Arnhem Healthy Skin Project, which concluded in 2007, and the first MDA treatment programme conducted by an aboriginal medical service as a local health intervention. The consideration of effective rapid mapping and regional control strategies is essential to tailor a public health response that addresses the high burden of skin disease in northern Australia.

P48 Clinical update: ivermectin access for scabies improved through the pharmaceutical benefits scheme change in Australia

Abstract Scabies is estimated to affect 455 million people worldwide and is a neglected tropical disease that is endemic in northern Australia. Indigenous communities in northern Australia are reported to have some of the highest rates of scabies in the Pacific, with recent prevalence reported to be as high as 25%, with secondary complications including rheumatic heart disease and poststreptococcal glomerulonephritis. However, the high burden of skin disease is still under-reported and under-represented on the national policy agenda. It is essential to consider public health strategies and therapeutic opportunities to address the high burden of disease and minimize serious secondary complications that contribute to the health and life expectancy gap that exists between aboriginal and Torres Strait Islander people and other Australians. Considering the clinical need of the patient population, the management of scabies in northern Australia highlights the impracticality and tolerability issues experienced, with topical permethrin 5% cream as the sole first-line treatment option and use of ivermectin only as a second-line treatment after treatment failure with permethrin cream. This is especially important as poor medication access and treatment failure are well known to perpetuate a cycle of health inequity in northern Australia. A multistakeholder submission to the Pharmaceutical Benefits Advisory Committee was developed to support a change to the listing of ivermectin on the Pharmaceutical Benefits Scheme (PBS) in Australia, and to recommend ivermectin as a first-line treatment option for the management of scabies in aboriginal and Torres Strait Islander people in Australia. The PBS listing was successfully changed after 9 months of review, and from 1 April 2022, oral ivermectin has been listed as a first-line treatment for the management of scabies in aboriginal and Torres Strait Islander people in Australia. It is anticipated that the change in national prescribing will have a large impact on a small number of Australians who face significant disadvantages and health inequity and will improve access of treatment to manage effectively a condition that disproportionately affects First Nations people in Australia. The successful PBS listing change occurred ahead of the release of the new edition of the Australian clinical guidelines, which at the time of writing are scheduled to be released in early 2023. The updated guidelines will include ivermectin as a co-first-line treatment alongside topical permethrin 5% cream for the management of scabies, in addition to considering an ivermectin-based mass-drug administration programme for endemic regions in which the burden of scabies is estimated to be &amp;gt; 10%, as recommended by the World Health Organization.

Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo

Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.

Health-seeking behaviour regarding schistosomiasis treatment in the absence of a mass drug administration (MDA) program: the case of endemic communities along Lake Albert in Western Uganda

IntroductionSchistosomiasis poses a serious public health problem and a social challenge affecting over 240 million people, the majority of whom live in sub-Saharan Africa. The World Health Organization (WHO) recommends praziquantel (PZQ) drug treatment through regular mass drug administration (MDA) accompanied by social mobilisation and health education and sensitisation. With social mobilisation and health education and sensitisation, there is bound to be increased demand for the PZQ, especially in the case of endemic communities. However, it is not clear where communities go for PZQ treatment in the absence of PZQ MDA. We explored the health-seeking behaviours regarding schistosomiasis treatment among communities along Lake Albert in Western Uganda when MDA had delayed, to inform a review of the implementation policy for the achievement of the WHO’s 2030 target of 75% coverage and uptake.Methods and materialsWe conducted a community-based qualitative study in Kagadi and Ntoroko, an endemic community in January and February 2020. We interviewed 12 individuals: local leaders, village health teams, and health workers, and conducted 28 focus group discussion sessions with 251 purposively selected community members. The audio recordings of the data were transcribed and analyzed using a thematic analysis model.ResultsGenerally, participants seldom seek medication for schistosomiasis-related signs and symptoms from government hospitals and health centres II, III and IV. Instead, they rely on community volunteers such as VHTs, private facilities, such as clinics and drug shops nearby, or traditional sources (e.g. witch doctors and herbalists). Results show that factors influencing people to seek treatment from sources other than the government are: the absence of PZQ drugs in the government health facility; health workers’ negative attitude towards patients; long distances to the government hospitals and health facilities; poor and inaccessible roads; medication-related costs; and negative perceptions of the PZQ drug.ConclusionsAvailability and accessibility of PZQ seem to be a big challenge. PZQ uptake is further hampered by health systems and community-related and socio-cultural factors. Thus there is a need to bring schistosomiasis drug treatment and services closer to endemic communities, stock nearby facilities with PZQ and encourage endemic communities to take the drug. Contextualised awareness-raising campaigns are needed to debunk myths and misconceptions surrounding the drug.

A Novel, Highly Sensitive Nucleic Acid Amplification Test Assay for the Diagnosis of Loiasis and its Use for Detection of Circulating Cell-Free DNA.

Mass drug administration programs targeting filarial infections depend on diagnostic tools that are sensitive and specific. The coendemicity of Loa loa with other filarial species often hampers the control programs. LL2634 was identified as the most promising target among several highly repeated targets, with sensitivity between 500 ag and 1 fg of genomic DNA. Using DNA from infected individuals, LL2643 quantitative polymerase chain reaction (qPCR) was positive in all individuals. LL2643 was detected in plasma-derived circulating cell-free DNA (ccfDNA) from 48 of 53 microfilariae-positive patients. Detection of ccfDNA in urine was possible, but it occurred rarely among those tested. Importantly, LL2643 ccfDNA became undetectable within 1 month following diethylcarbamazine (DEC) treatment and remained negative for at least a year. LL2643 offers a more sensitive and specific target for detection of L. loa infection and would be easily configurable to a point-of-contact assay. Clinical Trials Registration. NCT00001230 and NCT00090662.

Use of medicinal plants as a remedy against lymphatic filariasis: Current status and future prospect.

Despite the successes achieved so far with the Global Programme to Eliminate Lymphatic Filariasis, there is still an appreciable number of lymphatic filarial patients who need alternative treatment and morbidity management strategies. The unresponsiveness of some cohorts to the drugs used in the mass drug administration program is currently raising a lot of questions and this needs urgent attention. Natural medicinal plants have a long-standing history of being effective against most disease conditions. Countries such as India have been able to integrate their natural plant remedies into the treatment of lymphatic filarial conditions, and the results are overwhelmingly positive. Components of Azadirachta indica A. Juss, Parkia biglobosa, Adansonia digitata, and Ocimum spp have been shown to have anti-inflammatory, anticancerous, and antimicrobial activities in animal models. Therefore, this review calls for attention towardthe use of natural plant components as an alternate treatment against lymphatic filariasis to help reduce the World Health Organization's burden of providing drugs for people in need of treatment every year.

Safety of integrated mass drug administration of azithromycin, albendazole and ivermectin versus standard treatment regimens: a cluster-randomised trial in Ethiopia.

Neglected Tropical Disease (NTD) programs require separate and distinct drug regimens for treatment. This has required countries to undertake multiple independent mass drug administration (MDA) programmes, each targeting one or more diseases. The possibility of safely combining different drug regimens together in one MDA may offer several advantages to national programs. We conducted a study to assess the safety of combining ivermectin, albendazole and azithromycin in one integrated MDA. We conducted an open-label, non-inferiority cluster-randomised trial comparing the frequency of adverse events in communities receiving co-administered ivermectin, albendazole and azithromycin to that in communities given albendazole and ivermectin MDA followed by azithromycin MDA after a two-week interval. The study took place in 58 gares (small administrative units) across two kebeles (sub-districts) in Kofele woreda (district) in the Oromia region of Ethiopia. We randomly assigned 29 gares to the combined treatment arm and 29 gares to the control arm. The study team revisited all individuals within 48 h and actively collected data on the occurrence of adverse events using a dedicated questionnaire and a pre-specified list of adverse events. The study team followed the same process in the control arm for the azithromycin distribution and again after the ivermectin plus albendazole distribution. Following this initial active surveillance, passive surveillance was undertaken for one week after the first visit. The primary outcome was the frequency of adverse events occurring following MDA. The study team determined that the safety of the combined MDA would be non-inferior to that of separate MDAs if the upper limit of the two-sided CI for the difference in rates was equal to or lower than 5%. The trial was registered with ClinicalTrials.gov, NCT03570814. The study took place from December 2021 to January 2022. The combined MDA arm consisted of 7292 individuals who were eligible to participate, of whom 7068 received all three medications. The separate MDA arm consisted of 6219 eligible individuals of whom 6211 received ivermectin and albendazole and 4611 received azithromycin two weeks later. Overall, adverse events were reported by 197 (1.2%) of individuals. The most commonly reported adverse events included headache, gastrointestinal disturbance and dizziness. There were no serious adverse events in either arm. The cluster-level mean frequency of reported adverse events varied markedly between clusters, ranging from 0.1 to 10.4%. The cluster-level mean frequency of adverse events was 1.4% in the combined MDA arm and 1.2% following ivermectin and albendazole MDA (absolute difference 0.2%, 95% confidence interval [CI]-0.6% to+1.1%). This met the pre-defined 1.5% non-inferiority margin. For the combined MDA comparison to the stand-alone azithromycin MDA the absolute difference was-0.4% (1.4 versus 1.8%, 95% CI-0.8 to+1.5) which also met the pre-specified non-inferiority margin. This study is the largest of its kind to date and demonstrates that the safety of combined MDA of azithromycin, ivermectin and albendazole is non-inferior to the safety of ivermectin-plus-albendazole MDA then azithromycin MDA conducted separately although we may not have been powered to detect very small differences between arms. Co-administration of these three medicines is safe and feasible in this setting and allows national programs to develop new strategies for integrated MDA programs. Ivermectin (Mectizan) was donated by the Mectizan Donation Program, albendazole was donated by GlaxoSmithKline, and azithromycin (Zithromax®) was donated by Pfizer via the International Trachoma Initiative (ITI). The trial was funded by ITI using operational research funds from the Bill and Melinda Gates Foundation.

Reduced Type 2 Innate Lymphocyte Cell Frequencies in Patent Wuchereria bancrofti-Infected Individuals.

Approximately 51 million individuals suffer from lymphatic filariasis (LF) caused mainly by the filarial worm Wuchereria bancrofti. Mass drug administration (MDA) programs led to a significant reduction in the number of infected individuals, but the consequences of the treatment and clearance of infection in regard to host immunity remain uncertain. Thus, this study investigates the composition of myeloid-derived suppressor cells (MDSCs), macrophage subsets and innate lymphoid cells (ILCs), in patent (circulating filarial antigen (CFA)+ microfilariae (MF)+) and latent (CFA+MF-) W. bancrofti-infected individuals, previously W. bancrofti-infected (PI) individuals cured of the infection due to MDA, uninfected controls (endemic normal (EN)) and individuals who suffer from lymphoedema (LE) from the Western Region of Ghana. Frequencies of ILC2 were significantly reduced in W. bancrofti-infected individuals, while the frequencies of MDSCs, M2 macrophages, ILC1 and ILC3 were comparable between the cohorts. Importantly, clearance of infection due to MDA restored the ILC2 frequencies, suggesting that ILC2 subsets might migrate to the site of infection within the lymphatic tissue. In general, the immune cell composition in individuals who cured the infection were comparable to the uninfected individuals, showing that filarial-driven changes of the immune responses require an active infection and are not maintained upon the clearance of the infection.

Rapid ethnography and participatory techniques increase onchocerciasis mass drug administration treatment coverage in Benin: a difference-in-differences analysis

BackgroundOnchocerciasis, a neglected tropical disease (NTD) that causes blindness, is controlled via mass drug administration (MDA) where entire endemic communities are targeted with preventative chemotherapeutic treatment. However, in many settings, MDA coverage remains low. The purpose of this project was to determine if engaging communities in the development of implementation strategies improves MDA coverage.MethodsThis study took place in an intervention and a control commune in Benin, West Africa. We conducted rapid ethnography in each commune to learn about community member perceptions of onchocerciasis, MDA, and opportunities to increase MDA coverage. Findings were shared with key stakeholders and a structured nominal group technique was used to derive implementation strategies most likely to increase treatment coverage. The implementation strategies were delivered prior to and during onchocerciasis MDA. We conducted a coverage survey within 2 weeks of MDA to determine treatment coverage in each commune. A difference-in-differences design was used to determine if the implementation package effectively increased coverage. A dissemination meeting was held with the NTD program and partners to share findings and determine the perceived acceptability, appropriateness, and feasibility of implementing rapid ethnography as part of routine program improvement.ResultsDuring rapid ethnography, key barriers to MDA participation included trust in community drug distributors, poor penetration of MDA programs in rural or geographically isolated areas, and low demand for MDA among specific sub-populations driven by religious or socio-cultural beliefs. Stakeholders developed a five-component implementation strategy package, including making drug distributor trainings dynamic, redesigning distributor job aids, tailoring community sensitization messages, formalizing supervision, and preparing local champions. After implementing the strategy package, MDA coverage increased by 13% (95% CI: 11.0–15.9%) in the intervention commune relative to the control commune. Ministry of Health and implementing partners found the approach to be largely acceptable and appropriate; however, there was mixed feedback regarding the feasibility of future implementation of rapid ethnography.ConclusionsImplementation research conducted in Benin, and indeed throughout sub-Saharan Africa, is often implemented in a top-down manner, with both implementation determinants and strategies derived in the global North. This project demonstrates the importance of participatory action research involving community members and implementers to optimize program delivery.

Optimal Interruption of P. vivax Malaria Transmission Using Mass Drug Administration

Plasmodium vivax is the most geographically widespread malaria-causing parasite resulting in significant associated global morbidity and mortality. One of the factors driving this widespread phenomenon is the ability of the parasites to remain dormant in the liver. Known as ‘hypnozoites’, they reside in the liver following an initial exposure, before activating later to cause further infections, referred to as ‘relapses’. As around 79–96% of infections are attributed to relapses from activating hypnozoites, we expect it will be highly impactful to apply treatment to target the hypnozoite reservoir (i.e. the collection of dormant parasites) to eliminate P. vivax. Treatment with radical cure, for example tafenoquine or primaquine, to target the hypnozoite reservoir is a potential tool to control and/or eliminate P. vivax. We have developed a deterministic multiscale mathematical model as a system of integro-differential equations that captures the complex dynamics of P. vivax hypnozoites and the effect of hypnozoite relapse on disease transmission. Here, we use our multiscale model to study the anticipated effect of radical cure treatment administered via a mass drug administration (MDA) program. We implement multiple rounds of MDA with a fixed interval between rounds, starting from different steady-state disease prevalences. We then construct an optimisation model with three different objective functions motivated on a public health basis to obtain the optimal MDA interval. We also incorporate mosquito seasonality in our model to study its effect on the optimal treatment regime. We find that the effect of MDA interventions is temporary and depends on the pre-intervention disease prevalence (and choice of model parameters) as well as the number of MDA rounds under consideration. The optimal interval between MDA rounds also depends on the objective (combinations of expected intervention outcomes). We find radical cure alone may not be enough to lead to P. vivax elimination under our mathematical model (and choice of model parameters) since the prevalence of infection eventually returns to pre-MDA levels.

The Impact of Targeted Treatment and Mass Drug Administration Delivery Strategies on the Prevalence and Intensity of Schistosomiasis in School Aged Children in Africa: A Systematic Review.

Schistosomiasis is a public health problem in more than 78 countries in the world. The disease is most prevalent among children than adults due to their high exposure to infectious water sources. Various interventions such as mass drug administration (MDA), snail control, safe water provision and health education have been implemented independently or jointly to control, reduce and ultimately eliminate Schistosomiasis. This scoping review focused on studies reporting the impact of different delivery strategies of targeted treatment and MDA on the prevalence and intensity of schistosomiasis infection in school aged children in Africa. The review focused on Schistosoma haematobium and Schistosoma mansoni species. A systematic search for eligible literature from peer-reviewed articles was done from Google Scholar, Medline, PubMed and EBSCO host databases. The search yielded twenty-seven peer-reviewed articles. All articles found reported a decrease in the prevalence of schistosomiasis infection. Five studies (18.5%) reported a prevalence change below 40%, eighteen studies (66.7%) reported a change between 40% and 80%, and four studies (14.8%) reported a change above 80%. The infection intensity post-treatment was varied: twenty-four studies reported a decrease, while two studies reported an increase. The review showed that the impact of targeted treatment on the prevalence and intensity of schistosomiasis depended on the frequency at which it was offered, complementary interventions, and its uptake by the target population. Targeted treatment can significantly control the infection burden, but cannot eliminate the disease. Constant MDA programs coupled with preventative and health promotional programs are required to reach the elimination stage.