"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.

Contextual determinants of mass drug administration performance: Modelling fourteen years of lymphatic filariasis treatments in West Africa.

BACKGROUND: Effective mass drug administration (MDA) is the cornerstone in the elimination of lymphatic filariasis (LF) and a critical component in combatting all neglected tropical diseases for which preventative chemotherapy is recommended (PC-NTDs). Despite its importance, MDA coverage, however defined, is rarely investigated systematically across time and geography. Most commonly, investigations into coverage react to unsatisfactory outcomes and tend to focus on a single year and health district. Such investigations omit more macro-level influences including sociological, environmental, and programmatic factors. The USAID NTD database contains measures of performance from thousands of district-level LF MDA campaigns across 14 years and 10 West African countries. Specifically, performance was measured as an MDA's epidemiological coverage, calculated as persons treated divided by persons at risk. This analysis aims to explain MDA coverage across time and geography in West Africa using sociological, environmental, and programmatic factors. METHODOLOGY: The analysis links epidemiological coverage data from 3,880 LF MDAs with contextual, non-NTD data via location (each MDA was specific to a health district) and time (MDA month, year). Contextual data included rainfall, temperature, violence or social unrest, COVID-19, the 2014 Ebola outbreak, road access/isolation, population density, observance of Ramadan, and the number of previously completed MDAs. PRINCIPAL FINDINGS: We fit a hierarchical linear regression model with coverage as the dependent variable and performed sensitivity analyses to confirm the selection of the explanatory factors. Above average rainfall, COVID-19, Ebola, violence and social unrest were all significantly associated with lower coverage. Years of prior experience in a district and above average temperature were significantly associated with higher coverage. CONCLUSIONS/SIGNIFICANCE: These generalized and context-focused findings supplement current literature on coverage dynamics and MDA performance. Findings may be used to quantify typically anecdotal considerations in MDA planning. The model and methodology are offered as a tool for further investigation.

No evidence of lymphatic filariasis transmission in Bamako urban setting after three mass drug administration rounds.

Lymphatic filariasis (LF) elimination activities started in Mali in 2005 in the most endemic areas and reached countrywide coverage in 2009. In 2004, the district of Bamako was endemic for LF with a prevalence of 1.5%. The current study was designed to determine LF endemicity level in the urban area of Bamako after three rounds of ivermectin and albendazole mass drug administration (MDA). A cross-sectional study was conducted in 2011 in Bamako city, consisting of human prevalence and entomological surveys. Volunteers aged 14 years and above were invited to participate and tested for evidence of Wuchereria bancrofti using night time blood thick smear microfilarial count and blood spots for LF antibodies using the SD BIOLINE Oncho/LF IgG4 Biplex rapid test (Ov16/Wb123). Mosquitoes were collected using CDC light and gravid traps and tested using molecular methods. Poolscreen software v2.0 was used to estimate vector transmission potential. Of the 899 volunteers, one (0.11%) was found to be positive for LF using the Oncho/LF IgG4 Biplex rapid test, and none was found to have Wuchereria bancrofti microfilariae. No mosquitoes were found infected among 6174 Culex spp. (85.2%), 16 Anopheles gambiae s.l. (An. gambiae s.l.) (0.2%), 26 Aedes spp. (0.4%), 858 Ceratopogonidae (11.8%) and 170 other insects not identified (2.3%) tested. Our data indicate that there was no active LF transmission in the low prevalence urban district of Bamako after three MDA rounds. These data helped the National LF programme move forward towards the elimination goal.

Comparison of Different Sampling Methods to Catch Lymphatic Filariasis Vectors in a Sudan Savannah Area of Mali.

There is a need for better tools to monitor the transmission of lymphatic filariasis and malaria in areas undergoing interventions to interrupt transmission. Therefore, mosquito collection methods other than human landing catch (HLC) are needed. This study aimed to compare the Ifakara tent trap type C (ITTC) and the Biogents sentinel trap (BGST) to the HLC in areas with different vector densities. Mosquitoes were collected in two villages in Mali from July to December in 2011 and 2012. The three methods were implemented at each site with one ITTC, one BGST, and one HLC unit that consisted of one room with two collectors-one indoor and the other outdoor. The Anopheles collected in 2011 were individually dissected, whereas those from 2012 were screened in pools using reverse transcription-polymerase chain reaction (RT-PCR) to determine the maximum infection prevalence likelihood (MIPL) for Wuchereria bancrofti and Plasmodium falciparum. The dissection of the females also allowed to assess the parity rates, as well its results. Over the 2 years, the HLC method collected 1,019 Anopheles, yields that were 34- and 1.5-fold higher than those with the BGST and ITTC, respectively. None of the dissected Anopheles were infected. The RT-PCR results showed comparable MIPL between HLC and ITTC for W. bancrofti with one infected pool from each trap's yield (respectively 0.03% [0.0009-0.2%] and 0.04% [0.001-0.2%]). For P. falciparum, no infected pool was recovered from BGST. The ITTC is a good alternative to HLC for xenomonitoring of program activities.

Factors hindering health care delivery in nomadic communities: a cross-sectional study in Timbuktu, Mali.

BACKGROUND: In Mali, nomadic populations are spread over one third of the territory. Their lifestyle, characterized by constant mobility, excludes them from, or at best places them at the edge of, health delivery services. This study aimed to describe nomadic populations' characteristics, determine their perception on the current health services, and identify issues associated with community-based health interventions. METHODS: To develop a better health policy and strategic approaches adapted to nomadic populations, we conducted a cross-sectional study in the region of Timbuktu to describe the difficulties in accessing health services. The study consisted in administering questionnaires to community members in the communes of Ber and Gossi, in the Timbuktu region, to understand their perceptions of health services delivery in their settings. RESULTS: We interviewed 520 individuals, all members of the nomadic communities of the two study communes. Their median age was 38 years old with extremes ranging from 18 to 86 years old. Their main activities were livestock breeding (27%), housekeeping (26.4%), local trading (11%), farming (6%) and artisans (5.5%). The average distance to the local health center was 40.94 km and 23.19 km respectively in Gossi and Ber. In terms of barriers to access to health care, participants complained mainly about the transportation options (79.4%), the quality of provided services (39.2%) and the high cost of available health services (35.7%). Additionally, more than a quarter of our participants stated that they would not allow themselves to be examined by a health care worker of the opposite gender. CONCLUSION: This study shows that nomadic populations do not have access to community-based health interventions. A number of factors were revealed to be important barriers per these communities' perception including the quality of services, poverty, lifestyle, gender and current health policy strategies in the region. To be successful, future interventions should take these factors into account by adapting policies and methods.

Serological Evaluation of Onchocerciasis and Lymphatic Filariasis Elimination in the Bakoye and Falémé Foci, Mali.

BACKGROUND: Ivermectin-based onchocerciasis elimination, reported in 2009-2012, for Bakoye and Falémé, Mali, supported policy-shifting from morbidity control to elimination of transmission (EOT). These foci are coendemic with lymphatic filariasis (LF). In 2007-2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24-25 years of treatment to determine if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved. METHODS: The SD Bioline Onchocerciasis/LF Ig[immunoglobulin]G4 biplex rapid diagnostic test (RDT) was used in 2186 children aged 3-10 years in 13 villages (plus 2 hamlets) in Bakoye and in 2270 children in 15 villages (plus 1 hamlet) in Falémé. In Bakoye, all-age serosurveys were conducted in 3 historically hyperendemic villages (1867 individuals aged 3 -78 years). RESULTS: In Bakoye, IgG4 seropositivity was 0.27% (95% confidence interval [CI] = .13%-.60%) for both Ov16 and Wb123 antigens. In Falémé, Ov16 and Wb123 seroprevalence was 0.04% (95% CI = .01%-.25%) and 0.09% (95% CI = .02%-.32%), respectively. Ov16-seropositive children were from historically meso/hyperendemic villages. Ov16 positivity was <2% in ≤14 year-olds, and 16% in ≥40 year-olds. Wb123 seropositivity was <2% in ≤39 year-olds, reaching 3% in ≥40 year-olds. CONCLUSIONS: Notwithstanding uncertainty in the biplex RDT sensitivity, Ov16 and Wb123 seroprevalence among children in Bakoye and Falémé is consistent with EOT (onchocerciasis) and EPHP (LF) since stopping treatment in 2016. The few Ov16-seropositive children should be skin-snip polymerase chain reaction tested and followed up.

Integrated seroprevalence-based assessment of Wuchereria bancrofti and Onchocerca volvulus in two lymphatic filariasis evaluation units of Mali with the SD Bioline Onchocerciasis/LF IgG4 Rapid Test.

BACKGROUND: Mali has become increasingly interested in the evaluation of transmission of both Wuchereria bancrofti and Onchocerca volvulus as prevalences of both infections move toward their respective elimination targets. The SD Bioline Onchocerciasis/LF IgG4 Rapid Test was used in 2 evaluation units (EU) to assess its performance as an integrated surveillance tool for elimination of lymphatic filariasis (LF) and onchocerciasis. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional survey with SD Bioline Onchocerciasis/LF IgG4 Rapid Test was piggy-backed onto a transmission assessment survey (TAS) (using the immunochromatographic card test (ICT) Binax Filariasis Now test for filarial adult circulating antigen (CFA) detection) for LF in Mali among 6-7 year old children in 2016 as part of the TAS in two EUs namely Kadiolo-Kolondieba in the region of Sikasso and Bafoulabe -Kita-Oussoubidiagna-Yelimane in the region of Kayes. In the EU of Kadiolo- Kolondieba, of the 1,625 children tested, the overall prevalence of W. bancrofti CFA was 0.62% (10/1,625) [CI = 0.31-1.09]; while that of IgG4 to Wb123 was 0.19% (3/1,600) [CI = 0.04-0.50]. The number of positives tested with the two tests were statistically comparable (p = 0.09). In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of W. bancrofti CFA was 0% (0/1,700) and that of Wb123 IgG4 antibody was 0.06% (1/1,700), with no statistically significant difference between the two rates (p = 0.99). In the EU of Kadiolo- Kolondieba, the prevalence of Ov16-specific IgG4 was 0.19% (3/1,600) [CI = 0.04-0.50]. All 3 positives were in the previously O. volvulus-hyperendemic district of Kolondieba. In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of Ov16-specific IgG4 was 0.18% (3/1,700) [CI = 0.04-0.47]. These 3 Ov16 IgG4 positives were from previously O.volvulus-mesoendemic district of Kita. CONCLUSIONS/SIGNIFICANCE: The SD Bioline Onchocerciasis/LF IgG4 Rapid test appears to be a good tool for integrated exposure measures of LF and onchocerciasis in co-endemic areas.

Eliminating Neglected Tropical Diseases in Urban Areas: A Review of Challenges, Strategies and Research Directions for Successful Mass Drug Administration.

Since 1950, the global urban population grew from 746 million to almost 4 billion and is expected to reach 6.4 billion by mid-century. Almost 90% of this increase will take place in Asia and Africa and disproportionately in urban slums. In this context, concerns about the amplification of several neglected tropical diseases (NTDs) are warranted and efforts towards achieving effective mass drug administration (MDA) coverage become even more important. This narrative review considers the published literature on MDA implementation for specific NTDs and in-country experiences under the ENVISION and END in Africa projects to surface features of urban settings that challenge delivery strategies known to work in rural areas. Discussed under the thematics of governance, population heterogeneity, mobility and community trust in MDA, these features include weak public health infrastructure and programs, challenges related to engaging diverse and dynamic populations and the limited accessibility of certain urban settings such as slums. Although the core components of MDA programs for NTDs in urban settings are similar to those in rural areas, their delivery may need adjustment. Effective coverage of MDA in diverse urban populations can be supported by tailored approaches informed by mapping studies, research that identifies context-specific methods to increase MDA coverage and rigorous monitoring and evaluation.

Dynamics of antigenemia and transmission intensity of Wuchereria bancrofti following cessation of mass drug administration in a formerly highly endemic region of Mali.

BACKGROUND: After seven annual rounds of mass drug administration (MDA) in six Malian villages highly endemic for Wuchereria bancrofti (overall prevalence rate of 42.7%), treatment was discontinued in 2008. Surveillance was performed over the ensuing 5 years to detect recrudescence. METHODS: Circulating filarial antigen (CFA) was measured using immunochromatographic card tests (ICT) and Og4C3 ELISA in 6-7 year-olds. Antibody to the W. bancrofti infective larval stage (L3) antigen, Wb123, was tested in the same population in 2012. Microfilaraemia was assessed in ICT-positive subjects. Anopheles gambiae complex specimens were collected monthly using human landing catch (HLC) and pyrethrum spray catch (PSC). Anopheles gambiae complex infection with W. bancrofti was determined by dissection and reverse transcriptase polymerase chain reaction (RT-PCR) of mosquito pools. RESULTS: Annual CFA prevalence rates using ICT in children increased over time from 0% (0/289) in 2009 to 2.7% (8/301) in 2011, 3.9% (11/285) in 2012 and 4.5% (14/309) in 2013 (trend χ 2 = 11.85, df =3, P = 0.0006). Wb123 antibody positivity rates in 2013 were similar to the CFA prevalence by ELISA (5/285). Although two W. bancrofti-infected Anopheles were observed by dissection among 12,951 mosquitoes collected by HLC, none had L3 larvae when tested by L3-specific RT-PCR. No positive pools were detected among the mosquitoes collected by pyrethrum spray catch. Whereas ICT in 6-7 year-olds was the major surveillance tool, ICT positivity was also assessed in older children and adults (8-65 years old). CFA prevalence decreased in this group from 4.9% (39/800) to 3.5% (28/795) and 2.8% (50/1,812) in 2009, 2011 and 2012, respectively (trend χ 2 = 7.361, df =2, P = 0.0067). Some ICT-positive individuals were microfilaraemic in 2009 [2.6% (1/39)] and 2011 [8.3% (3/36)], but none were positive in 2012 or 2013. CONCLUSION: Although ICT rates in children increased over the 5-year surveillance period, the decrease in ICT prevalence in the older group suggests a reduction in transmission intensity. This was consistent with the failure to detect infective mosquitoes or microfilaraemia. The threshold of ICT positivity in children may need to be re-assessed and other adjunct surveillance tools considered.

Exploring innovative ways to conduct coverage surveys for neglected tropical diseases in Malawi, Mali, and Uganda.

Currently, a 30-cluster survey to monitor drug coverage after mass drug administration for neglected tropical diseases is the most common methodology used by control programs. We investigated alternative survey methodologies that could potentially provide an estimation of drug coverage. Three alternative survey methods (market, village chief, and religious leader) were conducted and compared to the 30-cluster method in Malawi, Mali, and Uganda. In Malawi, drug coverage for the 30-cluster, market, village chief, and religious leader methods were 66.8% (95% CI 60.3-73.4), 74.3%, 76.3%, and 77.8%, respectively. In Mali, results for round 1 were 62.6% (95% CI 54.4-70.7), 56.1%, 74.8%, and 83.2%, and 57.2% (95% CI 49.0-65.4), 54.5%, 72.2%, and 73.3%, respectively, for round 2. Uganda survey results were 65.7% (59.4-72.0), 43.7%, 67.2%, and 77.6% respectively. Further research is needed to test different coverage survey methodologies to determine which survey methods are the most scientifically rigorous and resource efficient.

Implementing preventive chemotherapy through an integrated National Neglected Tropical Disease Control Program in Mali.

BACKGROUND: Mali is endemic for all five targeted major neglected tropical diseases (NTDs). As one of the five 'fast-track' countries supported with the United States Agency for International Development (USAID) funds, Mali started to integrate the activities of existing disease-specific national control programs on these diseases in 2007. The ultimate objectives are to eliminate lymphatic filariasis, onchocerciasis and trachoma as public health problems and to reduce morbidity caused by schistosomiasis and soil-transmitted helminthiasis through regular treatment to eligible populations, and the specific objectives were to achieve 80% program coverage and 100% geographical coverage yearly. The paper reports on the implementation of the integrated mass drug administration and the lessons learned. METHODOLOGY/PRINCIPAL FINDINGS: The integrated control program was led by the Ministry of Health and coordinated by the national NTD Control Program. The drug packages were designed according to the disease endemicity in each district and delivered through various platforms to eligible populations involving the primary health care system. Treatment data were recorded and reported by the community drug distributors. After a pilot implementation of integrated drug delivery in three regions in 2007, the treatment for all five targeted NTDs was steadily scaled up to 100% geographical coverage by 2009, and program coverage has since been maintained at a high level: over 85% for lymphatic filariasis, over 90% for onchocerciasis and soil-transmitted helminthiasis, around 90% in school-age children for schistosomiasis, and 76-97% for trachoma. Around 10 million people have received one or more drug packages each year since 2009. No severe cases of adverse effects were reported. CONCLUSIONS/SIGNIFICANCE: Mali has scaled up the drug treatment to national coverage through integrated drug delivery involving the primary health care system. The successes and lessons learned in Mali can be valuable assets to other countries starting up their own integrated national NTD control programs.

The field-testing of a novel integrated mapping protocol for neglected tropical diseases.

BACKGROUND: Vertical control and elimination programs focused on specific neglected tropical diseases (NTDs) can achieve notable success by reducing the prevalence and intensity of infection. However, many NTD-endemic countries have not been able to launch or scale-up programs because they lack the necessary baseline data for planning and advocacy. Each NTD program has its own mapping guidelines to collect missing data. Where geographic overlap among NTDs exists, an integrated mapping approach could result in significant resource savings. We developed and field-tested an innovative integrated NTD mapping protocol (Integrated Threshold Mapping (ITM) Methodology) for lymphatic filariasis (LF), trachoma, schistosomiasis and soil-transmitted helminths (STH). METHODOLOGY/PRINCIPAL FINDINGS: The protocol is designed to be resource-efficient, and its specific purpose is to determine whether a threshold to trigger public health interventions in an implementation unit has been attained. The protocol relies on World Health Organization (WHO) recommended indicators in the disease-specific age groups. For each disease, the sampling frame was the district, but for schistosomiasis, the sub-district rather than the ecological zone was used. We tested the protocol by comparing it to current WHO mapping methodologies for each of the targeted diseases in one district each in Mali and Senegal. Results were compared in terms of public health intervention, and feasibility, including cost. In this study, the ITM methodology reached the same conclusions as the WHO methodologies regarding the initiation of public health interventions for trachoma, LF and STH, but resulted in more targeted intervention recommendations for schistosomiasis. ITM was practical, feasible and demonstrated an overall cost saving compared with the standard, non-integrated, WHO methodologies. CONCLUSIONS/SIGNIFICANCE: This integrated mapping tool could facilitate the implementation of much-needed programs in endemic countries.