The repository for NTD operational research studies

1. Can the O-150 LAMP assay be established on whole blood? 2. Can the O-150 qPCR methodology be adapted for human sampling?

Secondary

1. How does the performance of the O-150 LAMP compare to the O-150 qPCR assay?

2. What threshold be used to define positive vs negative results for both assays?

3. Can deep sequencing reveal over potential biomarkers for further investigation?

• An Ov16/OVOC3261 biplex IgG4 test, whereby we are confident that we can provide > 60% sensitivity and 99.8% specificity, as required by the TPP for Onchocerciasis Elimination Mapping.
• Demonstration that the Ov16/OVOC3261 biplex IgG4 test behaves at least as good with blood as with plasma/serum samples (notably a perceived weakness of the SD Ov16 RDT)

1. Can MDA resume and achieve high performance while minimizing risk of COVID-19 transmission through adherence to SOPs?

2. Can local teams easily implement the recommended modifications to MDAs; what is the added cost; and how do the above vary by context?

3. What aspects of local context influence implementation of SOPs?

This project intends to assess the effectiveness of using the Community Directed Intervention (CDI) approach as a vehicle for delivery of mass drug administration (MDA) campaigns against targeted NTDs namely, schistosomiasis and soil-transmitted helminths (STH) such as Ascaris lumbricoides (roundworms), Trichuris trichiura (whip worms) and Ancylostoma sp. (hookworms) in selected districts of Malawi. The idea is to take advantage of the logistical setup, organizational strength and high degree of efficiency of the national NTD programme to improve delivery of the current MDA efforts to control selected and highly prioritized NTDs of schistosomiasis and STH and to enhance community ownership of the interventions in selected rural and remote communities by using the CDI approach. The primary research question is: Can the CDI approach be effectively used to deliver MDA to control NTDs at community level in rural Malawian districts?

The question of how to conduct post-elimination surveillance is a high priority for the NTD community, given that most NTD programs scale back or shut down completely once elimination as a public health problem is achieved. Few solutions exist and this proposal provides an interesting and useful case study for surveillance moving forward. The study team plans to target 1708 pregnant women as a proxy for measuring LF resurgence in a post-elimination context. As a comparison group, they plan to conduct a prevalence survey of 427 households (1708 participants) in the same community to compare LF prevalence found in each methodology. Each participant at the health facility’s residence will be geo-referenced to understand the coverage area. They also plan to conduct interviews with patients and health workers, a time-motion study, and a cost analysis to assess the additional burden on health care workers and the health system. The study will occur in 14 facilities in one district of Malawi where LF was highly endemic prior to the launch of the program.

Urban dwellers have frequently been included as "hard to reach" when examining MDA coverage and uptake. Poor coverage in urban settings is a key factor that prevents programs in some settings from achieving success. This research study proposes a community-based participatory action research (CBPAR) strategy to better understand the reasons why this population isn’t reached and/or their decision not to participate in onchocerciasis and lymphatic filariasis MDAs. The results will help identify last mile strategies for urban populations and will generate a technical toolkit for how to conduct rapid participatory research in areas that require novel outreach methods amongst hard-to-reach populations. This form of social science methodology has not been used frequently within the NTD community and this proposal offers an opportunity to build the evidence base for these methods within the context of hard to reach populations.

The researchers plan to conduct a number of activities in order to determine the effectiveness of the participatory approach in targeting urban populations as compared to the standard mobilization and delivery approach.

1. Rapid ethnographic interviews, a new technique aimed at rapidly collecting and analyzing qualitative data, to gather community feedback regarding barriers in accessing treatment
2. An intervention development workshop with community leaders, health workers, researchers, and the ministry of health
3. Deliver the newly designed strategy in Za-Kpota district and compare coverage in urban settings to Ouinhi district
4. Finalize a rapid participatory approach toolkit and conduct a time-motion study of the approach to improve the business case to the MoH for uptake 5. Surveys and individual interviews with key stakeholders to determine acceptability, appropriateness, and feasibility of the proposed approach and toolkit

The researchers propose taking a novel approach to increase coverage and reach previously neglected populations by engaging non-compliant individuals in devising a more effective strategy through a technique called knowledge co-production. The researchers plan to address the following questions:

1. Can an intervention package co-produced with systematically non-compliant individuals result in increased MDA coverage between the 2019 and 2020 LF MDA rounds?
2. Who and where are the systematic non-compliers in Leogane and Gressier?
3. What are the reasons motivating systematic non-compliance?
4. Is MDA non-compliance associated with hotspots of LF transmission?

The researchers plan the following activities:

1. A household cluster survey with 1300 individuals of all ages. This will define coverage in the past MDA and identify non-compliant individuals. In addition, ‘hidden’ non-compliers (NCs) will be located by a networking approach (respondent-driven sampling [RDS]).
2. All NCs will then be eligible to be selected into groups of 10 by age (18-25; 26-50; >50), sex (M, F) and demography (urban/rural). These 12 groups will each work with the national health team to devise new approaches to the non-compliance issue. These will be put into place for the 2020 MDA and then assessed by the co-production strategy groups. After the 2020 MDA a second survey will occur to assess impact.
3. The relationship between non-compliance and hotspots will be assessed using spatial analysis and defined serologically (FTS and DBS for antibodies) in collaboration with CDC.

The study will take place in the context of a larger clinical trial (FIRM-UP) that includes 4000 women affected by schistosomiasis. For the current study, the team will develop the following “work packages” to better understand community awareness of FGS, clinical diagnosis, and how to provide enhanced training:

• Work Package 1: design and implement a community-based awareness campaign, using community surveys, focus group discussions, and in-depth interviews, to determine uptake and acceptability of FGS services. This will be followed with an end-line survey to assess change in the indicators following the campaign.
• Work Package 2: establish a diagnostic package with digital colposcopy (using smartphones to capture images) and on-site microscopy.
• Work Package 3: provide a refresher training for FIRM-UP study workers, organize a colposcopy and digital imaging workshop, and extended training for staff coming from other endemic regions in Madagascar. An open-source learning platform (‘Moodle’) will be developed to exchange training and learning materials.

Can geospatial algorithms be used by disease programs to help identify hotspots at community and Implementation Unit level?

To evaluate strategies to improve the sensitivity of the TAS for detecting evidence of recent lymphatic filariasis transmission in an evaluation unit (EU). The TAS Strengthening Study in American Samoa is designed to assess additional indicators that may be added to the current TAS platform in order to strengthen the resulting stopping or surveillance decisions. A comprehensive analysis will be conducted to understand the correlation between antigen and antibody in adults and children with the mosquito data. A spatial analysis looking at microfoci of infection will also be conducted. Xenomonitoring work to assess Aedes mosquitoes is underway.

Preliminary Findings and Lessons Learned

The ultimate goal of this study is to strengthen the existing TAS platform so that the programs can be more confident with their stopping and surveillance decisions. In order to strengthen the existing TAS platform we need to better understand which target population(s) and diagnostic indicator(s) are best-suited for identifying areas with persistent transmission that is not expected to cease on its own, knowing that the answer may vary according the primary vector and stage of the program. In the selected sites a community-based TAS was conducted using the standard sampling of 6-7 year olds while a community TAS (individuals >8 years) was conducted concurrently. All samples were tested via FTS and DBS (for Wb123 ELISA). In these same communities a molecular xenomonitoring study will take place and the mosquitoes will be tested for filarial DNA to relate back to the human specimens. To date human sampling has been completed in all sites and laboratory analysis of the specimens is complete. Mosquito collection has been completed in Haiti and Tanzania and the PCR analysis has been completed in Haiti and is planned for Tanzania (pending the arrival of a new PCR machine). In American Samoa xenomonitoring has been delayed due to weather conditions and arbovirus outbreaks; work is expected to commence spring 2018.