Neglected Tropical Diseases Support Center (NTD-SC)

• 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.

Organize existing data for preparation of LF elimination dossiers based on the PacELF programs.

Comparison of ICT, FST and Antibody tests in low-prevalence settings.

The multi-country studies on the same topic led to the endorsement by WHO for the FTS as an approved diagnostic tool.

The overall goal of this research proposal is to prioritize the five novel Bancroftian antigen candidates with respect to their ease-of-use and practicability within the frame of a future Wb123/WbAgx biplex test, based on their biophysical properties, stability data and behavior in our lateral flow assay setup. Along with the concurrent biochemical/clinical validation by the Nutman group. This will allow an informed choice as to which candidate antigen(s) should be used for the biplex assay development.

1. Development of spatio-temporal models and associated statistical methods to enable forward projections of the geographical distribution of prevalence, and hence the risk of resurgence, by combining model-based geostatistical analysis with mechanistic predictive modelling of disease transmission dynamics, using the most recent available data on disease prevalence and environmental risk-factors.

2. To use the results from aim 1 to derive statistically efficient and affordable designs for networks of sentinel sites to enable continued monitoring of prevalence in areas at high risk of resurgence."

CCA Protocol: To know the sensitivity and specificity of POC CCA in the detection of urinary schistosomiasis, as compared to traditional diagnostic tools.

This social science study will address the following:

Formative question: What are the strengths and weaknesses of the four models for case identification, confirmation and referral currently being implemented in Liberia for NTDs?

Intervention question: What is the optimal model for implementing case identification, confirmation and referral of NTD cases requiring case management, in terms of equity, effectiveness, economy and efficiency within the health system?"

To develop and pilot a standardised analytical framework for the spatial and temporal analysis of routinely collected gender disaggregated NTD programme data. This will allow increased understanding and spatial visualisation of the influence of gendered programmatic inputs, external geographic and social factors on the equity of programmatic outputs, particularly access to mass administration of medicines (MAM).

• What is the indicator(s) and accompanying M&E strategy that enables country programs to determine when the risk of ongoing transmission of lymphatic filariasis has been reduced so that triple drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) can be stopped with little risk of resurgence of transmission?
• Can the use of a tailored social mobilization package be used to strengthen community and health system participation and achieve >80% coverage for IDA in Kenya?

Intervention: The primary aim of this project is to determine if the introduction of a Chronic Disease Self-Management curriculum into existing Hope Clubs in Léogâne, Haiti will result in improvements in symptoms of depression, self-rated health, chronic disease self-efficacy, social support, and disability.

Formative: What are the barriers that prevent people with LF from participating in Hope Clubs?

This social science study will address the following:

Formative question: What were the successes and challenges of the LF MMDP pilot in the Upper East region for increasing the capacity of health workers of all levels and improving the ability of patients to manage LF morbidity?

Intervention question: Can a modified capacity strengthening package, developed based on the formative research results, be effective at increasing the capacity of health workers of all levels and improving the ability of patients to manage LF morbidity?

Assess the overall acceptability of the 3-drug treatment in the community as compared to the 2-drug treatment

RQ1 - Reliability assessment: What is the intra- and inter-rater reliability of current qualitative F and novel quantitative hygiene metrics across study contexts?

RQ2 – Validity assessment: What is the validity of each metric of interest (i.e., quantitative hygiene and qualitative F metrics) with regard to recent personal hygiene practices and trachoma outcomes?

RQ3 – Utility assessment: What is the utility of each metric (i.e., qualitative and quantitative)?

RQ4 – Risk factor assessment: Do proxy facial and hand hygiene outcomes, as measured by the novel quantitative hygiene metric, represent risk factors of incident C. trachomatis infection?

Research questions: Does an innovative community referral linkage improve VL case finding in hard-to-reach areas of Northwest Ethiopia? Does innovative community referral linkage improve patient adherence to VL treatment? Does innovative community referral linkage improve VL patient’s treatment outcomes? Does an electronic referral linkage system improve back and forth communication and feedback between the treatment centre and community?

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?

A pilot study to identify meaningful and measurable targets for detecting the control of schistosomiasis-related morbidity in Africa. The overall study is designed to answer the following primary evaluation questions:

• What are the infection levels of Schistosoma mansoni and S. haematobium below which there is little, or no, detectable schistosomiasis-associated morbidity?
• What are the optimal morbidity markers for S. mansoni and S. haematobium?
• What are the optimal species-specific morbidity goals for which schistosomiasis control programs should be aiming?

What is the effectiveness of appropriately dosed IDA in clearing microfilariae (Mf) from Mf positive people who (i) reported taking triple drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) in August 2018, and (ii) did not report recently taking IDA.

This will be investigated by:

• assessing the baseline (current) Mf presence and density before re/treatment with IDA, against which post-treatment Mf presence and density can be compared
• assessing the peak plasma concentration levels of ivermectin, DEC and albendazole in treated Mf positive individuals to identify whether the recommended dosages of medications are sufficient for achieving effective plasma concentrations
• assessing Mf clearance one week following directly observed IDA re/treatment

Assess the overall acceptability of the 3-drug treatment in the community as compared to the 2-drug treatment

Study the impact of WASH on Trachoma by adding an STH intervention and post-treatment evaluation. WASH intervention and control communities will be treated with albendazole and STH burden will be assessed pre-treatment and at annual intervals thereafter.

1. Do existing programs or activities address integrated MMDP for patients living with LF and Leprosy?
2. What is the impact of integrated MMDP in Luangwa district on access to healthcare?

To study the feasibility of LF and Oncho (Filariases) integrated transmission assessment survey iTAS) according to both LF and Onchocerciasis WHO elimination guidelines

• Is mobile outreach with a doxycycline test and treat strategy (TTd) an effective strategy in reducing onchocerciasis prevalence and intensity of infection amongst hard-to-reach nomadic groups in Massangam health area (HA)?
• What is the variation in prevalence of onchocerciasis and intensity of infection (community microfilaria load (CML)) in the different age and sex groups of hard-to-reach nomad community in the Massangam HA?
• What was the coverage of ivermectin mass drug administration in the nomad population with respect to the last round of ivermectin MDA?
• What is the cost of the mobile outreach strategy in this context, per person screened and treated?

To compare the sensitivity of double-slide Kato-Katz and multi-parallel real-time polymerase chain reaction (PCR) in the detection of Ascaris, hookworm, and Trichuris infection among children in rural Bangladesh

To understand the nature (quality and quantity) of post epilation lashes and their visual significance in unoperated minor trachomatous trichiasis (TT) cases and case with post-operative trichiasis

This study will address the characteristics of the ocular chlamydia trachomatis population structures within Amhara, a setting which has experienced repeated rounds of antibiotic for trachoma, and whether those circulating populations are different than known sequenced strains.

Innovative approach to exploit ongoing STH- SCH survey to conduct integrated surveillance for LF and oncho that will serve as a model for other programs

To assess the socio-economic factors contributing to low access to MDA, to identify the existing health services opportunities and other outlets specific to various socio-economic groups that could be used for improving access to MDA, and to develop feasible field-applicable strategies that can be used to reach groups with consistently low access to MDA.

The primary aim of this study is a first evaluation (384 samples) of the DjinniChip in ocular clinical samples in a trachoma-endemic region in-country, but initially in the controlled environment of a research laboratory setting. The second aim is to determine the DjinniChips resilience and usability by evaluating its performance with a concentration series of positive control swabs in various environmental conditions (hot, dry, dusty, humid).

Can geostatistical tools be used to develop a stop IDA strategy for LF that can measure <1% Mf prevalence in adults?

To determine the appropriate serologic threshold(s) to be used to initiate MDA for onchocerciasis.

Identify the sampling strategy for tracking positive cases after TAS 2 and TAS 3 that optimizes the chances of correctly identifying evidence of active transmission, while saving program resources

Main objectives are firstly to identify and understand better the factors behind low and unequal MDA coverage and compliance in trachoma endemic areas in Tanzania and Kenya with nomadic populations, secondly to prioritize factors in terms of amenability to intervention. The researcher will then use the evidence generated to design specific interventions that could improve the reach and impact of campaigns of Zithromax MDA in both countries.  While there are contextual differences between nomadic societies throughout Africa, research among the Masai in Tanzania and Kenya should inform programme services in other settings with nomadic populations. Particular attention will be given to gender-sensitivity; that is, interventions that will improve access and use by women as well as men.

To compare coverage evaluation methods to identify a method that is statistically rigorous and feasible for programs. This study will focus on assessing MDA coverage for lymphatic filariasis by comparing the cost, time and feasibility of 3 different methods: the EPI approach (n=1768), LQAS design (n=95) and probability sampling alternatives (n=1768).

Primary Findings and Lessons Learned

Coverage surveys are an important tool for programs to evaluate their reporting systems and to determine whether effective MDA coverage has been achieved. However, for various reasons coverage surveys are seldom implemented.  Some key challenges are: perceived technical difficulty, lack of resources, and lack of standardized guidance on how to conduct coverage surveys.  This protocol seeks to address the 1st and 3rd points by comparing the feasibility of three different coverage survey methods (EPI approach, LQAS, and segmentation).     This study was completed in 3 districts in Burkina Faso.  All 3 districts found that their survey coverage was above the WHO target threshold (65% for LF).  Furthermore, in all 3 cases the survey coverage validated (or nearly validated) the reported coverage. Taken together this suggests that the Burkina Faso program is working well.   The feasibility results found all 3 methods to be very similar with regards to time, cost and perceived difficulty.  Because only the segmentation approach results in a probability sample, this method was recommended by the M&E Working Group and ultimately approved by the STAG.  Since the approval, significant work has been underway to create guidelines for conducting coverage surveys for preventive chemotherapy.  An excel tool was created to improve the usability of the tool and online learning modules are currently in the works.

Non-compliance is a primary barrier to attaining elimination goals. This study aims to utilize data captured in MDA registers to address non-compliance in the Ahanta West District of Ghana, which has been identified as a hotspot of LF transmission with >1% microfilaria (mf) prevalence after 15-16 rounds of MDA. On the basis of information identified in the register, this study proposes to deploy two strategies:

1. Engage and Treat individuals who were ill, missed treatment, or were unable to participate during the last MDA, and
2. Test and Treat for individuals who might be systemically non-compliant or afraid of adverse events. The use of MDA registers to assist in locating non-compliant individuals is novel and would provide valuable evidence for other programs and represents an alternative strategy for countries struggling with the end game. It may also help provide insight as to whether systematically non-compliant individuals truly serve as a reservoir for LF in areas designated as hotspots. Qualitative data collection will aid in understanding reasons for systematic non-compliance and may lead to changes in social mobilization strategies.

The study aims to identify the most effective approaches for case management and delivery of surgical services for IDPs and migrants suffering from LF and/or trachoma in security compromised areas. Barriers to reaching morbidity patients will be assessed, in addition to determinants of the institutionalizatoin of NTD morbidity management within the national health system. Research aims will be addressed through the following key activities: document review and direct inspection protocols to determine health facilities' ability to provide MMDP services; active case finding including creation of WhatsApp groups and SMS messaging to help keep track of patients and refer them to care; key informant interviews with health workers and community leaders to assess behavior change communication strategies for raising awareness among affected individuals; one-on-one interviews and focus group discussions with patients to understand barriers to care; and stakeholder engagement to increase buy-in and identify ways to operationalize MMDP services within national program.

This study will pilot the Slash and Clear methodology in an oncho-Loa loa co-endemic setting. Previous pilots in Uganda and Nigeria have demonstrated that this simple strategy of removing breeding sites can result in significant black fly reductions that last for several months. This study will provide important data on the impact of Slash and Clear on black fly biting, and consequently its impact on oncho elimination. Two intervention and one control community will be compared for two years, with repeated measurements being taken of biting rates.

This study is designed as a proof-of-concept to test the feasibility and acceptability of a proposed intervention package outlined in a soon to be published WHO manual on NTDs and mental health. The primary output of this study is to adapt a model of intervention from the soon to be published WHO guide on Mental Health and NTDs. The team aims to achieve this output through:

• Screening 300 individuals for symptoms of depression and anxiety, refer where necessary, and sample 30 of those individuals for participation in qualitative interviews.
• Conducting peer-led focus group discussions (separate groups for leprosy and LF) to better understand the needs, priorities, and barriers related to affected individuals’ mental wellbeing and quality of life.
• Conducting a workshop with health leaders, community health workers, nurses, service users, family/caregivers, and experts to develop a feasible and applicable theory of change that aligns with WHO guidelines.
• Conducting in depth interviews with key stakeholders to assess the developed model’s feasibility and accessibility Conducting quantitative measures for feasibility and acceptability to assess the stepped-care approach model which involves: improved screening, referral, uptake of service, knowledge uptake following training, and an assessment of whether supervision was carried out. They also plan to triangulate health information data to determine uptake of services.
• Conducting follow-up FGDs with those 30 individuals after a one-month period to understand their experience with primary health center mental health services.

This study aims to integrate screening and preventive treatment with praziquantel for FGS into routine HIV and reproductive health care visits for women. A pilot study will be conducted in four health facilities with a target sample size of 4800 women over a six-month period. Trainings will be conducted for health workers and the team will use a participatory design process with key stakeholders to ensure that barriers to integration in the health system and community participation are addressed. A scale-up report will be written with stakeholder engagement and all training materials that were developed will be instantly available for use in other clinics in Cote d’Ivoire. Delivery of praziquantel to the four facilities in the pilot study will utilize existing drug-procurement and delivery systems to ensure sustainability.

Haiti, like many other countries, has made considerable progress in the elimination of lymphatic filariasis. To date, 118 out of 140 communes have passed TAS and stopped MDA. However, little is understood about why some communes have persistent transmission despite five or more rounds of MDA. The proposed study aims to identify alternative approaches to MDA that may help to increase access, uptake, and coverage, particularly for individuals who typically do not comply with MDAs. This cluster-randomized design will test a novel approach (door to door strategy) against the standard health post-based delivery method. Additionally, the study aims to identify non-compliant individuals and better understand their reasons for non-participation. Furthermore, a cost analysis will be undertaken as part of this study to understand the potential implications for the country program should the door-to-door strategy prove effective in reaching higher numbers of people.

To develop and pilot test an innovative standardized diagnostic algorithm for female genital schistosomiasis and other common causes of genital ulcerative and inflammatory disease that is feasible to use in Zambian government clinics

• Formative component: What is the capacity of the integrated morbidity management and disability prevention (MMDP) programme to incorporate a stigma reduction intervention for people with lower limb lymphoedema, and what are the barriers and facilitators to this?
• Intervention component: Is the stigma reduction intervention effective in increasing demand and access to services within an integrated MMDP programme for people with lower limb lymphoedema?

What is/are the most suitable indicator(s) for monitoring IDA treatment regimen against LF and for making IDA stopping decisions?

This study aims to understand and address several issues: lack of knowledge among health care workers (HCW) and community health workers (CHW) about FGS, knowledge and stigma at the community level, the potential for integrating FGS into existing sexual and reproductive health (SRH) education, and the potential for improving equity of MDAs for women of reproductive age.

Formative research will be used to develop HCW training modules, social mobilization and sensitization messaging, and to assess baseline knowledge. The team plans to conduct cross-sectional community surveys, focus groups with CHWs, and interviews with health workers that measure KAPs. In the intervention phase, the team plans to incorporate FGS material into existing SRH programs, including an online/social media platform used to teach teenage girls about HIV and STIs. They are also planning community outreach activities that coincide with the planned MDAs and are planning to field test the community-based drug delivery outlined in Kenya’s “Breaking Transmission” strategy. Testing and treatment for FGS will be improved at health facilities. Radio messaging using crafted behavior change messaging will be deployed.

This proof of concept study will take place over a 10-month period. They aim to compare the feasibility and acceptability of mobile gynecological clinics versus traditional, static health posts. The primary research question, Where urogenital schistosomiasis is endemic, can a static health outpost versus a mobile clinic deliver better diagnosis and treatmnet of FGS, HIV, HPV, and cervical cancer in an acceptable and cost-effective manner to women (14-30 years), will be answered through the following activities:

1. Development of a consortium on FGS bringing together high-profile researchers, policy makers, program implementers, and health professionals
2. Training of health professionals (nurses, physicians, community health workers) with follow up sessions to raise awareness and diagnostic capabilities through colposcopic imagery. Health workers in remote areas will utilize telehealth to transmit images for quality checks by a specialist. The team will measure the % correlation between field results and telemedicine results to determine feasibility.
3. Precision mapping in select districts to determine areas with the highest schistosomiasis prevalence through parasitological surveys
4. Pilot test mobile service delivery for FGS, HIV, HPV, and other common gynecological issues in two of the four districts. This will include a cost analysis to make a business case for scalability.

This study aims to answer: Can female genital schistosomiasis (FGS) screening be successfully promoted through a community-based teaching intervention addresing stigma and other socio-structural barriers to increase health-seeking behaviors nested in broader sexual and reproductive health prevention services. It pilots an approach that combines awareness, anti-stigma education, and integrated screening for FGS. Investigators will work with women, adolescent girls, and key stakeholders to develop a community-based teaching platform for FGS, cervical cancer, HIV, and STIs that could decrease the burden of genital tract morbidity in women of reproductive age. Zambia will serve as the main study site and once the team has developed the intervention, it will be rolled out remotely to Malawi and Tanzania. Additionally, the team plans to adapt validated HIV stigma indicators to include FGS and pilot test the scale throughout the course of the project.

This study will test the reliability of community health worker-led (CHW) MMDP burden estimates by having CHWs first estimate MMDP burden, followed by a rigorous population-based survey to get a representative estimate of MMDP burden for the district. Six months later, these cases will be followed up to see whether they accessed the MMDP services and assess the quality of care. The study will examine the accuracy of the CHW estimates, CHWs’ ability to diagnose properly, social biases of health care workers that may prevent equitable care delivery, and the cost comparison of the CHW method vs. population-based survey. In addition, the team plans to conduct an evaluation of the quality of MMDP service provision, including available psychosocial support, at all facilities in the selected health district. Programs need a feasible and reliable method for coming up with MMDP burden estimates for LF and strategies to ensure that people have access to care and utilize that care. This study addresses the two pillars of WHO dossier development for MMDP and will provide the Ministry of Health with essential information to plan and adapt their program to accommodate MMDP services.

Can a smartphone-based app with an integrated image analysis algorithm be used to increase accuracy and yield of trachomatous trichiasis (TT) screening compared to standard TT case finder screening?

After two decades of onchocerciasis control activities in Bioko island, transmission is expected to be interrupted. This study aims to demonstrate that WHO criteria to verify transmission interruption have been met. It also aims to standardize the reading of RDTs, particularly the FTS and Ov16, and reduce the potential for human error.

Preliminary Study Findings:

A cross-sectional study was conducted from September 2016 to January 2017. Participants were 5- to 9-year-old school children. Onchocerciasis/lymphatic Filariasis (LF, only in endemic districts) rapid diagnostic tests (RDTs) were performed. Blood spots were collected from RDT positive children and 10 percent of the RDT negatives to determine Ov16 and Wb123 IgG4 antibodies through enzyme-linked immunosorbent assay (ELISA). Skin snips were collected from RDT positives. Filarial detection was performed by PCR in positives and indeterminate sera. Black fly collection was carried out in traditional breeding sites. A total of 7,052 children, ranging from 5 to 9 years of age, were included in the study. Four children (0.06%) were Ov16 IgG4 RDT positives, but negative by ELISA Ov16, while 6 RDT negative children tested positive by ELISA. A total of 1,230 children from the Riaba and Baney districts were tested for LF. One child was Wb123 RDT positive (0.08%), but ELISA negative, while 3 RDT negative children were positive by Wb123 ELISA. All positive samples were negative by PCR for onchocerciasis and LF (in blood spot and skin snip). All fly collections and larval prospections in the traditional catching and prospection sites were negative.

Read more in Herrador et al.: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006471

This study aims to understand the relationship between trachomatous trichiasis (TT) and mental health disorders over an 18-month study period, by answering the following questions:

1. What is the impact of the blinding stage of trachoma (Trachomatous Trichiasis) on common mental disorders such as depression, anxiety and suicidality?
2. Will the validation of the 5-Question Stigma Indicators (5-QSI) generic stigma tool help to measure and monitor stigma in trachomatous trichiasis patients in Ethiopia
3. What are the drivers for mental disorders in TT patients
4. Is there a difference in depression, anxiety and suicidality prevalence between TT cases accepting vs declining TT surgery; and un-operated vs postoperative TT cases? The research team will be trained on good clinical practice through the WHO Mental Health Gap Action Programme (mhGAP). Following interviews, any patient with TT will be referred for surgery and patients found with a mental health disorder will be referred for care. If a negative impact of blinding trachoma on mental health is noted, the researchers plan to use the results of the study to advocate for additional funding for the trachoma program and highlight the need to address mental health in Ethiopia.

Ghana aims to eliminate onchocerciasis by 2025. Currently, all data points for mass drug administrations are collected on paper. Paper-based data collection does not allow for rapid evaluation and course correction throughout the implementation of the MDA. This study proposes a collaboration between the monitoring and evaluation division of the Ghana Health Service and the Clinical Informatics Research Unit at the University of Southampton. The study aims to answer the primary research question: Can community-driven electronic data collection, and near real-time provision of source data and interactive visualizations better support decision-makers on approaches to evaluating and managing MDAs for onchocerciasis?

• What factors are associated with the availability, accessibility, and acceptability of MDA?
• What is the impact of an adapted and tailored intervention package on effective coverage?

To assess the specificity of diagnostic tools in Loa co-endemic areas and to conduct a prospective assessment of the impact of ALB MDA and Vector control on malaria, LF and STH indicators.

The success of MDA programs requires effective planning, community engagement, and delivery by community drug distributors. This proposal seeks to assess barriers and facilitators of effective coverage. Using in depth interviews, focus group discussions, and surveys, they will investigate factors related to acceptance, availability, and accessibility of MDA from the perspectives of drug distributors, healthcare workers, community leaders, the NTD program, and community members. Using the findings from the formative phase, an intervention package will be developed and implemented during MDA, followed by an evaluation of the impact of the intervention on coverage.

This project is part of a larger series of four studies that use a mixed methods approach to understand why particular districts that have undergone 5+ years of MDA are failing or are likely to fail transmission assessment surveys (TAS). Other studies include 169.1D Ghana, 169.2U Burkina Faso, and 177U Nepal. This study in Uttar Pradesh also provides a second opportunity to deploy the rapid ethnographic approach that will be first tested in Nepal. Team members from HERD Nepal will be traveling to India to train their team on the technique and assist with roll out.

This study builds on the methods developed for the operational studies ongoing in Ghana and Burkina Faso. The first two research questions are the same as those earlier studies with two new questions added here- question 3 on triple drug therapy (ivermectin, DEC, albendazole – IDA) and 4 on the use of a new rapid ethnography approach.

1. What factors are associated with effective (and lower) MDA coverage as defined as availability, accessibility, and acceptability in settings that have repeatedly failed Pre-TAS?
2. What is the impact of an adapted and tailored intervention package on achieving effective coverage?
3. What messages and community engagement approaches are needed to ensure the acceptability of IDA triple drug therapy in Nepal?
4. How does the rapid ethnography approach compare to more traditional qualitative analysis methods in terms of cost, timeliness, and ability to provide required information for programmatic decisions? Can local capacity for use of this approach be built rapidly?

Mapping LF-Loa Coendemicity

Mapping LF-Loa Coendemity

The success of MDA programs requires effective planning, community engagement, and delivery by community drug distributors. This proposal seeks to assess barriers and facilitators of effective coverage. Using in depth interviews, focus group discussions, and surveys, they will investigate factors related to acceptance, availability, and accessibility of MDA from the perspectives of drug distributors, healthcare workers, community leaders, the NTD program, and community members. Using the findings from the formative phase, an intervention package will be developed and implemented during MDA, followed by an evaluation of the impact of the intervention on coverage.

This project is part of a larger series of four studies that use a mixed methods approach to understand why particular districts that have undergone 5+ years of MDA are failing or are likely to fail transmission assessment surveys (TAS). Other studies include 169.1D Ghana, 169.2U Burkina Faso, and 177U Nepal. This study in Uttar Pradesh also provides a second opportunity to deploy the rapid ethnographic approach that will be first tested in Nepal. Team members from HERD Nepal will be traveling to India to train their team on the technique and assist with roll out.

Monitor recrudescence of STH after TAS to improve planning of STH programs and more effective use of STH drugs.

To sustain the gains of active community drug distributors (CDDs) by enhancing their performance through intervention at the individual, community and primary health care center levels to reach NTD elimination and control goals.

• To define a cost-effective and accurate method to map ivermectin-naïve districts for Onchocerciasis, Lymphatic Filariasis and Loiasis and identify districts eligible for safe treatment with ivermectin MDA.
• To validate a statistical model of Loiasis prevalence and intensity by comparing the model results to data from a prevalence assessment.

Determine whether doxycycline treatment daily for 6 weeks improves clinical outcomes (swelling, acute attacks) in lymphedema patients.

Determine whether doxycycline treatment daily for 6 weeks improves clinical outcomes (swelling, acute attacks) in lymphedema patients.

To compare antigenemia results by ICT and FTS RDT, antibody responses to Wb123 and Ov 16 by ELISA , and Wb123/Ov16 Biplex RDT on LF sentinel sites.

Determine whether doxycycline treatment daily for 6 weeks improves clinical outcomes (swelling, acute attacks) in lymphedema patients.

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 Tanzania 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. Because the EU is also endemic for onchocerciasis, the new Ov16 monoplex RDT was used in the field. The Wb123 and Ov16 antibodies were assessed via ELISA in the NIMR lab in Tanga and the results will soon be compiled.  Xenomonitoring work to assess Culex and Anopheles mosquitoes, as well as black flies, 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.

Monitor recrudescence of STH after TAS to improve planning of STH programs and more effective use of STH drugs.

Determine age-specific prevalence of LF Antibody following MDA to inform surveillance strategies.

To compare the performance of antigen (FTS) and antibody (Wb123 monoplex) tools in programmatic settings (TAS).

Preliminary Findings and Lessons Learned

The goal of this study is to compare the performance of antigen (FTS) and antibody (Wb123 monoplex, Wb123 ELISA, multiplex) tools in programmatic settings (TAS). In order to strengthen the existing TAS platform we need to better understand which diagnostic indicator(s) are best-suited for making programmatic decisions. The TAS was conducted in Trou de Nord and Plaisance EUs.  Both EUs passed the TAS, but positive FTS were identified (4 and 2, respectively). However the Wb123 RDT found ZERO positive children, of the over 2000 tested. While the Wb123 ELISA testing is still ongoing, this initial result agrees with findings from other studies, all of which suggest that the Wb123 RDT is too insensitive a tool to be of programmatic use.

• To use the Supervisor's Coverage Tool (SCT) to monitor school-based deworming;
• To determine the feasibility of utilizing the Lot Quality Assurance Sampling (LQAS) methodology in a school-based SCT; and 
• To apply a checklist in schools to elicit information about the performance of the MDA.

While the Supervisor’s Coverage Tool (SCT), a rapid in-process monitoring tool for improving mass drug administration (MDA) coverage, has been approved by WHO for use in communities, questions still remain about its utility for school-based sampling. As a result, the SCT was implemented in 20 randomly selected schools in each of six sub-counties (used as Supervision Areas) in three Kenyan counties in March 2017. A total of 120 students were selected and interviewed. 

Findings and lessons learned:

• The coverage for albendazole was classified as “good”, meaning above the WHO threshold, in 5 of the 6 SAs; however, only 1 SA was classified as having “good” coverage for praziquantel. In 3 of the 6 SAs, the Praziquantel coverage was classified as “inadequate”, including an SA that did not receive a supply of praziquantel to distribute.
• The most common reasons for not swallowing the drugs were students’ absences and drugs being out of stock or expired. The most common reasons for refusing intake of praziquantel were fear of side effects and religious beliefs, including misinformation coming from teachers to students about beliefs that albendazole was safe for all children, whereas praziquantel was dangerous and only reserved for sick children.
• Some of the challenges during the SCT activity were schools that operated half day, schools that had ongoing examinations, and unforeseen closure of a school on the day of SCT implementation, which made the random selection of students difficult. In addition, when an absent student or a student over 15 years of age (ineligible due to age range) was selected, it resulted in a loss of time since the selection needed to be repeated. Class interruptions to conduct the study were also not welcomed by some schools.
• While implementing the SCT in schools seems efficient compared to community SCT implementation, it is important to make sure that enrolment registers are accurate. Often, teachers at the schools with incomplete registers do not want to be held accountable.
• The cost of the SCT could be greatly reduced by implementing it in a shorter time period of three days instead of five, and with a pair of individuals per SA instead of four. The SCT can easily be integrated into routine supervisory activities as part of the MDA, and it can be conducted immediately after the MDA. It is a feasible activity that should be considered for widespread adoption. 

Cambodia has been validated for eliminating LF since 2016 and for eliminating both measles and maternal and neonatal tetanus since 2015. These are tremendous achievements; however, recent drops in coverage for vaccine preventable diseases threatens some these gains and there is a need to conduct surveillance to ensure that gains are sustained and that there is no recrudescence in the high risk areas. Integrated serosurveillance in Cambodia would provide substantial cost savings over disease-specific surveys, is logistically easier, and is less disruptive for communities. Serosurveys can provide rich information on exposure patterns for NTDs as well as a measure of population-level immunity to VPDs (and hence may serve as a validation of coverage). In this study, the team in Cambodia will revisit 2 historically high risk provinces in the north. This study builds on the work of a 2012 national serosurvey, which found that this northern region had the highest LF antibody response and is consequently considered to be at highest risk for re-emergence of LF. This study will be an integrated assessment of tetanus and other VPDs (measles, rubella, diphtheria), as well as malaria.

Is there still LF transmission after successful TAS 3?

1. To evaluate strategies for the elimination of trachoma by evaluating potential makers that show interruption of transmission of C. trachomatis
2. To determine the prevalence of ocular chlamydial infection among children aged 1 – 9 years old in Mpwapwa and Kalambo District, Tanzania
3. To determine the associated risk factors of ocular Chlamydia infection among children aged 1 – 9 years old in Mpwapwa and Kalambo District, Tanzania
4. To determine the usability of antibody test to detect Chlamydia antigen pgp3 using lateral flow assay
5. To examine the longevity of the antibody response to trachoma antigens in a high and low-prevalence setting

To improve compliance and reduce the coverage-compliance gap in mass drug administration through enhanced and tailored social mobilization.

To determine if a standardized multi-parallel-PCR assay is a more sensitive diagnostic tool for detecting Hookworm (Ancylostoma duodenale and Necator americanus), Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, and Schistosoma mansoni prevalence compared to the Kato-Katz stool test.

The primary objective for this request is to evaluate the performance of the Biplex RDT in a cohort of 500 people previously tested for oncho and LF in 2014 (3-year follow up). The evaluation of the Biplex is an add-on to a study that will conduct a longitudinal follow up on a cohort of 500 people from the Tshopo Province. The primary outcomes are serology and clinical manifestations of onchocerciasis, This study also evaluates serology, parasitology and clinical manifestations for other filarial infections, mainly LF, Loa and Mansonella.

Preliminary Findings and Lessons Learned

This study built on an existing onchocerciasis longitudinal follow-up study in Banalia community, Tshopo province, DRC. The location is co-endemic for Oncho, LF, Loa loa and Mansonella perstans.  500 people previously tested in 2014 have been followed up and were retested in 2017.   A total of 239, out of 500, agreed to participate in the follow-up activity and provided a blood specimen.  Thirty percent were positive by skin snip, 3% were positive by FTS, 15% were found to have loa (thick blood film) and 41% had M. perstans.  Ov16 ELISA testing found 67% positive, while the Biplex found 38% Ov16 positive. The sensitivity of the Ov16 biplex compared to the ELISA was 53%.

To develop models that can predict MF prevalence after a given number of rounds of MDA as a tool to identify program settings in which the response to MDA is less than predicted. 

To determine if there is evidence of ongoing transmission of lymphatic filariasis in Mindoro Oriental, following a TAS 2 failure.

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 Haiti 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 Culex mosquitoes will be conducted in the same sites as the human sampling. 

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.

How does the performance of the new Ov16/Ov3261 test strip compare to that of the SD Ov16 RDT and the SD Ov16 ELISA?

To identify the sampling strategy for positive case follow-up after TAS 2 and TAS 3 that optimizes the chances of correctly identifying evidence of ongoing transmission, while saving program resources.

To assess Onchocerciasis transmission in the districts previously called hypo-endemic or of unknown endemicity using a new more sensitive diagnostic and sampling strategy

To define a cost-effective strategy to map Ivermectin-naïve districts for Onchocerciasis, Lymphatic Filariasis, and Loiasis in the context of elimination of these NTDs

To define a cost-effective and accurate method to map ivermectin-naïve districts for Onchocerciasis, Lymphatic Filariasis and Loiasis and identify districts eligible for safe treatment with ivermectin MDA.

To analyze the relationships between the currently used indicator for impact assessments - prevalence of the clincial sign TF - and the prevalence of infection and antibody among 1-9 year old children in hyperendemic districts prior to mass drug administration

Field validation of the diagnostic performance of the Wb123/Ov16 biplex rapid diagnostic test and Wb123 ELISA, compared to the filariasis test strip (FTS) in a setting initially found to be non-endemic for lymphatic filariasis, in which clinical cases have been identified.

What is the indicator(s) and accompanying monitoring and evaluation (M&E) strategy that enables country programs to determine when the risk of ongoing transmission of LF has been reduced so that IDA can be stopped with little risk of resurgence of transmission?

One of important pillar of Trachoma elimination as a public health problem is to manage through epilation and surgery trachomatous trichiasis (TT) to reach in endemic district less than 0.1% of TT prevalence or less than 0.2% prevalence in adults of 15 years and older. However, surveys in 3 districts of Tanzania where numbers of TT surgeries were performed showed an unexpected higher prevalence despite intervention. This mixed methods study will help to address the main question as to why trachoma impact surveys demonstrating unexpectedly high TT prevalence in communities where TT surgical intervention is ongoing and how could this intervention/burden gap be addressed? The aim is to look at the case finding techniques effectiveness in all the communities and factors that affect TT referral and quality surgical services.

To assess the programmatic feasibility of and determine the most appropriate age group and sampling strategy for an oncho mapping survey for ivermectin-naïve areas

To determine the current status of LF using a combination of seroepidemiological tools to determine prevalence of circulating filarial antigen (CFA) and antifilarial antibodies.

Preliminary study findings:

• 2,976 individuals (age: 2 to 100 years) were tested for circulating filariail antigen using the immunochromatographic (ICT) test during daytime visits. Night-time blood samples to detect microfilariae (MF) were requested from those who tested positive via the ICT test.
• Out of the 38 persons found to be positive for LF infection by ICT test, 33 provided a night-time blood sample for examination of MF. Overall, nine individuals were found to be MF positive, with the highest prevalence in Ndau Island.
• The current study suggests that LF transmission may be absent in Taita-Taveta and Tana River counties in coastal Kenya and therefore transmission assessment surveys (TAS) should be considered with a view to stopping MDA. By contrast, evidence for ongoing transmission in Kwale, Kilifi and Lamu counties indicates the need for further MDA rounds in these counties.

• Additionally, the study demonstrated the feasibility of conducting integrated serosurveillance of several infectious diseases of public health interest, as well as levels of seroprotection against vaccine preventable diseases. The findings of the current study underscore the added value of using multiplex antibody measurements to guide and monitor LF elimination efforts.

Evaluate the current status of transmission of onchocerciasis in a hyperendemic area treated for many years and in a hypoendemic area treated for lymphatic filariasis for 5 years using the Ov16 ELISA and supplemented by entomology results from a previous study

• Can the micro-stratification of lymphatic filariasis (LF) transmission assessment surveys positive case and clinical case data be used to identify, map and monitor transmission hotspots as part of an enhanced endgame surveillance strategy?
• Can targeted molecular xenomonitoring detect ongoing transmission [to the same extent as human surveillance] in defined LF transmission hotspots?

Formative: What is the capacity of the Mozambican health system in general, and the NTD programme more specifically, to provide MMDP/DMDI services for people affected by leprosy, LF and konzo, and what are some of the barriers and facilitators to access these services?

Intervention: Which strategies are currently in place to provide quality healthcare for persons with disabilities, especially those that are caused by leprosy, LF and konzo, and how are MMDP/DMDI services organized vis-à-vis other disease control programs/health service delivery platforms?

How does the performance of the AP ELISA compare to the Ov16 SD ELISA, when conducted in a country lab?

Ascertain whether the difference in outcome (measured in rate of post-operative trachomatous trichiasis, or TT), between the posterior lamellar tarsal rotation (PLTR) and bilamellar tarsal rotation (BLTR) is sustained at four years or whether they give different results from what has been found at 1 year.

To assess the relationships between the prevalence of the clinical sign TF compared to prevalence of infection and antibody in Chikwawa and Mchinji districts

To refine the use of multi-parallel quantitative real-time PCR (qPCR) for STH parasites. Those parasites included in this proposal are Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis and Trichuris trichiura. Collect parasites of all five species in Argentina.

To determine if the circulating cathodic antigen (CCA) rapid diagnostic test is as effective as the Kato-Katz (KK) test in diagnosing S. guinensis

Comparison of different diagnostic tools during onchocerciasis mapping, including Ov16 ELISA, OV16 rapid diagnostic test (RDT) and skin snip test.

Analyze the relationships between the prevalence of the clinical sign follicular trachoma (TF) and the prevalence of infection and antibody to determine whether it may be appropriate to consider one or more alternative indicators for deciding whether trachoma programs can stop MDA.

To compare the performance of the diagnostic tools currently available for O. volvulus in terms of their relative sensitivity, species-specificity and practical use by countries.  Comparison of the utility of these tools for mapping and surveillance in settings with different levels of endemicity for onchocerciasis (Oncho), lymphatic filariasis (LF) and/or loiasis.

Comparison of ICT and FTS.

Determine the best data-capture system and implementation model to overcome data flow challenges faced by national MDA programs. Test and compare the effectiveness of 4 different data-tracking platforms currently in use (or development) in NTD endemic countries: 1) Build on existing national capacity, 2) Cloud-based SMS system, 3) Robo-call platform.

To pilot a strategy for mapping and treating Onchocerciasis and Lymphatic Filariasis in Loa loa co-endemic areas.

Determine the Schistosoma prevalence in the Mekong River Basin on the border of Laos and Cambodia

To use DHS data from 40 countries to examine the extent to which deworming of children 1-4 years is associated with: 1) a range of individual- and family-related socioeconomic indicators, including wealth quintile and maternal education; and 2) access to health systems that could provide opportunities for deworming, independent of family-level socioeconomic status.

Formative: To what extent do individuals have quality of life and access to and utilize MMDP services within the healthcare system; and what are the barriers and facilitators (affordability, availability, approachability, acceptability, and appropriateness) of 1) access to and utilization of quality MMDP healthcare services and 2) management of morbidities at home?

Intervention: What is the effect of an integrated health system approach on access to MMDP healthcare services as measured by affordability, accessibility, acceptability, and availability; and on utilization of services and quality of life?

What is the indicator(s) and accompanying M&E strategy that enables country programs to determine when the risk of ongoing transmission of LF has been reduced so that IDA can be stopped with little risk of resurgence of transmission?

Would the same programmatic decisions for Oncho Elimination Mapping be made based off of the Ov16 RDT results as compared to the Ov16 SD ELISA results in 7 woredas included in OEM in Ethiopia?

To validate the reported coverage of the 2018 mass drug administration in American Samoa in order to assess the impact of triple drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) for lymphatic filariasis  on infection prevalence

Is the multiparallel quantitative polymerase chain reaction technique superior to Kato-Katz microscopy in assessing the intensity and prevalence of soil-transmitted helminth infections in stool?

Preliminary Findings and Lessons Learned

• qPCR was more sensitive than Kato-Katz at detecting Ascaris, Trichuris, and hookworm infections in child fecal samples.
• Very few samples were helminth positive by Kato-Katz microscopy that were not also positive by qPCR, suggesting minimal human classification error during microscopy.
• Duplicate qPCR analysis on ~10% of samples by two separate labs (Smith and KEMRI) showed excellent concordance (97-100% agreement for each helminth species).

• A reanalysis of the effect of a combined water, sanitation, and hand washing (WASH) intervention on child helminth infections with qPCR data compared to Kato-Katz data gave very similar results.

What is the most appropriate method to evaluate the presence of W. bancrofti transmission in urban conurbations to establish if MDA is necessary for LF elimination?

Can a biometric recognition system, in the context of “Test and Treat”, facilitate individual follow-up by linking participant data at different time-points?

Pilot a strategy for mapping and treating Onchocerciasis and Lymphatic Filariasis in Loa loa coendemic areas

Coverage Evaluation Survey

Is coverage, or a combination of coverage and systematic non-compliance, more effective than a diagnostic tool at predicting when it is safe to stop triple drug therapy?

Supervisor's Coverage Tool

Is the use of the SCT during IDA feasible to implement at the sub-county scale and does it lead to increased coverage?

To assess the programmatic feasibility of and determine the most appropriate age group and sample strategy for an onchocerciasis mapping survey for ivermectin-naïve areas.

How do we motivate community drug distributors (CDDs)?

To evaluate the utility of ongoing surveillance of adults in a post-treatment setting.

To determine if post-treatment surveillance of adults represents a more effective surveillance strategy than TAS or xenomonitoring.

Sample Size: 6,024 DBS and 2,854 anopheline mosquitoes

To determine the feasibility of the use of entomological traps by community members for onchocerciasis and lymphatic filariasis entomological assessments.

Defining what are the appropriate tools to map LF in Loa endemic areas. Identifying if there is a Loa infection threshold that triggers the cross-reactivity in the ICT cards.

To evaluate 3D photographs of trachomatous trichiasis (TT) in the training and assessment of trachoma graders.

Primary Objective: To evaluate and develop MMDP services in Nigeria to be responsive to patient and provider perspectives using community based participatory research approaches in a participatory action research cycle

Formative research question: To what extent are the support needs of people affected by NTDs being met?

Intervention research question: How can new programme strategies be adapted to meet outstanding need?

Currently MDA is stopped when TF in children aged 1-9 years is below 5%. However, the relationship between TF, presence of infection and antibody has not been studied in a sufficient number of settings to enable predictions of outcome to be confidently made based on baseline prevalence, intervention coverage, and the prevalence of disease and infection at the time of impact survey. There are several districts in Malawi with TF prevalence between 5 and 9.9% which are eligible for one year of interventions, including a single round of MDA. This study will add important data to be used to model outcomes of interventions conducted by trachoma elimination programs, and in particular, help develop operational guidelines for stopping MDA.

Would the same programmatic decisions for Oncho Elimination Mapping be made based off of the Ov16 rapid diagnostic test results as compared to the Ov16 SD ELISA results?

To study the feasibility of LF and Oncho (Filariases) integrated transmission assessment survey (iTAS)  according to both LF and Onchocerciasis  WHO elimination guidelines

To determine the viability of utilizing the polio program’s Vaccination Tracking System (VTS) to generate more accurate population, drug requirement and coverage estimates in NTD programs

To compare results from Brugia Rapid tests (in 3 districts) and FTS (in 2 districts) with Wb123 rapid tests and Wb123 and Bm14 ELISA testing.

Preliminary Findings

• In March and April 2017, NIMPE had organized teams to go to the field to collect samples. In Duy Tien district, all of 20 primary schools were visited and 320 pupils were tested. In Quang Ninh district, all of 21 primary schools were visited and 323 students participated in the survey. In Le Thuy district, 35 of 38 primary schools were visited and 344 pupils had blood samples taken. 

• In total, 987 serum samples were collected but one sample was ran out of serum after doing quick tests (Brugia rapid and FTS). Finally, 986 samples were collected for the antibodies test. The serum samples were kept in frieze (-20 0 C) until analysis. Base on the cut–off 0.096 that was calculated by CDC, no positive case was found by this technique.

• Wb123 testing was applied in all three districts to detect W. bancrofti antibody. All 986 samples were tested, but no positive case was found. This result did not indicate that the Wb123 testing accuracy is equivalent to FTS but did show that no cross action with B. malayi and other parasites was found within the study. 

• All 986 serum samples that collected from the three districts in the Mini TAS were tested by Bm14 to detect B.malayi antibody. No positive case was recorded and this result was comparable to the result from Brugia rapid test.

• Following these data, the researchers supposed that the ELISA testing could be comparable to the quick testing with regards to accuracy. However, since no positive case was found and we could not conclude about the sensitivity and the specificity of the test. Therefore, a further study should be continued especially in endemic areas in which possibly can find some positive cases for assessment and conclusion.

To investigate the presence and epidemiology of Schistosoma hybrids in Nigeria. The acquisition of new genes through hybridization may generate new phenotypes that might differ in virulence, drug resistance, pathology, and host use, ultimately leading to the emergence of new diseases. Hybrids can develop into a new emerging pathogen, necessitating new control strategies in zones where both parental species overlap, an intense and rapid control response is required to minimize further spread of the hybrid and possible escalation of human schistosomiasis.

Can a mobile reader be used to standardize the reading of rapid diagnostic tests (RDTs)?

What are the differences at 1 year post-baseline in the prevalence of trachoma and Ct infection in villages randomized to an enhanced antibiotic treatment regimen characterized by a routine community-wide MDA followed by two rounds of treatment targeted to children 6 months to 9 years in quick succession (1-2 weeks apart) compared to villages randomized to annual standard-of-care community-wide MDA?

To assess if introducing point-of-care Circulating Cathodic Antigen rapid test to community health workers will increase access, compliance and coverage to treatment among adult individuals at Kome Island in North-Western Tanzania, an area on the Lake Victoria highly endemic for schistosomiasis

To assess the programmatic feasibility of and determine the most appropriate age group and sampling strategy for an oncho mapping survey for ivermectin-naïve areas

To investigate the utility of an antibody test as a tool for surveillance during the elimination phase of trachoma programmes

Test STH-TAS.

Complete mapping of NTDs in AFRO. Support transitioning of new diagnostics tools into program use. (Refer to 23.1, 23.2, 23.3, 23.4, 23.5, 23.6, 23.7, 23.8, 23.9, 23.10.)

To assess if transmission assessment surveys (TAS) for lymphatic filariasis (LF) are a feasible platform to integrate transmission assessment for onchocerciasis, using the same age group (6-7 years old) and the same prevalence threshold (<2%) that the LF programs utilize.

1. To perform the TAS for stopping LF MDA and use it as platform for Oncho impact assessment. 
2. To assess the level of endemicity of Oncho following at least five rounds of MDA in hypo, meso and hyper endemic districts. 
3. To study the performance of the Wb123/Ov16 Biplex rapid diagnostic test (RDT) to assess Oncho and LF transmission interruption.

Determine whether school-based TAS results in the same programmatic conclusion as a community-based TAS in EUs where school attendance is poor.

Preliminary Findings and Lessons Learned

This USAID project represents an innovative approach to resolve critical questions about the performance of the TAS and in particular, the question of how important 75% school attendance is to a valid TAS result.  At its core, this study addresses the concern that LF (specifically antigenemia) could be associated with school attendance, which leads to the programmatic research question: does a school-based TAS result in the same programmatic conclusion as a community-based TAS in EUs where school attendance is poor? This study will lead to a better understanding of the validity of the TAS in programmatic settings where school attendance and/or reporting of school enrollment may be poor.  It will also generate important results for the Haitian program that is looking to the TAS for guidance on stopping MDA in several EUs. The school- and community-based TAS were both conducted in a commune considered to be highly endemic (‘zone rouge’) at baseline.  Both surveys passed the TAS, with only 1 ICT positive child identified in the school TAS and 4 ICT-positive children in the community-based TAS.  The conclusion is that there appears to be no meaningful difference between school- and community-based TAS for stopping MDA decisions, even where school attendance is poor. This is the third LFSC/NTDSC study to return a null result -- perhaps it can now be considered a "non-issue" for LF.

To identify antigens that can be produced as recombinant proteins and to document elimination of schistosomiasis.

To identify antigens that differentiate between infections with Schistosoma mansoni and Schistosoma haematobium and that can be used in an ELISA, lateral flow assay or multiplex format.

To validate the Brugia antibody tests as a tool for stopping LF MDA.

Non-inferiority study comparing a 20mg/kg dosing strategy of azithromycin to a 30mg/kg dosing strategy in the treatment of yaws 

To validate thresholds for stopping MDA and improve confidence that elimination goals have been achieved through post-MDA surveillance.

Determine the utility of xenomonitoring and serological assessments for the detection of residual transmission

To test alternative rapid diagnostic test (RDT) formats for the Wb123 rapid test. In field trials, the current test format was less sensitive that FTS in post-MDA settings whereas alternative Wb123 test formats (ELISA, multiplex) were more sensitive. Our group uses new detection systems, based on nanoshells, to improve RDT performance. 

Determine whether current or historic C. trachomatis (Ct) infection can be detected, and whether it is associated with clinical signs of ‘trachomatous inflammation – follicular’ (TF) in Vanuatu and Kiribati

Determine the utility of infection testing as a tool for operational surveillance and impact assessment in trachoma-endemic environments.

To improve STH detection by developing a reliable and easy to perform molecular diagnostic test for epidemiological surveillance and post-elimination monitoring of STH

To increase onchocerciasis treatment coverage and to optimize service delivery through community mobilization, disease sensitization, training and strengthening of community health extension workers (CHEW), and community control advocates

In March 2016, the Republic of Togo submitted an application for validation of the elimination of LF as a public health problem. However, healthcare facility managers in some health regions – especially in the Savanes Region, have reported the presence of migrant groups from neighboring countries which are still endemic to LF – i.e. Ghana, Burkina Faso, Nigeria. Migrants arrive and reside temporarily but recurrently in some localities of these regions. They constitute hotspots that can be source of resurgence, mainly because the nationwide passive surveillance has been stopped in 2016. 

In order to track all population movements that constitute a potential risk to the Republic of Togo, the country proposes to set up a strategy for the identification of these groups, with the contribution of Neglected Tropical Disease (NTD) Focal Points, followed by the research of potential parasite carriers. Isolated cases discovered will be investigated in order to track all imported W. bancrofti. They will be treated, but if an effective hotspot is discovered, rounds of Albendazole and Ivermectin MDA will be implemented a follow up of infected individuals will be maintained. 

The purpose of this study is to contribute maintaining the end of LF transmission across the country.

To field-test the Pgp3 lateral flow assay to compare data obtained in the field on the rapid test to that from DBS collected from the same individual tested on the Pgp3 multiplex bead array.

To compare the feasibility and programmatic implications of employing the Supervisor's Coverage Tool in schools vs. communities to monitor a school-based MDA.

The Supervisor’s Coverage Tool (SCT) is a rapid in-process monitoring tool for improving mass drug administration (MDA) coverage that has been approved by WHO for use in communities.  However, questions remain as to whether it may also serve as a useful tool when implemented in schools.  To answer this question, a direct comparison of school- vs. community-based SCT implementation was conducted in 13 Supervision Areas (SAs) in 7 Local Government Areas (LGAs), in 3 states in Nigeria.  Within each SA, one SCT was conducted in the school and an independent SCT was conducted in a village within the catchment area of the same school. The SCTs were all monitoring the coverage for the same school-based MDA for praziquantel and mebendazole. The goal was to understand how the information learned through the SCT would vary based on the two different sampling frames. 

Findings and lessons learned:

-          The SCT helped find targeted schools for which a mass drug administration (MDA) was planned but were missed. Several unregistered (illegal) schools were missed as their existence was not known, therefore they were not targeted and included in the MDA; however, upon identification of these schools through the SCT, the schools were reached during mop-up and added to the database for future MDAs.

-          An existing school feeding program increased students’ praziquantel intake in all northern Nigeria schools that were visited.

-          In two SAs, school SCT results showed good coverage; however, the actual reported school coverage was below the recommended threshold. The discrepancy was due to a great number of student absences because of farming activities or drop outs after enrolment. Since any selected student who is absent is skipped by the SCT and a new student is selected in their place, the resulting coverage classification could be an inflation of the true coverage.

-          Surveyors preferred SCT implementation in schools vs. community because household enumeration can be time-consuming.

-          When SCT results from the school and the village were directly compared for the same population, the community-based SCT always resulted in an equal or lower classification of coverage, likely because community-based SCTs include the entire target population in the sampling frame, as opposed to being limited to school-attending children.

Mass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including Bangladesh. Post-treatment surveillance activities as recommended by WHO include repeated transmission assessment surveys (TAS) among children and ongoing surveillance to detect new foci of transmission and collect data on infection trends in the general population. The contribution of molecular xenomonitoring (MX, or detection of filarial DNA in mosquitoes) to confirm the interruption of transmission during the post-treatment surveillance phase has not been well defined. There is also a need to better understand the relationship between the prevalence of W. bancrofti DNA in mosquitoes and infection in humans.

To determine the feasibility and best practices of using the Supervisor's Coverage Tool to monitor community and school-based distribution and integrated MDA.

The Supervisor’s Coverage Tool (SCT) is a rapid, simple, and inexpensive tool designed for use in Neglected Tropical Diseases (NTD) programs mass drug administration (MDA) to monitor drug coverage and compliance, to supervise community drug distributors (CDD), and to identify areas that may need mop-up. After successfully piloting the SCT in Ethiopia and Nigeria in 2015, additional testing of the tool was suggested to assess the feasibility of the tool in different regions and new settings. Therefore, the SCT was implemented in the Philippines in July 2016.

After the completion of training, the field work was conducted in two provinces, in six Supervision Areas (SA) consisting of one or more puroks (subdivisions) per barangay (village). Two survey populations were represented in the SCT implementation covering a community-based distribution for Lymphatic Filariasis (LF), excluding children aged 5-18 years and a school-based distribution for LF for all children aged 5-18 years. 

Findings and lessons learned:

• The most common reasons for not swallowing drugs were fear of side effects, not feeling well, forgetting, being too busy, and the taste of the medicine.
• When an accurate register of all the households in the SA exists, it is possible to complete the SCT in each SA in less than a day because the registers greatly aid the random selection process.
• Implementing the SCT during the last week or two of the MDA was advantageous as it enabled the program to implement the action plan to improve the current MDA using the personnel, budget, and infrastructure that was already in place for the MDA.
• It is important to consider whether or not Community Drug Distributors (CDD) should accompany the SCT teams during interviews, as their presence may influence the answers of the respondents.
• It is strongly recommended that when possible, CDDs use directly observed treatment (DOT). If DOT is not possible, CDDs should remind participants that there is no advantage in delaying swallowing the drugs, and that it is actually better when everyone swallows the drugs at the same time.
• Overall, the Philippines SCT pilot was a success, as it was the first time it was implemented in the Western Pacific region, and it was also used to monitor multiple distributions (both school- and community-based). 

To determine the feasibility of the use of entomological traps by community members for onchocerciasis and lymphatic filariasis entomological assessments.

To compare skin snip microfiladermia with antibody responses against Ov16 antigen in general population in epidemiological assessments post CDTi.

The purpose of this project is to create maps that utilize LF risk and prevalence data to predict risk of recrudescence, and to stratify this risk into 3-4 distinct groups. Such maps could subsequently be used to design and simulate the performance of different surveillance strategies. 

Preliminary study findings:

• The intensity of transmission was quantified by the basic reproductive number (R0).

• A map of predicted prevalence of microfilaraemia, developed through Bayesian geostatistical modelling, was linked to mathematical models of the transmission dynamics of lymphatic filariasis.

• The models predict a marked geographical heterogeneity in the intensity of lymphatic filariasis transmission in Sub-Saharan Africa.

• Further control efforts may be required in areas of higher intensity of transmission.

• Conversely, interruption of transmission might be achieved earlier in areas of low intensity of transmission.

• The results suggest that intensity of transmission at baseline (R0) and bednet use are the best indicators for the level of surveillance required sub-nationally post-MDA.

The purpose of this study is to analyze the relationships among clinical signs (follicular trachoma) and the prevalence of infection and antibody and to determine whether it may be appropriate to consider one or more alternative indicators for deciding whether trachoma programs can stop MDA.

Assess the performance of LF and Oncho diagnostic tools after stopping LF MDA but continuing Oncho MDA.

To implement a new re-mapping strategy for LF in low-prevalence areas.

To compare TAS-STH vs. a standalone STH survey in 5 schools surveying 250 kids. TAS-STH Community study will have 6-7 year olds while the STH survey focuses on 10-14 year olds.

To complete mapping of NTDs in AFRO and support transitioning of new diagnostics tools into program use.

To validate a new TAS-STH survery in a complex progammatic setting.

Test STH-TAS

How does the 3rd generation LoaScope perform when deployed in the field? Can it be validated for use in operational research and programmatic activities?

What is the indicator(s) and accompanying M&E strategy that enables country programs to determine when the risk of ongoing transmission of lymphatic filariasis (LF) has been reduced so that triple drug therapy with ivermectin, diethylcarbamazine, and albendazoe (IDA) can be stopped with little risk of resurgence of transmission?
To develop an M&E strategy that enables Samoa’s LF elimination program to determine when the risk of ongoing transmission of LF has been reduced so that IDA can be stopped with little risk of resurgence of transmission
What is the effectiveness of appropriately dosed IDA in clearing Mf from Mf positive people who (i) reported taking IDA in August 2018, and (ii) did not report recently taking IDA?

To determine non-inferiority of novel onchocerciasis diagnostics compared to the SD Bioline Ov16 rapid diagnostic test (RDT) on dried blood spots (DBS) and to one another using skin snip PCR as a gold standard measure.

To assess feasibility and ease of use of the GADx Oncho test and DDTD multi-antigen test at point of care in a field setting.

To determine non-inferiority of novel onchocerciasis diagnostics compared to the SD Bioline Ov16 rapid diagnostic test (RDT) on dried blood spots (DBS) and to one another using skin snip PCR as a gold standard measure.

To assess feasibility and ease of use of the GADx Oncho test and DDTD multi-antigen test at point of care in a field setting.

Will the performance of QFAT in detecting circulating filarial antigen of Wuchereria bancrofti be useful for program decision-making in comparison to FTS?

1. What will be the feasibility and ease of use of QFAT in field settings?
2. What will be the rate of invalid or indeterminate results of QFAT in comparison to FTS in field settings?
3. Will there be any cross reactivity of QFAT with B. malayi microfilarae positive individuals?

Can geospatial statistical tools identify “zones of concern” that have repeated/on-going above-threshold prevalence of trachomatous inflammation—follicular (TF) in children aged 1–9 years (TF1–9) over multiple surveys, which may warrant further survey or operational research activities within EUs and between EUs (within and between countries/border areas)?

In EUs that have had above-threshold prevalence in one or more Trachoma Impact Survey (TIS) and/or Trachoma Surveillance Survey (TSS), could this have been predicted based on the spatial distribution of cases at baseline and/or TIS and the distribution of geospatial covariates?

How can we improve the process and accuracy of trachoma prevalence estimation using model-based geostatistical methods?

How to develop a web-based user-friendly interface for trachoma prevalence prediction and be integrated into the Tropical Data service?

How is the sensitivity of Brugia Test Plus in endemic area?