Bill & Melinda Gates Foundation

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?

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.

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.

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

• 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?

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

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?

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

To assess community readiness to participate in LF activities (surveys, social mobilisation, MDA and evaluations) in the context of COVID-19 in Kenya.

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.

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

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

Are NTD programs in Anambra State, Nigeria, adopting and implementing prevention measures for COVID-19 in their drug delivery activities? What adaptations are required by staff and volunteers to adopt these measures? What are the barriers to doing so? What are the incremental costs associated with conducting MDA during a global pandemic?

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.

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 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.

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.

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.

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

Develop genetic markers for S. haematobium

SCORE Data Collection on Mobile Devises

The purpose of this study is to determine differences between cure rates vs re-infection levels.  The fundamental question is to see what the prevalence and intensity are before MDA, and then, see what those are 7 to 8 weeks after MDA.  Since there are villages that continue to have high prevalence from year to year, we will determine if this primarily represents reinfection occurring since the last annual MDA or if it is related more to treatment efficacy.

A selected number of 5 villages near Lake Victoria shown to maintain very high levels of infection with S. mansoni following at least three rounds of annual praziquantel chemotherapy will be compared with 5 villages where infection rates have been much more responsive to similar levels of treatment, with respect to the following general considerations and questions:

1) What is the general situation for each village with respect to proximity of water bodies where intensive human contact occurs?

2) For each village, what is the role of each major habitat in transmission, as assessed by three separate techniques: water filtration; use of sentinel mice; and standard snail survey techniques?                                                                                                                                                                                                                                                                    

Develop a mobile reader application for use at the point-of care for the POC-CCA assay used for mapping and surveillance of Schistosoma mansoni. The reader apk will provide results consistent with the visual human reading of the test. Distinguishing intensity bands and reading 'Trace' results can be problematic and leads commonly to 'false positive' readings. The apk being developed will utilize a testing algorithm to better distinguish between true positive and false positive "Trace" test results. 

POC/CCA tool ongoing studies: Use of testing standards; reader differences; ‘Trace’ result analyses

What is the the impact of riverine prawns on infections in humans? Studies are to be conducted on interrupting seasonal transmission of Schistosomiasis and ecologic assessment of riverine prawns on infections in humans.

Human Diagnostics Tool Development (CAA diagnostic tool)

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

Cost Studies in SCORE Gaining and Sustaining

Schistosome Population Genetics in Gaining Control Studies in Niger (Sh) and Tanzania (Sm)

Screening Tool POC/CCA: PCR comparative studies

Part of gaining control studies

The demonstration study of the SD BIOLINE Onchocerciasis IgG4 rapid test aims to provide operational research data on the use and implementation of the test. The performance of the SD BIOLINE Onchocerciasis IgG4 rapid test has been verified in both reference laboratories as well as in controlled field settings. PATH and partners will explore the feasibility of incorporating the test into multiple sites in sub-Saharan Africa, with Senegal as a pilot country.

 We aim to demonstrate the acceptability and feasibility of the SD BIOLINE Onchocerciasis IgG4 test in the Senegal Onchocerciasis Control Programme surveillance activities relative to the diagnostic and collection tools currently used. 

This is a cross-reactivity evaluation of rapid tests detecting Wb123 antibodies. The test should perform similarly in sub-populations of individuals who are positive and negative for other filarial diseases, most importantly Loa loa. This field evaluation will determine the specificity of the tests in two separate populations, those positive and negative for Loa loa, and will be used to inform the product design and the product insert. This evaluation will recruit adults and children from regions that are known to have Loa loa in Cameroon.

 The study’s principal objective is to determine test specificity in individuals who are positive and negative for the filarial worm Loa loa. Secondary objectives are to determine the test specificity in individuals who are positive and negative for Mansonella perstans, and identify failure modes and failure rates of the rapid tests under surveillance conditions.

This is a cross-reactivity evaluation of rapid tests detecting Wb123 antibodies. The test should perform similarly in sub-populations of individuals who are positive and negative for other filarial diseases, most importantly Loa loa. This field evaluation will determine the specificity of the tests in two separate populations, those positive and negative for Loa loa, and will be used to inform the product design and the product insert. This evaluation will recruit adults and children from regions that are known to have Loa loa in Cameroon.

The study’s principal objective is to determine test specificity in individuals who are positive and negative for the filarial worm Loa loa. Secondary objectives are to determine the test specificity in individuals who are positive and negative for Mansonella perstans, and identify failure modes and failure rates of the rapid tests under surveillance conditions.

Determine Co-Endemicity of Lymphatic Filariasis and Loiais in the Republic of Congo

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.

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.

Comparison of different diagnostic tools during onchocerciasis, lymphatic filariasis and Loa loa mapping and epidemiological assessments, including Ov16 ELISA, OV16 rapid diagnostic test (RDT) and skin snip test. (Refer to 065.1, 065.2, 065.3, 65.6 & 65.7.)

• 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.

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 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.

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.

Demonstrate the utility of a new mapping strategy based on school cluster random sampling Using PPES. A secondary objective is to assess the value of laboratory-based antibody assays as confirmatory tests and additional diagnostic tools for measuring LF transmission. 

Rigorous assessment of the efficacy of (multiple) doses with Praziquantel in the treatment of S. mansoni infections using standard and novel highly sensitive diagnostic tools.

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.

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. 

Comparison of 2X vs. 1X per year MDA on Brugia with MDA of DEC/Alb , plus STH evaluation

Comparison of safety profile and acceptability between triple drug therapy (IVM,DEC,ALB) and standard two-drug therapy (DEC, ALB), plus STH evaluation.

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

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.

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?

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

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

Literature review, meta-analyses; 3 RAPs published; one RAP white paper; see SCORE website http://score.uga.edu/projects/rapid-answers-project/

This study will include comparing 1) MDA as usual 2) double treatment with two closely-spaced MDAs (consistent with the recommendation based on mathematical models) 3) twice yearly MDA and 4) double MDA plus snail control.

Mapping of schistosomiasis (Sm)

Gaining Control: >25% Prevalence MDA strategies; and subtle morbidity of Cohort; Population genetics, and snail monitoring

MDA strategies: Sustaining control at 10 – 24% prevalence

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

Multi-lab comparison for STH PCR methods

Sustaining / Gaining Control with Single versus Double Treatment; and Population genetics, snail monitoring

(1) Is it possible to eliminate schistosomiasis as a public health problem on Unguja in three years and to interrupt transmission in five years? (2) Is it possible to control schistosomiasis throughout Pemba (prevalence <10%) in three years and to eliminate it as a public health problem in five years? (3) What are the costs, successful strategies, barriers, etc. associated with three different interventions (MDA, vector control, and behavior change)?

How do villages which do not show substantial decreases in the prevalence of schistosomiasis despite repeated, high coverage mass drug administration (persistent hot-spot villages) differ from villages which show substantial decrease in prevalence across various factors (declining prevalence villages)?

Is molecular detection of schistosome infection (patent and pre-patent) in snails a useful tool for program managers as prevalence and intensity of infection in people approaches very low levels?

Economic evaluation of SCORE projects with priority given to elimination studies

Will providing enhanced MDA at the community level while achieving treatment coverage of 75% or greater in children (5-17) and adults substantially decrease S. mansoni infection in previously identified persistent hot-spot communities?  

Determine the age prevalence of LF antibody following MDA to inform surveillance strategies. Yaws and trachoma testing will also occur during the survey.

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.

Late lead optimisation

Establish the best registered drug for deployment as a macrofilaricide alone and/or in combination with standard anti-filarial drugs.

Deliver at least one novel pre-clinical candidate capable of delivering a macrofilaricide treatment for onchocerciasis (and lymphatic filariasis) within a seven-day treatment period or less.

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.

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.

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)?

Improving effectiveness of vector control against Visceral Leishmaniasis

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.

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?

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

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 effectiveness of tiny target technology in controlling tsetse vectors for Human African Trypanomiasis

Follow-up LF TAS and comparison of ICT and Filariasis Strip Test in a post-MDA surveillance setting.

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

Comparison of 2X vs. 1X per year MDA, W. bancrofti with MDA of DEC/Alb, plus STH evaluation

Comparison of 2X vs. 1X per year MDA on W. bancrofti with MDA of IVM/Alb, plus STH evaluation (and Schistosoma in Foya only)

Community MDA with 2X Alb alone for W. bancrofti in areas co-endemic for L. loa, plus STH evaluation

Binax Now Filariasis Test vs. Alere Filariasis Test Strip Comparison

Randomized Clinical Trial comparing triple triple therapy of DEC/Alb/Iver vs. DEC/Alb alone

Randomized Clinical Trial of Albendazole vs Ivermectin+Albendazole for lymphatic filariasis treatment and elimination.

Randomized clinical trail comparing treatment with Albendazole and Ivermectin to Ivermectin alone for Onchocerciasis.

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.

To measure the feasibility of using a PPES sampling approach with segmentation within each EA to measure coverage. In addition to collecting data on coverage the team also used mobile devices to collect data on time and distance traveled as well as the availability of village registers. These data contribute to the larger coverage evaluation study taking place in multiple countries.

Preliminary 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 pilot a newly refined probability sampling with segmentation approach in 2 districts in Malawi.  The two surveys found that the survey coverage was above the WHO target thresholds for Zithromax. Furthermore, the team found the survey methodology to be clear and feasible to implement.  This adds further evidence to the previous studies that support the use of the segmentation approach for coverage surveys across all 5 PC NTDs.

This study is piloting the Supervisor's Coverage Tool (formerly the Coverage Supervision Tool, or CST) approach that is meant to provide a platform for district- and sub-district-level supervisors to monitor the success of the last MDA. It is meant to be conducted at the sub-district level two weeks following MDA and provides a pass/fail result regarding whether the target coverage threshold was met. It is designed as a quick and inexpensive in-process monitoring tool for use by sub-national level NTD management teams/supervisors to help improve or maintain the success of future MDA rounds.

The DeWorm3 Project is a series of hybrid trials testing the feasibility of interrupting the transmission of soil transmitted helminths (STH), while conducting implementation science research that contextualizes clinical research findings and provides guidance on opportunities to optimize delivery of STH interventions.

The purpose of DeWorm3 implementation science studies is to ensure rapid and efficient translation of evidence into practice. Research methods include: (1) stakeholder mapping and network analysis, (2) qualitative research, (3) structural readiness surveys, (4) process mapping, and (5) economic evaluation (costing and cost-effectiveness). 

 Implementation science research aims include:

1)To systematically identify stakeholders influencing standard of care targeted and community-wide MDA and map their potential role and involvement in scale-up of community-wide MDA for STH.

2)To identify implementation-related barriers and facilitators to community-wide MDA for STH from the perspective of various stakeholders.

3)To quantify the readiness of the health system to deliver community-wide MDA for STH programs.

4)To map the intervention delivery process and identify any discrepancies between planned and implemented activities in order to optimize the trial intervention.

5)To compare the financial and economic costs and incremental cost-effectiveness of community-wide and targeted MDA for STH in the short- and long-term.

Develop and validate sampling strategies for monitoring vector infection that would be useful to evaluate the success of LF-elimination programmes.

Findings and Lessons Learned:

This represents a follow-up to a longitudinal study with data collection in 2010 and 2012 (previous funding) and now with a third time point in 2015. At all 3 time points a rigorous mosquito sampling protocol was applied and the results were analyzed to detect filarial DNA by PCR. To test the reproducibility of the results, at each time point the survey teams conducted two independent, sequential samples of approximately 11,000 mosquitoes each. In addition to surveying the entire PHC area, a nested hotspot survey was conducted in areas where there has been historically high transmission. One very important outcome of this study is the development of a standardized protocol for sampling culex mosquitoes that is statistically rigorous and reproducible. The study showed that MX can be a valuable tool for monitoring decreasing prevalence over-time. The authors propose a threshold of 0.5% in culex be used to measure 0% Ag prevalence in children for stopping MDA.

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 

Assess Wb123 antibody responses in communities where LF transmission was interrupted without MDA.

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. 

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.

To pilot a rapid coverage supervision tool (now known as the Supervisor's Coverage Tool) that can be used to determine if the supervision areas under investigation are likely to have exceeded the WHO threshold for coverage and to serve as an in-process monitoring tool for supervising the MDA distribution. Report to WHO M&E working group; potential for inclusion in future WHO program assessment guidelines.

The Supervisor’s Coverage Tool (SCT) is a quick, simple, and inexpensive monitoring tool that can be used to assess preventive chemotherapy coverage of a mass drug administration (MDA). During the development and optimization process of the tool, the SCT was piloted in communities in Nigeria and Ethiopia. The pilot study in Cross River State, Nigeria, included seven first-level Supervision Areas (SA), which corresponded to villages in four Local Government Areas (LGAs). Drug coverage was assessed for ivermectin and albendazole in four SAs and only Ivermectin in three SAs. 

Findings and lessons learned:

-          The main reasons for not swallowing medicines were community drug distributor (CDD) not showing up, respondent being away at time of drug distribution or not collecting drug from a fixed point of distribution, fear of side effects, drug supply running out, recent migration, and lack of awareness about drug distribution.

-          The SCT permitted LGA coordinators to supervise the drug distribution systematically, which allowed them to find out that in most parts of one LGA treatment was suspended despite the CDD claiming the completion of treatment in the area.

-          Some treatment registers did not include all people living in the SA, therefore some households were not included in the CDDs treatment boundaries. On the other hand, some LGAs had very good treatment registers, proper documentation of treatment from CDDs, and their community also commended them during village gatherings expressing their gratitude.

-          All CDDs were making remarkable effort with little or no reward. Unlike previous monitoring visits where supervisors have to field numerous complaints around incentives, because the SCT gave supervisors an objective evaluation of their work, many CDDs did not feel justified in complaining about incentives.

-          Overall, the SCT was deemed feasible to implement at the supervisory area and the information generated led to programmatic action to improve treatment coverage.

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

POC/CCA screening/mapping tool initial Studies

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

Snail Control follow-up study of P. clarkii 20 years later

A comparison study of ICT cards and the new Filariasis Test Strip in Albay district, Philippines. Make recommendations for the new LF diagnostic test for the broader community.

Study Findings:

• A total of 60 primary schools were surveyed using ICT tests, while a total of 46 primary schools were surveyed using FTS. In some instances, additional blood was not collected for FTS due to parental refusal.

• Of the 2,944 children examined via ICT, 1 (0.034%) tested positive. No FTS was done on this child.

• Of the 1,885 children examined via FTS, 1 (0.05%) tested positive. That same child tested negative via ICT and via repeat FTS.

• FTS resulted in 57 invalid results due to: 1) test strips having no reaction, 2) detached sample pad on test strips, or 3) blood failing to travel upward after being absorbed by the test strips. In addition, some FTS foil pouches were empty.

• Wb123 antibody levels appear to be relatively low among younger age groups and increase with age.

• There was little observed change in antibody levels from Phase 1 (Oct 2014) to Phase 2 (Feb 2016).

The TUMIKIA Project aims to determine whether combining school- and community-based deworming is more effective at controling and eliminating soil-transmitted helminths (STH or intestinal worms) in Kenya than school-based deworming alone. 

The two-year trial will provide the drug albendazole to all residents from 150 communities in Kwale County, Kenya. There are three study groups:

1. Base: annual school-based deworming (ages 2-14)
2. Increased coverage: annual school- and community-based deworming (ages 2-99)
3. Increased coverage and frequency: bi-annual school- and community-based deworming (ages 2-99)

TUMIKIA stands for 'Tuangamize Minyoo Kenya Imarisha Afya,' which means “eradicate worms in Kenya to improve health,” in Swahili. 

Download the TUMIKIA Research Brief [pdf]

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.

The Starworms project aims to strengthen the monitoring and surveillance of drug efficacy and anthelmintic resistance in soil-transmitted helminth (STH) programs. As such, it will support deworming programs in their quest to eliminate STHs as a public health problem by 2020. The specific objectives are (1) to validate diagnostic tools to monitor drug efficacy and the spread of anthelmintic resistance, (2) to create a surveillance system that monitors the global patterns of drug efficacy and spread of anthelmintic resistance in STH programs, and (3) to develop supporting tools to plan, analyze and follow up on surveys on drug efficacy and the spread of anthelmintic resistance.

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.

Demonstrate the utility of a new mapping strategy based on school cluster random sampling Using PPES. A secondary objective is to assess the value of laboratory-based antibody assays as confirmatory tests and additional diagnostic tools for measuring LF transmission. 

Compare lymphatic filariasis FTS antigen prevalence to the Wb123 antibody prevalence in an area co-endemic with Loa-loa. Refine LF prevalence with FTS and provide evidence for MDA intervention by excluding areas where prevalence of ICT card is due to Loa loa cross reaction; 2) Provide additional data to address the influence of Loa loa cross-reaction and the specificity of antigen rapid test positive result alone to identify ongoing LF transmission in areas co-endemic for LF and Loiasis.

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.

The purpose of this study is to assess the feasibility of a community-based survey for measuring coverage of school-based MDA, specifically by looking at the reliability of child and parental recall for MDAs targeting soil-transmitted helminths.

Preliminary Findings and Lessons Learned:

There is currently little to no evidence on the reliability of young children at recalling whether or not they participated MDA. This issue is important because where MDA is school-based, parents may not be able to provide accurate proxy responses on behalf of their children. A study was conducted in Cambodia whereby gold standard registers of all children were created, based on school enrollment rosters. During the MDA outside observers (local to the region) recorder whether or not each child in the register received the drug. Then a month later the team went back and conducted a household survey and asked children to recall whether or not they participated in the MDA. The study was conducted according to the protocol. 600 children were followed up in the household survey, all of whom are enrolled in school and were listed on the gold standard register. Unfortunately there was some miscommunication and the site selected by the program team was one of the highest coverage sites in the country. While great for the Cambodian program, this means that the true coverage for the 600 individuals was 100%. All 600 children accurately recalled that they had participated in the MDA. With these results we are not able to assess recall. Of the parents who were surveyed, 97% correctly knew that their child had participated in MDA while 3% said that they did not know.

The result of greatest interest was the ability of the children to accurately identify which drug they took as part of the MDA. Children were shown 3 different drugs (Albendazole, Mebendazole and a decoy pill not available in the area). 15% of children and 5% of adults mistakenly believed the child had taken the decoy pill. This study did, however, gather interesting information on the frequency of unprogrammed deworming. 12% of parents (and 5% of children) said that the child had received some deworming medication outside of school. The majority of this came from health centers.

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

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 optimal sampling strategy for SCH impact assessments to enable sub-implementation unit decisions? 

To develop a loa algorithm that can predict the risk of a community having great than a set threshold value of individuals who have high intensity microfilaremia. 

Can geostatistical models leverage the wealth of well-characterized private and public sector data in Kenya to improve STH prevalence predictions, leading to better program decisions with minimal field cost?

Does greater program engagement and ownership lead to model adoption?

Can a rapid diagnostic test (RDT) for Loa loa antibodies be used successfully by field teams, in conjunction with the LoaScope, to map loaiasis and determine where it is safe to offer treatment for onchocerciasis? 

In principle, the Loa Antibody Rapid Test could be used to conduct rapid surveys to document that Loa prevalence in the surveyed community or district is below an agreed upon threshold, opening up areas to use the of MDA to eliminate onchocerciasis. This tool would complement the use of the Loascope to make treatment decisions. The antibody test would be used at the periphery of the Loa belt or in areas where Loa prevalence was thought to be low (based on previous RAPLOA or environmental factors) to carry out “confirmatory mapping.” The Loascope would be used to make treatment decisions at the community level using the Diggle model or to guide individual treatment decisions based on the TNT strategy. To design a confirmatory mapping survey for Loa based on antibody testing, a number of key scientific questions must be answered: 1) What is the relationship between community Loa prevalence as assessed by the Loascope and Loa rapid antibody test?

How is the epidemiological distribution of Schistosoma haematobium in school aged children (5 to 14 years) after multiple rounds of preventive chemotherapy across three districts in Togo.

What is the frequency, type and severity of adverse events following triple-drug therapy (IVM+DEC+ALB, IDA) compared to the standard two-drug treatment (DEC+ALB, DA) in infected and uninfected individuals in a community?

The primary research question for the field work in Cote d'Ivoire is: what is the fine scale prevalence of S. haematobium and S. mansoni in 3 districts among children 5-14 years old?

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?

What is the appropriate serologic threshold at which to initiate MDA for onchocerciasis? Does this threshold vary by vector species or geographic characteristic?

1. In areas with low coverage of MDA or a history of never treatment, low coverage for Expanded Programme on Immunization (EPI) vaccines, and/or high malaria prevalence in Ambon City and in Volta Region, Ghana, is never treatment/zero dose a household phenomenon that spans more than one health domain (e.g., neglected tropical diseases, vaccines, insecticide-treated bed net use)?

2. What are the features/traits of households or individuals who miss more than one public health intervention?

3. Does never treatment / zero dose / non-participation vary between public health interventions?

The overarching research question for this project was: “What is the impact of mainstreaming on the deworming program in four districts in Nigeria?” The question was addressed through three objectives:

1. Objective 1: Transition schistosomiasis and soil-transmitted helminth treatment programs to the primary health care system or routine health services in select districts currently supported by The Carter Center.
2. Objective 2: Evaluate the effects of transitioning the program to full government ownership by comparing treatment coverage among the target population before and after the transition to the primary health care system or routine health services to evaluate the success of the transition, supplementing the results with qualitative data. 
3. Objective 3: Develop recommendations based on study findings to inform schistosomiasis and soil-transmitted helminths transition plans for other districts and states in Nigeria.

1.    Does the Ct infection data among 1 -9 years suggest that there is ongoing transmission of trachoma within the EU?
2.    Does the serology data (either prevalence or force of infection using pgp3) among 1 – 9 years suggest that trachoma transmission is ongoing? 
3.    Is there correlation in the conclusions derived from TF, infection, and serology data at EU level?

4.    Is the prevalence of pgp3 serology and Ct infection correlated at the cluster level?
5.    Are there demographic, behavioral or WASH factors that are correlated with pgp3 and Ct infection positivity that could inform more effective program interventions at cluster level?

1.    Can recrudescence or persistence of trachoma in Narok South, Narok West and Narok East be confirmed through the use of alternative indicators (Ct infection and anti-Ct antibodies)? 
2.    What impact have programmatic adaptations been in addressing confirmed persistence and recrudescence in Kajiado West, Central and South?

3. Is there any evidence of geographical locations and/or particular groups of high on-going transmission that should be targeted through programmatic adaptations and innovative approaches? 
4. What are the key factors (programmatic, epidemiological or contextual) that are facilitating persistence or recrudescence in Narok South, West and East and how should trachoma programming be adapted accordingly to ensure trachoma elimination is achieved? 
5.  In communities in Kajiado South, Central and West, are communities with very high Ct infection (>20% in children aged 1-9 years), a result of severe re-infection events or issues with programme MDA coverage.

Is there concordance in the TF, infection and serology data (at EU level) in confirming persistence and/or recrudescence of trachoma and the need for on-going interventions?

(1)    How does TF, anti-Ct antibody and infection data correlate at cluster level and what implications does this have for targeting programmatic interventions? 

(2)    Are there treatment coverage, geographic, demographic, and WASH factors that are correlated with higher pgp3 antibody, Ct infection and/or TF prevalence that could inform more effective program interventions? 

(3)    Are there sociocultural and behavioural factors that are associated with higher TF prevalence that could inform more effective program interventions?