Centers for Disease Control and Prevention (CDC)
Field evaluation of two schistosome antibody-based rapid tests at point-of-care for prevalence mapping of urinary schistosomiasis in The Gambia
CCA Protocol: To know the sensitivity and specificity of POC CCA in the detection of urinary schistosomiasis, as compared to traditional diagnostic tools.
Monitor STH in PSAC and WCBA following cessation of LF MDA (Tanzania)
Monitor recrudescence of STH after TAS to improve planning of STH programs and more effective use of STH drugs.
Evaluation of Biplex RDT in Tshopo Province, DRC
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%.
Antibody Responses to Chlamydia trachomatis Antigens in Trachoma-Endemic Zones of Ethiopia
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
Ongoing Post-treatment Surveillance for Lymphatic Filariasis in Bangladesh
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.
Field validation of sampling strategies for integrating STH surveys into Transmission Assessment Surveys (Haiti)
Test STH-TAS.
A Programmatic Comparison of School- and Community-Based TAS
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.
Correlation of Xenomonitoring and LF-Antibody Responses as Measures of Transmission in American Samoa
Determine the utility of xenomonitoring and serological assessments for the detection of residual transmission
Field-testing a Lateral Flow Assay for anti-Chlamydial Antibody Responses
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.
Molecular Xenomonitoring for Lymphatic Filariasis in Bangladesh
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.
Field validation of sampling strategies for integrating STH surveys into Transmission Assessment Surveys (Tanzania)
Test STH-TAS
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?
Development of Tools to Re-Orient Social Mobilization Strategies to Close the MDA Coverage-Compliance Gap
To improve compliance and reduce the coverage-compliance gap in mass drug administration through enhanced and tailored social mobilization.
Gaining schistosomiasis control in Kenya, Mozambique, and Tanzania
Gaining Control: >25% Prevalence MDA strategies; and subtle morbidity of Cohort; Population genetics, and snail monitoring
Sustaining schistosomiasis control in Cote D'Ivoire and Kenya
MDA strategies: Sustaining control at 10 – 24% prevalence
Field validation of sampling strategies for integrating STH surveys into Transmission Assessment Surveys (Haiti)
Test STH-TAS.
POC/CCA screening/mapping tool initial Studies
Field validation of sampling strategies for integrating STH surveys into Transmission Assessment Surveys (Tanzania)
Test STH-TAS
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?
A knowledge co-production strategy to address systematic non-compliance with MDA for Lymphatic Filariasis in Leogane, Haiti
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:
- Can an intervention package co-produced with systematically non-compliant individuals result in increased MDA coverage between the 2019 and 2020 LF MDA rounds?
- Who and where are the systematic non-compliers in Leogane and Gressier?
- What are the reasons motivating systematic non-compliance?
- Is MDA non-compliance associated with hotspots of LF transmission?
The researchers plan the following activities:
- 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]).
- 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.
- 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.
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.
Addressing the Mental Health of Persons Living with Lymphatic Filariasis in Léogâne, Haiti: Effectiveness of a Chronic Disease Self-Management Program
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?
MORBID: Morbidity Operational Research for Bilharziasis Implementation Decisions (Pilot)
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?
The Impact of WASH on Re-infection with STH
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.
Investigating the role of drug delivery strategy in MDA drug coverage
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.
Developing an M&E strategy to guide stopping decisions for IDA in Kenya: the Year 2 Impact Assessment
What is/are the most suitable indicator(s) for monitoring IDA treatment regimen against LF and for making IDA stopping decisions?
Understanding areas of increased trachoma risk (hotspots) through the implementation of a post validation trachoma surveillance strategy
To determine if there is evidence of on-going or recent transmission in the “hotspot” communities of increased risk two years after they were identified during the pre-validation surveys (clinical, antibody and infection data).
Mapping LF-Loa Coendemicity in Chad
Mapping LF-Loa Coendemicity
Mapping LF-Loa Coendemicity in Angola
Mapping LF-Loa Coendemity
Exploring alternative indicators for trachoma endpoint decision-making (Malawi)
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.
Comparison of antigenemia by ICT and FTS RDT, antibody responses to Wb123 and Ov 16 by ELISA , and Wb123/Ov16 Biplex RDT on LF sentinel sites
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.
Defining the Profile of LF Antibody Reactivity following MDA
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.
Integrated serosurveillance for parasitic diseases and vaccine preventable diseases in Cambodia
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.
Development of Tools to Re-Orient Social Mobilization Strategies to Close the MDA Coverage-Compliance Gap
To improve compliance and reduce the coverage-compliance gap in mass drug administration through enhanced and tailored social mobilization.
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.
Production of a New Dual Antigen Test Strip as a Tool to Support Epidemiologic Assessments of Onchocerciasis
How does the performance of the new Ov16/Ov3261 test strip compare to that of the SD Ov16 RDT and the SD Ov16 ELISA?
Lymphatic filariasis positive-case follow-up after TAS 2 or TAS 3 in Philippines
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.
District Mapping Onchocerciasis and Lymphatic Filariasis in Ethiopia
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.
How does the performance of the AP ELISA compare to the Ov16 SD ELISA, when conducted in a country lab?
Ab assessment by multiplex for LF, Trachoma, and Yaws
Determine the age prevalence of LF antibody following MDA to inform surveillance strategies. Yaws and trachoma testing will also occur during the survey.
Exploring alternative indicators for trachoma endpoint decision-making (Tanzania)
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.
Assessing drug coverage following mass drug administration to monitor the impact of the WHO recommended three-drug regimen of ivermectin, diethylcarbamazine, and albendazole for the elimination of lymphatic filariasis
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
Investigation of communities at increased risk of trachoma recrudescence & a model post-elimination surveillance strategy
Primary research question
Is there evidence of on-going or recent ocular Ct transmission in communities of northern Ghana felt to be at increased risk of recrudescence, at least two years since they were identified with Ct infection and or high anti-Pgp3 seroprevalence during pre-validation trachoma surveillance surveys?
Secondary research questions
What is the geographical extent of the boundaries of any persistent Ct infection and on-going transmission in the post-elimination setting?
What is the community-level (anti-Pgp3) prevalence of seropositivity for the multiplex bead array (MBA) (and possibly ELISA) as compared to the lateral flow assay (LFA)?
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?
Development of a Mobile Reader for Rapid Diagnostic Tests
Can a mobile reader be used to standardize the reading of rapid diagnostic tests (RDTs)?
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.
Understanding Lymphatic Filariasis Antigenemia and Antibody responses in Sentinel sites post LF transmission interruption (The Gambia)
Assess Wb123 antibody responses in communities where LF transmission was interrupted without MDA.
Testing New RDT Formats to Improve Wb123 Test Sensitivity
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.
Lymphatic Filariasis Positive-Case Follow-up After TAS 2 in Haiti
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.