Diagnostics to Support Elimination of Lymphatic Filariasis-Development of Two Target Product Profiles

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: Product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools

Persons ‘never treated’ in mass drug administration for lymphatic filariasis: identifying programmatic and research needs from a series of research review meetings 2020–2021

As neglected tropical disease programs rely on participation in rounds of mass drug administration (MDA), there is concern that individuals who have never been treated could contribute to ongoing transmission, posing a barrier to elimination. Previous research has suggested that the size and characteristics of the never-treated population may be important but have not been sufficiently explored. To address this critical knowledge gap, four meetings were held from December 2020 to May 2021 to compile expert knowledge on never treatment in lymphatic filariasis (LF) MDA programs. The meetings explored four questions: the number and proportion of people never treated, their sociodemographic characteristics, their infection status and the reasons why they were not treated. Meeting discussions noted key issues requiring further exploration, including how to standardize measurement of the never treated, adapt and use existing tools to capture never-treated data and ensure representation of never-treated people in data collection. Recognizing that patterns of never treatment are situation specific, participants noted measurement should be quick, inexpensive and focused on local solutions. Furthermore, programs should use existing data to generate mathematical models to understand what levels of never treatment may compromise LF elimination goals or trigger programmatic action

Implementing Preventive Chemotherapy through an Integrated National Neglected Tropical Disease Control Program in Mali

Neglected tropical diseases (NTDs) are a group of chronic infections that affect the poorest group of the populations in the world. There are currently five major NTDs targeted through mass drug treatment in the affected communities. The drug delivery can be integrated to deliver different drug packages as these NTDs often overlap in distribution. Mali is endemic with all five major NTDs. The integrated national NTD control program was implemented through the primary health care system using the community health center workers and the community drug distributors aiming at long-term sustainability. After a pilot start in three regions in 2007 without prior examples to follow on integrated mass drug administration, treatment for the five targeted NTDs was gradually scaled up and reached all endemic districts by 2009, and annual drug coverage in the targeted population has since been maintained at a high level for each of the five NTDs. Around 10 million people received one or more drug treatments each year since 2009. The country is on the way to meet the national objectives of elimination or control of these diseases. The successes and lessons learned in Mali are valuable assets to other countries looking to start similar programs

Significantly reduced intensity of infection but persistent prevalence of schistosomiasis in a highly endemic region in Mali after repeated treatment.

BACKGROUND: Preventive chemotherapy against schistosomiasis has been implemented since 2005 in Mali, targeting school-age children and adults at high risk. A cross-sectional survey was conducted in 2010 to evaluate the impact of repeated treatment among school-age children in the highly-endemic region of Segou. METHODOLOGY/PRINCIPAL FINDINGS: The survey was conducted in six sentinel schools in three highly-endemic districts, and 640 school children aged 7-14 years were examined. Infections with Schistosoma haematobium and S. mansoni were diagnosed with the urine filtration and the Kato-Katz method respectively. Overall prevalence of S. haematobium infection was 61.7%, a significant reduction of 30% from the baseline in 2004 (p<0.01), while overall prevalence of S. mansoni infection was 12.7% which was not significantly different from the baseline. Overall mean intensity of S. haematobium and S. mansoni infection was 180.4 eggs/10 ml of urine and 88.2 epg in 2004 respectively. These were reduced to 33.2 eggs/10 ml of urine and 43.2 epg in 2010 respectively, a significant reduction of 81.6% and 51% (p<0.001). The proportion of heavy S. haematobium infections was reduced from 48.8% in 2004 to 13.8% in 2010, and the proportion of moderate and heavy S. mansoni infection was reduced from 15.6% in 2004 to 9.4% in 2010, both significantly (p<0.01). Mathematical modelling suggests that the observed results were in line with the expected changes. CONCLUSIONS/SIGNIFICANCE: Significant reduction in intensity of infection on both infections and modest but significant reduction in S. haematobium prevalence were achieved in highly-endemic Segou region after repeated chemotherapy. However, persistent prevalence of both infections and relatively high level of intensity of S. mansoni infection suggest that more intensified control measures be implemented in order to achieve the goal of schistosomiasis elimination. In addition, closer monitoring and evaluation activities are needed in the programme to monitor the drug tolerance and to adjust treatment focus

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

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

Results of STH infections in school age children from the 22 sentinel sites in Burkina Faso in 2013.

<p>Results of STH infections in school age children from the 22 sentinel sites in Burkina Faso in 2013.</p

Successful Control of Soil-Transmitted Helminthiasis in School Age Children in Burkina Faso and an Example of Community-Based Assessment via Lymphatic Filariasis Transmission Assessment Survey

<div><p>Background</p><p>Burkina Faso is endemic with soil-transmitted helminth infections. Over a decade of preventive chemotherapy has been implemented through annual lymphatic filariasis (LF) mass drug administration (MDA) for population aged five years and over, biennial treatment of school age children with albendazole together with schistosomiasis MDA and biannual treatment of pre-school age children through Child Health Days. Assessments were conducted to evaluate the current situation and to determine the treatment strategy for the future.</p><p>Methodology/Principal Findings</p><p>A cross-sectional assessment was conducted in 22 sentinel sites across the country in 2013. In total, 3,514 school age children (1,748 boys and 1,766 girls) were examined by the Kato-Katz method. Overall, soil-transmitted helminth prevalence was 1.3% (95% CI: 1.0–1.8%) in children examined. Hookworm was the main species detected, with prevalence of 1.2% (95% CI: 0.9–1.6%) and mean egg counts of 2.1 epg (95% CI: 0–4.2 epg). Among regions, the Centre Ouest region had the highest hookworm prevalence of 3.4% (95% CI: 1.9–6.1%) and mean egg counts of 14.9 epg (95% CI: 3.3–26.6 epg). A separate assessment was conducted in the Centre Nord region in 2014 using community-based cluster survey design during an LF transmission assessment survey (TAS). In this assessment, 351 children aged 6–7 years and 345 children aged 10–14 years were examined, with two cases (0.6% (95% CI: 0.2–2.1%)) and seven cases (2.0% (95% CI: 1.0–4.1%)) of hookworm infection was identified respectively. The results using both age groups categorized the region to be 2% to <10% in STH prevalence according to the pre-defined cut-off values.</p><p>Conclusions/Significance</p><p>Through large-scale preventive chemotherapy, Burkina Faso has effectively controlled STH in school age children in the country. Research should be conducted on future strategies to consolidate the gain and to interrupt STH transmission in Burkina Faso. It is also demonstrated that LF TAS provides one feasible and efficient platform to assess the STH situation for post LF MDA decision making.</p></div

Comparison of the observed <i>S. haematobium</i> prevalence and intensity with the predicted changes.

<p>Prevalence is shown in red and intensity of infection is shown in blue. <i>S. haematobium</i> infection is shown in 7–14 year group (A, C and E) and in entire population (B, D and F). A and B: Macina district; B and C: San district; and E and F: Segou district. Lines show the predicted changes and squares in A, C and E show the observed results. Error bars represent the 95% CI.</p

Prevalence of STH infections among school age children in 22 schistosomiasis sentinel sites, Burkina Faso from sentinel site surveys in 2008 and 2013.

<p>Prevalence of STH infections among school age children in 22 schistosomiasis sentinel sites, Burkina Faso from sentinel site surveys in 2008 and 2013.</p