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Investigation of Mixture Modelling Algorithms as a Tool for Determining the Statistical Likelihood of Serological Exposure to Filariasis Utilizing Historical Data from the Lymphatic Filariasis Surveillance Program in Vanuatu.

ABSTRACT: As the prevalence of lymphatic filariasis declines, it becomes crucial to adequately eliminate residual areas of endemicity and implement surveillance. To this end, serological assays have been developed, including the Bm14 Filariasis CELISA which recommends a specific optical density cut-off level. We used mixture modelling to assess positive cut-offs of Bm14 serology in children in Vanuatu using historical OD (Optical Density) ELISA values collected from a transmission assessment survey (2005) and a targeted child survey (2008). Mixture modelling is a statistical technique using probability distributions to identify subpopulations of positive and negative results (absolute cut-off value) and an 80% indeterminate range around the absolute cut-off (80% cut-off). Depending on programmatic choices, utilizing the lower 80% cut-off ensures the inclusion of all likely positives, however with the trade-off of lower specificity. For 2005, country-wide antibody prevalence estimates varied from 6.4% (previous cut-off) through 9.0% (absolute cut-off) to 17.3% (lower 80% cut-off). This corroborated historical evidence of hotspots in Pentecost Island in Penama province. For 2008, there were no differences in the prevalence rates using any of the thresholds. In conclusion, mixture modelling is a powerful tool that allows closer monitoring of residual transmission spots and these findings supported additional monitoring which was conducted in Penama in later years. Utilizing a statistical data-based cut-off, as opposed to a universal cut-off, may help guide program decisions that are better suited to the national program.

SUBMITTER: Joseph H

PROVIDER: S-EPMC6473238 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Investigation of Mixture Modelling Algorithms as a Tool for Determining the Statistical Likelihood of Serological Exposure to Filariasis Utilizing Historical Data from the Lymphatic Filariasis Surveillance Program in Vanuatu.

Joseph Hayley H Sullivan Sarah S Wood Peter P Melrose Wayne W Taleo Fasihah F Graves Patricia P

Tropical medicine and infectious disease 20190308 1

As the prevalence of lymphatic filariasis declines, it becomes crucial to adequately eliminate residual areas of endemicity and implement surveillance. To this end, serological assays have been developed, including the Bm14 Filariasis CELISA which recommends a specific optical density cut-off level. We used mixture modelling to assess positive cut-offs of Bm14 serology in children in Vanuatu using historical OD (Optical Density) ELISA values collected from a transmission assessment survey (2005) ...[more]

PMID: 30857178

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Project description:BackgroundThe prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission.Methodology/principal findingWe present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997-2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6-7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts.ConclusionsWe conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF.

Project description:IntroductionLymphatic filariasis (LF), a neglected tropical disease (NTD) preventable through mass drug administration (MDA), is one of six diseases deemed possibly eradicable. Previously we developed one LF elimination scenario, which assumes MDA scale-up to continue in all countries that have previously undertaken MDA. In contrast, our three previously developed eradication scenarios assume all LF endemic countries will undertake MDA at an average (eradication I), fast (eradication II), or instantaneous (eradication III) rate of scale-up. In this analysis we use a micro-costing model to project the financial and economic costs of each of these scenarios in order to provide evidence to decision makers about the investment required to eliminate and eradicate LF.Methodology/key findingsCosting was undertaken from a health system perspective, with all results expressed in 2012 US dollars (USD). A discount rate of 3% was applied to calculate the net present value of future costs. Prospective NTD budgets from LF endemic countries were reviewed to preliminarily determine activities and resources necessary to undertake a program to eliminate LF at a country level. In consultation with LF program experts, activities and resources were further reviewed and a refined list of activities and necessary resources, along with their associated quantities and costs, were determined and grouped into the following activities: advocacy and communication, capacity strengthening, coordination and strengthening partnerships, data management, ongoing surveillance, monitoring and supervision, drug delivery, and administration. The costs of mapping and undertaking transmission assessment surveys and the value of donated drugs and volunteer time were also accounted for. Using previously developed scenarios and deterministic estimates of MDA duration, the financial and economic costs of interrupting LF transmission under varying rates of MDA scale-up were then modelled using a micro-costing approach. The elimination scenario, which includes countries that previously undertook MDA, is estimated to cost 929 million USD (95% Credible Interval: 884m-972m). Proceeding to eradication is anticipated to require a higher financial investment, estimated at 1.24 billion USD (1.17bn-1.30bn) in the eradication III scenario (immediate scale-up), with eradication II (intensified scale-up) projected at 1.27 billion USD (1.21bn-1.33bn), and eradication I (slow scale-up) estimated at 1.29 billion USD (1.23bn-1.34bn). The economic costs of the eradication III scenario are estimated at approximately 7.57 billion USD (7.12bn-7.94bn), while the elimination scenario is projected to have an economic cost of 5.21 billion USD (4.91bn-5.45bn). Countries in the AFRO region will require the greatest investment to reach elimination or eradication, but also stand to gain the most in cost savings. Across all scenarios, capacity strengthening and advocacy and communication represent the greatest financial costs, whereas mapping, post-MDA surveillance, and administration comprise the least.Conclusions/significanceThough challenging to implement, our results indicate that financial and economic savings are greatest under the eradication III scenario. Thus, if eradication for LF is the objective, accelerated scale-up is projected to be the best investment.

Project description:BackgroundLymphatic filariasis (LF) is a major public health problem in the Pacific Region, including in Fiji. Through transmission by the mosquito vector Aedes, Fiji has suffered the burden of remaining endemic with LF despite efforts at elimination prior to 1999. In the year 1999, Fiji agreed to take part in the Pacific Programme for Elimination of LF (PacELF) and the Global Programme to Eliminate LF.MethodsThis study reviewed and collated past data on LF in Fiji between 1997 and 2007. Sources included published papers as well as unpublished PacELF and WHO program meeting and survey reports. Records were held at Fiji's Department of Health and Medical Services, James Cook University and the WHO office in Suva, Fiji.ResultsBaseline surveys between 1997 and 2002 showed that Fiji was highly endemic for LF with an estimated 16.6% of the population antigen positive and 6.3% microfilaria positive at that time. Five rounds of annual mass drug administration (MDA) using albendazole and diethylcarbamazine commenced in 2002. Programmatic coverage reported was 58-70% per year, but an independent coverage survey in 2006 in Northern Division after the fifth MDA suggested that actual coverage may have been higher. Monitoring of the program consisted of antigen prevalence surveys in all ages with sentinel and spot check surveys carried out in 2002 (pre MDA), 2004, and 2005, together with knowledge, attitude, and practice surveys. The stop-MDA survey (C survey) in 2007 was a nationwide stratified cluster survey of all ages according to PacELF guidelines, designed to sample by administrative division to identify areas still needing MDA. The national antigen prevalence in 2007 was reduced by more than a third to 9.5%, ranging from 0.9% in Western Division to 15.4% in Eastern Division, while microfilaria prevalence was reduced by almost four-fifths to 1.4%. Having not reached the target threshold of 1% prevalence in all ages, Fiji wisely decided to continue MDA after 2007 but to move from nationwide implementation to four (later five) separate evaluation units with independent timelines using global guidelines, building on program experience to put more emphasis on increasing coverage through prioritized communication strategies, community participation, and morbidity alleviation.ConclusionFiji conducted nationwide MDA for LF annually between 2002 and 2006, monitored by extensive surveys of prevalence, knowledge, and coverage. From a high baseline prevalence in all divisions, large reductions in overall and age-specific prevalence were achieved, especially in the prevalence of microfilariae, but the threshold for stopping MDA was not reached. Fiji has a large rural and geographically widespread population, program management was not consistent over this period, and coverage achieved was likely not optimal in all areas. After learning from these many challenges and activities, Fiji was able to build on the progress achieved and the heterogeneity observed in prevalence to realign towards a more stratified and improved program after 2007. The information presented here will assist the country to progress towards validating elimination in subsequent years.

Dataset Information

Investigation of Mixture Modelling Algorithms as a Tool for Determining the Statistical Likelihood of Serological Exposure to Filariasis Utilizing Historical Data from the Lymphatic Filariasis Surveillance Program in Vanuatu.

Publications

Investigation of Mixture Modelling Algorithms as a Tool for Determining the Statistical Likelihood of Serological Exposure to Filariasis Utilizing Historical Data from the Lymphatic Filariasis Surveillance Program in Vanuatu.

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