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Detecting infection hotspots: Modeling the surveillance challenge for elimination of lymphatic filariasis.

ABSTRACT: BACKGROUND:During the past 20 years, enormous efforts have been expended globally to eliminate lymphatic filariasis (LF) through mass drug administration (MDA). However, small endemic foci (microfoci) of LF may threaten the presumed inevitable decline of infections after MDA cessation. We conducted microsimulation modeling to assess the ability of different types of surveillance to identify microfoci in these settings. METHODS:Five or ten microfoci of radius 1, 2, or 3 km with infection marker prevalence (intensity) of 3, 6, or 10 times background prevalence were placed in spatial simulations, run in R Version 3.2. Diagnostic tests included microfilaremia, immunochromatographic test (ICT), and Wb123 ELISA. Population size was fixed at 360,000 in a 60 x 60 km area; demographics were based on literature for Sub-Saharan African populations. Background ICT prevalence in 6-7 year olds was anchored at 1.0%, and the prevalence in the remaining population was adjusted by age. Adults?18 years, women aged 15-40 years (WCBA), children aged 6-7 years, or children?5 years were sampled. Cluster (CS), simple random sampling (SRS), and TAS-like sampling were simulated, with follow-up testing of the nearest 20, 100, or 500 persons around each infection-marker-positive person. A threshold number of positive persons in follow-up testing indicated a suspected microfocus. Suspected microfoci identified during surveillance and actual microfoci in the simulation were compared to obtain a predictive value positive (PVP). Each parameter set was referred to as a protocol. Protocols were scored by efficiency, defined as the most microfoci identified, the fewest persons requiring primary and follow-up testing, and the highest PVP. Negative binomial regression was used to estimate aggregate effects of different variables on efficiency metrics. RESULTS:All variables were significantly associated with efficiency metrics. Additional follow-up tests beyond 20 did not greatly increase the number of microfoci detected, but significantly negatively impacted efficiency. Of 3,402 protocols evaluated, 384 (11.3%) identified all five microfoci (PVP 3.4-100.0%) and required testing 0.73-35.6% of the population. All used SRS and 378 (98.4%) only identified all five microfoci if they were 2-3 km diameter or high-intensity (6x or 10x); 374 (97.4%) required ICT or Wb123 testing to identify all five microfoci, and 281 (73.0%) required sampling adults or WCBA. The most efficient CS protocols identified two (40%) microfoci. After limiting to protocols with 1-km radius microfoci of 3x intensity (n = 378), eight identified all five microfoci; all used SRS and ICT and required testing 31.2-33.3% of the population. The most efficient CS and TAS-like protocols as well as those using microfilaremia testing identified only one (20%) microfocus when they were limited to 1-km radius and 3x intensity. CONCLUSION:In this model, SRS, ICT, and sampling of adults maximized microfocus detection efficiency. Follow-up sampling of more persons did not necessarily increase protocol efficiency. Current approaches towards surveillance, including TAS, may not detect small, low-intensity LF microfoci that could remain after cessation of MDA. The model provides many surveillance protocols that can be selected for optimal outcomes.

SUBMITTER: Harris JR

PROVIDER: S-EPMC5453617 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Detecting infection hotspots: Modeling the surveillance challenge for elimination of lymphatic filariasis.

Harris Julie R JR Wiegand Ryan E RE

PLoS neglected tropical diseases 20170519 5

<h4>Background</h4>During the past 20 years, enormous efforts have been expended globally to eliminate lymphatic filariasis (LF) through mass drug administration (MDA). However, small endemic foci (microfoci) of LF may threaten the presumed inevitable decline of infections after MDA cessation. We conducted microsimulation modeling to assess the ability of different types of surveillance to identify microfoci in these settings.<h4>Methods</h4>Five or ten microfoci of radius 1, 2, or 3 km with inf ...[more]

PMID: 28542274

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Project description:BackgroundThe Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in response to the call proposed at the 50th World Health Assembly. The goal of the GPELF is to ensure that all the countries where the disease is endemic would have been transmission-free or would have entered post-intervention mass drug administration (MDA) surveillance by 2020. However, several countries are still not on track to discontinue MDA as planned. Thus, issues remain regarding the achievement of stated goals and how to effectively monitor the disease in the post-control and post-elimination phases.Main textChina was once a lymphatic filariasis (LF) endemic country with heavy disease burden. There were three milestones in the LF control phase of China, including: the proposal that the major focus of the control strategy should be on infectious sources; the three regimens of diethylcarbamazine (DEC) administration according to LF endemic extent; and the establishment of the threshold for LF transmission interruption. It has been ten years since China entered the post-elimination stage (declaration of LF elimination in China was in 2007). Two schemes and a diagnostic criterion were issued to guide all levels of disease control and prevention workers that conduct LF surveillance, as well as those caring for chronic filariasis patients. Regular training courses are held to maintain LF control skills in grass-root institutions. The Notifiable Diseases Reporting System, which included LF in 2004, plays an important role in LF post-elimination surveillance. Until now, no resurgence of LF cases has been detected, except for LF residue foci being found in Fuchuan County of the Guangxi Zhuang Autonomous Region. To confirm that transmission is no longer achievable after a decade since the declaration of LF elimination in China, it is expected within the next two years a transmission assessment survey, conducted in previous LF-endemic areas.ConclusionsDEC-fortified salt can help accelerate the progress of GPELF before the sprite phase. Sophisticated diagnostic criteria, systematic surveillance regimes, the Direct Network Report system, and regular trainings can effectively prevent the recrudescence of LF during surveillance phases.

Project description:BackgroundMathematical models are increasingly being used to evaluate strategies aiming to achieve the control or elimination of parasitic diseases. Recently, owing to growing realization that process-oriented models are useful for ecological forecasts only if the biological processes are well defined, attention has focused on data assimilation as a means to improve the predictive performance of these models.Methodology and principal findingsWe report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations. The relative information contribution of site-specific data collected at the time points proposed by the WHO monitoring framework was evaluated using model-data updating procedures, and via calculations of the Shannon information index and weighted variances from the probability distributions of the estimated timelines to parasite extinction made by each model. Results show that data-informed models provided more precise forecasts of elimination timelines in each site compared to model-only simulations. Data streams that included year 5 post-MDA microfilariae (mf) survey data, however, reduced each model's uncertainty most compared to data streams containing only baseline and/or post-MDA 3 or longer-term mf survey data irrespective of MDA coverage, suggesting that data up to this monitoring point may be optimal for informing the present LF models. We show that the improvements observed in the predictive performance of the best data-informed models may be a function of temporal changes in inter-parameter interactions. Such best data-informed models may also produce more accurate predictions of the durations of drug interventions required to achieve parasite elimination.SignificanceKnowledge of relative information contributions of model only versus data-informed models is valuable for improving the usefulness of LF model predictions in management decision making, learning system dynamics, and for supporting the design of parasite monitoring programmes. The present results further pinpoint the crucial need for longitudinal infection surveillance data for enhancing the precision and accuracy of model predictions of the intervention durations required to achieve parasite elimination in an endemic location.

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:BackgroundThe World Health Organization (WHO) currently recommends height or age-based dosing as alternatives to weight-based dosing for mass drug administration lymphatic filariasis (LF) elimination programs. The goals of our study were to compare these alternative dosing strategies to weight-based dosing and to develop and evaluate new height-based dosing pole scenarios.Methodology/principal findingsAge, height and weight data were collected from >26,000 individuals in five countries during a cluster randomized LF clinical trial. Weight-based dosing for diethylcarbamazine (DEC; 6 mg/kg) and ivermectin (IVM; 200 ug/kg) with tablet numbers derived from a table of weight intervals was treated as the "gold standard" for this study. Following WHO recommended age-based dosing of DEC and height-based dosing of IVM would have resulted in 32% and 27% of individuals receiving treatment doses below those recommended by weight-based dosing for DEC and IVM, respectively. Underdosing would have been especially common in adult males, who tend to have the highest LF prevalence in many endemic areas. We used a 3-step modeling approach to develop and evaluate new dosing pole cutoffs. First, we analyzed the clinical trial data using quantile regression to predict weight from height. We then used weight predictions to develop new dosing pole cutoff values. Finally, we compared different dosing pole cutoffs and age and height-based WHO dosing recommendations to weight-based dosing. We considered hundreds of scenarios including country- and sex-specific dosing poles. A simple dosing pole with a 6-tablet maximum for both DEC and IVM reduced the underdosing rate by 30% and 21%, respectively, and was nearly as effective as more complex pole combinations for reducing underdosing.Conclusions/significanceUsing a novel modeling approach, we developed a simple dosing pole that would markedly reduce underdosing for DEC and IVM in MDA programs compared to current WHO recommended height or age-based dosing.

Project description:The Global Programme to Eliminate Lymphatic Filariasis has made significant progress toward interrupting transmission of lymphatic filariasis (LF) through mass drug administration (MDA). Operational challenges in defining endpoints of elimination programs include the need to determine appropriate post-MDA surveillance strategies. As humans are the only reservoirs of LF parasites, one such strategy is molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), to provide an indirect indicator of infected persons nearby. MX could potentially be used to evaluate program success, provide support for decisions to stop MDA, and conduct post-MDA surveillance. American Samoa has successfully completed MDA and passed WHO recommended Transmission Assessment Surveys in 2011 and 2015, but recent studies using spatial analysis of antigen (Ag) and antibody (Ab) prevalence in adults (aged ?18 years) and entomological surveys showed evidence of possible ongoing transmission. This study evaluated MX as a surveillance tool in American Samoa by linking village-level results of published human and mosquito studies. Of 32 villages, seropositive persons for Og4C3 Ag were identified in 11 (34.4%), for Wb123 Ab in 18 (56.3%) and for Bm14 Ab in 27 (84.4%) of villages. Village-level seroprevalence ranged from 0-33%, 0-67% and 0-100% for Og4C3 Ag, Wb123 Ab and Bm14 Ab respectively. PCR-positive Aedes polynesiensis mosquitoes were found in 15 (47%) villages, and their presence was significantly associated with seropositive persons for Og4C3 Ag (67% vs 6%, p<0.001) and Wb123 Ab (87% vs 29%, p = 0.001), but not Bm14 Ab. In villages with persons seropositive for Og4C3 Ag and Wb123 Ab, PCR-positive Ae. polynesiensis were found in 90.9% and 72.2% respectively. In villages without seropositive persons for Og4C3 Ag or Wb123 Ab, PCR-positive Ae. polynesiensis were also absent in 94.1% and 70.6% of villages respectively. Our study provides promising evidence to support the potential usefulness of MX in post-MDA surveillance in an Aedes transmission area in the Pacific Islands setting.

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.

Project description:The Global Programme to Eliminate Lymphatic Filariasis (LF) aims to eliminate the disease as a public health problem by 2020 by conducting mass drug administration (MDA) and controlling morbidity. Once elimination targets have been reached, surveillance is critical for ensuring that programmatic gains are sustained, and challenges include timely identification of residual areas of transmission. WHO guidelines encourage cost-efficient surveillance, such as integration with other population-based surveys. In American Samoa, where LF is caused by Wuchereria bancrofti, and Aedes polynesiensis is the main vector, the LF elimination program has made significant progress. Seven rounds of MDA (albendazole and diethycarbamazine) were completed from 2000 to 2006, and Transmission Assessment Surveys were passed in 2010/2011 and 2015. However, a seroprevalence study using an adult serum bank collected in 2010 detected two potential residual foci of transmission, with Og4C3 antigen (Ag) prevalence of 30.8% and 15.6%. We conducted a follow up study in 2014 to verify if transmission was truly occurring by comparing seroprevalence between residents of suspected hotspots and residents of other villages. In adults from non-hotspot villages (N = 602), seroprevalence of Ag (ICT or Og4C3), Bm14 antibody (Ab) and Wb123 Ab were 1.2% (95% CI 0.6-2.6%), 9.6% (95% CI 7.5%-12.3%), and 10.5% (95% CI 7.6-14.3%), respectively. Comparatively, adult residents of Fagali'i (N = 38) had significantly higher seroprevalence of Ag (26.9%, 95% CI 17.3-39.4%), Bm14 Ab (43.4%, 95% CI 32.4-55.0%), and Wb123 Ab 55.2% (95% CI 39.6-69.8%). Adult residents of Ili'ili/Vaitogi/Futiga (N = 113) also had higher prevalence of Ag and Ab, but differences were not statistically significant. The presence of transmission was demonstrated by 1.1% Ag prevalence (95% CI 0.2% to 3.1%) in 283 children aged 7-13 years who lived in one of the suspected hotspots; and microfilaraemia in four individuals, all of whom lived in the suspected hotspots, including a 9 year old child. Our results provide field evidence that integrating LF surveillance with other surveys is effective and feasible for identifying potential hotspots, and conducting surveillance at worksites provides an efficient method of sampling large populations of adults.

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Detecting infection hotspots: Modeling the surveillance challenge for elimination of lymphatic filariasis.

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Detecting infection hotspots: Modeling the surveillance challenge for elimination of lymphatic filariasis.

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