A comprehensive assessment of lymphatic filariasis in Sri Lanka six years after cessation of mass drug administration

The Sri Lankan Anti-Filariasis Campaign conducted 5 rounds of mass drug administration (MDA) with diethycarbamazine plus albendazole between 2002 and 2006. We now report results of a comprehensive surveillance program that assessed the lymphatic filariasis (LF) situation in Sri Lanka 6 years after cessation of MDA.Transmission assessment surveys (TAS) were performed per WHO guidelines in primary school children in 11 evaluation units (EUs) in all 8 formerly endemic districts. All EUs easily satisfied WHO criteria for stopping MDA. Comprehensive surveillance was performed in 19 Public Health Inspector (PHI) areas (subdistrict health administrative units). The surveillance package included cross-sectional community surveys for microfilaremia (Mf) and circulating filarial antigenemia (CFA), school surveys for CFA and anti-filarial antibodies, and collection of Culex mosquitoes with gravid traps for detection of filarial DNA (molecular xenomonitoring, MX). Provisional target rates for interruption of LF transmission were community CFA <2%, antibody in school children <2%, and filarial DNA in mosquitoes <0.25%. Community Mf and CFA prevalence rates ranged from 0-0.9% and 0-3.4%, respectively. Infection rates were significantly higher in males and lower in people who denied prior treatment. Antibody rates in school children exceeded 2% in 10 study sites; the area that had the highest community and school CFA rates also had the highest school antibody rate (6.9%). Filarial DNA rates in mosquitoes exceeded 0.25% in 10 PHI areas.Comprehensive surveillance is feasible for some national filariasis elimination programs. Low-level persistence of LF was present in all study sites; several sites failed to meet provisional endpoint criteria for LF elimination, and follow-up testing will be needed in these areas. TAS was not sensitive for detecting low-level persistence of filariasis in Sri Lanka. We recommend use of antibody and MX testing as tools to complement TAS for post-MDA surveillance

Multivariable logistic regression of risk factors for filarial antigenemia in community survey data.

a<p>Results from all 19 public health inspector (PHI) areas that were surveyed.</p>b<p>This analysis was restricted to results from 14 PHI areas where one or more persons tested had a positive filarial antigen test.</p><p>Multivariable logistic regression of risk factors for filarial antigenemia in community survey data.</p

Background information for Public Health Inspector (PHI) areas selected for comprehensive filariasis surveillance and demographic information for subjects enrolled in community studies conducted in these areas.

a<p>Sentinel sites (PHI) C3 and C4 were in the city of Colombo.</p>b<p>Sentinel site G3 is a Public Health Field Officer area (PHFO).</p><p>Background information for Public Health Inspector (PHI) areas selected for comprehensive filariasis surveillance and demographic information for subjects enrolled in community studies conducted in these areas.</p

Transmission assessment survey (TAS^a) results from 11 evaluation units (EUs) in 8 districts^b in in Sri Lanka.

a<p>The critical cutoff value for assessing interruption of transmission was 18 in all EUs.</p>b<p>The 8 endemic districts were MDA implementation units.</p>c<p>BinaxNOW Filariasis tests were used for detection of filarial antigenemia. Data shown are the number of positive tests (% positive and 95% CI).</p><p>Transmission assessment survey (TAS^{<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003281#nt110" target="_blank">a</a>}) results from 11 evaluation units (EUs) in 8 districts^{<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003281#nt111" target="_blank">b</a>} in in Sri Lanka.</p

Summary of filariasis parameters from community (Comm) and school surveys conducted in public health inspector (PHI) areas.

a<p>Surveyed rates for ingestion of antifilarial medications during the national mass drug administration (MDA) program 2002–06.</p>b<p>Prevalence rates are mean values (95% CI) by PHI. Results are shown as pass (regular font), borderline (<i>italics</i>) or fail (<b>bold</b>) based on provisional endpoint criteria described in the <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003281#s1" target="_blank">Introduction</a>.</p>c<p>Study sites C3 and C4 were in the city of Colombo.</p><p>Summary of filariasis parameters from community (Comm) and school surveys conducted in public health inspector (PHI) areas.</p

Filarial DNA rates in Sri Lankan <i>Culex quinquefasciatus</i> mosquitoes by Public Health Inspector area.

a<p>Sentinel sites (PHIs) C3 and C4 were located in the city of Colombo. Sentinel site G3 is a PHFO area.</p>b<p>Each pool included 20 mosquitoes (blood fed, gravid and semigravid).</p>c<p>Filarial DNA was detected by qPCR. Rates of filarial DNA in mosquitoes (maximum likelihood and 95% CI) were estimated using PoolScreen2. Results are shown as pass (regular font), borderline (<i>italics</i>) or fail (<b>bold</b>) based on provisional endpoint criteria described in the <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003281#s1" target="_blank">Introduction</a>.</p><p>Filarial DNA rates in Sri Lankan <i>Culex quinquefasciatus</i> mosquitoes by Public Health Inspector area.</p

Graphic summary of comprehensive filariasis surveillance data for Public Health Inspector areas in Sri Lanka.

<p>Data shown are rates (% with 95% confidence limits as vertical lines). The dotted line in the top panel and the lower dotted lines in the two lower panels show the old provisional targets for interruption of transmission. The upper dotted lines in the two lower panels are recommended revised targets for the upper confidence limits for antibody rates in first and second grade primary school children and for filarial DNA rates in mosquitoes, respectively.</p

Filariasis infection parameters by age and gender in Public Health Inspector^a areas.

a<p>Circulating filarial antigen (CFA) results from 14 public health inspector areas (PHIs) with one or more CFA positives were included in this analysis.</p>b<p>Data shown are CFA prevalence rates (95% CI).</p><p>Filariasis infection parameters by age and gender in Public Health Inspector^{<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003281#nt106" target="_blank">a</a>} areas.</p

Comparison of filarial infection parameters in Peliyagodawatta^a in 2008 and 2011.

a<p>Peliyagodawatta is a Public Health Field Officer area in Gampaha district.</p>b<p>Results shown are % positive (95% CI). Filarial DNA rates shown are maximum likelihood estimates (with 95% CI).</p>c<p><i>P</i> values are based on χ². NS, not significant.</p>d<p>Community microfilaremia (Mf) and circulating filarial antigenemia (CFA) rates are for ages ≥10 years. Mf rates are based on night blood smear results from all subjects in 2008 and from CFA positives only in 2011.</p><p>Comparison of filarial infection parameters in Peliyagodawatta^{<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003281#nt116" target="_blank">a</a>} in 2008 and 2011.</p

Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration: a multicenter evaluation.

BACKGROUND: Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. METHODOLOGY: The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6-7 year olds or 1(st)-2(nd) graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs. PRINCIPAL FINDINGS/CONCLUSIONS: In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance requires further investigation