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Preventive chemotherapy reverses covert, lymphatic-associated tissue change in young people with lymphatic filariasis in Myanmar.

ABSTRACT: OBJECTIVES:This longitudinal comparative study investigated the effect of preventive chemotherapy (PC) on covert tissue changes associated with lymphatic filariasis (LF) among young people living in an LF-endemic area in Myanmar. METHODS:Tissue compressibility and extracellular free fluid in the lower limbs of people aged 10-21 years were measured using indurometry and bioimpedance spectroscopy (BIS). Baseline measures were taken in October 2014, annual mass drug administration (MDA) of PC was delivered in December, and in March 2015 further PC was offered to LF-positive cases who had missed MDA. Follow-up measures were taken in February and June 2015. RESULTS:A total of 50 antigen-positive cases and 46 antigen-negative controls were included. Self-reported PC consumption was 60.1% during 2014 MDA and 66.2% overall. At second follow-up, 24 of 34 cases and 27 of 43 controls had consumed PC. Significant and clinically relevant between-group differences at baseline were not found post-PC. Bayesian linear mixed models showed a significant change in indurometer scores at both calves for antigen-positive cases who consumed any PC (dominant calf: -0.30 [95% CI -0.52, -0.07], P < 0.05 and non-dominant calf: -0.35 [95% CI -0.58, -0.12], P < 0.01). Changes in antigen-negative participants or those not consuming PC were not significant. CONCLUSION:This study is the first attempt to use simple field-friendly tools to track fluid and tissue changes after treatment of asymptomatic people infected with LF. Results suggested that PC alone is sufficient to reverse covert lymphatic disturbance. Longer follow-up of larger cohorts is required to confirm these improvements and whether they persist over time. These findings should prompt increased efforts to overcome low PC coverage, which misses many infected young people, particularly males, who are unaware of their infection status, unmotivated to take PC and at risk of developing lymphoedema. Indurometry and BIS should be considered in assessment of lymphatic filariasis-related lymphedema.

SUBMITTER: Douglass J

PROVIDER: S-EPMC6850631 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Preventive chemotherapy reverses covert, lymphatic-associated tissue change in young people with lymphatic filariasis in Myanmar.

Douglass Janet J Dykes Lukah L Kelly-Hope Louise L Gordon Susan S Leggat Peter P Aye Ni Ni NN Win San San SS Wai Tint T Win Yi Yi YY Nwe Thet Wai TW Graves Patricia P

Tropical medicine & international health : TM & IH 20190307 4

<h4>Objectives</h4>This longitudinal comparative study investigated the effect of preventive chemotherapy (PC) on covert tissue changes associated with lymphatic filariasis (LF) among young people living in an LF-endemic area in Myanmar.<h4>Methods</h4>Tissue compressibility and extracellular free fluid in the lower limbs of people aged 10-21 years were measured using indurometry and bioimpedance spectroscopy (BIS). Baseline measures were taken in October 2014, annual mass drug administration (M ...[more]

PMID: 30706585

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Project description:BackgroundMyanmar commenced a lymphatic filariasis (LF) elimination programme in 2000. Whilst the country has made considerable progress since then, a number of districts have demonstrated persistent transmission after many rounds of mass drug administration (MDA). The causes of unsuccessful MDA have been examined elsewhere; however, there remains little information on the factors that contribute in Myanmar.MethodsWe conducted an analysis of factors associated with persistent infection, LF-related hydrocoele and MDA participation in an area with ongoing transmission in 2015. A cross-sectional household survey was undertaken in 24 villages across four townships of Mandalay Region. Participants were screened for circulating filarial antigen (CFA) using immunochromatographic tests and, if positive, for microfilaria by night-time thick blood slide. Individuals 15 year and older were assessed for filariasis morbidity (lymphoedema and, if male, hydrocoele) by ultrasound-assisted clinical examination. A pre-coded questionnaire was used to assess risk factors for LF and for non-participation (never taking MDA). Significant variables identified in univariate analyses were included in separate step-wise multivariate logistic regressions for each outcome.ResultsAfter adjustment for covariates and survey design, being CFA positive was significantly associated with age [odds ratio (OR) 1.03, 95% CI 1.01-1.06), per year], male gender (OR 3.14, 1.27-7.76), elevation (OR 0.96, 0.94-0.99, per metre) and the density of people per household room (OR 1.59, 1.31-1.92). LF-related hydrocoele was associated with age (OR 1.06, 1.03-1.09, per year) and residing in Amarapura Township (OR 8.93, 1.37-58.32). Never taking MDA was associated with male gender [OR 6.89 (2.13-22.28)] and age, particularly in females, with a significant interaction term. Overall, compared to those aged 30-44 years, the proportion never taking MDA was higher in all age groups (OR highest in those < 5 years and > 60 years, ranging from 3.37 to 12.82). Never taking MDA was also associated with residing in Amarapura township (OR 2.48, 1.15-5.31), moving to one's current village from another (OR 2.62, 1.12-6.11) and ever having declined medication (OR 11.82, 4.25-32.91). Decreased likelihood of never taking MDA was associated with a higher proportion of household members being present during the last MDA round (OR 0.16, 0.03-0.74) and the number visits by the MDA programme (OR 0.69, 0.48-1.00).ConclusionsThese results contribute to the understanding of LF and MDA participation-related risk factors and will assist Myanmar to improve its elimination and morbidity management programmes.

Project description:ObjectiveTo estimate the impact of preventive chemotherapy on the prevalence and intensity of soil-transmitted helminth (STH) infections, schistosomiasis, and lymphatic filariasis in the Philippines, using systematic review and meta-analysis.MethodsWe included reports reporting prevalence of STH infections, schistosomiasis, or lymphatic filariasis in the Philippines published until 31 March 2021. Peer-reviewed studies were identified in electronic databases. Grey literature reports by the University of the Philippines and the Department of Health were also included. Pooled infection prevalence, before and after the initiation of preventive chemotherapy, stratified by age group, was calculated using the inverse variance heterogeneity model.FindingsA total of 109 reports were included in the review and meta-analysis. Overall prevalence of moderate-heavy intensity Ascaris lumbricoides (6.6%) and Trichuris trichiura (2.7%) infection after initiation of preventive chemotherapy were significantly lower than the prevalence prior to initiation (23.6% for A. lumbricoides and 12.2% for T. trichiura). Prevalence reductions were also found in school and preschool-age children for A. lumbricoides and T. trichiura. Studies conducted after preventive chemotherapy initiation had significantly lower overall prevalence of moderate-heavy intensity schistosomiasis (3.1% vs 0.2%) and of schistosomiasis in school-age children (30.5% vs 1%). Pooled prevalence of lymphatic filariasis prior to preventive chemotherapy initiation was 3.2% across 12 provinces, while currently only two provinces still have prevalence of more than 1%. There were no published studies reporting prevalence of lymphatic filariasis after initiation of preventive chemotherapy. Heterogeneity was high with I2 mostly above 90%.ConclusionThe burden of STH infections and schistosomiasis in children were significantly lower in studies conducted following the initiation of preventive chemotherapy. Eliminating morbidity and interrupting transmission, however, may require expanded control initiatives including community-wide treatment, and improved water, sanitation, and hygiene. Lymphatic filariasis burden has decreased since the implementation of preventive chemotherapy, with all but two provinces having reached the elimination of lymphatic filariasis as a public health problem.

Project description:The elimination of lymphatic filariasis (LF) is achieved through repeated mass drug administration (MDA) of anti-filarial medications, which interrupts transmission and prevents new infections. Accurate transmission assessments are critical to deciding when to stop MDA. Current methods for evaluating transmission may be insufficiently sensitive, resulting in post-MDA resurgence. We, therefore, evaluated potential diagnostic testing scenarios for post-MDA surveillance. Data were used from two surveys (a household cluster and a cohort) conducted in an area of Mandalay Region, Myanmar, with ongoing transmission following several rounds of MDA. First, age- and sex-adjusted seroprevalence were estimated for the area using the household survey. Next, three Bayesian networks were built from the combined datasets to compare antigens by immunochromatic testing (ICT) and/or Og4C3 enzyme-linked immunosorbent assay (ELISA) and antibody (Ab) detection methods (Wb123 or Bm14 Ab ELISA). The networks were checked for validity and then used to compare diagnostic testing scenarios. The adjusted prevalence from the household survey for antigen, Wb123 Ab and Bm14 Ab were 4.4% (95% CI 2.6-7.3%), 8.7% (5.96-12.5%) and 20.8% (16.0-26.6%), respectively. For the three networks, the True Skill Statistic and Area Under the Receiver Operating Characteristic Curve for antigen, Wb123 and Bm14 Ab were 0.79, 0.68 and 0.55; and 0.97, 0.92 and 0.80, respectively. In the Bayesian network analysis, a positive case was defined as testing positive to one or more infection markers. A missed result was therefore the probability of a positive case having a negative test result to an alternate marker. The probability of a positive case prior to any testing scenario was 17.4%, 16.8% and 26.6% for antigen, Wb123 Ab and Bm14 Ab, respectively. In the antigen-only testing scenario, the probability of a missed positive LF result was 5.2% for Wb123 and 15.6% for Bm14 Ab. The combination of antigen plus Bm14 Ab testing reduced the probability of missing a positive LF case as measured by Wb123 Ab to 0.88%. The combination of antigen plus Wb123 Ab was less successful and yielded an 11.5% probability of a missed positive result by Bm14 Ab testing. Across scenarios, there was a greater discordance between Bm14 and both antigen and Wb123 Ab in the 1-10 age group compared to older ages. These findings suggest that the addition of Bm14 Ab improves the sensitivity of LF testing for current or past infection. The combination of antigen plus Bm14 Ab should therefore be considered for inclusion in post-MDA surveillance to improve the sensitivity of transmission surveys and prevent the premature cessation of MDA.

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.

Dataset Information

Preventive chemotherapy reverses covert, lymphatic-associated tissue change in young people with lymphatic filariasis in Myanmar.

Publications

Preventive chemotherapy reverses covert, lymphatic-associated tissue change in young people with lymphatic filariasis in Myanmar.

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