Evaluating Molecular Xenomonitoring as a Tool for Lymphatic Filariasis Surveillance in Samoa, 2018-2019.
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SUBMITTER: McPherson B
PROVIDER: S-EPMC9414188 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Evaluating Molecular Xenomonitoring as a Tool for Lymphatic Filariasis Surveillance in Samoa, 2018-2019.
McPherson Brady B Mayfield Helen J HJ McLure Angus A Gass Katherine K Naseri Take T Thomsen Robert R Williams Steven A SA Pilotte Nils N Kearns Therese T Graves Patricia M PM Lau Colleen L CL
Tropical medicine and infectious disease 20220822 8
Molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), is a potentially useful surveillance strategy for lymphatic filariasis (LF) elimination programs. Delay in filarial antigen (Ag) clearance post-treatment is a limitation of using human surveys to provide an early indicator of the impact of mass drug administration (MDA), and MX may be more useful in this setting. We compared prevalence of infected mosquitoes pre- and post-MDA (2018 and 2019) ...[more]
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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.
| S-EPMC5089733 | biostudies-literature
Project description:BackgroundMass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed 'molecular xenomonitoring,' can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the inhabited islands of American Samoa to identify areas of possible continuing LF transmission after completion of MDA.Methodology/principle findingsMosquitoes were collected using BG Sentinel traps from most of the villages on American Samoa's largest island, Tutuila, and all major villages on the smaller islands of Aunu'u, Ofu, Olosega, and Ta'u. Real-time PCR was used to detect Wuchereria bancrofti DNA in pools of ≤ 20 mosquitoes, and PoolScreen software was used to infer territory-wide prevalences of W. bancrofti DNA in the mosquitoes. Wuchereria bancrofti DNA was found in mosquitoes from 16 out of the 27 village areas sampled on Tutuila and Aunu'u islands but none of the five villages on the Manu'a islands of Ofu, Olosega, and Ta'u. The overall 95% confidence interval estimate for W. bancrofti DNA prevalence in the LF vector Ae. polynesiensis was 0.20-0.39%, and parasite DNA was also detected in pools of Culex quinquefasciatus, Aedes aegypti, and Aedes (Finlaya) spp.Conclusions/significanceOur results suggest low but widespread prevalence of LF on Tutuila and Aunu'u where 98% of the population resides, but not Ofu, Olosega, and Ta'u islands. Molecular xenomonitoring can help identify areas of possible LF transmission, but its use in the LF elimination program in American Samoa is limited by the need for more efficient mosquito collection methods and a better understanding of the relationship between prevalence of W. bancrofti DNA in mosquitoes and infection and transmission rates in humans.
| S-EPMC4133231 | biostudies-literature
Project description:BackgroundScabies is a common skin infestation caused by the Sarcoptes scabei mite. Ivermectin, one of three drugs used in mass drug administration (MDA) for lymphatic filariasis, is also effective for treating scabies. Ivermectin-based MDA was first conducted in Samoa in August 2018, with ivermectin being offered to those aged ≥5 years. Here, we report scabies prevalence in Samoa after MDA.MethodsWe conducted household surveys 1.5-3.5 months (Survey 1) and 6-8 months (Survey 2) after the 2018 MDA in 35 primary sampling units. We conducted clinical examination for scabies-like rash and used International Alliance for the Control of Scabies classification criteria. We estimated scabies prevalence by age, gender and region. Multivariable logistic regression was used to assess factors associated with prevalence.ResultsWe surveyed 2868 people (499 households) and 2796 people (544 households) aged 0-75 years in Surveys 1 and 2, respectively. Scabies prevalence increased from 2.4% (95% CI 2.1-2.7%) to 4.4% (95% CI 4.0-4.9%) between surveys. Scabies was associated with younger age (0-4 years: aOR 3.5 [2.9-4.2]; 5-15 years: aOR 1.6 [1.4-1.8] compared to ≥16 years), female gender (aOR 1.2 [95% CI 1.1-1.4]; region (aOR range from 1.4 [1.1-1.7] to 2.5 [2.1-3.1] between regions), large households (aOR 2.6 [2.0-3.4] households ≥13), and not taking MDA in 2018 (aOR 1.3 [95% CI 1.1-1.6]).ConclusionsWe found moderate prevalence of scabies in two population-representative surveys conducted within 8 months of the 2018 MDA for lymphatic filariasis. Prevalence appeared to increase between the surveys, and ongoing surveillance is recommended, particularly in young children.
| S-EPMC10497159 | biostudies-literature
Project description:BackgroundMolecular xenomonitoring (MX), the detection of pathogen DNA in mosquitoes, is a recommended approach to support lymphatic filariasis (LF) elimination efforts. Potential roles of MX include detecting presence of LF in communities and quantifying progress towards elimination of the disease. However, the relationship between MX results and human prevalence is poorly understood.MethodsWe conducted a systematic review and meta-analysis from all previously conducted studies that reported the prevalence of filarial DNA in wild-caught mosquitoes (MX rate) and the corresponding prevalence of microfilaria (mf) in humans. We calculated a pooled estimate of MX sensitivity for detecting positive communities at a range of mf prevalence values and mosquito sample sizes. We conducted a linear regression to evaluate the relationship between mf prevalence and MX rate.ResultsWe identified 24 studies comprising 144 study communities. MX had an overall sensitivity of 98.3% (95% confidence interval, 41.5-99.9%) and identified 28 positive communities that were negative in the mf survey. Low sensitivity in some studies was attributed to small mosquito sample sizes (<1000) and very low mf prevalence (<0.25%). Human mf prevalence and mass drug administration status accounted for approximately half of the variation in MX rate (R2 = 0.49, P < .001). Data from longitudinal studies showed that, within a given study area, there is a strong linear relationship between MX rate and mf prevalence (R2 = 0.78, P < .001).ConclusionsMX shows clear potential as tool for detecting communities where LF is present and as a predictor of human mf prevalence.
| S-EPMC8201559 | biostudies-literature
Project description:BACKGROUND:Lymphatic filariasis (LF) is targeted for elimination by the year 2020. As of 2017, 67 of the 72 endemic countries have implemented annual Mass Drug Administration (MDA) for interrupting LF transmission. Transmission Assessment Survey (TAS) is the recommended protocol to evaluate the impact of MDA and to decide when to stop MDA in an Evaluation Unit (EU, population ≤2 million). As the human infection levels go down with repeated MDA rounds, it becomes a challenge to select the appropriate survey methods to assess transmission interruption. This study validates a standard protocol for molecular xenomonitoring of infection in vectors (MX) at an EU as a complementary tool for TAS to stop MDA and its utility for post-MDA or post-validation surveillance. METHODOLOGY:The study was conducted in Cuddalore district, Tamil Nadu, India, which was found eligible for TAS after 15 annual rounds of MDA (4 with DEC alone and 11 with DEC plus albendazole). The district was divided into two EUs as per the TAS protocol and one EU was randomly selected for the study. A two-stage cluster design vector sampling, developed and validated at a sub-district level, was implemented in 30 randomly selected clusters in the EU. Female Culex quinquefasciatus were collected placing gravid traps overnight (1800-0600 hrs) inside the premises of systematically selected households. Pools of 20-25 blood-fed, semi-gravid and gravid Cx. quinquefasciatus were subjected to real-time quantitative PCR (polymerase chain reaction) assay for detecting Wuchereria bancrofti DNA. Pool infection rate (% of pools positive for W. bancrofti DNA), and the estimated prevalence of W. bancrofti DNA in mosquitoes and its 95% confidence interval were calculated. Additionally, in these 30 clusters, microfilaria (Mf) survey among individuals >5 years old was carried out. School-based TAS was conducted using Immunochromatographic Card Test (ICT) in the EU. Prepared itemized cost-menu for different cost components of MX survey and TAS were estimated and compared. RESULTS:MX survey showed that only 11 (3.1%) of the 358 pools (8850 Cx.quinquefasciatus females), collected from 30 clusters, were found positive for W. bancrofti DNA. The estimated vector infection rate was 0.13% (95% CI: 0.07-0.22%), below the provisional threshold (0.25%) for transmission interruption. Of 1578 children tested in the TAS, only four (0.25%) were positive for filarial antigenemia, and it is well below the critical cut-off (18 positives) for stopping MDA. Among 9804 persons tested in the 30 clusters, only four were found positive for Mf (0.04%; 95% CI: 0.01-0.1%). The Mf-prevalence was <1% threshold for transmission interruption in humans. The estimated costs for TAS and MX per EU were $14,104 USD and $14,259 USD respectively. CONCLUSIONS:The result of MX protocol was in good agreement with that of TAS, providing evidence to recommend MX as a complementary tool to TAS to decide on stopping MDA. MX can also be a potential surveillance tool for post-MDA and post-validation phases as it could detect sites with residual infection and risk of resurgence of transmission. MX is economically feasible as its cost is slightly higher than that of TAS.
| S-EPMC7001988 | biostudies-literature
Project description:BackgroundSamoa conducted eight nationwide rounds of mass drug administration (MDA) for lymphatic filariasis (LF) between 1999 and 2011, and two targeted rounds in 2015 and 2017 in North West Upolu (NWU), one of three evaluation units (EUs). Transmission Assessment Surveys (TAS) were conducted in 2013 (failed in NWU) and 2017 (all three EUs failed). In 2018, Samoa was the first in the world to distribute nationwide triple-drug MDA using ivermectin, diethylcarbamazine, and albendazole. Surveillance and Monitoring to Eliminate LF and Scabies from Samoa (SaMELFS Samoa) is an operational research program designed to evaluate the effectiveness of triple-drug MDA on LF transmission and scabies prevalence in Samoa, and to compare the usefulness of different indicators of LF transmission. This paper reports results from the 2018 baseline survey and aims to i) investigate antigen (Ag) prevalence and spatial epidemiology, including geographic clustering; ii) compare Ag prevalence between two different age groups (5-9 years versus ≥10 years) as indicators of areas of ongoing transmission; and iii) assess the prevalence of limb lymphedema in those aged ≥15 years.MethodsA community-based cluster survey was conducted in 30 randomly selected and five purposively selected clusters (primary sampling units, PSUs), each comprising one or two villages. Participants were recruited through household surveys (age ≥5 years) and convenience surveys (age 5-9 years). Alere Filariasis Test Strips (FTS) were used to detect Ag, and prevalence was adjusted for survey design and standardized for age and gender. Adjusted Ag prevalence was estimated for each age group (5-9, ≥10, and all ages ≥5 years) for random and purposive PSUs, and by region. Intraclass correlation (ICC) was used to quantify clustering at regions, PSUs, and households.ResultsA total of 3940 persons were included (1942 children aged 5-9 years, 1998 persons aged ≥10 years). Adjusted Ag prevalence in all ages ≥5 years in randomly and purposively selected PSUs were 4.0% (95% CI 2.8-5.6%) and 10.0% (95% CI 7.4-13.4%), respectively. In random PSUs, Ag prevalence was lower in those aged 5-9 years (1.3%, 95% CI 0.8-2.1%) than ≥10 years (4.7%, 95% CI 3.1-7.0%), and poorly correlated at the PSU level (R-square = 0.1459). Adjusted Ag prevalence in PSUs ranged from 0% to 10.3% (95% CI 5.9-17.6%) in randomly selected and 3.8% (95% CI 1.3-10.8%) to 20.0% (95% CI 15.3-25.8%) in purposively selected PSUs. ICC for Ag-positive individuals was higher at households (0.46) compared to PSUs (0.18) and regions (0.01).ConclusionsOur study confirmed ongoing transmission of LF in Samoa, in accordance with the 2017 TAS results. Ag prevalence varied significantly between PSUs, and there was poor correlation between prevalence in 5-9 year-olds and older ages, who had threefold higher prevalence. Sampling older age groups would provide more accurate estimates of overall prevalence, and be more sensitive for identifying residual hotspots. Higher prevalence in purposively selected PSUs shows local knowledge can help identify at least some hotspots.
| S-EPMC7785238 | biostudies-literature
Project description:IntroductionMolecular xenomonitoring (MX)-pathogen detection in the mosquito rather than human-is a promising tool for lymphatic filariasis (LF) surveillance. In the Recife Metropolitan Region (RMR), the last LF focus in Brazil, Culex quinquefasciatus mosquitoes have been implicated in transmitting Wuchereria bancrofti parasites. This paper presents findings on the ideal mosquito collection method, mosquito dispersion, W. bancrofti infection in mosquitoes and W. bancrofti antigen in humans to aid MX development.MethodsExperiments occurred within two densely populated urban areas of Olinda, RMR, in July and August 2015. U.S. Centers for Disease Control and Prevention (CDC) light traps were compared to battery-powered aspirators as collection methods, and mosquito dispersion was measured by mosquito mark release recapture (MMRR). Female Cx. quinquefasciatus were tested by PCR for W. bancrofti infection, and study area residents were screened by rapid tests for W. bancrofti antigen.ResultsAspirators caught 2.6 times more total Cx. quinquefasciatus, including 38 times more blood-fed and 5 times more gravid stages, than CDC light traps. They also collected 123 times more Aedes aegypti. Of the 9,644 marked mosquitoes released, only ten (0.01%) were recaptured, nine of which were < 50m (34.8m median, 85.4m maximum) from the release point. Of 9,169 unmarked mosquitoes captured in the MMR, 38.3% were unfed, 48.8% blood-fed, 5.5% semi-gravid, and 7.3% gravid. PCR on 182 pools (1,556 mosquitoes) found no evidence of W. bancrofti infection in Cx. quinquefasciatus. Rapid tests on 110 of 111 eligible residents were all negative for W. bancrofti antigen.ConclusionsAspirators were more effective than CDC light traps at capturing Ae. aegypti and all but unfed stages of Cx. quinquefasciatus. Female Cx. quinquefasciatus traveled short (< 86m) distances in this urban area. Lack of evidence for W. bancrofti infection in mosquitoes and antigen in humans in these fine-scale studies does not indicate that LF transmission has ceased in the RMR. A MX surveillance system should consider vector-specific collection methods, mosquito dispersion, and spatial scale but also local context, environmental factors such as sanitation, and host factors such as infection prevalence and treatment history.
| S-EPMC6203399 | biostudies-literature
Project description:Monitoring Wuchereria bancrofti infection in mosquitoes (xenomonitoring) can play an important role in determining when lymphatic filariasis has been eliminated, or in focusing control efforts. As mosquito infection rates can be low, a method for collecting large numbers of mosquitoes is necessary. Gravid traps collected large numbers of Culex quinquefasciatus in Tanzania, and a collection method that targets mosquitoes that have already fed could result in increased sensitivity in detecting W. bancrofti-infected mosquitoes. The aim of this experiment was to test this hypothesis by comparing U.S. Centers for Disease Control and Prevention (CDC) light traps with CDC gravid traps in northeastern Tanzania, where Cx. quinquefasciatus is a vector of lymphatic filariasis. After an initial study where small numbers of mosquitoes were collected, a second study collected 16,316 Cx. quinquefasciatus in 60 gravid trap-nights and 240 light trap-nights. Mosquitoes were pooled and tested for presence of W. bancrofti DNA. Light and gravid traps collected similar numbers of mosquitoes per trap-night, but the physiological status of the mosquitoes was different. The estimated infection rate in mosquitoes collected in light traps was considerably higher than in mosquitoes collected in gravid traps, so light traps can be a useful tool for xenomonitoring work in Tanzania.
| S-EPMC4703286 | biostudies-literature
Project description:Following the first triple-drug mass drug administration (MDA) for lymphatic filariasis in Samoa in 2018, unexpected persistence of microfilaria (Mf) positivity in 18 (15%) of 121 antigen-positive persons was observed in a nationwide household survey 1-2 months later. Of the 18 Mf positive persons, 14 reported taking the MDA, raising concerns about MDA efficacy. In 2019, 5-6 months after the 2018 survey, a monitored treatment study was done to evaluate directly observed weight-based treatment in these Mf positive individuals. Mf presence and density were assessed before and 7 days after treatment, using 1 mL membrane filtered venous blood, and 60 uL thick blood films on slides prepared from venous or fingerprick blood. All 14 participants were still Mf positive on filters from venous blood pre-treatment samples, but two were negative by slide made from the same samples. Mf were cleared completely by day 7 in 12 of 13 participants followed up, and by day 30 in the remaining participant. Filtered blood using EDTA samples (to reduce clumping of Mf) is preferred over slides alone for improving the likelihood of detecting Mf and estimating their density. The triple-drug MDA strategy was effective at clearing Mf when given and taken at the correct dose.
| S-EPMC8167748 | biostudies-literature
Project description:Under the Global Program to Eliminate Lymphatic Filariasis (LF) American Samoa conducted seven rounds of mass drug administration (MDA) between 2000 and 2006. Subsequently, the territory passed the WHO recommended school-based transmission assessment survey (TAS) in 2011/2012 (TAS-1) and 2015 (TAS-2) but failed in 2016, when both TAS-3 and a community survey found LF antigen prevalence above what it had been in previous surveys. This study aimed to identify potential environmental drivers of LF to refine future surveillance efforts to detect re-emergence and recurrence. Data on five LF infection markers: antigen, Wb123, Bm14 and Bm33 antibodies and microfilaraemia, were obtained from a population-wide serosurvey conducted in American Samoa in 2016. Spatially explicit data on environmental factors were derived from freely available sources. Separate multivariable Poisson regression models were developed for each infection marker to assess and quantify the associations between LF infection markers and environmental variables. Rangeland, tree cover and urban cover were consistently associated with a higher seroprevalence of LF-infection markers, but to varying magnitudes between landcover classes. High slope gradient, population density and crop cover had a negative association with the seroprevalence of LF infection markers. No association between rainfall and LF infection markers was detected, potentially due to the limited variation in rainfall across the island. This study demonstrated that seroprevalence of LF infection markers were more consistently associated with topographical environmental variables, such as gradient of the slope, rather than climatic variables, such as rainfall. These results provide the initial groundwork to support the detection of areas where LF transmission is more likely to occur, and inform LF elimination efforts through better understanding of the environmental drivers.
| S-EPMC9609614 | biostudies-literature