Last data update: Mar 21, 2025. (Total: 48935 publications since 2009)
Records 1-30 (of 35 Records) |
Query Trace: Won KY[original query] |
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Laboratory comparison of rapid antigen diagnostic tests for lymphatic filariasis: STANDARD Q Filariasis Antigen Test (QFAT) versus Bioline Filariasis Test Strip (FTS)
Graves PM , Scott JL , Berg Soto A , Widi AYN , Whittaker M , Lau CL , Won KY . Trop Med Infect Dis 2025 10 (1) ![]() ![]() Accurate rapid diagnostic tests (RDTs) are needed to diagnose lymphatic filariasis (LF) in global elimination programmes. We evaluated the performance of the new STANDARD Q Filariasis Antigen Test (QFAT) against the Bioline Filariasis Test Strip (FTS) for detecting W. bancrofti antigen (Ag) in laboratory conditions, using serum (n = 195) and plasma (n = 189) from LF-endemic areas (Samoa, American Samoa and Myanmar) and Australian negative controls (n = 46). The prior Ag status of endemic samples (54.9% Ag-positive) was determined by rapid test (ICT or FTS) or Og4C3 ELISA. The proportion of samples testing positive at 10 min was similar for QFAT (44.8%) and FTS (41.3%). Concordance between tests was 93.5% (kappa 0.87, n = 417) at 10 min, and it increased to 98.8% (kappa 0.98) at 24 h. The sensitivities of QFAT and FTS at 10 min compared to the prior results were 92% (95% CI 88.0-96.0) and 86% (95% CI 80.0-90.0), respectively, and they increased to 97% and 99% at 24 h. Specificity was 98% for QFAT and 99% for FTS at 10 min. Both tests showed evidence of cross-reaction with Dirofilaria repens and Onchocerca lupi but not with Acanthochilonema reconditum or Cercopithifilaria bainae. Under laboratory conditions, QFAT is a suitable alternative RDT to FTS. |
Field laboratory comparison of STANDARD Q Filariasis Antigen Test (QFAT) with Bioline Filariasis Test Strip (FTS) for the detection of Lymphatic Filariasis in Samoa, 2023
Scott JL , Mayfield HJ , Sinclair JE , Martin BM , Howlett M , Muttucumaru R , Won KY , Thomsen R , Viali S , Tofaeono-Pifeleti R , Graves PM , Lau CL . PLoS Negl Trop Dis 2024 18 (8) e0012386 BACKGROUND: To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1-hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. CONCLUSION/SIGNIFICANCE: QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions. |
Geospatial analysis of Plasmodium falciparum serological indicators: school versus community sampling in a low-transmission malaria setting
Jaramillo-Underwood A , Herman C , Jean SE , Nace D , Elder ES , Robinson K , Knipes A , Worrell CM , Fox LM , Desir L , Fayette C , Javel A , Monestime F , Mace KE , Udhayakumar V , Won KY , Chang MA , Lemoine JF , Rogier E . BMC Med 2024 22 (1) 31 BACKGROUND: Due to low numbers of active infections and persons presenting to health facilities for malaria treatment, case-based surveillance is inefficient for understanding the remaining disease burden in low malaria transmission settings. Serological data through the detection of IgG antibodies from previous malaria parasite exposure can fill this gap by providing a nuanced picture of where sustained transmission remains. Study enrollment at sites of gathering provides a potential approach to spatially estimate malaria exposure and could preclude the need for more intensive community-based sampling. METHODS: This study compared spatial estimates of malaria exposure from cross-sectional school- and community-based sampling in Haiti. A total of 52,405 blood samples were collected from 2012 to 2017. Multiplex bead assays (MBAs) tested IgG against P. falciparum liver stage antigen-1 (LSA-1), apical membrane antigen 1 (AMA1), and merozoite surface protein 1 (MSP1). Predictive geospatial models of seropositivity adjusted for environmental covariates, and results were compared using correlations by coordinate points and communes across Haiti. RESULTS: Consistent directional associations were observed between seroprevalence and environmental covariates for elevation (negative), air temperature (negative), and travel time to urban centers (positive). Spearman's rank correlation for predicted seroprevalence at coordinate points was lowest for LSA-1 (ρ = 0.10, 95% CI: 0.09-0.11), but improved for AMA1 (ρ = 0.36, 95% CI: 0.35-0.37) and MSP1 (ρ = 0.48, 95% CI: 0.47-0.49). CONCLUSIONS: In settings approaching P. falciparum elimination, case-based prevalence data does not provide a resolution of ongoing malaria transmission in the population. Immunogenic antigen targets (e.g., AMA1, MSP1) that give higher population rates of seropositivity provide moderate correlation to gold standard community sampling designs and are a feasible approach to discern foci of residual P. falciparum transmission in an area. |
Potential strategies for strengthening surveillance of lymphatic filariasis in American Samoa after mass drug administration: targeting older age groups, hotspots, and household members of infected persons (preprint)
Lau CL , Sheel M , Gass K , Fuimaono S , David MC , Won KY , Sheridan S , Graves PM . medRxiv 2020 2020.04.07.20056549 Background Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Here, we explore the potential of targeted strategies to strengthen post-MDA surveillance.Methodology/Principal Findings Using Ag data plus new antibody data (Wb123, Bm14, Bm33) from the 2016 surveys, we identified risk factors for seropositivity using multivariable logistic regression. We compared TAS with strategies that targeted high-risk subpopulations (older ages, householders of Ag-positive TAS children [index children]) and/or known hotspots, and used NNTestav (average number needed to test to identify one positive) to compare sampling efficiency.Antibody prevalence in TAS-3 (n=1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n=2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of index children. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali’i (aOR 15.81), and outdoor workers (aOR 2.61). Using Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies.Conclusions/Significance We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS), followed by targeted strategies in subgroups and locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. The utility of antibodies in surveillance should also be explored.AUTHOR SUMMARY Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito bites. Globally, tens of millions are infected, with many disfigured and disabled by severe damage to their lymphatic systems, such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). The Global Programme to Eliminate LF (GPELF) aims to interrupt disease transmission through mass drug administration (MDA), and to control illness and suffering in affected persons. The World Health Organization recommends conducting Transmission Assessment Surveys (TAS) in school children aged 6 to 7 years, to determine if infection rates have dropped to levels where disease transmission is no longer sustainable. From 2000-2006, American Samoa conducted MDA and made significant progress towards eliminating LF. However, despite passing TAS in 2011/2012 and 2015, surveys in 2016 showed evidence of resurgence. Our study explored alternative surveillance strategies and compared their efficiency with TAS. Based on our findings, we recommended that in addition to TAS, strategies that target high-risk populations and hotspots would strengthen surveillance and help countries achieve their goals of LF elimination.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work received financial support from the Coalition for Operational Research on Neglected Tropical Diseases (COR-NTD), which is funded at The Task Force for Global Health primarily by the Bill & Melinda Gates Foundation [OPP1053230], the United Kingdom Department for International Development, and by the United States Agency for International Development through its Neglected Tropical Diseases Program. CLL was supported by an Australian National Health and Medical Research Council Fellowship (1109035). MS was supported by a fellowship funded by the Westpac Scholars Trust. The funders had no role in study design, data collection and analysis, decisi n to publish, or preparation of the manuscript.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated and analysed during the present study are available from the corresponding author upon reasonable request. |
Fine-scale heterogeneity in Schistosoma mansoni force of infection measured through antibody response (preprint)
Arnold BF , Kanyi H , Njenga SM , Rawago FO , Priest JW , Secor WE , Lammie PJ , Won KY , Odiere MR . medRxiv 2020 2020.04.10.20061101 Identifying populations with active transmission and monitoring changes in transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected in stool using microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to schistosomiasis soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. Serological measures of transmission closely aligned with stool-based measures of infection, and serological measures provided better resolution for between-community differences at lower levels of infection. Serology enabled fine- scale measures of heterogeneity in force of infection both geographically and by age. Our results show that serologic surveillance platforms represent an important new opportunity to guide and monitor schistosomiasis control programs.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by the National Institutes of Allergy and Infectious Diseases (K01 AI119180 to BFA) and the Bill & Melinda Gates Foundation (OPP1022543 to PJL). The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData and replication files required to conduct the analyses are available through GitHub and the Open Science Framework: https://osf.io/rnme8. Community location data required to replicate the geostatistical model fits is not publicly available to protect participant confidentiality but is available from the corresponding author upon request, pending appropriate human subjects review and approval. https://osf.io/rnme8 |
Multiplex serologic testing within a cross-sectional lymphatic filariasis sentinel site survey in coastal Kenya reveals community-level differences in IgG antibody responses to parasitic diseases and vaccines (preprint)
Njenga SM , Kanyi HM , Arnold BF , Matendechero SH , Onsongo JK , Won KY , Priest JW . bioRxiv 2019 604181 Accurate, cost-effective measurement of the burden of co-endemic infections would enable public health managers to identify opportunities for implementation of integrated control programs. Dried blood spots (DBS) collected during a cross-sectional lymphatic filariasis sentinel site survey in the Kenyan coastal counties of Lamu, Tana River, Kilifi, Kwale, and Taita-Taveta were used for the integrated detection of serologic IgG antibodies against antigens from several parasitic infections (Wuchereria bancrofti, Schistosoma mansoni, Plasmodium spp, Ascaris lumbricoides, and Strongyloides stercoralis) as well as markers for immunity to vaccine-preventable diseases (measles, diphtheria, and tetanus) on a multiplex bead assay (MBA) platform. High heterogeneity was observed in antibody responses by pathogen and antigen across the sentinel sites. Antibody seroprevalence against Wb123, Bm14, and Bm33 recombinant filarial antigens were generally higher in Ndau Island (p<0.0001), which also had the highest prevalence of filarial antigenemia compared to other communities. Antibody responses to the Plasmodium species antigens CSP and MSP-119 were higher in Kilifi and Kwale counties, with Jaribuni community showing higher overall mean seroprevalence (p<0.0001). Kimorigo community in Taita-Taveta County was the only area where antibody responses against Schistosoma mansoni Sm25 recombinant antigen were detected. Seroprevalence rates to Strongyloides antigen NIE ranged between 3% and 26%, and there was high heterogeneity in immune responses against an Ascaris antigen among the study communities. Differences were observed between communities in terms of seroprevalence to vaccine-preventable diseases. Seroprotection to tetanus was lower in all 3 communities in Kwale County compared to the rest of the communities. This study has demonstrated that the MBA platform holds promise for rapid integrated monitoring of trends of infections of public health importance in endemic areas, and assessing the effectiveness of control and elimination programs.Author Summary Establishment of successful private-public partnerships in the recent past has led to an increase in resources available for control and elimination of malaria and Neglected Tropical Diseases (NTDs). Implementation of control and elimination programs and their subsequent monitoring and evaluation would be greatly facilitated by development of new tools and strategies for rapid identification of areas of transmission so that interventions could be prioritized to regions where they were most needed. Since development of antibody responses in a host depend on exposure to an infectious agent, assessment of such serologic markers provides a sensitive way to measure differences between populations in pathogen exposure. Our study applied a state-of-the-art multiplex bead assay platform to perform integrated measurement of antibody responses to multiple parasitic diseases and immunizing antigens for vaccine-preventable diseases (VPDs) in ten lymphatic filariasis sentinel sites across the Kenyan coastal region. A community-level analysis of age-specific and overall mean seroprevalence fit using a flexible model ensemble provided an improved understanding about the distributions of the various parasitic infections and seroprotection to VPDs. This study provides an important proof of concept for how we could dramatically increase the value of existing surveillance activities using small volumes of blood collected on filter paper and analyzed using a single multiplex laboratory assay and novel data analysis techniques. |
Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug administration surveillance, American Samoa (preprint)
Cadavid Restrepo AM , Gass K , Won KY , Sheel M , Robinson K , Graves PM , Fuimaono S , Lau CL . medRxiv 2021 02 Objectives Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2) based on World Health Organization guidelines. In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa. Methods We examined school-level Ag and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson's chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. Results Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5). Conclusion Anti-filarial Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-MDA surveillance and decision making should be further investigated in other settings. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
The importance of partnership in the rollout of triple-drug therapy to eliminate lymphatic filariasis in the Pacific
Rainima-Qaniuci M , Lepaitai HB , Bhagirov R , Padmasiri E , Naseri T , Thomsen R , Won KY , Brant TA , Dodd E , Nua MT , Utu F , Tufa A , Chutaro E , Camacho J , Suiaunoa-Scanlan L , Thean LJ , Mani J , Hardy M , Samuela J , Romani L , Kaldor J , Steer AC , Faktaufon D , Bechu V , Naqio F , Sosene V , Sekihara M , Otaki J , Buhagiar TS , Yajima A . Am J Trop Med Hyg 2022 106 39-47 We discuss the experience of some Pacific island countries in introducing the new WHO-recommended treatment protocol for lymphatic filariasis-a triple-drug therapy composed of ivermectin, diethylcarbamazine, and albendazole. The successful rollout of the new treatment protocol was dependent on strong partnerships among these countries' ministries of health, WHO, and other stakeholders. Effective communication among these partners allowed for lessons learned to cross borders and have a positive impact on the experiences of other countries. We also describe various challenges confronted during this process and the ways these countries overcame them. |
Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug administration surveillance, American Samoa
Restrepo AMC , Gass K , Won KY , Sheel M , Robinson K , Graves PM , Fuimaono S , Lau CL . Int J Infect Dis 2022 117 378-386 OBJECTIVES: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2). In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa. METHODS: We examined school-level antigen (Ag) and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson's chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. RESULTS: Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5). CONCLUSION: Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-mass drug administration (MDA) surveillance and decision making should be further investigated in other settings. |
Diagnostics to support elimination of lymphatic filariasis-Development of two target product profiles
Won KY , Gass K , Biamonte M , Dagne DA , Ducker C , Hanna C , Hoerauf A , Lammie PJ , Njenga SM , Noordin R , Ramaiah KD , Ramzy R , Scholte RGC , Solomon AW , Souza AA , Tappero J , Toubali E , Weil GJ , Williams SA , King JD . PLoS Negl Trop Dis 2021 15 (11) e0009968 As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools. |
Potential strategies for strengthening surveillance of lymphatic filariasis in American Samoa after mass drug administration: Reducing 'number needed to test' by targeting older age groups, hotspots, and household members of infected persons
Lau CL , Sheel M , Gass K , Fuimaono S , David MC , Won KY , Sheridan S , Graves PM . PLoS Negl Trop Dis 2020 14 (12) e0008916 Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali'i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6-7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies. We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS or population representative survey of older ages), followed by strategies that target subpopulations and/or locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. Surveillance programs should also explore the utility of antibodies as indicators of transmission. |
Fine-scale heterogeneity in Schistosoma mansoni force of infection measured through antibody response
Arnold BF , Kanyi H , Njenga SM , Rawago FO , Priest JW , Secor WE , Lammie PJ , Won KY , Odiere MR . Proc Natl Acad Sci U S A 2020 117 (37) 23174-23181 Schistosomiasis is among the most common parasitic diseases in the world, with over 142 million people infected in low- and middle-income countries. Measuring population-level transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected using stool microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to S. mansoni soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. We estimated force of infection among children using the seroconversion rate and examined how it varied geographically and by age. At the community level, serological measures of transmission aligned with stool-based measures of infection (ρ = 0.94), and serological measures provided more resolution for between-community differences at lower levels of infection. Force of infection showed a clear gradient of transmission with distance from Lake Victoria, with 94% of infections and 93% of seropositive children in communities <1.5 km from the lake. Force of infection increased through age 3 y, by which time 65% (95% CI: 53%, 75%) of children were SEA positive in high-transmission communities-2 y before they would be reached by school-based deworming programs. Our results show that serologic surveillance platforms represent an important opportunity to guide and monitor schistosomiasis control programs, and that in high-transmission settings preschool-age children represent a key population missed by school-based deworming programs. |
Notes from the field: Impact of a mass drug administration campaign using a novel three-drug regimen on lymphatic filariasis antigenemia - American Samoa, 2019
Hast MA , Tufa A , Brant TA , Suiaunoa-Scanlan L , Camacho J , Vaifanua-Leo J , Robinson K , Dodd E , Sili B , Lees LS , Won KY , Utu F . MMWR Morb Mortal Wkly Rep 2020 69 (21) 656-657 Lymphatic filariasis is a debilitating and disfiguring mosquitoborne parasitic disease. As part of the Global Programme to Eliminate Lymphatic Filariasis, the World Health Organization (WHO) recommends at least five rounds of annual mass drug administration (MDA) in areas with endemic disease to reduce incidence and prevalence (1). Onward transmission is expected to end once community prevalence falls below 1% (1). | | American Samoa, located in the southern Pacific Ocean, is the only U.S. territory with evidence of ongoing lymphatic filariasis transmission. After 7 years of MDA (2000–2006), the prevalence of lymphatic filariasis antigenemia in American Samoa declined from 16.5% to 2.3%, and MDA was stopped (2,3). In 2016, a household survey among 2,507 participants revealed that the prevalence of antigenemia had rebounded to 6.2%, and transmission was ascertained to be widespread across the territory (4). MDA was resumed in 2018 using a novel three-drug regimen of ivermectin, diethylcarbamazine, and albendazole, which has been shown to more effectively clear filarial larvae from the blood than the standard two-drug treatment of albendazole with diethylcarbamazine or ivermectin alone (5,6). This WHO-recommended three-drug regimen is anticipated to accelerate progress toward global elimination goals in areas without other filarial infections that would contraindicate the use of diethylcarbamazine (onchocerciasis) or ivermectin (loiasis). |
Integrated cross-sectional multiplex serosurveillance of IgG antibody responses to parasitic diseases and vaccines in Coastal Kenya
Njenga SM , Kanyi HM , Arnold BF , Matendechero SH , Onsongo JK , Won KY , Priest JW . Am J Trop Med Hyg 2019 102 (1) 164-176 Accurate and cost-effective identification of areas where co-endemic infections occur would enable public health managers to identify opportunities for implementation of integrated control programs. Dried blood spots collected during cross-sectional lymphatic filariasis surveys in coastal Kenya were used for exploratory integrated detection of IgG antibodies against antigens from several parasitic infections (Wuchereria bancrofti, Schistosoma mansoni, Plasmodium spp., Ascaris lumbricoides, and Strongyloides stercoralis) as well as for detection of responses to immunizing agents used against vaccine-preventable diseases (VPDs) (measles, diphtheria, and tetanus) using a multiplex bead assay (MBA) platform. High heterogeneity was observed in antibody responses by pathogen and antigen across the sentinel sites. Antibody seroprevalence against filarial antigens were generally higher in Ndau Island (P < 0.0001), which also had the highest prevalence of filarial antigenemia compared with other communities. Antibody responses to the Plasmodium species antigens CSP and MSP-119 were higher in Kilifi and Kwale counties, with Jaribuni community showing higher overall mean seroprevalence (P < 0.0001). Kimorigo community in Taita-Taveta County was the only area where antibody responses against S. mansoni Sm25 recombinant antigen were detected. Seroprevalence rates to Strongyloides antigen NIE ranged between 3% and 26%, and there was high heterogeneity in immune responses against an Ascaris antigen among the study communities. Differences were observed between communities in terms of seroprevalence to VPDs. Seroprotection to tetanus was generally lower in Kwale County than in other counties. This study has demonstrated that MBA holds promise for rapid integrated monitoring of trends of infections of public health importance in endemic areas. |
Laboratory evaluation of a rapid IgG4 antibody test (BLF Rapid) for Bancroftian filariasis
Noordin R , Yunus MH , Robinson K , Won KY , Babu S , Fischer PU , Hisam S , Mahmud R . Am J Trop Med Hyg 2018 99 (6) 1587-1590 At the end phase of the Global Programme to Eliminate Lymphatic Filariasis, antibody testing may have a role in decision-making for bancroftian filariasis-endemic areas. This study evaluated the diagnostic performance of BLF Rapid(), a prototype immunochromatographic IgG4-based test using BmSXP recombinant protein, for detection of bancroftian filariasis. The test was evaluated using 258 serum samples, comprising 96 samples tested at Universiti Sains Malaysia (in-house) and 162 samples tested independently at three international laboratories in the USA and India, and two laboratories in Malaysia. The independent testing involved 99 samples from Wuchereria bancrofti microfilaria or antigen positive individuals and 63 samples from people who were healthy or had other infections. The in-house evaluation showed 100% diagnostic sensitivity and specificity. The independent evaluations showed a diagnostic sensitivity of 84-100% and 100% specificity (excluding non-lymphatic filarial infections). BLF Rapid has potential as a surveillance diagnostic tool to make "Transmission Assessment Survey"-stopping decisions and conduct post-elimination surveillance. |
Comparison of antigen and antibody responses in repeat lymphatic filariasis transmission assessment surveys in American Samoa
Won KY , Robinson K , Hamlin KL , Tufa J , Seespesara M , Wiegand RE , Gass K , Kubofcik J , Nutman TB , Lammie PJ , Fuimaono S . PLoS Negl Trop Dis 2018 12 (3) e0006347 BACKGROUND: Current WHO recommendations for lymphatic filariasis (LF) surveillance advise programs to implement activities to monitor for new foci of transmission after stopping mass drug administration (MDA). A current need in the global effort to eliminate LF is to standardize diagnostic tools and surveillance activities beyond the recommended transmission assessment survey (TAS). METHODOLOGY: TAS was first conducted in American Samoa in 2011 (TAS 1) and a repeat TAS was carried out in 2015 (TAS 2). Circulating filarial antigen (CFA) and serologic results from both surveys were analyzed to determine whether interruption of LF transmission has been achieved in American Samoa. PRINCIPAL FINDINGS: A total of 1,134 and 864 children (5-10 years old) were enrolled in TAS 1 and TAS 2, respectively. Two CFA-positive children were identified in TAS 1, and one CFA-positive child was identified in TAS 2. Results of both surveys were below the threshold for which MDA was warranted. Additionally, 1,112 and 836 dried blood spots from TAS 1 and TAS 2, respectively were tested for antibodies to Wb123, Bm14 and Bm33 by luciferase immunoprecipitation system (LIPS) assay and multiplex bead assay. In 2011, overall prevalence of responses to Wb123, Bm14, and Bm33 was 1.0%, 6.8% and 12.0%, respectively. In 2015, overall prevalence of positive Bm14 and Bm33 responses declined significantly to 3.0% (p<0.001) and 7.8% (p = 0.013), respectively. CONCLUSIONS/SIGNIFICANCE: Although passing TAS 1 and TAS 2 and an overall decline in the prevalence of antibodies to Bm14 and Bm33 between these surveys suggests decreased exposure and infection among young children, there were persistent responses in some schools. Clustering and persistence of positive antibody responses in schools may be an indication of ongoing transmission. There is a need to better understand the limitations of current antibody tests, but our results suggest that serologic tools can have a role in guiding programmatic decision making. |
Use of antibody tools to provide serologic evidence of elimination of lymphatic filariasis in the Gambia
Won KY , Sambou S , Barry A , Robinson K , Jaye M , Sanneh B , Sanyang A , Gass K , Lammie PJ , Rebollo M . Am J Trop Med Hyg 2017 98 (1) 15-20 A current need in the global effort to eliminate lymphatic filariasis (LF) is the availability of reliable diagnostic tools that can be used to guide programmatic decisions, especially decisions made in the final stages of the program. This study conducted in The Gambia aimed to assess antifilarial antibody levels among populations living in historically highly LF-endemic areas and to evaluate the use of serologic tools to confirm the interruption of LF transmission. A total of 2,612 dried blood spots (DBSs) collected from individuals aged 1 year and above from 15 villages were tested for antibodies to Wb123 by enzyme-linked immunosorbent assay (ELISA). A subset of DBS (N = 599) was also tested for antibodies to Bm14 by ELISA. Overall, the prevalence of Wb123 was low (1.5%, 95% confidence interval [CI] 1.1-2.1%). In 7 of 15 villages (46.7%), there were no Wb123-positive individuals identified. Individuals with positive responses to Wb123 ranged in age from 3 to 100 years. Overall, Bm14 prevalence was also low (1.5%, 95% CI 0.7-2.8%). Bm14 positivity was significantly associated with older age (P < 0.001). The low levels of antibody responses to Wb123 observed in our study strongly suggest that sustainable LF transmission has likely ceased in The Gambia. In addition, our results support the conclusion that serologic tools can have a role in guiding programmatic decision making and supporting surveillance. |
Translating research into reality: Elimination of lymphatic filariasis from Haiti
Lammie PJ , Eberhard ML , Addiss DG , Won KY , Beau de Rochars M , Direny AN , Milord MD , Lafontant JG , Streit TG . Am J Trop Med Hyg 2017 97 71-75 Research provides the essential foundation of disease elimination programs, including the global program to eliminate lymphatic filariasis (GPELF). The development and validation of new diagnostic tools and intervention strategies, critical steps in the evolution of GPELF, required a global effort. Lymphatic filariasis research in Haiti involved many partners and was directly linked to the development of the national elimination program and to the success achieved to date. Ongoing research efforts involving many partners will continue to be important in resolving the challenges faced by the program today in its final efforts to achieve elimination. |
Multiplex serologic assessment of schistosomiasis in Western Kenya: Antibody responses in preschool aged children as a measure of reduced transmission
Won KY , Kanyi HM , Mwende FM , Wiegand RE , Goodhew EB , Priest JW , Lee YM , Njenga SM , Secor WE , Lammie PJ , Odiere MR . Am J Trop Med Hyg 2017 96 (6) 1460-1467 Currently, impact of schistosomiasis control programs in Schistosoma mansoni-endemic areas is monitored primarily by assessment of parasitologic indicators only. Our study was conducted to evaluate the use of antibody responses as a way to measure the impact of schistosomiasis control programs. A total of 3,612 serum samples collected at three time points from children 1-5 years of age were tested for antibody responses to two schistosome antigens (soluble egg antigen [SEA] and Sm25) by multiplex bead assay. The overall prevalence of antibody responses to SEA was high at baseline (50.0%). After one round of mass drug administration (MDA), there was minimal change in odds of SEA positivity (odds ratio [OR] = 1.02, confidence interval [CI] = 0.79-1.32, P = 0.89). However, after two rounds of treatment, there was a slight decrease in odds of SEA positivity (OR = 0.80, CI = 0.63-1.02, P = 0.08). In contrast to the SEA results, prevalence of antibody responses to Sm25 was lowest at baseline (14.1%) and higher in years 2 (19.8%) and 3 (18.4%). After one round of MDA, odds of Sm25 positivity increased significantly (OR = 1.51, CI = 1.14-2.02, P = 0.005) and remained significantly higher than baseline after two rounds of MDA (OR = 1.37, CI = 1.07-1.76, P = 0.01). There was a significant decrease in the proportion of 1-year-olds with positive SEA responses from 33.1% in year 1 to 13.2% in year 3 and a corresponding decrease in the odds (OR = 3.25, CI = 1.75-6.08, P < 0.001). These results provide preliminary evidence that schistosomiasis program impact can be monitored using serologic responses. |
Assessment of lymphatic filariasis prior to re-starting mass drug administration campaigns in coastal Kenya
Njenga SM , Kanyi HM , Mutungi FM , Okoyo C , Matendechero HS , Pullan RL , Halliday KE , Brooker SJ , Wamae CN , Onsongo JK , Won KY . Parasit Vectors 2017 10 (1) 99 BACKGROUND: Lymphatic filariasis (LF) is a debilitating disease associated with extensive disfigurement and is one of a diverse group of diseases referred to as neglected tropical diseases (NTDs) which mainly occur among the poorest populations. In line with global recommendations to eliminate LF, Kenya launched its LF elimination programme in 2002 with the aim to implement annual mass drug administration (MDA) in order to interrupt LF transmission. However, the programme faced financial and administrative challenges over the years such that sustained annual MDA was not possible. Recently, there has been renewed interest to eliminate LF and the Kenyan Ministry of Health, through support from World Health Organization (WHO), restarted annual MDA in 2015. The objective of this study was to evaluate the current status of LF infection in the endemic coastal region of Kenya before MDA campaigns were restarted. RESULTS: Ten sentinel sites in Kwale, Kilifi, Tana River, Lamu, and Taita-Taveta counties in coastal Kenya were selected for participation in a cross-sectional survey of LF infection prevalence. At least 300 individuals in each sentinel village were sampled through random house-to-house visits. During the day, the point-of-care immunochromatographic test (ICT) was used to detect the presence of Wuchereria bancrofti circulating filarial antigen in finger prick blood samples collected from residents of the selected sentinel villages. Those individuals who tested positive with the ICT test were requested to provide a night-time blood sample for microfilariae (MF) examination. The overall prevalence of filarial antigenaemia was 1.3% (95% CI: 0.9-1.8%). Ndau Island in Lamu County had the highest prevalence (6.3%; 95% CI: 4.1-9.7%), whereas sites in Kilifi and Kwale counties had prevalences < 1.7%. Mean microfilarial density was also higher in Ndau Island (234 MF/ml) compared to sentinel sites in Kwale and Kilifi counties (< 25 MF/ml). No LF infection was detected in Tana River and Taita-Taveta counties. Overall, more than 88% of the study participants reported to have used a bed net the previous night. CONCLUSIONS: Prevalence of LF infection is generally very low in coastal Kenya, but there remain areas that require further rounds of MDA if the disease is to be eliminated as a public health problem in line with the ongoing global elimination efforts. However, areas where there was no evidence of LF transmission should be considered for WHO-recommended transmission assessment surveys in view of stopping MDA. |
Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti
Knipes AK , Lemoine JF , Monestime F , Fayette CR , Direny AN , Desir L , Beau de Rochars VE , Streit TG , Renneker K , Chu BK , Chang MA , Mace KE , Won KY , Lammie PJ . PLoS Negl Trop Dis 2017 11 (2) e0005387 BACKGROUND: Since 2001, Haiti's National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of LF through annual mass drug administration with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti's NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. METHODOLOGY/PRINCIPLE FINDINGS: The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment for STH to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. CONCLUSIONS/SIGNIFICANCE: Haiti's 2014-2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria. |
Tetanus immunity gaps in children 5-14 years and men ≥ 15 years of age revealed by integrated disease serosurveillance in Kenya, Tanzania, and Mozambique
Scobie HM , Patel M , Martin D , Mkocha H , Njenga SM , Odiere MR , Pelletreau S , Priest JW , Thompson R , Won KY , Lammie PJ . Am J Trop Med Hyg 2016 96 (2) 415-420 Recent tetanus cases associated with male circumcision in Eastern and Southern Africa (ESA) prompted an examination of tetanus immunity by age and sex using multiplex serologic data from community surveys in three ESA countries during 2012-2013. Tetanus seroprotection was lower among children 5-14 years versus 1-4 years of age in Kenya (66% versus 90%) and Tanzania (66% versus 89%), but not in Mozambique (91% versus 88%), where children receive two booster doses in school. Among males ≥ 15 years of age, tetanus seroprotection was lower than females in Kenya (45% versus 96%), Tanzania (28% versus 94%), and Mozambique (64% versus 90%). Tetanus immunity from infant vaccination doses wanes over time, and only women of reproductive age routinely receive booster doses. To prevent immunity gaps in older children, adolescents, and adult men, a life-course vaccination strategy is needed to provide the three recommended tetanus booster doses. |
Lymphatic Filariasis Elimination in American Samoa: Evaluation of Molecular Xenomonitoring as a Surveillance Tool in the Endgame.
Lau CL , Won KY , Lammie PJ , Graves PM . PLoS Negl Trop Dis 2016 10 (11) e0005108 ![]() 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. |
A cross-sectional study on schistosomiasis and soil-transmitted helminths in Mbita district, western Kenya using different copromicroscopic techniques
Ng'etich AI , Rawago FO , Jura WG , Mwinzi PN , Won KY , Odiere MR . Parasit Vectors 2016 9 (1) 87 BACKGROUND: Identification of populations to be targeted for individual treatment and broad-spectrum therapy in schistosomiasis-endemic areas, assessment of therapy efficacy, morbidity, and evaluation of control strategies need to be based on reliable diagnostic tools. Kato-Katz is routinely used and remains the standard diagnostic technique for schistosomiasis, despite its many challenges. This study was conducted in Nyamanga village, Mbita, western Kenya, and evaluated the diagnostic performance of Kato-Katz, Mini-Parasep and modified Mini-FLOTAC techniques in detection of Schistosoma mansoni and soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and hookworm) ova. METHODS: Stool samples from 132 individuals were screened for eggs of S. mansoni by the 3 techniques. Mini-Parasep(R) faecal parasite concentrator (Apacor Ltd, England), a single-use diagnostic device with a built-in filter for faecal concentration of helminth eggs by sedimentation was employed on stool samples fixed in 10 % formalin. A modified Mini-FLOTAC (University of Naples, Italy) was based on floatation of helminths eggs with two different solutions (FS2 and FS7) using a closed system (Fill-FLOTAC) with 5 % formalin. Kato-Katz was performed following WHO recommendation. Prevalence of S. mansoni and STH, sensitivity and degree of agreement among the 3 techniques were determined. RESULTS: Prevalence of S. mansoni was 47.0 %, 34.1 % and 20.5 % by Mini-Parasep, Kato-Katz and modified Mini-FLOTAC FS7 techniques, respectively. Prevalence of any STH infection was 6.1 %, 3.0 %, 6.1 % and 6.8 % by Mini-Parasep, Kato-Katz, modified Mini-FLOTAC FS2 and modified Mini-FLOTAC FS7 techniques, respectively. Considering the pooled results of the three methods (Mini-Parasep, Kato-Katz and modified Mini-FLOTAC FS7) as diagnostic 'gold' standard, the sensitivity of Mini-Parasep, Kato-Katz and modified Mini-FLOTAC FS7 for S. mansoni was 77.5 %, 56.1 %, and 33.8 %, respectively. Mini-Parasep and modified Mini-FLOTAC FS7 techniques had moderate (kappa = 0.46) and fairly good (kappa = 0.25) agreements with Kato-Katz for S. mansoni, respectively. Mini-Parasep detected a higher proportion of light intensity S. mansoni infections compared to Kato-Katz, which detected high proportions of heavy infections. Mini-Parasep detected a similar mean number of S. mansoni eggs per gram (EPG) of stool compared to the standard Kato-Katz (62.9 vs 97.3; t (131) = -0.49, P = 0.6265) and significantly higher EPG compared to the modified Mini-FLOTAC FS7 (62.9 vs 34.6; t (131) = 5.39, P < 0.0001). CONCLUSIONS: The high sensitivity of Mini-Parasep suggests its promising potential as an alternative tool in enhancing diagnosis and in monitoring schistosomiasis transmission and determining endpoint of intervention programs, especially in low endemicity areas. Mini-Parasep is also easy to operate, safe and also permits work with fresh stool. |
Morbidity associated with schistosomiasis before and after treatment in young children in Rusinga Island, Western Kenya
Davis SM , Wiegand RE , Mulama F , Kareko EI , Harris R , Ochola E , Samuels AM , Rawago F , Mwinzi PM , Fox LM , Odiere MR , Won KY . Am J Trop Med Hyg 2015 92 (5) 952-8 Schistosoma mansoni infection is a major cause of organomegaly and ultimately liver fibrosis in adults. Morbidity in pre-school-aged children is less defined, and they are currently not included in mass drug administration (MDA) programs for schistosomiasis control. We report results of a study of the association of schistosomiasis with organomegaly in a convenience sample of 201 children under 7 years old in Rusinga, Kenya on two cross-sectional visits, before and after praziquantel treatment. Data included stool examination and serology for schistosomiasis, the Niamey ultrasound protocol to stage hepatosplenic morbidity including organomegaly, and potential confounders including malaria. Unadjusted and adjusted Poisson regressions were performed. The baseline prevalence of schistosomiasis by antibody and/or stool was 80.3%. Schistomiasis was associated with hepatomegaly (adjusted prevalence ratio [aPR] = 1.4; 95% confidence interval [CI]: 1.0-2.1) and splenomegaly (aPR = 2.4; 95% CI: 1.4-4.2). The association with hepatomegaly persisted posttreatment (aPR = 1.4; 95% CI: 1.1-1.6). Schistosomiasis was associated with morbidity in this cohort. Efforts to include young children in mass treatment campaigns should intensify. |
Seroprevalence and spatial epidemiology of lymphatic filariasis in American Samoa after successful mass drug administration
Lau CL , Won KY , Becker L , Soares Magalhaes RJ , Fuimaono S , Melrose W , Lammie PJ , Graves PM . PLoS Negl Trop Dis 2014 8 (11) e3297 BACKGROUND: As part of the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006, and passed transmission assessment surveys in 2011-2012. We examined the seroprevalence and spatial epidemiology of LF post-MDA to inform strategies for ongoing surveillance and to reduce resurgence risk. METHODS: ELISA for LF antigen (Og4C3) and antibodies (Wb123, Bm14) were performed on a geo-referenced serum bank of 807 adults collected in 2010. Risk factors assessed for association with sero-positivity included age, sex, years lived in American Samoa, and occupation. Geographic clustering of serological indicators was investigated to identify spatial dependence and household-level clustering. RESULTS: Og4C3 antigen of >128 units (positive) were found in 0.75% (95% CI 0.3-1.6%) of participants, and >32 units (equivocal plus positive) in 3.2% (95% CI 0.6-4.7%). Seroprevalence of Wb123 and Bm14 antibodies were 8.1% (95% CI 6.3-10.2%) and 17.9% (95% CI 15.3-20.7%) respectively. Antigen-positive individuals were identified in all ages, and antibody prevalence higher in older ages. Prevalence was higher in males, and inversely associated with years lived in American Samoa. Spatial distribution of individuals varied significantly with positive and equivocal levels of Og4C3 antigen, but not with antibodies. Using Og4C3 cutoff points of >128 units and >32 units, average cluster sizes were 1,242 m and 1,498 m, and geographical proximity of households explained 85% and 62% of the spatial variation respectively. CONCLUSIONS: High-risk populations for LF in American Samoa include adult males and recent migrants. We identified locations and estimated the size of possible residual foci of antigen-positive adults, demonstrating the value of spatial analysis in post-MDA surveillance. Strategies to monitor cluster residents and high-risk groups are needed to reduce resurgence risk. Further research is required to quantify factors contributing to LF transmission at the last stages of elimination to ensure that programme achievements are sustained. |
Molecular xenomonitoring using mosquitoes to map lymphatic filariasis after mass drug administration in American Samoa.
Schmaedick MA , Koppel AL , Pilotte N , Torres M , Williams SA , Dobson SL , Lammie PJ , Won KY . PLoS Negl Trop Dis 2014 8 (8) e3087 ![]() BACKGROUND: Mass 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 FINDINGS: Mosquitoes 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/SIGNIFICANCE: Our 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. |
Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration: a multicenter evaluation
Chu BK , Deming M , Biritwum NK , Bougma WR , Dorkenoo AM , El-Setouhy M , Fischer PU , Gass K , Gonzalez de Pena M , Mercado-Hernandez L , Kyelem D , Lammie PJ , Flueckiger RM , Mwingira UJ , Noordin R , Offei Owusu I , Ottesen EA , Pavluck A , Pilotte N , Rao RU , Samarasekera D , Schmaedick MA , Settinayake S , Simonsen PE , Supali T , Taleo F , Torres M , Weil GJ , Won KY . PLoS Negl Trop Dis 2013 7 (12) e2584 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. |
Assessment of quality of life as a tool for measuring morbidity due to Schistosoma mansoni infection and the impact of treatment
Won KY , Abudho B , Blackstock A , Montgomery SP , Kennedy ED , Person B , Mwinzi PN , Ochola EA , Foo KT , Hightower AW , Karanja DM , Secor WE . Am J Trop Med Hyg 2013 90 (2) 322-8 Recently, health measurements have broadened to include the assessment of quality of life (QOL). This study was conducted to assess whether the short form of the World Health Organization (WHO) QOL questionnaire (WHOQOL-BREF) was an effective tool for measuring morbidity due to Schistosoma mansoni infection and whether it could detect an impact of treatment with praziquantel. A total of 724 adults 18-85 years of age were enrolled. At baseline, S. mansoni prevalence was 73.2% by stool examination and 75.4% by circulating cathodic antigen, and there was no association between infection status and WHOQOL-BREF scores. Six months after treatment, S. mansoni prevalence was lower and the proportion of persons with higher WHOQOL-BREF scores significantly increased among persons who were infected at baseline. However, a similar increase was observed in persons infected at baseline. In areas of high prevalence, the WHOQOL-BREF may not be able to detect the benefits of schistosomiasis control programs. |
Laboratory and field evaluation of a new rapid test for detecting Wuchereria bancrofti antigen in human blood
Weil GJ , Curtis KC , Fakoli L , Fischer K , Gankpala L , Lammie PJ , Majewski AC , Pelletreau S , Won KY , Bolay FK , Fischer PU . Am J Trop Med Hyg 2013 89 (1) 11-15 Global Program to Eliminate Lymphatic Filariasis (GPELF) guidelines call for using filarial antigen testing to identify endemic areas that require mass drug administration (MDA) and for post-MDA surveillance. We compared a new filarial antigen test (the Alere Filariasis Test Strip) with the reference BinaxNOW Filariasis card test that has been used by the GPELF for more than 10 years. Laboratory testing of 227 archived serum or plasma samples showed that the two tests had similar high rates of sensitivity and specificity and > 99% agreement. However, the test strip detected 26.5% more people with filarial antigenemia (124/503 versus 98/503) and had better test result stability than the card test in a field study conducted in a filariasis-endemic area in Liberia. Based on its increased sensitivity and other practical advantages, we believe that the test strip represents a major step forward that will be welcomed by the GPELF and the filariasis research community. |
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