Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 56 Records) |
Query Trace: Won K [original query] |
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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. |
Spatial, environmental, and individual associations with Anopheles albimanus salivary antigen IgG in Haitian children
Jaramillo-Underwood A , Herman C , Impoinvil D , Sutcliff A , Knipes A , Worrell CM , Fox LM , Desir L , Fayette C , Javel A , Monestime F , Mace KE , Chang MA , Lemoine JF , Won K , Udhayakumar V , Rogier E . Front Cell Infect Microbiol 2022 12 1033917 IgG serology can be utilized to estimate exposure to Anopheline malaria vectors and the Plasmodium species they transmit. A multiplex bead-based assay simultaneously detected IgG to Anopheles albimanus salivary gland extract (SGE) and four Plasmodium falciparum antigens (CSP, LSA-1, PfAMA1, and PfMSP1) in 11,541 children enrolled at 350 schools across Haiti in 2016. Logistic regression estimated odds of an above-median anti-SGE IgG response adjusting for individual- and environmental-level covariates. Spatial analysis detected statistically significant clusters of schools with students having high anti-SGE IgG levels, and spatial interpolation estimated anti-SGE IgG levels in unsampled locations. Boys had 11% (95% CI: 0.81, 0.98) lower odds of high anti-SGE IgG compared to girls, and children seropositive for PfMSP1 had 53% (95% CI: 1.17, 2.00) higher odds compared to PfMSP1 seronegatives. Compared to the lowest elevation, quartiles 2-4 of higher elevation were associated with successively lower odds (0.81, 0.43, and 0.34, respectively) of high anti-SGE IgG. Seven significant clusters of schools were detected in Haiti, while spatially interpolated results provided a comprehensive picture of anti-SGE IgG levels in the study area. Exposure to malaria vectors by IgG serology with SGE is a proxy to approximate vector biting in children and identify risk factors for vector exposure. |
Severe monkeypox in hospitalized patients - United States, August 10-October 10, 2022
Miller MJ , Cash-Goldwasser S , Marx GE , Schrodt CA , Kimball A , Padgett K , Noe RS , McCormick DW , Wong JM , Labuda SM , Borah BF , Zulu I , Asif A , Kaur G , McNicholl JM , Kourtis A , Tadros A , Reagan-Steiner S , Ritter JM , Yu Y , Yu P , Clinton R , Parker C , Click ES , Salzer JS , McCollum AM , Petersen B , Minhaj FS , Brown E , Fischer MP , Atmar RL , DiNardo AR , Xu Y , Brown C , Goodman JC , Holloman A , Gallardo J , Siatecka H , Huffman G , Powell J , Alapat P , Sarkar P , Hanania NA , Bruck O , Brass SD , Mehta A , Dretler AW , Feldpausch A , Pavlick J , Spencer H , Ghinai I , Black SR , Hernandez-Guarin LN , Won SY , Shankaran S , Simms AT , Alarcón J , O'Shea JG , Brooks JT , McQuiston J , Honein MA , O'Connor SM , Chatham-Stephens K , O'Laughlin K , Rao AK , Raizes E , Gold JAW , Morris SB . MMWR Morb Mortal Wkly Rep 2022 71 (44) 1412-1417 As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority. |
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. |
Spatial cluster analysis of Plasmodium vivax and P. malariae exposure using serological data among Haitian school children sampled between 2014 and 2016
Oviedo A , Herman C , Knipes A , Worrell CM , Fox LM , Desir L , Fayette C , Javel A , Monestime F , Mace KE , Chang MA , Lemoine JF , Won K , Udhayakumar V , Rogier E . PLoS Negl Trop Dis 2022 16 (1) e0010049 BACKGROUND: Estimation of malaria prevalence in very low transmission settings is difficult by even the most advanced diagnostic tests. Antibodies against malaria antigens provide an indicator of active or past exposure to these parasites. The prominent malaria species within Haiti is Plasmodium falciparum, but P. vivax and P. malariae infections are also known to be endemic. METHODOLOGY/PRINCIPAL FINDINGS: From 2014-2016, 28,681 Haitian children were enrolled in school-based serosurveys and were asked to provide a blood sample for detection of antibodies against multiple infectious diseases. IgG against the P. falciparum, P. vivax, and P. malariae merozoite surface protein 19kD subunit (MSP119) antigens was detected by a multiplex bead assay (MBA). A subset of samples was also tested for Plasmodium DNA by PCR assays, and for Plasmodium antigens by a multiplex antigen detection assay. Geospatial clustering of high seroprevalence areas for P. vivax and P. malariae antigens was assessed by both Ripley's K-function and Kulldorff's spatial scan statistic. Of 21,719 children enrolled in 680 schools in Haiti who provided samples to assay for IgG against PmMSP119, 278 (1.27%) were seropositive. Of 24,559 children enrolled in 788 schools providing samples for PvMSP119 serology, 113 (0.46%) were seropositive. Two significant clusters of seropositivity were identified throughout the country for P. malariae exposure, and two identified for P. vivax. No samples were found to be positive for Plasmodium DNA or antigens. CONCLUSIONS/SIGNIFICANCE: From school-based surveys conducted from 2014 to 2016, very few Haitian children had evidence of exposure to P. vivax or P. malariae, with no children testing positive for active infection. Spatial scan statistics identified non-overlapping areas of the country with higher seroprevalence for these two malarias. Serological data provides useful information of exposure to very low endemic malaria species in a population that is unlikely to present to clinics with symptomatic infections. |
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. |
HIV infection in Eastern and Southern Africa: Highest burden, largest challenges, greatest potential
Parker E , Judge MA , Macete E , Nhampossa T , Dorward J , Langa DC , de Schacht C , Couto A , Vaz P , Vitoria M , Molfino L , Idowu RT , Bhatt N , Naniche D , Le Souëf PN . South Afr J HIV Med 2021 22 (1) 1237 Background: The burden of HIV is especially concerning for Eastern and Southern Africa (ESA), as despite expansion of test-and-treat programmes, this region continues to experience significant challenges resulting from high rates of morbidity, mortality and new infections. Hard-won lessons from programmes on the ground in ESA should be shared. Objectives: This report summarises relevant evidence and regional experts’ recommendations regarding challenges specific to ESA. Method: This commentary includes an in-depth review of relevant literature, progress against global goals and consensus opinion from experts. Results: Recommendations include priorities for essential research (surveillance data collection, key and vulnerable population education and testing, in-country testing trials and evidence-based support services to improve retention in care) as well as research that can accelerate progress towards the prevention of new infections and achieving ambitious global goals in ESA. Conclusion: The elimination of HIV in ESA will require continued investment, commitment to evidence-based programmes and persistence. Local research is critical to ensuring that responses in ESA are targeted, efficient and evaluated. © 2021. The Authors. Licensee: AOSIS. |
Mapping the endemicity and seasonality of clinical malaria for intervention targeting in Haiti using routine case data
Cameron E , Young AJ , Twohig KA , Pothin E , Bhavnani D , Dismer A , Merilien JB , Hamre K , Meyer P , Le Menach A , Cohen JM , Marseille S , Lemoine JF , Telfort MA , Chang MA , Won K , Knipes A , Rogier E , Amratia P , Weiss DJ , Gething PW , Battle KE . Elife 2021 10 Towards the goal of malaria elimination on Hispaniola, the National Malaria Control Program of Haiti and its international partner organisations are conducting a campaign of interventions targeted to high-risk communities prioritised through evidence-based planning. Here we present a key piece of this planning: an up-to-date, fine-scale endemicity map and seasonality profile for Haiti informed by monthly case counts from 771 health facilities reporting from across the country throughout the 6-year period from January 2014 to December 2019. To this end, a novel hierarchical Bayesian modelling framework was developed in which a latent, pixel-level incidence surface with spatio-temporal innovations is linked to the observed case data via a flexible catchment sub-model designed to account for the absence of data on case household locations. These maps have focussed the delivery of indoor residual spraying and focal mass drug administration in the Grand'Anse Department in South-Western Haiti. |
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. |
Barriers and facilitators for cascade testing in genetic conditions: a systematic review
Srinivasan S , Won NY , Dotson WD , Wright ST , Roberts MC . Eur J Hum Genet 2020 28 (12) 1631-1644 Cascade testing is the process of offering genetic counseling and testing to at-risk relatives of an individual who has been diagnosed with a genetic condition. It is critical for increasing the identification rates of individuals with these conditions and the uptake of appropriate preventive health services. The process of cascade testing is highly varied in clinical practice, and a comprehensive understanding of factors that hinder or enhance its implementation is necessary to improve this process. We conducted a systematic review to identify barriers and facilitators for cascade testing and searched PubMed, CINAHL via EBSCO, Web of Science, EMBASE, and the Cochrane Library for articles published from the databases' inception to November 2018. Thirty articles met inclusion criteria. Barriers and facilitators identified from these studies at the individual-level were organized into the following categories: (1) demographics, (2) knowledge, (3) attitudes, beliefs, and emotional responses of the individual, and (4) perceptions of relatives, relatives' responses, and attitudes toward relatives. At the interpersonal-level, barriers and facilitators were categorized as (1) family communication-, support- and dynamics-, and (2) provider-factors. Finally, barriers at the environmental-level relating to accessibility of genetic services were also identified. Our findings suggest that several individual, interpersonal and environmental factors may play a role in cascade testing. Future studies to further investigate these barriers and facilitators are needed to inform future interventions for improving the implementation of cascade testing for genetic conditions in clinical practice. |
2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
Kuhn JH , Adkins S , Alioto D , Alkhovsky SV , Amarasinghe GK , Anthony SJ , Avšič-Županc T , Ayllón MA , Bahl J , Balkema-Buschmann A , Ballinger MJ , Bartonička T , Basler C , Bavari S , Beer M , Bente DA , Bergeron É , Bird BH , Blair C , Blasdell KR , Bradfute SB , Breyta R , Briese T , Brown PA , Buchholz UJ , Buchmeier MJ , Bukreyev A , Burt F , Buzkan N , Calisher CH , Cao M , Casas I , Chamberlain J , Chandran K , Charrel RN , Chen B , Chiumenti M , Choi IR , Clegg JCS , Crozier I , da Graça JV , Dal Bó E , Dávila AMR , de la Torre JC , de Lamballerie X , de Swart RL , Di Bello PL , Di Paola N , Di Serio F , Dietzgen RG , Digiaro M , Dolja VV , Dolnik O , Drebot MA , Drexler JF , Dürrwald R , Dufkova L , Dundon WG , Duprex WP , Dye JM , Easton AJ , Ebihara H , Elbeaino T , Ergünay K , Fernandes J , Fooks AR , Formenty PBH , Forth LF , Fouchier RAM , Freitas-Astúa J , Gago-Zachert S , Gāo GF , García ML , García-Sastre A , Garrison AR , Gbakima A , Goldstein T , Gonzalez JJ , Griffiths A , Groschup MH , Günther S , Guterres A , Hall RA , Hammond J , Hassan M , Hepojoki J , Hepojoki S , Hetzel U , Hewson R , Hoffmann B , Hongo S , Höper D , Horie M , Hughes HR , Hyndman TH , Jambai A , Jardim R , Jiāng D , Jin Q , Jonson GB , Junglen S , Karadağ S , Keller KE , Klempa B , Klingström J , Kobinger G , Kondō H , Koonin EV , Krupovic M , Kurath G , Kuzmin IV , Laenen L , Lamb RA , Lambert AJ , Langevin SL , Lee B , Lemos ERS , Leroy EM , Li D , Lǐ J , Liang M , Liú W , Liú Y , Lukashevich IS , Maes P , Marciel de Souza W , Marklewitz M , Marshall SH , Martelli GP , Martin RR , Marzano SL , Massart S , McCauley JW , Mielke-Ehret N , Minafra A , Minutolo M , Mirazimi A , Mühlbach HP , Mühlberger E , Naidu R , Natsuaki T , Navarro B , Navarro JA , Netesov SV , Neumann G , Nowotny N , Nunes MRT , Nylund A , Økland AL , Oliveira RC , Palacios G , Pallas V , Pályi B , Papa A , Parrish CR , Pauvolid-Corrêa A , Pawęska JT , Payne S , Pérez DR , Pfaff F , Radoshitzky SR , Rahman AU , Ramos-González PL , Resende RO , Reyes CA , Rima BK , Romanowski V , Robles Luna G , Rota P , Rubbenstroth D , Runstadler JA , Ruzek D , Sabanadzovic S , Salát J , Sall AA , Salvato MS , Sarpkaya K , Sasaya T , Schwemmle M , Shabbir MZ , Shí X , Shí Z , Shirako Y , Simmonds P , Širmarová J , Sironi M , Smither S , Smura T , Song JW , Spann KM , Spengler JR , Stenglein MD , Stone DM , Straková P , Takada A , Tesh RB , Thornburg NJ , Tomonaga K , Tordo N , Towner JS , Turina M , Tzanetakis I , Ulrich RG , Vaira AM , van den Hoogen B , Varsani A , Vasilakis N , Verbeek M , Wahl V , Walker PJ , Wang H , Wang J , Wang X , Wang LF , Wèi T , Wells H , Whitfield AE , Williams JV , Wolf YI , Wú Z , Yang X , Yáng X , Yu X , Yutin N , Zerbini FM , Zhang T , Zhang YZ , Zhou G , Zhou X . Arch Virol 2020 165 (12) 3023-3072 In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. |
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. |
Combination of Serological, Antigen Detection, and DNA Data for Plasmodium falciparum Provides Robust Geospatial Estimates for Malaria Transmission in Haiti.
Oviedo A , Knipes A , Worrell C , Fox LM , Desir L , Fayette C , Javel A , Monestime F , Mace K , Chang MA , Udhayakumar V , Lemoine JF , Won K , Lammie PJ , Rogier E . Sci Rep 2020 10 (1) 8443 Microscopy is the gold standard for malaria epidemiology, but laboratory and point-of-care (POC) tests detecting parasite antigen, DNA, and human antibodies against malaria have expanded this capacity. The island nation of Haiti is endemic for Plasmodium falciparum (Pf) malaria, though at a low national prevalence and heterogenous geospatial distribution. In 2015 and 2016, serosurveys were performed of children (ages 6-7 years) sampled in schools in Saut d'Eau commune (n = 1,230) and Grand Anse department (n = 1,664) of Haiti. Children received malaria antigen rapid diagnostic test and provided a filter paper blood sample for further laboratory analysis of the Pf histidine-rich protein 2 (HRP2) antigen, Pf DNA, and anti-Pf IgG antibodies. Prevalence of Pf infection ranged from 0.0-16.7% in 53 Saut d'Eau schools, and 0.0-23.8% in 56 Grand Anse schools. Anti-Pf antibody carriage exceeded 80% of students in some schools from both study sites. Geospatial prediction ellipses were created to indicate clustering of positive tests within the survey areas and overlay of all prediction ellipses for the different types of data revealed regions with high likelihood of active and ongoing Pf malaria transmission. The geospatial utilization of different types of Pf data can provide high confidence for spatial epidemiology of the parasite. |
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. |
Commensal Neisseria Kill Neisseria gonorrhoeae through a DNA-Dependent Mechanism.
Kim WJ , Higashi D , Goytia M , Rendon MA , Pilligua-Lucas M , Bronnimann M , McLean JA , Duncan J , Trees D , Jerse AE , So M . Cell Host Microbe 2019 26 (2) 228-239 e8 The mucosa is colonized with commensal Neisseria. Some of these niches are sites of infection for the STD pathogen Neisseria gonorrhoeae (Ngo). Given the antagonistic behavior of commensal bacteria toward their pathogenic relatives, we hypothesized that commensal Neisseria may negatively affect Ngo colonization. Here, we report that commensal species of Neisseria kill Ngo through a mechanism based on genetic competence and DNA methylation state. Specifically, commensal-triggered killing occurs when the pathogen takes up commensal DNA containing a methylation pattern that it does not recognize. Indeed, any DNA will kill Ngo if it can enter the cell, is differentially methylated, and has homology to the pathogen genome. Consistent with these findings, commensal Neisseria elongata accelerates Ngo clearance from the mouse in a DNA-uptake-dependent manner. Collectively, we propose that commensal Neisseria antagonizes Ngo infection through a DNA-mediated mechanism and that DNA is a potential microbicide against this highly drug-resistant pathogen. |
Taxonomy of the order Bunyavirales: update 2019.
Abudurexiti A , Adkins S , Alioto D , Alkhovsky SV , Avsic-Zupanc T , Ballinger MJ , Bente DA , Beer M , Bergeron E , Blair CD , Briese T , Buchmeier MJ , Burt FJ , Calisher CH , Chang C , Charrel RN , Choi IR , Clegg JCS , de la Torre JC , de Lamballerie X , Deng F , Di Serio F , Digiaro M , Drebot MA , Duan X , Ebihara H , Elbeaino T , Ergunay K , Fulhorst CF , Garrison AR , Gao GF , Gonzalez JJ , Groschup MH , Gunther S , Haenni AL , Hall RA , Hepojoki J , Hewson R , Hu Z , Hughes HR , Jonson MG , Junglen S , Klempa B , Klingstrom J , Kou C , Laenen L , Lambert AJ , Langevin SA , Liu D , Lukashevich IS , Luo T , Lu C , Maes P , de Souza WM , Marklewitz M , Martelli GP , Matsuno K , Mielke-Ehret N , Minutolo M , Mirazimi A , Moming A , Muhlbach HP , Naidu R , Navarro B , Nunes MRT , Palacios G , Papa A , Pauvolid-Correa A , Paweska JT , Qiao J , Radoshitzky SR , Resende RO , Romanowski V , Sall AA , Salvato MS , Sasaya T , Shen S , Shi X , Shirako Y , Simmonds P , Sironi M , Song JW , Spengler JR , Stenglein MD , Su Z , Sun S , Tang S , Turina M , Wang B , Wang C , Wang H , Wang J , Wei T , Whitfield AE , Zerbini FM , Zhang J , Zhang L , Zhang Y , Zhang YZ , Zhang Y , Zhou X , Zhu L , Kuhn JH . Arch Virol 2019 164 (7) 1949-1965 In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV). |
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. |
Identifying residual transmission of lymphatic filariasis after mass drug administration: Comparing school-based versus community-based surveillance - American Samoa, 2016
Sheel M , Sheridan S , Gass K , Won K , Fuimaono S , Kirk M , Gonzales A , Hedtke SM , Graves PM , Lau CL . PLoS Negl Trop Dis 2018 12 (7) e0006583 INTRODUCTION: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration (MDA) from 2000-2006. The World Health Organization recommends systematic post-MDA surveillance using Transmission Assessment Surveys (TAS) for epidemiological assessment of recent LF transmission. We compared the effectiveness of two survey designs for post-MDA surveillance: a school-based survey of children aged 6-7 years, and a community-based survey targeting people aged >/=8 years. METHODS: In 2016, we conducted a systematic school-based TAS in all elementary schools (N = 29) and a cluster survey in 28 villages on the two main islands of American Samoa. We collected information on demographics and risk factors for infection using electronic questionnaires, and recorded geo-locations of schools and households. Blood samples were collected to test for circulating filarial antigen (CFA) using the Alere Filariasis Test Strip. For those who tested positive, we prepared slides for microscopic examination of microfilaria and provided treatment. Descriptive statistics were performed for questionnaire variables. Data were weighted and adjusted to account for sampling design and sex for both surveys, and for age in the community survey. RESULTS: The school-based TAS (n = 1143) identified nine antigen-positive children and found an overall adjusted CFA prevalence of 0.7% (95% CI: 0.3-1.8). Of the nine positive children, we identified one microfilariaemic 7-year-old child. The community-based survey (n = 2507, 711 households) identified 102 antigen-positive people, and estimated an overall adjusted CFA prevalence of 6.2% (95% CI: 4.5-8.6). Adjusted village-level prevalence ranged from 0-47.1%. CFA prevalence increased with age and was higher in males. Of 86 antigen-positive community members from whom slides were prepared, 22 (25.6%) were microfilaraemic. School-based TAS had limited sensitivity (range 0-23.8%) and negative predictive value (range 25-83.3%) but had high specificity (range 83.3-100%) and positive predictive value (range 0-100%) for identifying villages with ongoing transmission. CONCLUSIONS: American Samoa failed the school-based TAS in 2016, and the community-based survey identified higher than expected numbers of antigen-positive people. School-based TAS was logistically simpler and enabled sampling of a larger proportion of the target population, but the results did not provide a good indication of the overall CFA prevalence in older age groups and was not sensitive at identifying foci of ongoing transmission. The community-based survey, although operationally more challenging, identified antigen-positive individuals of all ages, and foci of high antigen prevalence. Both surveys confirmed recrudescence of LF transmission. |
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. |
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