RESUMO
BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings. METHODS: We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84). RESULTS: Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective. CONCLUSIONS: Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.
Assuntos
Análise Custo-Benefício , Filariose Linfática , Administração Massiva de Medicamentos , Filariose Linfática/prevenção & controle , Filariose Linfática/epidemiologia , Filariose Linfática/economia , Humanos , Administração Massiva de Medicamentos/economia , Haiti/epidemiologia , Tanzânia/epidemiologia , Prevalência , Índia/epidemiologia , Animais , Erradicação de Doenças/economia , Erradicação de Doenças/métodos , Filaricidas/uso terapêutico , Filaricidas/administração & dosagem , Filaricidas/economia , Antígenos de Helmintos/sangue , CulexRESUMO
BACKGROUND: Lymphatic filariasis (LF) has been targeted for global elimination as a public health problem since 1997. The primary strategy to interrupt transmission is annual mass drug administration (MDA) for ≥5 years. The transmission assessment survey (TAS) was developed as a decision-making tool to measure LF antigenemia in children to determine when MDA in a region can be stopped. The objective of this study was to investigate potential sampling strategies for follow-up of LF-positive children identified in TAS to detect evidence of ongoing transmission. METHODOLOGY/PRINCIPLE FINDINGS: Nippes Department in Haiti passed TAS 1 with 2 positive cases and stopped MDA in 2015; however, 8 positive children were found during TAS 2 in 2017, which prompted a more thorough assessment of ongoing transmission. Purposive sampling was used to select the closest 50 households to each index case household, and systematic random sampling was used to select 20 households from each index case census enumeration area. All consenting household members aged ≥2 years were surveyed and tested for circulating filarial antigen (CFA) using the rapid filarial test strip and for Wb123-specific antibodies using the Filaria Detect IgG4 ELISA. Among 1,927 participants, 1.5% were CFA-positive and 4.5% were seropositive. CFA-positive individuals were identified for 6 of 8 index cases. Positivity ranged from 0.4-2.4%, with highest positivity in the urban commune Miragoane. Purposive sampling found the highest number of CFA-positives (17 vs. 9), and random sampling found a higher percent positive (2.4% vs. 1.4%). CONCLUSIONS/SIGNIFICANCE: Overall, both purposive and random sampling methods were reasonable and achievable methods of TAS follow-up in resource-limited settings. Both methods identified additional CFA-positives in close geographic proximity to LF-positive children found by TAS, and both identified strong signs of ongoing transmission in the large urban commune of Miragoane. These findings will help inform standardized guidelines for post-TAS surveillance.
Assuntos
Filariose Linfática , Filaricidas , Animais , Antígenos de Helmintos/uso terapêutico , Criança , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Filaricidas/uso terapêutico , Seguimentos , Haiti/epidemiologia , Humanos , Administração Massiva de Medicamentos/métodos , Prevalência , Wuchereria bancroftiRESUMO
BACKGROUND: The Transmission Assessment Survey (TAS) is a decision-making tool to determine when transmission of lymphatic filariasis is presumed to have reached a level low enough that it cannot be sustained even in the absence of mass drug administration. The survey is applied over geographic areas, called evaluation units (EUs); existing World Health Organization guidelines limit EU size to a population of no more than 2 million people. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, TASs were conducted in 14 small EUs in Haiti. Simulations, using the observed TAS results, were performed to understand the potential programmatic impact had Haiti chosen to form larger EUs. Nine "combination-EUs" were formed by grouping adjacent EUs, and bootstrapping was used to simulate the expected TAS results. When the combination-EUs were comprised of at least one "passing" and one "failing" EU, the majority of these combination-EU would pass the TAS 79% - 100% of the time. Even in the case when both component EUs had failed, the combination-EU was expected to "pass" 11% of the time. Simulations of mini-TAS, a strategy with smaller power and hence smaller sample size than TAS, resulted in more conservative "passing" and "failing" when implemented in original EUs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the high potential for misclassification when the average prevalence of lymphatic filariasis in the combined areas differs with regards to the TAS threshold. Of particular concern is the risk of "passing" larger EUs that include focal areas where prevalence is high enough to be potentially self-sustaining. Our results reaffirm the approach that Haiti took in forming smaller EUs. Where baseline or monitoring data show a high or heterogeneous prevalence, programs should leverage alternative strategies like mini-TAS in smaller EUs, or consider gathering additional data through spot check sites to advise EU formation.
Assuntos
Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Administração Massiva de Medicamentos , Densidade Demográfica , Simulação por Computador , Técnicas de Apoio para a Decisão , Filariose Linfática/transmissão , Filaricidas/administração & dosagem , Haiti/epidemiologia , Humanos , PrevalênciaRESUMO
Coverage evaluation surveys (CESs) are an important complement to routinely reported drug coverage estimates following mass drug administration for neglected tropical diseases (NTDs). Although the WHO recommends the routine use of CESs, they are rarely implemented. Reasons for this low uptake are multifaceted; one is uncertainty on the best sampling method. We conducted a multicountry study to compare the statistical characteristics, cost, time, and complexity of three commonly used CES sampling methods: the Expanded Program on Immunization's (EPI's) 30 × 7 cluster survey, a stratified design with systematic sampling within strata to enable lot quality assurance sampling (S-LQAS) decision rules, and probability sampling with segmentation (PSS). The three CES methods were used in Burkina Faso, Honduras, Malawi, and Uganda, and results were compared across the country sites. All three CES methods were found to be feasible. The S-LQAS approach took the least amount of time to complete and, consequently, was the least expensive; however, all three methods cost less than $5,000 per district. The PSS design resulted in an unbiased, equal-probability sample of the target populations. By contrast, the EPI approach had inherent bias related to the selection of households. Because of modifications needed to maintain feasibility, the S-LQAS method also resulted in a non-probability sample with less precision than the other two methods. Given the comparable cost and time of the three sampling methods and the statistical advantages of the PSS method, the PSS method was deemed to be the best for CESs in NTD programs.
Assuntos
Doenças Negligenciadas , Projetos de Pesquisa , Inquéritos e Questionários , Medicina Tropical , Burkina Faso , Custos e Análise de Custo , Honduras , Humanos , Amostragem para Garantia da Qualidade de Lotes , Malaui , Estudos de Amostragem , UgandaRESUMO
Antifilarial antibody testing has been established as a sensitive and specific method of diagnosing lymphatic filariasis. However, the development of serological responses to specific filarial antigens and their relationship to acquisition of infection is poorly understood. In order to evaluate whether the development of antigen specific antifilarial antibodies precedes microfilaremia and antigenemia, we compared the antibody responses of serum samples collected between 1990 and 1999 from a cohort of 142 Haitian children followed longitudinally. Antigen status was determined using the Og4C3 ELISA and the presence of microfilaremia was detected using microscopy. Antibody responses to Wb123, a Wuchereria bancrofti L3 antigen, were measured using a Luciferase Immunoprecipitation System (LIPS) assay. Antibody responses to Bm14 and Bm33, Brugia malayi antigens and to a major surface protein (WSP) from Wolbachia were analyzed using a multiplex bead assay. Over follow-up, 80 (56%) of the children became antigen-positive and 30 (21%) developed microfilaremia. Detectable antibody responses to Bm14, Bm33, Wb123, and WSP developed in 95%, 100%, 92%, and 29% of children, respectively. With the exception of WSP, the development of antibody responses generally preceded detection of filarial antigen. Our results show that antifilarial antibody responses can serve as an important epidemiological indicator in a sentinel population of young children and thus, may be valuable as tool for surveillance in the context of lymphatic filariasis elimination programs.