Increasing Compliance with Mass Drug Administration Programs for Lymphatic Filariasis in India through Education and Lymphedema Management Programs

Background

Nearly 45% of people living at risk for lymphatic filariasis (LF) worldwide live in India. India has faced challenges obtaining the needed levels of compliance with its mass drug administration (MDA) program to interrupt LF transmission, which utilizes diethylcarbamazine (DEC) or DEC plus albendazole. Previously identified predictors of and barriers to compliance with the MDA program were used to refine a pre-MDA educational campaign. The objectives of this study were to assess the impact of these refinements and of a lymphedema morbidity management program on MDA compliance.

Methods/Principal Findings

A randomized, 30-cluster survey was performed in each of 3 areas: the community-based pre-MDA education plus community-based lymphedema management education (Com-MDA+LM) area, the community-based pre-MDA education (Com-MDA) area, and the Indian standard pre-MDA education (MDA-only) area. Compliance with the MDA program was 90.2% in Com-MDA+LM, 75.0% in Com-MDA, and 52.9% in the MDA-only areas (p<0.0001). Identified barriers to adherence included: 1) fear of side effects and 2) lack of recognition of one''s personal benefit from adherence. Multivariable predictors of adherence amenable to educational intervention were: 1) knowing about the MDA in advance of its occurrence, 2) knowing everyone is at risk for LF, 3) knowing that the MDA was for LF, and 4) knowing at least one component of the lymphedema management techniques taught in the lymphedema management program.

Conclusions/Significance

This study confirmed previously identified predictors of and barriers to compliance with India''s MDA program for LF. More importantly, it showed that targeting these predictors and barriers in a timely and clear pre-MDA educational campaign can increase compliance with MDA programs, and it demonstrated, for the first time, that lymphedema management programs may also increase compliance with MDA programs.     

National mass drug administration costs for lymphatic filariasis elimination

Background

Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk.

Methodology/Principal Findings

To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications.

Conclusions/Significance

MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.     

Integrated Rapid Mapping of Neglected Tropical Diseases in Three States of South Sudan: Survey Findings and Treatment Needs

Background

Integrated rapid mapping to target interventions for schistosomiasis, soil-transmitted helminthiasis (STH) and lymphatic filariasis (LF) is ongoing in South Sudan. From May to September 2010, three states – Unity, Eastern Equatoria and Central Equatoria – were surveyed with the aim of identifying which administrative areas are eligible for mass drug administration (MDA) of preventive chemotherapy (PCT).

Methods and Principal Findings

Payams (third administrative tier) were surveyed for Schistosoma mansoni, S. haematobium and STH infections while counties (second administrative tier) were surveyed for LF. Overall, 12,742 children from 193 sites were tested for schistosome and STH infection and, at a subset of 50 sites, 3,980 adults were tested for LF. Either S. mansoni or S. haematobium or both species were endemic throughout Unity State and occurred in foci in Central and Eastern Equatoria. STH infection was endemic throughout Central Equatoria and the western counties of Eastern Equatoria, while LF was endemic over most of Central- and Eastern Equatoria, but only in selected foci in Unity. All areas identified as STH endemic were co-endemic for schistosomiasis and/or LF.

Conclusions

The distribution and prevalence of major NTDs, particularly schistosomiasis, varies considerably throughout South Sudan. Rapid mapping is therefore important in identifying (co)-endemic areas. The present survey established that across the three surveyed states between 1.2 and 1.4 million individuals are estimated to be eligible for regular MDA with PCT to treat STH and schistosomiasis, respectively, while approximately 1.3 million individuals residing in Central- and Eastern Equatoria are estimated to require MDA for LF.     

Non-Participation during Azithromycin Mass Treatment for Trachoma in The Gambia: Heterogeneity and Risk Factors

Background

There is concern that untreated individuals in mass drug administration (MDA) programs for neglected tropical diseases can reduce the impact of elimination efforts by maintaining a source of transmission and re-infection.

Methodology/Principal Findings

Treatment receipt was recorded against the community census during three MDAs with azithromycin for trachoma in The Gambia, a hypo-endemic setting. Predictors of non-participation were investigated in 1–9 year olds using random effects logistic regression of cross-sectional data for each MDA. Two types of non-participators were identified: present during MDA but not treated (PNT) and eligible for treatment but absent during MDA (EBA). PNT and EBA children were compared to treated children separately. Multivariable models were developed using baseline data and validated using year one and two data, with a priori adjustment for previous treatment status. Analyses included approximately 10000 children at baseline and 5000 children subsequently. There was strong evidence of spatial heterogeneity, and persistent non-participation within households and individuals. By year two, non-participation increased significantly to 10.4% overall from 6.2% at baseline, with more, smaller geographical clusters of non-participating households. Multivariable models suggested household level predictors of non-participation (increased time to water and household head non-participation for both PNT and EBA; increased household size for PNT status only; non-inclusion in a previous trachoma examination survey and younger age for EBA only). Enhanced coverage efforts did not decrease non-participation. Few infected children were detected at year three and only one infected child was EBA previously. Infected children were in communities close to untreated endemic areas with higher rates of EBA non-participation during MDA.

Conclusions/Significance

In hypo-endemic settings, with good coverage and no association between non-participation and infection, efforts to improve participation during MDA may not be required. Further research could investigate spatial hotspots of infection and non-participation in other low and medium prevalence settings before allocating resources to increase participation.     

Pilot Assessment of Soil-Transmitted Helminthiasis in the Context of Transmission Assessment Surveys for Lymphatic Filariasis in Benin and Tonga

Background

Mass drug administration (MDA) for lymphatic filariasis (LF) programs has delivered more than 2 billion treatments of albendazole, in combination with either ivermectin or diethylcarbamazine, to communities co-endemic for soil-transmitted helminthiasis (STH), reducing the prevalence of both diseases. A transmission assessment survey (TAS) is recommended to determine if MDA for LF can be stopped within an evaluation unit (EU) after at least five rounds of annual treatment. The TAS also provides an opportunity to simultaneously assess the impact of these MDAs on STH and to determine the frequency of school-based MDA for STH after community-wide MDA is no longer needed for LF.

Methodology/Principal Findings

Pilot studies conducted in Benin and Tonga assessed the feasibility of a coordinated approach. Of the schools (clusters) selected for a TAS in each EU, a subset of 5 schools per STH ecological zone was randomly selected, according to World Health Organization (WHO) guidelines, for the coordinated survey. In Benin, 519 children were sampled in 5 schools and 22 (4.2%) had STH infection (A. lumbricoides, T. trichiura, or hookworm) detected using the Kato-Katz method. All infections were classified as light intensity under WHO criteria. In Tonga, 10 schools were chosen for the coordinated TAS and STH survey covering two ecological zones; 32 of 232 (13.8%) children were infected in Tongatapu and 82 of 320 (25.6%) in Vava''u and Ha''apai. All infections were light-intensity with the exception of one with moderate-intensity T. trichiura.

Conclusions

Synchronous assessment of STH with TAS is feasible and provides a well-timed evaluation of infection prevalence to guide ongoing treatment decisions at a time when MDA for LF may be stopped. The coordinated field experiences in both countries also suggest potential time and cost savings. Refinement of a coordinated TAS and STH sampling methodology should be pursued, along with further validation of alternative quantitative diagnostic tests for STH that can be used with preserved stool specimens.     

Compliance with the Dietary Approaches to Stop Hypertension (DASH) Diet: A Systematic Review

Background

The Dietary Approaches to Stop Hypertension (DASH) diet has been recognized as effective to lower blood pressure in feeding trials, but compliance with the diet must be persistent to maximize health benefits in clinical practice. This paper reports a systematic review of the latest evidence on the method to assess DASH compliance and the corresponding patients'' compliance in interventional settings.

Methods

The databases including MEDLINE, EBM Reviews, EMBASE, and CINAHL Plus were searched for original research studies published in the period of January 1992- December 2012 that evaluated compliance with DASH diet. Studies written in English language, with DASH intervention, with complete documentation of the degree of DASH compliance and the assessment method used were included in this review. The search terms included: dietary approaches to stop hypertension, DASH, compliance, adherence, consistency, and concordance.

Results

Nine studies were included. Different types of interventions were identified, ranging from feeding trial to dietary counseling. These studies differed in the assessment methods used to evaluate DASH compliance, which included objective approaches like measurement of urinary excretion, and subjective approaches like dietary intake assessment for DASH target comparison and construction of DASH scoring systems. Compliance levels were lower in educational interventions than that of the original DASH feeding trial.

Conclusions

To conclude, although no consensus existed regarding the best approach to assess DASH compliance, its suboptimal compliance warrants attention. This study implied a need to investigate effective approaches to sustain the DASH dietary pattern beyond counselling alone.     

The Economic Benefits Resulting from the First 8 Years of the Global Programme to Eliminate Lymphatic Filariasis (2000–2007)

Background

Between 2000–2007, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) delivered more than 1.9 billion treatments to nearly 600 million individuals via annual mass drug administration (MDA) of anti-filarial drugs (albendazole, ivermectin, diethylcarbamazine) to all at-risk for 4–6 years. Quantifying the resulting economic benefits of this significant achievement is important not only to justify the resources invested in the GPELF but also to more fully understand the Programme''s overall impact on some of the poorest endemic populations.

Methodology

To calculate the economic benefits, the number of clinical manifestations averted was first quantified and the savings associated with this disease prevention then analyzed in the context of direct treatment costs, indirect costs of lost-labor, and costs to the health system to care for affected individuals. Multiple data sources were reviewed, including published literature and databases from the World Health Organization, International Monetary Fund, and International Labour Organization

Principal Findings

An estimated US$21.8 billion of direct economic benefits will be gained over the lifetime of 31.4 million individuals treated during the first 8 years of the GPELF. Of this total, over US$2.3 billion is realized by the protection of nearly 3 million newborns and other individuals from acquiring lymphatic filariasis as a result of their being born into areas freed of LF transmission. Similarly, more than 28 million individuals already infected with LF benefit from GPELF''s halting the progression of their disease, which results in an associated lifetime economic benefit of approximately US$19.5 billion. In addition to these economic benefits to at-risk individuals, decreased patient services associated with reduced LF morbidity saves the health systems of endemic countries approximately US$2.2 billion.

Conclusions/Significance

MDA for LF offers significant economic benefits. Moreover, with favorable program implementation costs (largely a result of the sustained commitments of donated drugs from the pharmaceutical industry) it is clear that the economic rate of return of the GPELF is extremely high and that this Programme continues to prove itself an excellent investment in global health.     

Assessing Progress in Reducing the At-Risk Population after 13 Years of the Global Programme to Eliminate Lymphatic Filariasis

Background

In 1997, the World Health Assembly adopted Resolution 50.29, committing to the elimination of lymphatic filariasis (LF) as a public health problem, subsequently targeted for 2020. The initial estimates were that 1.2 billion people were at-risk for LF infection globally. Now, 13 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) began implementing mass drug administration (MDA) against LF in 2000—during which over 4.4 billion treatments have been distributed in 56 endemic countries—it is most appropriate to estimate the impact that the MDA has had on reducing the population at risk of LF.

Methodology/Principal Findings

To assess GPELF progress in reducing the population at-risk for LF, we developed a model based on defining reductions in risk of infection among cohorts of treated populations following each round of MDA. The model estimates that the number of people currently at risk of infection decreased by 46% to 789 million through 2012.

Conclusions/Significance

Important progress has been made in the global efforts to eliminate LF, but significant scale-up is required over the next 8 years to reach the 2020 elimination goal.     

Increasing Coverage in Mass Drug Administration for Lymphatic Filariasis Elimination in an Urban Setting: a Study of Malindi Town,Kenya

Introduction

Implementation of Mass Drug Administration (MDA) in urban settings is an obstacle to Lymphatic Filariasis (LF) elimination. No urban-specific guidelines on MDA in urban areas exist. Malindi district urban area had received 4 MDA rounds by the time the current study was implemented. Programme data showed average treatment coverage of 28.4% (2011 MDA), far below recommended minimum of 65–80%.

Methods

To identify, design and test strategies for increased treatment coverage in urban areas, a quasi-experimental study was conducted in Malindi urban area. Three sub-locations with lowest treatment coverage in 2011 MDA were purposively selected. In the pre-test phase, 947 household heads sampled using systematic random method were interviewed for quantitative data. For qualitative data, 12 Focus Group Discussions (FGDs) with single sex adult and youth male and female groups and 3 with community drug distributors (CDDs) were conducted. Forty in-depth interviews with opinion leaders and self-administered questionnaires with District Public Health officers purposively selected were carried out. The quantitative data were analyzed using SPSS version 16 and statistical significance assessed by χ² test.The qualitative data were analyzed manually according to study''s themes.

Results and Discussion

The identified strategies were implemented prior to and during 2012 MDA in two sub-locations (experimental) while in the third (control), usual MDA strategies were applied. In the post-test phase, 2012 MDA coverage in experimental and control sub-locations was comparatively assessed for effect of the newly designed strategies on urban MDA. Results indicated improved treatment coverage in experimental sub-locations, 77.1% in Shella and 66.0% in Barani. Central (control) sub-location also attained high coverage, 70.4% indicating average treatment coverage of 71%.

Conclusion

The identified strategies contributed to increased treatment coverage in experimental sites and should be applied in urban areas. Due to closeness of sites, spillover effects may have contributed to increased coverage in the control site.     

The Role of Personal Opinions and Experiences in Compliance with Mass Drug Administration for Lymphatic Filariasis Elimination in Kenya

Background

The main strategy adopted for Lymphatic Filariasis (LF) elimination globally is annual mass drug administration (MDA) for 4 to 6 rounds. At least 65% of the population at risk should be treated in each round for LF elimination to occur. In Kenya, MDA using diethylcarbamazine citrate (DEC) and albendazole data shows declining compliance (proportion of eligible populations who receive and swallow the drugs) levels (85%–62.8%). The present study''s aim was to determine the role of personal opinions and experiences in compliance with MDA.

Methods/Findings

This was a retrospective cross-sectional study conducted between January and September 2009 in two districts based on December 2008 MDA round. In each district, one location with high and one with low compliance was selected. Through systematic sampling, nine villages were selected and interviewer-based questionnaires administered to 965 household heads or adult representatives also systematically sampled. The qualitative data were generated from opinion leaders, LF patients with clinical signs and community drug distributors (CDDs) all purposively selected and interviewed. Sixteen focus group discussions (FGDs) were also conducted with single-sex adult and youth male and female groups. Chi square test was used to assess the statistical significance of differences in compliance with treatment based on the records reviewed.The house-to-house method of drug distribution influenced compliance. Over one-quarter (27%) in low compared to 15% in high compliance villages disliked this method. Problems related to size, number and taste of the drugs were more common in low (16.4%) than in high (14.4%) compliance villages. Reasons for failure to take the drugs were associated with compliance (p<0.001). The reasons given included: feeling that the drugs were not necessary, CDD not visiting to issue the drugs, being absent and thinking that the drugs were meant for only the patients with LF clinical signs. A dislike for modern medicine prevailed more in low (6.7%) than in high (1.2%) compliance villages. Experience of side effects influenced compliance (P<0.001). The common side effects experienced included giddiness, fever, headache and vomiting. Social support, alcohol and substance use were not associated with compliance in both types of villages (p>0.05).

Conclusions/Significance

Community sensitization on treatment, drugs used, their regimen and distribution method involving all leaders should be strengthened by the Programme Implementers. The communities need to be made aware of the potential side effects of the drugs and that health personnel are on standby for the management of side effects in order to build confidence and increase the compliance levels.     

The Impact of Antiretroviral Therapy on Mortality in HIV Positive People during Tuberculosis Treatment: A Systematic Review and Meta-Analysis

Objective

To quantify the impact of antiretroviral therapy (ART) on mortality in HIV-positive people during tuberculosis (TB) treatment.

Design

We conducted a systematic literature review and meta-analysis. Studies published from 1996 through February 15, 2013, were identified by searching electronic resources (Pubmed and Embase) and conference books, manual searches of references, and expert consultation. Pooled estimates for the outcome of interest were acquired using random effects meta-analysis.

Subjects

The study population included individuals receiving ART before or during TB treatment.

Main Outcome Measures

Main outcome measures were: (i) TB-case fatality ratio (CFR), defined as the proportion of individuals dying during TB treatment and, if mortality in HIV-positive people not on ART was also reported, (ii) the relative risk of death during TB treatment by ART status.

Results

Twenty-one studies were included in the systematic review. Random effects pooled meta-analysis estimated the CFR between 8% and 14% (pooled estimate 11%). Among HIV-positive TB cases, those receiving ART had a reduction in mortality during TB treatment of between 44% and 71% (RR = 0.42, 95%CI: 0.29–0.56).

Conclusion

Starting ART before or during TB therapy reduces the risk of death during TB treatment by around three-fifths in clinical settings. National programmes should continue to expand coverage of ART for HIV positive in order to control the dual epidemic.     

Incidence of HIV-Associated Tuberculosis among Individuals Taking Combination Antiretroviral Therapy: A Systematic Review and Meta-Analysis

Background

Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis.

Methods

Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy.

Results

From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings) were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from Sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI) 3.39–5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23–0.69 per 100 person-years]) with significant heterogeneity observed between the studies.

Conclusions

Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis.     

Interspecific hybridization yields strategy for South Pacific filariasis vector elimination

Background

Lymphatic filariasis (LF) is a leading cause of disability in South Pacific regions, where >96% of the 1.7 million population are at risk of LF infection. As part of current global campaign, mass drug administration (MDA) has effectively reduced lymphatic filiariasis prevalence, but mosquito vector biology can complicate the MDA strategy. In some regions, there is evidence that the goal of LF elimination cannot be attained via MDA alone. Obligate vector mosquitoes provide additional targets for breaking the LF transmission cycle, but existing methods are ineffective for controlling the primary vector throughout much of the South Pacific, Aedes polynesiensis.

Methodology/Principal Findings

Here we demonstrate that interspecific hybridization and introgression results in an A. polynesiensis strain (‘CP’ strain) that is stably infected with the endosymbiotic Wolbachia bacteria from Aedes riversi. The CP strain is bi-directionally incompatible with naturally infected mosquitoes, resulting in female sterility. Laboratory assays demonstrate that CP males are equally competitive, resulting in population elimination when CP males are introduced into wild type A. polynesiensis populations.

Conclusions/Significance

The findings demonstrate strategy feasibility and encourage field tests of the vector elimination strategy as a supplement to ongoing MDA efforts.     

Factors Influencing Drug Uptake during Mass Drug Administration for Control of Lymphatic Filariasis in Rural and Urban Tanzania

Background

In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania.

Methods

A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years) were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control.

Findings

The overall drug uptake rate was 55.1% (range of 44.5–75.6% between districts). There was no overall major difference between children (54.8%) and adults (55.2%) or between females (54.9%) and males (55.8%), but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2%) followed by clinical contraindications to treatment (10.8%), missing household visits of drug distributors (10.6%), and households not being informed about the distribution (9.0%).

Conclusion

Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent) are likely to have considerable potential for increasing drug uptake, in support of successful LF transmission elimination.     

Progress and Impact of 13 Years of the Global Programme to Eliminate Lymphatic Filariasis on Reducing the Burden of Filarial Disease

Background

A Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, with mass drug administration (MDA) as the core strategy of the programme. After completing 13 years of operations through 2012 and with MDA in place in 55 of 73 endemic countries, the impact of the MDA programme on microfilaraemia, hydrocele and lymphedema is in need of being assessed.

Methodology/Principal findings

During 2000–2012, the MDA programme made remarkable achievements – a total of 6.37 billion treatments were offered and an estimated 4.45 billion treatments were consumed by the population living in endemic areas. Using a model based on empirical observations of the effects of treatment on clinical manifestations, it is estimated that 96.71 million LF cases, including 79.20 million microfilaria carriers, 18.73 million hydrocele cases and a minimum of 5.49 million lymphedema cases have been prevented or cured during this period. Consequently, the global prevalence of LF is calculated to have fallen by 59%, from 3.55% to 1.47%. The fall was highest for microfilaraemia prevalence (68%), followed by 49% in hydrocele prevalence and 25% in lymphedema prevalence. It is estimated that, currently, i.e. after 13 years of the MDA programme, there are still an estimated 67.88 million LF cases that include 36.45 million microfilaria carriers, 19.43 million hydrocele cases and 16.68 million lymphedema cases.

Conclusions/Significance

The MDA programme has resulted in significant reduction of the LF burden. Extension of MDA to all at-risk countries and to all regions within those countries where MDA has not yet reached 100% geographic coverage is imperative to further reduce the number of microfilaraemia and chronic disease cases and to reach the global target of interrupting transmission of LF by 2020.     

Seroprevalence and Spatial Epidemiology of Lymphatic Filariasis in American Samoa after Successful Mass Drug Administration

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.     

Lymphatic Filariasis Control in Tanzania: Effect of Repeated Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission

Background

In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs with this drug combination, as implemented by the Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP).

Methodology/Principal Findings

Infection and transmission was monitored during a five-year period (one pre-intervention and four post-intervention years) in a highly endemic community (Kirare village) in north-eastern Tanzania. The vectors were Anopheles gambiae, An. funestus and Cx. quinquefasciatus. After start of intervention, human microfilaraemia initially decreased rapidly and statistically significant (prevalence by 21.2% and 40.4%, and mean intensity by 48.4% and 73.7%, compared to pre-treatment values after the first and second MDA, respectively), but thereafter the effect levelled off. The initial decrease in microfilaraemia led to significant decreases in vector infection and vector infectivity rates and thus to a considerable reduction in transmission (by 74.3% and 91.3% compared to pre-treatment level after first and second MDA, respectively). However, the decrease in infection and infectivity rates subsequently also levelled off, and low-level transmission was still noted after the third MDA. The MDAs had limited effect on circulating filarial antigens and antibody response to Bm14.

Conclusion/Significance

Critical issues that may potentially explain the observed waning effect of the MDAs in the later study period include the long intervals between MDAs and a lower than optimal treatment coverage. The findings highlight the importance of ongoing surveillance for monitoring the progress of LF control programmes, and it calls for more research into the long-term effect of repeated ivermectin/albendazole MDAs (including the significance of treatment intervals and compliance), in order to optimize efforts to control LF in sub-Saharan Africa.     

Transmission Assessment Surveys (TAS) to Define Endpoints for Lymphatic Filariasis Mass Drug Administration: A Multicenter Evaluation

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.     

What Is Needed to Eradicate Lymphatic Filariasis? A Model-Based Assessment on the Impact of Scaling Up Mass Drug Administration Programs

Background

Lymphatic filariasis (LF) is a neglected tropical disease for which more than a billion people in 73 countries are thought to be at-risk. At a global level, the efforts against LF are designed as an elimination program. However, current efforts appear to aim for elimination in some but not all endemic areas. With the 2020 goal of elimination looming, we set out to develop plausible scale-up scenarios to reach global elimination and eradication. We predict the duration of mass drug administration (MDA) necessary to reach local elimination for a variety of transmission archetypes using an existing model of LF transmission, estimate the number of treatments required for each scenario, and consider implications of rapid scale-up.

Methodology

We have defined four scenarios that differ in their geographic coverage and rate of scale-up. For each scenario, country-specific simulations and calculations were performed that took into account the pre-intervention transmission intensity, the different vector genera, drug regimen, achieved level of population coverage, previous progress toward elimination, and potential programmatic delays due to mapping, operations, and administration.

Principal Findings

Our results indicate that eliminating LF by 2020 is unlikely. If MDA programs are drastically scaled up and expanded, the final round of MDA for LF eradication could be delivered in 2028 after 4,159 million treatments. However, if the current rate of scale-up is maintained, the final round of MDA to eradicate LF may not occur until 2050.

Conclusions/Significance

Rapid scale-up of MDA will decrease the amount of time and treatments required to reach LF eradication. It may also propel the program towards success, as the risk of failure is likely to increase with extended program duration.     

Integrated Mapping of Neglected Tropical Diseases: Epidemiological Findings and Control Implications for Northern Bahr-el-Ghazal State,Southern Sudan

Background

There are few detailed data on the geographic distribution of most neglected tropical diseases (NTDs) in post-conflict Southern Sudan. To guide intervention by the recently established national programme for integrated NTD control, we conducted an integrated prevalence survey for schistosomiasis, soil-transmitted helminth (STH) infection, lymphatic filariasis (LF), and loiasis in Northern Bahr-el-Ghazal State. Our aim was to establish which communities require mass drug administration (MDA) with preventive chemotherapy (PCT), rather than to provide precise estimates of infection prevalence.

Methods and Findings

The integrated survey design used anecdotal reports of LF and proximity to water bodies (for schistosomiasis) to guide selection of survey sites. In total, 86 communities were surveyed for schistosomiasis and STH; 43 of these were also surveyed for LF and loiasis. From these, 4834 urine samples were tested for blood in urine using Hemastix reagent strips, 4438 stool samples were analyzed using the Kato-Katz technique, and 5254 blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). 4461 individuals were interviewed regarding a history of ‘eye worm’ (a proxy measure for loiasis) and 31 village chiefs were interviewed regarding the presence of clinical manifestations of LF in their community. At the village level, prevalence of Schistosoma haematobium and S. mansoni ranged from 0 to 65.6% and from 0 to 9.3%, respectively. The main STH species was hookworm, ranging from 0 to 70% by village. Infection with LF and loiasis was extremely rare, with only four individuals testing positive or reporting symptoms, respectively. Questionnaire data on clinical signs of LF did not provide a reliable indication of endemicity. MDA intervention thresholds recommended by the World Health Organization were only exceeded for urinary schistosomiasis and hookworm in a few, yet distinct, communities.

Conclusion

This was the first attempt to use an integrated survey design for this group of infections and to generate detailed results to guide their control over a large area of Southern Sudan. The approach proved practical, but could be further simplified to reduce field work and costs. The results show that only a few areas need to be targeted with MDA of PCT, thus confirming the importance of detailed mapping for cost-effective control.