How lymphatic filariasis was eliminated from an urban poor setting in Santo Domingo, Dominican Republic.

BACKGROUND: While progress has been made in the elimination of lymphatic filariasis, challenges that call for innovative approaches remain. Program challenges are increasingly observed in 'hard-to-reach' populations: urban dwellers, migrant populations, those living in insecurity, children who are out of school and areas where infrastructure is weak and education levels are low. 'Business-as-usual' approaches are unlikely to work. Tailored solutions are needed if elimination goals are to be reached. This article focuses on mass drug administrations (MDAs) in urban settings. METHODS: We selected the urban poor area of Santo Domingo, Dominican Republic. With three rounds of MDA and with good coverage, elimination was achieved. We wanted to understand contributing factors to achieving good coverage. A qualitative study analyzed context, barriers and facilitators using a predefined framework based on review of the literature. RESULTS: Results show that barriers commonly reported in urban settings were present (population density, lack of organization in household layout, population mobility, violence, shortage of human resources and challenges in monitoring treatment coverage). Tactics used included strong visibility in the community leading to high levels of awareness, the use of laminated photo sheets during house-to-house visits and a 1:4 supervision strategy. The importance of working through community leadership structures and building relationships with the community was evident. DISCUSSION: The approach developed here has applications for large-scale treatment programs for lymphatic filariasis and other diseases in urban settings.

Improving drug delivery strategies for lymphatic filariasis elimination in urban areas in Ghana.

The Global Program to Eliminate Lymphatic Filariasis (GPELF) advocates for the treatment of entire endemic communities, in order to achieve its elimination targets. LF is predominantly a rural disease, and achieving the required treatment coverage in these areas is much easier compared to urban areas that are more complex. In Ghana, parts of the Greater Accra Region with Accra as the capital city are also endemic for LF. Mass Drug Administration (MDA) in Accra started in 2006. However, after four years of treatment, the coverage has always been far below the 65% epidemiologic coverage for interrupting transmission. As such, there was a need to identify the reasons for poor treatment coverage and design specific strategies to improve the delivery of MDA. This study therefore set out to identify the opportunities and barriers for implementing MDA in urban settings, and to develop appropriate strategies for MDA in these settings. An experimental, exploratory study was undertaken in three districts in the Greater Accra region. The study identified various types of non-rural settings, the social structures, stakeholders and resources that could be employed for MDA. Qualitative assessment such as in-depth interviews (IDIs) and focus group discussions (FGDs) with community leaders, community members, health providers, NGOs and other stakeholders in the community was undertaken. The study was carried out in three phases: pre-intervention, intervention and post-intervention phases, to assess the profile of the urban areas and identify reasons for poor treatment coverage using both qualitative and quantitative research methods. The outcomes from the study revealed that, knowledge, attitudes and practices of community members to MDA improved slightly from the pre-intervention phase to the post-intervention phase, in the districts where the interventions were readily implemented by health workers. Many factors such as adequate leadership, funding, planning and community involvement, were identified as being important in improving implementation and coverage of MDA in the study districts. Implementing MDA in urban areas therefore needs to be given significant consideration and planning, if the required coverage rates are to be achieved. This paper, presents the recommendations and strategies for undertaking MDA in urban areas.

Dynamics of antigenemia and transmission intensity of Wuchereria bancrofti following cessation of mass drug administration in a formerly highly endemic region of Mali.

BACKGROUND: After seven annual rounds of mass drug administration (MDA) in six Malian villages highly endemic for Wuchereria bancrofti (overall prevalence rate of 42.7%), treatment was discontinued in 2008. Surveillance was performed over the ensuing 5 years to detect recrudescence. METHODS: Circulating filarial antigen (CFA) was measured using immunochromatographic card tests (ICT) and Og4C3 ELISA in 6-7 year-olds. Antibody to the W. bancrofti infective larval stage (L3) antigen, Wb123, was tested in the same population in 2012. Microfilaraemia was assessed in ICT-positive subjects. Anopheles gambiae complex specimens were collected monthly using human landing catch (HLC) and pyrethrum spray catch (PSC). Anopheles gambiae complex infection with W. bancrofti was determined by dissection and reverse transcriptase polymerase chain reaction (RT-PCR) of mosquito pools. RESULTS: Annual CFA prevalence rates using ICT in children increased over time from 0% (0/289) in 2009 to 2.7% (8/301) in 2011, 3.9% (11/285) in 2012 and 4.5% (14/309) in 2013 (trend χ 2 = 11.85, df =3, P = 0.0006). Wb123 antibody positivity rates in 2013 were similar to the CFA prevalence by ELISA (5/285). Although two W. bancrofti-infected Anopheles were observed by dissection among 12,951 mosquitoes collected by HLC, none had L3 larvae when tested by L3-specific RT-PCR. No positive pools were detected among the mosquitoes collected by pyrethrum spray catch. Whereas ICT in 6-7 year-olds was the major surveillance tool, ICT positivity was also assessed in older children and adults (8-65 years old). CFA prevalence decreased in this group from 4.9% (39/800) to 3.5% (28/795) and 2.8% (50/1,812) in 2009, 2011 and 2012, respectively (trend χ 2 = 7.361, df =2, P = 0.0067). Some ICT-positive individuals were microfilaraemic in 2009 [2.6% (1/39)] and 2011 [8.3% (3/36)], but none were positive in 2012 or 2013. CONCLUSION: Although ICT rates in children increased over the 5-year surveillance period, the decrease in ICT prevalence in the older group suggests a reduction in transmission intensity. This was consistent with the failure to detect infective mosquitoes or microfilaraemia. The threshold of ICT positivity in children may need to be re-assessed and other adjunct surveillance tools considered.

Detection of benzimidazole resistance-associated mutations in the filarial nematode Wuchereria bancrofti and evidence for selection by albendazole and ivermectin combination treatment.

The Global Program to Eliminate Lymphatic Filariasis has been implemented to reduce human microfilaremia to levels low enough to break the transmission of the disease by using single annual doses of albendazole in combination with diethylcarbamazine or ivermectin. Many veterinary helminth parasites have developed resistance against both albendazole and ivermectin. Resistance to albendazole in veterinary nematodes is known to be caused by either of two single amino acid substitutions from phenylalanine to tyrosine in parasite beta-tubulin at position 167 or 200. We have developed assays capable of detecting these single nucleotide polymorphisms (SNPs) in Wuchereria bancrofti, and have applied them to microfilaria obtained from patients in Ghana and Burkina Faso. One of the SNPs was found in worms from untreated populations in both locations. Worms from treated patients had significantly higher frequencies of these mutations. These findings indicate that a beta-tubulin allele associated with benzimidazole resistance is being selected in these populations.

Baseline drivers of lymphatic filariasis in Burkina Faso.

Lymphatic filariasis (LF) is a parasitic disease that is endemic throughout sub-Saharan Africa, infecting approximately 40 million people. In Burkina Faso, mass drug administration (MDA) for LF with ivermectin and albendazole has been ongoing since 2001, and by 2006 all endemic health districts were receiving MDA with a therapeutic coverage of at least 65%. As MDA activities scale down, the focus is now on targeting areas where LF transmission persists with alternative elimination strategies. This study explored the relationship between village-level, baseline LF prevalence data collected in 2000 with publicly available meteorological, environmental and demographic variables in order to determine the factors that influence the geographical distribution of the disease. A fitted multiple logistic regression model indicated that the length of the rainy season, variability in normalized difference vegetation index (NDVI) and population density were significantly positively associated with LF prevalence, whereas total annual rainfall, average June-September temperature, mean NDVI, elevation and the area of cotton crops were significantly negatively associated. This model was used to produce a baseline LF risk map for Burkina Faso. An extended model which incorporated potential socio-demographic risk factors also indicated a significant positive relationship between LF prevalence and wealth. In overlaying the baseline LF risk map with the number of MDA rounds, plus an insecticide-treated net (ITN) ownership measure, the central southern area of the country was highlighted as an area where baseline LF prevalence was high and ITN coverage relatively low (<50%), while at least 10 rounds of MDA had been undertaken, suggesting that more concentrated efforts will be needed to eliminate the disease in these areas.

The effects of integration on financing and coverage of neglected tropical disease programs.

When the U.S. Agency for International Development (USAID) began to support national programs integrating their neglected tropical disease (NTD) program activities, the expected impact on individual disease-specific programs was unclear, particularly with respect to program financing and coverage. To assess this impact, data were collected by NTD program managers and their non-governmental organization (NGO) partners in Burkina Faso, Mali, and Uganda from 2 years prior and 2 years after their individual programs received funding for an integrated NTD program. Findings show that these countries experienced some increases in overall funding available for integrated NTD programs, an expansion of geographical coverage and of the number of persons treated, and the addition of treatments targeted at new diseases. What is not clear is whether these achievements can be sustained if there are decreases in external support in the future. Seeking increased government commitment or sustained external donor support should be a top priority.

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.

A multicenter evaluation of diagnostic tools to define endpoints for programs to eliminate bancroftian filariasis.

Successful mass drug administration (MDA) campaigns have brought several countries near the point of Lymphatic Filariasis (LF) elimination. A diagnostic tool is needed to determine when the prevalence levels have decreased to a point that MDA campaigns can be discontinued without the threat of recrudescence. A six-country study was conducted assessing the performance of seven diagnostic tests, including tests for microfilariae (blood smear, PCR), parasite antigen (ICT, Og4C3) and antifilarial antibody (Bm14, PanLF, Urine SXP). One community survey and one school survey were performed in each country. A total of 8,513 people from the six countries participated in the study, 6,443 through community surveys and 2,070 through school surveys. Specimens from these participants were used to conduct 49,585 diagnostic tests. Each test was seen to have both positive and negative attributes, but overall, the ICT test was found to be 76% sensitive at detecting microfilaremia and 93% specific at identifying individuals negative for both microfilariae and antifilarial antibody; the Og4C3 test was 87% sensitive and 95% specific. We conclude, however, that the ICT should be the primary tool recommended for decision-making about stopping MDAs. As a point-of-care diagnostic, the ICT is relatively inexpensive, requires no laboratory equipment, has satisfactory sensitivity and specificity and can be processed in 10 minutes-qualities consistent with programmatic use. Og4C3 provides a satisfactory laboratory-based diagnostic alternative.

Efficacy of home-based lymphoedema management in reducing acute attacks in subjects with lymphatic filariasis in Burkina Faso.

One of the two main goals of the Global Programme to Eliminate Lymphatic Filariasis (LF) is to provide care for those suffering from the devastating clinical manifestations of this filarial infection. Among the 120 million infected people worldwide, up to 16 million have lymphoedema. The WHO strategy for managing lymphoedema is based on rigorous skin hygiene, exercise, antibiotics and antifungals when indicated. The aim is to reduce acute attacks of adenolymphangitis and cellulitis responsible for lymphoedema progression and disability. The objective of our study was to assess the effectiveness of home-based lymphoedema management implemented by the national health system of Burkina Faso. Any patient was eligible to participate in the study if suffering from LF-related lymphoedema of a lower limb at any stage, and receiving care as part of the health education and washing project between April 2005 and December 2007. The primary readout was the occurrence of an acute attack in the month preceding the consultation reported by the patient or observed by the care-giver. In all, 1089 patients were enrolled in the study. Before lymphoedema management intervention, 78.1% (95%CI: 75.5-80.5) of the patients had an acute attack in the month preceding the consultation; after four and half months of lymphoedema management, this was reduced to 39.1% (95%CI: 36.2-42.1). A reduction of acute attacks related to the number of consultations or related to the patients' age and gender was not observed. Our results suggest that the home-based lymphoedema management programme in the primary health care system of Burkina Faso is effective in reducing morbidity due to LF in the short-term (4.5 months). The lymphoedema management requires no additional human resources, but whether its effect can be sustained remains to be seen.

Determinants of success in national programs to eliminate lymphatic filariasis: a perspective identifying essential elements and research needs.

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000. To understand why some national programs have been more successful than others, a panel of individuals with expertise in LF elimination efforts met to assess available data from programs in 8 countries. The goal was to identify: 1) the factors determining success for national LF elimination programs (defined as the rapid, sustained reduction in microfilaremia/antigenemia after repeated mass drug administration [MDA]); 2) the priorities for operational research to enhance LF elimination efforts. Of more than 40 factors identified, the most prominent were 1) initial level of LF endemicity; 2) effectiveness of vector mosquitoes; 3) MDA drug regimen; 4) population compliance. Research important for facilitating program success was identified as either biologic (i.e., [1] quantifying differences in vectorial capacity; [2] identifying seasonal variations affecting LF transmission) or programmatic (i.e., [1] identifying quantitative thresholds, especially the population compliance levels necessary for success, and the antigenemia or microfilaremia prevalence at which MDA programs can stop with minimal risk of resumption of transmission; [2] defining optimal drug distribution strategies and timing; [3] identifying those individuals who are "persistently non-compliant" during MDAs, the reasons for this non-compliance and approaches to overcoming it). While addressing these challenges is important, many key determinants of program success are already clearly understood; operationalizing these as soon as possible will greatly increase the potential for national program success.

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.

Short communication: Negative spatial association between lymphatic filariasis and malaria in West Africa.

OBJECTIVE: To determine the relationship between human lymphatic filariasis, caused by Wuchereria bancrofti, and falciparum malaria, which are co-endemic throughout West Africa. METHODS: We used geographical information systems and spatial statistics to examine the prevalence of lymphatic filariasis in relation to malaria prevalence, mosquito species distributions, vegetation and climate. RESULTS: A negative spatial association between W. bancrofti and falciparum malaria prevalence exists. Interspecies competition between parasites, seasonality, differences in the distribution and vector competence of Anopheles vectors, agricultural practices and insecticide resistance may be factors driving current (and potentially future) spatial distributions. CONCLUSION: Further investigating these factors will become crucial as large-scale lymphatic filariasis and malaria control programmes are implemented in West Africa that may influence the epidemiology of both diseases.