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 noncompliant" 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

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

Reduction in acute filariasis morbidity during a mass drug administration trial to eliminate lymphatic filariasis in Papua New Guinea.

Background Acute painful swelling of the extremities and scrotum are debilitating clinical manifestations of Wuchereria bancrofti infection. The ongoing global program to eliminate filariasis using mass drug administration is expected to decrease this and other forms of filarial morbidity in the future by preventing establishment of new infections as a consequence of eliminating transmission by the mosquito vector. We examined whether mass treatment with anti-filarial drugs has a more immediate health benefit by monitoring acute filariasis morbidity in Papua New Guinean communities that participated in a 5-year mass drug administration trial. Methodology/Principal Findings Weekly active surveillance for acute filariasis morbidity defined by painful swelling of the extremities, scrotum and breast was performed 1 year before and each year after 4 annual mass administrations of anti-filarial drugs (16,480 person-years of observation). Acute morbidity events lasted <3 weeks in 92% of affected individuals and primarily involved the leg (74–79% of all annual events). The incidence for all communities considered together decreased from 0.39 per person-year in the pre-treatment year to 0.31, 0.15, 0.19 and 0.20 after each of 4 annual treatments (p<0.0001). Residents of communities with high pre-treatment transmission intensities (224–742 infective bites/person/year) experienced a greater reduction in acute morbidity (0.62 episodes per person-year pre-treatment vs. 0.30 in the 4th post-treatment year) than residents of communities with moderate pre-treatment transmission intensities (24–167 infective bites/person/year; 0.28 episodes per person-year pre-treatment vs. 0.16 in the 4th post-treatment year). Conclusions Mass administration of anti-filarial drugs results in immediate health benefit by decreasing the incidence of acute attacks of leg and arm swelling in people with pre-existing infection. Reduction in acute filariasis morbidity parallels decreased transmission intensity, suggesting that continuing exposure to infective mosquitoes is involved in the pathogenesis of acute filariasis morbidity

Lymphatic filariasis in the Democratic Republic of Congo; micro-stratification overlap mapping (MOM) as a prerequisite for control and surveillance

<p>Abstract</p> <p>Background</p> <p>The Democratic Republic of Congo (DRC) has a significant burden of lymphatic filariasis (LF) caused by the parasite <it>Wuchereria bancrofti</it>. A major impediment to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic for onchocerciasis and loiasis. It is important to analyse these and other factors, such as soil transmitted helminths (STH) and malaria co-endemicity, which will impact on LF elimination.</p> <p>Results</p> <p>We analysed maps of onchocerciasis community-directed treatment with ivermectin (CDTi) from the African Programme for Onchocerciasis Control (APOC); maps of predicted prevalence of <it>Loa loa</it>; planned STH control maps of albendazole (and mebendazole) from the Global Atlas of Helminth Infections (GAHI); and bed nets and insecticide treated nets (ITNs) distribution from Demographic and Health Surveys (DHS) as well as published historic data which were incorporated into overlay maps. We developed an approach we designate as micro-stratification overlap mapping (MOM) to identify areas that will assist the implementation of LF elimination in the DRC. The historic data on LF was found through an extensive review of the literature as no recently published information was available.</p> <p>Conclusions</p> <p>This paper identifies an approach that takes account of the various factors that will influence not only country strategies, but suggests that country plans will require a finer resolution mapping than usual, before implementation of LF activities can be efficiently deployed. This is because 1) distribution of ivermectin through APOC projects will already have had an impact of LF intensity and prevalence 2) DRC has been up scaling bed net distribution which will impact over time on transmission of <it>W. bancrofti </it>and 3) recently available predictive maps of <it>L. loa </it>allow higher risk areas to be identified, which allow LF implementation to be initiated with reduced risk where <it>L. loa </it>is considered non-endemic. We believe that using the proposed MOM approach is essential for planning the expanded distribution of drugs for LF programmes in countries co-endemic for filarial infections.</p

National Mass Drug Administration Costs for Lymphatic Filariasis Elimination

Lymphatic filariasis (LF), commonly known as elephantiasis, is a profoundly disfiguring parasitic disease caused by thread-like nematode worms. This disease can often be disabling, thus reducing the potential productivity of the affected individuals. The WHO places the number of people at risk in 83 countries at 1.307 billion. This study was undertaken in seven countries—Burkina Faso, Ghana, Egypt, Tanzania, the Philippines, the Dominican Republic, and Haiti—using a common protocol to determine the costs of mass drug administration (MDA) programs to interrupt transmission of infection with LF, because there is lack of sufficient information about the costs of these programs. The results demonstrate that LF MDA is affordable and relatively inexpensive when compared to other public health programs. In the context of initiatives for integrating programs for the control and elimination of neglected tropical diseases, this study adds specifically to the relatively scarce body of information about the costs of MDA programs for LF. It also adds to the general knowledge about the application of methods that can be used to estimate the costs and cost-effectiveness of an integrated approach

The Impact of a Filariasis Control Program on Lihir Island, Papua New Guinea

Large-scale intervention programmes to control filariasis are currently underway worldwide. However, a major unresolved question remains: what is the appropriate duration for these programmes? Recent theoretical work and clinical field experience has highlighted how the ecological diversity between different endemic regions hinders decision making processes of when to stop ongoing MDA programs. The goal of our study was to identify the factors determining success for a five year LF elimination program. We undertook different types of surveys together with a pre-existing MDA program in villages from two regions that had different infection prevalence rates. Our study shows that the five yearly cycles of MDA could neither eliminate the disease nor stop transmission in the high prevalence villages, such that low baseline lymphatic filariasis prevalence has a positive influence on the outcome of a program. Thus, the study provides data supporting the recommendation that in certain high prevalence and transmission environments more sustained efforts may be necessary

Marriage, Sex, and Hydrocele: An Ethnographic Study on the Effect of Filarial Hydrocele on Conjugal Life and Marriageability from Orissa, India

Lymphatic filariasis, the second leading cause of permanent and long-term disability, affects 120 million people globally. Hydrocele, an accumulation of fluid in the scrotum that causes it to swell, is one of the chronic manifestations of LF among men and there are about 27 million men with hydrocele worldwide. We conducted ethnographic interviews and discussions with patients, women whose husbands have hydrocele, and the general public in a rural community of eastern India. The study describes how hydrocele impacts patients' sexual and marital life. It reveals the most worrisome effect of hydrocele for patients and their wives due to the inability to have a satisfactory sexual life. Patients expressed their incapacity during sexual intercourse. A majority of hydrocele patients' wives reported that their married life became burdened and couples were not living happily. This study also highlights the impact on marriageability, and some women expressed that a hydrocele patient is the “last choice”. In some cases, the patients were persuaded by their wives to remove hydrocele by surgery (hydrocelectomy). Hence, access to hydrocelectomy has to be strengthened under the Global Programme to Eliminate Lymphatic Filariasis, which is operational in several endemic areas in the world. Also, this activity may be integrated with primary healthcare services and interventions of other neglected tropical diseases

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

Lymphatic filariasis (LF) is a disabling mosquito borne parasitic disease and one of the major neglected tropical diseases. In most countries of Sub-Saharan Africa the control of LF is based on yearly mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We monitored the effect of 3 repeated MDAs with this drug combination, as implemented by the Tanzanian National Lymphatic Filariasis Elimination Programme, on human infection and mosquito transmission during a five-year period (one pre-intervention and four post-intervention years) in a highly endemic community in north-eastern Tanzania. After start of intervention, human infection with the blood-stage larva of the parasite (microfilaria) initially decreased rapidly, leading to considerable reduction in transmission. The effects thereafter levelled off and transmission still occurred at low level after the third MDA. The MDAs had limited effect on molecular markers of adult worm burden (circulating filarial antigens) and transmission exposure (antibodies to Bm14 antigen) in the human population. The study highlights the importance of monitoring and regular evaluation in order to make evidence based programme adjustments, and it points to a need for further assessment of the long-term effect of repeated ivermectin/albendazole MDAs (including the importance of application intervals and treatment coverage), in order to optimize efforts to control LF in sub-Saharan Africa