PCR and Mosquito dissection as tools to monitor filarial infection levels following mass treatment

BACKGROUND: Entomological methods may provide important tools for monitoring the progress of lymphatic filariasis elimination programs. In this study, we compared dissection of the vector, Culex quinquefasciatus, with the polymerase chain reaction (PCR) to assess filarial infection levels in mosquitoes in the context of a lymphatic filariasis elimination program in Leogane, Haiti. METHODS: Mosquitoes were collected using gravid traps located in 4 sentinel communities with Wuchereria bancrofti microfilaria prevalence that ranged from 0.8% to 15.9%. Captured mosquitoes were divided between dissection, to enumerate W. bancrofti larvae (L1, L2, L3) and desiccation for later analysis by PCR. PCR was conducted on DNA extracts from pooled mosquitoes (1–15 pooled females) utilizing a competitive PCR system with primers specific for the Ssp I repeat. PCR products were analyzed with a hybridization ELISA using probes specific for a control sequence and the Ssp I repeat. RESULTS: The prevalence of mosquito infection with W. bancrofti ranged from 0%–3.66% by dissection (L1–L3) and point estimates of infection prevalence, as assayed by PCR, ranged from 0.25% – 9.16%. Following mass treatment, W. bancrofti infection prevalence dropped significantly as determined by PCR and dissection in 2 of the 4 sentinel sites (Leogane and Barrier Jeudi, P = 0.04 and P = 0.005, respectively). Although transmission declined in the other two sites, larval recoveries were low and these changes were not statistically significant. DISCUSSION: Our results suggest that a single round of mass treatment can have an impact on transmission of lymphatic filariasis. The use of entomologic methods as a tool to monitor filariasis programs and the statistical limitations of mosquito trapping are discussed

Spatial clustering of filarial transmission before and after a Mass Drug Administration in a setting of low infection prevalence

BACKGROUND: In the global program for the elimination of lymphatic filariasis (LF) longitudinal assessment of the prevalence of microfilaremia and antigenemia is recommended to monitor the effect of mass treatment on transmission. Additional monitoring tools such as entomologic and antibody methods may be useful in identifying residual foci of infection. In this study, we characterized serologic markers of infection and exposure spatially both before and after mass treatment, in an area of initial low Wuchereria bancrofti infection prevalence. METHODS: Consenting persons in the sentinel community were tested for circulating microfilaria and antigen (by immunochromatographic test) before and after the 1(st )annual mass drug administration of diethylcarbamazine and albendazole. A cohort of 161 persons provided serum specimens both years that were tested for antifilarial IgG (1 and 4) antibody. Every house was mapped using a differential Global Positioning System; this information was linked to the serologic data. W. bancrofti infection in the mosquito vector was assessed with year-round collection. Multiple linear regression was used to investigate the influence of antigen-positive persons on the antifilarial antibody responses of antigen-negative neighbors. RESULTS: After mass treatment, decreases were observed in the sentinel site in the overall prevalence of antigen (10.4% to 6.3%) and microfilaremia (0.9 to 0.4%). Of the persons in the cohort that provided serum specimens both years, 79% received treatment. Antigen prevalence decreased from 15.0% to 8.7%. Among 126 persons who received treatment, antigen and antifilarial IgG1 prevalence decreased significantly (p = 0.002 and 0.001, respectively). Among 34 persons who did not receive treatment, antifilarial IgG1 prevalence increased significantly (p = 0.003). Average antifilarial IgG1 levels decreased in households with high treatment coverage and increased in households that refused treatment. Each 10-meter increase in distance from the residence of a person who was antigen-positive in 2000 was associated a 4.68 unit decrease in antifilarial IgG1 level in 2001, controlling for other factors (p = 0.04). DISCUSSION: Antifilarial antibody assays can be used as a measure of filarial exposure. Our results suggest that micro-scale spatial heterogeneity exists in LF exposure and infection. Treatment appeared to be associated with reduced exposure at the sub-community level, suggesting the need to achieve high and homogeneous coverage. Public health messages should note the benefits of having one's neighbors receive treatment with antifilarial drugs

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

Does mass drug administration for the integrated treatment of neglected tropical diseases really work? Assessing evidence for the control of schistosomiasis and soil-transmitted helminths in Uganda

This paper was one of four papers commissioned to review the role of social sciences in NTD control by TDR, the Special Programme for Research and Training on Tropical Diseases, which is executed by WHO and co-sponsored by UNICEF, UNDP, the World Bank and WHO.This article has been made available through the Brunel Open Access Publishing Fund.Background: Less is known about mass drug administration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. Methods: Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. Results: The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and more effective use of existing public health legislation. Conclusion: While it has been an achievement to have offered free drugs to so many adults, current standard practices of monitoring, evaluation and delivery of MDA for NTDs are inconsistent and inadequate. Efforts to integrate programmes have exacerbated the difficulties. Improved assessment of what is really happening on the ground will be an essential step in achieving long-term overall reduction of the NTD burden for impoverished communities.This article is available through the Brunel Open Access Publishing Fund

Vascular Cognitive Impairment Neuropathology Guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment

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Feasibility and Effectiveness of Basic Lymphedema Management in Leogane, Haiti, an Area Endemic for Bancroftian Filariasis

Lymphatic filariasis is a parasitic disease that is spread by mosquitoes. In tropical countries where lymphatic filariasis occurs, approximately 14 million people suffer from chronic swelling of the leg, known as lymphedema. Repeated episodes of bacterial skin infection (acute attacks) cause lymphedema to progress to its disfiguring form, elephantiasis. To help achieve the goal of eliminating lymphatic filariasis globally, the World Health Organization recommends basic lymphedema management, which emphasizes hygiene, skin care, exercise, and leg elevation. Its effectiveness in reducing acute attack frequency, as well as the role of compressive bandaging, have not been adequately evaluated in filariasis-endemic areas. Between 1995 and 1998, we studied 175 people with lymphedema of the leg in Leogane, Haiti. During Phase I of the study, when compression bandaging was used to reduce leg volume, the average acute attack rate was 1.56 episodes per year; it was greater in people who were illiterate and those who used compression bandages. After March 1997, when hygiene and skin care were emphasized and bandaging discouraged, acute attack frequency significantly decreased to 0.48 episodes per year. This study highlights the effectiveness of hygiene and skin care, as well as limitations of compressive bandaging, in managing lymphedema in filariasis-endemic areas

Endpoints for Lymphatic Filariasis Programs

In 2000, annual mass administration of diethlycarbamazine and albendazole began in Leogane Commune, Haiti, to interrupt transmission of lymphatic filariasis (LF). After 5 years of treatment, microfilaremia, antigenemia, and mosquito infection rates were significantly reduced, but LF transmission was not interrupted. These finding have implications for other LF elimination programs

Histopathologic Improvement with Lymphedema Management, Léogâne, Haiti

Basic management improves the histologic profile of limbs in patients with filarial lymphedema