The impact of six rounds of single-dose mass administration of diethylcarbamazine or ivermectin on the transmission of Wuchereria bancrofti by Culex quinquefasciatus and its implications for lymphatic filariasis elimination programmes

Lymphatic filariasis (LF) is targeted for global elimination. Transmission interruption through repeated annual single-dose mass administration of anti-filarial drugs is the mainstay of the LF elimination strategy. This study examined the ability of six rounds of mass administration of diethylcarbamazine (DEC) or ivermectin (IVM) to interrupt transmission of Wuchereria bancrofti by Culex quinquefasciatus, the predominant parasite and vector species, respectively. After six rounds of mass drug administration (MDA), received by 54-75% of the eligible population (> or =15 kg body weight), the resting vector infection and infectivity rates fell by 83% and 79% in the DEC arm, 85% and 84% in the IVM arm and 31% and 45% in the placebo arm, respectively. The landing vector infection and infectivity rates fell by 83% and 94% in the DEC arm, 63% and 75% in the IVM arm and 1% each in the placebo arm, respectively. The filarial larval load per resting mosquito declined by 92% and 93% and per landing mosquito by 83% and 69% in the DEC and IVM arms, respectively. The annual infective biting rate (AIBR) fell from 735 to 93 (87%) in the DEC arm, 422 to 102 (76%) in the IVM arm and 472 to 398 (16%) in the placebo arm. The annual transmission potential (ATP) declined from 2514 to 125 (95%), 1212 to 241 (80%) and 1547 to 1402 (9%) in the DEC, IVM and placebo arms, respectively. However, mosquitoes with infection [microfilaria/larva 1/larva 2 (Mf/L1/L2)] were found in all study villages. Three of five villages in the IVM arm and two of five in the DEC arm recorded no resting mosquitoes with infective-stage (L3) larva. Although the ATP, after six rounds of MDA, fell substantially and remained at 125 and 241 in the DEC and IVM arms, respectively, the cumulative exposure to infective stage larvae (ATP) during the treatment period of 6 years was as high as 2995 in the DEC arm and 1522 in the IVM arm, because of considerable level of transmission during the initial (1-3) rounds of MDA. We conclude that (i) six rounds of MDA, even with 54-75% treatment coverage, can reduce LF transmission very appreciably; (ii) better treatment coverage and a few more rounds of MDA may achieve total interruption of transmission; (iii) high vector densities may partly nullify the reductions achieved in vector infection and infectivity rates by MDA and (iv) achievement of 'true zero' Mf prevalence in communities and 0% infection rate (mosquitoes with Mf/L1/L2) in mosquitoes may be necessary to totally interrupt Culex-transmitted LF.     

Elimination of bancroftian filariasis (Wuchereria bancrofti) in Santa Catarina state, Brazil

Summary During the 1950s, three foci of Wuchereria bancrofti transmission were identified in the State of Santa Catarina, Brazil. In Florianópolis, São José da Ponta Grossa and Barra da Laguna community treatment of bancroftian filariasis with diethylcarbamazine (DEC) was performed using two distinct approaches, without vector control or improvements in sanitation. In two of the three communities only microfilaraemic individuals were treated, while in Barra da Laguna the entire population received DEC treatment regardless of their infection status. In both cases, transmission of the parasite was blocked and no new cases were detected in all localities for up to 10 years. Recently, a new survey in São José da Ponta Grossa and Barra communities revealed no microfilaria‐positive individuals, including residents that were positive in the 1950s. These data confirm that transmission of W. bancrofti was interrupted in Santa Catarina, and mass treatment appears to be more effective than treatment of microfilaraemic individuals only.     

The impact of 34 years of massive DEC chemotherapy on Wuchereria bancrofti infection and transmission: the Maupiti cohort

Semi-annual mass DEC chemotherapy combined with vector control at the beginning of the programme, has been administered on the remote island of Maupiti (French Polynesia) since 1955 (except two periods in 1960-67 and 1970-74). The results of two surveys in 1985 and 1989, reporting 0% microfilaraemia, led to the hope that the eradication of lymphatic filariasis had been achieved. We combined parasitological criteria (microfilaraemia by membrane filtration), immunological (antigenaemia and serum levels of specific IgG antibodies) and molecular (PCR-based evaluation of infection in mosquitoes) techniques and found only good control of the parasite: We found residual microfilaraemia in 0.4% of the sample (mean level in carriers: 101.2 mf/ml), antigenaemia in 4.6% (mean level in positive persons: 714.4 units/ml) and specific IgG in 21.6% (including in one very young child). In addition, an infection rate of 1.4% was calculated in the Aedes polynesiensis vector population. These data, obtained in 1997 just before a hurricane, were partially confirmed in 1999 (0.1% of infection rate in the vector). Together with the possibility of some resistance to DEC, various epidemiological factors critical for the eradication of lymphatic filariasis are discussed.     

Model-based analysis of trial data: microfilaria and worm-productivity loss after diethylcarbamazine-albendazole or ivermectin-albendazole combination therapy against Wuchereria bancrofti

OBJECTIVES: To determine the efficacies of combinations of ivermectin or diethylcarbamazine and albendazole, which are recommended for use in mass treatment programmes against lymphatic filariasis. METHOD: Review of published trends in microfilarial (mf) intensities after treatment with these combination therapies. By fitting a mathematical model of treatment effects to the trial data, we quantified the efficacy of treatment, distinguishing between the killing of mf (mf loss) and a reduction in mf production by adult worms (worm-productivity loss). After diethylcarbamazine-albendazole treatment mf density dropped immediately, then slowly but steadily decreased further (four trials). After ivermectin-albendazole treatment, mf densities immediately dropped to near-zero levels, followed by a small increase (five trials). For diethylcarbamazine-albendazole treatment the average mf loss was approximately 83% (ranging from 54% to 100% in the different studies) and worm-productivity loss was 100% (in all studies). For ivermectin-albendazole treatment, average mf loss was 100% (ranging from 98% to 100%) and worm productivity loss was 96% (ranging from 83% to 100%). The effects were dose-dependent. Sensitivity analysis showed that the estimates did not depend on assumptions on worm lifespan or premature period and little on assumptions on mf lifespan. CONCLUSION: The two therapies differ with respect to their direct effect on mf, but both are highly effective against adult worms. If mass treatment with these combination therapies achieves high coverage, they can have a large impact on lymphatic filariasis transmission.     

Prolonged persistence of residual Wuchereria bancrofti infection after cessation of diethylcarbamazine-fortified salt programme

Summary A diethylcarbamazine (DEC)‐fortified salt intervention programme was implemented between 1982 and 1986 in Karaikal district, Union territory of Pondicherry, south India, to control Culex transmitted bancroftian filariasis. The intervention reduced the microfilaria (Mf) rate from 4.49% to 0.08%. To eliminate the residual microfilaraemia, the health department detected and treated Mf carriers from 1987 to 2005 and mass‐administered drugs in 2004 and 2005. Surveillance from 1987 to 2005 revealed persistent microfilaraemia in 0.03–0.42% of the population. In 2006, we conducted a more detailed Mf survey and a child antigenaemia (Ag) survey in 15 urban wards and 17 rural villages. These surveys showed an overall Mf rate of 0.46% in the high‐risk urban areas and 0.18% in the rural areas; none of the sampled children was positive for Ag. All detected Mf carriers were >20 years old. The age of the youngest Mf carrier was 30 years in urban and 21 years in rural areas, which suggests that transmission was interrupted and there was no incidence of new Mf case after cessation of DEC salt programme. Eleven of 15 urban and 15 of 17 villages were totally free from microfilaraemia. Nevertheless, three of 15 surveyed urban localities and two of 17 villages showed >1% Mf rate. Thus, it seems that (i) post‐intervention very low levels of microfilaraemia can continue as long as 20 years; (ii) 0.60–0.70% Mf rate is a safe level and at this level recrudescence of infection may not occur; (iii) there can be isolated localities with >1% Mf rate and their detection for further intervention measures could be challenging in larger control/elimination programmes and (iv) the residual infection mostly gets concentrated in the adult population, in underdeveloped urban areas and in historically highly endemic or large endemic rural areas. These groups and areas should be targeted with rigorous intervention measures such as mass drug administration to eliminate the residual infection.     

Impact of seven rounds of mass administration of diethylcarbamazine and ivermectin on prevalence of chronic lymphatic filariasis in south India

Objective To evaluate the impact of seven rounds of mass administration of diethylcarbamazine (DEC) and ivermectin on the prevalence of chronic lymphatic filariasis and to compare it with that observed in a placebo arm in a community‐level trial. Methods Cross‐sectional clinical surveys were carried out before and after seven rounds of mass drug administration (MDA). About 54–75% of the target population were treated at each round of MDA. Results After seven rounds, the hydrocele prevalence had declined from the pre‐intervention level of 20.5–5.1% (P < 0.05) in the DEC arm, from 23.9% to 10.4% (P < 0.05) in the ivermectin arm and from 20.4% to 10.9% (P < 0.05) in the placebo arm, equivalent to reductions of 75.3%, 56.6% and 46.6%, respectively. The lymphoedema/elephantiasis prevalence declined only marginally and without statistical significance from 3.7% to 3.2%, 4.6% to 3.9% and 2.9% to 2.3% in the DEC, ivermectin and placebo arm. After the seventh MDA, none of the sampled people in the 0–20 age group was found with hydrocele and there was a statistically significant decline in hydrocele prevalence in all other age groups in the communities treated with DEC, the drug known to have macrofilaricidal effect. The impact was relatively less in ivermectin arm. Conclusion Repeated DEC administration has the potential to prevent incidence of new hydrocele cases and may resolve the manifestation at least in a proportion of affected people. Apart from reducing the microfilaraemia prevalence and transmission of infection, MDA also results in significant public health benefits by reducing the burden of hydrocele in treated communities.     

Regulation of the immune response in lymphatic filariasis: perspectives on acute and chronic infection with Wuchereria bancrofti in South India

Delineating the immune responses in lymphatic filariasis has been complicated not only by the rapidly expanding knowledge of new immunological mediators and effortors, but also by new methodologies (in particular, circulating filarial antigen detection) for defining and categorizing filarial-infected individuals. By using assays for circulating antigen in the sera collected as part of the many immunological studies performed on individuals in a Wuchereria bancrofti-endemic region of South India, we have attempted to explore the influence of patency on the antigen-driven proliferative and cytokine responses seen in peripheral blood mononuclear cells of individuals with varying clinical manifestations of lymphatic filarial infection. Moreover, we have provided perspectives on the differences between acute and chronic infection with W. bancrofti and suggested mechanisms that may underly the modulation of the immune response as patency occurs.     

Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment

Summary The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 μg/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.     

Macrofilaricidal effect of 4 weeks of treatment with doxycycline on Wuchereria bancrofti

Objective To evaluate the efficacy of doxycycline as a macrofilaricidal agent against Wuchereria bancrofti. Method In the Western Region of Ghana, 18 patients infected with W. bancrofti were recruited and treated with 200 mg doxycycline per day for 4 weeks. Seven untreated patients served as controls. Four months after doxycycline treatment, all patients received 150 μg/kg ivermectin. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia and filarial dance sign (FDS). Results Four months after doxycycline treatment, cases had a significantly lower Wolbachia load than controls; and 24 months after treatment, microfilaraemia, antigenaemia and frequency of FDS were significantly lower in cases than controls. Most importantly, 4 weeks of doxycycline killed 80% of macrofilariae, which is comparable with the results of a 6‐week regimen. Circulating filarial antigenaemia and FDS were strongly correlated. Conclusion A 4‐week regimen of doxycycline seems sufficient to kill adult W. bancrofti and could be advantageous for the treatment of individual patients, e.g. in outpatient clinics.     

Inadvertent exposure of pregnant women to ivermectin and albendazole during mass drug administration for lymphatic filariasis

The current strategy for the interruption of transmission of lymphatic filariasis in areas where the disease is co-endemic with onchocerciasis is repeated annual mass treatment of endemic communities with ivermectin and albendazole. These drugs are not recommended for use in pregnancy. Pregnant women are excluded on the basis of their last menses. This exclusion criterion based on recall carries some inherent errors, leading sometimes to inadvertent exposure of foetuses to these drugs. This study set out to document the extent of inadvertent exposure of pregnant women to albendazole and ivermectin and assess the relative risk of congenital malformations because of inadvertent treatment with these drugs in early pregnancy. The study was conducted in the Ahanta West District of Ghana. Local pregnancy revelation norms were studied, followed by a household survey of women aged 15-45 years to assess drug administration coverage. All infants born within 42 weeks of the mass drug treatment were examined to document any congenital malformations. Mothers who had lost any such infants responded to a verbal autopsy to ascertain the probable cause of death. Health facilities and local Traditional Birth Attendants were also visited to review maternity records. Of 2985 women of childbearing age (15-49 years) who were interviewed, 343 were pregnant during the mass drug administration. The sensitivity of the last menstrual period in detecting pregnancy and thus being excluded from treatment was 0.854 (293 of 343). Some pregnant women 50 of 343 (14.6%) had thus been inadvertently treated. This represents 1.7% of women in fertile age group (15-49 years). Of the six children found with some congenital malformations in these communities, one had been exposed to the drugs in-utero. The relative risk for congenital malformation after exposure was 1.05 (P=1.0). Two of nine reported spontaneous abortions had been exposed to the drugs (P=0.62). We conclude that the local mode of excluding pregnancy in the current programme, while not perfect, is sufficiently effective and reliable for such a public health intervention; and importantly, that there is no evidence of a higher risk of congenital malformation or abortions in those who are inadvertently exposed.     

Coverage, compliance and some operational issues of mass drug administration during the programme to eliminate lymphatic filariasis in Orissa, India

This paper reports the coverage, compliance and other operational issues of mass drug administration (MDA) of diethylcarbamazine and albendazole under a programme to eliminate lymphatic filariasis (LF) in Orissa state of India. Both quantitative and qualitative methods were used to collect data from 90 villages and nine urban areas of four districts of Orissa, India. In Orissa, 67% of people older than 2 years had received the drugs during MDA and 42% had consumed them. About 25% of people had not taken the tablets although they received them. Urban areas recorded lower rates than rural areas. The paper discusses some policy/health system-, community- and drug-related issues that influenced coverage and compliance of MDA. It is essential to improve compliance in future rounds of MDA to achieve targets of control and eventual elimination of LF in a reasonable time frame.     

Cost and cost effectiveness of mass diethylcarbamazine chemotherapy for the control of bancroftian filariasis: comparison of four strategies in Tanzania

This study examines the costs and cost effectiveness of four different mass diethylcarbamazine (DEC) chemotherapy regimens—standard dose, semi‐annual single dose, low monthly dose and DEC‐medicated salt—in reducing microfilarial (mf) prevalence at the community level. Costs were estimated for each intervention in relation to both ingredient and activity, by the derivation and use of detailed itemized cost menus. The most expensive and most effective strategy in reducing community mf prevalence over 2 years was DEC salt intervention, followed in order of costs by the standard, low monthly and semi‐annual DEC strategies. The most cost effective strategy was the low monthly DEC treatment. Cost and sensitivity analyses, however, suggest that the optimal choice of mass DEC strategy for reducing mf is very sensitive to programme design parameters. In particular, the results demonstrate that if the salt delivery structure is simplified, DEC salt has the potential to be the dominant intervention for filariasis control. The results suggest that economies of scale considerations might militate against the adoption of this intervention for large‐scale applications, unless perhaps offset by its potential for cost recovery by direct patient purchase. Further analyses require a more realistic evaluation of filariasis intervention effectiveness by addressing changes in infection intensity and by accounting for the population dynamics of parasite transmission and control.     

The prevalences of Wuchereria bancrofti antigenaemia in communities given six rounds of treatment with diethylcarbamazine, ivermectin or placebo tablets

The ICT filariasis card test was used to determine the prevalences of Wuchereria bancrofti antigenaemia among villagers in India. Prior to the tests, those living in the 15 study villages had been treated six times, in six rounds of mass treatment (with 54%-75% coverage) spread over 6 years, with single doses of diethylcarbamazine (five villages), ivermectin (five villages) or placebo (five villages). The corresponding overall prevalences (and ranges) of filarial antigenaemia were 20.2% (13.7%-28.6%), 22.6% (15.3%-34.3%) and 25.9% (22.6%-29.3%), respectively. The overall prevalence of antigenaemia in the villages where diethylcarbamazine (DEC) had been distributed (but not that in the 'ivermectin' villages) was significantly lower than that recorded in the 'placebo' villages (z =2.56; P <0.05). The prevalences of antigenaemia among the villagers aged 1-5 years (18.9%, 15.6% and 22.4% in the DEC, ivermectin and placebo villages, respectively) did not differ significantly with treatment (P >0.05). The results indicate that annual mass treatments based on DEC or ivermectin, with 54%-75% treatment coverage, may have only a limited effect on the prevalence of infection with adult W. bancrofti. The possible reasons for the antigenaemias observed are discussed.     

Effectiveness of two annual, single-dose mass drug administrations of diethylcarbamazine alone or in combination with albendazole on soil-transmitted helminthiasis in filariasis elimination programme

A longitudinal community-trial on the control of soil-transmitted helminths (STHs), as part of a lymphatic filariasis elimination campaign, was taken up in two revenue blocks of southern India in the years 2001 and 2002 to assess the impact of two annual single-dose mass drug administration (MDA) of diethylcarbamazine (DEC) + albendazole (ALB) with that of DEC alone. The prevalences and intensities of STHs were studied among cross-sectional samples of school children aged 9-10 years by using the Kato-Katz technique at baseline and 11 months after each MDA. The combined drug mass treatment produced a higher reduction in the prevalence (RIP) (51-77%) and the egg reduction rate (ERR) (92-98%) compared with 12-15% RIP and 58-62% ERR of DEC alone mass treatment. The effect of two-drug therapy after two annual treatments was relatively long lasting as shown by RIP and ERR indicating that the reinfection rates were relatively lower in this approach than single-drug therapy. This study demonstrates that mass drug co-administration of DEC + ALB in Global Programme for Elimination of Lymphatic Filariasis (GPELF) targeted at the community had a synergistic and sustainable effect against soil-transmitted helminthiasis and provided considerable 'beyond filariasis' benefits. The additional advantages accrued to the community underscore the importance of scaling-up GPELF to cover the entire population at risk.     

Effectiveness of community and health services-organized drug delivery strategies for elimination of lymphatic filariasis in rural areas of Tamil Nadu, India

Lymphatic filariasis (LF) is targeted for global elimination. Repeated annual single-dose mass treatment with antifilarials has been recommended as the principal strategy to achieve LF elimination. This requires an effective and sustainable strategy to deliver the drug, diethylcarbamazine (DEC), to communities. In this study, a new drug delivery strategy - community-directed treatment (comDT) - was developed and implemented and its effectiveness compared with that of the traditional health services-organized drug delivery, in rural areas of Tamil Nadu, India. Qualitative and quantitative data showed that the communities and health services were able to distribute the drug in almost all villages. The drug distribution rate and treatment compliance rate of comDT and health services treatment were statistically compared after adjusting them for clustering. Under the comDT 68% (n=20 villages; range: 0-97%) of the population received DEC, compared with 74% (n=20 villages; range: 48-95%) with the health services treatment strategy (P > 0.05). However, only about 53% (range: 0-91%) of comDT recipients and 59% (range: 32-79%) of those who received DEC from the health services consumed the drug (P > 0.05). Although statistically not significant, the distribution and compliance rates were lower under the comDT strategy. Also, the strategy's operationalization appears to be difficult because of some social factors, and the tradition of communities' dependence on health services for treatment, whereas health services-organized distribution was much less cumbersome and found to be more acceptable to people. However, the distribution (74%) and compliance rates (59%) achieved by health services were also only moderate and may not be adequate to eliminate LF in a reasonable time frame. Health services manpower alone may not be sufficient to distribute the drug. We conclude that drug distribution by health services is the best option for India and participation of the community volunteers and village level government staffs in the programme is necessary to effectively distribute the drug and attain the desirable levels of treatment compliance to eliminate LF.     

Using knowledge, attitudes and practice (KAP) surveys on lymphatic filariasis to prepare a health promotion campaign for mass drug administration in Alor District, Indonesia

We report the results of two surveys of people's knowledge, attitudes and practices (KAP) regarding lymphatic filariasis (LF) in Alor District, eastern Indonesia. The results of the surveys were used to prepare and evaluate the social mobilization component of a pilot mass drug administration (MDA) in five villages. In the study area, the filarial parasites Brugia timori and Wuchereria bancrofti are highly endemic. Frequent and severe adverse reactions after MDA may occur especially in areas endemic for B. timori and therefore, a special communication strategy was designed to inform and to educate communities about LF and its control. The first KAP survey was conducted as a baseline pre-MDA with diethylcarbamazine and albendazole and the second as a post-intervention evaluation in order to obtain information on the impact of the communication campaign. Before the information campaign and the subsequent MDA, 54% of the study population had heard of one of the three main terms for LF, whereas after health education and MDA, 89% had heard of at least one of the three terms. Similarly, pre-MDA, 21% reported having had previously taken the treatment for filariasis, while post-MDA, 88% reported having taken the treatment during the pilot treatment period. The historical fears and traumatic experiences associated with past LF treatment campaigns in Indonesia were averted since both the communication campaign and the MDA were designed appropriately for and together with the community. As a result, compliance was sufficient in the first round to successfully begin the elimination process.     

Long-term population migration: an important aspect to be considered during mass drug administration for elimination of lymphatic filariasis

Annual 2-drug, single-dose mass drug administration (MDA) to 80-90% of the eligible population for 4-6 years are pre-requisites for the successful elimination of lymphatic filariasis (LF) from endemic communities by interruption of transmission and eventual elimination of new infections. In an experimental intervention project on the control of LF in Villupuram district of Tamil Nadu state, India, migration patterns of the villagers were investigated to determine the appropriate timing to implement MDA in order to attain high coverage in a village-level study. Between January and December 1997, 16 observations took place at 3-week intervals, following MDA with two drugs viz., diethylcarbamazine and ivermectin, in July-August 1996. The migrants from the village constituted 17-27% at different points of time and both short-term and long-term migrating patterns were observed. More villagers were available during the agricultural season (September-January), peaking around mid-January [83%; significantly higher (P < 0.05)] than during most of the remaining months, including a substantial portion of the migrant population. There is an urgent need to reschedule the yearly MDA in this area to take place in January and to plan mopping up operations by involving local self-help groups to include migrants (both short-term and long-term) in the LF elimination efforts.     

Albendazole for the control and elimination of lymphatic filariasis: systematic review

OBJECTIVES: The Global Programme to Eliminate Lymphatic Filariasis recommends albendazole in combination with other antifilarial drugs. This systematic review examines albendazole in treatment and control of lymphatic filariasis. DATASOURCES: The Cochrane Controlled Trials Register, MEDLINE and EMBASE to April 2005; contacting experts, international organisations and drug manufacturers. METHODS: Randomised or quasi-randomised controlled trials included; two reviewers independently assessed eligibility, quality, and extracted data. We calculated the relative risk of microfilaraemia (mf) prevalence using fixed effect, or random effects model in case of heterogeneity. RESULTS: Six trials met inclusion criteria. Three trials compared albendazole with placebo: no effect was demonstrated on mf prevalence, but density was lower in one of the three studies at 6 months. Three trials added albendazole to ivermectin, with no demonstrable effect; prevalence tended to be lower at 4--6 months but not at 12 months (4--6 months; RR 0.49, 95% CI 0.18 to 1.39, n=255, 2 trials; 12 months: RR 1.00, 95% CI 0.88 to 1.13, n=348, 2 trials). Mf density was significantly lower in two of the three trials; one of two trials measuring density at 12 months showed a difference. Three trials added albendazole to diethylcarbamazine; two were small trials with no difference demonstrated; the third study tended to favour combination at 6 months (RR=0.62, 95% CI 0.32 to 1.21, n=491), with a significant difference for density. CONCLUSIONS: The effect of albendazole against adult and larval filarial parasites, alone and in combination with other antifilarial drugs, deserves further rigorous research.     

A programme to eliminate lymphatic filariasis in Tamil Nadu state, India: compliance with annual single-dose DEC mass treatment and some related operational aspects

This paper reports on DEC distribution and compliance with treatment in a large-scale annual single-dose mass treatment programme to eliminate lymphatic filariasis in the south Indian state of Tamil Nadu. 76.9% of households (82.5% in rural areas and 58.0% in urban areas) were aware of drug distribution for control of filariasis. DEC was given to 70% (= distribution rate) (range 0-92%) of the population and 53.5% (range 12-89%) complied with treatment. The distribution rate was more than 75% in 74% of the villages and compliance was in the range of 51-75% in 76% of the villages. About 5% of the treated population reported side-effects. Distribution and compliance were higher in rural than urban areas and similar between males and females. Qualitative data showed that some socio-economic factors, logistic and drug-related problems and people's poor knowledge and perceived benefits of treatment played a role in a proportion of the population not receiving or taking the drug. The Tamil Nadu programme showed that large-scale repeated annual DEC mass treatment is feasible and that existing health services are capable of delivering the drug to all communities. While even poor to moderate compliance rates can reduce the vector transmission of infection to some extent, improved drug distribution and compliance with treatment are necessary to consolidate the gains of earlier rounds of treatment and achieve the goal of filariasis elimination within a reasonable time frame.     

The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji

Diethylcarbamazine (DEC), first introduced in 1947, was shown to have strong efficacy and safety for treatment of human lymphatic filariasis, which is caused mostly by a species Wuchereria bancrofti. Many studies to optimize the dosage and treatment schedule of DEC followed, and, based on the results, control programs with various regimens were implemented in different endemic areas/countries. By the mid 1970s, with endorsement by the WHO Expert Committee on Filariasis (3rd report, 1974), the standard DEC regimen for W. bancrofti infection in mass treatment had been established in principle: a total dose of 72 mg/kg of body weight given in 12 divided doses, once weekly or monthly, at 6 mg/kg each. Not long after the committee report, the efficacy of annual single-dose treatment at 6 mg/kg, which is only one twelfth of the WHO-recommended dose in a year, was reported effective in French Polynesia (study period: 1973-78), and later in Samoa (study period: 1979-81). These results were published between 1978 and 1985 in the Bulletin of WHO but received little attention. In the mid 1980s, the efficacy of ivermectin, the first-choice drug for onchocerciasis, against lymphatic filariae came to light. Since the effect at a single dose was remarkable, and often better than DEC, it was predicted that the newly introduced drug would replace DEC. Treatment experiments with ivermectin increased quickly in number. Meanwhile, annual single-dose mass drug administration (MDA) with DEC at 6 mg/kg was under scrutiny in Samoa and Fiji. In the early 1990s, the Samoan study, which covered the entire population of 160,000 with 3 annual MDAs, reported a significant reduction in microfilaria (mf) prevalence and mean mf density, while in Fiji, the efficacy of 5 rounds of annual MDA (total dose, 30 mg/kg) was shown to be as effective as 28 multi-dose MDA spread over 2 years (6 weekly plus 22 monthly treatments at 5 mg/kg; total dose, 140 mg/kg). Several additional studies carried out in Samoa in relation to the annual single-dose MDAs revealed that low density mf carriers, who have a very low mf count of 1-20/ml of venous blood, could not play a significant role in filariasis transmission.From around 1990, studies on spaced low-dose DEC treatments and various types of combination chemotherapy with DEC and ivermectin increased. Albendazole, a well-known anti-intestinal helminths agent, was later added to the combination. The main findings of these studies with W. bancrofti are: (i) a single dose of DEC at 6 mg/kg reduced mean mf density by ca. 90% 1 year after treatment; (ii) the same dose could damage/kill adult worms; (iii) a single dose of ivermectin at ca. 400 μg/kg was more effective than DEC in reducing mf density during the first year and was similarly or less effective in the second year; (iv) ivermectin probably could not kill adult worms; (v) a single combined dose of albendazole (400 mg) and DEC (6 mg/kg) was effective to reduce mf density by 85 to nearly 100% 12-24 months after treatment; and (vi) ivermectin or albendazole included in the combination chemotherapy produced "beyond-filariasis" benefits: clearance/reduction of intestinal helminths, and, additionally, in the case of ivermectin, skin-dwelling ectoparasites.The Global Programme to Eliminate Lymphatic Filariasis (GPELF) started its worldwide activities in 2000, with the target of elimination by 2020. The basic strategy is to conduct annual single-dose MDAs for 4-6 years. In 2000-2007, a minimum of 570 million individuals were treated in 48 of 83 endemic countries. The drugs used are DEC 6 mg/kg plus albendazole 400 mg in most countries, or ivermectin 200-400 μg/kg plus albendazole 400 mg particularly in onchocerciasis endemic countries in Africa. (MDAs with DEC alone had been used in India.)The GPELF achieved impressive results in terms of parasitological cure/improvement, clinical benefits, social and economic impacts, etc. However, the most impressive result of all was the programme's success in mobilizing hundreds of millions of local people, who not only took drugs but many of them actively supported MDAs as drug distributors and volunteers. Beyond filariasis, the role people can play in supplementing rural health services is now a topic of discussion and a source of hope for a new sustainable system.