Prevalence of onchocerciasis and epilepsy in a Tanzanian region after a prolonged community-directed treatment with ivermectin.

INTRODUCTION: Epidemiological evidence suggests that Onchocerca volvulus is associated with epilepsy, although the exact pathophysiological mechanism is unknown. Mahenge is an endemic focus of onchocerciasis, with the longest-running ivermectin treatment intervention in Tanzania. We assessed the prevalence of onchocerciasis and epilepsy after 25 years of control using ivermectin. METHODS: This was a population-based cross-sectional study in 34 villages in Mahenge in 2021. Community health workers conducted door-to-door household surveys to enumerate the population and screen for individuals suspected of epilepsy using a standardised questionnaire. Trained physicians confirmed epilepsy. Children aged 6-11 years were screened for onchocerciasis antibodies using the Ov16 rapid test. Villages were stratified into three altitude levels (low [<400], medium [400-950], and high [>950 meters above sea level]) as a proxy for rapids, which black flies favour for breeding sites. Incidence of epilepsy was estimated as a ratio of new cases in the year preceding the survey per 100,000 population. RESULTS: 56,604 individuals (median age 20.2 years, 51.1% females) were surveyed. Onchocerciasis prevalence in children was 11.8% and was highest in villages at medium (21.7%) and lowest in low altitudes (3.2%), p<0.001. Self-reported use of ivermectin was 88.4%. Epilepsy prevalence was 21.1 (95%CI: 19.9-22.3) cases per 1000 persons and was highest in medium (29.5%) and lowest in the lowlands (12.7%). The odds ratio (OR) of having epilepsy was significantly higher in females (OR = 1.22, 95%CI: 1.08-1.38), middle altitudes (OR = 2.34 [95%CI: 2.04-2.68]), and in individuals positive for OV16 (OR = 1.98 [95%CI:1.57-2.50]). The incidence of epilepsy a year before the survey was 117 (95%CI: 99.7-160.4) cases per 100,000 person-years. CONCLUSION: Despite ivermectin use for 25 years, the prevalence of onchocerciasis and epilepsy remains high. It is crucial to strengthen bi-annual ivermectin treatment and initiate interventions targeting vectors to control onchocerciasis and epilepsy in the area.

Community knowledge, attitude, practices and beliefs associated with persistence of malaria transmission in North-western and Southern regions of Tanzania.

BACKGROUND: Despite significant decline in the past two decades, malaria is still a major public health concern in Tanzania; with over 93% of the population still at risk. Community knowledge, attitudes and practices (KAP), and beliefs are key in enhancing uptake and utilization of malaria control interventions, but there is a lack of information on their contribution to effective control of the disease. This study was undertaken to determine KAP and beliefs of community members and service providers on malaria, and how they might be associated with increased risk and persistence of the disease burden in North-western and Southern regions of Tanzania. METHODS: This was an exploratory study that used qualitative methods including 16 in-depth interviews (IDI) and 32 focus group discussions (FGDs) to collect data from health service providers and community members, respectively. The study was conducted from September to October 2017 and covered 16 villages within eight districts from four regions of mainland Tanzania (Geita, Kigoma, Mtwara and Ruvuma) with persistently high malaria transmission for more than two decades. RESULTS: Most of the participants had good knowledge of malaria and how it is transmitted but some FGD participants did not know the actual cause of malaria, and thought that it is caused by bathing and drinking un-boiled water, or consuming contaminated food that has malaria parasites without warming it. Reported barriers to malaria prevention and control (by FGD and IDI participants) included shortage of qualified health workers, inefficient health financing, low care-seeking behaviour, consulting traditional healers, use of local herbs to treat malaria, poverty, increased breeding sites by socio-economic activities and misconceptions related to the use of bed nets and indoor residual spraying (IRS). Among the misconceptions, some participants believed that bed nets provided for free by the government came with bedbugs while others reported that free bed nets caused impotence among men. CONCLUSION: Despite good knowledge of malaria, several risk factors, such as socio-economic and behavioural issues, and misconceptions related to the use of bed nets and IRS were reported. Other key factors included unavailability or limited access to health services, poor health financing and economic activities that potentially contributed to persistence of malaria burden in these regions. Relevant policies and targeted malaria interventions, focusing on understanding socio-cultural factors, should be implemented to reduce and finally eliminate the disease in the study regions and others with persistent transmission.

Community knowledge, attitudes, and practices regarding epilepsy in Mahenge, Tanzania: A socio-anthropological study in an onchocerciasis-endemic area with a high prevalence of epilepsy.

BACKGROUND: Throughout Africa, epilepsy is a highly stigmatized condition. It is often considered to be contagious. This study aimed to assess community knowledge, attitude, and practices toward epilepsy in four villages namely Mdindo, Msogezi, Mzelezi, and Sali within Mahenge division, in Morogoro region, Tanzania. These villages are located in an onchocerciasis-endemic area with a high prevalence of epilepsy. METHODS: A qualitative cross-sectional study was conducted between June and July 2019 within the framework of a multi-disciplinary research project investigating the association between onchocerciasis and epilepsy. Focus group discussions (FGDs) and in-depth interviews (IDIs) were held with persons with epilepsy (PWE) and their caretakers, community resource persons, and program coordinators of the neglected tropical diseases program. RESULTS: The main symptoms of epilepsy were well described by all participants in all villages. PWE and caretakers in all villages considered epilepsy to be a major health problem and some participants ranked it second in importance after malaria. The reported perceived causes of epilepsy included febrile seizures during childhood (locally known as degedege), heredity, evil spirits, and inhaling flatus or touching secretions from PWE, especially during seizures. Knowledge about the association between epilepsy and onchocerciasis was low. People with epilepsy are disregarded, stigmatized, and marginalized from various opportunities such as conjugal rights, schooling, leadership roles, and property inheritance. Traditional healers are often the first contact when seeking care after a person develops epilepsy. CONCLUSION: Epilepsy is a major health burden and public health concern in the Mahenge area. The negative attitudes toward PWE and misconceptions about the causes of epilepsy contribute to delays in seeking care at health facilities. Findings from this study will be used to optimize the comprehensive community-based epilepsy treatment program that was recently initiated in the area.

Ivermectin treatment response in two rural villages with a high prevalence of onchocerciasis and epilepsy, Mahenge Tanzania.

Background: Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages. Objectives: We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE). Methods: Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment. Results: The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean microfilarial density was significantly higher at baseline 1.45(95%CI:0.98-2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11-0.37), p<0.001. Three months after ivermectin, the microfilarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3-91.4) of the 66 individuals with positive skin snips at baseline. High microfilarial density at baseline was the only significant predictor associated with higher microfilarial density in the post-ivermectin skin snips. Conclusion: Our study reports a decrease in microfilarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge.

Prevalence and Correlates of Lymphatic Filariasis Infection and Its Morbidity Following Mass Ivermectin and Albendazole Administration in Mkinga District, North-Eastern Tanzania.

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1-6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age (p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA (p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.

Clinical presentation of epilepsy in six villages in an onchocerciasis endemic area in Mahenge, Tanzania.

To describe the clinical manifestations of epilepsy and access to antiseizure treatment in Mahenge in Central Tanzania, an onchocerciasis endemic area with a high prevalence of epilepsy. A door-to-door epilepsy prevalence survey was conducted in four rural and two sub-urban villages. Trained community workers used five screening questions to identify persons suspected to have epilepsy. Such individuals were interviewed and examined by a neurologist or a medical doctor with additional training in epilepsy, and were tested for Onchocerca volvulus antibodies. A total of 221 out of 8,062 (2.74%) surveyed individuals were confirmed to have epilepsy. The median age at seizure onset was 12 years (interquartile range: 7-16). Seventy-nine persons with epilepsy (PWE) (36.1%) had a family member with epilepsy, which was a sibling in 52.1%. Tonic-clonic seizures (142 individuals; 64.2%) were the most common seizure type. Nodding seizures were reported in 12.7% of PWE; the majority of them living in rural villages. Persons with nodding seizures reported more frequent seizures, presented with more psychiatric symptoms, and more often had onchocerciasis antibodies than those with other seizure types. The high rate of individuals with a seizure onset at between seven and 16 years is characteristic of onchocerciasis-associated epilepsy (OAE). Of the PWE, 77.9% met the criteria for the clinical case definition of OAE. Eighty-three PWE (37.6%) were not taking any antiepileptic medication. Phenobarbital was the antiepileptic drug most commonly prescribed in 76.1% of treated PWE. The high prevalence of epilepsy in rural villages in Mahenge most likely is related to the high prevalence of OAE. To prevent children developing OAE, strengthening the onchocerciasis elimination programme in Mahenge is urgently needed. Moreover, a decentralised epilepsy treatment programme is also needed to provide uninterrupted access to affordable antiepileptic drugs for the many PWE living in rural villages in the Mahenge area.

Onchocerciasis-associated epilepsy: another piece in the puzzle from the Mahenge mountains, southern Tanzania.

In a study from the onchocerciasis-endemic area of Mahenge in southern Tanzania, Mmbando et al. [Inf Dis Poverty. 2018;7:64] demonstrate that in four selected villages the overall epilepsy prevalence was high, and significantly more elevated in the two villages of higher onchocerciasis endemicity compared to those of lower endemicity. This is replicating earlier findings from many other areas of tropical Africa. The authors are also providing data indicating that in the Mahenge focus, the prevalence of nodding syndrome may be related to that of onchocerciasis in the same way as epilepsy in general. The application of a clinical case definition for onchocerciasis-associated epilepsy (OAE) as used in the study of Mmbando et al. [Inf Dis Poverty. 2018;7:64] faces some difficulties; indeed, its precision in discerning cases of OAE from epilepsy due to other etiologies is not known, and it does not allow for a specific diagnosis in the individual patient. Because an operational surveillance tool for assessing the number of patients in the population could mean substantial advance for better estimating the burden of OAE, the proposed definition should be tried in different settings and its performance reviewed in the process.

High prevalence of epilepsy in two rural onchocerciasis endemic villages in the Mahenge area, Tanzania, after 20 years of community directed treatment with ivermectin.

BACKGROUND: Epilepsy is a neurological disorder with a multitude of underlying causes, which may include infection with Onchocerca volvulus, the parasitic worm that causes human onchocerciasis. A survey carried out in 1989 revealed a high prevalence of epilepsy (1.02% overall, ranging from 0.51 to 3.71% in ten villages) in the Mahenge area of Ulanga district, an onchocerciasis endemic region in south eastern Tanzania. This study aimed to determine the prevalence and incidence of epilepsy following 20 years of onchocerciasis control through annual community directed treatment with ivermectin (CDTI). METHODS: The study was conducted in January 2017 in two suburban and two rural villages in the Mahenge area. Door-to-door household visits were carried out by trained community health workers and data assistants to screen for persons suspected of having epilepsy, using a standardised questionnaire. Persons with suspected epilepsy were then interviewed and examined by a neurologist for case verification. Onchocerciasis associated epilepsy was defined as epilepsy without an obvious cause, with an onset of seizures between the ages of 3-18 years in previously healthy children. In each village, fifty males aged ≥20 years were tested for onchocerciasis antibodies using an OV16 rapid test and were examined for presence of onchocerciasis nodules. Children aged 6-10 years were also tested using OV16 tests. RESULTS: 5117 individuals (median age 18.5 years, 53.2% female) from 1168 households were screened. 244 (4.8%) were suspected of having epilepsy and invited for neurological assessment. Prevalence of epilepsy was 2.5%, with the rural villages having the highest rate (3.5% vs 1.5%), P < 0.001. Overall incidence of epilepsy was 111 cases (95% CI: 73-161) per 100 000 person-years, while that of onchocerciasis associated epilepsy was 131 (95% CI: 70-223). Prevalence of OV16 antibodies in adult males and among children 6-10 years old was higher in rural villages than in suburban villages (76.5% vs 50.6, and 42.6% vs 4.7% respectively), (P < 0.001), while overall prevalence of onchocerciasis nodules was 1.8%. CONCLUSIONS: This survey revealed a high prevalence and incidence of epilepsy in two rural onchocerciasis endemic villages in the Mahenge area. Despite 20 years of CDTI, a high prevalence of OV16 antibodies in children aged 6-10 years suggests on-going O. volvulus transmission. Reasons for the persistence of on-going parasite transmission in the Mahenge area need to be investigated.

Evolution of epilepsy prevalence and incidence in a Tanzanian area endemic for onchocerciasis and the potential impact of community-directed treatment with ivermectin: a cross-sectional study and comparison over 28 years.

INTRODUCTION: Worldwide, there are an estimated 50 million people affected by epilepsy. Its aetiology is manifold, and parasitic infections play an important role, specifically onchocerciasis. In onchocerciasis endemic areas, a distinctive form of epilepsy has been described as nodding syndrome, affecting children and causing nodding seizures, mental retardation and debilitating physical development. Onchocerciasis control programmes using community-directed treatment with ivermectin (CDTI) are implemented in endemic countries. This study is designed to contribute to a better understanding of the linkage between the onset of epilepsy, onchocerciasis and CDTI. Comparing the epidemiological data on epilepsy and onchocerciasis from pre-CDTI and 20 years after its introduction will allow identifying a potential impact of ivermectin on the onset of epilepsy. METHODS AND ANALYSIS: The study will be conducted in the Mahenge highlands in Tanzania. Study site selection is based on an in-depth study on epilepsy in that area dating from 1989. CDTI was introduced in 1997. By a door-to-door approach, the population will be screened for epilepsy using a validated questionnaire. Suspected cases will be invited for a neurological examination for case verification. Onchocerciasis prevalence will be assessed by a rapid epidemiological assessment. As an indicator for ongoing transmission, children younger than 10 years of age will be tested for Ov16 antibodies. Ivermectin use will be assessed at household level. Epilepsy data will be analysed in comparison with the 1989 data to reveal pre-CDTI and post-CDTI prevalence and incidence. ETHICS AND DISSEMINATION: The protocol has received ethical approval from the ethics committees of the University of Antwerp, Belgium, and of the National Institut of Medical Research, Dar es Salaam, Tanzania. The findings will be published in peer-reviewed journals, and presented to the health authorities in Tanzania, at national, regional and village level.

Retinoid Expression in Onchocercal Skin Disease: Pilot Study.

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA ( r2 = 0.25, P = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light.

Correction: Prevalence of Lymphatic Filariasis and Treatment Effectiveness of Albendazole/ Ivermectin in Individuals with HIV Co-infection in Southwest-Tanzania.

[This corrects the article DOI: 10.1371/journal.pntd.0004618.].

Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania: a prospective cohort study.

BACKGROUND: The past decades have seen an ongoing controversial debate about whether the immune activation induced by helminths has an effect on the susceptibility of individuals to HIV. In view of this, we assessed the effect of lymphatic filariasis, a chronic helminth disease elicited by Wuchereria bancrofti, on HIV incidence in southwest Tanzania. METHODS: In this population-based cohort study, we enrolled a geographically stratified randomly chosen sample of about 10% of the households in nine distinct sites in southwest Tanzania. All household members present were followed up and tested for HIV and circulating filarial antigen, an indicator of W bancrofti adult worm burden. Our main outcome of interest was HIV incidence in participants with or without lymphatic filariasis. FINDINGS: Between May 29, 2006, and June 16, 2011, we enrolled 4283 households with roughly 18 000 participants. Of these, 2699 individuals from Kyela district participated in at least one round of the EMINI study. In the 1055 initially HIV-negative adolescents and adults with clearly defined lymphatic filariasis status, 32 new HIV infections were observed in 2626 person-years. HIV incidence in lymphatic filariasis-positive participants (1·91 cases per 100 person-years) was significantly higher than the incidence in lymphatic filariasis-negative participants (0·80 cases per 100 person-years). The age-adjusted and sex-adjusted incidence rate ratio was 2·17 (95% CI 1·08-4·37, p=0·0300). Lymphatic filariasis status remained an independent and significantly relevant risk factor for HIV infection when controlled for other known risk factors such as sexual behaviour and socioeconomic factors. INTERPRETATION: To our knowledge, this is the first prospective study demonstrating a significantly increased risk of acquiring HIV for lymphatic filariasis-infected individuals. Immunological studies and interventional treatment studies that eliminate the adult worms and not only the microfilariae are needed to follow up on the results presented. FUNDING: European Union as part of EuropAid; German Federal Ministry of Education and Research; German Center for Infection Research.

Prevalence of Lymphatic Filariasis and Treatment Effectiveness of Albendazole/ Ivermectin in Individuals with HIV Co-infection in Southwest-Tanzania.

BACKGROUND: Annual mass treatment with ivermectin and albendazole is used to treat lymphatic filariasis in many African countries, including Tanzania. In areas where both diseases occur, it is unclear whether HIV co-infection reduces treatment success. METHODOLOGY: In a general population study in Southwest Tanzania, individuals were tested for HIV and circulating filarial antigen, an indicator of Wuchereria bancrofti adult worm burden, before the first and after 2 consecutive rounds of anti-filarial mass drug administration. PRINCIPLE FINDINGS: Testing of 2104 individuals aged 0-94 years before anti-filarial treatment revealed a prevalence of 24.8% for lymphatic filariasis and an HIV-prevalence of 8.9%. Lymphatic filariasis was rare in children, but prevalence increased in individuals above 10 years, whereas a strong increase in HIV was only seen above 18 years of age. The prevalence of lymphatic filariasis in adults above 18 years was 42.6% and 41.7% (p = 0.834) in HIV-negatives and-positives, respectively. Similarly, the HIV prevalence in the lymphatic filariasis infected (16.6%) and uninfected adult population (17.1%) was nearly the same. Of the above 2104 individuals 798 were re-tested after 2 rounds of antifilarial treatment. A significant reduction in the prevalence of circulating filarial antigen from 21.6% to 19.7% was found after treatment (relative drop of 8.8%, McNemar's exact p = 0.036). Furthermore, the post-treatment reduction of CFA positivity was (non-significantly) larger in HIV-positives than in HIV-negatives (univariable linear regression p = 0.154). CONCLUSION/SIGNIFICANCE: In an area with a high prevalence for both diseases, no difference was found between HIV-infected and uninfected individuals regarding the initial prevalence of lymphatic filariasis. A moderate but significant reduction in lymphatic filariasis prevalence and worm burden was demonstrated after two rounds of treatment with albendazole and ivermectin. Treatment effects were more pronounced in the HIV co-infected subgroup, indicating that the effectiveness of antifilarial treatment was not reduced by concomitant HIV-infection. Studies with longer follow-up time could validate the observed differences in treatment effectiveness.

Current Epidemiological Assessment of Bancroftian Filariasis in Tanga Region, Northeastern Tanzania.

Background. Tanzania started a countrywide lymphatic filariasis elimination programme in 2000 adopting the mass drug administration (MDA) strategy. The drug used for the programme was the combination of ivermectin and albendazole. However, there is limited information on the current epidemiological trend of the infections, where MDA implementation is ongoing. The present study aimed at assessing the current status of Bancroftian filariasis infection rate and morbidity where MDA has been distributed and administered for over eight rounds. Methodology. The study was a cross-sectional descriptive study involving 272 individuals (>18 years) from endemic communities in Tanga region where MDA has been implemented. Clinical, sociodemographic, and circulating filarial antigen (CFA) test was undertaken using immune chromatographic card test according to the manufacturer's instructions. Results. A total of 472 individuals were screened: 307/472 (65.1%) were males while 165/472 (34.9%) were females. The overall prevalence of CFA was 5.51%, that of hydrocoele was 73.2%, and that of lymphoedema was 16.0%. The prevalence of hydrocoele combined with lymphoedema was 5.5%. Conclusion. Our findings demonstrate a considerable reduction in filarial infection. However, there is clear evidence of ongoing transmission despite the 8 rounds of MDA. It is unlikely that the annual MDA would interrupt filarial transmission; therefore, additional strategies are needed to accelerate lymphatic filariasis control and elimination.

Lost to follow up and clinical outcomes of HIV adult patients on antiretroviral therapy in care and treatment centres in Tanga City, north-eastern Tanzania.

Scaling up of Antiretroviral (ARV) drugs is crucial and should be a perpetual venture in developing countries in-order to increase the survival period of HIV/AIDS individuals. In Tanzania, information on the rate of patients considered as lost to follow up during treatment with ARVs is scarce. The objective of this study was to determine the rate of lost to follow up and treatment outcome among patients attending two care and treatment clinics (CTCs) in Tanga City in north-eastern Tanzania. A descriptive observational study was carried out on cohorts from Tanga AIDS Working Group and Bombo Regional Hospital. The total number of patients identified as "lost to follow up" were 89 of which 14 (15.7%) died. Among those who died, 3 (21.4%) died between the second week and 3 months after ARV initiation. Of those still alive (84.3%; 75/89), 25% (19/75) were still on ARVs, whereas 47 (62.7%) self transferred to other CTCs. Proper patient documentation with actual residence address is a crucial aspect for adherence. Similarly, frequent prompt tracing of patient should be part of any drug interventional programme linking facility and communities.

Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial.

BACKGROUND: Wolbachia endosymbionts of filarial nematodes are vital for larval development and adult-worm fertility and viability. This essential dependency on the bacterium for survival of the parasites has provided a new approach to treat filariasis with antibiotics. We used this strategy to investigate the effects of doxycycline treatment on the major cause of lymphatic filariasis, Wuchereria bancrofti. METHODS: We undertook a double-blind, randomised, placebo-controlled field trial of doxycycline (200 mg per day) for 8 weeks in 72 individuals infected with W bancrofti from Kimang'a village, Pangani, Tanzania. Participants were randomly assigned by block randomisation to receive capsules of doxycycline (n=34) or placebo (n=38). We assessed treatment efficacy by monitoring microfilaraemia, antigenaemia, and ultrasound detection of adult worms. Follow-up assessments were done at 5, 8, 11, and 14 months after the start of treatment. Analysis was per protocol. FINDINGS: One person from the doxycycline group died from HIV infection. Five (doxycycline) and 11 (placebo) individuals were absent at the time of ultrasound analysis. Doxycycline treatment almost completely eliminated microfilaraemia at 8-14 months' follow-up (for all timepoints p<0.001). Ultrasonography detected adult worms in only six (22%) of 27 individuals treated with doxycycline compared with 24 (88%) of 27 with placebo at 14 months after the start of treatment (p<0.0001). At the same timepoint, filarial antigenaemia in the doxycycline group fell to about half of that before treatment (p=0.015). Adverse events were few and mild. INTERPRETATION: An 8-week course of doxycycline is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia.