Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis

Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockade of embryogenesis, adult sterility and premature death 18–24 months post-treatment. Long treatment length and contraindications in children and pregnancy are obstacles to implementing doxycycline as a public health strategy. Here we determine, via preclinical infection models of Brugia malayi or Onchocerca ochengi that elevated exposures of orally-administered rifampicin can lead to Wolbachia depletions from filariae more rapidly than those achieved by doxycycline. Dose escalation of rifampicin achieves >90% Wolbachia depletion in time periods of 7 days in B. malayi and 14 days in O. ochengi. Using pharmacokinetic-pharmacodynamic modelling and mouse-human bridging analysis, we conclude that clinically relevant dose elevations of rifampicin, which have recently been determined as safe in humans, could be administered as short courses to filariasis target populations with potential to reduce anti-Wolbachia curative therapy times to between one and two weeks

Preliminary observations on the occurrence of lymphatic filariasis in Cross River State, Nigeria

A situation analysis of the occurrence of Lymphatic Filariasis (LF) in Cross River State, Nigeria, was conducted within the period November 2000 and March 2001. Information gathered from state and local Government Area (LGA) policy makers, health personnel and community key informants revealed that Lymphatic Filariasis occurred in 1 Local Government Areas:- Akamkpa, Bekwara, Biase, Boki, Etung, Ikom, Obanliku, Obubra, Obudu, Ogoja, Yala, Yakurr and Odukpani. All 19 villages mentioned as having current and past cases were visited and found to have a total of 13 current cases of lymphoedema. The cases (most farmers, all permanent residents of the village, and all within the age bracket of 28- years, complained of periodic fever, headache and chills particularly in rainy season. They had swollen limbs, usually unilateral with pain, itching, crawling sensation and tenderness. Key informants indicated that the disease had been in the village for a long time. This was confirmed by the existence of local names meaning “elephant legs” and “swollen legs” which appropriately describes the visible manifestation of Lymphatic Filariasis. The cases and key informants did not know the cause of the disease and attributed it to poison, witchcraft , bad food, bad water and violation of taboo. Most felt that traditional medicine including scarification for the purpose of “letting” blood and fluid was the best remedy. All 23 health workers interviewed had good knowledge about the proper remedy. Adequate number of health facilities and personnel exist at state, LGA and community levels. A total of 58 Doctors, 16 pharmacist, 1790 nurses and 1100 community Health Extension Workers (CHEWs) are employed by the State Government. These exclude health personnel working in private health facilities in the state. Two tertiary, 84 secondary and 485 primary health facilities exist in the state, twelve of which are equipped with surgery facilities. Twelve of the 19 villages visited have primary health care Canters/Pos. lymphatic Filariasis is not listed separate from other filariasis as a notifiable disease. There are therefore no records of the disease and plan for its control at any level. Having confirming the presence f lymphatic filariasis in Cross River State, it is necessary to conduct a survey to determine prevalence of the disease in all communities in he State and subsequently commence intervention (chemotherapy and morbidity control). Information gathered in this study and future Filariasis control programme in Nigeria. The Nigerian Journal of Parasitology Vol 24 2003: 9-1

The use of spatial analysis in mapping the distribution of bancroftian filariasis in four West African countries.

The geographical distribution of human infection with Wuchereria bancrofti was investigated in four West African countries (Benin, Burkina Faso, Ghana and Togo), using a commercial immunochromatographic test for filarial antigen. Efforts were made to cover each health-system implementation unit and to ensure no sampling point was >50 km from another, but otherwise the 401 study communities were selected at random. The aim was to enable spatial analysis of the data, to provide a prediction of the overall spatial relationships of the infection. The results, which were subjected to an independent random validation in Burkina Faso and Ghana, revealed that prevalence in the adult population of some communities exceeded 70% and that, over large areas of Burkina Faso, community prevalences were between 30% and 50%. Most of Togo, southern Benin and much of southern Ghana appeared completely free of the infection. Although there were foci on the Ghanaian coast with prevalences of 10%-30%, such high prevalences did not extend into coastal Togo or costal Benin. The prevalence map produced should be useful in prioritizing areas for filariasis control, identifying potential overlap with ivermectin-distribution activities undertaken by onchocerciasis-control programmes, and enabling inter-country and sub-regional planning to be initiated. The results indicate that bancroftian filariasis is more widely distributed in arid areas of Burkina Faso than hitherto recognized and that the prevalences of infection have remained fairly stable for at least 30 years. The campaign to eliminate lymphatic filariasis as a public-health problem in Africa will require significantly more resources (human, financial, and logistic) than previously anticipated