Filariasis in Africa--treatment challenges and prospects.

Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsible for a major disease burden in the African continent. Disease symptoms are induced by the immune reactions of the host, with lymphoedema and hydrocoele in LF, and dermatitis and ocular inflammation in onchocerciasis. Wuchereria bancrofti and Onchocerca volvulus, the species causing LF and onchocerciasis in Africa, live in mutual symbiosis with Wolbachia endobacteria, which cause a major part of the inflammation leading to symptoms and are antibiotic targets for treatment. The standard microfilaricidal drugs ivermectin and albendazole are used in mass drug administration programmes, with the aim of interrupting transmission, with a consequent reduction in the burden of infection and, in some situations, leading to regional elimination of LF and onchocerciasis. Co-endemicity of Loa loa with W. bancrofti or O. volvulus is an impediment to mass drug administration with ivermectin and albendazole, owing to the risk of encephalopathy being encountered upon administration of ivermectin. Research into new treatment options is exploring several improved delivery strategies for the classic drugs or new antibiotic treatment regimens for anti-wolbachial chemotherapy.

Elephantiasis of non-filarial origin (podoconiosis) in the highlands of north-western Cameroon.

Lymphoedema, a condition of localized fluid retention, results from a compromised lymphatic system. Although one common cause in the tropics is infection with filarial worms, non-filarial lymphoedema, also known as podoconiosis, has been reported among barefoot farmers in volcanic highland zones of Africa, Central and South America and north-western India. There are conflicting reports on the causes of lymphoedema in the highland regions of Cameroon, where the condition is of great public-health importance. To characterise the focus of lymphoedema in the highlands of the North West province of Cameroon and investigate its real causes, a cross-sectional study was carried out on the adults (aged > or =15 years) living in the communities that fall within the Ndop and Tubah health districts. The subjects, who had to have lived in the study area for at least 10 years, were interviewed, examined clinically, and, when possible, checked for microfilaraemia. The cases of lymphoedema confirmed by ultrasonography and a random sample of the other subjects were also tested for filarial antigenaemia. The interviews, which explored knowledge, attitudes and perceptions (KAP) relating to lymphoedema, revealed that the condition was well known, with each study community having a local name for it. Of the 834 individuals examined clinically, 66 (8.1%) had lymphoedema of the lower limb, with all the clinical stages of this condition represented. None of the 792 individuals examined parasitologically, however, had microfilariae of W. bancrofti (or any other filarial parasite) in their peripheral blood, and only one (0.25%) of the 399 individuals tested for the circulating antigens of W. bancrofti gave a positive result. In addition, none of the 504 mosquitoes caught landing on human bait in the study area and dissected was found to harbour any stage of W. bancrofti. These findings indicate that the elephantiasis seen in the North West province of Cameroon is of non-filarial origin.

Detection of adult Brugia malayi filariae by ultrasonography in humans in India and Indonesia.

In bancroftian filariasis, ultrasonography (USG) is a suitable tool to monitor infection by the detection of adult filariae in addition to antigen detection tests (ICT, Og4C3). However, in brugian filariasis, ultrasound examinations in humans have so far failed to detect adult worms and no antigen test is available to verify infections in patients who are carriers of adult worms but amicrofilaraemic. In this study, we describe the feasibility of detection of adult Brugia malayi filariae by USG. Worm nests were detected in 4 of 32 patients in India and Indonesia, located in the breast, the thigh, the calf and an inguinal lymph node. The study shows that adult filariae of B. malayi in humans can be detected by USG, but the technique is limited by the fact that worm nests seem not to be stable over time in humans, as is the case in bancroftian filariasis.

Ultrasonography in filaria-infected rodents: detection of adult Litomosoides sigmodontis and Brugia malayi filariae.

OBJECTIVE: To evaluate the usefulness of ultrasonography (USG) in the detection of adult filariae in rodents. Wuchereria bancrofti are frequently detected using USG in humans, whereas adult Brugia malayi have not been so far. METHODS: A Meriones unguiculatus with Litomosoides sigmodontis infection was examined to visualize adult filariae of a similar length as W. bancrofti. Similarly, three Mastomys coucha, infected with B. malayi, were examined using USG to verify whether the adult worms, which are far smaller than W. bancrofti and L. sigmodontis, can be located using USG in the animals. RESULTS: Adult L. sigmodontis were detected using USG in the pleural cavity of M. unguiculatus, and in M. coucha adult B. malayi were visualized in the hearts, lungs, axillary lymph nodes and scrotum. Ultrasound findings were verified by dissection of the rodents. CONCLUSIONS: Although adult B. malayi are far smaller than L. sigmodontis and W. bancrofti, they can be detected using USG in rodents. USG may serve as an adjunctive tool to support parasitological examinations and can add information on filarial infections at any time point of an observation period, particularly in cryptic infections and without the need for invasive measures or killing of the rodent. Thus, USG can support the early detection of macrofilaricidal activities of new compounds and can be used to determine the location of adult worms in the animals. It is possible to give a rough estimate of the number of adult worms, but determination of the exact numbers of adult filariae in various locations is impossible with USG.

Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment.

Ivermectin is the drug used for mass chemotherapy of onchocerciasis within the WHO African Programme for Onchocerciasis Control. This approach aims to eliminate the disease as a public health problem but using one dose per year may not completely interrupt transmission since it does not suppress microfilaridermia thoroughly enough. Here we show that additional treatment with doxycycline, previously shown to sterilise adult female worms for a few months by depletion of symbiotic wolbachia endobacteria, significantly enhances ivermectin-induced suppression of microfilaridermia, rendering anti-wolbachia treatment a promising basis for blocking transmission by a drug-based approach.