Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150–200 μg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS), dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with the mean stage of lymphedema in the doxycycline-treated patients being significantly lower compared to placebo patients 12 mo after treatment. The reduction in the stages manifested as better skin texture, a reduction of deep folds, and fewer deep skin folds. In conclusion, a 6-wk regimen of antifilarial treatment with doxycycline against W. bancrofti showed a strong macrofilaricidal activity and reduction in plasma levels of VEGF-C/sVEGFR-3, the latter being associated with amelioration of supratesticular dilated lymphatic vessels and with an improvement of pathology in lymphatic filariasis patients.

Land use changes have been suggested as one of the causes for malaria epidemics in the African highlands. This study investigated the effects of deforestation-induced changes in indoor temperature on the survivorship and reproductive fitness of Anopheles gambiae in an epidemic prone area in the western Kenya highlands. We found that the mean indoor temperatures of houses located in the deforested area were 1.2 degrees C higher than in houses located in the forested area during the dry season and 0.7 degrees C higher during the rainy season. The mosquito mortality rate was highly age-dependent regardless of study site or season. Mosquitoes that were placed in houses in the deforested area showed a 64.8-79.5% higher fecundity than those in houses located in the forested area, but the median survival time was reduced by 5-7 days. Female mosquitoes in the deforested area showed a 38.5-40.6% increase in net reproductive rate and an 11.6-42.9% increase in intrinsic growth rate than those in the forested area. Significant increases in net reproductive rate and intrinsic growth rate for mosquitoes in the deforested area suggest that deforestation enhances mosquito reproductive fitness, increasing mosquito population growth potential in the western Kenya highlands. The vectorial capacity of An. gambiae under study was estimated at least 106% and 29% higher in the deforested area than in the forested area in dry and rainy seasons, respectively.

We investigated the effects of deforestation on microclimates and sporogonic development of Plasmodium falciparum parasites in Anopheles gambiae mosquitoes in an area of the western Kenyan highland prone to malaria epidemics. An. gambiae mosquitoes were fed with P. falciparum-infected blood through membrane feeders. Fed mosquitoes were placed in houses in forested and deforested areas in a highland area (1,500 m above sea level) and monitored for parasite development. Deforested sites had higher temperatures and relative humidities, and the overall infection rate of mosquitoes was increased compared with that in forested sites. Sporozoites appeared on average 1.1 days earlier in deforested areas. Vectorial capacity was estimated to be 77.7% higher in the deforested site than in the forested site. We showed that deforestation changes microclimates, leading to more rapid sporogonic development of P. falciparum and to a marked increase of malaria risk in the western Kenyan highland.

In high-elevation areas in western Kenya, the abundance of Anopheles arabiensis is either very low or absent. The western Kenya highlands (an area with an elevation > 1,500m above sea level) have also been experiencing extensive deforestation, and deforestation has been suggested as one of the important factors that facilitate malaria transmission in the highlands. This study investigated whether climate conditions in the western Kenya highlands (Kakamega, elevation 1,500 m above sea level) were permissive to the development and survival of An. arabiensis and whether deforestation promoted An. arabiensis survivorship of immature and adult stages, using life-table analysis. We found that in larval habitats located in forested areas, only 4-9% of first-instar larvae developed into adults and the development length exceeded 20 days. Mean water temperature of aquatic habitats in the deforested area was 4.8-6.1 degrees C higher than that in the forested area, larval-to-adult survivorship was increased to 65-82%, and larval-to-adult development time was shortened by 8-9 days. The average indoor temperature in houses in the deforested area was 1.7-1.8 degrees C higher than in the forested area, and the relative humidity was 22-25% lower. The median survival time of adult mosquitoes in the deforested area was 49-55% higher than those in the forested area. The net reproductive rate of female mosquitoes in the deforested area was 1.7- to 2.6-fold higher than that in the forested area. Compared with previously published data on An. gambiae, the net reproductive rate of An. arabiensis was only 0.8-1.3% of Anopheles gambiae in the forested area and 2.3-2.6% in the deforested area. Therefore, the current ambient climate condition is less permissive to An. arabiensis than to An. gambiae in western Kenya highlands. However, environmental changes such as deforestation and global warming may facilitate the establishment of An. arabiensis populations in the highlands.