Wuchereria bancrofti transmission pattern in southern Mali prior to and following the institution of mass drug administration.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of stopping transmission of lymphatic filariasis (LF) through yearly mass drug administration (MDA). Although preliminary surveys of the human population in Mali suggested that Wuchereria bancrofti infection was highly endemic in the Sikasso district, baseline entomological data were required to confirm high levels of transmission prior to the selection of villages in this region for a study of the impact of MDA on transmission of LF by anopheline vectors. METHODS: W. bancrofti transmission was assessed in 2001 (pre-MDA) and 2002 (post-MDA) in the Central District of Sikasso in southern Mali by dissection of Anopheles mosquitoes caught using the human landing catch (HLC) method. The relative frequencies and molecular forms of An. gambiae complex were determined. RESULTS: The majority (86%) of the anopheline vectors captured were identified as An. gambiae complex, and these accounted for >90% of the entomological inoculation rate (EIR) during both years of the study. There was a dramatic decrease in the number of An. gambiae complex mosquitoes captured and in the An. gambiae complex infectivity rates following MDA, accounting for the observed decrease in EIR in 2002 (from 12.55 to 3.79 infective bites per person during the transmission season). An. funestus complex mosquitoes were responsible for a low level of transmission, which was similar during both years of the study (1.2 infective bites per person during the transmission season in 2001 and 1.03 in 2002). CONCLUSIONS: Based on the entomological data from this study, the district of Sikasso was confirmed as an area of high W. bancrofti transmission. This led to the selection of this area for a multi-national study on the effects of MDA on LF transmission by anopheline vectors. Comparison of vector transmission parameters prior to and immediately following the first round of MDA demonstrated a significant decrease in overall transmission. Importantly, the dramatic variability in EIR over the transmission season suggests that the efficacy of MDA can be maximized by delivering drug at the beginning of the rainy season (just prior to the peak of transmission).

Acceptability and efficacy of intra-rectal quinine alkaloids as a pre-transfer treatment of non-per os malaria in peripheral health care facilities in Mopti, Mali.

BACKGROUND: The acceptability and efficacy of a new kit with a new formulation of quinine alkaloids designed for the intra-rectal administration in the treatment of non-per os malaria was assessed in the peripheral health care system of Mopti, Mali. METHODS: A single-arm trial was conducted from August 2003 to January 2004. An initial dose of diluted quinine alkaloids (20 mg/kg Quinimax) was administered by the intra-rectal route to children with presumptive non per-os malaria at six peripheral heath care centres. The children were then referred to two referral hospitals where standard inpatient care including intravenous route were routinely provided. A malaria thick smear was done at inclusion and a second malaria thick smear after arrival at the referral facility, where a more complete clinical examination and laboratory testing was done to confirm diagnosis. Confirmed cases of severe malaria or others diseases were treated according to national treatment guidelines. Cases of non per-os malaria received a second dose of intra rectal quinine alkaloids. Primary outcome was acceptability of the intra rectal route by children and their parents as well as the ease to handle the kit by health care workers. RESULTS: The study included 134 children with a median age of 33 months and 53.7% were male. Most of the children (67%) and 92% of parents or guardians readily accepted the intra-rectal route; 84% of health care workers found the kit easy to use. At the peripheral health care centres, 32% of children had a coma score < or = 3 and this was reduced to 10% at the referral hospital, following one dose of intra-rectal quinine alkaloids (IRQA). The mean time to availability of oral route treatment was 1.8 +/- 1.1 days. Overall, 73% of cases were confirmed severe malaria and for those the case fatality rate was 7.2%. CONCLUSION: IRQA was well accepted by children, their parents/guardians and by the health workers at peripheral health facilities in Mopti, Mali. There was also a quick recovery from deep coma and a reduced case fatality rate in severe malaria.

Filaria-induced monocyte dysfunction and its reversal following treatment.

Monocyte dysfunction in filarial infection has been proposed as one mechanism underlying the diminished antigen-specific T-cell response seen in patent lymphatic filariasis. Cytokine/chemokine production and gene expression in monocytes from filaria-infected patients and uninfected healthy donors were assessed unstimulated and in response to stimulation with Staphylococcus aureus Cowan I bacteria plus gamma interferon both before and 8 months following treatment. Monocytes from filaria-infected individuals were studded with intracellular microfilarial antigens. Furthermore, monocytes from these individuals were less capable of producing interleukin-8 (IL-8), Exodus II, MIP-1alpha, MIP-1beta, and IL-1alpha and preferentially expressed genes involved in apoptosis and adhesion compared with monocytes from uninfected donors. Eight months following treatment with a single dose of ivermectin-albendazole, some of these defects were reversed, with monocyte production of IL-8, IL-1alpha, MIP-1alpha, and IL-10 being comparable to that seen in the uninfected controls. In addition, a marked increase in mRNA expression of genes associated with protein metabolism, particularly heat shock proteins, was seen compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria-infected patients are altered but that this dysfunction is partially reversible following antifilarial treatment.

Clinical characteristics of post-treatment reactions to ivermectin/albendazole for Wuchereria bancrofti in a region co-endemic for Mansonella perstans.

Post-treatment reactions to single-dose ivermectin (200 microg/kg) and albendazole (400 mg) were studied in a filarial endemic region of Mali. The prevalence of Wuchereria bancrofti in this region was 48.3% (69 of 143), and coinfection with Mansonella perstans was common (30 of 40, 75%). Microfilarial levels of M. perstans correlated positively with age (P = 0.006) and with W. bancrofti microfilarial levels (P = 0.006). Forty individuals (28 infected and 12 uninfected) were treated, with mild post-treatment reactions occurring in 35.7% (7 of 28) of the W. bancrofti-infected subjects. Reaction severity correlated with pretreatment W. bancrofti microfilarial levels (P = 0.001). There were no significant differences in the prevalence or severity of post-treatment reactions in those who were co-infected with M. perstans. It is concluded that co-infection with M. perstans does not significantly alter the post-treatment reaction profile to single-dose ivermectin/albendazole in W. bancrofti infection in this community, and that acute post-treatment reactions should not limit patient compliance in community-based programs to eliminate lymphatic filariasis.