Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria?

OBJECTIVES: To examine whether the humoural response to malaria vaccine candidate antigens, Plasmodium falciparum [circumsporozoite repetitive sequence (NANP)(5) GLURP fragments (R0 and R2) and MSP3] varies with the level of malaria transmission and to determine whether the antibodies (IgG) present at the beginning of the malaria transmission season protect against clinical malaria. METHODS: Cross-sectional surveys were conducted to measure antibody response before, at the peak and at the end of the transmission season in children aged 6 months to 10 years in two villages with different levels of malaria transmission. A cohort study was performed to estimate the incidence of clinical malaria. RESULTS: Antibodies to these antigens showed different seasonal patterns. IgG concentrations to any of the four antigens were higher in the village with high entomological inoculation rate. Multivariate analysis of combined data from the two villages indicated that children who were classified as responders to the selected antigens were at lower risk of clinical malaria than children classified as non-responders [(NANP)(5) (incidence rate ratio (IRR) = 0.65, 95% CI: 0.46-0.92; P = 0.016), R0 (IRR = 0.69, 95% CI: 0.48-0.97; P = 0.032), R2 (IRR = 0.73, 95% CI: 0.50-1.06; P = 0.09), MSP3 (IRR = 0.52, 95% CI: 0.32-0.85; P = 0.009)]. Fitting a model with all four antibody responses showed that MSP3 looked the best malaria vaccine candidate (IRR = 0.63; 95% CI: 0.38-1.05; P = 0.08). CONCLUSION: Antibody levels to the four antigens are affected by the intensity of malaria transmission and associated with protection against clinical malaria. It is worthwhile investing in the development of these antigens as potential malaria vaccine candidates.

Insecticide-treated materials, mosquito adaptation and mass effect: entomological observations after five years of vector control in Burkina Faso.

Insecticide-treated bednets and curtains have been shown to be successful in reducing malaria transmission and child mortality in Africa over periods of up to 2 years. A major concern relating to this approach is that, in time, it will be compromised by the selection of mosquito genotypes that are resistant at the biochemical or behavioural level. We report entomological data from a large area in Burkina Faso where insecticide-treated curtains have been in use for up to 5 years. Longitudinal indoor and outdoor CDC light-trap catches were performed in 4 sentinel villages. In addition cross-sectional surveys using indoor spray catches and outdoor CDC light-trap catches were performed each September in a larger number of villages, including 8 located outside the intervention area. We found no evidence of the selection of mosquito phenotypes that might compromise the intervention. Indoor and outdoor vector densities remained very low after 5 years of intervention, both compared with pre-intervention levels and with concurrent levels outside the intervention area. We found no evidence of a switch to outdoor rather than indoor biting. The proportion of blood meals taken on humans may have decreased but our data are inconclusive on this point. We observed higher vector densities and sporozoite rates at the periphery of the intervention zone than at the centre, which may reflect re-invasion of peripheral villages by mosquitoes from outside the intervention area. In 'real life' programmes, with perhaps patchy, less than optimal coverage, the protection against malaria transmission provided to individuals using insecticide-treated materials may be less than that achieved in the randomized controlled trials which demonstrated an impact of insecticide-treated materials on child mortality.

Chromosomal and bionomic heterogeneities suggest incipient speciation in Anopheles funestus from Burkina Faso.

Sampling of day-resting Anopheles funestus was carried out in September-November 1991, October-December 1992, and November 1994 at two sites near Ouagadougou, Burkina Faso: the small village of Noungou where humans outnumber cattle, and the nearby Fulani settlement of Loumbila where cattle outnumber humans. Collections made inside human dwellings were supplemented in 1992 by outdoor-resting samples from artificial pit-shelters. Indoor-resting An. funestus were also collected in November 1992 and November 1994 in four villages of the Banfora area (southern Burkina Faso) and in a sudanese-sahelian village in northern Burkina Faso (Tougouri). Half-gravid female sub-samples were preserved in carnoy's fixative and processed for polytene chromosome analysis. The material from the two villages near Ouagadougou was analysed by ELISA to know (i) the human/animal origin of the blood meal; (ii) the infectivity for Plasmodium falciparum malaria; and (iii) the possible correlation of these parameters with chromosomal variants. A total of 1416 An. funestus could be scored for the whole polytenic complement, while the origin of the blood meal and circumsporozoite protein (CSP) positivity were asserted from 1076 and 1154 specimens, respectively. With a few exceptions, four polymorphic paracentric inversions (3a, 3b, 2a and 5a in decreasing order of frequency) were observed in all populations. Inversion 2s, whose breaking points include those of inversion 2a, was found only as the heterokaryotype 2s/+ floating at an overall frequency of 3.7% in two villages of the Banfora area and in the two sites near Ouagadougou. Two heterokaryotypes 2a/t out of 186 scored specimens were observed in different years from one village of the Banfora area. Wide variations in inversion frequencies were observed among the samples without consistent geographical or temporal clines. Highly significant departures from Hardy-Weinberg equilibrium were recorded for inversions 3a and 3b in most samples, with the alternative homokaryotypes (standard and inverted) significantly more frequent than expected. Conversely, inversion 5a was in Hardy-Weinberg equilibrium in most samples, whereas the 2a-s inversion system was intermediate between these extremes. However, a deficit of heterokaryotypes was apparent practically in all samples. Significantly higher frequencies of the standard homokaryotypes were recorded (i) in the exophilic samples collected in Loumbila for arrangement 3a; (ii) in the animal-fed sub-sample collected outdoors in Noungou vs. the parallel human-fed sub-sample for arrangements 2a-s, 3a, and 3b, or vs. the samples obtained from indoor catches in both Loumbila and Noungou in the case of inversion 3a; (iii) in the December CSP-negative sub-sample from Loumbila vs. the parallel CSP-positive sub-sample for arrangement 2a. A plausible working hypothesis is that An. funestus in Burkina Faso includes two taxonomic units, one of which is mainly monomorphic standard with most inverted arrangements floating at very low frequencies, and probably uniquely characterised by arrangement 2s, while the other taxon is nearly fixed for arrangement 3ab and polymorphic for all the other inversions at intermediate to high frequencies. The latter would be characterised by a higher vectorial capacity and would probably correspond to An. funestus s.s. from East Africa. About the former hypothetical taxon, its endophily and anthropophily appear less marked and its relationship with other members of the An. funestus subgroup will require specific investigations.

Child mortality in a West African population protected with insecticide-treated curtains for a period of up to 6 years.

OBJECTIVES: To determine the impact of insecticide-treated curtains (ITC) on all-cause child mortality (6-59 months) over a period of six years. To determine whether initial reductions in child mortality following the implementation of ITC are sustained over the longer term or whether "delayed" mortality occurs. METHODS: A rural population of ca 100 000 living in an area with high, seasonal Plasmodium falciparum transmission was studied in Burkina Faso. Annual censuses were conducted from 1993 to 2000 to measure child mortality. ITC to cover doors, windows, and eaves were provided to half the population in 1994 with the remainder receiving ITC in 1996. Curtains were re-treated or, if necessary, replaced annually. FINDINGS: Over six years of implementation of ITC, no evidence of the shift in child mortality from younger to older children was observed. Estimates of the reduction in child mortality associated with ITC ranged from 19% to 24%. CONCLUSIONS: In our population there was no evidence to suggest that initial reduction in child mortality associated with the introduction of insecticide-treated materials was subsequently compromised by a shift in child mortality to older-aged children. Estimates of the impact of ITC on child mortality in this population range from 19% to 24%.

Comparative evaluation of carbosulfan- and permethrin-impregnated curtains for preventing house-entry by the malaria vector Anopheles gambiae in Burkina Faso.

Pyrethroid-impregnated bednets and curtains are widely employed to reduce the risk of malaria transmission, but pyrethroid-resistance is becoming more prevalent among malaria vector Anopheles mosquitoes (Diptera: Culicidae). As an alternative treatment for curtains, we assessed carbosulfan (a carbamate insecticide) in comparison with permethrin as the standard pyrethroid, against endophilic female mosquitoes of the Anopheles gambiae Giles complex in a village near Ouagadougou, Burkina Faso. The main criterion evaluated was the impact of curtains (hung inside windows, eaves and doorways) on the number of An. gambiae s.l. females active indoors at night. Light-traps were operated overnight (21.00-06.00 hours beside occupied untreated bednets) to sample mosquitoes in houses fitted with net curtains treated with carbosulfan 0.2 g ai/m2 or permethrin 1 g ai/m2 or untreated, compared with houses without curtains. The treated and untreated curtains significantly reduced the numbers of mosquitoes collected indoors, compared with houses without curtains. Carbosulfan-treated curtains had a highly significantly greater effect than permethrin-treated or untreated curtains, the scale of the difference being estimated as three-fold. However, there was no significant difference between the impact of untreated and permethrin-treated curtains on densities of An. gambiae s.l. trapped indoors. Samples of the An. gambiae complex comprised An. arabiensis Patton and both the S- and M-forms of An. gambiae Giles s.s. Susceptibility tests revealed some resistance to DDT and low frequencies of permethrin-resistance, insufficient to explain the poor performance of permethrin on curtains. Among survivors from the diagnostic dosage of permethrin were some specimens of all three members of the An. gambiae complex, but the kdr resistance mechanism was detected only in the S-form of An. gambiae s.s. Questions arising for further investigation include clarification of resistance mechanisms in, and foraging behaviour of, each member of the An. gambiae complex in this situation and the need to decide whether carbosulfan-treated curtains are acceptably safe for use to reduce risks of malaria transmission.