Pattern of antibody responses to Plasmodium falciparum antigens in individuals differentially exposed to Anopheles bites.

BACKGROUND: In malaria-endemic areas, human populations are frequently exposed to immunomodulatory salivary components injected during mosquito blood feeding. The consequences on pathogen-specific immune responses are not well known. This study evaluated and compared the humoral responses specific to merozoite stage vaccine candidates of Plasmodium falciparum, in children differentially exposed to Anopheles bites in a natural setting. METHODS: The cross-sectional study was carried out in Bouaké (Côte d'Ivoire) where entomological data and blood samples from children (0-14 years) were collected in two sites with similar malaria prevalence. Antibody (IgG, IgG1, IgG3) responses to PfAMA1 and PfMSP1 were evaluated by ELISA. Univariate and multivariate analysis were performed to assess the relationship between the immune responses to P. falciparum antigens and exposure to Anopheles bites in the total cohort and in each site, separately. The individual level of exposure to Anopheles bites was evaluated by quantifying specific IgG response to the Anopheles gSG6-P1 salivary peptide, which represents a proxy of Anopheles exposure. RESULTS: The anti-Plasmodium humoral responses were different according to the level of exposure of children, with those highly exposed to Anopheles presenting significantly lower antibody responses to PfMSP1 in total population (IgG and IgG3) and in Petessou village (IgG, IgG1, IgG3). No significant difference was seen for PfAMA1 antigen between children differently exposed to Anopheles. In Dar-es-Salam, a neighbourhood where a high Culex density was reported, children presented very low antibody levels specific to both antigens, and no difference according to the exposure to Anopheles bites was found. CONCLUSION: These findings may suggest that immunomodulatory components of Anopheles saliva, in addition to other factors, may participate to the modulation of the humoral response specific to Plasmodium merozoite stage antigens. This epidemiological observation may form a starting point for additional work to decipher the role of mosquito saliva on the modulation of the anti-Plasmodium acquired immunity and clinical protection in combining both field and ex vivo immunological studies.

Impact of sunlight exposure on the residual efficacy of biolarvicides Bacillus thuringiensis israelensis and Bacillus sphaericus against the main malaria vector, Anopheles gambiae.

BACKGROUND: Biotic and abiotic factors have been reported to affect the larvicidal efficacy of Bacillus thuringiensis israelensis (Bti) and Bacillus sphaericus (Bs), although the extent to which they are affected has been poorly documented. This paper studies the effect of sunlight exposure on the efficacy of a new larvicide formulation based on both Bti and Bs, herein after referred to as BTBSWAX, applied against two different larval stages. METHODS: The emergence of inhibition exhibited by BTBSWAX at three different dosages (1 g/m2, 1.5 g/m2, and 2 g/m2) was monitored under semi-field conditions using a total of 32 containers comprising 16 that were covered and 16 that were uncovered. Two experiments were conducted using first- and second-instar larvae of Anopheles gambiae, respectively. RESULTS: BTBSWAX at 2 g/m2 in covered containers exhibited high emergence inhibition (> 80%) when larvae were exposed from 1st instar on day-6 post-treatment, whereas the emergence inhibition was only 28% in uncovered containers. For larvae exposed from 1st instar on day-12 post-treatment, the emergence inhibition was moderate (70%) in covered containers but was low (< 20%) in uncovered containers. For larvae exposed from 2nd instar on day-10 post-treatment, the emergence inhibition was moderate (31%) in covered containers but was very low (< 10%) in uncovered containers. Moreover, the residual efficacy of BTBSWAX was markedly affected by environmental stresses, including sunlight exposure (Hazard ratio (HR) = 0.12, p < 0.001 and HR = 0.63, p = 0.033 for BTBSWAX at 2 g/m2 against 1st and 2nd instar larvae, respectively). CONCLUSION: These findings emphasize the impact of environmental variables (e.g., sunlight exposure) on the residual efficacy of Bti and Bs biolarvicides in the field. They hence highlight the need to take these factors into account for larvicide formulation development processes. Moreover, studies of the ecology of Anopheles larvae in targeted areas are also crucial for the integration of larval control strategies into malaria transmission plans devised by national malaria control programmes of endemic countries.

Operational Evaluation of the Effectiveness of Long-lasting Insecticidal Nets on Human-Vector Contact in an African Urban Malaria Context.

BACKGROUND: Malaria is still a major public health concern in Côte d'Ivoire despite mass distribution of long-lasting insecticidal nets (LLINs) as a key preventive strategy. This study intended to evaluate the operational effectiveness of LLINs on the level of human-vector contact using 1 antibody-based biomarker of exposure to Anopheles in urban areas. METHODS: This cross-sectional study collected socio-demographic data and use of LLINs from 9 neighborhoods in the city of Bouaké (Côte d'Ivoire). Dry blood spots performed in children aged >6 months and adults were used to evaluate immunoglobulin G (IgG) responses to the Anopheles gSG6-P1 salivary peptide. RESULTS: IgG response levels to the salivary peptide were significantly lower in individuals who declared having "always" (n = 270) slept under an LLIN compared with those who had "often" (n = 2087) and "never" (n = 88) slept under an LLIN (P < .0001). IgG response levels to gSG6-P1 between those who declared having "always" and "not always" slept under an LLIN varied according to neighborhood, socio-professional category, and age group. CONCLUSIONS: The human IgG level to this gSG6-P1 salivary peptide could be a useful tool to evaluate the actual effectiveness of LLINs and help design behavioral change interventions that are crucial for sustaining universal coverage.

Anopheles bionomics, insecticide resistance and malaria transmission in southwest Burkina Faso: A pre-intervention study.

BACKGROUND: Twenty-seven villages were selected in southwest Burkina Faso to implement new vector control strategies in addition to long lasting insecticidal nets (LLINs) through a Randomized Controlled Trial (RCT). We conducted entomological surveys in the villages during the dry cold season (January 2017), dry hot season (March 2017) and rainy season (June 2017) to describe malaria vectors bionomics, insecticide resistance and transmission prior to this trial. METHODS: We carried out hourly catches (from 17:00 to 09:00) inside and outside 4 houses in each village using the Human Landing Catch technique. Mosquitoes were identified using morphological taxonomic keys. Specimens belonging to the Anopheles gambiae complex and Anopheles funestus group were identified using molecular techniques as well as detection of Plasmodium falciparum infection and insecticide resistance target-site mutations. RESULTS: Eight Anopheles species were detected in the area. Anopheles funestus s.s was the main vector during the dry cold season. It was replaced by Anopheles coluzzii during the dry hot season whereas An. coluzzii and An. gambiae s.s. were the dominant species during the rainy season. Species composition of the Anopheles population varied significantly among seasons. All insecticide resistance mechanisms (kdr-w, kdr-e and ace-1 target site mutations) investigated were found in each members of the An. gambiae complex but at different frequencies. We observed early and late biting phenotypes in the main malaria vector species. Entomological inoculation rates were 2.61, 2.67 and 11.25 infected bites per human per month during dry cold season, dry hot season and rainy season, respectively. CONCLUSION: The entomological indicators of malaria transmission were high despite the universal coverage with LLINs. We detected early and late biting phenotypes in the main malaria vector species as well as physiological insecticide resistance mechanisms. These data will be used to evaluate the impact of complementary tools to LLINs in an upcoming RCT.

Anopheles bionomics, insecticide resistance mechanisms, and malaria transmission in the Korhogo area, northern Côte d'Ivoire: a pre-intervention study.

A better understanding of malaria transmission at a local scale is essential for developing and implementing effective control strategies. In the framework of a randomized controlled trial (RCT), we aimed to provide an updated description of malaria transmission in the Korhogo area, northern Côte d'Ivoire, and to obtain baseline data for the trial. We performed human landing collections (HLCs) in 26 villages in the Korhogo area during the rainy season (September-October 2016, April-May 2017) and the dry season (November-December 2016, February-March 2017). We used PCR techniques to ascertain the species of the Anopheles gambiae complex, Plasmodium falciparum sporozoite infection, and insecticide resistance mechanisms in a subset of Anopheles vectors. Anopheles gambiae s.l. was the predominant malaria vector in the Korhogo area. Overall, more vectors were collected outdoors than indoors (p < 0.001). Of the 774 An. gambiae s.l. tested in the laboratory, 89.65% were An. gambiae s.s. and 10.35% were An. coluzzii. The frequencies of the kdr allele were very high in An. gambiae s.s. but the ace-1 allele was found at moderate frequencies. An unprotected individual living in the Korhogo area received an average of 9.04, 0.63, 0.06 and 0.12 infected bites per night in September-October, November-December, February-March, and April-May, respectively. These results demonstrate that the intensity of malaria transmission is extremely high in the Korhogo area, especially during the rainy season. Malaria control in highly endemic areas such as Korhogo needs to be strengthened with complementary tools in order to reduce the burden of the disease.