Preliminary validation of the use of IgG antibody response to Anopheles gSG6-p1 salivary peptide to assess human exposure to malaria vector bites in two endemic areas of Cameroon in Central Africa

Abstract

The specific immune response to the Anopheles salivary peptide could be a pertinent and complementary tool to assess the risk of malaria transmission and the effectiveness of vector control strategies. This study aimed to obtain first reliable data on the current state of the Anopheles gSG6-P1 biomarker for assess the level of exposure to Anopheles bites in high malaria endemic areas in Cameroon. Blood smears were collected from people living in the neighborhoods of Youpwe (suburban area, continental) and Manoka (rural area, Island), both areas in the coastal region of Cameroon. Malaria infection was determined using thick blood smear microscopy, whereas the level of specific IgG response to gSG-P1 peptide was assessed by enzyme-linked immunosorbent assay from the dried blood spots. Of 266 (153 from Youpwe, 113 from Manoka) malaria endemic residents (mean age: 22.8±19.8 years, age range: 6 months–94 years, male/female sex ratio: 1/1.2, with Manoka mean age: 23.71±20.53, male/female sex ratio:1/1.13 and Youpwe mean age: 22.12±19.22, male/female sex ratio 1/0.67) randomly included in the study, Plasmodium infection prevalence was significantly higher in Manoka than in Youpwe (64.6% vs 12,4%, p = 0.0001). The anti-gSG6-P1 IgG response showed a high inter-individual heterogeneity and was significantly higher among individuals from Manoka than those from Youpwe (p = 0.023). Malaria infected individuals presented a higher anti-gSG6-P1 IgG antibody response than non-infected (p = 0.0004). No significant difference in the level of specific IgG response to gSG-P1 was observed according to long lasting insecticidal nets use. Taken together, the data revealed that human IgG antibody response to Anopheles gSG-P1 salivary peptide could be also used to assess human exposure to malaria vectors in Central African region. This finding strengthens the relevance of this candidate biomarker to be used for measuring human exposure to malaria vectors worldwide.

Use of anti-gSG6-P1 IgG as a serological biomarker to assess temporal exposure to Anopheles’ mosquito bites in Lower Moshi

“…Despite the observed seasonal variation, the sero-prevalence was unexpectedly lower during the second dry season when more Anopheles mosquitoes were collected when compared to the first dry season. This suggests that gSG6-P1 seroprevalence is not reflected by mosquito density as supported by several other studies [ 17 , 22 , 38 , 39 ].…”

“…This is probably due to behaviour as younger children are expected to sleep early and more hours and here the effect of bed net use is more apparent compared to the other age groups who probably get exposed before sleeping hours. A few studies conducted in different settings including Senegal, Cameroon and in the Solomon Islands reported findings similar to this study, where they have documented no statistical significant association between exposure to Anopheles mosquitoes and age [ 22 , 38 , 39 ], gender or use of anti-mosquito strategies such as LLINs [ 22 ]. Contrary to these studies, other studies have reported that levels of anti-gSG6-P1 IgG responses varied significantly by village and age; e.g.…”

“…High gSG6-P1 IgG titres were detected from individuals and households from which low numbers of Anopheles mosquitoes were collected and vice versa. Several other studies have observed lack of correlations between gSG6-P1 antibodies and entomological indices including human biting rate [ 17 , 22 , 38 ] and human landing catches [ 39 ]. Contrary to these findings, a study conducted in Korogwe Northern Tanzania found significant correlations between numbers of Anopheles mosquitoes collected and household levels of exposure to Anopheles bites [ 15 ].…”

“…Levels of gSG6-P1 antibodies against the antigen have shown individual and population differences correlating well with levels of exposure to Anopheles [ 15 , 17 , 21 ]. However, previous evaluations compared spatial exposure to Anopheles mosquitoes across altitude transects [ 15 , 16 ] and except for a study performed among Senegalese children, showing promise in measuring anti-gSG6-P1 as a proxy for Anopheles exposure in a low transmission setting [ 18 ], previous studies mainly focused on areas with moderate to high malaria transmission [ 15 , 16 , 22 – 24 ]. As assessment of gSG6-P1 antibody levels may also be used to determine efficacy of different interventions such as measures used for vector control [ 25 , 26 ], a prerequisite is that the estimation of gSG6-P1 antibodies is well measurable in areas with very low transmission.…”

Immunomodulation by Mosquito Salivary Protein AgSAP Contributes to Early Host Infection by Plasmodium

“…After continuous exposure to mosquito bites, humans develop a humoral response against mosquito salivary proteins, and this can be useful for surveillance and as a biomarker for exposure to bites and malaria disease risk ( 42 ). Individuals living in an area where malaria is endemic develop a humoral immune response to some salivary antigens such as AgSAP, SAMSP1, SG6, and 5-nucleotidase but not to other proteins like AgTRIO ( 12 , 38 , 43 ). Future studies are needed to understand if combining several salivary proteins will be a better approach than using individual proteins for identifying exposure to mosquitoes and malaria disease risk in areas of endemicity.…”