Accumulating evidence indicate that malaria burden in Africa is declining [
1,
2]. Several countries that previously had high malaria burden have seen over 50% reduction in malaria burden within the past ten years, including Eritrea, Rwanda, Zanzibar [
3], Pemba [
4], Tanzania mainland [
5], Kenya [
6], Gambia [
7], Zambia [
8], and Swaziland [
9]. Three countries, including Morocco, in Africa were certified as malaria-free in 2011 [
10]. Moreover, a longitudinal decline in the density of malaria vectors was observed during an 11-year study period, in spite of the absence of organized vector control [
11]. Guerra and others have estimated that there are about 1 billion people currently living under unstable or extremely low malaria risk globally. These areas are amenable for malaria elimination [
12]. As programmes successfully reduce transmission to near elimination levels, the measurement of malaria-associated morbidity and mortality as a means of tracking reducing burden will become difficult and insensitive. Novel approaches to surveillance are, therefore, necessary to ensure that once elimination has been achieved, it is not threatened by a rapid reintroduction [
13]. People living in areas of unstable or extremely low malaria risk may lose the ability of maintaining naturally acquired immunity [
14]. This presents a special challenge, i.e., the risk of possible catastrophic rebound such as the one occurred in the highlands of Madagascar in the 1980s where an epidemic killed more than 40,000 people [
15]. Thus, the quest for sensitive and robust surveillance tools has become imperative. Such surveillance tools are needed as an intervention to reduce transmission, to measure transmission interruption and maintenance of zero transmission; the tools should also be useful in mapping the risk of focal residues of transmission to enable targeted control. Unfortunately, the existing metrics of malaria transmission have serious limitations when transmission is approaching zero. The entomological inoculation rate (EIR), the gold standard of malaria transmission intensity (MTI) [
16], becomes difficult, expensive, and sometimes virtually impossible to measure when transmission is very low [
17,
18].
Serological tools based on antibody responses to parasite and vector antigens are potentially valuable for robust transmission measurement [
19‐
21]. Particularly, Merozoite Surface Protein 1 (MSP 1
19) seroconversion rates have been shown to correlate with malaria transmission intensity (EIR) [
22,
23]. MSP-1
19 seroprevalence and antibody level is robust and sensitive in distinguishing malaria exposures at different altitudes, age groups, and proximity to mosquito breeding habitats in populations separated by only 5 km apart [
24]. The parallel measure of the antibody response to
Anopheles salivary antigen would be especially convenient, because it will allow for assessment of
Anopheles exposure in children, which is ethically unfeasible by human landing catches. Moreover, serological markers of exposure to
Anopheles bites would represent a complementary tool in low malaria transmission areas for the monitoring of control interventions based on anti-vector measures [
17,
25]. The IgG response to whole saliva extracts of
Anopheles gambiae has been observed as a marker of exposure to
An. gambiae bite, and high anti-saliva IgG levels is a predictive indicator of malaria morbidity [
26,
27]. The
An. gambiae salivary gland gSG6 protein and derived P1 peptide are specific to
An. gambiae and elicit specific antibody response in the human host [
28,
29]. It is antigenic in travelers transiently exposed to
Anopheles bites in malaria endemic areas of Africa [
30]. The gSG6 protein has been recently reported to have the potential to represent a general epidemiological marker of exposure since it shares 99% and 80% identity with
Anopheles arabiensis and
Anopheles funestus, respectively, which constitutes the main Afro-tropical malaria vectorial system [
29,
31]. The synthetic peptide (gSG6-P1) derived from
An. gambiae salivary recombinant protein gSG6-P1 is reportedly highly specific to
Anopheles species and immunogenic [
21,
29] and its synthetic nature guarantees high reproducibility for the assay [
21]. It is also a biomarker in low exposure area [
28] and specific to
An. funestus bites [
32]. There is as yet, lack of information on the value of gSG6-P1 as a surveillance tool in assessing the risk of exposure to malaria parasites at the population and individual level. This study thus sought to evaluate anti-gSG6- P1 IgG responses in
Pf MSP-1
19 responders and non-responders across different altitudes under high, moderate and low transmission settings across different age groups and seasons. The robustness of the gSG6-P1 as a biomarker of parasite exposure and the possibility of utilizing the biomarker as a surveillance tool in an era of decreasing malaria transmission where traditional tools become insensitive and unfeasible to track malaria transmission is reported.