Evaluating seroprevalence to circumsporozoite protein to estimate exposure to three species of Plasmodium in the Brazilian Amazon

Abstract

BackgroundBrazil has seen a great decline in malaria and the country is moving towards elimination. However, for eventual elimination, the control program needs efficient tools in order to monitor malaria exposure and transmission. In this study, we aimed to evaluate whether seroprevalence to the circumsporozoite protein (CSP) is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon.MethodsCross-sectional surveys were conducted in a rural area of Porto Velho, Rondônia state. Parasite infection was detected by microscopy and polymerase chain reaction. Antibodies to the sporozoite CSP repeats of Plasmodium vivax, P. falciparum, and P. malariae (PvCS, PfCS, and PmCS) were detected using the enzyme-linked immunosorbent assay technique. Human leukocyte antigen (HLA)-DRB1 and DQB1 genes were typed using Luminex® xMAP® technology.ResultsThe prevalence of immunoglobulin G against P. vivax CSP peptide (62%) was higher than P. falciparum (49%) and P. malariae (46%) CSP peptide. Most of the studied individuals had antibodies to at least one of the three peptides (72%), 34% had antibodies to all three peptides and 28% were non-responders. Although the majority of the population was not infected at the time of the survey, 74.3% of parasite-negative individuals had antibodies to at least one of the CSPs. Importantly, among individuals carrying the haplotypes DRB1*04~DQB1*03, there was a significantly higher frequency of PfCS responders, and DRB1*16~DQB1*03 haplotype for PvCS and PfCS responders. In contrast, HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to P. vivax and P. falciparum CSP repeats, and the haplotype DRB1*01~DQB1*05 was also associated with non-responders, including non-responders to P. malariae.ConclusionsOur results show that in low transmission settings, naturally acquired antibody responses against the CSP repeats of P. vivax, P. falciparum, and P. malariae in a single cross-sectional study may not represent a valuable marker for monitoring recent malaria exposure, especially in an area with a high prevalence of P. vivax. Furthermore, HLA class II molecules play an important role in antibody response and require further study with a larger sample size. It will be of interest to consider HLA analysis when using serosurveillance to monitor malaria exposure among genetically diverse populations.Electronic supplementary materialThe online version of this article (10.1186/s40249-018-0428-1) contains supplementary material, which is available to authorized users.

Recombinant Plasmodium vivax circumsporozoite surface protein allelic variants: antibody recognition by individuals from three communities in the Brazilian Amazon

“…In 2018, Oliveira-Ferreira performed a study to evaluate seroprevalence to CSP and demonstrated that not only Brazilian naturally exposed individuals but also P. vivax infected ones, were unresponsive to peptides of this protein. In this same study, two specific allelic groups were associated with absence of antibodies against PvCSP (HLA-DRB1*01 and HLA-DQB1*05) 37 . In this scenario, we believe our findings can be explained by well documented associations of the immune response with specific HLA alleles against malaria antigens 38 , 39 .…”

Malaria serology data from the Guiana shield: first insight in IgG antibody responses to Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae antigens in Suriname

“…Besides the low transmission numbers in Suriname, none of the participants had reported any symptoms and all available real-time PCR results were P. falciparum negative. Nonetheless, others also report the presence of CSP antibodies in persons long after malaria infection and even postulated that CSP antibodies, despite their short-lived nature, do not necessarily correlate with recent exposure [36].…”

Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein

“…Three different variants of the central domain of PvCSP are described: VK210, VK247, and P. vivax-like [9][10][11]. These three variants present worldwide distribution and can be identified by both serological and molecular methods [12][13][14][15]. Antibodies directed against the PvCSP central repeats domain can neutralize the sporozoite infectivity, allowing for the acquisition of sterile protection [16].…”