Blood-stage Plasmodium vivax antibody dynamics in a low transmission setting: A nine year follow-up study in the Amazon region.

Camilla V Pires,Barbara A S Lima,Helena L Costa,Jessica R S Alves,Irene S Soares,Flora S Kano,Taís N Sousa,John H Adams,Cor J F Fontes,Bruno A M Sanchez,Ruth B Paula,Francis B Ntumngia,Leticia M Torres,Luzia H Carvalho,Gerhard Wunderlich

doi:10.1371/journal.pone.0207244

Abstract

Plasmodium vivax remains a global health problem and its ability to cause relapses and subpatent infections challenge control and elimination strategies. Even in low malaria transmission settings, such as the Amazon basin, where progress in malaria control has caused a remarkable reduction in case incidence, a recent increase in P. vivax transmission demonstrates the continued vulnerability of P.vivax-exposed populations. As part of a search for complementary approaches to P.vivax surveillance in areas in which adults are the majority of the exposed-population, here we evaluated the potential of serological markers covering a wide range of immunogenicity to estimate malaria transmission trends. For this, antibodies against leading P. vivax blood-stage vaccine candidates were assessed during a 9 year follow-up study among adults exposed to unstable malaria transmission in the Amazon rainforest. Circulating antibody levels against immunogenic P. vivax proteins, such as the Apical Membrane Antigen-1, were a sensitive measure of recent P. vivax exposure, while antibodies against less immunogenic proteins were indicative of naturally-acquired immunity, including the novel engineered Duffy binding protein II immunogen (DEKnull-2). Our results suggest that the robustness of serology to estimate trends in P.vivax malaria transmission will depend on the immunological background of the study population, and that for adult populations exposed to unstable P.vivax malaria transmission, the local heterogeneity of antibody responses should be considered when considering use of serological surveillance.

Highlights

Malaria remains a public health problem and its global distribution depends on environmental, economic, social and political factors affecting low-income tropical countries [1]
In order to determine whether serology is useful for monitoring temporal changes in low transmission malaria setting, we evaluated, over a 9 year study period, the antibody response of adult individuals from a well-characterized rural Amazon population [17,18,19] against three leading P. vivax merozoite-stage vaccine candidate antigens: the Apical Membrane Antigen-1 (AMA-1), that is expressed by merozoites and sporozoites, as a type I integral membrane protein [20]; the 19-kDa C-terminal region of the Merozoite Surface Protein-1 (MSP-119), which is a processed fragment of the MSP-1 polypeptide that remains on the merozoite surface and is carried into the parasitized erythrocyte [21]; and the Duffy Binding Protein region II (DBPII), a key ligand involved in the main P. vivax reticulocyte invasion pathway [22]
In the case of AMA-1, the proportion of responders was significantly associated with the pattern of vivax-malaria transmission, such that the high proportion of responders at enrollment (70%, Phase I) was drastically reduced in the low transmission period (20%, Phase II), but increased with re-exposure to malaria transmission (50%, Phase III) (P < 0.005, Fisher’s exact test) (Fig 2A)

Summary

Introduction

Malaria remains a public health problem and its global distribution depends on environmental, economic, social and political factors affecting low-income tropical countries [1]. Plasmodium vivax challenges control strategies because of its ability to cause relapses [4], early production of mosquito-infective stages [5], and significant proportion of subpatent infections, especially in low-transmission settings, such as the Amazon basin [6,7]. In the Amazon rainforest, high heterogeneity in risk factors for P. vivax, spatial clustering of transmission and subclinical reservoirs, strongly suggest that public health authorities should reformulate malaria control strategies to include a more sensitive parasite detection method for active surveillance [8,9]. As more sensitive diagnostic methods that could be deployed in the field are not available, the use of serological surveys to guide control programs has been suggested, as this strategy may provide more reliable estimates of infection exposure and transmission intensity [11,12,13]. Different surveillance approaches, such as serological surveys, need to be evaluated and their effectiveness in different epidemiological settings determined [14,15,16]

Methods

Results

Conclusion