Systematic Review of Sub-microscopic P. vivax Infections: Prevalence and Determining Factors

Abstract

BackgroundSub-microscopic (SM) Plasmodium infections represent transmission reservoirs that could jeopardise malaria elimination goals. A better understanding of the epidemiology of these infections and factors contributing to their occurrence will inform effective elimination strategies. While the epidemiology of SM P. falciparum infections has been documented, that of SM P. vivax infections has not been summarised. The objective of this study is to address this deficiency.Methodology/Principal FindingsA systematic search of PubMed was conducted, and results of both light microscopy (LM) and polymerase chain reaction (PCR)-based diagnostic tests for P. vivax from 44 cross-sectional surveys or screening studies of clinical malaria suspects were analysed. Analysis revealed that SM P. vivax is prevalent across different geographic areas with varying transmission intensities. On average, the prevalence of SM P. vivax in cross-sectional surveys was 10.9%, constituting 67.0% of all P. vivax infections detected by PCR. The relative proportion of SM P. vivax is significantly higher than that of the sympatric P. falciparum in these settings. A positive relationship exists between PCR and LM P. vivax prevalence, while there is a negative relationship between the proportion of SM P. vivax and the LM prevalence for P. vivax. Amongst clinical malaria suspects, however, SM P. vivax was not identified.Conclusions/SignificanceSM P. vivax is prevalent across different geographic areas, particularly areas with relatively low transmission intensity. Diagnostic tools with sensitivity greater than that of LM are required for detecting these infection reservoirs. In contrast, SM P. vivax is not prevalent in clinical malaria suspects, supporting the recommended use of quality LM and rapid diagnostic tests in clinical case management. These findings enable malaria control and elimination programs to estimate the prevalence and proportion of SM P. vivax infections in their settings, and develop appropriate elimination strategies to tackle SM P. vivax to interrupt transmission.

Higher Complexity of Infection and Genetic Diversity of Plasmodium vivax Than Plasmodium falciparum Across All Malaria Transmission Zones of Papua New Guinea

“…30 The contrasting complexity of infection for the two species is comparable to previous reports from the PNG north coast 39,68 and demonstrates that this pattern is also observed across areas with widely varying endemicity including areas with low parasite prevalence. 30 This may be in part due to lower transmission areas having increasing proportions of imported infections, which reflects the MOI and diversity of the infection origin, 22,69,70 and this effect would be enhanced for P. vivax by the fact that relapse can occur 1-3 years after the primary infection. 71 The high complexity of infection for P. vivax regardless of parasite prevalence is also comparable to other studies where high infection complexity and diversity were found even with sustained low parasite prevalence such as in South America 33,72,73 and Sri Lanka.…”

Uncovering the transmission dynamics ofPlasmodium vivaxusing population genetics

“…12 At low transmission, the strong LD could be explained by relapse because in the absence of a high rate of new infections containing distinct clones, there would be frequent recombination between meiotic siblings (inbreeding) and the maintenance of multiple non-recombining lineages. Furthermore, the longer relapse rates in P. vivax strains from temperate versus the shorter relapse rates of strains from tropical climates 4 has likely contributed to the complex patterns observed. The hypnozoite is therefore likely to play a major role in shaping P. vivax population structure.…”

“…Since the advancement of sensitive molecular diagnostics, it has been recognised that a significant proportion of the P. vivax burden is composed of low-density, asymptomatic infections that remain undetected by standard epidemiological tools (reviewed by Ref. 4 ) and that these proportions may increase with decreasing transmission. 5 Genotyping approaches that distinguish between different parasite clones within an infection to estimate the multiplicity of infection (MOI) have provided some insight into the intensity of transmission in different endemic areas.…”

Development of vaccines for Plasmodium vivax malaria

“…At all levels of transmission, asymptomatic and sub-microscopic P. vivax infections are very common [10]. Most if not all of these infections produce gametocytes [11] and likely contribute substantially to maintaining P. vivax transmission [12].…”