Systematic Review of Sub-microscopic <i>P. vivax</i> Infections: Prevalence and Determining Factors

<div><p>Background</p><p>Sub-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 <i>P. falciparum</i> infections has been documented, that of SM <i>P. vivax</i> infections has not been summarised. The objective of this study is to address this deficiency.</p><p>Methodology/Principal Findings</p><p>A systematic search of PubMed was conducted, and results of both light microscopy (LM) and polymerase chain reaction (PCR)-based diagnostic tests for <i>P. vivax</i> from 44 cross-sectional surveys or screening studies of clinical malaria suspects were analysed. Analysis revealed that SM <i>P. vivax</i> is prevalent across different geographic areas with varying transmission intensities. On average, the prevalence of SM <i>P. vivax</i> in cross-sectional surveys was 10.9%, constituting 67.0% of all <i>P. vivax</i> infections detected by PCR. The relative proportion of SM <i>P. vivax</i> is significantly higher than that of the sympatric <i>P. falciparum</i> in these settings. A positive relationship exists between PCR and LM <i>P. vivax</i> prevalence, while there is a negative relationship between the proportion of SM <i>P. vivax</i> and the LM prevalence for <i>P. vivax</i>. Amongst clinical malaria suspects, however, SM <i>P. vivax</i> was not identified.</p><p>Conclusions/Significance</p><p>SM <i>P. vivax</i> 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 <i>P. vivax</i> 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 <i>P. vivax</i> infections in their settings, and develop appropriate elimination strategies to tackle SM <i>P. vivax</i> to interrupt transmission.</p>