Factors determining the occurrence of submicroscopic malaria infections and their relevance for control

TLDR

Malaria prevalence is traditionally measured by microscopy, but increasingly sensitive molecular methods reveal higher infection rates, indicating that submicroscopic infections may be common and challenge current estimates of disease burden. The study analyzes multiple datasets to characterize the distribution and epidemiological factors of low‑density, submicroscopic malaria infections. The authors analyze a series of datasets to characterize the distribution and epidemiological factors of low‑density, submicroscopic malaria infections. The analysis shows that submicroscopic malaria infections are common in adults, low‑endemic settings, and chronic cases; they contribute 20–50 % of transmission when prevalence is very low; microscopy and PCR prevalence are non‑linearly related, allowing a predictive tool; and these findings suggest that even individuals with limited prior exposure can control parasitaemia, highlighting the importance of molecular screening.

Abstract

Malaria parasite prevalence in endemic populations is an essential indicator for monitoring the progress of malaria control, and has traditionally been assessed by microscopy. However, surveys increasingly use sensitive molecular methods that detect higher numbers of infected individuals, questioning our understanding of the true infection burden and resources required to reduce it. Here we analyse a series of data sets to characterize the distribution and epidemiological factors associated with low-density, submicroscopic infections. We show that submicroscopic parasite carriage is common in adults, in low-endemic settings and in chronic infections. We find a strong, non-linear relationship between microscopy and PCR prevalence in population surveys (n=106), and provide a tool to relate these measures. When transmission reaches very low levels, submicroscopic carriers are estimated to be the source of 20–50% of all human-to-mosquito transmissions. Our findings challenge the idea that individuals with little previous malaria exposure have insufficient immunity to control parasitaemia and suggest a role for molecular screening. Malaria can persist at levels that escape detection by standard microscopy, but can be detected by PCR. Okell et al.now show that rates of submicroscopic infection can be predicted using more widely available microscopy data, and are most epidemiologically significant in areas with low malaria transmission.