More than Half of Malaria Infections During Pregnancy Are Undetectable by Microscopy

More than half of malaria infections during pregnancy, and almost three out of four infections at delivery, are detected only by molecular testing, according to a study led by ISGlobal, an institution supported by "la Caixa" Foundation, and the Liverpool School of Medicine. The findings, published in the Lancet Global Health, have implications for the management and prevention of malaria in pregnant women, as well as for malaria elimination efforts.

Malaria infection during pregnancy poses a serious risk to the health of both mother and baby. However, many infections in pregnant women go undetected because they cause few symptoms and are "submicroscopic" (i.e. they are not detected by the usual microscopy test due to the low number of parasites in blood, but by more sensitive molecular tests such as PCR). These "silent" infections represent a challenge, not only for the management and prevention of malaria in pregnant women, but also for malaria elimination efforts.

To better understand how frequent these infections are at the global level, as well as the associated risk factors, Alfredo Mayor, ISGlobal and CISM researcher, and Anna Maria van Eijk, from the Liverpool School of Medicine, led a systematic review of studies published in the literature and a meta-analysis of data from these studies. The team identified 68 studies with individual or aggregated data from more than 60,000 participants, conducted between 1995 and 2017 in 27 countries (54 studies in Africa, 8 in Asia and 7 in the Americas).

The analysis shows that, on average, 13% of pregnant women had a submicroscopic infection and 8% had a microscopic infection. Of the total number of infections detected by molecular methods, the majority were submicroscopic: 59% during pregnancy and up to 74% at delivery. The highest percentage of submicroscopic infections was observed in the Americas and Asia, and in Africa a higher percentage of these infections were observed in areas with lower disease transmission. These findings - more submicroscopic infections in areas with lower transmission - confirm previous observations in non-pregnant populations. "The reasons are complex, but probably have to do with the type of parasite (P vivax or P falciparum), the genetic diversity of the parasite, and the persistence of immunity in areas where disease burden has declined rapidly," says Mayor.

As expected, the risk of fever was higher in women with high parasite density infections. But in Africa, 25% of submicroscopic infections were also associated with fever. "It is possible that, in areas with moderate to high transmission, infections fluctuate around the limit of detection by microscopy, and that some more virulent parasite strains cause fever," Mayor explains. Women under 30 and pregnant for the first time were less likely to have submicroscopic infections, as were HIV-positive women. 

The research team stresses the importance of using molecular methods to detect infections with low parasite density. "This will allow appropriate and timely treatment to be offered to pregnant women, and will ultimately contribute to reducing the parasite transmission reservoir and moving towards elimination of the disease," says Mayor.
 

Reference

van Eijk AM, Stepniewska K, Hill J, et al. Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analyses. Lancet Global Health. 2023. doi: 10.1016/S2214-109X(23)00194-8