Microscopic and submicroscopic malaria in pregnancy: a systematic review and meta-analysis investigates prevalence and associated risk factors

By Neha MathurReviewed by Danielle Ellis, B.Sc.Jun 22 2023

In a recent study published in The Lancet Global Health, researchers conducted a systematic review to describe the epidemiology of submicroscopic and microscopic malaria infections during pregnancy. 

To this end, they used aggregated and individual participant data (IPD) of representative pregnant females from Asia, the Americas, and Africa, gathered after an extensive search of published literature in research databases.

In most settings, submicroscopic malaria infections are more common than microscopic infections. Thus, the researchers also explored the relationship between submicroscopic malaria infections stratified by causal parasitic species, symptoms (e.g., fever), and patient age.

Background

Around 122 million pregnancies occurred in areas of malaria transmission in 2020 alone. Increased testing via nucleic acid amplification tests (NAATs) showed that most infections in pregnancy remained asymptomatic, hence, were difficult to diagnose. Invasion of the placenta by malarial parasites made it more challenging to diagnose malaria during pregnancy as it lowered parasite densities in peripheral blood.

Gathering insights into the epidemiology of submicroscopic malarial infections in pregnancy could serve several purposes. First, it could help devise strategies to prevent, detect, and manage malaria early, i.e., in the first trimester, which, in turn, would prevent adverse birth outcomes.

Second, it would give an idea of the contribution of submicroscopic infections to the total infectious reservoir, an estimate of which is necessary for implementing adequate mass-level malaria elimination efforts, e.g., drug administration campaigns.

Such programs do not usually cover pregnant females because of drug safety concerns for the fetus. Finally, insights into submicroscopic malarial infection patterns help interpret parasite prevalence data collected at antenatal clinics.

About the study

In the present systematic review and meta-analysis, researchers utilized studies published between January 1, 1997, and November 10, 2021, with data on microscopic and submicroscopic malaria infections during pregnancy. They retrieved aggregated and IPD data from all eligible studies in the Malaria-in-Pregnancy Library from Asia, the Americas, or Africa.

The team used publicly available data to fetch study location- and year-matched estimates of malaria transmission and sulfadoxine–pyrimethamine resistance. Likewise, they used one-stage multivariable logit and multinomial models to assess the prevalence and risk factors for submicroscopic infections during pregnancy and at delivery.

Results

The extensive search identified 87 eligible studies, of which 68, i.e., 78%, contributed to the analytic data. Of these, 45 and 23 studies with 48869 and 11863 participants contributed IPD and aggregated data, respectively. They noted average prevalence estimates for submicroscopic and microscopic malaria of 13.5% and 8% during pregnancy, respectively.

The average proportion of submicroscopic malaria infections was 58.7% in women with positive Plasmodium nucleic acid amplification tests (NAAT); this percentage was highest in the Americas, followed by Asia and Africa (73.3%, 67.2%, and 56.5%). 

Per the findings of individual patient data, women with submicroscopic malaria infections vs. those with no malaria presented with fever only in Africa, not in other regions, with an adjusted odds ratio (aOR) of 1.32 and 95% confidence interval (CI). In Asian and American women with NAAT-positive infections, Plasmodium vivax infections (not Plasmodium falciparum-caused infections) were likely submicroscopic, aOR =3.69. 

For women with NAAT-positive malaria infections and parasitaemia in Africa, risk factors for submicroscopic malaria infections were older age (aged ≥30 years) and multigravidity; whereas, in Asian and American women, only older age was a risk factor. The incidence of submicroscopic malaria was higher in Asia and the Americas relative to Africa, where it was more common due to malaria species other than Plasmodium falciparum. 

Plasmodium falciparum is responsible for most malaria cases, whereas the effects of Plasmodium vivax during pregnancy are generally less severe. Nine studies, of which five were clinical trials, provided information on submicroscopic malaria at a consecutive scheduled follow-up visit. In Asia and America combined, only 1% of women with submicroscopic infection at enrolment presented with submicroscopic malaria at the follow-up visit. Conversely, in Africa, of 1009 women with a submicroscopic infection at enrolment, on average, 18·5% of women presented with submicroscopic malaria at the follow-up visit.

The submicroscopic malaria incidence at follow-up visits was less likely in women who received dihydroartemisinin–piperaquine, an antimalarial treatment, at enrolment than women who received other or no treatment. Apparently, this treatment reduced the risk of submicroscopic malaria more in cohort studies than in trials in Africa.

Another factor associated with submicroscopic infections was sulfadoxine–pyrimethamine resistance, which was low in areas of high transmission but high in moderate-to-low transmission regions.

Conclusion

Taken together, the current study showed that submicroscopic infections were more common than microscopic infections during pregnancy. However, mitigation strategies should target both for effective malaria control.