Submicroscopic malaria infection during pregnancy and the impact of intermittent preventive treatment

Abstract

BackgroundMalaria during pregnancy results in adverse outcomes for mothers and infants. Intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) is the primary intervention aimed at reducing malaria infection during pregnancy. Although submicroscopic infection is common during pregnancy and at delivery, its impact throughout pregnancy on the development of placental malaria and adverse pregnancy outcomes has not been clearly established.MethodsQuantitative PCR was used to detect submicroscopic infections in pregnant women enrolled in an observational study in Blantyre, Malawi to determine their effect on maternal, foetal and placental outcomes. The ability of SP to treat and prevent submicroscopic infections was also assessed.Results2,681 samples from 448 women were analysed and 95 submicroscopic infections were detected in 68 women, a rate of 0.6 episodes per person-year of follow-up. Submicroscopic infections were most often detected at enrolment. The majority of women with submicroscopic infections did not have a microscopically detectable infection detected during pregnancy. Submicroscopic infection was associated with placental malaria even after controlling for microscopically detectable infection and was associated with decreased maternal haemoglobin at the time of detection. However, submicroscopic infection was not associated with adverse maternal or foetal outcomes at delivery. One-third of women with evidence of placental malaria did not have documented peripheral infection during pregnancy. SP was moderately effective in treating submicroscopic infections, but did not prevent the development of new submicroscopic infections in the month after administration.ConclusionsSubmicroscopic malaria infection is common and occurs early in pregnancy. SP-IPT can clear some submicroscopic infections but does not prevent new infections after administration. To effectively control pregnancy-associated malaria, new interventions are required to target women prior to their first antenatal care visit and to effectively treat and prevent all malaria infections.

What is the burden of submicroscopic malaria in pregnancy in central India?

“…We found a marked underestimation of malarial infection in pregnant women when diagnosed by standard microscopy in peripheral or placental blood compared with PCR, as has been reported previously in other settings outside South Asia. [12][13][14][15][16][17][18][19][20][21][22] Indeed, the majority of infections was submicroscopic (66.3% of peripheral and 64.4% of placental infections) in line with a meta-analysis suggesting higher proportions of submicroscopic infections in areas of lower malaria prevalence. 5 The association of malaria prevention measures with submicroscopic infections was inconsistent in our data.…”

“…[12][13][14][15][16][17][18][19][20][21][22] Nonetheless, the clinical relevance of these submicroscopic infections to the mother and fetus remains unclear. Submicroscopic infections were linked with maternal anemia in some 17,18,20,23 but not all 12,13,15,21 studies. Similarly, the data are conflicting about the impact of submicroscopic infections on LBW; some studies suggest an increased risk 16,24 in the setting of submicroscopic infections and others no association.…”

“…Similarly, the data are conflicting about the impact of submicroscopic infections on LBW; some studies suggest an increased risk 16,24 in the setting of submicroscopic infections and others no association. [20][21][22][23] Neither study that evaluated preterm birth found an increased risk associated with submicroscopic infection. 21,23 The proportion of malarial infections that are submicroscopic appears to be higher in areas of low transmission.…”

“…[20][21][22][23] Neither study that evaluated preterm birth found an increased risk associated with submicroscopic infection. 21,23 The proportion of malarial infections that are submicroscopic appears to be higher in areas of low transmission. A meta-analysis of surveys conducted in endemic areas reported that 88% of all infections went undetected by microscopy in areas of low transmission compared to only 25.5% in areas of high transmission.…”

Challenges of malaria diagnosis in clinical settings and disease surveillance under reduced malaria burden in Tanzania

“…Such submicroscopic parasitaemia contributes substantially to malaria transmission [41,42], and although their attribution to a febrile illness has not been well characterized, such a possibility exists [43,44]. The contribution of submicroscopic infections to malaria transmission and febrile illness is likely to increase with declining malaria burden as a result of lowered naturally acquired immunity to malaria [45]. The role of submicroscopic infections in lowering hemoglobin levels has also been documented [46,47].…”