Evaluation of the usefulness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in a context with increased resistance of Plasmodium falciparum in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo

Abstract

Background: Increasing resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) threatens its usefulness for intermittent preventive treatment in pregnancy (IPTp-SP). The prophylactic effects of IPTp-SP on maternal malaria and adverse pregnancy outcomes were evaluated in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo (DRC).

Methods: Laboring women (n = 844) and respective newborns were investigated. Blood samples collected from women were tested for malaria using rapid diagnostic test (RDT), blood smears examination, and real-time PCR. The hemoglobin level was measured by HemoCue© analyzer. A PCR-RFLP method was applied for detecting N51I, C59R, and S108N mutations on dhfr along with A437G and K540E mutations on dhps in P. falciparum positive samples. Logistic regression models assessed relationships between IPTp-SP uptake and pregnancy outcomes.

Results: P. falciparum malaria was detected at delivery in 10.8% of women and was statistically associated with fever during the pregnancy (OR = 2.9 [1.5; 6.3]; p = 0.004) and maternal anemia (OR = 3.9 [2.4; 6.3]; p < 0.001). One out of five parasites was a quintuple mutant encoding dhfr mutations 51I, 59R, and 108 N along with dhps mutations 437G and 540E. The molecular profile of parasites (i.e., 32.6% of parasites carrying dhps K540E) was suitable with continued use of SP for IPTp. IPTp-SP uptake was not associated with reduced maternal malaria, fever reported in pregnancy, or fetal deaths (p > 0.05). Conversely, three or more doses of SP were associated with reduced maternal anemia at delivery (OR = 0.4 [0.2; 0.9]; p = 0.024), shortened gestation (OR = 0.4 [0.2; 0.8]; p = 0.009), and low-birth weights (OR = 0.2 [0.1; 0.5]; p < 0.001).

Conclusion: IPTp-SP was not associated with reduced maternal malaria in our study, but evidence was found of a prophylactic effect against adverse pregnancy outcomes. To counteract further loss of clinical effects of IPTp-SP in the study population, alternative strategies able to improve its anti-malarial efficacy such as combination of SP with partner molecules should be implemented.

Keywords: Democratic Republic of Congo; Intermittent preventive treatment in pregnancy; Laboring woman; Malaria; Resistance; Sulfadoxine-Pyrimethamine.