Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda

Briggs, Jessica; Ategeka, John; Kajubi, Richard; Ochieng, Teddy; Kakuru, Abel; Ssemanda, Cephus; Wasswa, Razack; Jagannathan, Prasanna; Greenhouse, Bryan; Rodríguez-Barraquer, Isabel; Kamya, Moses R.; Dorsey, Grant

doi:10.1093/infdis/jiz130

Cited by 27 publications

(28 citation statements)

References 33 publications

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“…past and chronic infection) is associated with a higher risk of LBW or IUGR [16,19,20]. The risk of placental malaria is, in turn, affected by gravidity, age, number of malaria infections, and parasite density [16,47], which was confirmed in this IPD meta-analysis (with the exception of frequency of parasitaemia, which could not be assessed). Additionally, a higher risk of placental malaria was observed in women with higher body temperature before treatment, which can be a surrogate for the severity of the infection; inflammatory cytokines causing fever (e.g.…”

Section: Discussionsupporting

confidence: 66%

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Saito

Mansoor

Kennon

et al. 2020

BMC Med

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Section: Discussionsupporting

confidence: 66%

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Saito

Mansoor

Kennon

et al. 2020

BMC Med

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“…Heterogeneity in the study designs, population demographics, surveillance protocols, diagnostic and treatment methodologies, and regional malaria characteristics may explain at least some of the discrepancies in these studies. Recently, an analysis of a separate cohort of women in Uganda found that burden of infection and timing of parasitemia impact risk for placental malaria, which is consistent with our ndings [32]. Our study suggests that the importance of timing of infection on the development of placental malaria may vary based on gravidity.…”

Section: Discussionsupporting

confidence: 91%

The impact of gravidity, symptomatology and timing of infection on placental malaria

Tran

Cheeks

Kakuru

et al. 2020

Preprint

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Background Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. Methods The aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection. Results Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34-18.2, p<0.001), and each episode of malaria was associated with over a 2-fold increase in placental malaria (aOR 2.35, 95% CI 1.69-3.26, p<0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02-1.27, p=0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23-28.43, p<0.001). Conclusions Total number of Plasmodium falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were more frequently identified in those with placental malaria, whereas in multigravidas, parasitemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.

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“…Recently, an analysis of a separate cohort of women in Uganda found that burden of infection and timing of parasitemia impact risk for placental malaria, which is consistent with our findings. 32 Our study suggests that the importance of timing of infection on the development of placental malaria may vary based on gravidity. This finding may further explain why prior literature has painted an unclear picture of the impact of timing of infection on placental malaria.…”

Section: Discussionmentioning

confidence: 76%

The Impact of Gravidity, Symptomatology and Timing of Infection on Placental Malaria

Tran

Cheeks

Kakuru

et al. 2020

Preprint

Self Cite

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Background : Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. Methods : Our aim was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. We performed subgroup analysis based on the presence of symptomatic malaria, gravidity, and timing of infection. Results : Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34-18.2, p<0.001), and each episode of malaria was associated with over a 2-fold increase in placental malaria (aOR 2.35, 95% CI 1.69-3.26, p<0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02-1.27, p=0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23-28.43, p<0.001). Conclusions : Total number of Plasmodium falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were associated with placental malaria, whereas in multigravidas, parasitemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.

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Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda

Abstract: In pregnant women assessed for parasitemia every 28 days, the risk of placental malaria increased in a dose-response relationship with both increasing frequency and density of parasitemia; however, even women with only submicroscopic parasitemia were at risk for placental malaria.

Cited by 27 publications

References 33 publications

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

The impact of gravidity, symptomatology and timing of infection on placental malaria

The Impact of Gravidity, Symptomatology and Timing of Infection on Placental Malaria

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