Human immunodeficiency virus co-infection increases placental parasite density and transplacental malaria transmission in Western Kenya

Abstract

Plasmodium falciparum malaria and human immunodeficiency virus (HIV)-1 adversely interact in the context of pregnancy, however little is known regarding the influence of co-infection on the risk of congenital malaria. We aimed to determine the prevalence of placental and congenital malaria and impact of HIV co-infection on trans-placental malaria transmission in 157 parturient women and their infants by microscopy and by quantitative real-time polymerase chain reaction (PCR) in western Kenya. The prevalence of placental and cord blood infections were 17.2% and 0% by microscopy, and 33.1% and 10.8% by PCR. HIV co-infection was associated with a significant increase in placental parasite density (P < 0.05). Cord blood malaria prevalence was increased in co-infected women (odds ratio [OR] = 5.42; 95% confidence interval [CI] = 1.90-15.47) and correlated with placental parasite density (OR = 2.57; 95% CI = 1.80-3.67). A 1-log increase in placental monocyte count was associated with increased risk of congenital infection (P = 0.001) (OR = 48.15; 95% CI = 4.59-505.50). The HIV co-infected women have a significantly increased burden of placental malaria that increases the risk of congenital infection.

Figure 1

Detected rates of malaria infection in peripheral, placental, and cord blood samples from the sampled population. A, Prevalence of malaria infection was determined by both a real-time, quantitative polymerase chain reaction (PCR) assay and by microscopy. The PCR assay detected significantly higher rates of infection (* P < 0.05) in all blood sample types. B, Women from Siaya and Kisumu regions of Kenya were compared for prevalence of malaria infection in peripheral, placental, and cord blood samples, with Siaya found to have consistently higher rates (* P <0.05).

Figure 2

Odds ratios ± 95% confidence intervals were calculated for various risk factors examined. Odds ratios greater than 1.0 indicate a significantly higher (P < 0.05) risk in the first group listed, i.e., women in Siaya were found to have a higher risk of peripheral malaria than those in Kisumu.

Figure 3

Risk of placental parasitemia is parity and region dependent. Regression of the percent of women positive for placental infection against parity count demonstrates that risk of infection decreases with successive pregnancies. The rate of change in Siaya (p) was measured at 11.2% per pregnancy, compared with a 5.3% per pregnancy decrease in Kisumu (l).

Figure 4

Human immunodeficiency virus (HIV) co-infection with malaria increases parasite burden and risk of congenital malaria. A , HIV seropositive individuals were found to have higher rates of both placental and cord blood parasitemia, measured by the real-time polymerase chain reaction (PCR) assay. B, HIV seropositive women were found to have higher burdens of malaria in placental and cord blood. Placental blood contained a nearly 15-fold increase in parasites (* P < 0.05). C, Women in Siaya with placental malaria were stratified according to their log-transformed parasitemia. Each stratified group was then analyzed for percent free of cord blood malaria. Regression against placental parasite burden demonstrates that higher placental parasitemia increases risk of cord blood infection. D, Placental parasite burden was increased by HIV co-infection in both Kisumu and Siaya, with the increase in Siaya being more significant. Using the Siaya-based regression analysis in C, a predicted increase in risk of congenital malaria from HIV is found to be similar to the actual relative risk measured for both Siaya and Kisumu.

Figure 5

Monocyte counts in placental blood correlates with placental parasite burden. A, Examination of the correlation between increasing placental monocyte cells with increasing placental parasite burden revealed a significant trend (P < 0.05). B, Women with placental malaria were found to have a high average number and range of monocytes in placental blood.