Transcription of var genes other than var2csa in Plasmodium falciparum parasites infecting Mozambican pregnant women

Abstract

Background: Increased susceptibility to Plasmodium falciparum infection during pregnancy has been attributed to the accumulation of infected erythrocytes in the placenta. This phenomenon is mediated by a var gene coding for VAR2CSA, which adheres to chondroitin sulphate A. However, the contribution of parasites transcribing other var genes to maternal infections has not been well characterized.

Methods: Transcription of var2csa and var groups A, B, and C was measured by real-time polymerase chain reaction in 30 placental and 21 peripheral P. falciparum isolates from pregnant women and in 42 isolates from nonpregnant adults and children. Associations of infections with non-var2csa isolates with maternal parasitemia and immune responses were assessed.

Results: Placental parasites showed the highest levels of var2csa. ABC var genes were transcribed by 20 (67%) of 30 placental isolates and were associated with higher parasitemia compared with infections by parasites only transcribing var2csa (P = .004). Peripheral isolates from pregnant women transcribed ABC var genes at levels similar to those of parasites infecting nonpregnant adults with clinical malaria (P[varA] = .420, P[varB] = .808, and P[varC] = .619).

Conclusions: Transcripts of var2csa are abundant in pregnancy-associated P. falciparum infections; however, ABC var types are also common, especially in peripheral blood, with transcription levels similar to those of infections out of pregnancy. These findings are of interest for the design of malaria vaccines for pregnant women.

Figure 1.

Transcription of var genes of Plasmodium falciparum in pregnant women (PW), nonpregnant adults, and children, as well as in 4 laboratory strains (CS2_CSA, 193T_CSA, FCR3_CSA, and R29). Data are shown as log-transformed relative copy numbers. Boxes delimit medians and interquartile ranges; bars indicate extreme values. Transcription prevalence is indicated inside boxes. Plac, placental isolates; per, peripheral isolates.

Figure 2.

Parasitemia and immunoglobulin G (IgG) levels against Plasmodium falciparum antigens in pregnant women infected in their placentas with isolates transcribing A, B, or C var gene groups (plus signs, gray boxes) and isolates not transcribing that particular var subgroup (minus signs, white boxes). Placental isolates transcribing at least 1 of the A, B, or C var groups (ABCvar+) were compared with isolates exclusively transcribing var2csa (ABCvar−). Data are shown as log-transformed number of parasites per microliter, mean fluorescence intensity (MFI), or optical density (OD) values, respectively. Boxes delimit medians and interquartile ranges; bars indicate extreme values. *P < .05, Kruskal-Wallis test.

Figure 3.

Parasitemia and immunoglobulin G (IgG) levels against Plasmodium falciparum antigens in pregnant women infected in their peripheral blood with isolates transcribing A, B, or C var gene groups (plus signs, gray boxes) and isolates not transcribing that particular var subgroup (minus signs, white boxes). Data are shown as log-transformed number of parasites per microliter, mean fluorescence intensity (MFI), or optical density (OD) values, respectively. Boxes delimit medians and interquartile ranges; bars indicate extreme values. *P < .05, Kruskal-Wallis test.