Submicroscopic Plasmodium infection during pregnancy is associated with reduced antibody levels to tetanus toxoid

Abstract

Submicroscopic Plasmodium infections in pregnancy are common in endemic areas, and it is important to understand the impact of these low-level infections. Asymptomatic, chronic infections are advantageous for parasite persistence, particularly in areas where the optimal eco-epidemiological conditions for parasite transmission fluctuate. In chronic infections, the persistence of the antigenic stimulus changes the expression of immune mediators and promotes constant immune regulation, including increases in regulatory T cell populations. These alterations of the immune system could compromise the response to routine vaccination. This study aimed to evaluate the effect of submicroscopic plasmodial infection with P. falciparum and P. vivax during pregnancy on the immune response to the tetanus toxoid vaccine in Colombian women. Expression of different cytokines and mediators of immune regulation and levels of anti-tetanus toxoid (TT) immunoglobulin (Ig)G were quantified in pregnant women with and without submicroscopic plasmodial infection. The anti-TT IgG levels were significantly lower in the infected group compared with the uninfected group. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF) and forkhead box protein 3 (FoxP3) was significantly higher in the infected group, while the expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and transforming growth factor (TGF)-β was lower in the group of infected. In conclusion, submicroscopic Plasmodium infection altered the development of the immune response to the TT vaccine in Colombian pregnant women. The impact of Plasmodium infections on the immune regulatory pathways warrants further exploration.

Negative immunomodulation by parasitic infections in the human response to vaccines

“…However, it is important to note that each study includes different groups and different clinical presentation of malaria. In a recent study carried out in pregnant women, submicroscopic infection by Plasmodium was associated with a decrease in the levels of IgG against tetanus toxoid [37]. In the same way, of four studies that evaluated the effect of filarioidosis in the immune response against tetanus toxoid, two showed a decrease in IgG levels against tetanus toxoid vaccine [38,39], while two did not show differences between the groups [33,40] (Table 1).…”

Placental Malaria: Histological Findings and Immune Cell Infiltrates in Submicroscopic Infections

“…An important achievement of this study was to describe the histological alterations that are frequent in placentas with submicroscopic infections. There are reports that do not show associations between submicroscopic infections and negative pregnancy outcomes [10,32,[54][55][56], but there are also reports that submicroscopic infection during pregnancy affects the health of the mother and the fetus [10-12, 32, 55, 57-59]. These infections in maternal peripheral blood or in the placenta may cause pathological effects on maternal and infant health, although, apparently, with lesser magnitude than microscopic infections.…”

“…In Colombia, an area of low transmission of both P. falciparum and P. vivax, there is a high frequency of submicroscopic gestational and placental infections, 49% and 57%, respectively [11]. The impact of submicroscopic infections of both species in pregnancy in this area is being explored, and it has been shown that submicroscopic infection during pregnancy is frequent and can affect the health of women and their offspring [32][33][34][35].…”

Overview of Epidemiology of Malaria Associated with Pregnancy in Northwestern Colombia, 1985-2020

“…41 Most of the studies on the immune response in MAP focus mainly on P. falciparum infections, they agree that the consequences of MAP go beyond infection during pregnancy, since its effects extend to the neonate and the first years of life. 25 In pregnancy is not known how antiplasmodial antibodies (Ab) maintain protective levels, and its levels in reinfections are not known either. Despite this absence, a study in northwestern Thailand measured Ab levels against merozoite antigens (m-Ag) from both species and against VAR2CSA antigens from P. falciparum.…”

“…Something similar occurs with the prevalence of PM and CM, demonstrating that submicroscopic infections (detected with PCR, but not with TBS) affect maternal health, the placenta and affect the gestational product. 23,25,26 Coexistence of GM and PM GM is prior to infection of the placenta (PM). The first can exist without the second and PM can be without GM, but the usual is their coexistence.…”