Intermittent Preventive Sulfadoxine-Pyrimethamine Treatment of Primigravidae Reduces Levels of Plasma Immunoglobulin G, Which Protects against Pregnancy-Associated Plasmodium falciparum Malaria

Abstract

Pregnancy-associated malaria (PAM) is an important cause of maternal and neonatal suffering. It is causedby Plasmodium falciparum capable of inhabiting the placenta through expression of particular variant surface antigens (VSA) with affinity for proteoglycans such as chondroitin sulfate A. Protective immunity to PAM develops following exposure to parasites inhabiting the placenta, and primigravidae are therefore particularly susceptible to PAM. The adverse consequences of PAM in primigravidae are preventable by intermittent preventive treatment (IPTp), where women are given antimalarials at specified intervals during pregnancy, but this may interfere with acquisition of protective PAM immunity. We found that Kenyan primigravidae receiving sulfadoxine-pyrimethamine IPTp had significantly lower levels of immunoglobulin G (IgG) with specificity for the type of parasite-encoded VSA-called VSA PAM -that specifically mediate protection against PAM than did women receiving a placebo. VSA PAM -specific IgG levels depended on the number of IPTp doses received and were sufficiently low to be of clinical concern among multidose recipients. Our data suggest that IPTp should be extended to women of all parities, in line with current World Health Organization recommendations.

Influence of Intermittent Preventive Treatment on Antibodies to VAR2CSA in Pregnant Cameroonian Women

“…This is the first study to report the influence of IPT on Ab levels to the FV2 in longitudinal cohort of primigravidae. Similar to previous studies that measured Abs to the surface of CSA-binding IE, 21 reduced exposure to malaria in primigravidae resulted in reduced Ab acquisition to VAR2CSA (Figures 1-3). After the first dose of SP, a general decline in Abs to VAR2CSA in primigravidae was observed, suggesting that only short-lived plasma cells had been produced.…”

“…19 Unfortunately, the use of IPT and ITN remains low throughout Africa. 20 Studies have reported IPT and/or ITN may reduce the Ab response to placental-binding IE or VAR2CSA in primigravidae and multigravidae, [21][22][23][24][25] but many questions remain. In particular, a limited understanding exists about how these interventions affect the quality and specificity of the anti-VAR2CSA Ab response acquired by primigravidae and if multigravidae, who acquired immunity to PM in previous pregnancies, maintain their immunity.…”

Sulfadoxine-Pyrimethamine–Based Intermittent Preventive Treatment, Bed Net Use, and Antenatal Care during Pregnancy: Demographic Trends and Impact on the Health of Newborns in the Kassena Nankana District, Northeastern Ghana

“…19 In defense of limited S/P use during pregnancy, plasma IgG, which mediates protection against placental malaria, was reportedly unaffected in primigravidae given single-dose S/P, but was reduced 2-8-fold in those given multiple doses. 20 In rural Burkina Faso, where 23% of primigravid women were parasitemic at delivery and 24% of their newborns were LBW, > 1 IPTp dose of S/P was associated with fewer parasitemias, but 2-3 doses were associated with significantly fewer LBW deliveries, and birth weights that increased in direct proportion to IPTp dosing. 21 Irrespective of parity, single-dose S/P in pregnant, human immunodeficiency virus-positive, Zambian women was associated with poorer outcomes than two doses for both mother and newborn, but three or more doses yielded no further benefits.…”

Influence du traitement présomptif intermittent par la sulfadoxinepyriméthamine sur l’acquisition d’anticorps anti-VAR2CSA chez la femme enceinte vivant en zone hypoendémique au Sénégal

“…Cet antigène fait l'objet de plusieurs études pour une meilleure compréhension et une amélioration de la prise en charge du paludisme au cours de la grossesse. En effet, les femmes ayant présenté une grossesse impaludée développent des anticorps spécifiques anti-VAR2CSA qui seraient associés à une meilleure protection contre le paludisme au cours des grossesses ultérieures [8,30,31]. L'antigène VAR2CSA connaît un polymorphisme.…”

“…Toutefois, il existe peu de données immunologiques, concernant l'influence du TPI sur l'acquisition d'anticorps antipalustres chez la femme enceinte [30,31].…”