Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

Abstract

Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns.

Intermittent Preventive Treatment in Pregnant Women Is Associated with Increased Risk of Severe Malaria in Their Offspring

“…In addition, it is possible that IPTp may reduce the diversity of maternal antimalarial antibodies and as a result increase offspring susceptibility to a heterogeneous parasite population. In mice, treatment of malaria infections prior to pregnancy is associated with decreased antimalarial antibodies in dams, resulting in decreased antimalarial antibodies, increased parasitemia, and increased mortality in their malaria-infected pups [23]. In the present cohort, the difference in risk of severe malaria between offspring whose mothers did or did not receive IPTp appeared to develop around six months of age, when maternal antimalarial antibodies have significantly waned and infant immune responses take precedence [19].…”

Maternally derived anti-helminth antibodies predict offspring survival in a wild mammal

“…Further support for this is provided by the positive association between neonatal antibody levels and the mother's own anti-strongyle antibody levels in the summer prior to giving birth. Previous experimental studies in captive rodents have demonstrated that maternal antibodies provide strain-specific protection which depends on the infection history of the mother [ 46 , 47 ]. Given that exposure to worms starts early, we would expect that all females would be sufficiently exposed to have developed an acquired immune response to strongyles by sexual maturity, despite exposure varying in time and space [ 19 ].…”

Early Plasmodium‐induced inflammation does not accelerate aging in mice

“…Control groups of uninfected mice received an intraperitoneal injection with 10 6 heat‐killed P. yoelii ‐infected red blood cells, or an intraperitoneal injection of anti‐IL‐10R antibodies at the same dose during four nonconsecutive days, or were left unmanipulated. At day 39 postinfection, all mice were given 7 mg/ml Pyrimethamine (Vetranal TM ‐ Sigma Aldrich) in their drinking water for five consecutive days to clear the infection (Staszewski, Reece, O'Donnell, & Cunningham, ).…”