Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning

Abstract

We developed a newborn (NB) mouse Plasmodium yoelii NL infection model to study malaria in early age. Surprisingly, the onset of parasitemia in P. yoelii challenged NB mice was delayed compared to adults and coincided with the weaning date when weanlings switched from maternal milk to normal chow diet. Also, compared to adult mice, parasitemia resolved much later (48 days vs 20 days post challenge) and the peak parasitemia was twice as high in weanlings. Concurrently, weanlings’ germinal center reaction was delayed and diminished compared to adult mice. Maternal milk is deficient in para-aminobenzoic acid (PABA), which is required for de novo folate synthesis by Plasmodium. Suggesting a possible role for the protection afforded by PABA-deficient maternal milk, mice fed with a PABA-deficient diet after the weaning continued to control parasitemia. Despite the reduced parasitemia, these mice developed robust T follicular helper (Tfh) responses and were protected from a second P. yoelii challenge. The NB malaria model provides mechanistic insight into the human infant malaria manifestations where a diet solely based on breast-feeding reduces the incidence of severe malaria in infants. NB mice experiments also support further studies to investigate dietary PABA restriction in the management of severe malaria in infants.

Standard selection treatments with sulfadiazine limit Plasmodium yoelii host-to-vector transmission

“…In agreement with this, earlier work reported that pABA-deficient diets in rodent hosts is responsible for poor parasite growth and infection, indicating that pABA is an essential host-derived nutrient [10][11]. Indeed, newborn mice on naturally pABA-deficient milk diets suppressed parasitemia with Py17XNL infection and removal of pABA from the rodent diet reduced parasite load [12]. Therefore, it is notable that pABA is present in normal laboratory mouse feed at levels that allow for asexual blood stages to progress without additional supplementation (~175 ug/kg in conventional mouse feed) [9].…”

Prolonged Breastfeeding and the Risk of Plasmodium vivax Infection and Clinical Malaria in Early Childhood: A Birth Cohort Study

“…Exclusive (but not necessarily partial) breastfeeding has been suggested to reduce the risk of P. falciparum infection in neonates and young infants from the Gambia, 2 most likely because maternal milk is deficient in para-aminobenzoic acid, which is required for de novo folate synthesis by malaria parasites. 32,33 More recent evidence that exclusive breastfeeding protects infants from clinical malaria comes from a birth cohort study in Malawi 34 and cross-sectional surveys in the Democratic Republic of Congo 35 and Cameroon, 36 all in Sub-Saharan African settings where P. falciparum is the dominant human malaria parasite.…”

Standard Selection Treatments with Sulfadiazine Limit Plasmodium yoelii Host-to-Vector Transmission

“…In agreement with this, earlier work reported that pABA-deficient diets in rodent hosts are responsible for poor parasite growth and infection, indicating that pABA is an essential host-derived nutrient ( 10 , 11 ). Indeed, newborn mice on naturally pABA-deficient milk diets suppressed parasitemia with Py17XNL infection and removal of pABA from the rodent diet reduced parasite load ( 12 ). Therefore, it is notable that pABA is present in normal laboratory mouse feed at levels that allow for asexual blood stages to progress without additional supplementation (~175 μg/kg of body weight in conventional mouse feed) ( 9 ).…”