Effects of sex and maternal immunity on protozoan and helminth infections

Abstract

Protozoan and helminth parasites infect billions of people throughout the world and are responsible for significant morbidity and mortality of millions of people annually. Gender and cultural differences account for some dichotomy in the prevalence and intensity of infection between male and female humans. However, intrinsic differences in the biology, including the endocrine and immune systems, of male and female humans exert profound influence on disease pathogenesis. Generally, females are more resistant than males to many parasitic diseases, although exceptions exist, such as some cestode infections and Toxoplasma gondii. However, during pregnancy when a number of hormones are significantly increased and the immune system altered, females tend to be more susceptible than nonpregnant females and males to a number of parasitic infections. This is most notable for infections that rely on a helper T cell type 1 (Th1) response for resolution that is antagonized by the Th2/regulatory T (Treg) environment induced during pregnancy. As a corollary, infections that induce a strong Th1 response can disrupt pregnancy through ablating pregnancy-induced immune alterations. Some evidence is emerging that children born to mothers with parasitic infections can have lesions in their immune systems leading to tolerance or allergy as well as potential psycho-neurological changes leading to disease. There is increasing evidence that pharmacokinetics of drugs including anti-infectives can vary between the sexes. Many drugs used to treat parasitic infection (particularly protozoan infections) are far from ideal and have associated side effects. Tailored optimization of dosing regimens for men, women, and pregnant women for these drugs might be especially beneficial. New interventions optimized for sex and endocrine conditions could have greatest impact on the most disadvantaged groups in terms of susceptibility of disease including men and pregnant women.