The development of TH2 responses from infancy to 4 years of age and atopic sensitization in areas endemic for helminth infections

BACKGROUND: Helminth infections and allergies are associated with TH(2) responses. Whereas the development of TH(2) responses and allergic disorders in pediatric populations has been examined in affluent countries, no or little data exist from low income regions of the world. The aim of this study is to examine factors influencing the development of TH(2) responses of children born in areas endemic for helminth infections and to relate these factors to atopic sensitization at 4 years of age. METHODS: Data were collected from pregnant mothers on helminth infections, education and socioeconomic status (SES). Total IgE, IL-5 in response to mitogen, and helminth antigens were measured in children at 2, 5, 12, 24 and 48 months of age. Skin prick testing (SPT) and allergen-specific IgE were determined at 4 years of age. RESULTS: Strong TH(2) responses were seen at 5 months of age and increased with time. Although maternal filarial infection was associated with helminth-antigen specific TH(2) responses, it was low maternal education or SES but not helminth infection, which was associated with the development of high total IgE and PHA-induced IL-5. At 4 years of age when allergen reactivity was assessed by SPT, the high general TH(2) responses did not translate into higher prevalence of SPT. The risk factor for SPT reactivity was low maternal education which decreased the risk of SPT positivity to allergens (adjusted OR, 0.32; 95% CI, 0.12 – 0.87) independently of maternal filarial infection which tended to reduce the child’s risk for being SPT positive (adjusted OR, 0.35; 95% CI, 0.07 – 1.70). CONCLUSIONS: In areas endemic for helminths, potent TH(2) responses were seen early in life, but did not translate into a higher SPT reactivity to allergens. Therefore, in many parts of the world TH(2) responses in general and IgE in particular cannot be used for diagnosis of allergic diseases

Effects of sex and maternal immunity on protozoan and helminth infections

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