Hookworm Parasitism Shapes Energy Status and Cardiovascular Disease Risk in Northeast Madagascar

OBJECTIVE: Cardiometabolic diseases are rising in low- and middle-income countries, which also bear high burdens of helminth infection and malnutrition. Untangling the relationships among helminth infection, energy status, and cardiovascular disease is important for reducing these burdens. METHODS: We investigated the interacting risks and moderating variables associated with cardiometabolic health using demographic, health, and hookworm infection data from 874 participants in rural northeast Madagascar. RESULTS: We observed wide variation in body-mass index (BMI) and blood pressure, alongside high prevalences of two helminth infections: the human hookworm Necator americanus (53.6%) and the zoonotic hookworm Ancylostoma ceylanicum (20.4%). We hypothesized that hookworm infections would be associated with reduced BMI and lower blood pressure through energetic and immunomodulatory pathways. Yet, the two hookworm species showed different associations, with N. americanus infection negatively associated with BMI and A. ceylanicum infection positively associated with blood pressure. Wealthier individuals had higher BMI, but this positive effect was attenuated if they were infected with A. ceylanicum. Coinfection with both hookworms did not significantly modify these associations with BMI or blood pressure. Structural equation modeling indicated that N. americanus infection was associated with reduced blood pressure both directly and through its negative association with BMI, while A. ceylanicum infection was associated with increased blood pressure independent of BMI. CONCLUSIONS: Our findings shed new light on the interacting burdens of malnutrition, parasitism, and chronic diseases with implications for public health, highlighting that these associations are dependent on parasite species.