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Advisory Committee Chair

Pauline E Jolly

Advisory Committee Members

T Mark Beasley

Emily B Levitan

J Martin Rodriguez

Jonathon K Stiles

Document Type

Dissertation

Date of Award

2016

Degree Name by School

Doctor of Philosophy (PhD) School of Public Health

Abstract

Malaria remains an important public health problem, with over three billion people at risk of infection and as many as 214 million new cases each year. Of particular concern is the effect Plasmodium falciparum malaria has on reproductive health. Malaria is responsible for a wide array of adverse birth outcomes including infant death, low birth weight, preterm delivery and small for gestational age. The mechanism by which malaria influences adverse birth outcomes remains poorly understood. Cross-sectional data from 291 women delivering infants in Ghana are used to investigate whether malaria during pregnancy was associated with select cytokines or angiogenesis factors and to evaluate which factors were associated with adverse birth outcomes. Notably, in this study population each of the malaria positive (54.3%) women were asymptomatic. With regards to the association of malaria with cytokines and angiogessis factors, levels of G-CSF (p<0.001), IL-10 (p=0.005), TGF-α (p<0.001), and TNF-β (p<0.001) were significantly higher in malaria negative women. Malaria positive women had higher median ratios of INF-ɣ:G-CSF (p<0.001), INF-ɣ:IL-10 (p<0.001), TNF-β:IL-10 (p=0.038), TNF-α:G-CSF (p<0.001), and TNF-α:IL-10 (p=0.030). High levels of cytokines or angiogenesis factors were tested to see if they interacted with malaria to influence adverse birth outcomes. Overall, 29.6% of women had an adverse birth outcome. With regards to factors associated with adverse birth outcomes, the frequency of adverse birth outcomes did not differ between malaria positive and malaria negative women (p=0.94). Significant associations between adverse birth outcomes were noted with antenatal care visits (p<0.01), malaria prophylaxis (p<0.01), lower hemoglobin levels (p<0.01), and elevated levels of TNF-β (p=0.04) and INF-γ (0.04). Additive or multiplicative interactions between malaria and any of the biomarkers were examined and found to be null. With regard to levels of cytokines and angiogessis factors, malaria positive women in the study population had significantly higher Th1 to Th2 ratios and demonstrated a lower Th2 shift. Asymptomatic malaria positive women did not have significantly more adverse birth outcomes. Tests for interactions between malaria and select biomarkers were similarly non-significant. TNF-β and INF-γ, each inflammatory cytokines, were associated with adverse birth outcomes in asymptomatic infections.

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