Ongoing Research at the Center for International Health Research
Ongoing Research: Faculty at CIHR work across the globe including multiple sites in Sub-Saharan Africa, The Philippines, and Brazil.
Current studies focus on:
- Rational identification of drug and vaccine targets for malaria, based on a field to bench to field model.
- Identifying and mapping malaria parasite resistance to current drug regimens.
- Understanding mechanisms of morbidity in the context of the parasitic worm, schistosomiasis, with a focus on pregnant women and children, and identifying optimal ways to address these.
- Optimizing diagnostic tests and treatments for children with sickle cell disease in Sub-Saharan Africa.
- Advancing care for adolescents with Tuberculosis (TB) globally: understanding disease in this age group and optimizing therapy.
- Rational identification of drug and vaccine targets for schistosomiasis based on field to bench to field model.
An In-Depth Look at Our Research
The CIHR conducts studies addressing the mechanisms of parasitic disease morbidity. A recently completed R01 study has addressed mechanisms of morbidity in S. japonicum infection and identified potential vaccine candidates. This study employed a population-based, longitudinal design which characterizes morbidity in the study population over time, relates this to basic biologic mechanisms of disease (such as cytokine-mediated under-nutrition and dyserythropoiesis), assesses host resistance to infection over time and relates this to immune responses to identify potential vaccine candidates. It also identifies host factors that may modify development of immune responses to vaccine candidates. A follow-on R01 is using these sera and epi data to identify new vaccine candidates.
A recent pilot study conducted in the Philippines has examined the impact of S. japonicum infection on pregnancy outcomes and identified potential mechanisms mediating the poor birth outcomes in S. japonicum-infected women. This work identified placental inflammatory responses and alternations in iron metabolism in the context of S. japonicum as potential mediating factors. That study laid the groundwork for an R01 that will utilize a randomized controlled design to more precisely measure the impact of this infection on maternal and birth outcomes. This work will also characterize alterations in iron metabolism, nutritional parameters and placental immune responses that may be responsible for adverse birth outcomes. This study is one model of cooperation between clinician scientists and basic immunologists designed to understand mechanisms of morbidity that should, in turn, guide therapeutic options for pregnant women with this infection and other inflammatory diseases during pregnancy.
A recent NIH-funded study in malaria further exemplifies the CIHR's trans-disciplinary approach to vaccine development. A cohort of individuals living in a P. falciparum holoendemic area of Kenya were enrolled and treated with anti-malarials and the heterogeneity in reinfection was measured over four months. Sera from the ten most resistant and ten least resistant individuals was used to screen a parasite cDNA library to identify parasite genes that encode proteins that are only recognized by the resistant individuals.
Three vaccine candidates were identified using this approach and an R01 application is being prepared to test the hypothesis that antibody and cytokine responses to these antigens will predict resistance to reinfection. This work culminated in a paper published in Science.