John Muriuki: Iron and life-threatening infections

I am John Muriuki, a postdoctoral research fellow based at the KEMRI Wellcome Trust Research Programme in Kenya. My area of research is nutrition and infection. I mainly focus on iron deficiency and infection.

I previously showed that iron deficiency affects one in two African children. Severe infections are a major cause of hospital admissions and death in African children. The interaction between iron and severe infection is complex and possibly bidirectional. For example, pathogens require iron to grow and multiply. And iron is an important component of immunity against pathogens.

Iron deficiency is treated using iron supplements. However, there are safety concerns regarding giving iron to patients, especially in populations where infections are incident. This is because some studies show that iron supplementation increases the risk of infection. In a paradigm-shifting study, we asked the opposite question. That is whether infection itself causes iron deficiency. To answer this question, we used a novel innovative approach called Mendelian randomisation, which is a natural experiment that uses genetic variations that are randomly allocated at conception to proxy modifiable environmental factors. In our study, we used sickle cell trait as a genetic variation. Sickle cell trait is known to protect against malaria. If malaria causes iron deficiency, then individuals carrying sickle cell trait who are protected against malaria are also likely to be protected against iron deficiency, and that is what we found. Overall, an intervention that prevents malaria by half would also reduce iron deficiency by half, thereby killing two birds using one stone.

Although iron deficiency has been associated with infection or poor clinical outcome, we still do not know whether it is iron itself or the improved iron status that's associated with infection. And to answer the question, I'm applying Mendelian randomisation in two steps. The first step involves conducting the first genome-wide association study of iron status in African children to identify genetic variants that are associated with iron status in this population. So far, I have identified novel African-specific mutations that are associated with iron status or iron deficiency in African children. The second step will be to identify the genetic mutations in large-case control studies of severe malaria, tuberculosis, and bacteraemia to determine whether genetic variation in iron status also influences risk of infection.

Our study on malaria causing iron deficiency is an important finding, and has major clinical or public health implications in that it highlights a shifting in thinking away from the safety concerns of iron supplements to malaria control to prevent iron deficiency. Our genetic work also provides some evidence linking iron deficiency and vitamin A deficiency such that if you are vitamin A-deficient, you're also likely to be iron-deficient. However, we need studies to show the effectiveness of simultaneous supplementation of iron and vitamin A in comparison to iron supplementation alone.

Africa is home for high genetic and environmental diversity, and there are novel variations that are only seen in African population. However, Africans are still underrepresented in global genomic databases. Our work on iron, on the genetics of iron status, we have identified novel African-specific variations that are associated with iron status in African population.

This interview was recorded in January 2024