Pia Wintermark of McGill University in Canada and Cally Tann of the London School of Hygiene & Tropical Medicine in the United Kingdom will establish a pilot cohort in Uganda of term newborns who suffered from asphyxia at birth, which means that their brain and other organs did not receive enough blood or oxygen, and conduct a clinical test of a novel neurorestorative agent (i.e., to repair brain injuries) to see if it can improve early brain development in this setting. Birth asphyxia and the resulting neonatal encephalopathy is the third leading cause of mortality in infants under five and leads to significant brain damage and long-term neurodevelopmental morbidities. In a rat model of term neonatal brain damage, they found that a compound, sildenafil, reduced brain damage and inflammation, and increased nerve cell growth. This compound has already proven safe for use in humans for other purposes. They will first assemble a pilot cohort of 100 neonates with neonatal encephalopathy in Uganda, and clinically evaluate them over the first three months of age to better characterize the disease in this setting. From this cohort, 30 newborns will be selected to test whether daily treatment of sildenafil from day 2 to day 9 of life can improve brain growth and development and is a feasible and acceptable neurorestorative treatment strategy in this setting.

Anne CC Lee and Mandy Brown Belfort of Brigham and Women's Hospital in the U.S. along with Stéphane Sizonenko and Petra Huppi of the University of Geneva in Switzerland will test whether lactoferrin, a breast milk nutrient, can promote growth and reduce injury in the developing infant brain. Of the 15 million annual preterm births, almost a million of the surviving babies have severe neurological defects such as cerebral palsy. However, there are limited treatments available. Breast milk has a positive effect on the infant brain, but the mechanisms for this are unclear. Their preliminary data showed that lactoferrin, a glycoprotein found in breast milk, has a neuroprotective effect in several rat models of neonatal brain injury. They will build on this to study the effect of different concentrations of lactoferrin in the rat models, as well as assaying candidate inflammation, cell death, and neurotrophic factors to identify the molecular mechanisms involved. They will perform a human observational study to associate the different levels of lactoferrin found in breast milk samples from a cohort of mothers of preterm infants at Brigham and Women's Hospital with the infant's brain development as assessed by magnetic resonance imaging. They will also measure lactoferrin levels in samples collected from 100 mothers in Bangladesh to see how they compare. Together, they will generate essential data on lactoferrin for future human clinical trials in low- to middle-income countries.

Iruka Okeke of the University of Ibadan, College of Medicine in Nigeria and Kat Holt of Monash University in Australia will set-up a remote laboratory that uses nanopore sequencing as a low-cost, portable method to monitor the spread of antimicrobial resistance in rural areas of Africa and combine it with genome editing tools for more rapid diagnosis and improved treatment. Antimicrobial resistance (AMR) occurs when pathogens are able to survive treatments that previously would have killed them. Infection persists in these patients and spreads to others in the community, increasing both the risk of serious complications and the economic costs. To combat AMR, it needs to be tracked locally and quickly enough to inform treatment. However, traditional tracking methods are slow, and difficult to use in rural settings because of limited resources. Nanopore sequencing technology is a highly portable method of sequencing DNA that is suitable for resource-poor settings. They will setup a prototype minimal bacterial genomics lab at a provincial hospital laboratory in Africa, and use nanopore sequencing to catalog pathogens collected from patients and monitor AMR. They will also combine the sequencing with a genome editing tool - CRISPR-Cas - to enrich for known resistant pathogens and enable much faster diagnosis directly from blood or stool samples. Once optimized in the initial location, the remote lab can be recreated in other areas of Africa.

Mohlopheni Marakalala of the Africa Health Research Institute in South Africa will study the role of specific proteins associated with immune cell death in tuberculosis patients to better understand how the disease progresses and help develop new diagnostics and therapies. Tuberculosis (TB) is a bacterial disease that causes 1.5 million deaths per year, mostly in poor countries. Understanding how the human immune system responds to TB infection could help develop more effective, host-targeted treatments. Granulomas - tissues that form as a result of inflammation - are commonly seen in the lungs of TB patients. Their characteristics change as the disease progresses and they can cause severe lung damage. Granulomas are thought to be formed by the death of white blood cells called neutrophils, which are also abundant in the airways of patients. He will study granulomas isolated from patients at different stages of the disease to identify proteins linked to neutrophil cell death and see if they are linked with lung damage and disease progression. He will then determine whether the levels of these proteins in the blood can be used as disease biomarkers for the early detection of TB. Lastly, he will use molecular genetic techniques to reduce the level of these proteins in neutrophils and evaluate the effect on TB infection to see if the approach could be exploited as a potential therapy.