Two UCSF teams have received a total of $16 million from the Bill & Melinda Gates Foundation to study new ways to significantly reduce childhood mortality and disease in developing nations.
An international team led by Thomas M. Lietman, MD, associate director of the UCSF Francis I. Proctor Foundation for Research in Ophthalmology, received $12 million for a multi-year trial to study the effectiveness of mass oral administration of the antibiotic azithromycin in reducing childhood mortality in Niger, Tanzania and Malawi - three nations with severe childhood mortality rates.
A second team, led by James H. McKerrow, MD, PhD, professor of pathology and pharmaceutical chemistry, received $4.3 million to identify and develop a drug that kills the parasitic roundworms known as filiariae that cause river blindness, the leading cause of blindness in parts of West Africa.
If successfully developed, the same drug will have a high probability of killing the closely related parasite that causes lymphatic filariasis, or elephantiasis, a crippling and disfiguring disease that affects millions of people in Africa, Asia, the Indian subcontinent and South America.
Expanding Prevention of Child Mortality
Lietman's project is based on an earlier study in which communities in Ethiopia that received mass doses of azithromycin to treat trachoma - a strain of chlamydia that causes blindness - experienced an overall reduction in childhood mortality from all causes.
"Now we need to see whether that effect can be replicated in areas that don't have a lot of trachoma," said Lietman, a UCSF professor in the departments of Ophthalmology and Epidemiology & Biostatistics. "If we want to make a public health difference, we have to show that we can reduce childhood mortality in areas that are not otherwise receiving mass antibiotics."
Community-wide antibiotic administration is common in African nations where trachoma is usually found, he said.
Preschool children in Lietman's study will be randomized to receive either a cherry-flavored oral suspension of azithromycin or a placebo every six months for two years. If there is a significant reduction in mortality in the communities that receive the antibiotic, the study will be extended for another two years and all communities will receive antibiotics.
Lietman and his team will closely monitor for development of antibiotic resistant diseases in the communities treated with azithromycin. "It's a complicated question," he said. "We think we will select for antibiotic resistance. However, many of us believe that might be a price worth paying if there is truly a reduction in childhood mortality."
Lietman noted two mitigating factors with regard to antibiotic resistance. In communities treated with azithromycin for trachoma, resistance to the antibiotic gradually disappears over the two years after such treatments stop. In addition, he said, azithromycin belongs to a class of antibiotic that is rarely used in sub-Saharan Africa, so even if an infection is resistant to azithromycin, it could still be treatable by one of six other classes of antibiotics.
Finding New Drugs for Parasitic Disease
The goal of McKerrow's study is to find a drug that kills the adult form of the parasitic filarial worm, which is spread by a fly that breeds near fast-flowing rivers.
When the fly bites, it deposits larvae under the skin that grow into worms several inches long. The parasite associated with river blindness attacks the eye, while its relative that is responsible for lymphatic filariasis blocks the lymphatic channels in the groin, resulting in extreme swelling of the lower extremities.