October 11, 2015

Research Roundup: TB R&D, malaria in pregnancy, and treatments for filarial diseases

Senior Program Assistant

A new briefing paper from the Infectious Diseases Society of America Center for Global Health Policy explores the state of tuberculosis (TB) research and development (R&D) including challenges for products currently in the pipeline and gaps in TB research. The paper notes that existing TB diagnostic tools are not practical for low-resource settings, as the leading device is expensive and requires electricity and skilled health workers. Alternative diagnostic approaches are unreliable, missing nearly half of cases, and there’s a paucity of tools to detect drug-resistant strains. In terms of treatment, there is very limited access to novel drugs, due in part to delayed regulatory review and delivery. While the report notes that the “world still waits for a significant tuberculosis vaccine breakthrough,” more than a dozen experimental vaccines are currently being tested in clinical trials.

New research suggests that malaria in pregnancy could impact fetal brain development, which is particularly concerning as pregnant women are at increased risk for malaria. The study, which was conducted in mice, suggests that a mother’s immune response to malaria disrupts the production of certain proteins involved in brain development, resulting in depression or cognitive disorders. Upon further investigation, the team was able to prevent the immune system disruption and successfully prevent any brain damage. While this approach would be impractical and too expensive for scale-up in humans in low-resource settings, the team plans to confirm the phenomenon in humans and search for a safe, affordable alternative.

Lymphatic filariasis (Photo: CDC)
A patient with lymphatic filariasis (Photo: CDC)

Last week, three researchers were awarded the Nobel Prize for Physiology and Medicine for discovery of artemisinin and avermectin, the leading treatments for malaria and two filarial diseases caused by roundworm parasites: lymphatic filariasis and onchocerciasis. Both treatments were identified in the 1970s and are currently facing challenges: resistance to artemisinin has been growing and avermectin treats the symptoms of these filarial diseases by killing the larvae, but is unable to kill the adult worms, ultimately requiring years of treatment. A team led by Professor Mark Taylor of the Liverpool School of Tropical Medicine is searching for new ways to treat filarial diseases by targeting Wolbachia, a bacterium that is critical to roundworms’ ability to both mature and elicit the symptoms associated with lymphatic filariasis and onchocerciasis. In the 1990s, Taylor’s team determined that the antibiotic doxycycline could combat Wolbachia, killing the adult worms in three-fourths of patients within 18 months. However, as ensuring access to doxycycline and retaining patients over 18 months can be challenging, Taylor’s team has been searching for alternatives through the Anti-Wolbachia Consortium (A-WOL), established in 2007 and funded by the Bill & Melinda Gates Foundation. A-WOL has facilitated the screening of nearly sixty thousand chemical compounds and is currently testing the antibiotic minocycline for treatment of lymphatic filariasis and onchocerciasis in Ghana and Cameroon. Early results suggest that minocycline, a more expensive drug, is 50 percent more effective than doxycycline. Neither are safe for use in children or pregnant women, however, Professor Taylor believes the team has enough drug candidates to overcome this challenge, as they’ve developed dozens of promising compounds to test further.