By Alberto Leny

David Meya, an infectious disease physician at Makerere University’s College of Health Sciences and a DELTAS Africa programme fellow, is conducting research on improving the management of fungal meningitis in HIV patients.

His research on how to prevent fungal meningitis in the context of HIV infections interventions has contributed to the shaping of World Health Organization (WHO) policy as well as HIV guidelines around the world.

David Meya

Meya is currently a PhD fellow with the Training Health Researchers into Vocational Excellence in East Africa (THRiVE) consortium, one of the awardees of the DELTAS Africa programme supporting Africa-led development of world-class researchers and scientific leaders in Africa.

THRiVE strives to stimulate research excellence and progression to research leadership and opportunities to researchers in the consortium composed of Gulu University, Kilimanjaro Christian Medical Centre, Makerere University, National Institute of Medical Research-Mwanza, Uganda Virus Research Institute and International Centre of Insect Physiology and Ecology, University of Cambridge and London School of Hygiene and Tropical medicine.

The network and collaborations with partners have yielded more than 400 publications. The training and mentorship for post-doctoral and PhD fellowship training has supported 79 fellows and 300 first-class potential supervisors with expertise in research since 2010.

The DELTAS Africa programme is being implemented by The African Academy of Sciences (The AAS) through its programmatic platform, the Alliance for Accelerating Excellence in Science in Africa (AESA) with the support of Wellcome Trust and the UK Department for International Development (DfID).

For over a decade, Meya has led faculty collaboration between Makerere, where he attained his Master’s degree in internal medicine in 2005 and the University of Minnesota, where he is an adjunct professor, on research projects. He is co-chair of a partnership which houses “Uganda Hub”, a platform to address global health challenges.

He has been a lead investigator on clinical research projects related to HIV-related meningitis, with additional interest in sepsis research in collaboration with the London School of Hygiene and Tropical Medicine.

“In the first six years I benefited from training under THRiVE-1 in a research collaboration group as I built my own skills as an independent investigator, because we don’t have our own funding for research. As a clinician, I am learning skills in THRIVE-2 as part of the training for basic scientists to see clinical observations – thinking how to solve them from the perspective of basic science,” notes Meya.

He describes it as a “bench-to-bedside” approach to solving clinical problems. “It is important to solve our own problems in Africa. The DELTAS Africa programme has given me the opportunity to learn how to be a better mentor and to encourage younger scientists to successfully define their career paths.”

This is part of the challenges in Africa, with the limited capacity to absorb all the training needs and money to pay trainees. He commends DELTAS Africa for engaging with universities around Africa to open up opportunities for trainees when they complete their training for a “multiplier effect” as they become mentors and train younger scientists.

In his research Improving outcomes of HIV-related meningitis in sub-Saharan Africa, Meya observes that over the last decade, there have been tremendous strides in improving outcomes of individuals affected with HIV, especially in terms of access to long-term Antiretroviral Therapy (ART) and improved life expectancy.

Although there have been rapid and significant declines in the incidence rates of opportunistic infections in the developed countries, this decline has not been dramatic in sub-Saharan Africa.

One such infection is caused by the fungus, Cryptococcus, which has sadly not seen the expected dip in number of cases even with the rapid rollout of ART across Africa reaching the thousands and millions that continue to be infected by HIV daily.

He has been involved in clinical research of central nervous system infections and complications with a focus on HIV Immune Reconstitution Inflammatory Syndrome (IRIS). He has led epidemiological and translational research studies as well as randomized clinical trials in the prevention of Cryptococcus meningitis.

Meya has a specific interest in public health interventions to prevent meningitis at population level and has advocated for Cryptococcal antigen (CrAg) screening as a strategy to reduce deaths and hospitalizations from Cryptococcal meningitis.

Sub-Saharan Africa bears the burden of this disease (73%), with approximately 136,000 deaths annually. “Over the last six to eight years, I have been supported by the Wellcome Trust Deltas Africa programme to conduct research aimed at improving the grim outlook of cryptococcal disease in sub-Saharan Africa through observational, translational science and clinical trials.”

“The cryptococcal outcomes on ART (COAT) trial, for which I was the Uganda principal coordinator, was conducted in Kampala, Mbarara in Uganda and Cape Town in South Africa, enrolled 177 participants with cryptococcal meningitis,” he adds.

“We were able to demonstrate that starting ART too soon (7-11 days) after the diagnosis of cryptococcal meningitis was detrimental, with lower survival rates (55%) compared to starting 4-6 weeks after initiating antifungal therapy (survival rate 70%),” recalls Meya. The clinical trial was carried out between November 2010 and March 2013.

“This definitive trial answered the question on the optimal timing of ART on cryptococcal meningitis and led to a policy shift in WHO guidance.

“Similarly, during this trial, we demonstrated that electrolyte pre-supplementation rather than waiting to replace deficiencies in electrolytes following administration of the antifungal drug, amphotericin, for cryptococcal meningitis prevented mortality during induction treatment of cryptococcal meningitis. This strategy too was adopted in the WHO guidelines.”

Meya believes implementing these two clinical strategies have prevented thousands of cryptococcal-related deaths. More recently during his PhD training he explored immunopathogenesis of immune reconstitution inflammatory syndrome, a complication of starting ART in which patients previously treated successfully for an opportunistic infection seemingly worsen after they initiate ART.

“I demonstrated through immunology assays using cells obtained from spinal fluid and blood that during complication, there is specific immunological signature and type of cell that migrates into the central nervous system, making the spinal fluid more inflammatory from the migration of these innate immune cells known as monoclytes.”

Meya was the principal investigator on a randomised clinical trial in 17 clinics in Uganda to evaluate the screen and treat strategy for cryptococcal antigenemia in patients to determine the effectiveness of this intervention on decreasing mortality among the general population of HIV-infected patients with CD4<100 cells/mL.

Cryptococcal disease is not the only cause of HIV-related meningitis in sub-Saharan Africa. Tuberculosis (TB) remains the etiological agent in 10-15% of HIV-associated meningitis. As part of the meningitis screening, the researchers investigated the utility of newer rapid diagnostic tests. These are unique tests that employ DNA amplification techniques to determine the presence of Mycobacterium Tuberculosis that causes human Tuberculosis. This work helped consolidate the Xpert Ultra as the recommended test for tuberculosis meningitis.

He says DELTAS Africa is uniting Africa through science and research by bridging the divide between Anglophone and Francophone Africa, investing in actual research, and also training people in research.

“Twenty years from now, I would wish to comfortably look back, and say, see how research has impacted on people’s lives. But it is early days,” says Meya.