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Research from UNC Project-Malawi's Cecilia Kanyama Prompts Change in WHO Guidelines

March 22, 2018

Cecilia Kanyama is an internal medicine physician and infectious diseases researcher with the University of North Carolina at Chapel Hill School of Medicine’s UNC Project-Malawi. She also teaches at the University of Malawi College of Medicine. She was recently part of a research team investigating cryptococcal meningitis. Their results prompted the World Health Organization to change its treatment guidelines.

Q. How long have you worked at UNC Project-Malawi?

A. I have worked with UNC Project-Malawi since 2003. From 2008 to 2012, I was fully supported by UNC Project for my postgraduate training in internal medicine at the University of Cape Town in South Africa. I returned to the Project in 2013.

Q. Why did you want to become a physician-researcher?

A. This is the ultimate work satisfaction for me – to be a physician and treat my patients with expertise, yet at the same time to be able to identify clinical problems and change the clinical practice policies through evidence-based medicine.

Q. What attracted you to the field of infectious diseases?

A.  One cannot practice medicine in low- and middle income countries without a thorough knowledge of infectious diseases since this is the most common reason for hospital attendance, mortality and morbidity. For example, at our hospital, Kamuzu Central Hospital, 63 percent of medical admissions are due to infectious diseases. Of course, non-communicable diseases are on the rise in Malawi, but still the bulk of hospital attendance remains infectious diseases.

Q. You are an internal medicine doctor and infectious diseases researcher at UNC Project-Malawi. You also teach at the Malawi College of Medicine. What do you like best about these jobs?

A.  I like the fantastic opportunity to do ground-breaking, clinical research and contribute to science and health policies in Malawi. And at the same time, I get to impart the zeal in young, upcoming doctors for clinical research whilst teaching them evidence-based medicine.

Q. You recently had a paper published in the New England Journal of Medicine about Cryptococcal meningitis. Do you see this disease in your practice? How does it affect patients?

A. Cryptococcal meningitis is the number one cause of adult meningitis in Malawi. About 70 percent of culture positive adult meningitis cases are due to cryptococcal meningitis. Cryptococcal meningitis has an insidious course, and I see a lot of patients who have been ill with severe headaches weeks before presentation and only present later with unbearable headaches or complications of this disease e.g convulsions, blindness, focal neurological deficits. Usually the patients buy over the counter analgesics for a long time before presentation and this has health and cost implications to patients.

At the moment, 5FC is not available in Malawi for the oral option of treatment. Therefore, all cryptococcal meningitis patients are required to be hospitalized for intravenous infusion and some laboratory monitoring for the duration of treatment. This has a lot of social and financial implications. About 50 percent of these patients have just had a recent diagnosis of HIV and they require a lot of psychosocial support. We have also seen deafness, blindness and memory loss post-treatment.

Q. What did your study find?

A.  The Advancing Cryptococcal meningitis Treatment for Africa (ACTA) trial’s aim was to find alternative and more practical treatments to cryptococcal meningitis. When we started the study, the World Health Organization (WHO) recommendation was an induction phase of treatment with two weeks Amphotericin B (AmB) and Flucytosine (5FC). These drugs are either unavailable in the case of 5FC, or relatively unsafe to give in resource-limited settings (AmB). AmB requires prolonged hospitalization and laboratory monitoring.

The results of the ACTA trial demonstrated firstly that short course (one week) AmB and 5FC reduced mortality from the 70 percent found in routine care in many resource-limited setting down to 24 percent. Secondly, the oral combination of two weeks’ 5FC and Fluconazole performed well and reduced mortality down to 35 percent. Lastly, we showed that 5-FC, rather than Fluconazole, is better and the best companion drug to AmB.

In conclusion, we have identified alternative combination treatment options: 1) Short course (one week) AmB and 5FC, and 2) oral combination therapy of two weeks’ 5FC and Fluconazole. These findings have now been incorporated into WHO guidelines for management of cryptococcal meningitis.

Q. Are there other research questions you would like to see answered?

A.  We have a follow up trial to ACTA. This is called the AMBITION study, which is looking at giving a single dose of ambisome instead of seven days of amphotericin B for treatment of cryptococcal meningitis. We look forward to conducting this trial and its outcomes.

We need more implementation research in this field. I would like to see cryptococcal disease screening at health centers with treatment of cryptococcaemia and see if this will have an impact on hospitilization and mortality from cryptococcal disease.

I am also interested in clinical research focusing on optimizing diagnosis and treatment for tuberculosis meningitis.

Q. When you are not working, what do you like to do for fun?

A. I love animals, and I usually visit my animal farm or get close to nature and see animals in the wild.

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