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KAMPALA — Recent studies on HIV associated meningitis, commonly caused by the fungus, Cryptococcocus, show that close to half of those infected with this meningitis die if they don’t receive timely treatment.
Over the last few years, studies on Cryptococcal meningitis have been conducted by Dr. David Meya, who recently completed his tenure as a post-doctoral research fellow with THRiVE (Training Health Researchers into Vocational Excellence in East Africa).
His studies suggest that despite the availability of antiretroviral therapy (ARVs), this opportunistic infection remains a significant health problem and is associated with death among people living with HIV. Cryptococcal meningitis is an invasive fungal infection that affects the membranes lining the brain and spinal cord. A person with this fungal meningitis may present with severe headache, stiff neck, seizures, visual impairment and altered consciousness.
These symptoms develop gradually after weeks of being exposed to the fungus. This HIV related fungal meningitis is more common among men aged 25 to 37.
Dr. Meya attributes the stagnating number of people with cryptococcal meningitis in Uganda to late diagnosis and delay in starting treatment.
“Often, people present late to the hospital when the fungal infection has already developed into meningitis. This is because the symptoms may delay to present themselves and patients may get treated for other infections like suspected malaria if the healthcare workers do not suspect the possibility of this fungal infection ,” Dr. Meya said in an interview.
On average, 250- 300 patients with cryptococcal meningitis present to Kiruddu hospital. Some of these succumb to the disease because they present very late. The actual cost of treating this infection could be as much as $400-$500 (Shs. 1.4-1.8M) over two weeks when treated with antifungal drugs such as Fluconazole and Amphotericin.
Over the last few years, studies also reveal that those who recover from this fungal meningitis and are started on ARVs present with re occurrence of symptoms of meningitis.
Globally, among people living with HIV, almost 6-10% are infected with this fungus. Previously, among those who survived this fungal meningitis, almost half returned with recurrence of symptoms as a result of a phenomenon referred to as Immune Reconstitution Inflammatory Syndrome (IRIS). That proportion has now fallen to approximately 10-15% due to improved antifungal treatment. Explaining why these symptoms may reoccur, Dr. Meya says that it is a sign of one’s immune system recovering following the ARV treatment, albeit responding inappropriately to the fungus that may still be present in the body.
Explaining this phenomenon, which Dr. Meya studied as part of his THRIVE funded PhD, he says:
“As the immune system recovers after one has recently initiated ARVs, certain types of immune cells encounter residual fungus, which could be in the brain, resulting in an inappropriate immune response causing the symptoms to reoccur.”
The IRIS phenomenon leads to fatal outcomes in about a third of those who experience it. To study the phenomenon, Dr. Meya looked at data from the Infectious Diseases Institute (IDI) of patients with a CD4 of less than 100 who had been screened for this fungal infection between 2004- 2010.
He found that of those who had received antifungal therapy (when they had evidence of this fungal infection), 70% were alive two years later while all those who had not received antifungal therapy had died. This study also showed that screening all HIV infected patients with a CD4 of less than 100 for this fungal infection was cost effective and could save lives. Current guidelines by the Word Health Organization recommend HIV infected individuals with CD4 counts less than 200 should be screened for cryptococcal disease. This practice is now part of Ugandan guidelines.
Dr. Meya is currently leading a trial at IDI to determine whether other antifungal regimens could prevent people from developing this meningitis.
This trial followed a CDC funded trial at the Institute (ORCAS trial), which revealed that 25% of HIV infected individuals with a CD4 less than 100 and cryptococcal infection went on to develop fungal meningitis or died despite the antifungal therapy they received for 10 weeks.
“For those who develop overt meningitis, we also hope to conduct a multi-center clinical trial to determine whether the course of treatment can be shortened from two weeks to one week while improving survival,” Dr. Meya said.
In order to curb the stagnating number of people acquiring cryptococcal meningitis, Meya advises government to provide the anti-fungal drugs-Amphotericin and Fluconazole in all public health facilities and for health facilities to screen people whose CD4 count is less than 200.
