A new meningitis screening test could help cut South Africa’s HIV/AIDS deathtoll

A photomicrograph of the Cryptococcus fungus. www.einstein.yu.edu

South Africa has launched the world’s largest national screening programme to detect cryptococcal meningitis – an AIDS-defining fungal opportunistic infection in patients living with HIV – sooner than it would have been picked up in the past. The fungus (Cryptococcus) can be detected by dipping a test strip in leftover blood collected for CD4 testing. More than 250 000 patients at high risk for cryptococcal meningitis, but with no symptoms, will be screened in the country annually and those who screen positive will be treated with antifungal medicines. Health and medicine editor Candice Bailey spoke to Nelesh Govender about the significance of this new screening programme.

What is cryptococcal disease and why should we know about it?

This is a fungal meningitis that usually occurs in people who have AIDS. The fungus called Cryptococcus is found in the environment and while everyone is exposed to it, usually only those who have weakened immune systems become ill. In immuno-suppressed people, the fungus reactivates or “wakes up” and causes meningitis. This type of meningitis can’t be passed from person to person. Three different antifungal medicines are needed to treat this meningitis. South Africa has only registered two of these medicines for use so far.

The fungus has a very large jelly-like capsule that covers it. This capsule protects Cryptococcus from the body’s immune system by allowing it to hide in plain sight. When Cryptococcus reactivates in the body and starts spreading through the bloodstream, it drops parts of its capsule in the blood. The dipstick test is able to detect these pieces of the fungus (also called cryptococcal antigen) in the blood several weeks to months before the fungus crosses from the blood into the brain and causes meningitis.

Cryptococcal meningitis is very common. There are thousands of cases of this type of meningitis in South Africa every year. After tuberculosis, it is the most common cause of death in people with AIDS in sub-Saharan Africa. Almost seven in 10 patients with cryptococcal meningitis die in sub-Saharan Africa. Annually this amounts to about 125 000 people.

What are the challenges around cryptococcal disease and how does the new test help?

Many people living with HIV are still at very high risk of cryptococcal meningitis even though antiretroviral treatment is now widely and easily available in South Africa. One of the main problems is that many patients only start antiretroviral treatment when their CD4 count is below 200, which is very late. At this point, their immune system is very weak. In addition to the late start, another challenge is that some people do not stick to their antiretroviral treatment regime. This means that that their immune system weakens again.

Before the blood dipstick test was introduced, people were only tested for cryptococcal disease when they had symptoms of meningitis such as a severe headache or confusion. This was problematic because at this stage, the fungus had grown or multiplied in the brain, the meningitis was already very advanced and the risk of dying was very high even with antifungal treatment. In addition, people with meningitis need to be admitted to hospital for two weeks to get antifungal medicines through a drip.

The arrival of the dipstick test means that patients can be screened cheaply and easily before they present with symptoms of meningitis, but when they have low CD4 counts. The test picks up those jelly-like pieces of the capsule in the blood so that people can be treated with antifungal medicines before they develop meningitis. This also avoids costly hospital admissions.

So when patients have a CD4 count that is below 100, the laboratory will automatically do the dipstick test to pick up the fungus. Picking up this disease at an earlier point in its trajectory is important to reduce AIDS deaths.

In South Africa, an estimated 250 000 patients living with HIV and with a CD4 count below 100 will be screened for the cryptococcal antigen annually.

Are there cryptococcal meningitis cases in any other countries?

In developed (resource-rich) countries, cryptococcal meningitis was a common AIDS-defining opportunistic infection before antiretroviral therapy became available. In the late 1980s and 1990s, highly active (or combination) antiretroviral treatment resulted in a big reduction in disease burden. New antifungal medicines to treat cryptococcal meningitis were also introduced.

When antiretroviral treatment became widely available in 2004 in South Africa, we expected to see a drop in case numbers. While the number of cases has largely stabilised over the last five years or so, South Africa has not been able to reduce the caseload significantly because we still have a very big population with low CD4 counts at high risk of this disease.

What is next?

Screening for cryptococcal antigen, early antifungal treatment of those who screened positive and antiretroviral treatment reduced deaths by almost 30% among people with a CD4 count below 200 in a recent large study.

But the real world is always more complex than a study setting. So in addition to rolling out the new laboratory screening test for cryptococcal disease, several extra interventions will be explored by the National Institute for Communicable Diseases over the next five years to ensure that the programme has the most impact on reducing deaths. This includes intensive training of health care workers, educating patients about “crypto” and other opportunistic infections, ensuring that antifungal medicines are delivered to clinics and enhancing the delivery of screening test results to health care workers.