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Improving Treatment for People with HIV and Cryptococcal Meningitis

When Hazel, a Malawian mother of three, experienced a splitting headache weeks ago, she had no idea just how serious her condition was. Shortly thereafter, she began convulsing and passed out. The 40 year-old is lucky to have survived the attack, which turned out to be caused by cryptococcal meningitis.

Cryptococcal meningitis is an infection of the brain and spinal cord caused by a yeast known as Cryptococcus neoformans. The yeast is commonly found in soil and bird droppings and while most people have been exposed to it at some point during their lives, our immune systems are generally able to protect us from any harm.

However, people with compromised immune systems, particularly those with HIV and a poor immunity, are more likely to experience cryptococcal meningitis. The condition results in inflammation and swelling of the brain and can be extremely debilitating and/or painful. If not treated correctly, cryptococcal meningitis causes brain damage and is fatal. In fact, it is a major cause of death in people with HIV in Asia and Africa. Globally, 625,000 people die from the condition each year.

There have been no major advances in the treatment of cryptococcal meningitis since the 1970s. The main drugs we use to treat cryptococcal meningitis are over 50 years old and are often not available in resource-limited countries like Malawi. Even when cryptococcal meningitis patients in Africa receive treatment with the current regimen of antifungal drugs, 70% are likely to die within a year. Given the high mortality rates, new research into augmenting the current treatment regimen offers the greatest potential for improving patient health.

Edson talks with Hazel at Zomba Central Hospital.

Through the Joint Global Health Trials Initiative funded by the UK Department for International Development (DFID), Wellcome Trust (UK) and the Medical Research Council (UK), the Oxford University Clinical Research Unit is collaborating with colleagues in Malawi, Uganda, Vietnam, Laos, Thailand and Indonesia to conduct the CryptoDex clinical trial. This study will find out whether an inexpensive and readily available drug known as dexamethasone may be a practical and beneficial adjunctive treatment for cryptococcal meningitis. Dignitas International and Malawi-Liverpool Wellcome Trust are the study collaborators in Malawi.

This, of course, is welcome news for Hazel, who recounted the ordeal from her bed at Zomba Central Hospital.

“My head felt like it was going to crack open. I felt terrible pain and my neck stiffened,” she said.

“She couldn’t bend the head forward, backward or turn it sideways,” added her mother who stood vigil by her bedside. “I have never seen this disease in our family,” said her mother.

According to Edson Mwinjiwa, a clinician with Dignitas International, the stiffness of the neck occurs in many patients with the condition.

“The patient fails to bend the head towards the chest or turn it sideways. It is caused by an irritation of the nerves in the lining of the brain. It’s not a permanent abnormality. It is treatable and the stiffness may stop within 14 days. The more serious complication of cryptococcal meningitis is the increased intracranial pressure caused by abnormalities in the flow of cerebral spinal fluid (a fluid that cushions the brain around the skull).”

It was Edson who determined that Hazel was suffering from the condition and counselled her to enrol in the trial. Health care providers are able to detect cryptococcal meningitis by testing fluid from a spinal tap.

If treatable, why does cryptococcal meningitis kill so many people in countries like Malawi? Edson offers a few reasons.

“The first signs of the condition are subtle and can be confusing. The symptoms of a headache and fever are quite similar to malaria.”

In addition, Malawi can’t afford the recommended treatment as stipulated by the World Health Organization (WHO). Patients receive a drug known as fluconazole to treat cryptococcal meningitis but the WHO recommends amphotericin B and flucytosine, a more powerful drug regimen.

“We don’t have amphotericin B and flucytosine in Malawi. It is too expensive,” says Edson. The laboratory infrastructure required to monitor the use of these drugs is also not always available.

Edson also remembers that the first patient he enrolled in the study was convinced that his relatives had bewitched him. Edson laments such cultural beliefs, which prevent people from seeking timely treatment and care at the hospital.

“The aim of the CryptoDex study is to determine whether dexamethasone in addition to the standard antifungal therapy will reduce mortality in patients with HIV and cryptococcal meningitis,” says Edson.

Edson, who also serves as the Study Coordinator, hopes that the treatment will reduce the impact of the yeast on the brain, making the condition less severe and minimizing the risk of death. However, this may not be the outcome if people ignore their symptoms and visit the hospital too late. Hazel is one of the lucky ones.

“I gladly accepted the chance to participate in the study. I am feeling a lot better. In fact, my health improved just after three days after I started the treatment,” Hazel explains. She then turns her head sideways and expresses her hope to reunite soon with her children and husband.

Hazel is among hundreds of patients being enrolled into the CryptoDex clinical trial. The three-year study concludes in 2016.

Dignitas InternationalImproving Treatment for People with HIV and Cryptococcal Meningitis