Screening ART patients for cryptococcal disease is cost effective and will save lives

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All patients with a CD4 cell count below 100 cells/mm3 should be routinely screened for cryptococcal meningitis as part of antiretroviral treatment programmes, South African doctors argue in the December 15th edition of Clinical Infectious Diseases.

They believe that routine testing would save lives and be highly cost-effective. The doctors were prompted to write to the journal by a recent Ugandan study.

This showed that serum cryptococcal antigen (GRAG) screening was cost effective for patients with CD4 cell counts of 100 cell/mm3 or below who were starting HIV therapy. 



Inflammation of the outer lining of the brain. Potential causes include bacterial or viral infections.



A type of fungal infection usually affecting the membrane around the brain, causing meningitis. It can also affect the lungs and chest.


Cost-effectiveness analyses compare the financial cost of providing health interventions with their health benefit in order to assess whether interventions provide value for money. As well as the cost of providing medical care now, analyses may take into account savings on future health spending (because a person’s health has improved) and the economic contribution a healthy person could make to society.

lumbar puncture

A small hole made in the spinal column to take out spinal fluid for tests or to inject drugs. Also called a spinal tap. It involves the insertion of a needle through the tissue between the vertebrae to access the spinal canal.


Clear, non-cellular portion of the blood, containing antibodies and other proteins and chemicals.


Cryptococcal meningitis is one of the most common causes of adult meningitis in South Africa. Increasing access to antiretroviral therapy means that evermore patients starting such treatment will develop this potentially life-threatening infection.

In Cape Town, 20% of all cases of cryptococcal meningitis involve patients taking anti-HIV drugs. The average interval between the initiation of HIV therapy and the diagnosis of the disease is 41 days. The mortality rate for these patients is 29%.

“Nearly all such cases could be identified with CRAG screening at entry into ART programs,” writes Dr Jarvis. The incidence of the infection falls rapidly with effective HIV treatment. Moreover, patients with positive CRAG screening results could be offered pre-emptive therapy, followed by secondary prophylaxis.

The authors believe that such therapy “could potentially prevent most, if not all cryptococcal meningitis cases that occur after ART.”

As 58% of all patients with cryptococcal meningitis in Cape Town are HIV-positive, the investigators also advocate that also patients newly diagnosed with HIV should be tested for the disease.

“CRAG screening at the time of HIV diagnosis may…identify these patients, allowing for preemptive therapy and fast-tracking of ART,” comment the researchers.

Cost need not be a barrier to expanded screening. Bulk purchasing would mean that each test for the infection would cost $5.61.

Early identification of the infection would prevent substantial healthcare costs later. The average of treating each patient admitted to hospital with cryptococcal meningitis is almost $3000.

But the doctors believe that an expansion of screening must be accompanied by guidelines for the treatment of asymptomatic infection.

Cryptococcal meningitis resolves in 56% of HIV-positive patients with antiretroviral therapy alone.

But for other patients a more aggressive treatment strategy may be needed. The Ugandan study showed that low-dose fluconazole was inadequate for some individuals. It is also unclear if patients need to have a lumbar puncture to rule out disease in the central nervous system. In addition, the best time to start HIV therapy requires definition.

“Studies are underway to answer these questions in South Africa,” note the authors, who conclude, “any programmatic screening intervention must be closely monitored, and data should be reported to help formulate optimal strategies for this important intervention.”


Jarvis JN et al. Cryptococcal antigen screening for patients initiating antiretroviral therapy: time for action. Clin Infect Dis, 51: 1463-65, 2010 (click here for access to the journal).