Clinical Pearls & Morning Reports

Published March 15, 2017

The differential diagnosis for meningitis is highly influenced by the immune status of the patient. In many parts of southern Africa, where the prevalence of HIV exceeds 10% among adults and 70% among hospitalized patients, HIV has had a massive effect on the causes of meningitis. A Case Record of the Massachusetts General Hospital explains.

Clinical Pearls

Q: What are some of the most frequent causes of meningitis in a person with HIV infection who is living in Africa?

A: The differential diagnosis for subacute meningitis in a person with HIV infection is broad; however, the most frequent causes in Africa are Cryptococcus neoformans and Mycobacterium tuberculosis. In central, east, and southern Africa, cryptococcal meningitis is more common than all other types of meningitis combined.

Q: What cerebrospinal fluid (CSF) findings are associated with cryptococcal meningitis?

A: In patients with cryptococcal meningitis, findings in the CSF are highly variable, and up to 40% of such patients have a normal CSF profile. The CSF white-cell count is generally relatively low, with the cells composed predominantly of lymphocytes; the median count is approximately 20 per cubic millimeter, and only 25% of patients have a count of more than 100 per cubic millimeter. In patients undergoing antiretroviral therapy, CSF white-cell counts can often be higher. The CSF glucose level may be low or normal, and the CSF protein level is sometimes elevated. Elevated intracranial pressure is common and occurs in up to 65% of persons with cryptococcal meningitis.


Table 2. Typical Laboratory Features of Bacterial, Tuberculous, Cryptococcal, and Viral Meningitis.

Morning Report Questions

Q: How is cryptococcal meningitis treated?

A: Because of the cost of some antifungal medications, treatment strategies differ between the United States and resource-limited settings. In the United States, standard treatment includes induction therapy with amphotericin B (typically liposomal amphotericin B) plus flucytosine for 14 days, consolidation therapy with high-dose fluconazole, and maintenance therapy and secondary prophylaxis with a lower dose of fluconazole. The addition of flucytosine to amphotericin B results in a clinically significant increase in 6-month survival; however, flucytosine costs more than $2,000 per day in the United States and is unavailable in resource-limited countries. In resource-limited countries, recommended therapy consists of amphotericin B deoxycholate plus high-dose fluconazole.

Q: What are the United States guidelines for initiating antiretroviral therapy for HIV in a patient with cryptococcal meningitis?

A: In most patients presenting with an opportunistic infection and a CD4+ T-cell count of less than 50 per cubic millimeter, early initiation of HIV therapy results in a higher rate of survival but also probably results in a higher risk of developing the paradoxical immune reconstitution inflammatory syndrome (IRIS). However, there is a clear exception in patients with cryptococcal meningitis, in whom early initiation of HIV therapy results in an approximately 15% increase in the rate of death occurring during the first 30 days, which is most likely due to IRIS. In such patients, both immediate initiation of HIV therapy and initiation during the second week of hospitalization are associated with higher mortality. Patients with a very low CSF white-cell count (i.e., <5 per cubic millimeter) have a higher risk of death if HIV therapy is started within 10 days after the initiation of antifungal therapy. Guidelines in the United States recommend deferring the initiation of HIV therapy until 4 to 6 weeks after the initiation of antifungal therapy.

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