Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-infected patients
- Gary M Cox, MD
Gary M Cox, MD
- Professor of Medicine
- Duke University Medical Center
- John R Perfect, MD
John R Perfect, MD
- Professor of Medicine
- Duke University Medical Center
Disseminated Cryptococcus neoformans infection is a serious opportunistic infection that occurs in patients with untreated AIDS . Although cryptococcal infection begins in the lungs, meningitis is the most frequently encountered manifestation of cryptococcosis among those with advanced immunosuppression. However, the infection is more properly characterized as "meningoencephalitis" rather than meningitis since the brain parenchyma is almost always involved on histologic examination [2,3].
The clinical manifestations and diagnosis of C. neoformans meningoencephalitis in AIDS patients will be reviewed here. Treatment and monitoring of AIDS patients with cryptococcal meningoencephalitis is found elsewhere. The microbiology, clinical manifestations, and treatment of this infection in other patient populations, such as transplant patients, are discussed elsewhere. C. gattii infection is also presented separately. (See "Treatment of Cryptococcus neoformans meningoencephalitis in HIV-infected patients" and "Clinical management and monitoring during antifungal therapy of the HIV-infected patient with cryptococcal meningoencephalitis" and "Microbiology and epidemiology of Cryptococcus neoformans infection" and "Clinical manifestations and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-seronegative patients" and "Treatment of Cryptococcus neoformans meningoencephalitis and disseminated infection in HIV seronegative patients" and "Cryptococcus neoformans infection outside the central nervous system" and "Cryptococcus gattii infection: Microbiology, epidemiology, and pathogenesis" and "Cryptococcus gattii infection: Clinical features and diagnosis" and "Cryptococcus gattii infection: Treatment".)
Globally, it has been estimated that approximately 957,900 cases of cryptococcal meningoencephalitis occur each year, resulting in more than 600,000 deaths [4,5]. The vast majority of cases occur among patients with AIDS and a CD4 count <100 cells/microL. The region with the highest number of estimated cases in 2006 was sub-Saharan Africa (720,000 cases; range, 144,000 to 1.3 million), followed by South and Southeast Asia (120,000 cases; range, 24,000 to 216,000) . Although the incidence of cryptococcal meningoencephalitis has declined in patients who have access to antiretroviral therapy (ART) , cryptococcal disease remains a leading cause of mortality in the developing world where access to ART is limited and HIV prevalence remains high .
Early diagnosis and treatment may help reduce cryptococcal meningitis-related mortality . One way to diagnose cryptococcal infection early in the course disease is through the detection of serum cryptococcal antigen (CrAg), which can be detected at least three weeks prior to the onset of neurologic symptoms. The prevalence of antigenemia has been found to vary depending upon the geographical area. As an example, in the United States, the prevalence of cryptococcal antigenemia among patients with a CD4 count <100 cells/microL was reported to be approximately 3 percent, whereas in Uganda the prevalence among such patients was 13.5 percent [9,10]. A discussion on the use of screening and early therapy to prevent meningoencephalitis is found elsewhere. (See "Treatment of Cryptococcus neoformans meningoencephalitis in HIV-infected patients", section on 'Screening and treatment of early infection'.)
Symptoms — Symptoms of cryptococcal meningoencephalitis typically begin indolently over a period of one to two weeks. The most common symptoms are fever, malaise, and headache . Stiff neck, photophobia, and vomiting are seen in one-fourth to one-third of patients. Patients rarely present with coma and fulminant death in days.
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- CLINICAL MANIFESTATIONS
- Physical examination
- Importance of neuroimaging
- Lumbar puncture
- Cryptococal culture
- India ink staining
- Cryptococcal antigen (CrAg)
- - Spinal fluid
- - Serum
- Extraneural cultures
- Resource limited settings
- DIFFERENTIAL DIAGNOSIS
- PROGNOSTIC FACTORS
- SUMMARY AND RECOMMENDATIONS