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December 2000
Answer: HIV Infection and Cryptococcal Meningitis
Head CT revealed bilateral lentiform nuclear calcifications. These sometimes are observed in children with vertical HIV infection. India ink preparation of the cerebrospinal fluid (CSF) was positive for Cryptococcus neoformans and the cryptococcal antigen titer in CSF was positive at greater than 1:32,000. CSF and blood cultures ultimately grew C. neoformans. Although the patient previously had been healthy, the head CT scan findings and diagnosis of cryptococcal meningitis prompted a laboratory evaluation for HIV. The HIV ELISA and Western blot tests were positive. The plasma HIV RNA concentration was 19,277 copies/ml, and the CD4+ lymphocyte count was 1 (4%). More in-depth questioning of the family revealed that the patient had been adopted, and it was learned subsequently that her birth mother is HIV-infected.
C. neoformans is a ubiquitous fungus isolated commonly from soil contaminated with bird droppings. Humans acquire the infection after inhaling aerosolized fungal elements from contaminated soil. Person-to-person transmission does not occur. Clinical manifestations include primary pulmonary disease and disseminated disease of the central nervous system, bones, joints, and skin. Cryptococcosis is an AIDS–defining disease.
Cryptococcal meningitis, the most common and serious form of cryptococcal disease, often follows an indolent course. Symptoms are characteristic of meningitis, meningoencephalitis, or space-occupying lesions. C. neoformans causes basilar meningitis with cranial nerve involvement manifested by diplopia, blurred vision, ophthalmoplegia, or nystagmus in approximately one-third of patients. Thus, careful examination for cranial nerve palsies should be performed. Hydrocephalus and cryptococcal granulomas can occur in the brain, resulting in signs suggestive of tumor, abscess, subdural hematoma, or uncinate herniation.
India ink stain from patient’s CSF with C. neoformans cell.
Note characteristic “halo” effect from cell capsule
A variety of diagnostic tools are available for identification of C. neoformans. Direct examination of the CSF using the India ink test can provide an immediate presumptive diagnosis of cryptococcal meningitis (see above photograph). The cryptococcal capsular polysaccharide antigen test also is useful diagnostically. Antigen detection in CSF or serum is at least 90% sensitive in cryptococcal meningitis, although it may be lower in cryptococcosis without CNS disease. Culture remains the gold standard for diagnosis and monitoring success of therapy.
Amphotericin B in combination with oral flucytosine for two weeks is indicated for patients with meningeal and other serious cryptococcal infections. AIDS patients do not achieve a permanent microbiologic cure with therapy, and relapse occurs in 50% of more if therapy is discontinued. Therefore, most experts recommend lifelong maintenance therapy with fluconazole.
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