Background: Cryptococcal meningitis is an important opportunistic fungal infection that became very common after the era of HIV infection. Objectives: To ...
Teshale Seboxa, Shitaye Alemu, Abraham Assefa, Atakilti Asefa, Ermias Diro. 2010. Ethiop Med, J, Vol.48, No. 3 BRIEF COMMUNICATION
CRYPTOCOCCAL MENINGITIS IN PATIENTS WITH ACQUIRED IMMUNUDEFICIENCY SYNDROME IN PREHAART ERA AT GONDAR COLLEGE OF MEDICAL SCIENCES HOSPITAL NORTH-WEST ETHIOPIA Teshale Seboxa1, Shitaye Alemu2, Abraham Assefa3, Atakilti Asefa, Ermias Diro2
Background: Cryptococcal meningitis is an important opportunistic fungal infection that became very common after the era of HIV infection. Objectives: To determine the magnitude of cryptococcal meningitis and study the clinical pattern among inpatients with HIV infection at Gondar Hospital. Methods: A descriptive study was done among ELISA confirmed admitted HIV patients. Clinically suspected cases of meningitis underwent lumbar puncture and cerebrospinal fluid analysis. The clinical profile and outcomes of the confirmed cryptococcal meningitis cases were described. Results: Among 375 HIV serology positive patients 31 were confirmed to have cryptococcal meningitis. Their median age was 29 years (range 16-64); and 22 were males. The major manifestation at presentation included, headache and fever each in 90%, malaise (65%), stiffness of the neck (48%), altered mentation (32%) and nausea and vomiting (32%), photophobia (23%) and seizure (3.6%). Median duration of illness was 16 days; ranging from 140 days. Temperature was above 38.4oC in 80%. Meningial signs were observed in 32%, altered mentation was noted in 29% and focal neurologic deficit in 19%. Cerebrospinal fluid examination revealed visually increased pressure (measured opening pressure >200mmH2O in six patients) in 81%, glucose 40 mg/dl (15-40mg/dl) in 35%, leukocytes count 38.40C Meningeal signs Altered mentation Focal deficit
25 (80) 10 (32) 9 (29) 6 (19)
CSF Findings: Samples of CSF frequently showed minimal lymphocyte response with mild elevation of protein and decreased glucose (Table 2). Most of the patients, 18 (58%) were having leukocyte count of less than 20/mm3 and decreased CSF glucose was measured in 17 (55%).
Indian ink preparation was positive in 22 of 31 CSF samples in patients with suspected meningitis and 28 out of 31 CSF samples grew the yeast in culture media.
All 31 patients died: 17 before anti-fungal therapy could be administered and 14 during the course of treatment with Amphothericin B.
Table 2: CSF findings of AIDS patients with cryptococcal meningitis (n=31). CSF findings
Frequency (%)
Increased opening pressure (> 200 mm H20) Glucose < 50 mg/100ml (n = 50 – 70mg/dl) Protein > 40 mg/100ml (n = 15 – 40mg/dl) Leukocytes count < 20/mm3 (poor prognostic in the presence of meningitis) Positive Indian ink Preparation Positive cerebrospinal fluid culture
25 (81) 17 (55) 11 (35) 18 (58 22 (71) 28 (90)
Cryptococcal meningitis occurred in 31 of 375 (8.3%) admitted AIDS patients at our hospital over the four-year period from 1994-1997. This is comparable with the finding at Tikur Anbessa Hospital, 7% (4). This shows the high prevalence of cryptococcal infection and indicates that this type of meningitis is one of the most frequent manifestations of HIVinfected patients (17 - 22).
is an AIDS defining illness and carries a high case fatality rate if treatment is not started early, a high index of suspicion is necessary to detect cases. How early cryptococcal meningitis occurs in our HIVinfected patients in the course of their illness is difficult to determine because time of seroconversion is generally unknown. Which patient is at risk in the immediate future is also difficult to predict since CD4 levels are seldom measured in our set-up and we do not have data regarding the levels of CD4 in the patients studied.
Although the reported incidence of cryptococcosis can vary depending on index of suspicion, patient selection and intensity of evaluation, the occurrence of 31 patients suggests that C. Neoformans is an important opportunistic pathogen in the area as was see in Addis Ababa (3). This still is underestimation since the basis of diagnosis in this study, identification of C. Neoformans in India ink preparations of CSF, carries a sensitivity rate in the range of only 70% (23).
Since not all patients with cryptococcal meningitis are positive in India ink stain, others have suggested the use of latex agglutination tests of CSF for cryptococcal antigens to improve sensitivity (1, 4, 16). Cost would however limit the widespread implementation of this recommendation. India ink stain is very simple to carry out in any set-up where a microscope is available and specificity is nearly 100% in expert hands. But physicians should be aware of the associated rate of false negativity and missed diagnoses.
Meningeal signs were present in only a quarter of patients with cryptococcal meningitis although 46% complained of neck stiffness and 89% had headache. None of the presenting symptoms or signs of cryptococcal infection are sufficiently characteristic to distinguish it from other chronic CNS infections that occur in patients with HIV-infection including tuberculous meningitis (18 - 22). Because cryptococcosis
In the present series, the high mortality associated with cryptococcal meningitis is probably related to a combination of factors. Most of the patients had poor prognostic conditions like low CSF pleocytosis and glucose levels. Additionally, delay in the diagnosis and administration of antifungal therapy, profound emaciation and associated metabolic derangement of the patients, intolerance to the only available sys-
DISCUSSION
temic anti-fungal agent (Amphothericin B) and poor patient immunity and lack of HAART also play a role. Even in modern well equipped centers, standard courses of Amphothericin B alone or combined with flucytosine were frequently ineffective in patients with this disease (9, 11, 12, 15, 17 -21). Further research is therefore needed to develop recommendations for treatment (18). In conclusion, it is clear from the findings that HIVinfected patients in this region are also at risk of cryptoccocal meningitis as are seropositive patients elsewhere.
A high index of suspicion is necessary to detect the disease early and institute systemic antifungal therapy and the necessary supportive care.
Headache not explained by other causes and not responding to common analgesics associated with fever should raise the suspicion in all HIV patients irrespective of their stage or their treatment. Improving the immune status of the patients with HAART may be a good alternative.
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