Outcomes of Cryptococcal Meningitis in Uganda Before and After the Availability of Highly Active Antiretroviral Therapy

Infectious Disease Institute, Makerere University, Kampala Uganda.
Clinical Infectious Diseases (Impact Factor: 8.89). 06/2008; 46(11):1694-701. DOI: 10.1086/587667
Source: PubMed


Cryptococcal meningitis (CM) is the proximate cause of death in 20%-30% of persons with acquired immunodeficiency syndrome in Africa.
Two prospective, observational cohorts enrolled human immunodeficiency virus (HIV)-infected, antiretroviral-naive persons with CM in Kampala, Uganda. The first cohort was enrolled in 2001-2002 (n = 92), prior to the availability of highly active antiretroviral therapy (HAART), and the second was enrolled in 2006-2007 (n = 44), when HAART was available.
Ugandans presented with prolonged CM symptoms (median duration, 14 days; interquartile range, 7-21 days). The 14-day survival rates were 49% in 2001-2002 and 80% in 2006 (P < .001). HAART was started 35 +/- 13 days after CM diagnosis and does not explain the improved 14-day survival rate in 2006. In 2006-2007, the survival rate continued to decrease after hospitalization, with only 55% surviving to initiate HAART as an outpatient. Probable cryptococcal-related immune reconstitution inflammatory syndrome occurred in 42% of patients, with 4 deaths. At 6 months after CM diagnosis, 18 persons (41%) were alive and receiving HAART in 2007. The median cerebral spinal fluid (CSF) opening pressure was 330 mm H(2)O; 81% of patients had elevated pressure (>200 mm H(2)O). Only 5 patients consented to therapeutic lumbar puncture. There was a trend for higher mortality for pressures >250 mm H(2)O (odds ratio [OR], 2.1; 95% confidence interval [CI], 0.9-5.2; P = .09). Initial CSF WBC counts of <5 cells/mL were associated with failure of CSF sterilization (OR, 17.3; 95% CI, 3.1-94.3; P < .001), and protein levels <35 mg/dL were associated with higher mortality (OR, 2.0; 95% CI, 1.2-3.3; P = .007).
Significant CM-associated mortality persists, despite the administration of amphotericin B and HIV therapy, because of the high mortality rate before receipt of HAART and because of immune reconstitution inflammatory syndrome-related complications after HAART initiation. Approaches to increase acceptance of therapeutic lumbar punctures are needed.

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Available from: Meagan O'Brien, Feb 28, 2014
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    • "Human Immunodeficiency Virus (HIV)-associated Cryptococcal meningitis (CM) is an opportunistic fungal infection of the brain and spinal cord and a common cause of adult meningitis in sub- Saharan Africa due to the high prevalence of HIV [1] [2]. With a mortality rate of 17–36%, CM is responsible for approximately 25% of HIV/AIDS related deaths in sub-Saharan Africa [3]. Cryptococcomas are rare mass lesions caused by the dissemination of Cryptococcus neoformans and establishment of focal tissue infection . "
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    ABSTRACT: Mortality due to AIDS-related Cryptococcal meningitis (CM) is often >50% in low-middle income countries. Dissemination of CM can result in intracranial mass lesions known as cryptococcoma. Patients who develop cryptococcomas often have worse outcomes when compared to patients with cryptococcosis without cryptococcoma. We describe a cryptococcoma in the central nervous system (CNS) in a Ugandan patient with AIDS, and review the diagnosis and management with special focus on difficulties encountered in low or middle-income countries.
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    • "Even with potent antifungal therapy, cryptococcal disease continues to be associated with substantial morbidity and mortality [12]. Several factors are associated with mortality in central nervous system (CNS) cryptococcosis, these include: CSF white blood cell count o20 cells/μL, high initial CSF CrAg titer 41:32, untreated elevated intracranial pressure, and altered mental status [13] [14] [15]. Our patient initially had all these risk factors. "
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    ABSTRACT: Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune Reconstitution Inflammatory Syndrome (IRIS) is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS) and markedly worsened postpartum after delivery (paradoxical IRIS).
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    • "We found the numbers of ART-naive persons not yet accessing HIV care until they presented with low CD4+ T-cells counts remained high, and cryptococcal antigenemia was predominantly diagnosed among this group. With this late presentation to HIV care, these persons are at high risk of OIs, and the Cryptococcus burden is likely to continue undiminished in many areas [43], [44]. "
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    ABSTRACT: Cryptococcal meningitis is a major cause of HIV/AIDS-related deaths in Africa. Cryptococcosis is a neglected killer. However, meningitis can be prevented by early cryptococcal antigen (CrAg) screening and preemptive antifungal treatment during a prolonged period of detectable, subclinical infection. We determined the prevalence of cryptococcal antigenemia in comparison to CD4 count and clinical symptoms. We surveyed 254 consenting HIV-infected participants to obtain demographic information and clinical history. Serum CrAg was measured by latex agglutination at two sites in the Oromia region of Ethiopia among all persons receiving a CD4 count. Of the 254 participants, 127(50.0%) were ART-naïve, 121(47.6%) were ART-experienced, and 6(2.4%) were ART-defaulters. The prevalence of cryptococcal antigenemia was 10.2% overall being 14.2% among ART-naive, 4.1% among ART-experienced, and 50% (3/6) among ART-defaulters, irrespective of CD4 count. Cryptococcal antigenemia was more frequently detected from ART-naïve patients (p = 0.012) and ART-defaulters (p = 0.001) compared with ART-experienced. Serum CrAg positivity was 20.9% in persons with CD4≤150 cells/µL, 12.2% in 151-200 cells/µL, 5.8% among 201-350 CD4/µL, and none above 350 cells/µL. Potential meningitis symptoms were common in the outpatient cohort irrespective of CrAg-status, with only fever and altered mental status statistically more common in CrAg-positive compared to CrAg-negative persons (P<0.05), yet no symptom had a positive predictive value >33%. We report a 20.9% cryptococcal antigenemia prevalence among those with CD4+ T cells count ≤150 cells/µL, irrespective of ART status, with even higher CrAg prevalence in ART-naïves and ART-defaulters. These groups are target populations for CrAg screening at entry into HIV care.
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