Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults

University of Liverpool, Liverpool, England, United Kingdom
AIDS (Impact Factor: 5.55). 05/2002; 16(7):1031-8. DOI: 10.1097/00002030-200205030-00009
Source: PubMed


Despite the recognition of Cryptococcus neoformans as a major cause of meningitis in HIV-infected adults in sub-Saharan Africa, little is known about the relative importance of this potentially preventable infection as a cause of mortality and suffering in HIV-infected adults in this region.
A cohort study of 1372 HIV-1-infected adults, enrolled and followed up between October 1995 and January 1999 at two community clinics in Entebbe, Uganda.
Systematic and standardized assessment of illness episodes to describe cryptococcal disease and death rates.
Cryptococcal disease was diagnosed in 77 individuals (rate 40.4/1000 person-years) and was associated with 17% of all deaths (77 out of 444) in the cohort. Risk of infection was strongly associated with CD4 T cell counts < 200 x 10(6) cells/l(75 patients) and World Health Organization (WHO) clinical stage 3 and 4 (68 patients). Meningism was present infrequently on presentation (18%). Clinical findings had limited discriminatory diagnostic value. Serum cryptococcal antigen testing was the most sensitive and robust diagnostic test. Cryptococcal antigenaemia preceded symptoms by a median of 22 days (> 100 days in 11% of patients). Survival following diagnosis was poor (median survival 26 days; range 0-138).
Cryptococcal infection is an important contributor to mortality and suffering in HIV-infected Ugandans. Improvements in access to effective therapy of established disease are necessary. In addition, prevention strategies, in particular chemoprophylaxis, should be evaluated while awaiting the outcome of initiatives to make antiretroviral therapy more widely available.

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Available from: Jessica Nakiyingi-Miiro
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    • "Cryptococcal meningitis is the most common cause of adult meningitis in Africa [1], and results in approximately 20–25% of AIDS-related deaths. [2]–[4]. The majority of cases occur in sub-Saharan Africa with an estimated 6-month survival of 20–60% [4]–[6]. "
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    ABSTRACT: Background Cryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva. Methods We screened HIV-infected, antiretroviral therapy naïve persons with symptomatic meningitis (n = 130) and asymptomatic persons with CD4+<100 cells/µL entering into HIV care (n = 399) in Kampala, Uganda. The diagnostic performance of testing saliva was compared to serum/plasma cryptococcal antigen as the reference standard. Results The saliva lateral flow assay performance was overall more sensitive in symptomatic patients (88%) than in asymptomatic patients (27%). The specificity of saliva lateral flow assay was excellent at 97.8% in the symptomatic patients and 100% in asymptomatic patients. The degree of accuracy of saliva in diagnosing cryptococcosis and the level of agreement between the two sample types was better in symptomatic patients (C-statistic 92.9, κ-0.82) than in asymptomatic patients (C-statistic 63.5, κ-0.41). Persons with false negative salvia CrAg tests had lower levels of peripheral blood CrAg titers (P<0.001). Conclusion There was poor diagnostic performance in testing saliva for cryptococcal antigen, particularly among asymptomatic persons screened for preemptive treatment of cryptococcosis.
    Full-text · Article · Jul 2014 · PLoS ONE
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    • "A large proportion of CM is preventable for several reasons. First, CrAg is present in peripheral blood for an average of 22 days before the onset of CM, and in 10% of cases it may be present for more than 100 days before the onset of meningitis [10]. As seen with our first patient, this asymptomatic phase is important for identifying those at risk of developing clinical disease at a later stage. "
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    ABSTRACT: Despite access to antiretroviral therapy, mortality from cryptococcal meningitis (CM) is high among persons with advanced HIV infection in sub-Saharan Africa. Cryptococcal antigen (CrAg) is present several weeks to months before the onset of symptoms of meningitis and can be screened to prevent life threatening meningitis. Recently, the World Health Organisation recommended that a new rapid CrAg lateral flow ''dipstick" assay (LFA) is to be used to screen HIV-infected persons with CD4 counts of less than 100 cells/µL. In this paper, we describe two cases of cryptococcosis with differing outcomes. In the first case, the new CrAg LFA was used as part of a screen and preemptive treatment strategy to prevent CM. In the second case, our patient had no access to the CrAg LFA and subsequently developed life threatening meningitis. To the best of our knowledge, this is the first case report of cryptococcosis diagnosed using this novel assay.
    Full-text · Article · Nov 2013 · Case Reports in Medicine
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    • "Among those CrAg-positive, 88.5% had CD4+ T-cells count ≤200 cells/µL. These results are in agreement with the findings from Uganda, Tanzania, and South Africa where >90% had CD4+ T cells counts ≤200 cells/µL [11], [38], [39]. Another finding of the present study is among those with CD4+ T cells count between 201–350 cells/µL, 5.8% were CrAg+. "
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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.
    Full-text · Article · Oct 2013 · PLoS ONE
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