HIV-associated cryptococcal meningitis

Topic: Risk, prevention and care in population studies

There was a significant clustering of isolates from African compared with European patients, suggesting that the patients had acquired their isolates long before the development of clinical disease. A proportion of HIV-related cases, however, may result from dissemination of new or primary infection [16], as has been observed in the recent outbreak of C. gattii infection in British Columbia [17]. Those who have a negative result with India ink can be diagnosed by highly sensitive and specific cryptococcal antigen testing of CSF, or serum if CSF cannot be obtained [18]. High organism burden at baseline (indicated by quantitative CSF culture or CSF antigen titre) and abnormal mental status are the most important predictors of death [19,20], while high opening pressures and a poor inflammatory response in the CSF have also been associated with poor outcome [19,21,22]. There is extensive involvement of brain parenchyma in addition to meningitis and higher organism burdens (which are predominantly extracellular) compared with the infection in HIV-seronegative individuals [23–25]. For example, cryptococcal disease appears to be more common in southern and east Africa than in west Africa [53], and in north and northeast Thailand compared with southern Thailand [43]. Of note, mortality is higher in less selected series [55] compared with clinical trails in which very sick patients are excluded [21]. In South Africa, in a recent unselected prospective series [60], overall 10-week mortality was 37% despite initial treatment with amphotericin B for most patients and access to ART (Fig. 1).Fig. 1: Prospective observational study of survival of 54 patients with HIV-associated cryptococcal meningitis treated according local protocol (49 with amphotericin B 1 mg/kg daily, 5 with fluconazole) in Cape Town South Africa. Antifungal therapy Current antifungal treatment guidelines (Table 1; [61,62]) are based in large part on the results of a large, randomized trial published a decade ago [21]. The addition of flucytosine was associated with a trend towards a higher proportion of patients with sterile CSF at 2 weeks and reduced relapse. That the combination of amphotericin B plus flucytosine is more rapidly fungicidal than amphotericin B alone has been demonstrated in a subsequent study in Thailand using serial quantitative cultures to assess the rate of clearance of cryptococcal colony-forming units from the CSF or early fungicidal activity. The clearance of cryptococci from

Key findings

• There was a significant clustering of isolates from African compared with European patients, suggesting that the patients had acquired their isolates long before the development of clinical disease.
• A proportion of HIV-related cases, however, may result from dissemination of new or primary infection [16], as has been observed in the recent outbreak of C. gattii infection in British Columbia [17].
• Those who have a negative result with India ink can be diagnosed by highly sensitive and specific cryptococcal antigen testing of CSF, or serum if CSF cannot be obtained [18].
• High organism burden at baseline (indicated by quantitative CSF culture or CSF antigen titre) and abnormal mental status are the most important predictors of death [19,20], while high opening pressures and a poor inflammatory response in the CSF have also been associated with poor outcome [19,21,22].
• There is extensive involvement of brain parenchyma in addition to meningitis and higher organism burdens (which are predominantly extracellular) compared with the infection in HIV-seronegative individuals [23–25].

Why it matters

This review covers HIV-associated cryptococcal meningitis, noting that high organism burden at baseline and abnormal mental status are the most important predictors of death. It also describes geographic variation in cryptococcal disease and higher mortality in less selected series compared with clinical trials.

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Study details

• Study designrandomized controlled trial
• Participants54
• Effect sizeor 26.5; 9.4%
• Evidence strengthHigh

Read the original

• DOI: 10.1097/qad.0b013e3282a4a64d
• PubMed: 18090038
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{jarvis2007-18090038,
  author  = {Jarvis, Joseph N and Harrison, Thomas Stephen},
  title   = {{HIV-associated cryptococcal meningitis}},
  journal = {AIDS},
  year    = {2007},
  doi     = {10.1097/qad.0b013e3282a4a64d},
  pmid    = {18090038},
  url     = {https://doi.org/10.1097/qad.0b013e3282a4a64d}
}

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