CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis

Ford, Nathan; Shubber, Zara; Jarvis, Joseph N; Chiller, Tom; Greene, Greg; Migone, Chantal; Vitória, Marco; Doherty, Meg; Meintjes, Graeme

doi:10.1093/cid/cix1143

Cited by 87 publications

(75 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this cohort of PLWH in sub-Saharan Africa, serum CrAg positivity was associated with increased risk of death or cryptococcal meningitis among participants with CD4 100-200 cells/mm 3 as well as those with CD4 < 100 cells/mm 3 . The prevalence of CrAg positivity among those with CD4 100-200 cells/mm 3 was 1.9%, which is consistent with prior studies [7]. There was one participant who was CrAg positive who had CD4 > 200 cells/mm 3 .…”

Section: Discussionsupporting

confidence: 89%

“…South Africa is one of many countries in sub-Saharan Africa that now incorporates CrAg screening into its national HIV guidelines for people with CD4 < 100 cells/ mm 3 [6]. A previous meta-analysis established a pooled CrAg positivity prevalence of 2.0% for PLWH with CD4 100-200 cells/mm 3 [7], and recent data from sub-Saharan Africa suggests that at least 9% of cases of cryptococcal meningitis present in individuals with CD4 > 100 cells/ mm 3 [8,9]. We sought to characterize the association of CrAg positivity by the standard of care serum enzyme immunoassay (EIA) with cryptococcal meningitis or death among PLWH with CD4 100-200 cells/mm 3 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cryptococcal antigenemia is associated with meningitis or death in HIV-infected adults with CD4 100–200 cells/mm3

et al. 2020

View full text Add to dashboard Cite

Background: Cryptococcal antigen (CrAg) screening with fluconazole prophylaxis has been shown to prevent cryptococcal meningitis and mortality for people living with HIV (PLWH) with CD4 < 100 cells/mm 3 . While cryptococcal meningitis occurs in individuals with CD4 100-200 cells/mm 3 , there is limited evidence that CrAg screening predicts cryptococcal meningitis or mortality among this group with moderate immunosuppression. Current IDSA and WHO clinical guidelines recommend restricting CrAg screening to PLWH with CD4 < 100 cells/ mm 3 . Methods: We conducted a prospective cohort study of PLWH 18+ years who had not initiated ART in South Africa. We followed participants for 14 months to determine onset of cryptococcal meningitis or all-cause mortality. At study completion, we retrospectively tested stored serum samples for CrAg using an enzyme immunoassay (EIA). We calculated CD4-stratified incidence rates of outcomes and used Cox proportional hazards to measure associations between CrAg positivity and outcomes. Results: We enrolled 2383 PLWH, and 1309 participants had serum samples tested by CrAg EIA. The median CD4 was 317 cells/mm 3 (interquartile range: 173-491 cells/mm 3 ). By CD4 count at baseline, there were 209 individuals with a CD4 count of 100-200 cells/mm 3 and available CrAg test results. Of these, four (1.9%) tested positive. Two of four (IR: 58.8 per 100 person-years) CrAg+ participants and 11 of 205 (IR: 5.6 per 100 person-years) CrAgparticipants developed cryptococcal meningitis or died for an overall rate of death or cryptococcal meningitis that was 10.0-times higher for those who were CrAg+ (95% confidence interval: 2.2-45.3). Among those with CD4 < 100 cell/mm 3 and CrAg EIA test results (N = 179), ten (5.6%) participants tested CrAg+. Among this group, seven of ten (IR: 137.6 per 100 person-years) CrAg+ participants and 26 of 169 (IR: 17.8 per 100 person-years) CrAg-participants developed cryptococcal meningitis or died, for a rate of death or cryptococcal meningitis that was 6.3-times higher for those who were CrAg+ (95% confidence interval: 2.7-14.6). Conclusions: Although few PLWH with moderate immunosuppression screened CrAg positive, a positive CrAg test was predictive of increased risk of cryptococcal meningitis or death. Similar to those with a CD4 < 100 cell/mm 3 , systematic CrAg screening may reduce morbidity and mortality in PLWH with CD4 100-200 cells/mm 3 .

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Cryptococcal antigenemia is associated with meningitis or death in HIV-infected adults with CD4 100–200 cells/mm3

et al. 2020

View full text Add to dashboard Cite

show abstract

“…CrAg is detectable in blood weeks to months before onset of meningitis symptoms (21). Prevalence of asymptomatic cryptococcal antigenemia varies from 1% to 15% among HIV-infected persons with advanced HIV disease (1,22). In high-income countries, the average prevalence of asymptomatic CrAg is 2.6% (1).…”

Section: Minireviewmentioning

confidence: 99%

Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing

et al. 2019

View full text Add to dashboard Cite

Over the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evolved from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent development and distribution of a point-of-care lateral flow assay. This assay is highly sensitive and specific in cerebrospinal fluid (CSF), but is also sensitive in the blood to detect CrAg prior to meningitis symptoms. CrAg screening of HIV-infected persons in the blood prior to development of fulminant meningitis and preemptive treatment for CrAg-positive persons are recommended by the World Health Organization and many national HIV guidelines. Thus, CrAg testing is occurring more widely, especially in resource-limited laboratory settings. CrAg titer predicts meningitis and death and could be used in the future to customize therapy according to burden of infection.

show abstract

“…A recent systematic review examining the global prevalence of cryptococcal antigenaemia (CrAg) in HIV-infected individuals with low CD4 cell counts found a pooled global CrAg prevalence of 6.5% in individuals with CD4<100 cells/µl, and 2% among those with CD4 counts 101-200 cells/µl (5). Updated global burden of disease estimates suggest there were approximately 278,000 HIV-infected people positive for CrAg, and an estimated 223,100 incident cases of CM globally in 2014, with 73% of these occurring in sub-Saharan Africa.…”

Section: Epidemiologymentioning

confidence: 99%

Emerging concepts in HIV-associated cryptococcal meningitis

Lawrence

Boyer-Chammard

Jarvis

2019

Current Opinion in Infectious Diseases

View full text Add to dashboard Cite

Purpose of review: HIV-associated cryptococcal meningitis (CM) remains a significant contributor to AIDS-related mortality despite widened access to antiretroviral therapy. Even in clinical trial settings 10-week mortality is roughly 40%. A number of important clinical trials have either recently concluded or are actively recruiting. Recent findings: Global burden of disease etimates suggest CM causes 181,100 deaths annualy. Screening blood for cryptococcal antigen (CrAg) in HIV-infected individuals with CD4 cell counts <100 cells/µL and pre-emptive antifungal treatment for those with detectable CrAg reduces the incidence of CM and is likely to reduce mortality. CM treatment with conventional 14-day courses of amphotericin are associated with high toxicity and mortality and can be reduced to seven days if given alongside flucytosine. Flucytosine is a significantly superior adjunct to amphotericin treatment compared to fluconazole. In settings without amphotericin B dual oral antifungal combinations of flucytosine and fluconazole offer an effective alternative treatment. A single, high-dose of liposomal amphotericin is effective at reducing fungal burden and is being tested in a phase III trial. Summary: Recently completed and ongoing clinical trials are increasing our understanding of how to optimise induction therapy for CM. Advocacy efforts are needed to broaden access to amphotericin formulations and flucytosine.

show abstract

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis

Cited by 87 publications

References 56 publications

Cryptococcal antigenemia is associated with meningitis or death in HIV-infected adults with CD4 100–200 cells/mm3

Cryptococcal antigenemia is associated with meningitis or death in HIV-infected adults with CD4 100–200 cells/mm3

Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing

Emerging concepts in HIV-associated cryptococcal meningitis

Contact Info

Product

Resources

About