Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Letang, Emílio; Müller, Matthias C.; Ntamatungiro, Alex J; Kimera, Namvua; Faini, Diana; Furrer, Hansjakob; Battegay, Manuel; Tanner, Marcel; Hatz, Christoph; Boulware, David R.; Glass, Tracy R.

doi:10.1093/ofid/ofv046

Cited by 76 publications

(84 citation statements)

References 30 publications

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“…Estimates of adults who are positive for cryptococcal antigenaemia who go on to develop symptomatic cryptococcal meningitis were from published cohort studies. 10–12,30–32 We estimated that 70% (range 56–84%) of people positive for cryptococcal antigenaemia would progress to develop cryptococcal disease or died without diagnosis, unless treated with ART or pre-emptive fluconazole (appendix p 6). Without ART or pre-emptive fluconazole therapy, we assumed 95% (uncertainty interval 90–100) progression in all regions (opinion of authors) with a 5% competing risk of death from other causes or comorbid conditions.…”

Section: Methodsmentioning

confidence: 99%

“…Without ART or pre-emptive fluconazole therapy, we assumed 95% (uncertainty interval 90–100) progression in all regions (opinion of authors) with a 5% competing risk of death from other causes or comorbid conditions. 10,11,45,50,51 …”

Section: Methodsmentioning

confidence: 99%

“…14–16 Cryptococcal antigenaemia screening coupled with pre-emptive antifungal therapy has a proven survival benefit, 10,12,17 and has been incorporated into HIV national guidelines in Botswana, Kenya, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Uganda, USA, and Zimbabwe with consideration elsewhere. Estimation of the cryptococcal disease burden helps stakeholders weigh the costs and resources required for hospital-based meningitis treatment versus investment of resources into a pre-emptive cryptococcal antigenaemia screen-and-treat strategy.…”

Section: Introductionmentioning

confidence: 99%

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Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

Rajasingham

Smith

Park

et al. 2017

The Lancet Infectious Diseases

1,677

1,552

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Summary Background Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. Methods We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per µL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/µL not on ART, and those with CD4 less than 100 cells per µL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. Findings We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8–6·2) among people with a CD4 cell count of less than 100 cells per µL, with 278 000 (95% CI 195 500–340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600–282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600–193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400–234 300), with 135 900 (75%; [95% CI 93 900–163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10–19). Interpretation Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority. Funding None.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

Rajasingham

Smith

Park

et al. 2017

The Lancet Infectious Diseases

1,677

1,552

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“…In Uganda it was 1.1% of all HIV patients [17] and 12% in all HIV Sub Saharan Africa [18][19][20]. There is evidence that earlier screening and prophylactictreatment with fluconazole prevents cryptococcal meningitis infections in HIV patients [17] and is a less expensive therapy option [21][22][23]. However, fluconazole resistance could reduce the efficacy of this strategy [3].…”

Section: Fungal Infections Complicating Hiv/aidsmentioning

confidence: 99%

Estimated burden of fungal infections in Kenya

Guto

Bii

Denning

2016

J Infect Dev Ctries

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“…A growing body of evidence is showing that blood Cryptococcal antigen (CrAg) screening and treatment with fluconazole is an effective way of preventing meningitis (9–13) for patients with advanced HIV and positive cryptococcal antigenemia. The CrAg lateral flow assay (LFA) is the most sensitive and specific method for detecting early disseminated infection (14, 15), and is the preferred first-line recommended test for diagnosis (16, 17).…”

Section: Screening Asymptomatic Patients At Risk For Meningitismentioning

confidence: 99%

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings

Lofgren

Abassi

Rhein

et al. 2017

Expert Review of Anti-infective Therapy

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Introduction Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths. Areas covered Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent. Expert Commentary Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.

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Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Cited by 76 publications

References 30 publications

Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

Estimated burden of fungal infections in Kenya

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings

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