Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS

Park, Benjamin J.; Wannemuehler, Kathleen; Marston, Barbara J.; Govender, Nelesh P.; Pappas, Peter G.; Chiller, Tom

doi:10.1097/qad.0b013e328322ffac

Cited by 1,877 publications

(1,665 citation statements)

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“…grubii (16,24,25,34). Even though cryptococcosis in patients with impaired immunity is rarely caused by serotype B, in this study we found 2 patients with AIDS, and in the period 1997-2005, 1 of the 30 cases caused by C. gattii had HIV infection (16).…”

Section: Discussionmentioning

confidence: 50%

“…The most important issue being highlighted by this study, is the high cryptococcocal morbidity in Colombia both in immunocompetent, as well as in immunosuppressed populations, illustrating that although advances in the antiretroviral therapy have occurred, cryptococcosis is still being diagnosed in Colombia and several other countries (16,(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 83%

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Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

et al. 2012

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Introduction: A survey on cryptococcosis is being conducted regularly in Colombia since 1997. We present hereby the results corresponding to patients diagnosed from 2006 to 2010. Objective: To analyze the data obtained during this period. Materials and methods:Retrospective analysis of the corresponding surveys. Results: A total of 526 surveys originating from 72% of the Colombian political divisions were received during the 5-year period. Most patients (76.6%) were males and 74.9% were 21-50 years old. The most prevalent risk factor was HIV infection (83.5%) with cryptococcosis defining AIDS in 23% of the cases. In the general population the estimated mean annual incidence rate for cryptococcosis was 2.4 x 10 6 inhabitants while in AIDS patients this rate rose to 3.3 x 10 3 . In 474 surveys stating clinical features, most frequent complaints were headache 84.5%, fever 63.4%, nausea and vomiting 57.5%, mental alterations 46.3%, meningeal signs 33.0%, cough 26.4% and visual alterations 24.5%. Neurocryptococcosis was recorded in 81.8% of the cases. Laboratory diagnosis was based on direct examination, culture and latex in 29.3% cases. From 413 Cryptococcus isolates analyzed, 95.6% were identified as C. neoformans var. grubii, 1% C. neoformans var. neoformans, and 3.4% C. gattii. Treatment was reported for 71.6% of the cases with amphotericin B alone or in combination with fluconazole prescribed in 28%. Conclusions: Surveys done through passive surveillance continue to be sentinel markers for HIV infection and represent a systematic approach to the study of opportunistic problems regularly afflicting AIDS patients since cryptococcosis requires no compulsory notification in Colombia. Author contributions:Patricia Escandón: played an important role in writing and preparing the manuscript, in charge of the surveillance at the Instituto Nacional de Salud, controlled receipt of questionnaires. Catalina de Bedout: in charge of the mycological diagnosis for all Corporación para Investigaciones Biológicas cases, established links with physicians in charge of patients, controlled receipt of questionnaires and performed the susceptibility testing in all isolates. Jairo Lizarazo: physician in charge of the patients from Norte de Santander, checked the questionnaire's contents for medical accuracy, analyzed the data through statistical analysis. Clara Inés Agudelo: worked all long in the surveillance study, played an important role in preparation of the manuscript and in the analysis of the data, including statistical tests. Ángela Tobón: examined many of the Corporación para Investigaciones Biológicas patients, filled in the corresponding questionnaires, supervised the clinical aspects of most patients and served as a consultant for other physicians in charge of cryptococcosis patients. Solmara Bello: in charge of the mycological diagnosis for Instituto Nacional de Salud cases. Ángela Restrepo: surveillance of the whole program, contacting physicians and serving as consultant for all participants, analyzing data, writing of ...

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 83%

Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

et al. 2012

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“…1 The development of cryptococcal meningitis occurs mainly in immunocompromised HIV-1-infected patients, most likely by reactivation of latent pulmonary C. neoformans infection. 2 It is estimated that 504,000 HIV-1-infected patients die every year from cryptococcal meningitis in sub-Saharan Africa, 3 which surprisingly exceeds the annual death rate of tuberculosis-associated HIV cases. Resistance against C. neoformans primarily involves monocytic effector mechanisms.…”

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confidence: 99%

Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis

Piehler

Stenzel

Grahnert

et al. 2011

The American Journal of Pathology

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Susceptibility to infection with Cryptococcus neoformans is tightly determined by production of IL-4. In this study, we investigated the time course of IL-4 production and its innate cellular source in mice infected intranasally with C. neoformans. We show that pulmonary IL-4 production starts surprisingly late after 6 weeks of infection. Interestingly, in the lungs of infected mice, pulmonary T helper (Th) cells and eosinophils produce significant amounts of IL-4. In eosinophil-deficient ⌬dblGATA mice, IL-33 receptor-expressing Th2s are significantly reduced, albeit not absent, whereas protective Th1 and Th17 responses are enhanced. In addition, recruitment of pulmonary inflammatory cells during infection with C. neoformans is reduced in the absence of eosinophils. These data expand previous findings emphasizing an exclusively destructive effector function by eosinophilic granulocytes. Moreover, in ⌬dblGATA mice, fungal control is slightly enhanced in the lung; however, dissemination of Cryptococcus is not prevented. Therefore, eosinophils play an immunoregulatory role that contributes to Th2-dependent susceptibility in allergic inflammation during bronchopulmonary mycosis. Cryptococcus neoformans is a facultative intracellular pathogen that is acquired by inhalation of spores and/or desiccated yeasts and leads to latent pulmonary infection in immunocompetent humans. 1 The development of cryptococcal meningitis occurs mainly in immunocompromised HIV-1-infected patients, most likely by reactivation of latent pulmonary C. neoformans infection. 2 It is estimated that 504,000 HIV-1-infected patients die every year from cryptococcal meningitis in sub-Saharan Africa, 3 which surprisingly exceeds the annual death rate of tuberculosis-associated HIV cases. Resistance against C. neoformans primarily involves monocytic effector mechanisms. 4 -6 In this context, T helper (Th) cells are central regulatory players with profound effects. Whereas IL-12-dependent Th1 responses are protective, with an additional contribution by IL-23-dependent Th17 responses, 7-9 Th2 cells producing IL-4, IL-13, and IL-5 are detrimental. 10,11 Studies 12-14 that used i.v. inoculation examined the traversal of the blood-brain barrier by C. neoformans and led to the conclusion that transmigration can occur with intracellular and extracellular fungi. In case of bronchopulmonary infection, dissemination seems to rely more on Th2 cytokines. This allergic Th2-driven inflammation represents the immunopathological pathway promoting disease by allowing cryptococci to grow inside the lung and finally enabling dissemination to the brain, ultimately causing fatal meningoencephalitis. 15 This sequela is accompanied by development of IL-4/IL-13-dependent alternatively activated macrophages, suggesting that those cells may be involved in dissemination. Alternatively activated macrophages are found only in susceptible mice 15 and show significantly reduced control of intracellular growth. 5 In addition, IL-13-dependent mucus production by goblet cells, IL-4 -...

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“…Cryptococcus is the most common cause of fungal meningitis and meningoencephalitis. Global estimates suggest that 1 million cases of cryptococcal meningitis occur each year, with approximately 600,000 fatalities [65]. CNS disease resulting from C. neoformans strains are most common in patients with advanced HIV, while C. gattii strains are emerging pathogens in immunocompetent individuals [66,67].…”

Section: Fungal: Cryptococcusmentioning

confidence: 99%

Vaccinations for Neuroinfectious Disease: A Global Health Priority

Leibovitch

Jacobson

2016

Neurotherapeutics

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Vaccines for neuroinfectious diseases are becoming an ever-increasing global health priority, as neurologic manifestations and sequelae from existing and emerging central nervous system infections account for significant worldwide morbidity and mortality. The prevention of neurotropic infections can be achieved through globally coordinated vaccination campaigns, which have successfully eradicated nonzoonotic agents such as the variola viruses and, hopefully soon, poliovirus. This review discusses vaccines that are currently available or under development for zoonotic flaviviruses and alphaviruses, including Japanese and tick-borne encephalitis, yellow fever, West Nile, dengue, Zika, encephalitic equine viruses, and chikungunya. Also discussed are nonzoonotic agents, including measles and human herpesviruses, as well as select bacterial, fungal, and protozoal pathogens. While therapeutic vaccines will be required to treat a multitude of ongoing infections of the nervous system, the ideal vaccination strategy is preexposure vaccination, with the ultimate goals of minimizing disease associated with zoonotic viruses and the total eradication of nonzoonotic agents.

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Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS

Cited by 1,877 publications

References 41 publications

Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis

Vaccinations for Neuroinfectious Disease: A Global Health Priority

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