Cryptococcosis: Population‐Based Multistate Active Surveillance and Risk Factors in Human Immunodeficiency Virus–Infected Persons

Hajjeh, Rana; Conn, Laura A.; Stephens, David S.; Baughman, Wendy; Hamill, Richard J.; Graviss, Edward A.; Pappas, Peter G.; Thomas, Cynthia M.; Reingold, Arthur; Rothrock, Gretchen; Hutwagner, Lori; Schuchat, Anne; Brandt, Mary E.; Pinner, Robert W.

doi:10.1086/314606

Cited by 249 publications

(181 citation statements)

References 14 publications

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“…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%

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: 83%

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

et al. 2012

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“…15 Regional differences in the incidence of symptomatic cryptococcal infection for both HIV ϩ and HIV Ϫ individuals have been described. 16 It is conceivable that the high density of people and pigeons in an urban environment like the Bronx contributes to the early age and high prevalence of C neoformans infection.…”

Section: Discussionmentioning

confidence: 99%

Serologic Evidence forCryptococcus neoformansInfection in Early Childhood

et al. 2001

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ABSTRACT. Objective. Cryptococcus neoformans is an important cause of central nervous system infection in adults with acquired immunodeficiency syndrome (AIDS) but an unusual cause of disease in children with AIDS. The basis for this age-related difference in incidence is not known but may be caused by differences in exposure or immune response. The objective of this study was to determine whether the low prevalence of cryptococcal disease among children is related to a lack of exposure to C neoformans.Methods. Sera were obtained from 185 immunocompetent individuals ranging in age from 1 week to 21 years who were being evaluated in an urban emergency department. Sera were analyzed for antibodies to C neoformans and Candida albicans proteins by immunoblotting. Immunoblot patterns were compared with those obtained from sera of patients with cryptococcosis (n ‫؍‬ 10) and workers in a laboratory devoted to the study of C neoformans. The specificity of our results was confirmed by several approaches, including antibody absorption and blocking studies. Sera were also analyzed for the presence of cryptococcal polysaccharide by both enzyme-linked immunosorbent assay and latex agglutination assays.Results. Sera from children 1.1 to 2 years old demonstrated minimal reactivity to C neoformans proteins. In contrast, the majority of sera from children >2 years old recognized many (>6) C neoformans proteins. For children between 2.1 and 5 years old, 56% of sera (n ‫؍‬ 25) reacted with many proteins, whereas for children >5 years old (n ‫؍‬ 120), 70% of samples reacted with many proteins. Reactivity was decreased by absorbing sera with C neoformans extracts or by preincubating blots with sera from experimentally infected but not from control rats. Reactivity to C neoformans proteins did not correlate with reactivity to C albicans proteins, which was common in sera from children between the ages of 1.1 and 2 years. Cryptococcal polysaccharide was detected at a titer of 1:16 (ϳ10 ng/mL) in the sera of 1 child, a 5.6-year-old boy who presented to the emergency department with vomiting.Conclusions. Our findings provide both indirect and direct evidence of C neoformans infection in immunocompetent children. Our results indicate that C neoformans infects a majority of children living in the Bronx after 2 years old. These results are consistent with several observations: the ubiquitous nature of C neoformans in the environment, including its association with pigeon excreta; the large number of pigeons in urban areas; and the increased likelihood of environmental exposure for children once they have learned to walk. The signs and symptoms associated with C neoformans infection in immunocompetent children remained to be determined. Primary pulmonary cryptococcosis may be asymptomatic or produce symptoms confused with viral infections and, therefore, not recognized as a fungal infection. Our results suggest that the low incidence of symptomatic cryptococcal disease in children with AIDS is not a result of lack of exposure to C neoforman...

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“…Another factor to be considered in the risk of developing cryptococcosis among our patients may be the geographical region where they reside. Early studies conducted in the US [7,8,241 among transplant and non-transplant patients have pointed out a higher risk for cryptococcosis in individuals from the eastern part than in those from the western part of the country. The reported frequency of this fungal infection was 6-83% in SOT recipients residing in the eastern continental US, compared to only 1.5% in those residing in the western part.…”

Section: Microbiologymentioning

confidence: 99%

Longitudinal study of cryptococcosis in adult solid-organ transplant recipients

Vilchez¹,

Shapiro²,

McCurry³

et al. 2003

Transplant Int

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While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solidorgan transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n = 13), lung (n = 4), liver (n = 28), kidney (n = 9) and small bowel (n = 1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation ( P = 0.02). In contrast, pneumonia ( P = 0.003) and meningitis ( P = 0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia ( P = 0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.

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Cryptococcosis: Population‐Based Multistate Active Surveillance and Risk Factors in Human Immunodeficiency Virus–Infected Persons

Cited by 249 publications

References 14 publications

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

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

Serologic Evidence forCryptococcus neoformansInfection in Early Childhood

Longitudinal study of cryptococcosis in adult solid-organ transplant recipients

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