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      Disseminated cryptococcosis with gastrointestinal involvement and false-negative cryptococcal antigen testing due to postzone phenomenon: a case report and review of the literature

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          Abstract

          Background

          Cryptococcosis is an increasingly common infection given the growing immunocompromised population worldwide. Cryptococcal antigen (CrAg) testing demonstrates excellent sensitivity and specificity and is the mainstay of diagnosis. However, there may be rare instances in which false-negative CrAg results can delay diagnosis and early treatment, which are critical to ensure positive outcomes.

          Case presentation

          A 31-year-old man living with HIV/AIDS who was not taking antiretroviral therapy was hospitalized with fever, diarrhea, and headaches. CD4 count on presentation was 71 cells/uL, and HIV viral load was 3,194,949 copies/mL. Serum CrAg testing was initially negative, however CSF CrAg performed several days later was positive at 1:40 and blood and CSF cultures grew Cryptococcus neoformans. Colonoscopy revealed mucosal papules throughout the sigmoid colon, and tissue biopsy showed yeast within the lamina propria consistent with GI cryptococcosis. Given the high burden of disease, the original serum CrAg specimen was serially diluted and subsequently found to be positive at 1:2,560, confirming the postzone phenomenon.

          Conclusion

          Cryptococcosis has a wide array of presentations including intraluminal GI disease, as seen in this patient. While serum CrAg testing displays excellent test characteristics, it is important for clinicians to be aware of the rare instances in which false-negative results may occur in the presence of excess antigen, as in this case.

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          Most cited references18

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          Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).

          Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.
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            Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults.

            Despite the recognition of Cryptococcus neoformans as a major cause of meningitis in HIV-infected adults in sub-Saharan Africa, little is known about the relative importance of this potentially preventable infection as a cause of mortality and suffering in HIV-infected adults in this region. A cohort study of 1372 HIV-1-infected adults, enrolled and followed up between October 1995 and January 1999 at two community clinics in Entebbe, Uganda. Systematic and standardized assessment of illness episodes to describe cryptococcal disease and death rates. Cryptococcal disease was diagnosed in 77 individuals (rate 40.4/1000 person-years) and was associated with 17% of all deaths (77 out of 444) in the cohort. Risk of infection was strongly associated with CD4 T cell counts 100 days in 11% of patients). Survival following diagnosis was poor (median survival 26 days; range 0-138). Cryptococcal infection is an important contributor to mortality and suffering in HIV-infected Ugandans. Improvements in access to effective therapy of established disease are necessary. In addition, prevention strategies, in particular chemoprophylaxis, should be evaluated while awaiting the outcome of initiatives to make antiretroviral therapy more widely available.
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              Rapid diagnosis of cryptococcal meningitis by use of lateral flow assay on cerebrospinal fluid samples: influence of the high-dose "hook" effect.

              Cryptococcal meningitis is the most frequent cause of meningitis and a major cause of mortality in HIV-infected adults in Africa. This study evaluated the performance of the lateral flow assay (LFA) on cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcal meningitis against that of existing diagnostic tests. LFA performed on 465 undiluted CSF samples had a sensitivity of 91%. When the LFA was paired with Gram staining, a sensitivity of 100% was achieved after implementation of a dilution step for samples with negative LFA results and the presence of yeasts on microscopy. Microscopy is essential for preventing the reporting of false-negative results due to the high-dose "hook" effect.
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                Author and article information

                Contributors
                azimmet@stanford.edu
                Journal
                BMC Infect Dis
                BMC Infect Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                6 April 2023
                6 April 2023
                2023
                : 23
                : 217
                Affiliations
                [1 ]GRID grid.168010.e, ISNI 0000000419368956, Division of Infectious Diseases and Geographic Medicine, , Stanford University School of Medicine, ; Stanford, CA USA
                [2 ]GRID grid.415182.b, ISNI 0000 0004 0383 3673, Department of Pathology, , Santa Clara Valley Medical Center, ; San Jose, CA USA
                [3 ]GRID grid.415182.b, ISNI 0000 0004 0383 3673, Division of Infectious Diseases, , Santa Clara Valley Medical Center, ; San Jose, CA USA
                [4 ]GRID grid.415182.b, ISNI 0000 0004 0383 3673, Clinical Microbiology, , Santa Clara Valley Medical Center, ; San Jose, CA USA
                [5 ]GRID grid.280062.e, ISNI 0000 0000 9957 7758, Division of Infectious Diseases, , Kaiser Permanente Medical Group, ; Redwood City, CA USA
                Article
                8141
                10.1186/s12879-023-08141-y
                10080792
                37024821
                38e37b0d-0fe5-4e3b-ab65-09170856dae7
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 23 January 2023
                : 8 March 2023
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2023

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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