Serum Cryptococcal Antigen Test Research Articles

Cryptococcosis with pulmonary cavitation in an immunocompetent child: a case report and literature review

BackgroundPulmonary cryptococcosis (PC) rarely occurs in immunocompetent children.Case presentationA 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive.ConclusionPC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.

Cryptococcal Infection Presenting as a Pleural Effusion in a Liver Transplant Recipient

Abstract We report a rare case of a liver transplant recipient who experienced acute respiratory failure early posttransplantation because of cryptococcal pleural effusion. Although cryptococcal disease presenting solely as pleural effusion has been reported in the literature, it is not widely described in liver transplant recipients. Cryptococcal disease usually manifests late in the posttransplant period, whereas our patient was diagnosed with the infection early posttransplant. Diagnosis was made by pleural fluid culture. The initial serum cryptococcal antigen testing was negative. This case demonstrates the potential of subclinical or latent infections in patients with cirrhosis and liver transplant recipients and the importance of considering pleural fluid culture in the diagnostic evaluation of pleural effusions in cirrhotic patients.

Cryptococcal Meningitis Developing in a Patient with Neurosarcoidosis.

Cryptococcal meningitis is a critical disease that occasionally involves immunosuppressed patients. We herein report a 79-year-old Japanese man who received low-dose prednisolone therapy for neurosarcoidosis and panhypopituitarism. He presented a 10-day history of a fever and altered mental status. The FilmArray® Meningitis/Encephalitis Panel and serum cryptococcal antigen tests were both negative, but the cerebrospinal fluid sample became positive for Cryptococcus neoformans after seven-day incubation. After the diagnosis of cryptococcal meningitis, we successfully treated the patient with a recommended treatment regimen. When an immunocompromised patient presents with a subacute fever accompanying any central nervous symptoms, cryptococcal meningitis should be screened for.

Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

False-negative cerebral spinal fluid cryptococcal antigen lateral flow assay due to postzone phenomenon in a patient with disseminated cryptococcal disease: a case report

This report presents the case of false-negative cerebral spinal fluid (CSF) cryptococcal antigen (CrAg) lateral flow assay (LFA) in a HIV-positive 25-year-old male. The patient presented with headache, nausea and vomiting for 5 days and syncope for 1 day. An initial CSF CrAg LFA test was negative, but a 1:4 dilution of the CSF was weakly positive and a 1:8 dilution was positive. A serum cryptococcal antigen test was weakly positive. Cultures of blood and CSF were all positive for Cryptococcus neoformans. The explanation for the false-negative CSF CrAg LFA test is that the antigen concentration was too high causing the postzone phenomenon.

Clinicoradiological Features of Pulmonary Cryptococcosis in Immunocompetent Patients.

To assess the clinicoradiological features of pulmonary cryptococcosis in immunocompetent patients. This retrospective study included immunocompetent patients who had been diagnosed with pulmonary cryptococcosis on the histopathologic exam and underwent chest CT between January 2008 and November 2019. Imaging features were divided into major imaging patterns, distributions, and ancillary imaging findings. Univariable analysis was performed to evaluate clinicoradiological features according to the presence of serum cryptococcal antigen. Thirty-one patients were evaluated (mean age: 60 years, range: 19-78 years). A single nodular lesion confined to a single lobe was the most common imaging pattern (14/31, 45.2%). Serum cryptococcal antigen tests were performed in 19 patients (19/31, 61.3%). The presence of serum cryptococcal antigen was observed in six patients (6/19, 31.6%), all of whom showed a consolidation-dominant pattern. The presence of serum cryptococcal antigen was significantly associated with the consolidation-dominant pattern compared to those associated with a nodule-dominant pattern (p = 0.011). A combination of CT findings of consolidation and a positive serum cryptococcal antigen test may be helpful for diagnosing pulmonary cryptococcosis in immunocompetent patients.

Clinical characteristics and image features of pulmonary cryptococcosis: a retrospective analysis of 50 cases in a Chinese hospital

ObjectiveTo investigate the clinical manifestations and imaging characteristics of pulmonary cryptococcosis, and discuss its guidance in diagnosing.MethodsThe clinical data of patients diagnosed with cryptococcosis in our hospital from January 2014 to May 2020 were collected and retrospectively analyzed. Patients were divided into the immunocompromised group and the immunocompetent group. The symptomatic features, laboratory examination, imaging manifestations, and curative effect were analyzed.ResultsThe most common symptoms of patients were cough and sputum production, followed by fever. The immunocompetent group has a significantly higher accident rate of cough and fever than the immunocompromised group, while the immunocompromised group has a significantly higher accident rate of headache and dizziness (P < 0.05). The positive rate of serum cryptococcal capsular antigen (CrAg) test of the two groups were 83.33% and 86.96%, respectively. While the positive rate of CrAg test in cerebrospinal fluid of the immunocompromised group was significantly higher than that of the immunocompetent group (P < 0.05). The lesions of pulmonary cryptococcosis were predominantly present in the lower part of the lung periphery and significantly distributed in the right lung (P < 0.05). The most common imaging finding of pulmonary cryptococcosis was halo sign (64.58%), followed by multiple nodules, and trachea sign was significantly more common in the immunocompetent group.ConclusionsCryptococcosis has an insidious onset, which can infect healthy people as well. Conducting a CrAg test is good for screening and diagnosing cryptococcosis. We should be alert for the high risk of cryptococcal meningoencephalitis in patients with compromised immune function.

Associations of serum cryptococcal antigen with different of clinical characteristics: a comprehensive analysis of 378 pulmonary cryptococcosis patients.

Pulmonary cryptococcosis (PC) is an infection typically diagnosed in immunocompromised or immunocompetent patients, which can lead to severe disease if not treated appropriately. We aimed to determine the association between clinical manifestations, computed tomography (CT) findings, and host immune status with the serum cryptococcal antigen (CRAG) test results of PC patients. The clinical data of 378 PC patients over a 12-year period were retrospectively reviewed at Shanghai Pulmonary Hospital (Shanghai, China). Serum CRAG was detected by a latex agglutination (LA) test using CryptoTrol (Immuno-Mycologics Inc., Norman, OK, USA). Patients were categorized according to their serum LA results, and their clinical characteristics were analyzed: 244 of 378 patients showed positive serum LA results and 134 had negative results. Immunocompromised hosts (ICH) were more likely to present positive LA results. The ICH group had higher titers of LA test than the non-immunocompromised host (NICH) group. Patients with negative LA results often had no symptoms and their CT findings presented a solitary nodule or mass, while LA-positive patients had variable symptoms such as cough, expectoration, fever, etc. A large diversity of CT manifestations were observed in the LA-positive patients, such as multiple nodules, patchy shadows, interstitial infiltrates, and diffuse granular shadows. Patients with a solitary nodule or mass had lower titers than did the patients with other manifestations. The clinical characteristics of LA-positive patients were different from those of LA-negative patients. Serum CRAG test results were found to be associated with the clinical manifestations, CT findings, and host immune status of PC patients.

Serum cryptococcal antigen testing in immunosuppressed HIV-positive children and adolescents

Background: Describe the epidemiology of immunocompromised HIV-infected paediatric (children and adolescents <19 years) and adults (>19 years) with positive serum Cryptococcal Antigen Lateral Flow Assay (CrAg-LFA) in KwaZulu-Natal (KZN). Methods & Materials Design: Retrospective review of laboratory-based database and clinical charts Methods: A review of the National Health Laboratory Services (NHLS) database of all serum CrAg-LFA performed in KZN between June 2015-December 2016 and comparison of the epidemiology of paediatric and adult patients was conducted. A reflex serum CrAg-LFA (IMMY CrAg® LFA) was performed on samples with CD4 counts <100 cells/μL. Charts of all paediatric patients with a positive CrAgLFA at Prince Mshyeni Memorial Hospital (PMMH) were reviewed and 1 year outcome assessed. Results: A total of 22,741 laboratory records were retrieved and 1140 records were removed due to duplicate entries (1074) and insufficient data (64). There was a statistically significant difference in the incidence of positive CrAg-LFA in paediatrics and adults respectively (40 (3.5%) vs 1194 (5.8%), p = 0.001). The incidence of positive CrAg-LFA in Ethekwini district was 59 and 56 cases per 100,000 persons in adolescents 10–14 years and 15–19 years respectively. Six of the eight patients with available treatment history were on antiretroviral treatment (ART) with immune failure at the time of CrAg-LFA testing. Conclusion: Severe immune suppression in adolescents on ART is a risk factor for cryptococcal antigenaemia. A concerted effort to timeously manage ART failure in adolescents with appropriate changing of ART regimens is urgently warranted.

Epidemiology of Cryptococcal antigenemia among HIV infected patients in South-western Nigeria

Background: Cryptococcosis is a life-threatening fungal infection that presents diversely with no specific pathognomonic features. Cryptococcal disease is one of the most important opportunistic infections, and a major contributor to early mortality in HIV infected subjects. Cryptococcal antigenemia occurs in Nigeria, but the magnitude of this disease remains unclear. This study was carried out to determine the prevalence of CrAg among HIV seropositive and seronegative individuals attending Adeoyo Maternity Teaching Hospital (AMTH), Yemetu, Ibadan. Methods and materials: This was a case-control study in which 114 cases and 228 controls were recruited. Cases were HIV seropositive individuals while controls were HIV seronegative individuals receiving care at AMTH. Adult male and female (age range: 18–65 years) who agree to participate in the study were recruited. Simple random sampling was used to select subjects. Semi-structured interviewer administered questionnaire was used to collect data from subjects and retrospective review of CD4 count records in HIV infected subjects. Five millilitres venous blood was collected from each participant. Serum Cryptococcal antigen testing was done using CrAg Lateral Flow Assay. Data was analyzed using descriptive statistics and bivariate analysis at 5% level of significance. Results: Mean age of cases was 41.2 ± 10.0 years and 85 (74.6%) were females while mean age of control subjects was 38.9 ± 13.7 years 156 (68.4%) were females. The cumulative prevalence of CrAg was 8.5%. However, the prevalence of CrAg among cases was 11.4% and 7.0% among controls. Age groups 41-50 years and 21-30 years were the most affected among cases and controls respectively. HIV positive subjects were about two times more likely to test positive for CrAg. Individuals with CD4 counts of ≤100cells/μl were 20 times more likely to have positive serum cryptococcal antigen than individuals with CD4 counts >100 cells/μl (OR: 20.3, 95%CI: 5.23-78.9). Conclusion: Cryptococcal antigen was present among both cases and controls; however, the prevalence was higher among cases. Since asymptomatic cryptococcal antigenemia predicts impending cryptococcal infection (pneumonia and meningitis) with probable mortality, screening for CrAg should be part of the routine tests amongst all confirmed HIV seropositive cases

Performance of the Lateral Flow Assay and the Latex Agglutination Serum Cryptococcal Antigen Test in Cryptococcal Disease in Patients with and without HIV.

Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed in 227 patients with cryptococcosis. Of 141 HIV-negative patients, 107 had LA testing and 34 had LFA testing. In patients with disseminated disease, serum CrAg sensitivity by LA was 78.1% compared to 82.6% for LFA. In patients with localized pulmonary disease, serum CrAg sensitivity was 23.5% compared to 90.9% for LFA. Of 86 people living with HIV (PLWH), 76 had LA testing, and 10 had LFA testing. Serum CrAg sensitivity for LA was 94.7% compared to 100% for LFA in patients with disseminated disease. We noted a significant improvement in sensitivity from LA testing to LFA testing, predominantly in those with localized pulmonary disease. However, both LFA and LA appear to be less sensitive in HIV-negative patients than previously described in PLWH.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up Risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India: A Prospective Cohort Study.

Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy, the incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and preemptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /μL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. A total of 116 patients were analyzed. Asymptomatic cryptococcal antigenemia was detected in 5.17% of patients and is correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Serum cryptococcal antigen positivity is correlated with an increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/μL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

Clinicopathological features of isolated pulmonary cryptococcosis in HIV-negative patients.

ObjectiveTo analyse the clinicopathological features of isolated pulmonary cryptococcosis in human immunodeficiency virus (HIV)-negative patients.MethodsThis retrospective study analysed the following data from HIV-negative patients diagnosed with pulmonary cryptococcosis: demographics, underlying diseases, clinical manifestations on admission, laboratory tests, imaging data, results of histopathology, treatment options and outcomes. Sputum samples from all patients were collected and assessed for the presence of yeast or fungi. Cryptococcal antigen testing was performed for some patients. Histopathological analysis was also undertaken for some samples of lung tissue.ResultsThe study analysed 37 patients (22 males). Thirteen (35.14%) patients were asymptomatic, 24 (64.86%) were symptomatic and 17 (45.95%) patients had no underlying disease. Out of 25 tested patients, 23 (92.00%) tested positive on the serum cryptococcal capsular polysaccharide antigen test. During 6 to 24 months of follow-up, all 37 patients that were either treated with or without antifungal therapy alone or combined with surgical resection showed complete recovery. One patient made a full recovery without any treatment.ConclusionEarly identification of pulmonary cryptococcosis in HIV-negative patients and timely detection of cryptococcal antigens in serum or respiratory specimens may help to improve diagnosis, prognosis and treatment of the disease.

Presentation and outcome of suspected sepsis in a high-HIV burden, high antiretroviral coverage setting

ObjectiveTo define sepsis syndromes in high-HIV burden settings in the antiretroviral therapy (ART) era. MethodsWe characterized a prospective cohort of adults presenting to a tertiary emergency department in Harare, Zimbabwe with suspected community-acquired sepsis using blood and urine cultures, urine tuberculosis lipoarabinomannan (TB LAM), and serum cryptococcal antigen (CrAg) testing. The primary outcome was 30-day all-cause mortality. ResultsOf 142 patients enrolled 68% (n=96/142, 95% confidence interval (CI) [60–75%]) were HIV-positive, 41% (n=39/96, 95% CI [31–50%]) of whom were ART-naïve. Among HIV-positive patients, both opportunistic pathogens (TB LAM-positivity, 36%, 95% CI [24–48%]; CrAg-positivity, 15%, 95% CI [7–23%]) and severe non-AIDS infections (S. pneumoniae urine antigen-positivity 12%, 95% CI [4–20%]; bacteraemia 17% (n=16/96, 95% CI [9–24%]), of which 56% (n=9/16, 95% CI [30–80%]) were gram-negative organisms) were common. Klebsiella pneumoniae recovered from blood and urine was uniformly resistant to ceftriaxone, as were most Escherichia coli isolates. Acknowledging the power limitations of our study, we conclude that relative to HIV-negative patients, HIV-positive patients had modestly higher 30-day mortality (adjusted hazard ratio (HR) 1.88, 95% CI [0.78–4.55]; p=0.16, and 3.59, 95% CI [1.27–10.16], p=0.02) among those with and without viral suppression, respectively. ConclusionRapid point-of-care assays provide substantial clinically actionable information in the setting of suspected sepsis, even in areas with high ART coverage. Antimicrobial resistance to first-line antibiotics in high burden settings is a growing threat.

Serum Cryptococcal Antigen Testing in Immunosuppressed HIV-positive Children and Adolescents.

Describe the epidemiology of immunocompromised HIV-infected pediatric (children and adolescents ≤ 19 years) and adults (> 19 years) with positive serum cryptococcal antigen lateral flow assay (CrAg-LFA) in KwaZulu-Natal. Retrospective review of laboratory-based database and clinical charts. A review of the National Health Laboratory Services database of all serum CrAg-LFA performed in KwaZulu-Natal between June 2015 and December 2016 and comparison of the epidemiology of pediatric and adult patients was conducted. A reflex serum CrAg-LFA (IMMY CrAg-LFA) was performed on samples with CD4 counts < 100 cells/μL. Charts of all pediatric patients with a positive CrAg-LFA at Prince Mshiyeni Memorial Hospital were reviewed and 1-year outcome assessed. A total of 22,741 laboratory records were retrieved, and 1140 records were removed because of duplicate entries (1074) and insufficient data (64). There was a statistically significant difference in the incidence of positive CrAg-LFA in pediatrics and adults, respectively [40 (3.5%) versus 1194 (5.8%), P = 0.001]. The incidence of positive CrAg-LFA in Ethekwini district was 59 and 56 cases per 100,000 persons in adolescents 10-14 years and 15-19 years, respectively. Six of the 8 patients with available treatment history were on antiretroviral treatment (ART) with immune failure at the time of CrAg-LFA testing. Severe immune suppression in adolescents on ART is a risk factor for cryptococcal antigenemia. A concerted effort to timeously manage ART failure in adolescents with appropriate changing of ART regimens is urgently warranted.

Should we perform the serum cryptococcal antigen test in people living with HIV hospitalized due to a community-acquired pneumonia episode?

Community-acquired pneumonia (CAP) is a common cause of hospitalization among people living with human immunodeficiency virus (PLWH), particularly those with severe immunosuppression. Pulmonary disease due to cryptococcosis is uncommonly reported and likely under-diagnosed. There is scarce information about cryptococcal antigen (CrAg) prevalence in PLWH with CAP. The objectives of this study were to identify among PLWH who were hospitalized with CAP: (i) the prevalence of serum CrAg positivity, (ii) the proportion with asymptomatic vs. symptomatic cryptococcosis; and (iii) the prevalence of serum CrAg positivity in CD4+ T-cell count &lt;100 cells/mm3. We performed a sub-analysis of a prospective cohort of hospitalized adults enrolled into a randomized clinical trial testing therapy for CAP. We included 202 participants who had serum CrAg testing performed. We found a 3.5% prevalence of serum CrAg-positivity overall, being higher (5.7%) in CD4+ T-cell count &lt;100 cells/mm3. Overall, asymptomatic and symptomatic cryptococcosis were present in 2.0% and 1.5%, respectively. This study identifies a target population for CrAg testing: PLWH hospitalized with diagnosis of CAP, particularly those with CD4+ T-cell count &lt;100 cells/mm3 where the number needed to test was 18 to detect 1 CrAg-positive person. This approach may facilitate the detection of asymptomatic cryptococcal infection and allow a timely diagnosis of symptomatic cryptococcal disease.

Cryptic pulmonary cryptococcosis: An atypical presentation of pulmonary cryptococcosis in a HIV-infected patient

Pulmonary cryptococcosis is a fungal infection caused by inhalation of Cryptococcus gattii and/or C. neoformans spores. It mostly affects HIV-infected patients. This is a case report of a severely immunocompromised HIV-infected patient, presenting with respiratory symptoms and atypical chest X-ray features for pulmonary cryptococcosis. A serum cryptococcal latex antigen test is positive in a majority of HIV-infected patients with pulmonary cryptococcosis. This case report demonstrates the occurrence of a false negative serum cryptococcal latex antigen test, becoming positive with the development of an unmasking immune reconstitution syndrome (after antiretroviral therapy was commenced). This also resulted in the characteristic cryptococcal lung cavities observed on computed tomography chest images. Duration of fluconazole therapy should be individualised, and serial chest imaging (e.g. chest X-ray) should be performed to monitor treatment response.

Epidemiology of Cryptococcal antigenemia among HIV infected patients in southwestern Nigeria

Cryptococcosis is a life-threatening fungal infection that presents diversely with no specific pathognomonic features. Cryptococcal disease is one of the most important opportunistic infections, and a significant contributor to early mortality in HIV infected subjects. Cryptococcal antigenemia occurs in Nigeria, but the magnitude of this disease remains unclear. This study was carried out to determine the prevalence of CrAg among HIV infected and HIV seronegative subjects and to assess the relationship between CD4 count and CrAg in HIV-positive subjects attending Adeoyo Maternity Teaching Hospital, Yemetu, Ibadan. In an hospital-based case-control study using simple random sampling, 114 HIV-seropositive individuals (cases) and 228 HIV-seropositive individuals (controls) were recruited. A semi-structured interviewer-administered questionnaire was used to collect data from subjects and retrospective review of CD4 count records in HIV infected subjects. Five millilitres of venous blood were collected from each participant. Serum Cryptococcal antigen testing was done using CrAg Lateral Flow Assay. Data was analyzed using descriptive statistics and bivariate analysis at 5% level of significance. Mean age of cases was 41.2 ± 10.0 years and 85 (74.6%) were females while mean age of controls was 38.9 ± 13.7 years and 156 (68.4%) were females. The prevalence of CrAg among cases was 11.4% and 7.0% among controls. Cases were about two times more likely to test positive for CrAg. However, the association was not statistically significant (OR: 1.71, 95%CI: 0.79 - 3.68). Individuals with CD4 counts of ≤100 cells/µl were 20 times more likely to have positive serum cryptococcal antigen than individuals with CD4 counts >100 cells/µl (OR: 20.3, 95%CI: 5.23-78.9). This study has demonstrated significant prevalence of Cryptococcal antigenemia among the study population; however, prevalence was higher among cases. Screening for CrAg should therefore be part of routine tests amongst all confirmed HIV seropositive cases, since asymptomatic cryptococcal antigenemia predicts impending cryptococcal infection with probable mortality.

2272 A Case of Cryptococcal Hepatitis in HIV Patient With a Negative Serum Cryptococcal Antigen

INTRODUCTION: Infectious Cryptococcus neoformans occurs primarily in immunocompromised patients. The primary organ affected is the lungs, but CNS and skin involvement can also be seen. Disseminated Cryptococcosis can involve any organ in the body. However, hepatic involvement is rare. Here we offer a case of Cryptococcus hepatitis in a patient who presented with persistently elevated liver enzymes. CASE DESCRIPTION/METHODS: A 56-year-old Hispanic female with no known past medical history presented with fever, abdominal pain, nausea, unintentional weight loss, and diarrhea for two months. On physical examination, she was tachycardic with a heart rate of 110 bpm, and her abdomen was soft but tender to palpation in the right upper quadrant. Her liver function tests (LFTs) revealed elevated Aspartate Aminotransferase (AST) (415 U/L), elevated Alanine Aminotransferase (ALT) (201 U/L), elevated Alkaline Phosphatase (ALP) (763 U/L), normal total Bilirubin (0.9 mg/dl), and additional laboratory results in Table 1. Her HIV antigen screening was reactive, and absolute CD4 count was 22/ mcL. CT scan of the chest revealed two small calcified granulomas, for which she was started prophylactically on Azithromycin and TMP/SMZ. Over the course of her hospital stay, the patient's liver enzymes continued to trend upward while further workup ruled out hepatitis A, B, C, Wilson's disease, Hemochromatosis, AIH, PBC, PSC, other causes of viral hepatitis (CMV, EBV, HSV), with negative Histoplasma antibodies and negative serum Cryptococcal antigen titers. During the second week of hospitalization, her liver enzymes continued to rise with an ALP of 4046 U/L, AST of 407 U/L, and ALT of 276 U/L. With a persistent elevation of the liver enzymes without any definitive cause, an ultrasound-guided biopsy was warranted and performed. Pathology revealed Cryptococcal hepatitis (Figures 1 and 2), and the patient was started on a 15-day course of Amphotericin B with an 8-week course of Fluconazole 400 mg with LFTs nearly normalizing at 6 weeks. DISCUSSION: This case demonstrates an unusual manifestation of Cryptococcosis. Our patient did not present with the typical Cryptococcal pulmonary or central nervous system infection. As well, our patient's serum Cryptococcal antigen titers were negative, but biopsy results revealed Cryptococcal hepatitis, despite a very high sensitivity and specificity of the serum Cryptococcal antigen test. This case demonstrates the importance of maintaining a broad differential, specifically in immunocompromised patients.

Validation of clinic-based cryptococcal antigen lateral flow assay screening in HIV-infected adults in South Africa

Since rapid cryptococcal antigen lateral flow assays (CrAg LFA) may expedite treatment of HIV-associated cryptococcal infections, we sought to validate clinic-based CrAg LFA testing. Among newly-diagnosed HIV-infected adults in South Africa, a trained nurse performed clinic-based testing of urine, fingerprick capillary and venous whole blood with rapid CrAg LFA (Immy Diagnostics, Norman, USA). We performed matched laboratory-based serum cryptococcal antigen testing with an enzyme immunoassay (EIA). We assessed diagnostic accuracy using EIA as the gold-standard, and performed additional validation testing on serum and among hospitalized adults with cryptococcal meningitis. Among 5,618 participants enrolled, 1,296 were HIV-infected and screened for cryptococcal antigenemia. Overall CrAg prevalence by serum EIA was 3.6% (95% CI 2.0–6.0%) for adults with CD4 < 200 cells/mm3, and 5.7% (95% CI 2.8–10.2%) for adults with CD4 < 100 cells/mm3. Using expanded screening guidelines (CD4 < 200 cells/mm3), CrAg LFA testing of venous whole blood, fingerprick capillary blood, and urine had diagnostic sensitivities of 46% (95% CI 19–75%), 38% (95% CI 14–68%), and 54% (95% CI 25–81%), and specificities of 97%, 97%, and 86%, respectively. When tested on serum samples, CrAg LFA had sensitivity of 93% (95% CI 66–100%) and specificity of 100% (95% CI 88–100%). All venous and fingerprick whole blood CrAg LFA tests were positive among 30 hospitalized adults with cryptococcal meningitis. Two independent readers had strong agreement for all LFA results (p < 0.0001). When performed at the point-of-care by trained nurses, CrAg LFA testing was feasible, had the highest accuracy on serum specimens, and may accelerate treatment of HIV-associated cryptococcal infections.