Serum Cryptococcal Antigen Test Research Articles

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.

64-Year-Old Man With Subacute Altered Mental Status and Headache

64-Year-Old Man With Subacute Altered Mental Status and Headache

The performance of serum cryptococcal capsular polysaccharide antigen test, histopathology and culture of the lung tissue for diagnosis of pulmonary cryptococcosis in patients without HIV infection.

BackgroundClinicians may fail to make an early diagnosis of pulmonary cryptococcosis (PC) without HIV infection. Serum cryptococcal capsular polysaccharide antigen (CrAg) test, histopathology and culture of lung tissue play different roles in diagnosis of PC.ObjectiveTo investigate the performance of serum CrAg test, histopathology and culture of the lung tissue in diagnosis of PC without HIV infection.Patients/methodsFrom January 2011 to September 2017, patients with proven PC were recruited from a teaching hospital in southern China. Those patients with HIV infection, PC confirmed by surgery or PC with probable or possible diagnosis were excluded from the study. Latex agglutination test and CrAg lateral flow assay were used for detection of serum CrAg. Lung biopsy and needle aspiration were performed under computed tomography guidance.ResultsEighty-nine patients with proven PC including 41 male (46.1%) and 48 female (53.9%) were enrolled. Fifty-one (57.3%) patients had underlying disease. Positive CrAg test was found in 83 (93.3%) cases. Among six cases with negative CrAg test, PC was confirmed by histology in two cases and positive culture in four cases. The histopathological results of 77 (86.5%) cases revealed cryptococcal granuloma and 12 cases showed chronic inflammation, which was confirmed by positive culture. Among 65 cases, the diseased tissue of 46 (70.8%) cases presented Cryptococcus neoformans in the culture and one case was diagnosed with lung cancer coexisting with PC.ConclusionOur findings showed that serum CrAg test is rapid and sensitive in diagnosing PC, histology is important for confirming PC and culture plays a complementary role. Biopsied lung tissue should be submitted for cultures whenever feasible.

Serum cryptococcal antigen titre as a diagnostic tool and a predictor of mortality in HIV-infected patients with cryptococcal meningitis.

The aim was to determine the effectiveness of the serum cryptococcal antigen (CrAg) test in the diagnosis of concurrent cryptococcal meningitis (CM) and as a predictor of mortality in HIV-infected patients. In this retrospective study, all HIV-infected patients admitted to Shanghai Public Health Clinical Center from 1 January 2014 to 31 August 2016 were screened for serum CrAg using the latex agglutination test. Serum CrAg-positive patients underwent lumbar puncture to confirm CM prior to the initiation of appropriate antifungal therapy and were followed up for at least 6months. One hundred and four (7.1%) of the total of 1474 HIV-infected patients screened were serum CrAg-positive. CM was diagnosed in the majority of serum CrAg-positive patients (71.3%; 67 of 94) and was confirmed in all (46 of 46) of the patients with headache or coma and in 43.8% (21 of 48) of patients without neurological symptoms. CrAg titres ≥1:1024 showed a sensitivity of 82.5% and a specificity of 86.7% for the diagnosis of concurrent CM (P<0.001). The positive predictive value for CM in this population was 94.3%. A total of 13 serum CrAg-positive patients [13.8%; 95% confidence interval (CI) 7.5-22.4%] died (11 as a result of CM and two others as a result of bacterial pneumonia) despite early antifungal treatment initiation. Serum CrAg titres ≥1:1024 predicted all-cause mortality (hazard ratio3.69; P=0.03). Serum CrAg titres ≥1:1024 not only were associated with concurrent CM but also predicted mortality. HIV-infected patients with a positive serum CrAg test during screening should receive lumbar punctures regardless of symptoms to rule out CM and patients with serum CrAg titres ≥1:1024 should be offered immediate care.

Extent of Lung Involvement and Serum Cryptococcal Antigen Test in Non-Human Immunodeficiency Virus Adult Patients with Pulmonary Cryptococcosis.

Background:Serum cryptococcal antigen (CrAg) test is the most used noninvasive method to detect cryptococcal infection. However, false-negative CrAg test is not uncommon in clinical practice. Then, the aim of this study was to investigate the factors associated with false-negative CrAg test among non-human immunodeficiency virus (HIV) adult patients with pulmonary cryptococcosis and its clinical features.Methods:One hundred and fourteen non-HIV adult patients with pulmonary cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85 patients were enrolled; 56 were CrAg positive (CrAg+ group) and 29 were negative (CrAg− group). It was a cross-sectional study. Then, baseline characteristics, underlying diseases, clinical symptoms, laboratory findings, and chest radiological findings were reviewed and analyzed. Chi-square test was used to analyze categorical variable. Odds ratio (OR) was used to measure correlation. Student's t-test was obtained to analyze continuous variable.Results:No difference in baseline characteristics, underlying diseases, clinical symptoms, and laboratory findings were found between two groups (P > 0.05 in all). Nevertheless, diffuse extent lesion was 82.1% in CrAg+ group and 10.3% in CrAg− group (χ2= 40.34, P < 0.001; OR = 39.87).Conclusions:Among patients with limited pulmonary involvement, a negative serum CrAg does not preclude the diagnosis of pulmonary cryptococcosis. However, among patients with extensive pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary cryptococcosis. Furthermore, we also noticed that the untypical and mild presentations with extensive pulmonary lesion might be the features of pulmonary cryptococcosis, which needs further investigation.

Miliary tuberculosis with co-existing pulmonary cryptococcosis in non-HIV patient without underlying diseases: a case report

BackgroundTuberculosis and cryptococcosis co-infection usually occurs in immunosuppressed patients with impaired cell-mediated immunity. However, there are few reports about such co-infection in non-HIV patients without underlying diseases. Here, we report a case of miliary tuberculosis with co-existing pulmonary cryptococcosis in non-HIV patient without underlying diseases.Case presentationAn 84-year-old Asian female presented to our hospital with complaints of a 1-week history of abdominal pain and appetite loss. Chest computed tomography (CT) showed diffuse micronodules in random patterns in both lung fields. Liver, skin and bone marrow biopsies showed epithelioid cell granuloma. Polymerase chain reaction of gastric aspirate was positive for Mycobacterium tuberculosis. According to these findings, miliary tuberculosis was suspected and antimycobacterial therapy was initiated. After a 6-month treatment course, chest radiograph showed new multiple nodules in the right middle lung field. Chest CT showed that a right S6 small nodule was increased and new multiple nodules appeared in the right lower lobe. Flexible fiberoptic bronchoscopy was subsequently perfomed. Cytology of the bronchial lavage showed a small number of Periodic acid-Schiff-positive bodies, suggesting Cryptococcus species. Moreover, serum cryptococcal antigen testing was positive. According to these findings, pulmonary cryptococcosis was diagnosed, although the culture was negative. Oral fluconazole therapy was subsequently initiated. After a 6-month treatment course, chest radiograph showed gradual improvement.ConclusionAlthough tuberculosis and cryptococcosis co-infection is relatively rare in immunocompromised hosts, such as those with acquired immunodeficiency syndrome, clinicians should be aware that these infections can co-exist even in non-HIV patients without underlying diseases.

Disseminated Cryptococcal Disease of the Bone Marrow, Cerebrospinal Fluid and Blood in an ART-Naive Patient with Advanced HIV: A Case Report

Background: Cryptococcosis affects 10-30% of patients with acquired immunodeficiency syndrome (AIDS) resulting in significant morbidity and mortality. The primary sites of cryptococcal disease are the lung and central nervous system with bone marrow involvement being rare.Case presentation: This case report describes a human immunodeficiency virus (HIV) positive, anti-retroviral therapy (ART) naive female with pancytopenia who demonstrated no significant symptoms nor clinical signs as well as a negative serum cryptococcal antigen (CrAg) test. A bone marrow biopsy was then performed which resulted in a diagnosis of disseminated cryptococcal disease of the bone marrow. Blood and cerebrospinal fluid (CSF) fungal cultures confirmed the presence of Cryptococcus neoformans. The patient was then successfully treated with antifungal agents-amphotericin B and fluconazole.Conclusion: Bone marrow examination may therefore be a useful method in early diagnosis of disseminated cryptococcosis as a cause of cytopenias in immunocompromised patients, thus enabling early appropriate treatment and improved outcomes.

Epidemiology of Cryptococcal Infections in a General Hospital Over 4 Years

SESSION TITLE: Chest Infections SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: To evaluate the epidemiology, clinical presentation, treatments and outcomes of patients with cryptococcosis in Singapore. METHODS: A electronic medical record search was performed for patients admitted from 2012 to 2015. 7 patients were identified to have cryptococcosis. 4 patients were infected by C. neoformans and 3 by C. gattii. Diagnosis was made by imaging, serum or cerebral spinal fluid (CSF) cryptococcal antigen testing, India ink staining, and culture of CSF or bronchoalveolar lavage. RESULTS: Cryptococcosis is an uncommon fungal infection, caused by Cryptococcus neoformans or Cryptococcus gattii, that affects both immunosuppressed and immunocompetent hosts. Cryptococcosis can be localised or disseminated, giving rise to pulmonary, neurological or cutaneous manifestations. Of the 7 patients with cryptococcosis, 4 were infected by C. neoformans. 3 of those infected were immunosuppressed (43%), with HIV infection or on long-term high dosage corticosteroids. Clinical manifestations of cryptococcosis included cough (42.8%), fever (42.8%), headache (42.8%), dyspnea (28.5%), chest pain (28.5%), loss of appetite (28.5%), loss of weight (14.3%), hearing loss (14.3%), focal limb weakness (14.3%) and rash (14.3%). Abnormal radiological findings such as lung consolidations (57.1%), lung cryptococcomas (42.8%), brain cyptococcomas (42.8%), pleural effusions (4.3%), cavitations (14.3%), leptomeningeal enhancements (28.5%) were evident. All patients affected by C. gattii were immunocompetent, and had disseminated disease with pulmonary and cerebral involvement. Treatment was with fluconazole as initial therapy, with 57.1% of these patients receiving concurrent amphotericin B due to cerebral involvement. Outcome was generally good with treatment, with 85.7% survival within 6 months of diagnosis. CONCLUSIONS: Cryptococcus infections, while uncommon, can present in both immunocompromised and immunocompetent hosts. CLINICAL IMPLICATIONS: Early diagnosis and treatment of cryptococcus infections with antifungal therapy, and regular follow-up monitoring is important to achieve good outcomes. DISCLOSURE: The following authors have nothing to disclose: Jaslyn Gao, Jessica Quah, Teck Boon Low No Product/Research Disclosure Information

High Prevalence of Cryptococcal Antigenaemia and Disseminated Cryptococcal Disease Amongst Patients with Advanced HIV Disease in Pune, India

Background The World Health Organization (WHO) recommends routine cryptococcal antigen (CrAg) screening in patients with advanced HIV disease initiating antiretroviral treatment (ART). India has yet to adopt this strategy as the burden of cryptococcal disease is unknown.Methods This was a prospective cohort study conducted between March 1, 2010 and March 1, 2017 at three private hospitals in Pune, India. All HIV-positive patients (symptomatic and asymptomatic) with CD4 counts ≤ 200 cells/µL were screened for serum cryptococcal antigen. Serum CrAg was measured using latex agglutination (LA) test. Both, ART naïve and ART experienced patients were included in the study. All HIV infected patients who were CrAg-positive were offered lumbar puncture (LP) and worked up for disseminated cryptococcal disease.ResultsA total of 785 HIV-positive patients (24.2% females) were included. Median age of cohort was 42 years (IQR, 35–49) and median CD4 count was 79 cells/mm3 (IQR, 37–82). 182/785(23.2%) patients were ART experienced. A total of 6.75% (53/785) of patients were CrAg positive in serum. Thirty-nine of 53 (73.6%) patients with positive serum cryptococcal antigen test had CD4 count ≤100 cells/mm3 while 14/53 (26.4%) had CD4 between 100 and 200 cells/mm3. Cerebrospinal fluid (CSF) CrAg was positive in 44/53(83%) patients. Two of 53(3.78%) had non-CNS, diffuse pulmonary cryptococcal disease and 7/53(13.2%) patients had isolated cryptococcal antigenemia. Patients with cryptococcal meningitis and crptococcal pulmonary disease were treated with Amphotericin-B plus oral Fluconazole. Patients with isolated cryptococcal antigenemia were treated with oral Fluconazole. Mortality at 6 months for patients with positive CrAg test was 22.6% (12/53).Conclusion We found 6.75% prevalence of cryptococcaemia amongst HIV patients with CD4 <200 cells/mm3. Given the high fatality rates observed, routine CrAg screening should be considered for all Indians with advanced HIV disease.Disclosures All authors: No reported disclosures.

Risk Factors for Cryptococcal Meningitis: A Single United States Center Experience.

Cryptococcal meningitis carries a high mortality. Further understanding of immune suppression factors associated with neuroinvasive infection will improve risk stratification and enhance early diagnosis and treatment with antifungal therapy. The aim of the study was to corroborate established or find novel clinical predictors for cryptococcal meningitis. We performed a matched case-control study of Cryptococcus infection in immunocompromised patients with or without cryptococcal meningitis. Data of all patients with a diagnosis of cryptococcal disease were collected at University of Colorado Hospital between 2000 and 2015 (n=51). Thirty patients were diagnosed with cryptococcal meningitis. We built a logistic regression model for risk factors associated with cryptococcal meningitis. The single-predictor univariate model found that a positive blood culture, positive serum cryptococcal antigen, current malignancy, and headaches were significantly associated with cryptococcal meningitis (p=0.02). In the adjusted multivariate model, central nervous system disease was significantly associated with a diagnosis of HIV infection (OR 24.45, 95% CI 1.62-350.37; p=0.022) and a positive serum cryptococcal antigen test (OR 42.92, 95% CI 3.26-555.55; p=0.0055). In patients with HIV infection or a positive serum cryptococcal antigen, the pretest probability of neuroinvasive Cryptococcus infection is increased and an aggressive diagnostic evaluation should be conducted to exclude infection and consider empiric therapy.

Cryptococcus: Shedding New Light on an Inveterate Yeast.

Cryptococcus has emerged as a significant pathogen in immunocompromised patients. While the diagnostic testing and the antifungal treatment of cryptococcal infections have become firmly established in clinical practice, new developments and areas of ambiguity merit further consideration. These include the potential for donor transmission of Cryptococcus; cirrhosis-associated cryptococcosis, particularly during transplant candidacy; the utility of serum cryptococcal antigen testing of asymptomatic individuals in high-prevalence, poor-resource areas; pathogenesis and treatment of the immune reconstitution syndrome, specifically in relation to antiretroviral therapy and immunosuppressive medications; and new challenges posed by the emerging species of Cryptococcus gatti. In this article, we summarize the literature pertaining to these topics, focusing on recent progress.

Disseminated fatal Talaromyces (Penicillium) marneffei infection in a returning HIV-infected traveller

We report a case of disseminated fatal Talaromyces (Penicillium) marneffei infection in an HIV-infected, antiretroviral treatment-experienced South African woman who had travelled to mainland China. The 37-year-old woman was admitted to a private hospital in fulminant septic shock and died within 12 h of admission. Intracellular yeast-like bodies were observed on the peripheral blood smear. A serum cryptococcal antigen test was negative. Blood cultures flagged positive after 2 days; on direct microscopy, yeast-like bodies were observed and a thermally dimorphic fungus, confirmed as T. marneffei, was cultured after 5 days. The clinical features of HIV-associated disseminated penicilliosis overlap with those of tuberculosis and endemic deep fungal infections. In the southern African context, where systemic opportunistic fungal infections such as cryptococcosis are more common among HIV-infected patients with a CD4+ count of &lt;100 cells/µL, this infection is not likely to be considered in the differential diagnosis unless a travel history is obtained.

Disseminated fatal Talaromyces (Penicillium) marneffei infection in a returning HIV-infected traveller

We report a case of disseminated fatal Talaromyces (Penicillium) marneffei infection in an HIV-infected, antiretroviral treatment-experienced South African woman who had travelled to mainland China. The 37-year-old woman was admitted to a private hospital in fulminant septic shock and died within 12 h of admission. Intracellular yeast-like bodies were observed on the peripheral blood smear. A serum cryptococcal antigen test was negative. Blood cultures flagged positive after 2 days; on direct microscopy, yeast-like bodies were observed and a thermally dimorphic fungus, confirmed as T. marneffei, was cultured after 5 days. The clinical features of HIV-associated disseminated penicilliosis overlap with those of tuberculosis and endemic deep fungal infections. In the southern African context, where systemic opportunistic fungal infections such as cryptococcosis are more common among HIV-infected patients with a CD4+ count of <100 cells/µL, this infection is not likely to be considered in the differential diagnosis unless a travel history is obtained.

The impact of routine cryptococcal antigen screening on survival among HIV‐infected individuals with advanced immunosuppression in Kenya

To test the hypothesis that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV-infected individuals with low CD4 cell counts. Newly enrolled patients at Family AIDS Care and Education Services (FACES) in Kenya with CD4≤100 cells/μl were tested for serum cryptococcal antigen (sCrAg). Individuals with sCrAg titre≥1:2 were treated with high-dose fluconazole. Cox proportional hazard models of Kaplan-Meier curves were used to compare survival among individuals with CD4≤100 cells/μl in the intervention and historical control groups. The median age was 34years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/μl [IQR: 18,71]. Follow-up time was 1224 person-years. In the intervention group, 66% (514/782) were tested for sCrAg; of whom, 11% (59/514) were sCrAg positive. Mortality was 25% (196/782) in the intervention group and 25% (191/771) in the control group. There was no significant difference between the intervention and control group in overall survival [hazard ratio (HR): 1.1 (95%CI:0.9,1.3)] or three-month survival [HR: 1.0 (95%CI:0.8,1.3)]. Within the intervention group, sCrAg-positive individuals had significantly lower survival rates than sCrAg-negative individuals [HR:1.8 (95%CI: 1.0, 3.0)]. A screening and treatment intervention to identify sCrAg-positive individuals and treat them with high-dose fluconazole did not significantly improve overall survival among HIV-infected individuals with CD4 counts≤100 cells/μl compared to a historical control, perhaps due to intervention uptake rates or poor efficacy of high-dose oral fluconazole.

Clinical features and epidemiology of cryptococcosis in cats and dogs in California: 93 cases (1988–2010)

To compare clinical features of cryptococcosis among cats and dogs in California, determine whether the distribution of involved tissues differs from distribution reported previously in a study in southeastern Australia, and identify Cryptococcus spp isolated from the study population. Retrospective case series. 62 cats and 31 dogs with cryptococcosis. Medical records of cats and dogs with cryptococcosis were reviewed. Information collected included geographic location, species, signalment, and tissues or organs involved. Cryptococcosis was confirmed via serology, cytology, histology, or microbial culture, and molecular typing was performed. Odds ratios and 95% confidence intervals were calculated to determine significant associations among variables. Other comparisons were evaluated via χ(2) or unpaired t tests. American Cocker Spaniels were overrepresented, compared with other dog breeds. Serum cryptococcal antigen test results were positive in 51 of 53 cats and 15 of 18 dogs tested. Cryptococcus gattii was more commonly detected in cats (7/9 for which species identification was performed), and Cryptococcus neoformans was more commonly detected in dogs (6/8). Six of 7 C gattii isolates from cats were molecular type VGIII. Distribution of involved tissues was different between cats and dogs in California and between populations of the present study and those of the previously reported Australian study. Strains of Cryptococcus spp appeared to have host specificity in dogs and cats. Differences in lesion distribution between geographic locations may reflect strain differences or referral bias. Antigen assays alone may not be sufficient for diagnosis of cryptococcosis in cats and dogs.

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania.

To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV-1 RNA PCR was performed on those aged <18 months. HIV-infected patients also received serum cryptococcal antigen testing and had their CD4-positive T-lymphocyte count and percent determined. A total of 467 patients were enrolled whose median age was 2 years (range 2 months-13 years); Of those patients, 57.2% were female and 12.2% were HIV-infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV-uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively. Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over-diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co-infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.

Invasive Bacterial and Fungal Infections Among Hospitalized HIV-Infected and HIV-Uninfected Adults and Adolescents in Northern Tanzania

few studies describe patterns of human immunodeficiency virus (HIV) co-infections in African hospitals in the antiretroviral therapy (ART) era. we enrolled consecutive admitted patients aged ≥ 13 years with oral temperature of ≥ 38.0°C during 1 year in Moshi, Tanzania. A standardized clinical history and physical examination was done and hospital outcome recorded. HIV antibody testing, aerobic and mycobacterial blood cultures, and malaria film were performed. HIV-infected patients also received serum cryptococcal antigen testing and CD4(+) T lymphocyte count (CD4 cell count). of 403 patients enrolled, the median age was 38 years (range, 14-96 years), 217 (53.8%) were female, and 157 (39.0%) were HIV-infected. Of HIV-infected patients, the median CD4 cell count was 98 cells/μL (range, 1-1,105 cells/ μL), 20 (12.7%) were receiving ART, and 29 (18.5%) were receiving trimethoprim-sulfamethoxazole prophylaxis. There were 112 (27.7%) patients who had evidence of invasive disease, including 26 (23.2%) with Salmonella serotype Typhi infection, 24 (21.4%) with Streptococcus pneumoniae infection, 17 (15.2%) with Cryptococcus neoformans infection, 12 (10.7%) with Mycobacterium tuberculosis complex infection, 8 (7.1%) with Plasmodium falciparum infection, and 7 (6.3%) with Escherichia coli infection. HIV infection was associated with M. tuberculosis and C. neoformans bloodstream infection but not with E. coli, S. pneumoniae, or P. falciparum infection. HIV infection appeared to be protective against Salmonella. Typhi bloodstream infection (odds ratio, .12; P = .001). while Salmonella Typhi and S. pneumoniae were the most common causes of invasive infection overall, M. tuberculosis and C. neoformans were the leading causes of bloodstream infection among HIV-infected inpatients in Tanzania in the ART era. We demonstrate a protective effect of HIV against Salmonella. Typhi bloodstream infection in this setting. HIV co-infections continue to account for a large proportion of febrile admissions in Tanzania.

A Case of Cryptococcal Lymphadenitis in an HIV-Infected Child

An 8-year-old HIV-positive antiretroviral therapy-naive child developed severe headache and generalized lymphadenopathy. The serum cryptococcal antigen (CRAG) test was positive, the histology on the lymph node biopsy revealed budding yeast cells, and Cryptococcus neoformans was isolated on culture of his cerebrospinal fluid. He was treated with intravenous amphotericin B followed by oral fluconazole with a good response. Therefore cryptococcal lymphadenitis should be considered in the differential diagnosis of children presenting with lymphadenopathy and a positive serum CRAG.

Pulmonary cryptococcosis misdiagnosed as smear-negative pulmonary tuberculosis with fatal consequences

HIV-associated pulmonary cryptococcosis is under diagnosed, and may progress to fatal meningoencephalitis. We present a case of HIV-associated pulmonary Cryptococcus neoformans infection, initially mis-diagnosed as smear-negative pulmonary TB, which progressed to fatal cryptococcal meningitis. Autopsy series suggest that pulmonary cryptococcosis is common in African AIDS patients, and, due to limited diagnostic capacity, often mis-diagnosed as smear negative TB. Serum cryptococcal antigen testing may facilitate diagnosis in such cases.

Cryptococcal immune reconstitution inflammatory syndrome presenting with erosive bone lesions, arthritis and subcutaneous abscesses

Cryptococcal immune reconstitution inflammatory syndrome presenting with erosive bone lesions, arthritis and subcutaneous abscesses