Concurrent Cryptococcal Meningitis Research Articles

Newly Diagnosed Severe AIDS with Recovery of CMV Retinitis with concurrent Cryptococcal Meningitis

Newly Diagnosed Severe AIDS with Recovery of CMV Retinitis with concurrent Cryptococcal Meningitis

Association of semi-quantitative cryptococcal antigen results in plasma with subclinical cryptococcal meningitis and mortality among patients with advanced HIV disease.

We evaluated two single-step laboratory tests that can quantify the amount of cryptococcal antigen in plasma of patients with advanced HIV disease and could thus gauge the risk of concurrent cryptococcal meningitis and subsequent mortality. These tests are not a substitute for a lumbar puncture.

A case report of disseminated histoplasmosis and concurrent cryptococcal meningitis in a patient treated with ruxolitinib

BackgroundRuxolitinib is a highly potent janus kinase inhibitor that places its users at risk for various bacterial infections and viral reactivation. However new reports are also emerging that suggest greater immunosuppression and risk for fungal disease.Case presentationWe report the case of a 51 year-old veteran from Guam, treated with ruxolitinib for polycythemia vera, who developed disseminated histoplasmosis and concurrent cryptococcal meningitis.ConclusionThis case draws attention to the degree of immunosuppression that may be seen with this drug and the need for heightened vigilance for opportunistic infections in those treated with inhibitors of janus kinase/signal transducers and activators of transcription (JAK/STAT) such as ruxolitinib.

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.

Concurrent cryptococcal meningitis and pulmonary cryPtococcosis in an immunocompetent patient: A case report

Background: Cryptococcal infection occurs worldwide and is caused by Cryptococcus neoformans and Cryptococcus gattii. Cryptococcosis presents with serious morbidity and mortality concerns in immunocompromised patients but can rarely also be encountered in immunocompetent individuals.

High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients.

High mortality rates among asymptomatic cryptococcal antigen (CrAg)-positive patients identified through CrAg screening, despite preemptive fluconazole treatment, may be due to undiagnosed cryptococcal meningitis. Symptoms were reviewed in CrAg-positive patients identified by screening 19233 individuals with human immunodeficiency virus infection and CD4 cell counts <100/µL at 17 clinics and 3 hospitals in Johannesburg from September 2012 until September 2015, and at 2 hospitals until June 2016. Cerebrospinal fluid samples from 90 of 254 asymptomatic patients (35%) and 78 of 173 (45%) with headache only were analyzed for cryptococcal meningitis, considered present if Cryptococcus was identified by means of India ink microscopy, culture, or CrAg test. CrAg titers were determined with stored blood samples from 62 of these patients. The associations between blood CrAg titer, concurrent cryptococcal meningitis, and mortality rate were assessed. Cryptococcal meningitis was confirmed in 34% (95% confidence interval, 25%-43%; 31 of 90) of asymptomatic CrAg-positive patients and 90% (81%-96%; 70 of 78) with headache only. Blood CrAg titer was significantly associated with concurrent cryptococcal meningitis in asymptomatic patients (P < .001) and patients with headache only (P = .003). The optimal titer for predicting cryptococcal meningitis was >160 (sensitivity, 88.2%; specificity, 82.1%); the odds ratio for concurrent cryptococcal meningitis was 34.5 (95% confidence interval, 8.3-143.1; P < .001). About a third of asymptomatic CrAg-positive patients have concurrent cryptococcal meningitis. More effective clinical assessment strategies and antifungal regimens are required for CrAg-positive patients, including investigation for cryptococcal meningitis irrespective of symptoms. Where it is not possible to perform lumbar punctures in all CrAg-positive patients, blood CrAg titers should be used to target those most at risk of cryptococcal meningitis.

Occam's Razor Need Not Apply: A Case of Concurrent Cryptococcal Meningitis and Primary Central Nervous System Lymphoma in an Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patient

A 28-year-old man with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (CD4 cells 4/1%) was diagnosed and treated for cryptococcal meningitis (CM) 3 weeks before admission with a 14-day course of amphotericin and flucytosine and subsequently discharged on oral fluconazole. However, surveillance of cerebrospinal fluid (CSF) cultures collected before discharge later turned positive for Cryptococcus neoformans and he was called back for evaluation. On admission, the patient reported headache, diplopia, and overall malaise. A head computed tomography showed new enhancing mass lesions in the left and right caudate nuclei with vasogenic edema (Figure 1). Repeat lumbar puncture showed a high opening pressure of 35 mmH2O and C neoformans detected by antigen and CSF culture. He was resumed on amphotericin and flucytosine induction therapy for presumed relapsed CM with possible cryptococcoma. A magnetic resonance imaging (MRI) of the brain was obtained and showed 2 different lesions with increased density, restricted diffusion, and low T2 signal relative to normal brain parenchyma, which were most concerning for central nervous system (CNS) lymphoma or toxoplasmosis and less concerning for cryptococcoma by radiographic appearance (Figure 2). Further CSF studies ruled out toxoplasmosis but showed positive Epstein-Barr virus DNA polymerase chain reaction, again concerning for CNS lymphoma. A brain biopsy could not be obtained due to the location of lesions. Therefore, MRI spectroscopy was performed and showed an increase in the size of both masses suggestive of malignancy (Figure 3) and an elevated choline peak with decreased N-acetylaspartate (NAA) peak, consistent with high-grade CNS lymphoma (Figure 4). The patient was started on antiretroviral therapy and steroids with initial improvement in symptoms, but he subsequently developed acute neurologic decompensation requiring emergent whole brain radiation therapy, which was complicated by hemodynamic instability and hypothermia. He eventually stabilized and was discharged on oral fluconazole and to complete radiation as an outpatient followed by high-dose methotrexate therapy (Figure 5).

Optimal timing for antiretroviral therapy initiation in patients with HIV infection and concurrent cryptococcal meningitis

Currently, initiation of antiretroviral therapy (ART) in most patients with human immunodeficiency virus (HIV) infection is based on the CD4-positive-t-lymphocyte count. However, the point during the course of HIV infection at which ART should be initiated in patients with concurrent cryptococcal meningitis remains unclear. The aim of this systematic review was to summarise the evidence on the optimal timing of ART initiation in patients with cryptococcal meningitis for use in clinical practice and guideline development. To compare the clinical and immunologic outcomes for early initiation ART (less than four weeks after starting antifungal treatment) versus later initiation of HAART (four weeks or more after starting antifungal treatment) in HIV-positive patients with concurrent cryptococcal meningitis. We searched the following databases from January 1980 to February 2011: PubMed, EMBASE, and WHO International Clinical Trials Registry Platform, AEGIS database for conference abstracts, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A total of 35 full text articles were identified and supplemented by a bibliographic search. We contacted researchers and relevant organizations and checked reference lists of all included studies. Randomized controlled trials that compared the effect of ART (consisting of three drug combinations) initiated early or delayed in HIV patients with cryptococcal meningitis. Two review authors independently assessed study eligibility, extracted data, and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. Where clinically meaningful, we performed a meta-analysis of dichotomous outcomes using the relative risk (RR) and report the 95% confidence intervals (95% CIs). Two eligible randomized controlled trials were included (N = 89). In our pooled analysis, we combined the clinical data for both trials comparing early initiation ART versus delayed initiation of ART. There was no statistically significant difference in mortality (RR=1.40, 95% CI [0.42, 4.68]) in the group with early initiation of ART compared to the group with delayed initiation of ART. This systematic review shows that there is insufficient evidence in support of either early or late initiation of ART. For the moment, because of the high risk of immune reconstitution syndrome in patients with cryptococcal meningitis, we recommend that ART initiation should be delayed until there is evidence of a sustained clinical response to antifungal therapy. However, large studies with appropriate comparison groups, and adequate follow-up are warranted to provide the evidence base for effective decision making.

Pulmonary cryptococcosis in non-AIDS patients

ObjectiveTo investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients. Method24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied. Results15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2±11.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients. ConclusionNon-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.

PREVALENCE OF CENTRAL NERVOUS SYSTEM CRYPTOCOCCOSIS IN HUMAN IMMUNODEFICIENCY VIRUS REACTIVE HOSPITALIZED PATIENTS

Central nervous system cryptococcosis is an important cause of mortality among human immunodeficiency virus (HIV) reactive patients. A retrospective study was conducted on a total of 1,863 HIV reactive hospitalized patients suspected of cryptococcal meningitis. Three hundred and fifty-nine cerebrospinal fluid specimens of these cases were screened for various cryptococcal investigations. Thirty-nine out of 359 (10.86%) showed a definite diagnosis of cryptococcosis with a mortality rate of 25.64%. Prevalence of cryptococcal meningitis in the total HIV reactive cohort was 2.09%. Concurrent cryptococcal meningitis and tuberculosis was seen in 33.3% cases. A high index of clinical suspicion and routine mycological surveillance is required to help an early diagnosis and appropriate therapy, as majority of patients respond well to therapy if treated early.

Prevalence of central nervous system cryptococcosis in human immunodeficiency virus reactive hospitalized patients

Central nervous system cryptococcosis is an important cause of mortality among human immunodeficiency virus (HIV) reactive patients. A retrospective study was conducted on a total of 1,863 HIV reactive hospitalized patients suspected of cryptococcal meningitis. Three hundred and fifty-nine cerebrospinal fluid specimens of these cases were screened for various cryptococcal investigations. Thirty-nine out of 359 (10.86%) showed a definite diagnosis of cryptococcosis with a mortality rate of 25.64%. Prevalence of cryptococcal meningitis in the total HIV reactive cohort was 2.09%. Concurrent cryptococcal meningitis and tuberculosis was seen in 33.3% cases. A high index of clinical suspicion and routine mycological surveillance is required to help an early diagnosis and appropriate therapy, as majority of patients respond well to therapy if treated early.