[Cryptococcal meningitis associated with hydrocephalus in an immunocompetent patient].

Cryptococcal meningitis is an infrequent infection with high morbidity and mortality. Its presentation in immunocompetent patients is rare. We present the case of a 67-year-old male who was admitted for subacute symptoms of gait disturbance and urinary incontinence. Neurological examination revealed inability to stand and memory impairment. Cranial imaging showed obstructive tetraventricular hydrocephalus with areas of gliosis in the cerebellar peduncles. Endoscopic treatment of hydrocephalus was performed and cerebrospinal fluid samples taken revealing the growth of Cryptococcus neoformans. The patient improved with the endoscopic treatment and after completing intravenous antifungal therapy with liposomal amphotericin B and fluconazole for ten weeks. Antifungals are used to treat cryptococcal meningitis in immunocompetent patients. On rare occasions, it presents with hydrocephalus, a situation that requires surgical treatment using cerebrospinal fluid diversions or endoscopic techniques.

A comparison of the surgical outcomes of ventriculoperitoneal versus lumbar peritoneal shunts in the management of intracranial hypertension secondary to cryptococcal meningitis in HIV infected adult patients.

OBJECTIVE: Cryptococcal meningitis (CM), an AIDS-defining illness, significantly impacts morbidity and mortality. This study aims to compare complications arising from ventriculoperitoneal shunt (VPS) and lumbar peritoneal shunt (LPS) procedures used to manage refractory intracranial hypertension (IH) secondary to CM in HIV-infected patients. METHODS: Retrospective data were collected from January 2003 to January 2015 for HIV-infected adults diagnosed with refractory IH secondary to CM and subsequently shunted. Demographics, clinical characteristics, antiretroviral therapy, laboratory findings (including CD4 count and CSF results), CT brain scan results, shunt-related complications, and mortality were compared between VPS and LPS groups. RESULTS: This study included 83 patients, with 60 (72%) undergoing VPS and 23 (28%) receiving LPS. Mean ages were comparable between VPS (32.5) and LPS (32.2) groups (p = 0.89). Median CD4+ counts were 76 cells/µl (IQR= 30-129) in VPS versus 54 cells/µl (IQR= 31-83) in LPS (p=0.45). VPS group showed a higher mean haemoglobin of 11.5 g/dl compared to 9.9 g/dl in the LPS group (p=0.001). CT brain scans showed hydrocephalus in 55 VPS and 13 LPS patients respectively. Shunt complications were observed in 17 (28%) VPS patients versus 10 (43.5%) LPS patients (p=0.5). Patients developing shunt sepsis in the VPS group exhibited a median CD4+ count of 117 cells/µl (IQR= 76-129) versus 48 cells/µl (IQR= 31- 66) in the LPS group (p=0.03). Early shunt malfunction occurred more frequently in the LPS group compared to VPS group (p=0.044). The mean hospital stay was 6.2 days for VPS versus 5.4 days for LPS patients (p=0.9). In-hospital mortality was 6%, occurring in three VPS and two LPS patients respectively. CONCLUSION: Shunting procedures remain important surgical interventions for refractory IH secondary to HIV-related CM. However, cautious consideration is warranted for patients with CD4 counts below 200 cells/µL due to increased shunt complications. This study suggests a trend toward higher complication rates in patients undergoing LPS insertion.

Prevalence, treatment, and factors associated with cryptococcal meningitis post introduction of integrase inhibitors antiretroviral based regimens among People Living with HIV in Tanzania.

OBJECTIVE: This study aimed to assess the prevalence of Cryptococcal Meningitis (CM), treatment practice, and the associated factors post-introduction of Tenofovir Lamivudine and Dolutegravir (TLD) regimen among People Living with HIV (PLHIV) in Tanzania. METHODS: This was an analytical cross-sectional study, and the data was collected retrospectively in three public regional referral hospitals (RRHs) in Dar es Salaam, Tanzania. A total of 405 files of the PLHIV admitted in the medical wards on the TLD regimen from January 2019 to December 2022 were reviewed. The collected information includes the patient's demographic characteristics, Cryptococcal status, CD4 level at the time of CM diagnosis, status of using ART, CM treatment approach, and outcome. Data was analyzed using SPSS software version 23. RESULTS: Out of 405 patients, the majority 267(65.9%) were female, 224(55.3%) were aged between 36-55 years, and 293(72.3%) were married. ART defaulters were found to be 37(9.1%). The prevalence of CM was found to be 48(11.9%), out of which 42(87.5%) received fluconazole alone. ART defaulter and marital status significantly (p-value < 0.05) were associated with those who tested CM positive. CONCLUSION: The study found the prevalence of CM among PLHIV to be significantly high and the majority were treated with fluconazole alone. ART defaulters and marital status were significantly associated with one being CM positive. Responsible authorities and stakeholders should enforce guideline adherence and PLHIV should be encouraged on medication adherence.

The prognostic factors for cryptococcal meningitis in non-human immunodeficiency virus patients: An observational study using nationwide database.

BACKGROUND: Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies. OBJECTIVE: To identify the pretreatment prognostic factors for CM in non-HIV patients. METHODS: We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group. RESULTS: Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis. CONCLUSION: More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis.

Analysis of the relationship between drug susceptibility of Cryptococcus neoformans isolates and mortality in HIV-negative cryptococcal meningitis.

OBJECTIVES: The relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood. METHODS: We conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year. RESULTS: All of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality. CONCLUSION: Most Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.

A case of hypophysis with HIV negative cryptococcal meningitis. / 垂体功能减退症伴HIV阴性的隐球菌性脑膜炎1例.

The clinical mortality of cryptococcal meningitis (CM) is high. There is no report of hypopituitarism associated with HIV negative CM so far. The patients with hypopituitarism complicated with CM are easy to be misdiagnosed and mistreated. A patient with hypopituitarism and HIV negative CM was admitted to Weihai Municipal Hospital on August 27, 2021. The patient was treated for 18 years after craniopharyngioma with headache for more than 2 months, nausea and vomiting for 4 days. MRI showed abnormal enhancement of the right basal ganglia, edema of surrounding tissue, and multiple striated enhancement of the bilateral cerebellar hemisphere. The smear of cerebrospinal fluid showed a large number of fungi and Cryptococcus. Culture of cerebrospinal fluid showed positive in Cryptococcus. The patient's HIV and syphilis antibodies were negative. The condition of the patient was improved after active antifungal therapy. The clinician should make a definite diagnosis and give early treatment as soon as possible.

Cryptococcal meningitis.

Cryptococcus neoformans and Cryptococcus gattii species complexes cause meningoencephalitis with high fatality rates and considerable morbidity, particularly in persons with deficient T cell-mediated immunity, most commonly affecting people living with HIV. Whereas the global incidence of HIV-associated cryptococcal meningitis (HIV-CM) has decreased over the past decade, cryptococcosis still accounts for one in five AIDS-related deaths globally due to the persistent burden of advanced HIV disease. Moreover, mortality remains high (~50%) in low-resource settings. The armamentarium to decrease cryptococcosis-associated mortality is expanding: cryptococcal antigen screening in the serum and pre-emptive azole therapy for cryptococcal antigenaemia are well established, whereas enhanced pre-emptive combination treatment regimens to improve survival of persons with cryptococcal antigenaemia are in clinical trials. Short courses (≤7 days) of amphotericin-based therapy combined with flucytosine are currently the preferred options for induction therapy of cryptococcal meningitis. Whether short-course induction regimens improve long-term morbidity such as depression, reduced neurocognitive performance and physical disability among survivors is the subject of further study. Here, we discuss underlying immunology, changing epidemiology, and updates on the management of cryptococcal meningitis with emphasis on HIV-associated disease.

Immune-related neurodegeneration in the midbrain causes pulmonary dysfunction in murine cryptococcal IRIS.

Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) is a condition that affects immunosuppressed individuals recruited to antiretroviral therapy. In a recent publication, Kawano and colleagues used a mouse model to demonstrate that pulmonary dysfunction, one of the fatal complications of C-IRIS, is caused by T cell-driven neurodegeneration in a vital medullary nucleus of the brain responsible for respiratory control.

Cryptococcal meningitis and cerebral vasculitis in a patient with primary intestinal lymphangiectasia: a case report.

Primary intestinal lymphangiectasia (Waldmann's disease) is a rare exudative enteropathy without precisely assessed infectious risk. We report the case of a 49-year-old male patient with meningitis and cerebral vasculitis due to Cryptococcus neoformans complicating Waldmann's disease diagnosed 12 years ago. The treatment combined liposomal amphotericin B, 3 mg/kg daily plus flucytosine 25 mg/kg/6 h, both intravenously during 15 days, then fluconazole 800 mg daily during 8 weeks, and finally 200 mg daily indefinitely. Dexamethasone 0.4 mg/kg daily during the first week was gradually decreased over 2 months. The outcome was good, and the patient is still followed 3 years later without any recurrence.

Post-infectious inflammatory response syndrome in an HIV-negative patient after Cryptococcus gattii meningoencephalitis: a case report and review of the literature.

BACKGROUND: Cryptococcal meningitis (CM) is an inflammatory mycosis of the central nervous system caused by meninge infection or brain parenchyma with Cryptococcus species. It is associated with high morbidity and mortality, and patients with acquired immune deficiency syndrome are particularly susceptible. There have been increasing reports of CM in HIV-negative patients in China over the last few years. CASE PRESENTATION: A 31-year-old healthy Chinese male presented with fever and gradually developed headache, projectile vomiting, and other manifestations that were later confirmed as Cryptococcus gattii meningoencephalitis. However, multiple disease changes occurred during the course of treatment, and the regimen was accordingly modified after the diagnosis of post-infectious inflammatory response syndrome (PIIRS). The patient eventually recovered. CONCLUSION: There has been a growing trend in the incidence of C. gattii meningoencephalitis in HIV-negative patients. It shows rapid onset and severe prognosis. This case report can provide a reference to treat PIIRS following CM in HIV-negative patients.

Screening for cryptococcal antigen in asymptomatic people with HIV: urgent need in Eastern India.

OBJECTIVE: Cryptococcal meningitis (CM) is a leading cause of mortality in people with HIV (PWH). Despite recommendation by the National programme, cryptococcal antigen (CrAg) screening in PWH with CD4 + <200/µl has not been implemented in practice. Therefore, we conducted a prospective study in government funded Antiretroviral treatment centre to determine the prevalence of asymptomatic cryptococcal antigenemia in PWH with CD4 + cell count <200 cells/µl, subclinical cryptococcal meningitis in serum CrAg positive subjects and their outcome. METHOD: Serum CrAg (BIOSYNEX CryptoPS) screening was conducted in newly diagnosed asymptomatic retro-positive adults with CD4 + <200/µl between January 2021 and March 2022. We also conducted cerebrospinal fluid (CSF) CrAg testing in all PWH who were serum CrAg positive and appropriate therapy was instituted. All the enrolled participants were followed up till February 2023. RESULT: Among enrolled 142 PWH patients, 22 (15.49%) were positive for serum CrAg. Among these 22, seven (31.8%) patients had CD4 + cell count between 100 and 199 cells/µl. CSF CrAg was positive in 11 (50%) serum CrAg positive cases. Serum CrAg positivity was significantly associated with low CD4 + cell count, poor clinical stage and concomitant Pneumocystis pneumonia. However, mortality was not significantly different in Serum CrAg positive and negative PWH. None of the deaths in CrAg positive PWH was due to cryptococcal disease. CONCLUSION: Higher prevalence of cryptococcal antigenemia and subclinical CM among PWH with CD4 + cell count <200 cells/µl with good treatment outcomes with therapy reiterates the need for CrAg screening among PWH in Eastern India.

Clinical presentation of idiopathic CD4 lymphocytopenia.

An otherwise healthy man (60s) presented to our emergency department 5 years ago with stroke-like symptoms. Underlying cryptococcal meningitis infection was ultimately discovered leading to extensive workup to rule out underlying malignancy and HIV infection. Results returned negative with the exception of a CD4 count less than 25 /mm3 Several years later, he again presented to the emergency department with fatigue. He was then found to have severe anaemia with underlying Mycobacterium avium complex (MAC) infection involving the bone marrow and a left psoas abscess. After multiple courses of antibiotic therapy targeted towards MAC, the infection persisted due to bone marrow involvement. By diagnosis of exclusion, he was eventually found to have idiopathic CD4 lymphocytopenia. Here we describe this condition, which has the potential to cause significant morbidity, and obligates the need for high clinical suspicion for timely diagnosis to enhance life quality and outcomes for patients.

Neurological worsening during treatment of HIV-negative cryptococcal meningitis in a patient with Evans syndrome.

A 49-year-old woman with a rare autoimmune hematological disease, Evans syndrome, was admitted to the authors' hospital with immune reconstitution inflammatory syndrome-like reconstitution syndrome after effective antifungal therapy for cryptococcal meningitis. She initially improved after receiving corticosteroid treatment; after prednisone was tapered, her clinical presentation and brain imaging deteriorated but finally improved with the addition of thalidomide. Immune reconstitution inflammatory syndrome-like reconstitution syndrome is a rare complication in cryptococcal meningitis patients receiving immunosuppressive therapy. Thalidomide can be given in addition to corticosteroid therapy to effectively control the paradoxical inflammatory response and improve clinical outcomes.

Cryptococcal meningoencephalitis: Risk factors associated to death in a hospital in Northeastern Brazil.

INTRODUCTION: Cryptococcosis is an opportunistic systemic mycosis caused by pathogenic encapsulated yeasts of the genus Cryptococcus. The objective of the present study was to evaluate the risk factors associated with death of patients diagnosed with meningitis due to Cryptococcus spp. METHODS: This retrospective cohort study included patients admitted to the São José Hospital (SJH) with Cryptococcal Meningoencephalitis (CM) who were diagnosed between 2010 and 2018. Data collection was carried out by reviewing the patients' medical records. Death during hospitalization was considered the primary outcome. RESULTS: From 2010 to 2018, 21,519 patients were admitted to the HSJ, 124 of whom were hospitalized due to CM. The CM incidence rate was 5.8 cases/103 hospitalizations. We included 112 patients in the study. Male patients were the most affected (82.1%), and the median age was 37 years [IQR: 29-45]. HIV coinfection occurred in 79.4% of the patients. Fever (65.2%) and headache (88.4%) were the most frequent symptoms. Greater cellularity in the CSF was the most related factor to CM in non-HIV individuals (p < 0.05). Death during hospitalization occurred in 28.6% (n = 32) of the patients. The independent risk factors associated with death during the hospitalization were women (p = 0.009), age > 35 years (p = 0.046), focal neurological deficits (p = 0.013), altered mental status (p = 0.018) and HIV infection (p = 0.040). The twelve-month survival was lower in HIV-positive patients (p < 0.05). CONCLUSION: Early diagnosis, optimal treatment, and clinical follow-up strategies, especially in HIV patients, should be prioritized.

Cryptococcal meningitis in a non-HIV patient with solid organ transplantation.

Cryptococcal meningitis (CM) is often associated with human immunodeficiency virus (HIV). Recently, this microorganism has been increasingly identified in HIV-negative patients. CM cases are encountered in HIV-negative individuals, especially secondary to liver disease, solid organ transplantation (SOT), tuberculosis, lymphoproliferative diseases with T-cell-mediated immunological disorders, long-term corticosteroid use, malignancies, diabetes mellitus, and sarcoidosis. Our patient is an HIV-negative, SOT case with CM. It should be considered that CM can also occur in HIV-negative patients. As in our case, patients receiving long-term immunosuppressive therapy should be evaluated for CM, and renal functions should be closely monitored during treatment. There is a need for more case reports on the subject, especially in CM detected HIV-negative patients, due to the different treatment protocols and challenging clinical conditions compared to HIV-positive cases.