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Background: Primary bilateral macronodular adrenal hyperplasia (PMAH) combined with infection by an opportunistic pathogen is complicated. Clinical evidence on managing PMAH patients with infections by opportunistic pathogens is insufficient., Case Presentation: A 66-year-old male was admitted with bilateral adrenal masses and was diagnosed with PMAH. Fever and disturbance of consciousness appeared after laparoscopic left adrenalectomy. Cryptococcal meningitis was confirmed by cerebrospinal fluid (CSF) culture. The exacerbation of his medical condition was suspected to result from immune reconstitution inflammatory syndrome (IRIS), and he had been treated with antifungal therapy and glucocorticoid replacement, but he responded poorly and eventually died of multiorgan failure. We summarized the clinical observations of 12 Cushing's syndrome (CS) patients infected by Cryptococcus. Seven out of nine patients who were treated for cryptococcus infection before receiving CS survived, while three patients treated for cryptococcus infection after CS treatment developed signs of IRIS and eventually died., Conclusion: Cushing's syndrome, complicated with cryptococcal infection, has a high mortality rate, mainly when IRIS emerges. Carefully identifying the presence of the suspected infection, and controlling cryptococcal infection before removing the culprit adrenals could be the rational choice., (© 2023. BioMed Central Ltd., part of Springer Nature.)

BACKGROUND Cryptococcal meningitis (CM) is one of the most common opportunistic neuroinfections in patients with HIV. Most studies have focused on non-HIV CM and there are only a few studies on HIV CM in China. The purpose of the present study was to evaluate the characteristics and risk factors for CM recurrence in patients infected with HIV in the Chongqing Public Health Treatment Center in China. MATERIAL AND METHODS From January 2014 to December 2017, all patients with CM aged 18 years or older were enrolled and a case-control study was performed to determine the risk factors associated with recurrence of CM. Antimicrobial susceptibility was determined with a fungal drug sensitivity kit and the sequence types (STs) were analyzed with multilocus sequence typing. RESULTS The incidence of CM in the 5185 HIV-infected patients was 3.5% (179). Follow-up data were available for 82 of the patients for whom complete medical records were available and they were included in the present study. There were 7 STs among 82 Cryptococcus neoformans isolates; ST5 and ST31 were the most prevalent genotypes. Testing showed that C. neoformans had high sensitivity to 5 antifungal drugs and no differences in resistance were observed, even when different STs were tested. Risk factors for recurrence were analyzed in 69 patients, excluding those who died. The results of multivariate analysis showed that only hospital stay was associated with recurrence of CM. CONCLUSIONS Our results indicated that combining education about medication with clinical treatment could help prevent recurrence of CM.

Growing evidence suggests that autoimmune diseases (AIDs) are risk factors for cryptococcal meningitis (CM). Therefore, understanding the epidemiological and clinical profile of CM in patients with AIDs is important. This meta-analysis assessed the prevalence, clinical profiles, and clinical outcomes of CM in AIDs. Studies on CM in patients with AIDs were searched for in PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure, and meta-analyses were performed using the statistical program of R. Nineteen studies with 36,631 patients with AIDs were analyzed. The overall pooled CM prevalence was 0.4% (95% confidence interval [CI], 0.3-0.6%), 90.7% of which occurred in female patients. Thirteen studies with 77 patients with AIDs diagnosed with CM were analyzed, and the mortality rate was 26.7% (95% CI, 9.5-47.2%). Of patients with systemic lupus erythematosus, 30.1% of CM cases were initially misdiagnosed (95% CI, 0-65.6%). The primary symptom of CM with AIDs was headache (99.4%; 95% CI, 92.1-100%), followed by fever (93.7%; 95% CI, 82.8-100%) and vomiting (37.2%; 95% CI, 13.2-61.2%). The prevalence of CM infections among patients with AIDs should not be underestimated despite non-specific clinical presentations as there were fatal outcomes. Our results suggest that more research is needed to understand the relationship between AIDs and CM, and clinical trials are necessary to improve treatment strategies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The roles of cytokines and chemokines in HIV-associated cryptococcal meningitis (HCM) and HIV-associated tuberculous meningitis (HTBM) are debatable. In sum, 34 HIV-infected patients without meningitis, 44 HCM patients and 27 HTBM patients were enrolled for study. The concentrations of 22 cytokines/chemokines in cerebrospinal fluid (CSF) were assayed at admission. Principal component analysis (PCA), Pearson's and logistic regression analyses were used to assess the role of cytokines/chemokines in HCM and HTBM. We found the levels of T helper (Th)17, Th1 [interleukin (IL)-12p40, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and TNF-β and Th2 (IL-2/4/5/6/10)] cytokines were elevated in patients with meningitis compared with those in HIV-infected patients without central nervous system (CNS) infection. Furthermore, the IL-1Ra, IL-12p40, IL-17α and monocyte chemotactic protein-1 (MCP-1) levels were higher in HCM patients, while the IFN-γ, regulated upon activation, normal T cell expressed and secreted (RANTES) and interferon-inducible protein-10 (IP)-10 levels were higher in HTBM patients. Elevated CSF concentrations of IL-17a, TNF-β, IL-5, IL-12p40 and IL-1Rα were closely related to meningitis, but elevated IP-10, MCP-1, RANTES and IFN-γ levels and CSF white blood cells (WBCs) were protective factors against HCM. Our study suggested that HIV-infected patients with low CSF WBCs have a high risk of HCM. Th1, Th2 and Th17 cytokines/chemokines mediate differences in the pathogenesis of HCM and TBM. Overexpressed proinflammatory MCP-1, RANTES, IFN-γ and IP-10 in CSF are protective factors against HCM but not HTBM., (© 2021 British Society for Immunology.)

The hyper IgM syndromes are a rare group of primary immunodeficiency. The X-linked Hyper IgM syndrome (HIGM), due to a gene defect in CD40L, is the commonest variant; it is characterized by an increased susceptibility to a narrow spectrum of opportunistic infection. A few cases of HIGM patients with Cryptococcal meningoencephalitis (CM) have been described in the literature. Herein we report the case of a young male diagnosed in infancy with HIGM who developed CM complicated by a post-infectious inflammatory response syndrome (PIIRS), despite regular immunoglobulin replacement therapy and appropriate antimicrobial prophylaxis. The patient was admitted because of a headache and CM was diagnosed through detection of Cryptococcus neoformans in the cerebrospinal fluid. Despite the antifungal therapy resulting to negative CSF culture, the patient exhibited persistent headaches and developed diplopia. An analysis of inflammatory cytokines on CSF, as well as the brain MRI, suggested a diagnosis of PIIRS. Therefore, a prolonged corticosteroids therapy was started obtaining a complete resolution of symptoms without any relapse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Romani, Williamson, Di Cesare, Di Matteo, De Luca, Carsetti, Figà-Talamanca, Cancrini, Rossi and Finocchi.)

Objective: 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., Method and Materials: 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., Results: 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., Conclusion: 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

HIV-1 compartmentalization in reservoir sites remains a barrier to complete HIV eradication. It is unclear whether there is variation in HIV-1 env and gag between cerebrospinal fluid (CSF) and plasma of individuals with HIV-associated cryptococcal meningitis (CM). We compared HIV-1 env characteristics and the gag cytotoxic T-lymphocyte (CTL) escape mutations from CSF and plasma samples. Employing population-based Sanger sequencing, we sequenced HIV-1 env from CSF of 25 patients and plasma of 26 patients. For gag , 15 CSF and 21 plasma samples were successfully sequenced. Of these, 18 and 9 were paired env and gag CSF/plasma samples, respectively. There was no statistically significant difference in the proportion of CCR5-using strains in the CSF and plasma, ( p = 0.50). Discordant CSF/plasma virus co-receptor use was found in 2/18 pairs (11.1%). The polymorphisms in the HIV-1 V3 loop were concordant between the two compartments. From the HIV-1 gag sequences, three pairs had discordant CTL escape mutations in three different epitopes of the nine analyzed. These findings suggest little variation in the HIV-1 env between plasma and CSF and that the CCR5-using strains predominate in both compartments. HIV-1 gag CTL escape mutations also displayed little variation in CSF and plasma suggesting similar CTL selective pressure.

Aim: To evaluate the clinical data and quantitative cerebrospinal fluid for associations with the outcome of cryptococcal meningitis (CM) patients in the hospital. Patients & methods: We retrospectively analyzed a total of 139 CM patients comprising 108 without HIV and 31 with HIV admitted in a Jiang Xi hospital. Resμlts: We found that CM patients with the high fungal burden (≥10 yeasts/μl) (26.3%) had a worse prognosis than those with the low fungal burden (<10 yeasts/μl). (4.9%) (p = 0.0007 <0.05). Conclusion: In CM patients, a fungal burden of 10 yeasts/μl in the first cerebrospinal fluid test may be used as an indicator of patient prognosis, and we can personalize patients' treatment based on the fungal burden to improve prognosis.

We report a case of rheumatoid meningitis complicated with cryptococcal meningitis in a 59-year-old female with rheumatoid arthritis. Migraine symptoms were followed by abnormal behavior, and the patient was admitted with fever and headache. On admission, her cerebrospinal fluid (CSF) contained 115 cells/μl, a protein content of 95 mg/dl, and a sugar level of 47 mg/dl; Her serum anti-cyclic citrullinated peptide (CCP) antibody value was high (174 U/ml), and a brain MRI showed enhanced gadolinium lesions in the cerebral/cerebellar pia mater and subarachnoid space, etc. Probable rheumatoid meningitis was clinically diagnosed, and a prednisolone (PSL) pulse was started. Several days later, a CSF culture test was positive for Cryptococcus neoformans, and the antigen titer was 128-fold. Liposomal-amphotericin B (L-AMB) was started for cryptococcal meningitis, combined with three PSL pulses for rheumatoid meningitis. After about 4 weeks, the number of CSF cells and anti-CCP antibodies decreased rapidly. At 2 months after the onset, the meningitis recurred. The MRI contrast lesions reappeared, and the CSF cells increased to 24/μl. Serum and CSF anti-CCP antibodies increased at the time of recurrence, but the cryptococcal antigen titer decreased. Thus, we concluded that the rheumatoid meningitis mainly involved the pathogenesis of both types of meningitis. The number of PSL pulses was limited to four. Post-perioral therapy was avoided. Methotrexate was continued for the rheumatoid meningitis, fluconazole was continued for the cryptococcal meningitis, and neither type of meningitis has recurred.

Background: Clinicians may be less inclined to consider a diagnosis of cryptococcal meningitis in people without HIV infection or transplant-related immunosuppression. This may lead to a delay in diagnosis particularly if disseminated cryptococcal disease mimics cerebral septic emboli in injection drug use (IDU) leading to a search for endocarditis or other infectious sources. Though, IDU has been described as a potential risk for disseminated cryptococcal disease., Case Presentations: We present two cases of cryptococcal meningitis in IDU without HIV or other obvious immune deficits. Both patients presented with at least 2 weeks of headache and blurred vision. They developed central nervous system (CNS) vasculitis, one of which mimicked septic cerebral emboli, but both resulted with poor neurologic outcomes., Conclusions: IDU likely induces an underappreciated immune deficit and is a risk factor for developing cryptococcal meningitis. This diagnosis, which can mimic cerebral septic emboli through involvement of a CNS vasculitis, should be considered in the setting of IDU.

We herein report a 76-year-old Japanese man with myelofibrosis who developed cryptococcal meningitis. After treatment for 5 months with ruxolitinib, the patient presented with fever and disturbance of consciousness. Marked nuchal stiffness was noted. The magnetic resonance imaging results of the brain were normal. Lumbar puncture showed an opening cerebrospinal fluid (CSF) pressure of 110 mm H2O, pleocytosis (85 mononuclear cells and 222 polymorphonuclear cells/μL), decreased CSF/serum glucose ratio (43%), and elevated protein (194 mg/dL). Blood and CSF cultures grew no bacteria or fungi. However, cryptococcal antigen was detected in the blood and CSF samples. We discontinued ruxolitinib and started administration of amphotericin B. His condition improved gradually 1 week after initiation of treatment. There have been only a few reports on cryptococcal meningitis associated with ruxolitinib. Physicians should consider the possibility of cryptococcal meningitis in patients receiving ruxolitinib.

Background: Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system and has high morbidity and mortality. Almost studies about prognostic factors have largely focused on the immunocompromised population rather than immunocompetent patients. So that we sought to conduct a retrospective study to determine prognostic factors which predict the outcomes in immunocompetent patients with CM., Methods: We retrospectively collected and analyzed the demographic and clinical data of 76 apparently immunocompetent patients with cryptococcal meningitis from January 2003 to June 2019 in China. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1-4) outcome groups, potential prognostic factors were analyzed., Results: Non-parametric test confirmed that unfavorable outcome was associated with lower glucose level of CSF(P = 0.001), and Pearson's χ2 analysis confirmed that unfavorable outcome was associated with opening pressure of CSF(>300mmH20, P = 0.038), impaired consciousness (P = 0.001), hydrocephalus(P = 0.045), and Shunt surgery (P = 0.045), and then multiple logistic regression analysis confirmed that impaired consciousness(P = 0.015) and lower glucose concentration of CSF(P = 0.012) increased the likelihood of unfavorable outcome in CM patients., Conclusion: Impaired consciousness and decreased glucose concentration of CSF were independently prognostic factors which predict the unsatisfactory outcome in immunocompetent patients with CM.

Background: Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published., Case Presentation: A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free., Conclusions: We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.

Introduction: HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and meta-analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings., Methods: We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized-controlled trials (RCTs) or investigator-managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short-term (in-hospital or two weeks), medium-term (up to 10 weeks) and long-term (up to six months)., Results and Discussion: Seventy-nine studies met inclusion criteria. In routine care settings, pooled short-term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole-based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short-term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short-term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized-controlled trials. Few studies evaluated long-term outcomes., Conclusions: Mortality rates from HIV-associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV-associated meningitis in the region., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Cryptococcal meningitis (CM) causes high rates of HIV-related mortality, yet the Cryptococcus factors influencing patient outcome are not well understood. Pathogen-specific traits, such as the strain genotype and degree of antigen shedding, are associated with the clinical outcome, but the underlying biology remains elusive. In this study, we examined factors determining disease outcome in HIV-infected cryptococcal meningitis patients infected with Cryptococcus neoformans strains with the same multilocus sequence type (MLST). Both patient mortality and survival were observed during infections with the same sequence type. Disease outcome was not associated with the patient CD4 count. Patient mortality was associated with higher cryptococcal antigen levels, the cerebrospinal fluid (CSF) fungal burden by quantitative culture, and low CSF fungal clearance. The virulence of a subset of clinical strains with the same sequence type was analyzed using a mouse inhalation model of cryptococcosis. We showed a strong association between human and mouse mortality rates, demonstrating that the mouse inhalation model recapitulates human infection. Similar to human infection, the ability to multiply in vivo , demonstrated by a high fungal burden in lung and brain tissues, was associated with mouse mortality. Mouse survival time was not associated with single C. neoformans virulence factors in vitro or in vivo ; rather, a trend in survival time correlated with a suite of traits. These observations show that MLST-derived genotype similarities between C. neoformans strains do not necessarily translate into similar virulence either in the mouse model or in human patients. In addition, our results show that in vitro assays do not fully reproduce in vivo conditions that influence C. neoformans virulence., (Copyright © 2019 American Society for Microbiology.)

Background: The coexistence of neuromeningeal cryptococcosis and Kaposi's sarcoma is not surprising in a patient with human immunodeficiency virus infection and a low CD4 count, although it is rarely described. However, we describe such an association in a patient with human immunodeficiency virus infection and a relatively high CD4 count., Case Presentation: A 41-year old Cameroonian woman presented to our hospital with subacute occipital headaches associated with photophobia, blurred vision, phonophobia, projectile vomiting, and tonic seizures. In her past history, there was an human immunodeficiency virus infection known for 12 years, for which she had been taking (with good compliance) tenofovir-lamivudine-efavirenz-based antiretroviral therapy for the same period of time. One month before the consultation, gastric Kaposi's sarcoma had been diagnosed, justifying the treatment with doxorubicin she had received. A clinical examination was unremarkable. A computed tomography scan of her brain was normal, and cerebrospinal fluid analysis revealed Cryptococcus neoformans. Her CD4 count was 353/mm 3 . Orally administered antifungal treatment with fluconazole (1200 mg/day) and flucytosine (1500 mg × 4/day) was started immediately, but she died on the sixth day of this treatment., Conclusion: This clinical case shows that the coexistence of neuromeningeal cryptococcosis and gastric Kaposi's sarcoma is possible in all patients with human immunodeficiency virus infection, regardless of CD4 count.

Fingolimod is an oral medication approved by the Food and Drug Administration in 2009 for the treatment of relapsing remitting multiple sclerosis (RRMS). Initial clinical trials did not show a significantly increased rate of serious infections with fingolimod therapy. However, a mildly increased risk of less serious infections, such as varicella zoster virus and herpes simplex virus, was reported. Recently, however, several instances of serious opportunistic infections have been reported. In the years following approval of fingolimod for use in multiple sclerosis (MS), seven cases of cryptococcal meningitis in patients undergoing treatment have been described in the literature. We present a 40-year old woman with RRMS on fingolimod therapy presenting with a rare case of cryptococcal meningitis exhibiting alterations of consciousness, which was initially diagnosed as an MS relapse., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Cryptococcal meningitis can occur in persons with less-apparent immunosuppression. We evaluated clinical characteristics and outcomes of persons with HIV-related Cryptococcus presenting with higher CD4 counts., Methods: We enrolled 736 participants from 2 prospective cohorts in Uganda and South Africa from November 2010 to May 2017. We compared participants with CD4 <50, 50-99, or ≥100 cells/μL by clinical characteristics, cerebrospinal fluid (CSF) parameters, and 18-week survival., Results: Among first episode of cryptococcosis, 9% presented with CD4 ≥100 cells/μL. Participants with CD4 ≥100 cells/μL presented more often with altered mental status (52% vs 39%; P = .03) despite a 10-fold lower initial median CSF fungal burden of 7850 (interquartile range [IQR] 860-65500) versus 79000 (IQR 7400-380000) colony forming units/mL (P < .001). Participants with CD4 ≥100 cells/μL had higher median CSF levels of interferon-gamma, interleukin (IL)-6, IL-8, and IL-13, and lower monocyte chemokine, CCL2 (P < .01 for each). Death within 18 weeks occurred in 47% with CD4 <50, 35% with CD4 50-99, and 40% with CD4 ≥100 cells/μL (P = .04)., Conclusion: HIV-infected individuals developing cryptococcal meningitis with CD4 ≥100 cells/μL presented more frequently with altered mental status despite having 10-fold lower fungal burden and with greater Th2 (IL-13) immune response. Higher CD4 count was protective despite an increased propensity for immune-mediated damage, consistent with damage-response framework., Clinical Trial Registration: NCT01075152 and NCT01802385., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Cryptococcal antigen (CrAg) screening in persons with advanced HIV/AIDS is recommended to prevent death. Implementing CrAg screening only in outpatients may underestimate the true CrAg prevalence and decrease its potential impact. Our previous 12-month survival/retention in CrAg-positive persons not treated with fluconazole was 0%., Methods: HIV testing was offered to all antiretroviral therapy-naive outpatients and hospitalized patients in Ifakara, Tanzania, followed by laboratory-reflex CrAg screening for CD4 <150 cells/μL. CrAg-positive individuals were offered lumbar punctures, and antifungals were tailored to the presence/absence of meningitis. We assessed the impact on survival and retention-in-care using multivariate Cox-regression models., Results: We screened 560 individuals for CrAg. The median CD4 count was 61 cells/μL (interquartile range 26-103). CrAg prevalence was 6.1% (34/560) among individuals with CD4 ≤150 and 7.5% among ≤100 cells/μL. CrAg prevalence was 2.3-fold higher among hospitalized participants than in outpatients (12% vs 5.3%, P = 0.02). We performed lumbar punctures in 94% (32/34), and 31% (10/34) had cryptococcal meningitis. Mortality did not differ significantly between treated CrAg-positive without meningitis and CrAg-negative individuals (7.3 vs 5.4 deaths per 100 person-years, respectively, P = 0.25). Independent predictors of 6-month death/lost to follow-up were low CD4, cryptococcal meningitis (adjusted hazard ratio 2.76, 95% confidence interval: 1.31 to 5.82), and no antiretroviral therapy initiation (adjusted hazard ratio 3.12, 95% confidence interval: 2.16 to 4.50)., Conclusions: Implementing laboratory-reflex CrAg screening among outpatients and hospitalized individuals resulted in a rapid detection of cryptococcosis and a survival benefit. These results provide a model of a feasible, effective, and scalable CrAg screening and treatment strategy integrated into routine care in sub-Saharan Africa.

Background: This case report emphasizes the need to recognize cryptococcus as a possible cause of meningitis in non-HIV patients in Sub-Saharan Africa and to highlight the possibility of grave outcomes due to the paradoxical immune response in diabetic patients with cryptococcus meningitis. It also highlights the need for widespread availability of amphotericin-B and flucytosine in hospitals in Sub-Saharan Africa., Case Presentation: A 27 year old African lady was admitted with generalized tonic clonic seizures lasting 5 to 10 min. These seizures were preceded by severe frontal headaches radiating to the occiput and neck and associated with chills, photophobia and loss of consciousness. She was tachycardic and had tongue bites on the lateral aspects of her tongue. Kernig's and Brudzinski's signs were positive. India ink was positive on two cerebrospinal fluid (CSF) samples. She had hyperglycemia and glucosuria as well. She was diagnosed with cryptococcal meningitis in diabetes and had a remarkable response to fluconazole monotherapy. She went home on maintenance dose of fluconazole having made full recovery. and is currently on prophylactic doses of fluconazole., Conclusions: With the rising prevalence of diabetes in Sub-Saharan Africa, coupled with the low levels of adequate glucose control, cryptococcal meningitis should be considered in the differential diagnosis for diabetic patients presenting with chronic headache, fever and neurologic deficits.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of the JC virus under an immunosuppressed state. This condition carries a high risk of cryptococcal meningitis. We herein report a 65-year-old woman who simultaneously developed PML and cryptococcal meningitis and presented with bilateral sixth nerve palsy. She had been treated with methotrexate and infliximab for rheumatoid arthritis. Her symptoms improved with antifungal drug treatment and discontinuation of immunosuppression therapy. Although concurrent PML and cryptococcal meningitis is rare, it should be considered in immunosuppressed patients.

Background:  HIV-associated cryptococcal meningitis (CCM) and related mortality may be prevented by the effective implementation of a screen-and-treat intervention. Aim: The aim of this study was to assess the effectiveness of the screen-and-treat intervention at a regional hospital in KwaZulu-Natal province, South Africa. Method: This was a descriptive study in which the records of patients seen in 2015 and 2016 with a CD4 count ≤ 100 cell/mm3 were retrieved from National Health Laboratory Service (NHLS) records and matched against patients admitted for HIV-associated CCM. Results: A total of 5.1% (190 out of 3702) patients with CD4 count ≤ 100 cell/mm3 were cryptococcal antigen positive (CrAg +ve), of whom 22.6% (43 out of 190) were admitted with CCM. Patients who were CrAg +ve had significantly lower CD4 counts (mean CD4 = 38.9 ± 28.5) when compared to CrAg -ve patients (mean CD4 = 49.9 ± 37.4) with p = 0.0001. Only 2.6% (5 out of 190) of patients were referred for a lumbar puncture (LP) as part of the screen-and-treat intervention, whilst 38 who were CrAg +ve self-presented with CCM. Eighty-eight patients were admitted for suspected CCM: eight because of the screen-and-treat-intervention (none of whom had meningitis based on cerebrospinal fluid results) and 80 of whom self-presented and had confirmed CCM. The overall mortality of patients admitted with CCM was 30% (24 out of 80). Conclusion: The current ad-hoc screen-and-treat intervention was ineffective in detecting patients at risk of developing CCM. Systems need to be put in place to ensure that all CrAg +ve patients have an LP to detect subclinical CCM to improve the outcome for those with HIV-associated CCM.

Purpose of Review: Cryptococcosis has become a common opportunistic infection among non-HIV immunocompromised hosts. Recent reports have shown the incidence of Cryptococcosis among HIV-negative immunocompromised patients reaches close to half of the overall cases reported in the USA. Management of this infection in this population carries unique challenges. We aim to review relevant and recent research findings to develop treatment recommendations for this type of population., Recent Findings: Most of the recommendations for the management of non-HIV immunocompromised host are extrapolated from HIV studies. Cryptococcosis among non-HIV patients is common but often overlooked. Some clinical factors, when present, may increase the risk of Cryptococcosis among HIV-negative patients and appropriate screening and assessment for the disease is necessary. Treating clinicians should consider a longer duration of induction with Amphotericin B depending on the type of host, immunocompromised state, antifungal response and presence of neurological complications. Baseline fluconazole resistance can reach up to 12%, which is an important consideration for cryptococcal meningitis relapses or suboptimal responses to therapy., Summary: Cryptococcus spp. conveys a high disease burden among immunocompromised hosts. Clinicians must consider numerous variables and factors in a dynamic way to offer the best possible treatment and to monitor their response to therapy. Due to the high cost and associated toxicities, we still need new affordable therapies and studies among non-HIV immunocompromised patients.

In 2017, the World Health Organization (WHO) published guidelines for the management of advanced human immunodeficiency virus (HIV) disease within a public health approach. Recent data suggest that more than a third of people starting antiretroviral therapy (ART) do so with advanced HIV disease, and an increasing number of patients re-present to care at an advanced stage of HIV disease following a period of disengagement from care. These guidelines recommend a standardized package of care for adults, adolescents, and children, based on the leading causes of morbidity and mortality: tuberculosis, severe bacterial infections, cryptococcal meningitis, toxoplasmosis, and Pneumocystis jirovecii pneumonia. A package of targeted interventions to reduce mortality and morbidity was recommended, based on results of 2 recent randomized trials that both showed a mortality reduction associated with delivery of a simplified intervention package. Taking these results and existing recommendations into consideration, WHO recommends that a package of care be offered to those presenting with advanced HIV disease; depending on age and CD4 cell count, the package may include opportunistic infection screening and prophylaxis, including fluconazole preemptive therapy for those who are cryptococcal antigen positive and without evidence of meningitis. Rapid ART initiation and intensified adherence interventions should also be proposed to everyone presenting with advanced HIV disease.

We conducted a retrospective study of 549 adults admitted with community-acquired meningitis (CAM) to several hospitals in New Orleans, LA and Houston, TX between 1999 and 2014 to characterize the current epidemiology, clinical manifestations, cerebrospinal fluid (CSF) characteristics, and outcomes of CAM between HIV-infected and uninfected patients and to identify risk factors for adverse outcomes in CAM. Bivariate analysis and logistic regression analysis were used to identify prognostic factors. A total of 1022 patients with CAM were screened. Only 549 (53.7%) subjects had an HIV test and were included in the study. Of those, 138 (25%) had HIV infection. HIV-infected patients presented with less meningeal symptoms (headache, neck stiffness, and Kernig sign), but with higher rates of hypoglycorrhachia, elevated CSF protein, and an abnormal cranial imaging (p < 0.05). More than 50% of all the patients had an unknown etiology. Cryptococcal meningitis was the most common identified etiology of CAM in HIV-infected patients followed by neurosyphilis and varicella-zoster virus (VZV). Viral and bacterial etiologies were the most frequent etiologies in non-HIV-infected patients. Streptococcus pneumoniae was the most common bacterial pathogen in both groups, but it was rare overall (2%). Adverse clinical outcomes were similar in both groups (27% vs. 24%). Logistic regression identified hypoglycorrhachia and an abnormal neurological examination as independent predictor factors of worse outcome in all patients with meningitis. Our results demonstrate that the etiology, clinical presentation, and CSF findings differ between HIV-infected and HIV-uninfected adults with CAM, but clinical outcomes are similar.

Rationale: Microbial infection should be regarded in the differential diagnosis of neurosurgical complications after transnasal transsphenoidal pituitary microsurgery, albeit cryptococcal meningitis is rare. This article will discuss the risk factors of cryptococcal meningitis in patients underwent transnasal transsphenoidal pituitary microsurgery, and summary the potential origins of infection., Patient Concerns and Diagnosis: Here, we report a case of 37-year-old male who had cryptococcal meningitis after transnasal transsphenoidal pituitary microsurgery of a relapsing ACTH-secreting pituitary adenoma., Intervention: Standard therapy for Cryptococcus neoformans (fluconazole [400 mg per day] and flucytosine) was administered and followed by maintenance dose., Outcomes: The patient had been on treatment for one and a half years during follow-up and reported neurologically well with repeated negative cerebrospinal fluid (CSF) culture until sudden death of heart arrest., Main Lessons to Learn: C neoformans can be a possible cause of meningitis in immunocompetent patients after transnasal transsphenoidal pituitary microsurgery. Risk factors, such as pre-existed pulmonary infection and Cushing-associated hypercortisolemia, should be stressed. Promising preventive measures may include preoperative routine sputum smear and India-ink stain for screening, preoperative treatment of cryptococcal pneumonia, postoperative antibiotic management, and a more secure skull base reconstruction. Radiation and pharmaceutical treatment may be alternative for recurrent Cushing disease.

Background: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus neoformans and most remarkably manifests in HIV-infected individuals, especially in the settings of very low CD4 count. Development of cryptococcosis in HIV-uninfected individuals is exceedingly rare and usually signifies a marked immunodeficiency. Cryptococcosis in association with myasthenia gravis or thymoma has been previously documented in only very few cases in the literature., Case Presentation: We reported a complicated case of severe cutaneous cryptococcosis in a 39-year-old Vietnamese male patient with myasthenia gravis on long-term immunosuppressive therapy. The patient presented with a five month history of recurrent and progressive skin lesions that later on progressed into cryptococcal meningitis., Conclusion: Through this case, we aimed to emphasize the importance of including cutaneous cryptococcosis in the differential diagnosis of cutaneous lesions in patients on chronic immunosuppressive therapy. The cutaneous manifestations of cryptococcosis can be the first clue for a disseminated disease, which makes early recognition crucial and life-saving.

Background: The nervous system is among the most frequent and serious targets of human immunodeficiency virus (HIV) infection. The infection usually occurs in patients with profound immunosuppression. In 10 - 20% of the patients, the presence of a neurological disease is the first manifestation of symptomatic HIV infection., Aims and Objective: Despite the wide prevalence of neurological manifestations in HIV, there is no study examining the clinical manifestations of this disease in the resource- limited communities from north-eastern parts of India. To characterize the neurological involvement in patients with HIV infection at a tertiary care institute in northeast India, we studied various neurological presentations of HIV., Setting and Design: This was a retrospective observational study done at a tertiary care institute in northeast India over a period of 6 years from August 2008 to September 2014., Material and Methods: A total of 91 HIV seropositive patients of both genders, aged >18 years, showing clinical evidence of central nervous system (CNS) involvement, and admitted in a tertiary care institute were included. Their clinical manifestations, laboratory investigations, and imaging were studied., Result: Tuberculous meningitis was the most common presentation as secondary CNS illness (43.9%), followed by cryptococcal meningitis (14.2%) and cerebrovascular accidents (5.49%). Furthermore, 6.59% had neurosyphilis, 6.59% had acquired immune deficiency syndrome (AIDS) - associated dementia, and peripheral neuropathy occurred in 16.4% of the patients. Headache was the most common neurological symptom seen in 25% of the patients. Seizures were noted in 25% of the pateints. CD4 was significantly low in most of the patients with progressive multifocal leukoencephalopathy, HIV associated encephalopathy (HAD) and cryptococcal meningitis compared with other neurological manifestations. CD4 counts in tuberculous meningitis and HAD were 110.3/μl and 95/μl, respectively., Conclusion: CNS tuberculosis was the most common secondary infection seen in HIV patients followed by cryptococcal meningitis. A high index of clinical suspicion of neurological involvement in HIV patients helps in the early diagnosis and early institution of specific treatment, which in turn decreases the morbidity and mortality considerably.

HIV and cryptococcal meningitis co-infection is a major public health problem in most developing countries. Cryptococcus neoformans sensu stricto is responsible for the majority of HIV-associated cryptococcosis cases in sub-Saharan Africa. Despite the available information, little is known about cryptococcal population diversity and its association with clinical outcomes in patients with HIV-associated cryptococcal meningitis in sub-Saharan Africa. In a prospective cohort, we investigated the prevalence and clinical outcome of Cryptococcusneoformans sensu stricto meningitis among HIV-infected patients in Harare, Zimbabwe, and compared the genotypic diversity of the isolates with those collected from other parts of Africa. Molecular typing was done using amplified fragment length polymorphism genotyping and microsatellite typing. The majority of patients with HIV-associated Cryptococcusneoformans sensu stricto meningitis in this cohort were males (n=33/55; 60.0 %). The predominant Cryptococcus neoformans sensu stricto genotype among the Zimbabwean isolates was genotype AFLP1/VNI (n=40; 72.7 %), followed by AFLP1A/VNB/VNII (n=8; 14.6 %), and AFLP1B/VNII was the least isolated (n=7; 12.7 %). Most of the isolates were mating-type α (n=51; 92.7 %), and only four (7.3 %) were mating-type a. Overall in-hospital mortality was 55.6 % (n=30), and no difference between infecting genotype and clinical outcome of patient (P=0.73) or CD4+ counts (P=0.79) was observed. Zimbabwean Cryptococcusneoformans sensu stricto genotypes demonstrated a high level of genetic diversity by microsatellite typing, and 51 genotypes within the main molecular types AFLP1/VNI, AFLP1A/VNB/VNII and AFLP1B/VNII were identified. This study demonstrates that Cryptococcusneoformans sensu stricto in Zimbabwe has a high level of genetic diversity when compared to other regional isolates.

Nearly 30 years after the advent of antiretroviral therapy (ART), CNS opportunistic infections remain a major cause of morbidity and mortality in HIV-positive individuals. Unknown HIV-positive disease status, antiretroviral drug resistance, poor drug compliance, and recreational drug abuse are factors that continue to influence the morbidity and mortality of infections. The clinical and radiographic pattern of CNS opportunistic infections is unique in the setting of HIV infection: opportunistic infections in HIV-positive patients often have characteristic clinical and radiological presentations that can differ from the presentation of opportunistic infections in immunocompetent patients and are often sufficient to establish the diagnosis. ART in the setting of these opportunistic infections can lead to a paradoxical worsening caused by an immune reconstitution inflammatory syndrome (IRIS). In this Review, we discuss several of the most common CNS opportunistic infections: cerebral toxoplasmosis, progressive multifocal leukoencephalopathy (PML), tuberculous meningitis, cryptococcal meningitis and cytomegalovirus infection, with an emphasis on clinical pearls, pathological findings, MRI findings and treatment. Moreover, we discuss the risk factors, pathophysiology and management of IRIS. We also summarize the challenges that remain in management of CNS opportunistic infections, which includes the lack of phase II and III clinical trials, absence of antimicrobials for infections such as PML, and controversy regarding the use of corticosteroids for treatment of IRIS.

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection., (© 2016 Blackwell Verlag GmbH.)

Background: We aimed to establish the prevalence of amphotericin B deoxycholate (AmBd)-related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations to prevent, monitor and manage AmBd-related toxicities., Methods: Clinical data were collected from cases of laboratory-confirmed cryptococcosis at 25 hospitals, October 2012 -February 2013. Anemia was defined as hemoglobin (Hb) concentration <10 g/dl, hypokalemia as serum potassium (K) <3.4 mEq/L and nephrotoxicity as an increase in serum creatinine (Cr) to >1.1 times the upper limit of normal. To determine adherence to toxicity prevention recommendations, we documented whether baseline Hb, K and Cr tests were performed, whether pre-emptive hydration and IV potassium chloride (KCl) was administered prior to 80% and 60% of AmBd doses and whether daily oral KCl supplementation was given ≥60% of the time. To determine adherence to monitoring recommendations, we ascertained whether a daily fluid chart was completed, Hb was monitored weekly and K or Cr were monitored bi-weekly., Results: Of 846 patients, clinical data were available for 76% (642/846), 82% (524/642) of whom received AmBd. Sixty-four per cent (n = 333) had documented baseline laboratory tests, 40% (n = 211) were given pre-emptive hydration and 14% (n = 72) and 19% (n = 101) received intravenous and oral KCl. While on AmBd, 88% (n = 452) had fluid monitoring; 27% (n = 142), 45% (n = 235) and 44% (n = 232) had Hb, K and Cr levels monitored. Toxicities developed frequently during treatment: anemia, 16% (86/524); hypokalemia, 43% (226/524) and nephrotoxicity, 32% (169/524)., Conclusion: AmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.

Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) is an increasingly important manifestation among patients with HIV/AIDS, especially as the use of antiretroviral therapy (ART) is expanding worldwide. Cryptococcus and associated C-IRIS are common causes of meningitis. While intracranial lesions are common in HIV/AIDS, they are rarely due to cryptococcosis or C-IRIS. We describe two cases of paradoxical C-IRIS associated with the development of intracranial cryptococcomas in HIV/AIDS. Both patients had an initial episode of cryptococcal meningitis treated with antifungal therapy. At the time, they had initiated or modified ART with subsequent evidence of immune reconstitution. Two months later, they developed aseptic meningitis with intracranial lesions. After exhaustive work ups, both patients were diagnosed with paradoxical C-IRIS and biopsy confirmed intracranial cryptococcomas. We review the important clinical, diagnostic and therapeutic features of cryptococcomas associated with C-IRIS in HIV/AIDS., (2015 BMJ Publishing Group Ltd.)

Objective: Systemic lupus erythematosus (SLE) is a chronic immunologic disorder that can affect multiple organ systems and makes the patient susceptible to infection. Cryptococcal meningitis (CM) is a rare but often fatal complication of SLE., Design: In this study, 6 patients with CM were identified among 631 patients with SLE. The demographic, clinical, laboratory profiles, serological features and outcomes of these 6 SLE patients with CM were retrospectively analyzed., Results: The mean age of these patients was 24.1 years (range 12-42) at the time of SLE diagnosis, and 27.1 years (range 14-42) at the time of Cryptococcus neoformans infection, with mean disease duration of 37 months (range 3-72). Four patients had active SLE. All patients were receiving glucocorticoids therapy (mean prednisone dose of 20.5 (5.0-36.0) mg/day) at the onset of infection. Five patients had received other immunosuppressive drugs. The most common presentations of CM were headache and fever and 4 of the 6 patients were normal on physical examination. The cerebrospinal fluid (CSF) indices (protein and glucose) were normal in 4 cases, whereas they were mildly abnormal in the other 2 patients. White counts in the CSF ranged from 8 to 240 cells/mm. C. neoformans were isolated from CSF of 4 patients. The isolation of crytococci from extraneural sites, including blood and lungs, was found in 2 patients. Results of the head computed tomography scan were unremarkable in 5 of the patients. The infection was completely resolved in 5 patients, and it was resolved with serious sequelae in one patient., Conclusions: In conclusion, the key to a rapid diagnosis of CM in patients with SLE is to maintain a high degree of awareness which will help avoid delays in treatment. This is mainly due to the fact that the clinical presentation and laboratory results from routine hematological, biochemical and CSF analyses of CM in patients with SLE are mostly non-specific., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Cryptococcus neoformans is a ubiquitous environmental fungus that can cause life-threatening meningitis and fungemia, often in the presence of acquired immunodeficiency syndrome (AIDS), liver cirrhosis, diabetes mellitus, or other medical conditions. To distinguish risk factors from comorbidities, we performed a hospital-based, density-sampled, matched case-control study., Methods: All new-onset cryptococcal meningitis cases and cryptococcemia cases at a university hospital in Taiwan from 2002-2010 were retrospectively identified from the computerized inpatient registry and were included in this study. Controls were selected from those hospitalized patients not experiencing cryptococcal meningitis or cryptococcemia. Controls and cases were matched by admission date, age, and gender. Conditional logistic regression was used to analyze the risk factors., Results: A total of 101 patients with cryptococcal meningitis (266 controls) and 47 patients with cryptococcemia (188 controls), of whom 32 patients had both cryptococcal meningitis and cryptococcemia, were included in this study. Multivariate regression analysis showed that AIDS (adjusted odds ratio [aOR] = 181.4; p < 0.001), decompensated liver cirrhosis (aOR = 8.5; p = 0.008), and cell-mediated immunity (CMI)-suppressive regimens without calcineurin inhibitors (CAs) (aOR = 15.9; p < 0.001) were independent risk factors for cryptococcal meningitis. Moreover, AIDS (aOR = 216.3, p < 0.001), decompensated liver cirrhosis (aOR = 23.8; p < 0.001), CMI-suppressive regimens without CAs (aOR = 7.3; p = 0.034), and autoimmune diseases (aOR = 9.3; p = 0.038) were independent risk factors for developing cryptococcemia. On the other hand, diabetes mellitus and other medical conditions were not found to be risk factors for cryptococcal meningitis or cryptococcemia., Conclusions: The findings confirm AIDS, decompensated liver cirrhosis, CMI-suppressive regimens without CAs, and autoimmune diseases are risk factors for invasive C. neoformans diseases.

Background: Cryptococcal meningoencephalitis (CM) is the most common opportunistic infection of the central nervous system (CNS). Despite this observation, there have only been a few studies analyzing clinical characteristics as well as cerebrospinal fluid (CSF), electroencephalograph (EEG), and magnetic resonance imaging (MRI) features in CM patients of all ages., Methods: We reviewed the medical records of all patients diagnosed with cryptococcal meningoencephalitis from 1998 to 2013 in the Nanfang Hospital in China and gathered data on the underlying diseases, bird exposure history, and clinical features, including those from CSF, EEG and MRI., Results: CM is more likely to infect adults younger than 60 years old. 71.3% of CM patients were male. Unlike data from other countries, we found that chronic use of corticosteroids or other immunosuppressants (17.59%) was the most frequent risk factor in CM patients rather than HIV infection (1.85%). Clear exposure with bird/ bird droppings before CM onset is obvious in a previous study in CM children. However, our study found that 4.63% CM patients had such an exposure. More importantly, patients with brain tissue damage (p = 0.021) and decreased CSF/blood glucose ratio (p = 0.008) were significantly associated with death, but only the decreased CSF/blood glucose ratio was the contributing factor of prognosis (odds ratio, 0.047; p = 0.025). Decreased CSF/blood glucose ratio was significantly related to the survival length of CM (odds ratio, 0.134; p = 0.033)., Conclusions: Our study shows that CM has predilection for young male adults. The chronic use of corticosteroids or other immunosuppressants, rather than HIV infection or bird/bird droppings exposure, was the most frequent risk factor in CM patients in our study. Decreased CSF/blood glucose ratio was both an independent contributing factor to death and was significantly related to the survival length of CM patients. The more decreased the CSF/blood glucose ratio was, the worse prognosis and shorter survival length CM patients had.

There is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains needed, and implementation of cryptococcal diagnostics is critical., (© The American Society of Tropical Medicine and Hygiene.)

In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis-associated IRIS 1 week after immunosuppression reduction. High-dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor-α (TNF-α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: Cryptococcal meningitis is a severe AIDS-related infectious disease, with a high mortality rate. Diabetes mellitus (DM) is a metabolic disorder very common worldwide. Infectious diseases in diabetic patients are always more severe than in non-diabetic ones. The aim of this study was to compare the outcome of a group of HIV-positive patients with DM and cryptococcal meningitis with a similar group HIV-positive patients with cryptococcal meningitis, but without DM., Material and Methods: A total of 182 clinical records of HIV-positive patients suffering cryptococcal meningitis were reviewed, and 28 of them with similar clinical and epidemiological characteristics, were chosen. They included 14 patients with DM (group A) and the remaining 14 who did not suffer this metabolic disorder (group B)., Results: Only 21.4% (3/14 cases) of group A patients had negative CSF cultures after 10 weeks of treatment. In group B patients, 78.5% (11/14 cases) achieved negative CSF cultures before 10 weeks. A higher overall mortality rate was observed in the diabetic patients (85.7%, 12/14 cases) than in the non-diabetic group (21.4%, 3/14 cases). All CSF isolates were identified as Cryptococcus neoformans, and all strains were susceptible in vitro to amphotericin B and fluconazole., Conclusions: Cryptococcal meningitis in diabetic patients was associated with a poor clinical outcome and a high mortality rate. A longer treatment induction period is suggested in order to improve the outcome of cryptococcal meningitis in diabetic patients., (Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Objectives: To investigate the epidemiology and outcomes of community-acquired meningitis in older adults., Design: Retrospective study., Setting: Participants adults in Houston, Texas, with community-acquired meningitis hospitalized between January 1, 2005, and January 1, 2010 (N = 619; n = 54, 8.7%, aged ≥65; n = 565 aged <65)., Methods: An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less., Results: Older adults had higher rates of comorbidities, abnormal neurological and laboratory (serum white blood cell count >12,000/μL, and cerebrospinal fluid protein >100 mg/dL) findings (P < .001), abnormalities on computed tomography and magnetic resonance imaging of the head (P = .002), and adverse clinical outcomes (ACOs) (P < .001). The majority of participants (65.8%) had meningitis of unknown etiology. Bacterial meningitis was an infrequent cause of community-acquired meningitis (7.4%). Of the known causes, bacterial meningitis and West Nile virus were more common in older than younger adults; younger participants more frequently had cryptococcal and viral meningitis. On logistic regression, female sex was predictive of a poor outcome in the older participants (P = .002), whereas abnormal neurological examination (P < .001), fever (P = .01), and a cerebrospinal fluid glucose level less than 45 mg/dL (P = .002) were significant poor prognostic factors in younger participants., Conclusion: Most cases of community-acquired meningitis are of unknown origin. Older adults are more likely than younger adults to have bacterial meningitis and West Nile virus infection when a cause can be identified. They also have more neurological abnormalities, laboratory and imaging abnormalities, and adverse clinical outcomes., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)