Cryptococcal Meningoencephalitis in an Immunocompetent Patient: A Case Report.

Co-infections involving dengue virus (DENV) and opportunistic fungal pathogens are rarely reported alongside human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). To our knowledge, no prior cases of DENV and Cryptococcus neoformans coinfection have been documented. This case highlights a novel presentation of concurrent DENV and cryptococcal meningoencephalitis in an immunocompromised host, reinforcing the importance of considering multiple etiologies in patients from tropical regions presenting with neurological symptoms. A 21-year-old Brazilian male with previously unknown HIV status presented with fever and signs of meningeal irritation, without neurological deficits. Initial laboratory evaluations revealed lymphopenia, thrombocytopenia, and elevated transaminase levels. DENV infection was confirmed by serological testing (NS1 antigen and IgM positivity) and by cerebrospinal fluid with DENV IgM reactivity, leading to a diagnosis of dengue meningoencephalitis. HIV serology subsequently tested positive. After the initiation of antiretroviral therapy, he developed worsening headaches followed by neurological deficits. A second lumbar puncture confirmed cryptococcal meningitis by India ink staining and multiplex PCR, with additional confirmation by fungal culture. The patient was diagnosed with concomitant dengue fever and cryptococcal meningoencephalitis. This is the first reported case of concurrent DENV and C. neoformans meningoencephalitis in a patient with HIV. The overlapping symptomatology of arboviral and opportunistic infections can complicate diagnosis, particularly in endemic areas with limited resources. This case underscores the importance of maintaining a broad differential diagnosis in patients presenting with systemic and neurological symptoms who are immunocompromised, especially in tropical regions where multiple pathogens may co-circulate. Awareness of unusual co-infections is essential to ensure timely diagnosis and appropriate management, ultimately improving patient outcomes. Not applicable.

Introduction: Cryptococcal meningoencephalitis (CM) carries a mortality rate of 15% to 30%. It is rarely seen in immunocompetent patients, making the diagnosis challenging in normal individuals. Case: The patient is a young adult male with a medical history of substance use disorder who presents to the emergency room with altered mental status and falls. He had a partial improvement in alertness after naloxone administration and was admitted to the intensive care unit on a naloxone drip. The admission's computerized tomography (CT) of the head and the brain magnetic resonance imaging (MRI) were unremarkable. Relevant labs included a urine drug screen positive for opiates, fentanyl, buprenorphine, a reactive hepatitis C virus (HCV) antibody, an elevated white cell count of 20,000, and a negative HIV test. A lumbar puncture showed an opening pressure of 53 cm H20 and a positive cryptococcal antigen titer at 1:80, prompting the diagnosis of CM. Given the high opening pressure, we repeated daily lumbar punctures and initiated amphotericin B and flucytosine after consultation with infectious diseases. Due to a lack of neurologic improvement, a repeat CT performed two days later revealed multiple late acute infarcts throughout the cerebral and cerebellar hemispheres and in the basal ganglia, plus a hypodensity in the right temporal lobe suggestive of acute infarct (image 1). After extensive conversations with family members, the patient eventually transitioned to comfort care. Discussion: Cryptococcal meningoencephalitis is common among immunocompromised individuals. However, its occurrence in immunocompetent individuals is rare, making it hard to recognize early. The causative agent enters the respiratory tract and spreads hematogenously, with affinity for the central nervous system (CNS). We suspect that the patient's hepatitis C and intravenous drug use (IVDU) may have predisposed him to cryptococcal infection. Hepatitis C affects innate and adaptive immune systems that can cause defective cytokine production — impairing lymphocyte activation and dysfunctional natural killer cell responses. IVDA can compromise immunity in different ways, including changes in the hypothalamic-pituitary-adrenal axis and autonomic nervous system and suppression of T lymphocytes. There are only a handful of reports associating HCV (without cirrhosis) with CM. Recent reports suggest that IVDU may be a new risk factor for CM. Given the high mortality risk of CM, a higher index of suspicion is needed to diagnose immunocompetent patients with cryptococcal meningoencephalitis, especially in the presence of IVDU or HCV.

BackgroundGastrointestinal mucormycosis (GIM) is a rare, opportunistic fungal infection with poor prognosis. Clinically, it is difficult to diagnose GIM owing to its nonspecific clinical symptoms and poor suspicion. The estimated incidence of GIM is inaccurate, and most cases are diagnosed accidentally during surgery or upon postmortem examination. GIM usually occurs in patients with immune deficiencies or diabetes. Here, we report two cases of immunocompetent young patients with GIM who had good prognosis after treatment. Compared to other case reports on GIM, our cases had unusual infection sites and no obvious predisposing factors, which make it important to highlight these cases.Case presentationThe first case was that of a 16-year-old immunocompetent boy who was admitted with gastrointestinal bleeding and perforation due to a gastric ulcer. Strategies used to arrest bleeding during emergency gastroscopy were unsuccessful. An adhesive mass was then discovered through laparoscopy. The patient underwent type II gastric resection. Pathological examination of the mass revealed bacterial infection and GIM. The second case was of a 33-year-old immunocompetent woman with a recent history of a lower leg sprain. The patient subsequently became critically ill and required ventilatory support. After hemodynamic stabilization and extubation, she presented with hematemesis due to exfoliation and necrosis of the stomach wall. The patient underwent total gastrectomy plus jejunostomy. The pathology results revealed severe bacterial infection and fungal infection that was confirmed as GIM. The patient fully recovered after receiving anti-infective and antifungal treatments.ConclusionsNeither patient was immunosuppressed, and both patients presented with gastrointestinal bleeding. GIM was confirmed via pathological examination. GIM is not limited to immunocompromised patients, and its diagnosis mainly relies on pathological examination. Early diagnosis, timely surgical treatment, and early administration of systemic drug treatment are fundamental to improving its prognosis.

Article1 July 1968Serology of Human CryptococcosisDARRYL D. BINDSCHADLER, M.D., JOHN E. BENNETT, M.D., F.A.C.P.DARRYL D. BINDSCHADLER, M.D.Search for more papers by this author, JOHN E. BENNETT, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-69-1-45 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSixty-nine patients with cryptococcal meningoencephalitis and six patients with nonmeningeal cryptococcosis were studied serologically. Twenty-nine of the 75 patients had serum anticryptococcal antibody by an indirect fluorescence test (IFA). Titers ranged from 1:1 to 1:32. Forty-seven patients had cryptococcal antigen in serum or cerebrospinal fluid (CSF) detected by a complement fixation (CF) test. Of the 47, 7 also had serum antibody. Antigen titers ranged from 1:1 to 1:2048 in CSF and from 1:4 to 1:512 in serum. Only six patients, four with cryptococcal meningoencephalitis, were negative to both serologic tests.Among the patients with cryptococcal meningoencephalitis, those with Cryptococcus in india ink smears of CSF usually had cryptococcal antigen in blood, CSF, or both. Patients with negative india ink smears despite positive CSF cultures tended to have serum anticryptococcal antibody. The patients with anticryptococcal antibody were generally less ill than those with antigen and obtained a better response to therapy with amphotericin B.Although the CF test for antigen has been specific for cryptococcosis, a few false-positive tests for antibody were found. Among 253 control sera, 1.6% were IFA positive, as were sera from 6% of blastomycosis patients and from 12% of histoplasmosis patients. A cryptococcal skin test was also noted to produce false-positive IFA reactions in 31% of 48 patients and could create errors in serologic diagnosis.The two serologic tests used together have sufficient specificity and sensitivity to be a useful aid in the rapid diagnosis of cryptococcosis....

status: Published

BackgroundAlthough male predominance was documented in previous studies on cryptococcal meningoencephalitis (CM), there has been no statistical study about female CM patients despite recently noticeable increase in female prevalence. In the current study, we aimed to investigate the independent gender-specific contributing risk factors for onset of CM and factors related to survival time in female patients by chosen statistical tools.MethodsThere have been 108 patients diagnosed with CM from July 1, 1998 to June 30, 2013 in Nanfang Hospital that were included in our study. This 15-year retrospective study compared demographic and clinical features of 31 female patients with 77 males. Multivariate analysis was performed for detection of the contributors to the onset of CM in female patients. The independent variables for multivariate analysis were selected according to statistical significance in univariate analysis. Furthermore, Cox regression model was used to evaluate the factors related to survival length.ResultsUse of corticosteroids or other immunosuppressants (32.3 % versus 11.7 %; p = 0.011) and history of systemic lupus erythematosus (SLE) and other autoimmune diseases (29 % versus 3.9 %; p < 0.001) were more common in females, but only the history of SLE or other autoimmune diseases was significant (OR 10.59, 95 % CI 1.49-74.77, p = 0.02) by multivariate analysis. The ratio of cerebrospinal fluid (CSF) glucose-to-blood glucose was related to the survival time (p = 0.03, 95 % CI 0-0.71).ConclusionsThe results showed that the history of SLE or other autoimmune diseases rather than chronic use of corticosteroids and/or immunosuppressants was the independent gender-specific contributing risk factor in female CM patients. Therefore, more attention should be made to the prevention of infection from the genus Cryptococcus spp. in female patients with SLE or other autoimmune diseases. In addition, decreased ratio of CSF glucose-to-blood glucose before antifungal therapy predicted the worse prognosis.

Cryptococcus species are life-threatening human fungal pathogens that cause cryptococcal meningoencephalitis in both immunocompromised and healthy hosts. The natural environmental niches of Cryptococcus include pigeon (Columba livia) guano, soil, and a variety of tree species such as Eucalyptus camaldulensis, Ceratonia siliqua, Platanus orientalis, and Pinus spp. Genetic and genomic studies of extensive sample collections have provided insights into the population distribution and composition of different Cryptococcus species in geographic regions around the world. However, few such studies examined Cryptococcus in Turkey. We sampled 388 Olea europaea (olive) and 132 E. camaldulensis trees from seven locations in coastal and inland areas of the Aegean region of Anatolian Turkey in September 2016 to investigate the distribution and genetic diversity present in the natural Cryptococcus population. We isolated 84 Cryptococcus neoformans strains (83 MATα and 1 MATa) and 3 Cryptococcus deneoformans strains (all MATα) from 87 (22.4% of surveyed) O. europaea trees; a total of 32 C. neoformans strains were isolated from 32 (24.2%) of the E. camaldulensis trees, all of which were MATα. A statistically significant difference was observed in the frequency of C. neoformans isolation between coastal and inland areas (P < 0.05). Interestingly, the MATa C. neoformans isolate was fertile in laboratory crosses with VNI and VNB MATα tester strains and produced robust hyphae, basidia, and basidiospores, thus suggesting potential sexual reproduction in the natural population. Sequencing analyses of the URA5 gene identified at least five different genotypes among the isolates. Population genetics and genomic analyses revealed that most of the isolates in Turkey belong to the VNBII lineage of C. neoformans, which is predominantly found in southern Africa; these isolates are part of a distinct minor clade within VNBII that includes several isolates from Zambia and Brazil. Our study provides insights into the geographic distribution of different C. neoformans lineages in the Mediterranean region and highlights the need for wider geographic sampling to gain a better understanding of the natural habitats, migration, epidemiology, and evolution of this important human fungal pathogen.

BackgroundCryptococcosis is a major opportunistic invasive mycosis in immunocompromised patients, but it is also increasingly seen in immunocompetent patients. In the early stages of cryptococcosis, limitations of the detection method may hinder the diagnosis. A molecular diagnostic technique based on nucleic acid sequence-based amplification (NASBA) method was developed to fulfil the need for efficient diagnosis of cryptococcosis.MethodsWe compared the diagnostic performance of NASBA, PCR and cryptococcal antigen (CrAg) test (colloidal gold method) in clinical samples from 25 cryptococcosis patients (including 8 cryptococcal meningoencephalitis and 17 pulmonary cryptococcosis) who were categorized as proven cases (n = 10) and probable cases (n = 15) according to the revised EORTC/MSG definitions. 10 patients with non-Cryptococcus infection and 30 healthy individuals were categorized as control group.ResultsThe lowest detection limit of NASBA was 10 CFU/mL, and RNA of non-target bacteria or fungi was not amplified. The sensitivity of NASBA, PCR and colloidal gold method was 92.00% (95% CI 72.50–98.60%), 64.00% (95% CI 42.62–81.29%), 100.00% (95% CI 83.42–100.00%), and the specificity was 95.00% (95% CI 81.79–99.13%), 80.00% (95% CI 63.86–90.39%) and 82.50% (95% CI 66.64–92.11%) respectively. The highest specificity (97.50%), accuracy (95.38%) and k value (0.90) were achieved when both NASBA and colloidal gold results were positive.ConclusionsNASBA is a new alternative detection method for cryptococcosis which is both accurate and rapid without expensive equipment and specialised personnel. It may be used as a tool for confirming current infection as well as monitoring the effectiveness of antifungal treatment. The use of NASBA to detect Cryptococcus RNA in blood samples is of great significance for the diagnosis of pulmonary cryptococcosis. The combination of NASBA and colloidal gold can improve the diagnostic accuracy of cryptococcosis.

Nocardia is an opportunistic pathogen from environment, which is generally thought to infect immunosuppressed patients (ISPs), but recent studies showed it could also cause infections in immunocompetent patients (ICPs).The aim of this study was to compare the clinical characteristics, patients’ outcome, Nocardia species’ identification, and antibiotic susceptibility profiles of nocardiosis between ICPs and ISPs.The detailed clinical data were collected from all the nonrepetitive nocardiosis patients during 2011 and 2018, from a tertiary general hospital in Beijing, China. Then each Nocardia isolate was identified to species level by DNA sequencing. The antibiotic susceptibility testing was performed by E test method, and interpreted following CLSI M24 document. The clinical and microbiological characteristics between ICPs and ISPs were compared statistically.A total of 23 nonrepetitive nocardiosis patients with detailed clinical data were enrolled in this study. Among them, 9 were ICPs and 14 were ISPs. All the skin and soft tissue infections occurred in ICPs (33.3% vs 0%, P < .05). Bronchiectasis occurred more frequently in ICPs (44.4% vs 21.4%), whereas chronic kidney diseases and coinfection with aspergillosis occurred more frequently in ISPs (35.7% vs 0%, 35.7% vs 0%, respectively), although they did not reach the statistical significance. There were no significant differences in other clinical characteristics, Nocardia species’ identification, and antibiotic susceptibility between ISPs and ICPs (P > .05).Nocardiosis could occur in both ISPs and ICPs. Skin and soft tissue infection and bronchiectasis occurred more frequently in ICPs. Chronic kidney diseases and co-infection with aspergillosis occurred more frequently in ISPs. These characteristics should be noticed by physicians in diagnosis of nocardiosis.

Idiopathic CD4+ lymphopenia (ICL) predisposes to opportunistic infections (OIs) but can often remain asymptomatic and does not have a strong association with monogenic mutations. Likewise, cryptococcal meningoencephalitis, the most common OI in ICL, is not strongly associated with monogenic mutations. In this study, we describe 2 patients with ICL plus an additional immune defect: one from an E57K genetic mutation in the nuclear factor-κβ essential modulator, and the other with acquired autoantibodies to granulocyte-macrophage colony-stimulating factor. Thus, these cases may exemplify a "multi-hit model" in patients with ICL who acquire OIs.

A RARE FATAL CASE OF DISSEMINATED MUCORMYCOSIS IN AN IMMUNOCOMPETENT PATIENT DIAGNOSED ON AUTOPSY

Central nervous system (CNS) histoplasmosis is a rare manifestation of Histoplasma capsulatum infection and is typically associated with disseminated disease in immunocompromised individuals. However, isolated CNS involvement in immunocompetent patients remains uncommon and poses a diagnostic challenge due to its nonspecific clinical presentation. We report the case of a 44-year-old immunocompetent male patient with a history of intravenous drug use who presented with seizures and progressive headache. Brain imaging revealed a left frontal ring-enhancing lesion with midline shift and surrounding edema. Despite negative systemic workup and serologies, the patient underwent surgical drainage of the abscess, and histopathological analysis confirmed infection by H. capsulatum. He was treated with liposomal amphotericin B for 50 days, resulting in full clinical recovery without neurological deficits. This case highlights the importance of including histoplasmosis in the differential diagnosis of cerebral abscesses, even in immunocompetent individuals from endemic areas, especially when noninvasive diagnostics are inconclusive. Early surgical intervention combined with appropriate antifungal therapy can lead to excellent outcomes.

Pneumocystis jirovecii testing by real-time polymerase chain reaction and direct examination among immunocompetent and immunosuppressed patient groups and correlation to disease specificity

A bstract Bacterial meningitis is common and may lead to long-term complications or death. It is usually acute in presentation and may involve more than one bacterial organism. Fungal meningitis is an opportunistic infection, that is, rare outside immunocompromised hosts. The occurrence of the two types simultaneously in an individual is a rare occurrence, especially in immunocompetent persons. We report a case of mixed bacterial and fungal meningitis in an immunocompetent 11-year-old Nigerian male who was apparently well, before the onset of symptoms. Clinical symptoms and laboratory findings were in keeping with mixed bacterial and fungal meningitis, and treatment with intravenous and oral anti-fungal with broad-spectrum antibiotics resulted in marked clinical improvement. The patient is currently being followed up and has demonstrated no sequelae. This case report is intended to highlight the possibility of encountering coexisting bacterial and fungal meningitis in an immunocompetent individual.

Invasive forms of aspergillosis of the nervous system are relatively rare and are usually diagnosed in immunocompromised patients. We present the case of a young female patient, treated in the last two months with corticosteroids and antifungal drug for pulmonary aspergillosis, who developed progressive paraparesis. An intramedullary abscess at the C7–D1 level was identified and the lesion was treated with a combination of surgery and antifungal therapy. Histopathologic findings of surgical specimens showed myelomalacia with Aspergillus hyphae and a peripheral rim of neutrophils. We consider that the use of multiple drugs and corticosteroids for our patient’s initial community pneumonia could be the factor that transformed her into a mildly immunocompromised individual and permitted the Aspergillus spp. to disseminate through the blood and into the spinal cord. Moreover, we highlight the fact that more attention should be paid to living and working conditions of the patients, as a simple colonization of the lung with Aspergillus spp. could develop, in a short time, into an invasive disease with a high risk of mortality.