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Item Cerebrospinal fluid levels of extracellular heat shock protein 72: A potential biomarker for bacterial meningitis in children(Thieme, 2014-03) Standage, Stephen W.; Lahni, Patrick M.; Ma, William; Kernie, Steven G.; Wong, Hector R.; Wheeler, Derek S.; Pediatrics, School of MedicineExtracellular heat shock protein 72 (Hsp72) is an endogenous danger signal and potential biomarker for critical illness in children. We hypothesized that elevated levels of extracellular Hsp72 in the cerebrospinal fluid (CSF) of children with suspected meningitis could predict bacterial meningitis. We measured extracellular Hsp72 levels in the CSF of 31 critically ill children with suspected meningitis via a commercially available enzyme-linked immunosorbent assay. Fourteen had bacterial meningitis based on CSF pleocytosis and bacterial growth in either blood or CSF culture. Seventeen children with negative cultures comprised the control group. CSF Hsp72 was significantly elevated in children with bacterial meningitis compared to controls. Importantly, CSF Hsp72 levels did not correlate with the CSF white blood cell count. On receiver operator characteristic analysis, using a cut-off of 8.1 ng/mL, CSF Hsp72 has a sensitivity of 79% and a specificity of 94% for predicting bacterial meningitis. We therefore conclude that CSF extracellular Hsp72 levels are elevated in critically ill children with bacterial meningitis versus controls. Hsp72 potentially offers clinicians improved diagnostic information in distinguishing bacterial meningitis from other processes.Item Cryptococcal Meningitis in Young, Immunocompetent Patients: A Single-Center Retrospective Case Series and Review of the Literature(Oxford University Press, 2023-08-11) Stack, Matthew; Hiles, Jon; Valinetz, Ethan; Gupta, Samir K.; Butt, Saira; Schneider, Jack G.; Medicine, School of MedicineBackground: Cryptococcal meningitis is an uncommon but serious infection with high mortality and morbidity. Classically described in immunocompromised patients, including those with solid organ transplants or HIV/AIDS, cryptococcosis has also been reported in young and otherwise healthy patients, albeit rarely. Methods: We retrospectively searched for all cases of cryptococcal meningitis in young (≤50 years) and previously healthy patients with no known immunocompromising conditions from January 2015 to January 2022 at Indiana University Health (IU Health). Additionally, a PubMed literature review was performed with the keywords "cryptococcal meningitis" and "immunocompetent" from January 1988 to January 2022. Clinical courses, including outcomes and treatment regimens, were evaluated. Results: We identified 4 local cases of cryptococcal meningitis in otherwise healthy patients age ≤50 years. Three cases were due to Cryptococcus neoformans, with 1 experiencing a postinfectious inflammatory response syndrome (PIIRS). The PubMed search identified 51 additional cases, with 32 (63%) being caused by Cryptococcus neoformans and 8 (17%) by Cryptococcus gattii. Of the 51 cases, only 2 resulted in death directly due to cryptococcosis. Fifteen (29%) had PIIRS, with steroid treatment documented in 11 of 15. Antifungal induction regimens and duration were varied but predominately consisted of amphotericin and flucytosine, with a mean induction duration of 5.0 weeks. Conclusions: Cryptococcal meningitis in young, previously healthy patients is likely under-recognized. PIIRS (akin to immune reconstitution inflammatory syndrome observed in HIV/AIDS) with prolonged recovery should be of concern. Determining risk factors for cryptococcosis in these patients remains elusive.Item Detection of (1,3)-β-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis(American Society for Microbiology, 2018-09-25) Myint, Thein; Chow, Felicia C.; Bloch, Karen C.; Raymond-Guillen, Luke; Davis, Thomas E.; Wright, Patty W.; Woc-Colburn, Laila; Khairy, Raed N.; Street, Alan C.; Yamamoto, Tomotaka; Albers, Amanda; Wheat, L. Joseph; Hage, Chadi A.; Medicine, School of MedicineThe diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to <31 pg/ml for all controls (P < 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis.Item Indiana State Board of Health Monthly Bulletin, 1909 Vol. 12 No. 12(1909) J. P. SimonsItem Multifaceted realities of scrub typhus: a case series from southern India(Department of Medicine and Surgery, University of Salerno, 2023-09-01) Ravikumar, Diviya Bharathi; Sivasubramanian, Barath Prashanth; Shanmugam, Sruthi Nandhaa; Krishnaswamy, Vanitha; Rabaan, Ali; Al-Tawfig, Jaffar A.; Tirupathi, Raghavendra; Medicine, School of MedicineScrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, a Gram-negative bacillus, commonly occurring in the Asia-Pacific region. It is transmitted to humans by the bite of an infected Leptotrombidium mite and the bacterium causes endothelial dysfunction resulting in widespread vasculitis and the possible development of thrombocytopenia, meningitis, acute respiratory distress syndrome, and infrequently, myocarditis. Early diagnosis and prompt treatment are crucial in managing scrub typhus. Here, we present four cases of scrub typhus with a comprehensive literature review. This study highlights the significance of considering scrub typhus as a possible diagnosis in patients of all ages from endemic regions who exhibit symptoms such as fever, thrombocytopenia, or transaminitis, even in the absence of typical clinical features. Two cases exhibited the characteristic lesion of eschar at the site of mite feeding. One case involved a middle-aged woman who was diagnosed with typhus-induced myocarditis with left ventricular dysfunction. Another case involved a 23-day-old neonate with poor feeding and seizures, who was diagnosed with late-onset sepsis with meningitis. Scrub typhus was confirmed in all cases using a positive qualitative IgM ELISA. However, it is preferred to use paired (ELISA before and after antibiotic therapy) or quantitative titers for confirmation. Healthcare providers must consider the patient’s exposure history and clinical presentation to diagnose and treat scrub typhus promptly.Item Mycobacterium mucogenicum meningitis due to external ventricular drain(Microbiology, 2020-09-03) Moiz, Salwa; Rahman, Omar; Morcos, Mark; Siddiqui, Asma; Bin Hameed, Usman; Medicine, School of MedicineIntroduction: Mycobacterium mucogenicum is a rare non-tuberculous organism associated with catheter-related infections when pathogenic in humans. We present the first case of an external ventricular drain (EVD)-associated M. mucogenicum meningitis. Case presentation: A 55-year-old woman had EVD placement for obstructive hydrocephalus following traumatic subarachnoid haemorrhage. Cerebrospinal fluid (CSF) was obtained 5 days later for fever and neurological changes. M. mucogenicum was ultimately isolated from the CSF and the patient was placed on appropriate antibiotics. Her management included replacement of the EVD and a prolonged course of anti-mycobacterial antibiotics. CSF findings showed her response to therapy and neurological exam improved after 6 weeks. Conclusion: M. mucogenicum infections are very rare and existing reports indicate that it may be a device- or catheter-related pathogen. This microorganism has not been previously associated with an EVD. Ours may be the first documented report of EVD-related M. mucogenicum infection.