Background Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. Methods HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n=100). Comparison was made with an HIV-infected, non-meningitis cohort (n=110). Results Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P=0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores<-1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P=0.002). Conclusions Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.

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BackgroundHIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia.MethodsParticipants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants.ResultsCryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/μL, respectively) than the HIV-infected control cohort (233 cells/μL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (−1.80 Z-score) fell between the cryptococcal meningitis cohort (−2.22 Z-score, P = 0.02) and HIV-infected controls (−1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (−1.0 Z-score, P < 0.001).ConclusionSignificant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-017-0878-2) contains supplementary material, which is available to authorized users.

Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women.

Infections due to Pseudomonas fulva remain a rare but emerging concern. A case of ventriculitis due to Enterobacter cloacae and Pseudomonas fulva following placement of an external ventricular drain is described. Similar to other reports, the organism was initially misidentified as Pseudomonas putida. The infection was successfully treated with levofloxacin. CASE REPORTA 55-year-old woman with a history of chronic migraines and hypertension was transferred to Emory University Hospital for management of a spontaneous subarachnoid hemorrhage. The patient complained of 1 week of worsening migraine headaches but denied nausea, vomiting, and neurologic disturbances until the day of admission, when she developed generalized paresthesia and progressive decline in the level of consciousness. On initial examination, she was lethargic and confused but her motor, sensory, and cranial nerves were intact. A computed tomography (CT) scan of the head showed a large subarachnoid hemorrhage in the basilar cisterns, bilateral sylvian fissures, and the interhemispheric fissure with hydrocephalus. Subsequently, an external ventricular drain (EVD) was placed. A saccular anterior communicating aneurysm was identified on a CT angiogram of the head, and the patient underwent coil embolization. On day 3 of hospitalization, the patient developed a temperature of 38.1°C and was diagnosed with an Escherichia coli urinary tract infection for which she was given levofloxacin (750 mg daily) during hospital days 4 to 8. Fevers persisted, however, and on day 5 of hospitalization, a grossly bloody cerebrospinal fluid (CSF) specimen from the EVD showed a white blood cell (WBC) count of 350 ϫ 10 6 cells/liter. CSF Gram stain and culture at that time were negative. Over the next several days, the CSF cell count progressively increased and on the day 9 of hospitalization was 14,000 ϫ 10 6 cells/liter with 80% neutrophils. During the same time period, the CSF glucose level ranged between 59 and 68 mg/dl (with corresponding plasma glucose levels of 112 to 131 mg/dl) and protein levels ranged between 159 and 270 mg/dl. Three CSF cultures obtained with each EVD aspiration during concurrent levofloxacin treatment for urinary tract infection were negative.Given worsening fever, three CSF specimens were sent for culture on hospital days 12 to 14. Each culture was positive for two different Gram-negative rods, which were detected on blood agar, chocolate agar, and MacConkey agar and in thioglycolate broth (Remel, Lenexa, KS) after overnight incubation at 35°C in 5% CO 2 . The first organism was present in a lower quantity than the second (2ϩ [moderate] in the first two cultures and 1ϩ [few] in the third) and was identified as Enterobacter cloacae. The other organism was present in high quantity (4ϩ [many]) in all three cultures, was a lactose nonfermenter, and formed smooth, wet colonies with a yellow nondiffusible pigment (Fig. 1). The oxidase reaction was inconclusive but was ultimately determined to be weakly positive after repeat testing. Biochemical ...