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Sample records for hiv-associated cryptococcal meningitis

  1. Psychiatric Manifestations in a Patient with HIV-Associated Neurocognitive Symptoms and Cryptococcal Meningitis

    PubMed Central

    Holikatti, Prabhakar C.; Kar, Nilamadhab

    2012-01-01

    We report here a case that presented as mania followed by depression and mild cognitive impairment, which was misinterpreted and treated as a depressive episode of bipolar disorder and planned for electroconvulsive therapy, but was ultimately found to have cryptococcal meningitis and HIV-associated neurocognitive symptoms. PMID:23723549

  2. Cryptococcal Meningitis

    MedlinePlus

    ... in Reviewed May 19, 2014 Select a Language: Fact Sheet 503 Cryptococcal Meningitis WHAT IS CRYPTOCOCCAL MENINGITIS? HOW ... as part of the immune reconstitution syndrome (see fact sheet 483 .) A study in 2011 showed that starting ...

  3. Neuroimaging of HIV-associated cryptococcal meningitis: comparison of magnetic resonance imaging findings in patients with and without immune reconstitution.

    PubMed

    Katchanov, Juri; Branding, Gordian; Jefferys, Laura; Arastéh, Keikawus; Stocker, Hartmut; Siebert, Eberhard

    2016-02-01

    To determine the frequency, imaging characteristics, neuroanatomical distribution and dynamics of magnetic resonance imaging findings in HIV-associated cryptococcal meningitis in immunocompromised patients we compared patients without antiretroviral therapy with patients undergoing immune reconstitution. Neuroimaging and clinical data of 21 consecutive patients presenting to a German HIV centre in a 10-year period between 2005 and 2014 were reviewed. We identified eight patients with magnetic resonance imaging findings related to cryptococcal disease: five patients without antiretroviral therapy and three patients receiving effective antiretroviral therapy resulting in immune reconstitution. The pattern of magnetic resonance imaging manifestations was different in the two groups. In patients not on antiretroviral therapy, pseudocysts (n = 3) and lacunar ischaemic lesions (n = 2) were detected. Contrast-enhancing focal leptomeningeal and/or parenchymal lesions were found in all patients under immune reconstitution (n = 3). Magnetic resonance imaging lesions suggestive of leptomeningitis or meningoencephalitis were detected in all patients with a recurrence of cryptococcal meningitis under immune reconstitution, which differs from the classical magnetic resonance imaging findings in patients without antiretroviral therapy. In antiretroviral therapy-treated patients with past medical history of cryptococcal meningitis, detection of contrast-enhancing focal meningeal and/or parenchymal lesions should prompt further investigations for a recurrence of cryptococcal meningitis under immune reconstitution. PMID:25693580

  4. Cost Effectiveness of Cryptococcal Antigen Screening as a Strategy to Prevent HIV-Associated Cryptococcal Meningitis in South Africa

    PubMed Central

    Jarvis, Joseph N.; Harrison, Thomas S.; Lawn, Stephen D.; Meintjes, Graeme; Wood, Robin; Cleary, Susan

    2013-01-01

    Objectives Cryptococcal meningitis (CM)-related mortality may be prevented by screening patients for sub-clinical cryptococcal antigenaemia (CRAG) at antiretroviral-therapy (ART) initiation and pre-emptively treating those testing positive. Prior to programmatic implementation in South Africa we performed a cost-effectiveness analysis of alternative preventive strategies for CM. Design Cost-effectiveness analysis. Methods Using South African data we modelled the cost-effectiveness of four strategies for patients with CD4 cell-counts <100 cells/µl starting ART 1) no screening or prophylaxis (standard of care), 2) universal primary fluconazole prophylaxis, 3) CRAG screening with fluconazole treatment if antigen-positive, 4) CRAG screening with lumbar puncture if antigen-positive and either amphotericin-B for those with CNS disease or fluconazole for those without. Analysis was limited to the first year of ART. Results The least costly strategy was CRAG screening followed by high-dose fluconazole treatment of all CRAG-positive individuals. This strategy dominated the standard of care at CRAG prevalence ≥0.6%. Although CRAG screening followed by lumbar puncture in all antigen-positive individuals was the most effective strategy clinically, the incremental benefit of LPs and amphotericin therapy for those with CNS disease was small and additional costs were large (US$158 versus US$51per person year; incremental cost effectiveness ratio(ICER) US$889,267 per life year gained). Both CRAG screening strategies are less costly and more clinically effective than current practice. Primary prophylaxis is more effective than current practice, but relatively cost-ineffective (ICER US$20,495). Conclusions CRAG screening would be a cost-effective strategy to prevent CM-related mortality among patients initiating ART in South Africa. These findings provide further justification for programmatic implementation of CRAG screening. PMID:23894442

  5. Adjunctive Interferon-γ Immunotherapy for the Treatment of HIV-associated Cryptococcal Meningitis: A Randomized Controlled Trial.

    PubMed Central

    Jarvis, Joseph N; Meintjes, Graeme; Rebe, Kevin; Williams, Gertrude Ntombomzi; Bicanic, Tihana; Williams, Anthony; Schutz, Charlotte; Bekker, Linda-Gail; Wood, Robin; Harrison, Thomas S

    2013-01-01

    Background Interferon-γ is of key importance in the immune response to Cryptococcus neoformans. Mortality related to cryptococcal meningitis (CM) remains high, and novel treatment strategies are needed. We performed an RCT to determine whether addition of IFNγ to standard therapy increased the rate of clearance of cryptococcal infection in HIV-associated CM. Methods Patients were randomized to: (1) Amphotericin-B 1mg/kg/day plus 5-FC 100mg/kg/day for 2-weeks (Standard therapy), (2) Standard therapy plus IFNγ1b 100μg days 1 and 3 (IFNγ 2-doses), or (3) Standard therapy plus IFNγ1b 100μg days 1, 3, 5, 8, 10 and 12 (IFNγ 6-doses). Primary outcome was rate of clearance of cryptococcus from the CSF (early fungicidal activity, EFA) calculated from serial quantitative cultures, previously shown to be independently associated with survival. Results Rate of fungal clearance was significantly faster in IFNγ containing groups than with standard treatment. Mean EFA (logCFU/ml/day) was −0.49 with standard treatment, −0.64 with IFNγ 2-doses, and −0.64 with IFNγ 6-doses. Difference in EFA was −0.15 (95%CI −0.02- −0.27, p=0.02) between standard treatment and IFNγ 2-doses, and −0.15 (95%CI-0.05- −0.26, p=0.006) between standard treatment and IFNγ 6-doses. Mortality was 16% (14/88) at 2 weeks and 31% (27/87) at 10 weeks, with no significant difference between groups. All treatments were well tolerated. Conclusions Addition of short-course IFNγ to standard treatment significantly increased the rate of clearance of cryptococcal infection from the CSF, and was not associated with any increase in adverse events. Two doses of IFNγ are as effective as 6 doses. PMID:22421244

  6. Meningitis - cryptococcal

    MedlinePlus

    Antifungal medicines are used to treat this form of meningitis. Intravenous (IV, through a vein) therapy with ... treatment. It is often combined with an oral antifungal medicine called 5-flucytosine. Another oral medication, fluconazole, ...

  7. Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis

    PubMed Central

    Bottomley, Christian; Loyse, Angela; Brouwer, Annemarie E.; Muzoora, Conrad; Taseera, Kabanda; Jackson, Arthur; Phulusa, Jacob; Hosseinipour, Mina C.; van der Horst, Charles; Limmathurotsakul, Direk; White, Nicholas J.; Wilson, Douglas; Wood, Robin; Meintjes, Graeme; Harrison, Thomas S.; Jarvis, Joseph N.

    2015-01-01

    Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses

  8. Determinants of Mortality in a Combined Cohort of 501 Patients With HIV-Associated Cryptococcal Meningitis: Implications for Improving Outcomes

    PubMed Central

    Jarvis, Joseph N.; Bicanic, Tihana; Loyse, Angela; Namarika, Daniel; Jackson, Arthur; Nussbaum, Jesse C.; Longley, Nicky; Muzoora, Conrad; Phulusa, Jacob; Taseera, Kabanda; Kanyembe, Creto; Wilson, Douglas; Hosseinipour, Mina C.; Brouwer, Annemarie E.; Limmathurotsakul, Direk; White, Nicholas; van der Horst, Charles; Wood, Robin; Meintjes, Graeme; Bradley, John; Jaffar, Shabbar; Harrison, Thomas

    2014-01-01

    Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. Methods. Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. Results. Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0–1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4–11.1), high peripheral white blood cell count (>10 × 109 cells/L; OR, 8.7; 95% CI, 2.5–30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART). Conclusions. CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes. PMID:24319084

  9. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.

    PubMed

    Jarvis, Joseph N; Meintjes, Graeme; Bicanic, Tihana; Buffa, Viviana; Hogan, Louise; Mo, Stephanie; Tomlinson, Gillian; Kropf, Pascale; Noursadeghi, Mahdad; Harrison, Thomas S

    2015-04-01

    Understanding the host immune response during cryptococcal meningitis (CM) is of critical importance for the development of immunomodulatory therapies. We profiled the cerebrospinal fluid (CSF) immune-response in ninety patients with HIV-associated CM, and examined associations between immune phenotype and clinical outcome. CSF cytokine, chemokine, and macrophage activation marker concentrations were assayed at disease presentation, and associations between these parameters and microbiological and clinical outcomes were examined using principal component analysis (PCA). PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines. The presence of this CSF cytokine response was associated with evidence of increased macrophage activation, more rapid clearance of Cryptococci from CSF, and survival at 2 weeks. The key components of this protective immune-response were interleukin (IL)-6 and interferon-γ, IL-4, IL-10 and IL-17 levels also made a modest positive contribution to the PC1 score. A second component of co-correlated chemokines was identified by PCA, consisting primarily of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α). High CSF chemokine concentrations were associated with low peripheral CD4 cell counts and CSF lymphocyte counts and were predictive of immune reconstitution inflammatory syndrome (IRIS). In conclusion CSF cytokine and chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM. We speculate that the presence of even minimal Cryptococcus-specific Th1-type CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes and monocytes into the central nervous system (CNS), more effective activation of CNS macrophages and microglial cells, and faster organism clearance; while high CNS chemokine levels may predispose to over recruitment or inappropriate recruitment of immune cells to the CNS and IRIS

  10. Cryptococcal meningitis complicating sarcoidosis

    PubMed Central

    Leonhard, Sonja E.; Fritz, Daan; van de Beek, Diederik; Brouwer, Matthijs C.

    2016-01-01

    Abstract Background: Cryptococcal meningitis is an uncommon but severe complication of sarcoidosis. Methods: We present 2 patients with cryptococcal meningitis complicating sarcoidosis and compared findings with 38 cases reported in the literature. Results: When analyzing our patients and 38 cases reported in the literature, we found that median age of sarcoidosis patients with cryptococcal meningitis was 39 years (range 30–48); 27 of 33 reported cases (82%) had a history of sarcoidosis. Only 16 of 40 patients (40%) received immunomodulating therapy at the time of diagnosis of cryptococcal meningitis. The diagnosis of cryptococcal meningitis was delayed in 17 of 40 patients (43%), mainly because of the initial suspicion of neurosarcoidosis. Cerebrospinal fluid (CSF) examination showed mildly elevated white blood cell count (range 23–129/mm3). Twenty-nine of 32 cases (91%) had a positive CSF culture for Cryptococcus neoformans and 25 of 27 cases (93%) had a positive CSF C neoformans antigen test. CD4 counts were low in all patients in whom counts were performed (84–228/mL). Twelve patients had an unfavorable outcome (32%), of which 7 died (19%) and 24 patients (65%) had a favorable outcome. The rate of unfavorable outcome in patients with a delayed diagnosis was 7 of 17 (41%) compared to 5 of 28 (21%) in patients in whom diagnosis was not delayed. Conclusion: Cryptococcal meningitis is a rare but life-threatening complication of sarcoidosis. Patients were often initially misdiagnosed as neurosarcoidosis, which resulted in considerable treatment delay and worse outcome. CSF cryptococcal antigen tests are advised in patients with sarcoidosis and meningitis. PMID:27583871

  11. Cryptococcal Meningitis: Diagnosis and Management Update

    PubMed Central

    Abassi, Mahsa; Boulware, David R; Rhein, Joshua

    2015-01-01

    Recent advances in the diagnosis and management of cryptococcal meningitis are promising and have been improving long-term survival. Point of care testing has made diagnosing cryptococcal meningitis rapid, practical, and affordable. Targeted screening and treatment programs for cryptococcal antigenemia are a cost effective method for reducing early mortality on antiretroviral therapy (ART). Optimal initial management with amphotericin and flucytosine improves survival against alternative therapies, although amphotericin is difficult to administer and flucytosine is not available in middle or low income countries, where cryptococcal meningitis is most prevalent. Controlling increased intracranial pressure with serial therapeutic lumbar punctures has a proven survival benefit. Delaying ART initiation for 4 weeks after the diagnosis of cryptococcal meningitis is associated with improved survival. Fortunately, new approaches have been leading the way toward improving care for cryptococcal meningitis patients. New trials utilizing different combinations of antifungal therapy are reviewed, and we summarize the efficacy of different regimens. PMID:26279970

  12. Cryptococcal meningitis in a patient with sarcoidosis

    PubMed Central

    Gibson, Maeghan

    2016-01-01

    Sarcoidosis is a multisystem granulomatous disease characterized by the presence of noncaseating granulomas. Case reports have previously described an association between sarcoidosis and cryptococcal infection, but many of these patients were receiving immunosuppression at the time of diagnosis or had limited cutaneous disease. We report a case of cryptococcal meningitis in a 65-year-old man with a new presentation of sarcoidosis who was not receiving immunosuppressive medications. PMID:27034573

  13. Cryptococcal meningitis: epidemiology and therapeutic options

    PubMed Central

    Sloan, Derek J; Parris, Victoria

    2014-01-01

    Cryptococcal meningitis causes morbidity and mortality worldwide. The burden of disease is greatest in middle- and low-income countries with a high incidence of human immunodeficiency virus (HIV) infection. Patients taking immunosuppressive drugs and some immunocompetent hosts are also at risk. Treatment of cryptococcal meningitis consists of three phases: induction, consolidation, and maintenance. Effective induction therapy requires potent fungicidal drugs (amphotericin B and flucytosine), which are often unavailable in low-resource, high-endemicity settings. As a consequence, mortality is unacceptably high. Wider access to effective treatment is urgently required to improve outcomes. For human immunodeficiency virus-infected patients, judicious management of asymptomatic cryptococcal antigenemia and appropriately timed introduction of antiretroviral therapy are important. PMID:24872723

  14. Cryptococcal meningitis post autologous stem cell transplantation.

    PubMed

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving. PMID:24750320

  15. Preventing deaths from cryptococcal meningitis: from bench to bedside.

    PubMed

    Roy, Monika; Chiller, Tom

    2011-09-01

    Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus spp., is the most common form of meningitis and a leading cause of death among persons with HIV/AIDS in sub-Saharan Africa. Detection of cryptococcal antigen, which is present several weeks before overt signs of meningitis develop, provides an opportunity to detect infection early. Screening persons with HIV for cryptococcal infection when they access healthcare can identify asymptomatic infected patients allowing for prompt treatment and prevention of death. A newly developed point-of-care assay for cryptococcal antigen, as well as growing evidence supporting the utility and cost-effectiveness of screening, are further reasons to consider broad implementation of cryptococcal screening in countries with a high burden of cryptococcal disease. PMID:21905781

  16. Comparative effectiveness of induction therapy for human immunodeficiency virus-associated cryptococcal meningitis: a network meta-analysis.

    PubMed

    Campbell, Jeffrey I; Kanters, Steve; Bennett, John E; Thorlund, Kristian; Tsai, Alexander C; Mills, Edward J; Siedner, Mark J

    2015-01-01

    Background.  Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin-fluconazole. Methods.  We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine +triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results.  In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not identify a benefit for combination therapy in restricted analyses in either resource-rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions.  Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virus-associated cryptococcal meningitis. PMID:26034761

  17. Comparative Effectiveness of Induction Therapy for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: A Network Meta-Analysis

    PubMed Central

    Campbell, Jeffrey I.; Kanters, Steve; Bennett, John E.; Thorlund, Kristian; Tsai, Alexander C.; Mills, Edward J.; Siedner, Mark J.

    2015-01-01

    Background. Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin-fluconazole. Methods. We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine +triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results. In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not identify a benefit for combination therapy in restricted analyses in either resource-rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions. Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virus-associated cryptococcal meningitis. PMID:26034761

  18. Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis

    PubMed Central

    Boulware, David R.; Meya, David B.; Muzoora, Conrad; Rolfes, Melissa A.; Huppler Hullsiek, Katherine; Musubire, Abdu; Taseera, Kabanda; Nabeta, Henry W.; Schutz, Charlotte; Williams, Darlisha A.; Rajasingham, Radha; Rhein, Joshua; Thienemann, Friedrich; Lo, Melanie W.; Nielsen, Kirsten; Bergemann, Tracy L.; Kambugu, Andrew; Manabe, Yukari C.; Janoff, Edward N.; Bohjanen, Paul R.; Meintjes, Graeme

    2014-01-01

    Background Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome–related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered. Methods We assessed survival at 26 weeks among 177 human immunodeficiency virus–infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole. Results The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P = 0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P = 0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P = 0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P = 0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups. Conclusions Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with

  19. Cryptococcus neoformans meningitis with negative cryptococcal antigen: Evaluation of a new immunochromatographic detection assay

    PubMed Central

    Opota, O.; Desgraz, B.; Kenfak, A.; Jaton, K.; Cavassini, M.; Greub, G.; Prod'hom, G.; Giulieri, S.

    2014-01-01

    Detection of cryptococcal antigen in serum or cerebrospinal fluid allows cryptococcal meningitis diagnosis within few hours with >90% sensitivity. In an HIV-positive patient with Cryptococcus neoformans meningitis, initial antigen detection by immunoagglutination was negative. We thus evaluated a new immunochromatographic detection assay that exhibited a higher sensitivity. PMID:25755893

  20. Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis.

    PubMed

    Rolfes, Melissa A; Rhein, Joshua; Schutz, Charlotte; Taseera, Kabanda; Nabeta, Henry W; Huppler Hullsiek, Kathy; Akampuira, Andrew; Rajasingham, Radha; Musubire, Abdu; Williams, Darlisha A; Thienemann, Friedrich; Bohjanen, Paul R; Muzoora, Conrad; Meintjes, Graeme; Meya, David B; Boulware, David R

    2015-12-01

    Background.  Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%-50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods.  Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7-1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by "enhanced consolidation" therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1-2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results.  Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6-2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions.  Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes. PMID:26716103

  1. Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis

    PubMed Central

    Rolfes, Melissa A.; Rhein, Joshua; Schutz, Charlotte; Taseera, Kabanda; Nabeta, Henry W.; Huppler Hullsiek, Kathy; Akampuira, Andrew; Rajasingham, Radha; Musubire, Abdu; Williams, Darlisha A.; Thienemann, Friedrich; Bohjanen, Paul R.; Muzoora, Conrad; Meintjes, Graeme; Meya, David B.; Boulware, David R.

    2015-01-01

    Background. Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%–50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods. Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7–1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by “enhanced consolidation” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1–2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results. Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6–2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions. Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes. PMID:26716103

  2. Isavuconazole Is Effective for the Treatment of Experimental Cryptococcal Meningitis.

    PubMed

    Wiederhold, Nathan P; Kovanda, Laura; Najvar, Laura K; Bocanegra, Rosie; Olivo, Marcos; Kirkpatrick, William R; Patterson, Thomas F

    2016-09-01

    We evaluated the efficacy of isavuconazole against cryptococcal meningitis. Treatment with either oral isavuconazole (120 mg/kg and 240 mg/kg twice a day [BID]) or fluconazole as the positive control significantly improved survival in mice infected intracranially with either Cryptococcus neoformans USC1597 or H99 and significantly reduced brain fungal burdens for both isolates. Concentrations of isavuconazole in plasma and brain tissue also demonstrated that the greatest improvements in survival and fungal burden were associated with elevated exposures. PMID:27324761

  3. Cellular Immune Activation in Cerebrospinal Fluid From Ugandans With Cryptococcal Meningitis and Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Meya, David B.; Okurut, Samuel; Zziwa, Godfrey; Rolfes, Melissa A.; Kelsey, Melander; Cose, Steve; Joloba, Moses; Naluyima, Prossy; Palmer, Brent E.; Kambugu, Andrew; Mayanja-Kizza, Harriet; Bohjanen, Paul R.; Eller, Michael A.; Wahl, Sharon M.; Boulware, David R.; Manabe, Yuka C.; Janoff, Edward N.

    2015-01-01

    Background. Human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fungal burden and limited leukocyte trafficking to cerebrospinal fluid (CSF). The immunopathogenesis of CM immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy at the site of infection is poorly understood. Methods. We characterized the lineage and activation status of mononuclear cells in blood and CSF of HIV-infected patients with noncryptococcal meningitis (NCM) (n = 10), those with CM at day 0 (n = 40) or day 14 (n = 21) of antifungal therapy, and those with CM-IRIS (n = 10). Results. At diagnosis, highly activated CD8+ T cells predominated in CSF in both CM and NCM. CM-IRIS was associated with an increasing frequency of CSF CD4+ T cells (increased from 2.2% to 23%; P = .06), a shift in monocyte phenotype from classic to an intermediate/proinflammatory, and increased programmed death ligand 1 expression on natural killer cells (increased from 11.9% to 61.6%, P = .03). CSF cellular responses were distinct from responses in peripheral blood. Conclusions. After CM, T cells in CSF tend to evolve with the development of IRIS, with increasing proportions of activated CD4+ T cells, migration of intermediate monocytes to the CSF, and declining fungal burden. These changes provide insight into IRIS pathogenesis and could be exploited to more effectively treat CM and prevent CM-IRIS. PMID:25492918

  4. Interleukin-17 mediated differences in the pathogenesis of HIV-1-associated tuberculous and cryptococcal meningitis

    PubMed Central

    Marais, Suzaan; Meintjes, Graeme; Lesosky, Maia; Wilkinson, Katalin A.; Wilkinson, Robert J.

    2016-01-01

    Objective: Mycobacterium tuberculosis and Cryptococcus neoformans are major causes of meningitis in HIV-1-infected patients. Identifying differences in the inflammatory profiles of HIV-1-associated tuberculous meningitis (TBM) and cryptococcal meningitis may inform differences in immunopathogenic mechanisms in these diseases. In this study we compared the clinical and inflammatory features of HIV-1-associated TBM, and cryptococcal meningitis. Methods: A prospective study of HIV-1-infected adults who presented with either TBM [antiretroviral therapy (ART)-naive] or cryptococcal meningitis (regardless of ART prescription). Clinical and laboratory findings and concentrations of 40 inflammatory mediators measured in cerebrospinal fluid (CSF, 33 paired with blood) were compared between TBM and cryptococcal meningitis patients regardless of ART prescription and between TBM and cryptococcal meningitis patients not receiving ART. Results: Clinical and laboratory findings were similar in TBM (n=34) and cryptococcal meningitis (n = 19; ART prescribed: n = 10, no ART prescribed: n = 9). Exceptions included a higher median CD4+ cell count [interquartile: 113 (69–199) vs. 25 (8–49) cells/μl, P = 0.0001] and higher HIV-1 median viral load [plasma: 5.46 (4.82–5.89) vs. 4.87 (4.36–5.17) log10copies/ml, P = 0.037; CSF: 6.05 (5.43–6.56) vs. 5.56 (4.52–5.80) log10copies/ml, P = 0.03] in TBM vs. cryptococcal meningitis patients not receiving ART. CSF interleukin (IL)-17A was lower in TBM compared with cryptococcal meningitis [1.00 (0.25–2.35) vs. 9.31 (1.24–23.36) pg/ml, P-adjusted = 0.03]. Conclusion: Despite presenting with higher peripheral CD4+ cell counts, TBM patients also presented with higher HIV-1 viral loads compared with cryptococcal meningitis patients, suggesting a greater propensity of M. tuberculosis compared with C. neoformans to increase HIV-1 replication in vivo. CSF IL-17A was lower in TBM; its role in the

  5. Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries.

    PubMed

    Loyse, Angela; Thangaraj, Harry; Easterbrook, Philippa; Ford, Nathan; Roy, Monika; Chiller, Tom; Govender, Nelesh; Harrison, Thomas S; Bicanic, Tihana

    2013-07-01

    Cryptococcal meningitis is the leading cause of adult meningitis in sub-Saharan Africa, and contributes up to 20% of AIDS-related mortality in low-income and middle-income countries every year. Antifungal treatment for cryptococcal meningitis relies on three old, off-patent antifungal drugs: amphotericin B deoxycholate, flucytosine, and fluconazole. Widely accepted treatment guidelines recommend amphotericin B and flucytosine as first-line induction treatment for cryptococcal meningitis. However, flucytosine is unavailable in Africa and most of Asia, and safe amphotericin B administration requires patient hospitalisation and careful laboratory monitoring to identify and treat common side-effects. Therefore, fluconazole monotherapy is widely used in low-income and middle-income countries for induction therapy, but treatment is associated with significantly increased rates of mortality. We review the antifungal drugs used to treat cryptococcal meningitis with respect to clinical effectiveness and access issues specific to low-income and middle-income countries. Each drug poses unique access challenges: amphotericin B through cost, toxic effects, and insufficiently coordinated distribution; flucytosine through cost and scarcity of registration; and fluconazole through challenges in maintenance of local stocks--eg, sustainability of donations or insufficient generic supplies. We advocate ten steps that need to be taken to improve access to safe and effective antifungal therapy for cryptococcal meningitis. PMID:23735626

  6. Management of cryptococcal meningitis in HIV-infected patients: Experience from western India

    PubMed Central

    Patel, Atul K.; Patel, Ketan K.; Ranjan, Rajiv; Shah, Shalin; Patel, Jagdish K.

    2010-01-01

    Introduction: Cryptococcal meningitis is one of the acquired immunodeficiency syndrome defining infections with high mortality. Amphotericin B is the preferred drug for induction therapy. Despite advances in human immunodeficiency virus (HIV) treatment, Antiretroviral Treatment (ART) roll-out programs and availability of amphotericin B, cryptococcal meningitis remains an important cause of mortality in the African and other developing countries. Materials and Methods: We carried out a prospective observational study to determine the treatment response rate, tolerability and outcome of patients with cryptococcal meningitis in HIV treated with amphotericin B. Descriptive statistic was used to analyze the data. Results: A total of 27 patients were diagnosed with cryptococcal meningitis during the study period. Headache (96.29%) was the single most common presenting symptom of cryptococcal meningitis in HIV-infected patients, followed by vomiting (77.77%) and fever (66.66%). Cerebrospinal fluid (CSF) routine and microscopic examination was within normal limits in six patients. CSF became sterile on the 12th day of Amphotericin B in 55.55% of the patients while 33.33% had positive CSF cultures. Patients were started with ART after achieving sterile CSF and tolerated at least 2 weeks of fluconazole consolidation treatment and were free from symptoms. Median time for antiretroviral treatment initiation was 35 (14–90) days after completion of Amphotericin B treatment. One patient developed immune reconstitution inflammatory syndrome (IRIS) after ART. Conclusions: We found that the recommended 2 weeks induction treatment with Amphotericin B monotherapy for HIV patients with cryptococcal meningitis in resource-limited settings may be suboptimal for at least one-third of the patients. Extending the therapy to 3 weeks is likely to result in sterilization of the CSF in a majority of these patients. This finding requires confirmation by a larger sample size in appropriately

  7. Fc Gamma Receptor 3A Polymorphism and Risk for HIV-Associated Cryptococcal Disease

    PubMed Central

    Rohatgi, Soma; Gohil, Shruti; Kuniholm, Mark H.; Schultz, Hannah; Dufaud, Chad; Armour, Kathryn L.; Badri, Sheila; Mailliard, Robbie B.; Pirofski, Liise-anne

    2013-01-01

    ABSTRACT Cryptococcus neoformans is one of the most common causes of fungal disease in HIV-infected persons, but not all of those who are infected develop cryptococcal disease (CD). Although CD4+ T cell deficiency is a risk factor for HIV-associated CD, polymorphisms of phagocytic Fc gamma receptors (FCGRs) have been linked to CD risk in HIV-uninfected persons. To investigate associations between FCGR2A 131 H/R and FCGR3A 158 F/V polymorphisms and CD risk in HIV-infected persons, we performed PCR-based genotyping on banked samples from 164 men enrolled in the Multicenter AIDS Cohort Study (MACS): 55 who were HIV infected and developed CD and a matched control group of 54 who were HIV infected and 55 who were HIV uninfected. Using additive and allelic statistical models for analysis, the high-affinity FCGR3A 158V allele was significantly associated with CD status after adjusting for race/ethnicity (odds ratio [OR], 2.1; P = 0.005), as was the FCGR3A 158 VV homozygous genotype after adjusting for race/ethnicity, rate of CD4+ T cell decline, and nadir CD4+ T cell count (OR, 21; P = 0.005). No associations between CD and FCGR2A 131 H/R polymorphism were identified. In binding studies, human IgG (hIgG)-C. neoformans complexes exhibited more binding to CHO-K1 cells expressing FCGR3A 158V than to those expressing FCGR3A 158F, and in cytotoxicity assays, natural killer (NK) cells expressing FCGR3A 158V induced more C. neoformans-infected monocyte cytotoxicity than those expressing FCGR3A 158F. Together, these results show an association between the FCGR3A 158V allele and risk for HIV-associated CD and suggest that this polymorphism could promote C. neoformans pathogenesis via increased binding of C. neoformans immune complexes, resulting in increased phagocyte cargo and/or immune activation. PMID:23982074

  8. A rare case of neonatal cryptococcal meningitis in an HIV-unexposed 2-day-old infant: the youngest to date?

    PubMed

    O'Reilly, Dominic Anthony

    2016-05-01

    Cryptococcal meningitis is uncommon in children, particularly in infants. A 2-day-old boy was admitted with signs suggestive of meningitis. Lumbar puncture confirmed meningitis and cryptococcal infection (cryptococcal antigen and Indian ink stain-positive). His mother was HIV-negative. This is thought to be the youngest case of cryptococcal meningitis to be reported. Cryptococcal infection should be considered in children of all ages with meningitis where there is possible immunodeficiency or failure to respond to initial treatment with antibiotics. PMID:25839243

  9. Reversible Deafness and Blindness in a Patient with Cryptococcal Meningitis in Tanzania

    PubMed Central

    Douglas-Vail, Matt; Bechamp, Taylor; Gohal, Simran; Soegtrop, Robert; Vitali, Sarah; Rugemalila, Joan

    2015-01-01

    Cryptococcal meningitis is a common and devastating complication of advanced HIV, and is most prevalent in low resource settings in sub Saharan Africa. Raised intracranial pressure is one of the hallmarks of the disease, which can lead to visual and hearing loss and ultimately death. We present the case of a patient with visual and hearing impairment secondary to Cryptococcal meningitis successfully managed by serial cerebrospinal fluid drainage. This case highlights some of the challenges of managing this severe opportunistic infection in a low resource setting. PMID:26753085

  10. Retrospective Study of Cryptococcal Meningitis With Elevated Minimum Inhibitory Concentration to Fluconazole in Immunocompromised Patients

    PubMed Central

    Nasri, Hashem; Kabbani, Sarah; Bou Alwan, Melhim; Wang, Yun F.; Rebolledo, Paulina A.; Kraft, Colleen S.; Nguyen, Minh L.; Anderson, Albert M.; Rouphael, Nadine

    2016-01-01

    Background. Mortality for cryptococcal meningitis remains significant, in spite of available treatment. Resistance to first-line maintenance therapy, particularly fluconazole, has been reported. Methods. A retrospective chart review was performed on immunocompromised patients with cryptococcal meningitis, who had susceptibility testing performed between January 2001 and December 2011, at 3 hospitals in Atlanta, Georgia. Results. A total of 35 immunocompromised patients with cryptococcal meningitis were identified, 13 (37.1%) of whom had an elevated minimum inhibitory concentration (MIC) to fluconazole (MIC ≥16 µg/mL). Eighty percent of patients were males with African American predominance, the median age was 37 years, and 80% of the patients were human immunodeficiency virus (HIV) positive. Subsequent recurrence of cryptococcal meningitis was more likely in HIV patients compared with solid organ transplant patients (P = .0366). Overall, there was a statistically significant increase in an elevated MIC to fluconazole in patients who had a history of prior azole use (odds ratio, 10.12; 95% confidence interval, 2.04–50.16). Patients with an elevated MIC to fluconazole and those with a high cerebrospinal fluid cryptococcal antigen load (≥1:512) were more likely to have central nervous system complications (P = .0358 and P = .023, respectively). Although no association was observed between an elevated MIC to fluconazole and mortality, those who received voriconazole or high-dose fluconazole (≥800 mg) for maintenance therapy were more likely to survive (P = .0288). Conclusions. Additional studies are required to further investigate the morbidity and mortality associated with an elevated MIC to fluconazole in cryptococcal meningitis, to determine when it is appropriate to perform susceptibility testing, and to evaluate its cost effectiveness. PMID:27419153

  11. Reversible blindness in cryptococcal meningitis with normal intracranial pressure: case report and review of the literature.

    PubMed

    Ghatalia, Pooja A; Vick, Amanda; Vattoth, Surjith; Roberson, Glenn H; Pappas, Peter G

    2014-07-15

    Ocular complications in cryptococcal meningitis (CM) are commonly attributed to elevated intracranial pressure (ICP). We report a case of reversible vision loss complicating AIDS-related CM with a normal ICP. We review other cases of blindness in CM with normal ICP and the potential role of corticosteroids as treatment. PMID:24704725

  12. Flow Cytometry To Assess Cerebrospinal Fluid Fungal Burden in Cryptococcal Meningitis

    PubMed Central

    Graham, Lisa M.; Schutz, Charlotte; Scriba, Thomas J.; Wilkinson, Robert J.; Boulware, David R.; Meintjes, Graeme; Lalloo, David G.; Urban, Britta C.

    2015-01-01

    Fungal burden in the cerebrospinal fluid is an important determinant of mortality in cryptococcal meningitis, but its use in aiding clinical decision making is hampered by the time involved to perform quantitative cultures. Here, we demonstrate the potential of flow cytometry as a novel and rapid technique to address this issue. PMID:26719441

  13. Cryptococcal meningitis in systemic lupus erythematosus patients: pooled analysis and systematic review.

    PubMed

    Fang, Wenjie; Chen, Min; Liu, Jia; Hagen, Ferry; Ms, Abdullah; Al-Hatmi; Zhang, Peilian; Guo, Yun; Boekhout, Teun; Deng, Danqi; Xu, Jianping; Pan, Weihua; Liao, Wanqing

    2016-01-01

    Cryptococcal meningitis is an important fungal infection among systemic lupus erythematosus patients. We conducted a pooled analysis and systematic review to describe the epidemiological and clinical profile of cryptococcal meningitis in systemic lupus erythematosus patients. From two hospitals in China and nine literature databases, cases and prevalence data were collected for pooled analysis and meta-analysis, respectively. Categorical variables of cases were compared using a χ(2)-test on the statistical program of SAS. A multiple regression analysis was performed to ascertain independent predictors significantly correlated with prognosis. Meta-analysis was conducted by the statistical program of R. The prevalence of cryptococcal meningitis in systemic lupus erythematosus patients was 0.5%. Patients were predominantly females and adults. A prednisone equivalent of more than 30 mg/day before infection was associated with higher mortality (odds ratio (OR)=9.69 (1.54, 60.73)). In all, 36.8-38.9% patients showed low lupus activity when they developed the crytococcal infection. Moreover, 38.2% of the patients were misdiagnosed. The estimated case-fatality rate was 23.6%. Our results suggest that more emphasis should be placed to further understand lupus-related cryptococcal meningitis and to develop better prophylaxis and management strategies to combat this condition. PMID:27599471

  14. A paradoxical decline: intracranial lesions in two HIV-positive patients recovering from cryptococcal meningitis.

    PubMed

    Pettersen, Kenneth D; Pappas, Peter G; Chin-Hong, Peter; Baxi, Sanjiv M

    2015-01-01

    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. PMID:26475880

  15. Amphotericin B lipid complex available for AIDS related cryptococcal meningitis. South Africa.

    PubMed

    1993-10-11

    Amphotericin B is generally considered to be the standard treatment against candidiasis, cryptococcal meningitis, and aspergillosis. The potential side effects of kidney toxicity and anemia, however, limit its use. Amphotericin B has therefore been incorporated into a lipid complex and clinical results thus far suggest that this ensemble may significantly reduce the risk of toxicity while maintaining or increasing drug efficacy. This modified version of amphotericin B (ABLC) is available on a compassionate use basis in the US and Europe for patients with life-threatening systemic fungal infections for whom currently marketed drugs are ineffective or too toxic. 250 patients have thus far been treated with ABLC under the compassionate use program; several hundred more have received it in controlled clinical trials; and additional large US phase 3 trials are being planned. The Liposome Company, Inc., of Princeton, New Jersey, has initiated named patient distribution of ABLC in the Republic of South Africa. 2 patients with cryptococcal meningitis have thus far received it. Cryptococcal meningitis is a type of fungal infection occurring in up to 10% of patients with AIDS; 20% of patients die within 30 days of diagnosis. The chairman and CEO of Liposome argues that getting the drug to AIDS patients in South Africa will help the company accumulate data quickly on the drug's efficacy and safety. The company is also working upon an application to get ABLC approved for use in Europe. PMID:12345310

  16. Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis

    PubMed Central

    Wu, Tianxia; Zhang, Nannan; Kosa, Peter; Komori, Mika; Blake, Andrew; Browne, Sarah K.; Rosen, Lindsey B.; Hagen, Ferry; Meis, Jacques; Levitz, Stuart M.; Quezado, Martha; Hammoud, Dima; Bennett, John E.; Bielekova, Bibi; Williamson, Peter R.

    2015-01-01

    The fungus Cryptococcus is a major cause of meningoencephalitis in HIV-infected as well as HIV-uninfected individuals with mortalities in developed countries of 20% and 30%, respectively. In HIV-related disease, defects in T-cell immunity are paramount, whereas there is little understanding of mechanisms of susceptibility in non-HIV related disease, especially that occurring in previously healthy adults. The present description is the first detailed immunological study of non-HIV-infected patients including those with severe central nervous system (s-CNS) disease to 1) identify mechanisms of susceptibility as well as 2) understand mechanisms underlying severe disease. Despite the expectation that, as in HIV, T-cell immunity would be deficient in such patients, cerebrospinal fluid (CSF) immunophenotyping, T-cell activation studies, soluble cytokine mapping and tissue cellular phenotyping demonstrated that patients with s-CNS disease had effective microbiological control, but displayed strong intrathecal expansion and activation of cells of both the innate and adaptive immunity including HLA-DR+ CD4+ and CD8+ cells and NK cells. These expanded CSF T cells were enriched for cryptococcal-antigen specific CD4+ cells and expressed high levels of IFN-γ as well as a lack of elevated CSF levels of typical T-cell specific Th2 cytokines -- IL-4 and IL-13. This inflammatory response was accompanied by elevated levels of CSF NFL, a marker of axonal damage, consistent with ongoing neurological damage. However, while tissue macrophage recruitment to the site of infection was intact, polarization studies of brain biopsy and autopsy specimens demonstrated an M2 macrophage polarization and poor phagocytosis of fungal cells. These studies thus expand the paradigm for cryptococcal disease susceptibility to include a prominent role for macrophage activation defects and suggest a spectrum of disease whereby severe neurological disease is characterized by immune-mediated host cell

  17. Simultaneous cryptococcal and tuberculous meningitis in a patient with systemic lupus erythematosus.

    PubMed

    Mete, Bilgul; Saltoglu, Nese; Vanli, Ersin; Ozkara, Cigdem; Arslan, Ferhat; Mert, Ali; Ozaras, Resat; Tabak, Fehmi; Ozturk, Recep

    2016-04-01

    Simultaneous central nervous system (CNS) infection with Cryptococcus and tuberculosis (TB) is very rare. Despite improved therapeutic options, treatment of CNS cryptococcosis is still difficult and needs invasive treatment modalities, such as intrathecal or intraventricular amphotericin B, in refractory cases. We describe a patient with systemic lupus erythematosus diagnosed with simultaneous cryptococcal and TB meningitis who had a poor response to intravenous liposomal amphotericin B and fluconazole, but was successfully treated with intraventricular amphotericin B, in addition to anti-TB therapy. PMID:23751767

  18. Cryptococcal meningitis initially presenting with eye symptoms in an immunocompetent patient: A case report

    PubMed Central

    Li, Jun; Wang, Peipei; Ye, Ling; Wang, Yanfang; Zhang, Xiuzhen; Yu, Songping

    2016-01-01

    Although cryptococcal meningitis (CM) typically occurs in immunocompromised hosts, immunocompetent humans are susceptible to CM. In humans with an intact immune system, CM presents with signs and symptoms typical of meningitis, including fever, headache and neck stiffness. The present study reported the case of a female immunocompetent patient who presented visual blurring in both eyes and bilateral papilledema for ~1 month. Following hospital admission, the patient was diagnosed with optic nerve inflammation and was treated with intravenous methylprednisolone and oral prednisone. However, the initial symptoms failed to improve and the patient developed a headache. The microscopic examination and India ink test performed using the cerebrospinal fluid of the patient showed the presence of Cryptococcus neoformans. Following combined treatment with amphotericin B and fluconazole, the patient made a full recovery with total resolution of the initial symptoms. This case demonstrates that CM in immunocompetent patients may initially include eye symptoms, which may result in a delayed diagnosis of CM. PMID:27446330

  19. Genotypic Diversity Is Associated with Clinical Outcome and Phenotype in Cryptococcal Meningitis across Southern Africa

    PubMed Central

    Beale, Mathew A.; Sabiiti, Wilber; Robertson, Emma J.; Fuentes-Cabrejo, Karen M.; O’Hanlon, Simon J.; Jarvis, Joseph N.; Loyse, Angela; Meintjes, Graeme; Harrison, Thomas S.; May, Robin C.; Fisher, Matthew C.; Bicanic, Tihana

    2015-01-01

    Cryptococcal meningitis is a major cause of mortality throughout the developing world, yet little is known about the genetic markers underlying Cryptococcal virulence and patient outcome. We studied a cohort of 230 Cryptococcus neoformans (Cn) isolates from HIV-positive South African clinical trial patients with detailed clinical follow-up using multi-locus sequence typing and in vitro phenotypic virulence assays, correlating these data with clinical and fungal markers of disease in the patient. South African Cn displayed high levels of genetic diversity and locus variability compared to globally distributed types, and we identified 50 sequence types grouped within the main molecular types VNI, VNII and VNB, with 72% of isolates typed into one of seven 'high frequency' sequence types. Spatial analysis of patients’ cryptococcal genotype was not shown to be clustered geographically, which might argue against recent local acquisition and in favour of reactivation of latent infection. Through comparison of MLST genotyping data with clinical parameters, we found a relationship between genetic lineage and clinical outcome, with patients infected with the VNB lineage having significantly worse survival (n=8, HR 3.35, CI 1.51-7.20, p=0.003), and this was maintained even after adjustment for known prognostic indicators and treatment regimen. Comparison of fungal genotype with in vitro phenotype (phagocytosis, laccase activity and CSF survival) performed on a subset of 89 isolates revealed evidence of lineage-associated virulence phenotype, with the VNII lineage displaying increased laccase activity (p=0.001) and ex vivo CSF survival (p=0.0001). These findings show that Cryptococcus neoformans is a phenotypically heterogeneous pathogen, and that lineage plays an important role in cryptococcal virulence during human infection. Furthermore, a detailed understanding of the genetic diversity in Southern Africa will support further investigation into how genetic diversity is

  20. Cryptococcal meningitis due to Cryptococcus neoformans genotype AFLP1/VNI in Iran: a review of the literature.

    PubMed

    Badali, Hamid; Alian, Shahriar; Fakhim, Hamed; Falahatinejad, Mahsa; Moradi, Ali; Mohammad Davoudi, Mehrnaz; Hagen, Ferry; Meis, Jacques F

    2015-12-01

    Cryptococcal meningitis is the most important opportunistic fungal infection with a high mortality in HIV-patients in less developed regions. Here, we report a case of cryptococcal meningitis in a 49-year-old HIV-positive female due to Cryptococcus neoformans (serotype A, mating-type alpha, genotype AFLP1/VNI) in Sari, Iran. In vitro antifungal susceptibility tests showed MICs of isavuconazole (0.016 μg ml(-1) ), voriconazole (0.031 μg ml(-1) ), posaconazole (0.031 μg ml(-1) ), itraconazole (0.063 μg ml(-1) ), amphotericin B (0.125 μg ml(-1) ) and fluconazole (8 μg ml(-1) ). Despite immediate antifungal therapy, the patient died 4 days later due to respiratory failure. Cryptococcal infections have been infrequently reported from Iran and therefore we analysed all published cases of cryptococcosis in Iran since the first reported case from 1969. PMID:26444438

  1. Drug-induced haemolysis, renal failure, thrombocytopenia and lactic acidosis in patients with HIV and cryptococcal meningitis: a diagnostic challenge.

    PubMed

    Camara-Lemarroy, Carlos R; Flores-Cantu, Hazael; Calderon-Hernandez, Hector J; Diaz-Torres, Marco A; Villareal-Velazquez, Hector J

    2015-12-01

    Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole. PMID:25614519

  2. Paradoxical immune reconstitution inflammatory syndrome associated with cryptococcal meningitis in China: a 5-year retrospective cohort study.

    PubMed

    Yan, S; Chen, L; Wu, W; Li, Z; Fu, Z; Zhang, H; Xue, J; Hu, Y; Mou, J; Fu, C

    2015-04-01

    We performed a retrospective cohort study of hospitalised cryptococcal meningitis (CM) patients at a single centre to evaluate the clinical epidemiological features of paradoxical cryptococcal-related immune reconstitution inflammatory syndrome (CM-IRIS) in a setting in China. A total of 154 AIDS patients with CM were involved, and 17.5% experienced IRIS at a median of 27 days after initiation of antiretroviral therapy (ART). Overall, 3 deaths were directly attributed to IRIS. The occurrences of CM-IRIS were independently associated with the pre-ART CD4+count, pre-C-reactive protein level, and the timing of ART initiation. PMID:25658526

  3. Early Fungicidal Activity as a Candidate Surrogate Endpoint for All-Cause Mortality in Cryptococcal Meningitis: A Systematic Review of the Evidence

    PubMed Central

    Montezuma-Rusca, Jairo M.; Powers, John H.; Follmann, Dean; Wang, Jing; Sullivan, Brigit; Williamson, Peter R.

    2016-01-01

    Background Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality. In clinical trials evaluating treatments for CM, biomarkers of early fungicidal activity (EFA) in cerebrospinal fluid (CSF) have been proposed as candidate surrogate endpoints for all- cause mortality (ACM). However, there has been no systematic evaluation of the group-level or trial-level evidence for EFA as a candidate surrogate endpoint for ACM. Methods We conducted a systematic review of randomized trials in treatment of CM to evaluate available evidence for EFA measured as culture negativity at 2 weeks/10 weeks and slope of EFA as candidate surrogate endpoints for ACM. We performed sensitivity analysis on superiority trials and high quality trials as determined by Cochrane measures of trial bias. Results Twenty-seven trials including 2854 patients met inclusion criteria. Mean ACM was 15.8% at 2 weeks and 27.0% at 10 weeks with no overall significant difference between test and control groups. There was a statistically significant group-level correlation between average EFA and ACM at 10 weeks but not at 2 weeks. There was also no statistically significant group-level correlation between CFU culture negativity at 2weeks/10weeks or average EFA slope at 10 weeks. A statistically significant trial-level correlation was identified between EFA slope and ACM at 2 weeks, but is likely misleading, as there was no treatment effect on ACM. Conclusions Mortality remains high in short time periods in CM clinical trials. Using published data and Institute of Medicine criteria, evidence for use of EFA as a surrogate endpoint for ACM is insufficient and could provide misleading results from clinical trials. ACM should be used as a primary endpoint evaluating treatments for cryptococcal meningitis. PMID:27490100

  4. Cryptococcal Genotype Influences Immunologic Response and Human Clinical Outcome after Meningitis

    PubMed Central

    Wiesner, Darin L.; Moskalenko, Oleksandr; Corcoran, Jennifer M.; McDonald, Tami; Rolfes, Melissa A.; Meya, David B.; Kajumbula, Henry; Kambugu, Andrew; Bohjanen, Paul R.; Knight, Joseph F.; Boulware, David R.; Nielsen, Kirsten

    2012-01-01

    ABSTRACT In sub-Saharan Africa, cryptococcal meningitis (CM) continues to be a predominant cause of AIDS-related mortality. Understanding virulence and improving clinical treatments remain important. To characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 Cryptococcus isolates from 111 Ugandans with AIDS and CM. Isolates consisted of 107 nonredundant Cryptococcus neoformans var. grubii strains and 8 C. neoformans var. grubii/neoformans hybrid strains. Multilocus sequence typing (MLST) was used to characterize genotypes, yielding 15 sequence types and 4 clonal clusters. The largest clonal cluster consisted of 74 isolates. The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). Patient mortality was differentially associated with the different evolutionary groups (P = 0.04), with the highest mortality observed among Burst group 1, Burst group 2, and hybrid strains. Compared to Burst group 3 strains, Burst group 1 strains were associated with higher mortality (P = 0.02), exhibited increased capsule shedding (P = 0.02), and elicited a more pronounced Th2 response during ex vivo cytokine release assays with strain-specific capsule stimulation (P = 0.02). The results of these analyses suggest that cryptococcal strain variation can be an important determinant of human immune responses and mortality. PMID:23015735

  5. [Cryptococcal meningitis in a patient with a ventriculoperitoneal shunt and monitoring for pulmonary sarcoidosis].

    PubMed

    Baallal, H; El Asri, A C; Eljebbouri, B; Akhaddar, A; Gazzaz, M; El Mostarchid, B; Boucetta, M

    2013-02-01

    The fungus Cryptococcus neoformans can cause common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients. But other conditions can be associated with sarcoidosis. Meningoencephalitis is the most common manifestation of this disease. One of the most important neurological complications is the development of intracranial hypertension (ICH), which may result in high morbidity and mortality. We report the case of a patient harboring a ventriculoperitoneal shunt, and having contracted a cryptococcal meningitis as a risk factor for pulmonary sarcoidosis. Brain MRI showed arachnoiditis, with a mass in contact with the right frontal horn. Indian ink staining of the cerebrospinal fluid (CSF) showed positivity that was confirmed by the identification of Cryptococcus neoformans after culture. The evolution was favorable under medical treatment with removal of material. The relationship between sarcoidosis and cryptococcosis, described in the literature is not coincidental but is a rare complication of sarcoidosis of potential severity (40% of mortality). Sarcoidosis is a common systemic disease that may increase host susceptibility to CNS cryptococcal infection without any other signs or symptoms of host immunosuppression. The diagnosis of cryptococcosis should be evoked as a differential diagnosis of neuro-sarcoidosis. PMID:23395187

  6. Treatment of murine cryptococcal meningitis with an SCH 39304-amphotericin B combination.

    PubMed Central

    Albert, M M; Graybill, J R; Rinaldi, M G

    1991-01-01

    Cryptococcal meningitis was induced in BALB/c mice by intracerebral infection with Cryptococcus neoformans. Drug therapy was initiated 1 day later, with mice receiving amphotericin B (AMB), SCH 39304, combination therapy, or no drug therapy (controls). Most, but not all, combinations showed additive benefits, significantly prolonging survival and reducing organism counts in tissues compared with those in controls and groups which received the drugs independently. Optimum protection was obtained when a single dose of 10 mg of AMB per kg of body weight was combined with a fairly narrow SCH 39304 dose range. AMB antagonism did not occur with any regimen tested. AMB-azole combinations may be reasonable alternatives for patients who fail standard cryptococcosis therapeutic regimens. PMID:1952837

  7. Clinical Immunophenotype at Disease Onset in Previously Healthy Patients With Cryptococcal Meningitis

    PubMed Central

    Xu, Lie; Huang, Qin; Lin, Jin-Ran; Zhu, Cui-Yun; Li, Xin-Hua; Ye, Shan-Ke; Zhu, Ai-Hong; Chen, Dai-Hong; Zhang, Cheng-Feng; Chen, Liang; Ling, Yun

    2016-01-01

    Abstract Cryptococcal meningitis (CM) is a global disease with significant morbidity and mortality. Although low peripheral blood cluster of differentiation 4 (CD4)+ cell counts are found to be related to a high burden of cryptococcus in HIV-infected patients, little is known about possible immune defects in previously healthy patients (PHPs). We performed a retrospective study of 41 CM patients treated from January 2005 to December 2014 who did not have HIV-infection. There were 33 PHPs and 8 not previously healthy patients (non-PHPs). We analyzed clinical test data pertaining to peripheral blood T cells, antibodies, inflammation markers, and cerebral spinal fluid (CSF) completed during the disease onset phase and 5 years following diagnosis. PHPs had significantly higher counts of cluster of differentiation 3 (CD3)+, cluster of differentiation 4 (CD4)+, and cluster of differentiation 45 (CD45)+ cells, and lower percentages of CD8+ cells than non-PHPs (P < 0.05). Measurements of inflammatory markers and immunoglobulin in blood were comparable except for lower immunoglobulin A (IgA) levels in non-PHPs (P = 0.0410). Examination of CSF revealed lower white blood cell (WBC) counts in non-PHPs. Five-year mortality in PHPs was higher than in non-PHPs (22.0% vs 12.5%) but this was not statistically significant (P > 0.05). Multivariate analysis revealed that higher immunoglobulin G (IgG) levels in serum during disease onset may be an independent predictor of mortality (P = 0.015). In conclusion, PHPs demonstrate an immunophenotype that is distinct from that of non-PHPs, leading to an improved understanding of the immunology of cryptococcal meningitis. PMID:26871820

  8. Cerebrospinal fluid macrophage response to experimental cryptococcal meningitis: relationship between in vivo and in vitro measurements of cytotoxicity.

    PubMed Central

    Perfect, J R; Hobbs, M M; Granger, D L; Durack, D T

    1988-01-01

    The functional abilities of macrophages from cerebrospinal fluid (CSF) have so far been little studied. We examined the acquisition of activation characteristics by CSF macrophages during the course of experimental cryptococcal meningitis. CSF macrophages developed the ability for increased reactive oxidative intermediate (H2O2) production and tumor and fungal cytotoxicity. Despite having been activated, CSF macrophages could not inhibit the growth of Cryptococcus neoformans in vitro. Immunosuppression with cyclosporine, which eliminates the natural resistance of rabbits to cryptococcal meningitis, did not prevent or diminish H2O2 production by CSF macrophages but did reduce their tumoricidal activity. Activation of CSF macrophages appears to be an integral part of the central nervous system immune response to C. neoformans in this model, but alone is insufficient to eliminate C. neoformans from the central nervous system. PMID:3346075

  9. A Prospective Study of Mortality from Cryptococcal Meningitis following Treatment Induction with 1200mg Oral Fluconazole in Blantyre, Malawi

    PubMed Central

    Gaskell, Katherine M.; Rothe, Camilla; Gnanadurai, Roshina; Goodson, Patrick; Jassi, Chikondi; Heyderman, Robert S.; Allain, Theresa J.; Harrison, Thomas S.; Lalloo, David G.

    2014-01-01

    Objective We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200mg. We assessed whether this has improved outcomes. Design This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800mg/day. Results 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200mg vs. 800mg fluconazole: 1.29 (95% CI: 0.77–2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07–1.03, p = 0.055]). Conclusion There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis. PMID:25375145

  10. LATERAL FLOW ASSAY FOR CRYPTOCOCCAL ANTIGEN: AN IMPORTANT ADVANCE TO IMPROVE THE CONTINUUM OF HIV CARE AND REDUCE CRYPTOCOCCAL MENINGITIS-RELATED MORTALITY

    PubMed Central

    VIDAL, Jose E.; BOULWARE, David R.

    2015-01-01

    SUMMARY AIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcus species. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die. PMID:26465368

  11. Detection of High Cerebrospinal Fluid Levels of (1→3)-β-d-Glucan in Cryptococcal Meningitis

    PubMed Central

    Rhein, Joshua; Bahr, Nathan C.; Morawski, Bozena M.; Schutz, Charlotte; Zhang, Yonglong; Finkelman, Malcolm; Meya, David B.; Meintjes, Graeme; Boulware, David R.

    2014-01-01

    Background  (1→3)-β-d-Glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an adjunct diagnostic tool for patients infected with human immunodeficiency virus (HIV) and presenting with suspected cryptococcal meningitis. Methods  The Fungitell assay was used to measure BDG concentrations in cerebrospinal fluid (CSF) (n = 177) and serum (n = 109) of HIV-infected Ugandans and South Africans with suspected meningitis. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses were used to evaluate BDG's relationship with mortality. Results  The Fungitell BDG assay provided 89% sensitivity and 85% specificity in CSF for cryptococcal meningitis. Serum sensitivity was suboptimal (79%). Cerebrospinal fluid BDG concentrations at diagnosis were median (interquartile range) 343 (200–597) pg/mL in cryptococcal patients and 37 (23–46) pg/mL in patients without cryptococcosis. Sensitivity in CSF improved to 98% (53 of 54) when initial fungal burdens were ≥10 000 colony-forming units/mL. (1→3)-β-d-Glucan normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations correlated with CSF fungal burden (rho = 0.820; P < .001), CSF CRAG lateral flow assay titers (rho = 0.780, P < .001), and monocyte chemotactic protein-1 levels in CSF (P = .047). In patients with cryptococcal meningitis, BDG ≥500 pg/mL at diagnosis was associated with increased 10-week mortality. Conclusions  (1→3)-β-d-Glucan is detectable in the CSF of HIV-infected patients with Cryptococcus, and it may provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly

  12. Standardized Electrolyte Supplementation and Fluid Management Improves Survival During Amphotericin Therapy for Cryptococcal Meningitis in Resource-Limited Settings

    PubMed Central

    Bahr, Nathan C.; Rolfes, Melissa A.; Musubire, Abdu; Nabeta, Henry; Williams, Darlisha A.; Rhein, Joshua; Kambugu, Andrew; Meya, David B.; Boulware, David R.

    2014-01-01

    Background  Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa. Methods  Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001–2002, and universal in 2006–2012. In 2001–2009, serum potassium (K+) was monitored on days 1, 7, and 14 of treatment with replacement (K+, Mg2+) per clinician discretion. In 2011–2012, K+ was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K+, Mg2+) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies. Results  With limited intravenous fluids, the 14-day survival was 49% in 2001–2002. With universal intravenous fluids, the 30-day survival improved to 62% in 2006–2010 (P = .003). In 2011–2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006–2010 cohort). The cumulative incidence of severe hypokalemia (<2.5 mEq/L) decreased from 38% in 2010 to 8.5% in 2011–2012 with universal supplementation (P < .001). Conclusions  Improved survival was seen in a resource-limited setting with proactive fluid and electrolyte management (K+, Mg2+), as part of comprehensive amphotericin-based cryptococcal therapy

  13. Evaluation of five conventional and molecular approaches for diagnosis of cryptococcal meningitis in non-HIV-infected patients.

    PubMed

    Chen, Min; Zhou, Jie; Li, Juan; Li, Meng; Sun, Jun; Fang, Wen J; Al-Hatmi, Abdullah M S; Xu, Jianping; Boekhout, Teun; Liao, Wan Q; Pan, Wei H

    2016-08-01

    Cryptococcal meningitis (CM) is a life-threatening mycosis primarily occurring in HIV-infected individuals. Recently, non-HIV-infected hosts were increasingly reported to form a considerable proportion. However, the majority of the reported studies on the diagnosis of CM patients were performed on HIV-infected patients. For evaluation of various diagnostic approaches for CM in non-HIV-infected patients, a range of conventional and molecular assays used for diagnosis of CM were verified on 85 clinical CSFs from non-HIV-infected CM patients, including India ink staining, culture, a newly developed loop-mediated isothermal amplification (LAMP), the lateral flow assay (LFA) of cryptococcal antigen detection and a qPCR assay. The LFA had the highest positive detection rate (97.6%; 95% CI, 91.8-99.7%) in non-HIV-infected CM patients, followed by the LAMP (87.1%; 95% CI, 78.0-93.4%), the qPCR (80.0%; 95% CI, 69.9-87.9%), India ink staining (70.6%; 95% CI, 59.7-80.0%) and culture (35.3%; 95% CI, 25.2-46.4%). All culture positive specimens were correctly identified by the LFA. PMID:27061343

  14. A Glucuronoxylomannan-Associated Immune Signature, Characterized by Monocyte Deactivation and an Increased Interleukin 10 Level, Is a Predictor of Death in Cryptococcal Meningitis

    PubMed Central

    Scriven, James E.; Graham, Lisa M.; Schutz, Charlotte; Scriba, Thomas J.; Wilkinson, Katalin A.; Wilkinson, Robert J.; Boulware, David R.; Urban, Britta C.; Lalloo, David G.; Meintjes, Graeme

    2016-01-01

    Background. Cryptococcal meningitis remains a significant cause of death among human immunodeficiency virus type 1 (HIV)–infected persons in Africa. We aimed to better understand the pathogenesis and identify immune correlates of mortality, particularly the role of monocyte activation. Methods. A prospective cohort study was conducted in Cape Town, South Africa. Patients with a first episode of cryptococcal meningitis were enrolled, and their immune responses were assessed in unstimulated and stimulated blood specimens, using flow cytometry and cytokine analysis. Results. Sixty participants were enrolled (median CD4+ T-cell count, 34 cells/µL). Mortality was 23% (14 of 60 participants) at 14 days and 39% (22 of 57) at 12 weeks. Nonsurvivors were more likely to have an altered consciousness and higher cerebrospinal fluid fungal burden at presentation. Principal component analysis identified an immune signature associated with early mortality, characterized by monocyte deactivation (reduced HLA-DR expression and tumor necrosis factor α response to lipopolysaccharide); increased serum interleukin 6, CXCL10, and interleukin 10 levels; increased neutrophil counts; and decreased T-helper cell type 1 responses. This immune signature remained an independent predictor of early mortality after adjustment for consciousness level and fungal burden and was associated with higher serum titers of cryptococcal glucuronoxylomannan. Conclusions. Cryptococcal-related mortality is associated with monocyte deactivation and an antiinflammatory blood immune signature, possibly due to Cryptococcus modulation of the host immune response. Validation in other cohorts is required. PMID:26768248

  15. Cryptococcal antigen screening and preemptive therapy in patients initiating antiretroviral therapy in resource-limited settings: a proposed algorithm for clinical implementation.

    PubMed

    Jarvis, Joseph N; Govender, Nelesh; Chiller, Tom; Park, Benjamin J; Longley, Nicky; Meintjes, Graeme; Bekker, Linda-Gail; Wood, Robin; Lawn, Stephen D; Harrison, Thomas S

    2012-01-01

    HIV-associated cryptococcal meningitis (CM) is estimated to cause over half a million deaths annually in Africa. Many of these deaths are preventable. Screening patients for subclinical cryptococcal infection at the time of entry into antiretroviral therapy programs using cryptococcal antigen (CRAG) immunoassays is highly effective in identifying patients at risk of developing CM, allowing these patients to then be targeted with "preemptive" therapy to prevent the development of severe disease. Such CRAG screening programs are currently being implemented in a number of countries; however, a strong evidence base and clear guidance on how to manage patients with subclinical cryptococcal infection identified by screening are lacking. We review the available evidence and propose a treatment algorithm for the management of patients with asymptomatic cryptococcal antigenemia. PMID:23015379

  16. Short-Course Induction Treatment with Intrathecal Amphotericin B Lipid Emulsion for HIV Infected Patients with Cryptococcal Meningitis

    PubMed Central

    Alvarez-Uria, Gerardo; Midde, Manoranjan; Pakam, Raghavakalyan; Yalla, Pradeep Sukumar; Naik, Praveen Kumar; Reddy, Raghuprakash

    2015-01-01

    Cryptococcal meningitis (CM) is a common cause of death among HIV infected patients in developing countries, especially in sub-Saharan Africa. In this observational HIV cohort study in a resource-limited setting in India, we compared the standard two-week intravenous amphotericin B deoxycholate (AmBd) (Regimen I) with one week of intravenous AmBd along with daily therapeutic lumbar punctures and intrathecal AmB lipid emulsion (Regimen II) during the intensive phase of CM treatment. 78 patients received Regimen I and 45 patients received Regimen II. After adjustment for baseline characteristics (gender, age, altered mental status or seizures at presentation, CD4 cell count, white blood cells, cerebrospinal fluid white cells, and haemoglobin), the use of Regimen II was associated with a significant relative risk reduction in mortality (adjusted hazard ratio 0.4, 95% confidence interval, 0.22–0.76) and 26.7% absolute risk reduction (95% confidence interval, 9.9–43.5) at 12 weeks. The use of Regimen II resulted in lower costs of drugs and hospital admission days. Since the study is observational in nature, we should be cautious about our results. However, the good tolerability of intrathecal administration of AmB lipid emulsion and the clinically important mortality reduction observed with the short-course induction treatment warrant further research, ideally through a randomized clinical trial. PMID:26448766

  17. Paucity of Initial Cerebrospinal Fluid Inflammation in Cryptococcal Meningitis is associated with subsequent Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Boulware, David R.; Bonham, Shulamith C.; Meya, David B.; Wiesner, Darin L.; Park, Gregory S.; Kambugu, Andrew; Janoff, Edward N.; Bohjanen, Paul R

    2010-01-01

    Background Cryptococcal meningitis (CM)-related immune reconstitution inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20–40% of ART-naïve persons with AIDS and prior CM. Pathogenesis is unknown. Methods We compared initial CSF cultures, inflammatory markers and cytokine profiles in ART-naïve AIDS patients who did or did not subsequently develop IRIS after starting ART. We also compared results obtained at IRIS events or CM-relapse. Results Of 85 subjects with CM, 33 (39%) developed CM-IRIS and 5 (6%) developed culture-positive CM-relapse. At CM diagnosis, subjects subsequently developing IRIS had less inflammation, with decreased CSF leukocytes, protein, interferon-gamma (IFN-g), interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-a) compared with subjects not developing IRIS (P<.05). Initial CSF WBCs ≤25 cells/μL and protein ≤50 mg/dL were associated with development of IRIS (OR=7.2, 95%CI: 2.7 to 18.7, P<.001). Compared to baseline levels, we identified CSF elevations of IFN-g, TNF-a, G-CSF, VEGF, and eotaxin (CCL11) (P<.05) at IRIS but minimal inflammatory changes in those with CM relapse. Conclusions Patients who subsequently develop CM-IRIS exhibit less initial CSF inflammation at the time of CM diagnosis compared to those who do not develop IRIS. The inflammatory CSF cytokine profiles observed at time of IRIS can distinguish IRIS from CM-relapse. PMID:20677939

  18. Comparison of Antigen Detection and Nested PCR in CSF Samples of HIV Positive and Negative Patients with Suspected Cryptococcal Meningitis in a Tertiary Care Hospital

    PubMed Central

    Kumari, Sunita; Singh, Dharmendra Prasad; Yadav, Ramakant

    2016-01-01

    Introduction The cases of cryptococcal meningitis and other forms of cryptococcosis have increased in recent time and the present scenario of the condition with significant morbidity and mortality is actually posing a serious threat to the community, so an early and prompt diagnosis is necessary to prevent serious complications and thus improving the overall disease outcome. Aim Comparison of diagnostic efficacy of nested Polymerase Chain Reaction (PCR) with Latex Agglutination Test (LAT) in the Cerebro Spinal Fluid (CSF) samples of the cases of meningitis in HIV positive and negative cases. Materials and Methods We have compared the diagnostic efficacy of Latex Agglutination Test (LAT) with nested Polymerase Chain Reaction (PCR) in 200 Cerebrospinal Fluid (CSF) samples, including 14 HIV positive also, in the cases of suspected cryptococcal meningitis. Nested PCR was done in all cases reporting positive by LAT and results were then compared with that of India ink and culture on Sabouraud Dextrose Agar (SDA), and the isolates were further identified by urease, nitrate and sugar assimilation tests. Results Of the 200 cases, including 14 HIV positive, LAT was positive in 46 cases while 154 were negative. Out of these 46 LAT positive cases, nested PCR was positive in 40 cases only, while culture and India ink was positive in 38 and 33 cases respectively. Majority of the cases, 30 (65.2%) were between age group 21-50 years, while 2 (4.3%) in 0-20, and 14 (30.4%) in 51-80 years age group. Conclusion Although negative staining like India ink and nigrosin are most widely used techniques, but these suffer with subjective error. Rapid method like LAT is available but it always has the scope of false positive and negative results. In such cases nested PCR can help in establishing final diagnosis. PMID:27190801

  19. Meningitis

    MedlinePlus

    ... system, infecting the meninges and causing meningitis. continue Bacteria and Viruses Many viruses can cause viral meningitis. ... examined under a microscope to see if any bacteria, cells, or substances that indicate inflammation or infection ...

  20. [Simultaneous association of tubercular meningitis and cryptococcal meningitis in an African with human immunodeficiency virus HIV positive serology. University Hospital Center of Bujumbura,Burundi].

    PubMed

    Niyongabo, T; Aubry, P

    1992-01-01

    The authors report a connection between a meningitis tuberculosis and a meningoencephalitis with cryptococcus in the case of an african VIH+. The diagnostic of a meningitis tuberculosis was retained on an indirect arguments, this of meningoencephalitis of direct arguments (antigen cryptococcus, cultivation on Sabouraud environment). The pulmonary tuberculosis and/or extrapulmonary tuberculosis is current in Central Africa during HIV infection, as well as the crytococcosis during AIDS. But, any observation on neuromeningitis strike of those two infections have been reported up to now. PMID:1406216

  1. Prevalence and Hospital Management of Amphotericin B Deoxycholate-Related Toxicities during Treatment of HIV-Associated Cryptococcal Meningitis in South Africa

    PubMed Central

    Fortuin-de Smidt, Melony; Kularatne, Ranmini; Dawood, Halima; Govender, Nelesh P.

    2016-01-01

    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. PMID:27467556

  2. Prevalence of Cryptococcal Antigenemia and Cost-Effectiveness of a Cryptococcal Antigen Screening Program – Vietnam

    PubMed Central

    Smith, Rachel M.; Nguyen, Tuan Anh; Ha, Hoang Thi Thanh; Thang, Pham Hong; Thuy, Cao; Xuan Lien, Truong; Bui, Hien T.; Le, Thai Hung; Struminger, Bruce; McConnell, Michelle S.; Fanfair, Robyn Neblett; Park, Benjamin J.; Harris, Julie R.

    2013-01-01

    Background An estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm3 for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam. Methods Serum samples were collected and stored during 2009–2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm3 were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines. Results Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm3 were available for CrAg testing. Median CD4 count was 40 (range 0–99) cells/mm3. Nine (4%; 95% CI 2–7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3–11%) than in North Vietnam (2%; 95% CI 0–6%) (p = 0.18). Cost per life-year gained under a screening scenario was $190, $137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively. Conclusion CrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care. PMID:23626792

  3. Meningitis

    MedlinePlus

    ... be caused by: Chemical irritation Drug allergies Fungi Parasites Tumors Many types of viruses can cause meningitis: Enteroviruses: These are viruses that also can cause intestinal illness. Herpes viruses: These are the same viruses ...

  4. Meningitis

    MedlinePlus

    ... medications. Viral meningitis is caused by viruses like enteroviruses , which are very common in summer and early ... or when they sneeze without covering their mouths. Enteroviruses begin to multiply in the digestive tract and ...

  5. Neuroimaging in tuberculous meningitis.

    PubMed

    Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Jain, Amita

    2016-01-01

    Tuberculous meningitis is a serious infection caused by Mycobacterium tuberculosis. Early diagnosis is the key to success of treatment. Neuroimaging plays a crucial role in the early and accurate diagnosis of tuberculous meningitis and its disabling complications. Magnetic resonance imaging is considered superior to computed tomography. Neuroimaging characteristics include leptomeningeal and basal cisternal enhancement, hydrocephalus, periventricular infarcts, and tuberculoma. Partially treated pyogenic meningitis, cryptococcal meningitis, viral encephalitis, carcinomatous, and lymphomatous meningitis may have many similar neuroimaging characteristics, and differentiation from tuberculous meningitis at times on the basis of neuroimaging characteristics becomes difficult. PMID:26954796

  6. Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis

    PubMed Central

    Sabiiti, Wilber; Robertson, Emma; Beale, Mathew A.; Johnston, Simon A.; Brouwer, Annemarie E.; Loyse, Angela; Jarvis, Joseph N.; Gilbert, Andrew S.; Fisher, Matthew C.; Harrison, Thomas S.; May, Robin C.; Bicanic, Tihana

    2014-01-01

    Background. Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality globally. High fungal burden in cerebrospinal fluid (CSF) at diagnosis and poor fungal clearance during treatment are recognized adverse prognostic markers; however, the underlying pathogenic factors that drive these clinical manifestations are incompletely understood. We profiled a large set of clinical isolates for established cryptococcal virulence traits to evaluate the contribution of C. neoformans phenotypic diversity to clinical presentation and outcome in human cryptococcosis. Methods. Sixty-five C. neoformans isolates from clinical trial patients with matched clinical data were assayed in vitro to determine murine macrophage uptake, intracellular proliferation rate (IPR), capsule induction, and laccase activity. Analysis of the correlation between prognostic clinical and host immune parameters and fungal phenotypes was performed using Spearman’s r, while the fungal-dependent impact on long-term survival was determined by Cox regression analysis. Results. High levels of fungal uptake by macrophages in vitro, but not the IPR, were associated with CSF fungal burden (r = 0.38, P = 0.002) and long-term patient survival (hazard ratio [HR] 2.6, 95% CI 1.2–5.5, P = 0.012). High-uptake strains were hypocapsular (r = –0.28, P = 0.05) and exhibited enhanced laccase activity (r = 0.36, P = 0.003). Fungal isolates with greater laccase activity exhibited heightened survival ex vivo in purified CSF (r = 0.49, P < 0.0001) and resistance to clearance following patient antifungal treatment (r = 0.39, P = 0.003). Conclusion. These findings underscore the contribution of cryptococcal-phagocyte interactions and laccase-dependent melanin pathways to human clinical presentation and outcome. Furthermore, characterization of fungal-specific pathways that drive clinical manifestation provide potential targets for the development of therapeutics and the management of CM. Funding. This work

  7. Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV-infected adults in Uganda: a cross-sectional study

    PubMed Central

    2012-01-01

    Background Cryptococcal infection is a common opportunistic infection among severely immunosuppressed HIV patients and is associated with high mortality. Positive cryptococcal antigenemia is an independent predictor of cryptococcal meningitis and death in patients with severe immunosuppression. We evaluated the prevalence and factors associated with cryptococcal antigenemia among patients with CD4 counts of 100 cells/mm3 or less in Mulago Hospital, Kampala, Uganda. Screening of a targeted group of HIV patients may enable early detection of cryptococcal infection and intervention before initiating antiretroviral therapy. Factors associated with cryptococcal antigenemia may be used subsequently in resource-limited settings in screening for cryptococcal infection, and this data may also inform policy for HIV care. Methods In this cross-sectional study, HIV-infected patients aged 18 years and older with CD4 counts of up to 100 cells/mm3 were enrolled between December 2009 and March 2010. Data on socio-demographics, physical examinations and laboratory tests were collected. Factors associated with cryptococcal antigenemia were analyzed using multiple logistic regression. Results We enrolled 367 participants and the median CD4 count was 23 (IQR 9-51) cells/mm3. Sixty-nine (19%) of the 367 participants had cryptococcal antigenemia. Twenty-four patients (6.5%) had cryptococcal meningitis on cerebrospinal fluid analysis and three had isolated cryptococcal antigenemia. Factors associated with cryptococcal antigenemia included: low body mass index of 15.4 kg/m2 or less (adjusted odds ratio, AOR = 0.5; 95% CI 0.3-1.0), a CD4+ T cell count of less than 50 cells/mm3 (AOR = 2.7; 95% CI1.2-6.1), neck pain (AOR = 2.3; 95% CI 1.2-4.6), recent diagnosis of HIV infection (AOR = 1.9; 95% CI 1.1-3.6), and meningeal signs (AOR = 7.9; 95% CI 2.9-22.1). However, at sub-analysis of asymptomatic patients, absence of neck pain (AOR = 0.5), photophobia (AOR = 0.5) and meningeal signs (AOR = 0

  8. The cryptococcal antigen lateral flow assay: A point-of-care diagnostic at an opportune time.

    PubMed

    Tang, Michele W; Clemons, Karl V; Katzenstein, David A; Stevens, David A

    2016-08-01

    Cryptococcal meningitis is a devastating HIV-related opportunistic infection, affecting nearly 1 million individuals and causing over 500 000 deaths each year. The burden of disease is greatest in sub-Saharan Africa and Southeast Asia, where cryptococcal disease is the most common cause of meningitis. Rapid, accurate and affordable diagnosis of cryptococcal disease has been lacking in many of the most heavily affected areas. Here, we review a point-of-care assay for cryptococcal disease, the dipstick-formatted cryptococcal antigen lateral flow assay (LFA) (IMMY, Norman, OK). In comparison to culture, the assay is 99.5% sensitive and 98% specific. In comparison to other commercially available tests for cryptococcal antigen, the LFA has equal or superior sensitivity and specificity in CSF, plasma and serum samples. We discuss potential applications for the use of the assay in resource-limited settings, including what is likely to be an important role of the LFA in screening for early cryptococcal infection before clinical disease and in evaluating pre-emptive treatment. PMID:25612826

  9. HIV Associated Opportunistic Pneumonias.

    PubMed

    Ismail, T; Lee, C

    2011-03-01

    Opportunistic pneumonias are major causes of morbidity and mortality in HIV infected individuals. The majority of new HIV infections in Malaysia are adults aged 20 to 39 years old and many are unaware of their HIV status until they present with an opportunistic infection. HIV associated opportunistic pneumonias can progress rapidly without appropriate therapy. Therefore a proper diagnostic evaluation is vital and prompt empiric treatment of the suspected diagnosis should be commenced while waiting for the results of the diagnostic studies. Tuberculosis, Pneumocystis pneumonia (PCP) and recurrent bacterial pneumonias are common causes of AIDS-defining diseases and are discussed in this article. PMID:23765154

  10. Comparison of commercial kits for detection of cryptococcal antigen.

    PubMed Central

    Tanner, D C; Weinstein, M P; Fedorciw, B; Joho, K L; Thorpe, J J; Reller, L

    1994-01-01

    Although kits to detect cryptococcal antigen are used widely to diagnose cryptococcal infection, the comparative performance of commercially available assays has not been evaluated in the past decade. Therefore, we compared the sensitives and specificities of five commercially available kits for detecting cryptococcal antigen (four latex agglutination test kits--Calas [Meridian Diagnostics])--Crypto-LA [International Biological Labs], Myco-Immune [MicroScan], and Immy [Immunomycologics]--and an enzyme immunoassay kit, Premier [Meridian Diagnostics]) with culture for the diagnosis of cryptococcal meningitis and fungemia. Of 182 cerebrospinal fluid (CSF) and 90 serum samples submitted for cryptococcal antigen and fungal culture, 49 (19 and 30 samples, respectively) from 20 patients had a culture positive for Cryptococcus neoformans. For CSF specimens, the sensitivities and specificities of all kits were comparable (sensitivity, 93 to 100%; specificity, 93 to 98%). There was a significant difference in sensitivities of the kits when serum samples were tested with the International Biological Labs and MicroScan kits, which do not pretreat serum with pronase. These kits were less sensitive (sensitivity, 83%) than the Immy and Meridian latex kits (sensitivity, 97%), which do pretreat with pronase. The sensitivity of the Meridian enzyme immunoassay kit was comparable to that of the pronase-containing latex kits. These kits were of equivalent specificities (93 to 100%) when testing serum. Some of the currently available kits have limitations that need to be recognized for proper interpretation of results. Specifically, the use of pronase on serum samples reduces the number of false-positive results, and a titer of < or = 1:4 can be a false-positive result when CSF samples are being tested. PMID:7929757

  11. Development of cryptococcal immune reconstitution inflammatory syndrome 41 months after the initiation of antiretroviral therapy in an AIDS patient.

    PubMed

    Hashimoto, Hideki; Hatakeyama, Shuji; Yotsuyanagi, Hiroshi

    2015-01-01

    Cryptococcal meningitis is one of the most lethal fungal infections in patients with acquired immune deficiency syndrome (AIDS). The incidence of and mortality from cryptococcal meningitis have markedly decreased since the introduction of combination antiretroviral therapy (cART). However, despite its benefits, the initiation of cART results in immune reconstitution inflammatory syndrome (IRIS) in some patients. Although IRIS is occasionally difficult to distinguish from relapse or treatment failure, the distinction is important because IRIS requires a different treatment. Here, we present the case of a patient with AIDS who developed symptoms of cryptococcal IRIS 41 months after starting cART. To the best of our knowledge, the time between cART initiation and the onset of cryptococcal IRIS in this patient is the longest that has been reported in the literature. PMID:26425133

  12. Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort

    PubMed Central

    Rajasingham, Radha; Rhein, Joshua; Klammer, Kate; Musubire, Abdu; Nabeta, Henry; Akampurira, Andrew; Mossel, Eric C.; Williams, Darlisha A.; Boxrud, Dave J.; Crabtree, Mary B.; Miller, Barry R.; Rolfes, Melissa A.; Tengsupakul, Supatida; Andama, Alfred O.; Meya, David B.; Boulware, David R.

    2015-01-01

    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. PMID:25385864

  13. Meningitis - pneumococcal

    MedlinePlus

    ... and older People at high risk for pneumococcus infection Alternative Names Pneumococcal meningitis Images Pneumococci organism Pneumococcal pneumonia References Swartz MN. Meningitis: bacterial, ...

  14. Prevalence and correlates of cryptococcal antigen positivity among AIDS patients--United States, 1986-2012.

    PubMed

    McKenney, Jennie; Smith, Rachel M; Chiller, Tom M; Detels, Roger; French, Audrey; Margolick, Joseph; Klausner, Jeffrey D

    2014-07-11

    Cryptococcal meningitis (CM) is one of the leading opportunistic infections associated with human immunodeficiency virus (HIV) infection. The worldwide burden of CM among persons living with HIV/acquired immunodeficiency syndrome (AIDS) was estimated in 2009 to be 957,900 cases, with approximately 624,700 deaths annually. The high burden of CM globally comes despite the fact that cryptococcal antigen (CrAg) is detectable weeks before the onset of symptoms, allowing screening for cryptococcal infection and early treatment to prevent CM and CM-related mortality (2). However, few studies have been conducted in the United States to assess the prevalence of cryptococcal infection. To quantify the prevalence of undiagnosed cryptococcal infection in HIV-infected persons in the United States during 1986-2012, stored sera from 1,872 participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study with CD4 T-cell counts <100 cells/µL were screened for CrAg, using the CrAg Lateral Flow Assay (LFA) (Immy, Inc.). This report describes the results of that analysis, which indicated the overall prevalence of CrAg positivity in this population to be 2.9% (95% confidence interval [CI] = 2.2%-3.7%). PMID:25006824

  15. Extensive Central Nervous System Cryptococcal Disease Presenting as Immune Reconstitution Syndrome in a Patient with Advanced HIV: Report of a Case and Review of Management Dilemmas and Strategies.

    PubMed

    Ogbuagu, Onyema; Villanueva, Merceditas

    2014-11-19

    One of the complications of the use of antiretroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS), is particularly problematic in the management of cryptococcal meningitis. We present the case of a 35-year-old male with acquired immune deficiency syndrome diagnosed with extensive central nervous system (CNS) cryptococcal disease, including meningitis and multiple intracranial cysts, diagnosed eight weeks after the initiation of ART. The patient experienced a relapsing and remitting clinical course despite repeated courses of potent antifungal therapy and aggressive management of raised intracranial pressure. This review highlights therapeutic dilemmas and strategies in the management of CNS cryptococcosis complicated with IRIS and highlights gaps in available treatment guidelines. PMID:25568756

  16. Aetiology, Clinical Presentation, and Outcome of Meningitis in Patients Coinfected with Human Immunodeficiency Virus and Tuberculosis

    PubMed Central

    Bhagwan, Smita; Naidoo, Kogieleum

    2011-01-01

    We conducted a retrospective review of confirmed HIV-TB coinfected patients previously enrolled as part of the SAPiT study in Durban, South Africa. Patients with suspected meningitis were included in this case series. From 642 individuals, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients. Mortality was 70% (7/10), with 4 deaths directly due to meningitis. In an HIV TB endemic region we identified cryptococcus followed by tuberculosis as the leading causes of meningitis. We highlight the occurrence of tuberculous meningitis in patients already receiving antituberculous therapy. The development of meningitis heralded poor outcomes, high mortality, and relapsing meningitis despite ART. PMID:22216407

  17. Integrated Pre-Antiretroviral Therapy Screening and Treatment for Tuberculosis and Cryptococcal Antigenemia

    PubMed Central

    Pac, Lincoln; Horwitz, Mara; Namutebi, Anne Marion; Auerbach, Brandon J.; Semeere, Aggrey; Namulema, Teddy; Schwarz, Miriam; Bbosa, Robert; Muruta, Allan; Meya, David; Manabe, Yukari C.

    2015-01-01

    Objective To demonstrate the feasibility of integrated screening for cryptococcal antigenemia and tuberculosis (TB) prior to antiretroviral therapy (ART) initiation and to assess disease specific and all-cause mortality in the first 6 months of follow-up. Methods We enrolled a cohort of HIV-infected, ART-naïve adults with CD4 counts ≤ 250 cells/µL in rural Uganda who were followed for 6 months after ART initiation. All subjects underwent screening for TB; those with CD4 ≤ 100 cells/µL also had cryptococcal antigen (CrAg) screening. For those who screened positive, standard treatment for TB or preemptive treatment for cryptococcal infection was initiated, followed by ART two weeks later. Results Of 540 participants enrolled, pre-ART screening detected 10.6% (57/540) with prevalent TB and 6.8% (12/177 with CD4 count ≤ 100 cells/µL) with positive serum CrAg. After ART initiation, 13 (2.4%) patients were diagnosed with TB and one patient developed cryptococcal meningitis. Overall 7.2% of participants died (incidence rate 15.6 per 100 person years at risk). Death rates were significantly higher among subjects with TB and cryptococcal antigenemia compared to subjects without these diagnoses. In multivariate analysis, significant risk factors for mortality were male sex, baseline anemia of hemoglobin ≤ 10 mg/dL, wasting defined as body mass index ≤ 15.5 kg/m2, and opportunistic infections (TB, positive serum CrAg). Conclusion Pre-ART screening for opportunistic infections detects many prevalent cases of TB and cryptococcal infection. However, severely immunosuppressed and symptomatic HIV patients continue to experience high mortality after ART initiation. PMID:25761234

  18. Viral meningitis.

    PubMed

    Chadwick, David R

    2005-01-01

    Viruses probably account for most cases of acute meningitis. Viral meningitis is often assumed to be a largely benign disease. For the commonest pathogens causing meningitis, enteroviruses, this is usually the case; however, for many of the other pathogens causing viral meningitis, and for common pathogens in the immunocompromised or infants, viral meningitis is frequently associated with substantial neurological complications and a significant mortality. Diagnostic methods for rapid and accurate identification of pathogens have improved over recent years, permitting more precise and earlier diagnoses. There have been fewer developments in therapies for viral meningitis, and there remain no effective therapies for most pathogens, emphasising the importance of prevention and early diagnosis. This review focuses on the presentation, diagnosis and management of viral meningitis and also covers the prevention of meningitis for pathogens where effective vaccines are available. PMID:16474042

  19. Viral Meningitis

    MedlinePlus

    ... especially from late spring to fall when these viruses spread most often. However, only a small number ... infected with enteroviruses will actually develop meningitis. Other viruses that can cause meningitis are Mumps virus Herpesviruses, ...

  20. Cryptococcal Brainstem Abscess Mimicking Brain Tumors in an Immunocompetent Patient

    PubMed Central

    Hur, Jong Hee; Kim, Jang-Hee; Park, Seoung Woo

    2015-01-01

    Usually fungal infections caused by opportunistic and pathogenic fungi had been an important cause of morbidity and mortality among immunocompromised patients. However clinical data and investigations for immunocompetent pathogenic fungal infections had been rare and neglected into clinical studies. Especially Cryptococcal brainstem abscess cases mimicking brain tumors were also much more rare. So we report this unusual case. This 47-year-old man presented with a history of progressively worsening headache and nausea for 1 month and several days of vomituritions before admission. Neurological and laboratory examinations performed demonstrated no abnormal findings. Previously he was healthy and did not have any significant medical illnesses. A CT and MRI scan revealed enhancing 1.8×1.7×2.0 cm mass lesion in the left pons having central necrosis and peripheral edema compressing the fourth ventricle. And also positron emission tomogram scan demonstrated a hot uptake of fluoro-deoxy-glucose on the brainstem lesion without any evidences of systemic metastasis. Gross total mass resection was achieved with lateral suboccipital approach with neuronavigation system. Postoperatively he recovered without any neurological deficits. Pathologic report confirmed Cryptococcus neoformans and he was successively treated with antifungal medications. This is a previously unreported rare case of brainstem Cryptococcal abscess mimicking brain tumors in immunocompetent host without having any apparent typical meningeal symptoms and signs with resultant good neurosurgical recovery. PMID:25674344

  1. CSF ADA Determination in Early Diagnosis of Tuberculous Meningitis in HIV-Infected Patients

    PubMed Central

    Ghosh, Gopal Chandra; Sharma, Brijesh; Gupta, B. B.

    2016-01-01

    Tuberculous and Cryptococcal meningitis are common in HIV patients. A highly specific and sensitive rapid test for diagnosis of Tuberculous meningitis especially in setting of HIV is not available in developing countries where the burden of disease is high. We measured ADA (adenosine deaminase) levels using spectrophotometric method in the CSF of HIV patients with meningitis to differentiate Tuberculous meningitis from meningitis due to other causes. Kruskal-Wallis test was used to compare ADA values between tuberculous meningitis (TBM) and nontuberculous (non-TB) meningitis patients and a receiver-operating characteristic (ROC) analysis curve was drawn from these values. Levels of ADA in the CSF of patients with TBM were significantly higher than those in patients with meningitis due to other causes. CSF ADA level determination with a cut-off value of 6 IU/L was found to be highly specific and fairly sensitive test for the diagnosis of TBM in HIV positive patients. PMID:27144055

  2. Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda.

    PubMed

    Rhein, Joshua; Bahr, Nathan C; Hemmert, Andrew C; Cloud, Joann L; Bellamkonda, Satya; Oswald, Cody; Lo, Eric; Nabeta, Henry; Kiggundu, Reuben; Akampurira, Andrew; Musubire, Abdu; Williams, Darlisha A; Meya, David B; Boulware, David R

    2016-03-01

    Meningitis remains a worldwide problem, and rapid diagnosis is essential to optimize survival. We evaluated the utility of a multiplex PCR test in differentiating possible etiologies of meningitis. Cerebrospinal fluid (CSF) from 69 HIV-infected Ugandan adults with meningitis was collected at diagnosis (n=51) and among persons with cryptococcal meningitis during therapeutic lumbar punctures (n=68). Cryopreserved CSF specimens were analyzed with BioFire FilmArray® Meningitis/Encephalitis panel, which targets 17 pathogens. The panel detected Cryptococcus in the CSF of patients diagnosed with a first episode of cryptococcal meningitis by fungal culture with 100% sensitivity and specificity and differentiated between fungal relapse and paradoxical immune reconstitution inflammatory syndrome in recurrent episodes. A negative FilmArray result was predictive of CSF sterility on follow-up lumbar punctures for cryptococcal meningitis. EBV was frequently detected in this immunosuppressed population (n=45). Other pathogens detected included: cytomegalovirus (n=2), varicella zoster virus (n=2), human herpes virus 6 (n=1), and Streptococcus pneumoniae (n=1). The FilmArray Meningitis/Encephalitis panel offers a promising platform for rapid meningitis diagnosis. PMID:26711635

  3. HIV-associated neurocognitive disorders.

    PubMed

    Sanmarti, Montserrat; Ibáñez, Laura; Huertas, Sonia; Badenes, Dolors; Dalmau, David; Slevin, Mark; Krupinski, Jerzy; Popa-Wagner, Aurel; Jaen, Angeles

    2014-01-01

    Currently, neuropsychological impairment among HIV+ patients on antiretroviral therapy leads to a reduction in the quality of life and it is an important challenge due to the high prevalence of HIV-associated neurocognitive disorders and its concomitant consequences in relation to morbidity and mortality- including those HIV+ patients with adequate immunological and virological status. The fact that the virus is established in CNS in the early stages and its persistence within the CNS can help us to understand HIV-related brain injury even when highly active antiretroviral therapy is effective. The rising interest in HIV associated neurocognitive disorders has let to development new diagnostic tools, improvement of the neuropsychological tests, and the use of new biomarkers and new neuroimaging techniques that can help the diagnosis. Standardization and homogenization of neurocognitive tests as well as normalizing and simplification of easily accessible tools that can identify patients with increased risk of cognitive impairment represent an urgent requirement. Future efforts should also focus on diagnostic keys and searching for useful strategies in order to decrease HIV neurotoxicity within the CNS. PMID:25945248

  4. Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response

    PubMed Central

    Gish, Stacey R.; Maier, Ezekiel J.; Haynes, Brian C.; Santiago-Tirado, Felipe H.; Srikanta, Deepa L.; Ma, Cynthia Z.; Li, Lucy X.; Williams, Matthew; Crouch, Erika C.; Khader, Shabaana A.

    2016-01-01

    ABSTRACT Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth: GAT201, RIM101, and SP1. Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes. PMID:27094327

  5. Meningitis - staphylococcal

    MedlinePlus

    Staphylococcal meningitis is caused by Staphylococcus bacteria. When it is caused by Staphylococcus aureus or Staphylococcus epidermidis bacteria, it usually develops as a complication of surgery or ...

  6. Meningitis - pneumococcal

    MedlinePlus

    ... History of meningitis Infection of a heart valve Injury or trauma to the head Meningitis in which there is leakage of spinal fluid Recent ear infection Recent pneumonia Recent upper respiratory infection Spleen removal or a spleen that does not function

  7. Rheumatoid meningitis.

    PubMed

    Nihat, Akin; Chinthapalli, Krishna; Bridges, Leslie; Johns, Paul; Sofat, Nidhi; Moynihan, Barry

    2016-08-01

    Rheumatoid meningitis is a rare, potentially treatable condition that can mimic a wide range of neurological conditions, including vascular syndromes and encephalopathies. Despite a concurrent history of rheumatoid arthritis, patients often have no active synovitis. Here we describe a patient with rheumatoid meningitis who presented to a hyperacute stroke unit with dysarthria on waking and transient facial droop. PMID:27029468

  8. Treating Meningitis

    MedlinePlus

    ... ways to treat bacterial meningitis. 1 They compared steroids (dexamethasone) with pla- cebo. The doctors gave medication ( ... compared anti- biotics by themselves with antibiotics plus steroids. Dr. Fritz and colleagues compared the mortality (deaths) ...

  9. Meningococcal Meningitis

    MedlinePlus

    ... cord. The extended meningitis belt of sub-Saharan Africa, stretching from Senegal in the west to Ethiopia ... ampicillin, chloramphenicol and ceftriaxone. Under epidemic conditions in Africa in areas with limited health infrastructure and resources, ...

  10. Meningitis - meningococcal

    MedlinePlus

    ... spring. It may cause local epidemics at boarding schools, college dormitories, or military bases. Risk factors include ... and close contacts (especially in health care or school settings) of people with this type of meningitis ...

  11. Meningitis - meningococcal

    MedlinePlus

    ... the most commonly used antibiotics for meningococcal meningitis. Penicillin in high doses is almost always effective, too. If the patient is allergic to penicillin, chloramphenicol may be used. Sometimes corticosteroids may be ...

  12. Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence

    PubMed Central

    Oladele, Rita O.; Akanmu, Alani S.; Nwosu, Augustina O.; Ogunsola, Folasade T.; Richardson, Malcolm D.; Denning, David W.

    2016-01-01

    Background. Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods. Sera were collected from 214 consenting HIV-infected participants with CD4+ counts <250 cells/mm3, irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results. Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4+ cell count was 160 cells/mm3 (interquartile range, 90–210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4+ cell counts <100 cells/mm3, 4 of 80 (5.0%) in the 100–200 group, and 9 of 73 (12.3%) in 200–250 cells/mm3 group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm3, which was unrelated to CrAg positivity (P = .018). Conclusions. We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We recommend Cr

  13. Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence.

    PubMed

    Oladele, Rita O; Akanmu, Alani S; Nwosu, Augustina O; Ogunsola, Folasade T; Richardson, Malcolm D; Denning, David W

    2016-03-01

    Background.  Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods.  Sera were collected from 214 consenting HIV-infected participants with CD4(+) counts <250 cells/mm(3), irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results.  Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4(+) cell count was 160 cells/mm(3) (interquartile range, 90-210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4(+) cell counts <100 cells/mm(3), 4 of 80 (5.0%) in the 100-200 group, and 9 of 73 (12.3%) in 200-250 cells/mm(3) group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm(3), which was unrelated to CrAg positivity (P = .018). Conclusions.  We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We

  14. Cryptoccocal meningitis in Yaoundé (Cameroon) HIV infected patients: Diagnosis, frequency and Cryptococcus neoformans isolates susceptibility study to fluconazole.

    PubMed

    Kammalac Ngouana, T; Dongtsa, J; Kouanfack, C; Tonfack, C; Fomena, S; Mallié, M; Delaporte, E; Boyom, F-Fekam; Bertout, S

    2015-03-01

    Cryptococcal meningitis is a mycosis encountered especially in patients with Acquired Immunodeficiency Syndrome and is fatal in the absence of treatment. Information on epidemiology, diagnosis and susceptibility profile to antifungal drugs, are scarce in Cameroon. Authors evaluated the diagnosis possibilities of the cryptococcal meningitis in Cameroon, and studied the antifungal susceptibility of isolated strains to fluconazole, used as first line treatment of the disease in Cameroon. Between December 2009 and July 2011, 146 cerebrospinal fluids obtained from HIV patients with suspicion of meningitis were analysed. The diagnosis procedure involved macroscopic and cyto-chemical analysis, India ink test, culture on Sabouraud chloramphenicol medium and antigen latex agglutination test. Antifungal susceptibility testing of isolated strains to fluconazole was done by the E-test(®) method. The diagnosis of cryptococcal meningitis gave 28.08% positive cases. Among these patients, 80% were at stages III and IV and 20% at stage I of the HIV infection, according to the WHO previous classification. Cyto-chemical analysis showed current findings in the case of cryptococcal meningitis. India ink test and latex agglutination test exhibited very high sensitivity and specificity (>94%). Fluconazole antifungal susceptibility testing gave MICs lower than 32μg/mL to 92.7% of isolated strains and MICs greater than this value to 7.3% of isolates. These results showed that cryptococcal meningitis remains a real problem among HIV infected patients in Yaoundé. The emergence of fluconazole reduced susceptibility strains is worrying. Nevertheless, efficacy of rapid detection tests is interesting because this will help in rapid diagnosis and treatment of patients. PMID:25467817

  15. Thoracolumbar Scoliosis Due to Cryptococcal Osteomyelitis

    PubMed Central

    Li, Zheng; Liang, Jinqian; Shen, Jianxiong; Qiu, Guixing; Weng, Xisheng

    2016-01-01

    Abstract Cryptococcus neoformans causes opportunistic infections in immunocompromised patients, with vertebral osteomyelitis being a very rare involvement. This study is to present a case of thoracolumbar scoliosis occurring in the setting of cryptococcal osteomyelitis. Pharmacological intervention with anticryptococcal medicine and medical management of immune hemolytic anemia were administered. After initial acute stabilization, she underwent spinal debridement and fusion on October 29, 2008. She eventually recovered fully from this episode with no subsequent mechanical instability or neurological deficits on subsequent clinic follow-ups. To the best of our knowledge, there have been no reports describing the onset of spinal cryptococcal osteomyelitis along with immune hemolytic anemia. We suggest a comprehensive algorithm for the diagnosis of vertebral cryptococcal osteomyelitis. PMID:26844472

  16. Cryptococcal glucuronoxylomannan induces interleukin (IL)-8 production by human microglia but inhibits neutrophil migration toward IL-8.

    PubMed

    Lipovsky, M M; Gekker, G; Hu, S; Ehrlich, L C; Hoepelman, A I; Peterson, P K

    1998-01-01

    On the basis of the clinical observation that the cerebrospinal fluid (CSF) of patients with cryptococcal meningitis contains high levels of the chemokine interleukin (IL)-8 but few polymorphonuclear leukocytes (PMNL), the production of IL-8 by cultured brain glial cells after stimulation with two serotypes of cryptococcal capsular polysaccharide glucuronoxylomannan (GXM) was studied, followed by an assessment of the effect of GXM on PMNL migration toward IL-8. GXM serotype A but not D was capable of inducing IL-8 production in human fetal microglial cell but not in astrocyte cultures. When added directly to the PMNL, GXM (both serotypes) potently blocked PMNL migration toward IL-8. The mechanism of GXM's inhibitory effect appeared to involve cross-desensitization. These findings suggest that GXM can induce IL-8 production in the brain but that GXM in the systemic circulation inhibits migration of PMNL toward IL-8. PMID:9419203

  17. Neonatal meningitis.

    PubMed

    Heath, P T; Nik Yusoff, N K; Baker, C J

    2003-05-01

    Twelve years ago an annotation was published in Archives of Disease in Childhood regarding the antibiotic treatment of suspected neonatal meningitis. The authors recommended the use of cephalosporins rather than chloramphenicol and advocated intraventricular aminoglycoside treatment in selected cases. They noted the absence of clinical trials with third generation cephalosporins that showed an improvement in mortality or neurological outcome. PMID:12719388

  18. Meningitis - gram-negative

    MedlinePlus

    Gram-negative meningitis ... Acute bacterial meningitis can be caused by Gram-negative bacteria. Meningococcal and H. influenzae meningitis are caused by Gram-negative bacteria and are covered in detail in other articles. This article ...

  19. Cryptococcal pleuritis developing in a patient on regular hemodialysis.

    PubMed

    Kinjo, K; Satake, S; Ohama, T

    2009-09-01

    A 64-year-old male on regular hemodialysis who was a human T lymphotrophic virus Type I (HTLV-I) carrier developed cryptococcal pleuritis. The initial manifestations of the present case were a persistent cough and the accumulation of unilateral pleural effusion. A culture of the pleural fluid of the patient grew cryptococcus neoformans and a test for antigens against cryptococcus neoformans in the pleural fluid was also positive, therefore, cryptococcal pleuritis was diagnosed. Pleural cryptococcosis per se is rare and it is extremely rare for a dialysis patient to develop pleural cryptococcosis. To our knowledge, only a few cases of cryptococcal pleuritis have so far been reported in patients on dialysis. Furthermore, an isolated occurrence of cryptococcal pleuritis with no cryptococcal pulmonary parenchymal lesions, as was seen in the present case, is rare because cryptococcal pleuritis is usually associated with underlying cryptococcal pulmonary parenchymal lesions. Patients on chronic dialysis are susceptible to developing pleural effusion from many etiologies such as congestive heart failure, infection (tuberculosis, bacterial, viral, parasitic, fungal), collagen vascular disease, drug reaction, metastasis, or uremia itself. Cryptococcal pleuritis developing in a dialysis patient is extremely rare, but physicians should consider cryptococcal infection as a possible cause when pleural effusion develops in a dialysis patient and no other cause is identified, as occurred in the present case. PMID:19761731

  20. The Treatment of HIV-Associated Nephropathy

    PubMed Central

    Kalayjian, Robert C.

    2010-01-01

    Antiretroviral therapy (ART) preserves kidney function in patients with human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). Emerging data also document substantial renal benefits of ART in the general HIV-infected population, which is associated in part with suppression of HIV-1 viral replication. The extent to which the response to ART differs in persons with HIVAN, compared to those with other HIV-associated kidney disorders, is unknown. Beneficial effects of corticosteroids and angiotensin-converting enzyme (ACE) inhibitors on kidney function also are suggested by retrospective cohort studies and uncontrolled trials of patients with HIVAN. Underexposure to ART, or inadequate ART dosing in HIV-infected patients with CKD, may curtail the optimal benefits that may be derived from this therapy. PMID:20005490

  1. [Pain therapy in HIV-associated polyneuropathy].

    PubMed

    Husstedt, I W; Böckenholt, S; Kammer-Suhr, B; Evers, S

    2001-04-01

    Only some patients with HIV-infection receive an adequate pain therapy. In later stages of HIV-infection up to 50% 6 of patients perform extraordinary doctor visits because of pain. Principally primary and secondary neuromanifestations of HIV-infection have to be differentiated. Rare forms of HIV-associated polyneuropathies represent mononeuropathy or mononeuritis multiple acute and chronic inflammatory demyelinating polyneuropathy and polyneuropathy caused by opportunistic infections. HIV-associated distal-symmetric polyneuropathy represents the most common form during HIV-infection with a prevalence up to 50%. Typical clinical symptoms and signs are pain, hyp- and dysaesthesia, diminuted deep tendon reflexes, motor deficits and autonomic disturbances. Always neurological examination and neurophysiologic investigation on the sural and peronaeal nerve are necessary for monitoring progression of polyneuropathy and as basics before starting antiretroviral therapy with neurotoxic substances. According to momentary opinion, HIV-associated distal-symmetric polyneuropathy represents no indication for antiretroviral therapy. Symptomatic therapy includes antiepileptic medication as gabapentine, antidepressive drugs as amitiptyline and additionally retarded opiates. Depressive disorders ma y accentuate pain problems a n d need psychotherapeutic and thymoleptic therapy. Special problems occur when neurotoxic substances evoke or deteriorate polyneuropathy. In these cases an individual therapeutic proceeding about continuation or discontinuation of neurotoxic medication is necessary. Symptoms of myopathy during HIV-infection are muscle pain, elevation of CK and typical changes of motor units detected by electromyography. In most cases biopsy is necessary for diagnosis of specific forms of HN-associated myopathy. HIV-associated polymyositis is treated by non-steroid analgetics, corticoids, immunoglobulines and plasmapheresis, myopathy induced by neurotoxic medication analogous

  2. Primary cryptococcal prostatitis--rare occurrence.

    PubMed

    Shah, Vinaya B; Patil, Pallavi A; Agrawa, Vipul; Kaswan, Harish K

    2012-05-01

    Cryptococcosis is a well recognized infection in immunocompromised patients. Cryptococcal infection primarily involves the lung and is hematogeneously spread to other organs. Sometimes it might affect the genitourinary tract. The prostate gland is a rare site of primary infection due to cryptococcus neoformans. We report a case of granulomatous inflammation in the prostate as a result of crypyococcus neoformans infection in a 70 year old immunocompetent patient, a non diabetic, which was diagnosed by transrectal ultrasound guided biopsy. PMID:23029729

  3. Methods of rapid diagnosis for the etiology of meningitis in adults

    PubMed Central

    Bahr, Nathan C; Boulware, David R

    2014-01-01

    Infectious meningitis may be due to bacterial, mycobacterial, fungal or viral agents. Diagnosis of meningitis must take into account numerous items of patient history and symptomatology along with regional epidemiology and basic cerebrospinal fluid testing (protein, etc.) to allow the clinician to stratify the likelihood of etiology possibilities and rationally select additional diagnostic tests. Culture is the mainstay for diagnosis in many cases, but technology is evolving to provide more rapid, reliable diagnosis. The cryptococcal antigen lateral flow assay (Immuno-Mycologics) has revolutionized diagnosis of cryptococcosis and automated nucleic acid amplification assays hold promise for improving diagnosis of bacterial and mycobacterial meningitis. This review will focus on a holistic approach to diagnosis of meningitis as well as recent technological advances. PMID:25402579

  4. HIV-associated memory B cell perturbations

    PubMed Central

    Hu, Zhiliang; Luo, Zhenwu; Wan, Zhuang; Wu, Hao; Li, Wei; Zhang, Tong; Jiang, Wei

    2015-01-01

    Memory B-cell depletion, hyperimmunoglobulinemia, and impaired vaccine responses are the hallmark of B cell perturbations inhuman immunodeficiency virus (HIV) disease. Although B cells are not the targets for HIV infection, there is evidence for B cell, especially memory B cell dysfunction in HIV disease mediated by other cells or HIV itself. This review will focus on HIV-associated phenotypic and functional alterations in memory B cells. Additionally, we will discuss the mechanism underlying these perturbations and the effect of anti-retroviral therapy (ART) on these perturbations. PMID:25887082

  5. Approach to diagnosis of meningitis. Cerebrospinal fluid evaluation.

    PubMed

    Greenlee, J E

    1990-12-01

    CSF evaluation is the single most important aspect of the laboratory diagnosis of meningitis. Analysis of the CSF abnormalities produced by bacterial, mycobacterial, and fungal infections may greatly facilitate diagnosis and direct initial therapy. Basic studies of CSF that should be performed in all patients with meningitis include measurement of pressure, cell count and white cell differential; determination of glucose and protein levels; Gram's stain; and culture. In bacterial meningitis, Limulus lysate assay and tests to identify bacterial antigens may allow rapid diagnosis. Where there is strong suspicion of tuberculous or fungal meningitis, CSF should also be submitted for acid-fast stain, India ink preparation, and cryptococcal antigen; unless contraindicated by increased intracranial pressure, large volumes (up to 40-50 mL) should be obtained for culture. If a history of residence in the Southwest is elicited, complement-fixing antibodies to Coccidioides immitis should also be ordered. Newer tests based on immunologic methods or gene amplification techniques hold great promise for diagnosis of infections caused by organisms that are difficult to culture or present in small numbers. Despite the great value of lumbar puncture in the diagnosis of meningitis, injudicious use of the procedure may result in death from brain herniation. Lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion, as in brain abscess, and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension. Institution of antibiotic therapy for suspected meningitis should not be delayed while neuroradiologic studies are obtained to exclude abscess or while measures are instituted to reduce intracranial pressure. PMID:2277190

  6. New technology and resources for cryptococcal research

    PubMed Central

    Zhang, Nannan; Park, Yoon-Dong; Williamson, Peter R.

    2014-01-01

    Rapid advances in molecular biology and genome sequencing have enabled the generation of new technology and resources for cryptococcal research. RNAi-mediated specific gene knock down has become routine and more efficient by utilizing modified shRNA plasmids and convergent promoter RNAi constructs. This system was recently applied in a high-throughput screen to identify genes involved in host-pathogen interactions. Gene deletion efficiencies have also been improved by increasing rates of homologous recombination through a number of approaches, including a combination of double-joint PCR with split-marker transformation, the use of dominant selectable markers and the introduction of Cre-Loxp systems into Cryptococcus. Moreover, visualization of cryptococcal proteins has become more facile using fusions with codon-optimized fluorescent tags, such as green or red fluorescent proteins or, mCherry. Using recent genome-wide analytical tools, new transcriptional factors and regulatory proteins have been identified in novel virulence-related signaling pathways by employing microarray analysis, RNA-sequencing and proteomic analysis. PMID:25460849

  7. HIV-associated immune complex kidney disease.

    PubMed

    Nobakht, Ehsan; Cohen, Scott D; Rosenberg, Avi Z; Kimmel, Paul L

    2016-05-01

    The introduction in the late 20(th) century of combination antiretroviral therapy (cART) to treat patients infected with HIV has changed the natural history of the disease from an acute illness that rapidly culminates in death, to a chronic condition that can be managed with medications. Over the past decade the epidemiology of kidney disease in US patients infected with HIV has changed, perhaps because of the increased availability and use of cART. Patients with HIV infection exhibit unique immunologic characteristics, including immunodeficiency and dysregulation of immunoglobulin synthetic responses and T-cell function, which can result in glomerular immune complex deposition and subsequent kidney injury. This Review examines the differential diagnoses of HIV-associated immune complex kidney diseases (HIVICD), and discusses the clinical manifestations and mechanisms underlying their development. We address the issues associated with treatment, clinical outcomes, and research needs to enhance our ability to diagnose and optimally treat patients with HIVICD. PMID:26782145

  8. Meningitis and Encephalitis

    MedlinePlus

    ... No. 04-4840 Back to Meningitis and Encephalitis Information Page See a list of all NINDS Disorders Publicaciones en Español Meningitis y Encefalitis Prepared by: Office of Communications and Public Liaison National Institute of Neurological Disorders ...

  9. Meningitis (For Parents)

    MedlinePlus

    ... cord. Most cases are caused by bacteria or viruses, but some can be due to certain medications or illnesses. Bacterial meningitis is rare, but is usually serious and can be life threatening if not treated right away. Viral meningitis ( ...

  10. Meningitis Myths and Facts

    MedlinePlus

    ... Diseases Infographic Prevention and Control of Meningococcal Disease Meningitis Myths and Facts Myth: Meningococcal disease is easy ... infected person, such as shaking hands. Fact: Meningococcal meningitis is spread through air droplets and direct contact ...

  11. Acupuncture to Reduce HIV-Associated Inflammation

    PubMed Central

    Swanson, Barbara; Keithley, Joyce K.; Johnson, Angela; Fogg, Louis; Adeyemi, Oluwatoyin; Sha, Beverly E.; Snell, Kimberly A.

    2015-01-01

    Background. HIV infection is associated with systemic inflammation that can increase risk for cardiovascular events. Acupuncture has been shown to have immunomodulatory effects and to improve symptoms in persons with inflammatory conditions. Objective. To test the anti-inflammatory effects of an acupuncture protocol that targets the cholinergic anti-inflammatory pathway (CAIP), a neural mechanism whose activation has been shown to reduce the release of proinflammatory cytokines, in persons with HIV-associated inflammation. Design, Setting, Participants, and Interventions. Double-blind, placebo-controlled clinical trial conducted in an outpatient clinic located in a medically underserved urban neighborhood. Twenty-five clinically-stable HIV-infected persons on antiretroviral therapy were randomized to receive once weekly CAIP-based acupuncture or sham acupuncture. Main Outcome Measures. Outcomes included plasma concentrations of high sensitivity C-reactive protein and D-dimer and fasting lipids. Results. Twenty-five participants completed the protocol (treatment group n = 12, control group n = 13). No adverse events related to the acupuncture protocol were observed. Compared to baseline values, the two groups did not significantly differ in any outcome measures at the end of the acupuncture protocol. Conclusions. CAIP-based acupuncture did not favorably modulate inflammatory or lipid parameters. Additional studies are warranted of CAIP-based protocols of different frequencies/durations. PMID:25922615

  12. Oligodendrocytes in HIV-associated pain pathogenesis

    PubMed Central

    Shi, Yuqiang; Shu, Jianhong; Liang, Zongsuo; Yuan, Subo

    2016-01-01

    Background Although the contributions of microglia and astrocytes to chronic pain pathogenesis have been a focal point of investigation in recent years, the potential role of oligodendrocytes, another major type of glial cells in the CNS that generates myelin, remains largely unknown. Results We report here that cell markers of the oligodendrocyte lineage, including NG2, PDGFRα, and Olig2, are significantly increased in the spinal dorsal horn of HIV patients who developed chronic pain. The levels of myelin proteins myelin basic protein and proteolipid protein are also aberrant in the spinal dorsal horn of “pain-positive” HIV patients. Similarly, the oligodendrocyte and myelin markers are up-regulated in the spinal dorsal horn of a mouse model of HIV-1 gp120-induced pain. Surprisingly, the expression of gp120-induced mechanical allodynia appears intact up to 4 h after myelin basic protein is knocked down or knocked out. Conclusion These findings suggest that oligodendrocytes are reactive during the pathogenesis of HIV-associated pain. However, interfering with myelination does not alter the induction of gp120-induced pain. PMID:27306410

  13. Immunogenetics of HIV and HIV associated tuberculosis.

    PubMed

    Raghavan, S; Alagarasu, K; Selvaraj, P

    2012-01-01

    Tuberculosis (TB) is the frequent major opportunistic infection in HIV-infected patients, and is the leading cause of mortality among HIV-infected patients. Genetic susceptibility to TB in HIV negative subjects is well documented. Since coinfections can influence the way in which immune system respond to different pathogens, genetic susceptibility to TB in HIV patients might also change. Studies from India and other parts of the world have shown that genetic susceptibility to TB is influenced by HIV infection. In the present review, we emphasize the role of genetic factors in determining susceptibility to HIV infection, disease progression and development of TB in HIV-infected patients. Polymorphisms in human leukocyte antigen (HLA), MBL2, CD209, vitamin D receptor, cytokine, chemokine and chemokine receptor genes have been shown to be associated with development of TB in HIV patients. However, the results are inconclusive and larger well-defined studies with precise clinical data are required to validate these associations. Apart from candidate gene approach, genome-wide association studies are also needed to unravel the unknown or to establish the previously reported genetic associations with HIV associated TB. Despite the preliminary status of the reported associations, it is becoming clear that susceptibility to development of TB in HIV patients is influenced by both environmental and genetic components. Understanding the genetic and immunologic factors that influence susceptibility to TB in HIV patients could lead to novel insights for vaccine development as well as diagnostic advances to target treatment to those who are at risk for developing active disease. PMID:21943869

  14. A Single Protein S-acyl Transferase Acts through Diverse Substrates to Determine Cryptococcal Morphology, Stress Tolerance, and Pathogenic Outcome

    PubMed Central

    Santiago-Tirado, Felipe H.; Peng, Tao; Yang, Meng; Hang, Howard C.; Doering, Tamara L.

    2015-01-01

    Cryptococcus neoformans is an opportunistic yeast that kills over 625,000 people yearly through lethal meningitis. Host phagocytes serve as the first line of defense against this pathogen, but fungal engulfment and subsequent intracellular proliferation also correlate with poor patient outcome. Defining the interactions of this facultative intracellular pathogen with host phagocytes is key to understanding the latter’s opposing roles in infection and how they contribute to fungal latency, dissemination, and virulence. We used high-content imaging and a human monocytic cell line to screen 1,201 fungal mutants for strains with altered host interactions and identified multiple genes that influence fungal adherence and phagocytosis. One of these genes was PFA4, which encodes a protein S-acyl transferase (PAT), one of a family of DHHC domain-containing proteins that catalyzes lipid modification of proteins. Deletion of PFA4 caused dramatic defects in cryptococcal morphology, stress tolerance, and virulence. Bioorthogonal palmitoylome-profiling identified Pfa4-specific protein substrates involved in cell wall synthesis, signal transduction, and membrane trafficking responsible for these phenotypic alterations. We demonstrate that a single PAT is responsible for the modification of a subset of proteins that are critical in cryptococcal pathogenesis. Since several of these palmitoylated substrates are conserved in other pathogenic fungi, protein palmitoylation represents a potential avenue for new antifungal therapeutics. PMID:25970403

  15. Drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV-associated dementia.

    PubMed

    Purohit, Vishnudutt; Rapaka, Rao; Shurtleff, David

    2011-08-01

    Although the incidence of HIV-associated dementia (HAD) has declined, HIV-associated neurocognitive disorders (HAND) remain a significant health problem despite use of highly active antiretroviral therapy. In addition, the incidence and/or severity of HAND/HAD are increased with concomitant use of drugs of abuse, such as cocaine, marijuana, and methamphetamine. Furthermore, exposure to most drugs of abuse increases brain levels of dopamine, which has been implicated in the pathogenesis of HIV. This review evaluates the potential role of dopamine in the potentiation of HAND/HAD by drugs of abuse. In the brain, multiplication of HIV in infected macrophages/microglia could result in the release of HIV proteins such as gp120 and Tat, which can bind to and impair dopamine transporter (DAT) functions, leading to elevated levels of dopamine in the dopaminergic synapses in the early asymptomatic stage of HIV infection. Exposure of HIV-infected patients to drugs of abuse, especially cocaine and methamphetamine, can further increase synaptic levels of dopamine via binding to and subsequently impairing the function of DAT. This accumulated synaptic dopamine can diffuse out and activate adjacent microglia through binding to dopamine receptors. The activation of microglia may result in increased HIV replication as well as increased production of inflammatory mediators such as tumor necrosis factor (TNF)-alpha and chemokines. Increased HIV replication can lead to increased brain viral load and increased shedding of HIV proteins, gp120 and Tat. These proteins, as well as TNF-alpha, can induce cell death of adjacent dopaminergic neurons via apoptosis. Autoxidation and metabolism of accumulated synaptic dopamine can lead to generation of reactive oxygen species (hydrogen peroxide), quinones, and semiquinones, which can also induce apoptosis of neurons. Increased cell death of dopaminergic neurons can eventually lead to dopamine deficit that may exacerbate the severity and

  16. Correlation of Fluconazole MICs with Clinical Outcome in Cryptococcal Infection

    PubMed Central

    Aller, A. I.; Martin-Mazuelos, E.; Lozano, F.; Gomez-Mateos, J.; Steele-Moore, L.; Holloway, W. J.; Gutiérrez, M. J.; Recio, F. J.; Espinel-Ingroff, A.

    2000-01-01

    We have correlated the in vitro results of testing the susceptibility of Cryptococcus neoformans to fluconazole with the clinical outcome after fluconazole maintenance therapy in patients with AIDS-associated cryptococcal disease. A total of 28 isolates of C. neoformans from 25 patients (24 AIDS patients) were tested. The MICs were determined by the broth microdilution technique by following the modified guidelines described in National Committee for Clinical Standards (NCCLS) document M27-A, e.g., use of yeast nitrogen base medium and a final inoculum of 104 CFU/ml. The fluconazole MIC at which 50% of isolates are inhibited (MIC50) and MIC90, obtained spectrophotometrically after 48 h of incubation, were 4 and 16 μg/ml, respectively. Of the 25 patients studied, 4 died of active cryptococcal disease and 2 died of other causes. Therapeutic failure was observed in five patients who were infected with isolates for which fluconazole MICs were ≥16 μg/ml. Four of these patients had previously had oropharyngeal candidiasis (OPC); three had previously had episodes of cryptococcal infection, and all five treatment failure patients had high cryptococcal antigen titers in either serum or cerebrospinal fluid (titers, >1:4,000). Although 14 of the 18 patients who responded to fluconazole therapy had previously had OPC infections, they each had only a single episode of cryptococcal infection. It appears that the clinical outcome after fluconazole maintenance therapy may be better when the infecting C. neoformans strain is inhibited by lower concentrations of fluconazole for eradication (MICs, <16 μg/ml) than when the patients are infected with strains that require higher fluconazole concentrations (MICs, ≥16 μg/ml). These findings also suggest that the MICs determined by the modified NCCLS microdilution method can be potential predictors of the clinical response to fluconazole therapy and may aid in the identification of patients who will not respond to fluconazole

  17. Non-Infectious Meningitis

    MedlinePlus

    ... Resources for Healthcare Professionals Related Links Vaccine Schedules Preteen & Teen Vaccines Meningococcal Disease Sepsis Non-Infectious Meningitis ... confusion) Top of Page Related Links Vaccine Schedules Preteen & Teen Vaccines Meningococcal Disease Sepsis File Formats Help: ...

  18. Meningitis - H. influenzae

    MedlinePlus

    ... and close contacts (especially in health care or school settings) of people with this type of meningitis ... first visit. Close contacts in the same household, school, or day care center should be watched for ...

  19. Syphilitic aseptic meningitis

    MedlinePlus

    Syphilitic aseptic meningitis is a complication of untreated syphilis. It involves inflammation of the tissues covering the ... Syphilis is a sexually transmitted disease caused by the spirochete bacteria Treponema pallidum . Syphilis has three main ...

  20. Meningitis and Encephalitis

    MedlinePlus

    ... Funding Information Research Programs Training & Career Awards Enhancing Diversity Find People About NINDS NINDS Meningitis and Encephalitis ... News From NINDS | Find People | Training | Research | Enhancing Diversity Careers@NINDS | FOIA | Accessibility Policy | Contact Us | Privacy ...

  1. The HIV-Associated Enteric Microbiome Has Gone Viral.

    PubMed

    Palmer, Brent E; Li, Sam X; Lozupone, Catherine A

    2016-03-01

    HIV infection is associated with dramatic alterations in enteric bacteria, but little is known about other microbiome components. In this issue of Cell Host & Microbe, studies by Monaco et al. (2016) and Handley et al. (2016) reveal an under-appreciated role of the enteric virome in HIV-associated gastroenteritis and pathogenesis. PMID:26962936

  2. DISCUSSION ON MENINGITIS

    PubMed Central

    1929-01-01

    (1) Meningitis: two groups of cases. (2) A method of washing out the subarachnoid space in cases of septic meningitis secondary to infection of the ear. (3) Discussion on the value of maintaining a positive pressure of the cerebrospinal fluid when operating on a septic region communicating with the subarachnoid space. (4) Leaking cerebrospinal fluid from the region of the ear: operative treatment. PMID:19986899

  3. Approach to Chronic Lymphocytic Meningitis.

    PubMed

    Khadilkar, Satish V; Nadkarni, Nilesh

    2015-09-01

    Chronic meningitis is a common clinical problem. Early diagnosis and appropriate therapy is important in improving the overall outcome and to prevent long-lasting sequels. As many etiological agents lead to the development of chronic lymphocytic meningitis, it is important to develop a systematic approach to the diagnosis; taking clues from history, examination and laboratory tests, to make an accurate diagnosis and institute appropriate therapy. This review focuses on the diagnostic approach towards the commonly encountered situation of chronic lymphocytic meningitis. Chronic meningitis is defined as meningeal inflammation that persists for more than 4 weeks. Chronic meningitis accounts for less than 10% of all the cases of meningitis.1 Causes of chronic lymphocytic meningitis are mainly divided into infectious and non-infectious listed in Table 1.2 Due to advancement in investigations, diseases causing chronic meningitis may be diagnosed earlier than 4 weeks and hence the definition should be considered as a rough guideline. PMID:27608867

  4. Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)–Associated Tuberculous Meningitis

    PubMed Central

    Török, M. Estee; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Mai, Pham Phuong; Dung, Nguyen Thi; Van Vinh Chau, Nguyen; Bang, Nguyen Duc; Tien, Nguyen Anh; Minh, N. H.; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Dong, Doan The; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hai, Nguyen Ngoc; Lan, Nguyen Ngoc; Lan, Nguyen Thi Ngoc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron Paul; de Jong, Menno; Wolbers, Marcel; Farrar, Jeremy James

    2015-01-01

    Background The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81–1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87–1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration ISRCTN63659091. PMID:21596680

  5. Disturbed Amino Acid Metabolism in HIV: Association with Neuropsychiatric Symptoms

    PubMed Central

    Gostner, Johanna M.; Becker, Kathrin; Kurz, Katharina; Fuchs, Dietmar

    2015-01-01

    Blood levels of the amino acid phenylalanine, as well as of the tryptophan breakdown product kynurenine, are found to be elevated in human immunodeficiency virus type 1 (HIV-1)-infected patients. Both essential amino acids, tryptophan and phenylalanine, are important precursor molecules for neurotransmitter biosynthesis. Thus, dysregulated amino acid metabolism may be related to disease-associated neuropsychiatric symptoms, such as development of depression, fatigue, and cognitive impairment. Increased phenylalanine/tyrosine and kynurenine/tryptophan ratios are associated with immune activation in patients with HIV-1 infection and decrease upon effective antiretroviral therapy. Recent large-scale metabolic studies have confirmed the crucial involvement of tryptophan and phenylalanine metabolism in HIV-associated disease. Herein, we summarize the current status of the role of tryptophan and phenylalanine metabolism in HIV disease and discuss how inflammatory stress-associated dysregulation of amino acid metabolism may be part of the pathophysiology of common HIV-associated neuropsychiatric conditions. PMID:26236243

  6. Controversies in the pathogenesis of HIV-associated renal diseases

    PubMed Central

    Bruggeman, Leslie A.; Nelson, Peter J.

    2009-01-01

    The two most common HIV-associated renal diseases, HIV-associated nephropathy and HIV-immune-complex kidney disease, share the common pathologic finding of hyperplasia within the glomerulus. Podocyte injury is central to the pathogenesis of these diseases; however, the source of the proliferating glomerular epithelial cell remains a topic of debate. Parenchymal injury has been linked to direct infection of renal epithelial cells by HIV-1, although the mechanism of viral entry into this non-lymphoid compartment is unclear. Although transgenic rodent models have provided insight into viral proteins responsible for inducing renal disease, such models have important limitations. Rodent HIV-1 models, for instance, cannot replicate all aspects of immune activation, a process that could have an important role in the pathogenesis PMID:19776779

  7. HIV-associated neurocognitive disorders: perspective on management strategies.

    PubMed

    Nabha, Linda; Duong, Lan; Timpone, Joseph

    2013-06-01

    Potent combination antiretroviral therapy (ART) has resulted in dramatic improvements in AIDS-associated morbidity and mortality. Although combination ART has resulted in a significant reduction in HIV-associated dementia, the most severe of the HIV-associated neurocognitive disorders (HAND), the overall prevalence of HAND among this population is estimated at 40%. It has been recognized that the central nervous system (CNS) serves as a reservoir for HIV, and neuronal damage begins at the time of acute infection and persists due to chronic infection of microglial and perivascular macrophages. Although combination ART has resulted in virologic control in the plasma compartment, virologic breakthrough can potentially ensue within the CNS compartment due to limited ART drug exposure. The purpose of this review is to discuss the definition, clinical spectrum, and risk factors associated with HAND, review the pathogenesis of HAND, and address the pharmacologic challenges associated with ART drug exposure in the CNS compartment. PMID:23733447

  8. Clinical management of HIV-associated hematologic malignancies.

    PubMed

    Wang, Chia-Ching J; Kaplan, Lawrence D

    2016-01-01

    HIV is associated with an excess risk for lymphoid malignancies. Although the risk of lymphoma has decreased in HIV-infected individuals in the era of effective combination antiretroviral therapy, it remains high. Treatment outcomes have improved due to improvements in HIV and cancer therapeutics for the common HIV-associated lymphomas. R-CHOP/R-EPOCH are the standard of care for HIV-associated diffuse large B-cell lymphoma. HIV-infected patients with Burkitt lymphoma and good performance status should receive dose-intensive regimens. HIV-infected patients with primary central nervous system lymphoma can respond favorably to high-dose methotrexate-based therapy. In many cases, treatment and expected outcomes for HIV-infected patients with either Hodgkin or non-Hodgkin's lymphomas are very similar to HIV-negative patients. There is currently no standard treatment for HIV-associated multicentric Castleman disease or primary effusion lymphoma. For those hematologic cancers in which transplantation is part of standard care, this modality should be considered an option in those with well-controlled HIV infection. PMID:26652941

  9. [Angiostrongylosis or eosinophilic meningitis].

    PubMed

    Bourée, Patrice; Dumazedier, Déborah; Dahane, Naïma

    2010-04-20

    Eosinophilic meningitis, or angiostrongyliasis, is a common disease in Asia, in the Caribbean and in the Pacific islands. It is caused by a rat lungworm Angiostrongylus cantonensis. Infection occurs by consumption of raw or undercooked snails. Diagnosis is based on epidemiological criteria, clinical manifestations, elevated count of eosinophils in the cerebrospinal fluid and serological tests. Treatment is symptomatic and supportive. PMID:20465114

  10. Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders

    PubMed Central

    Merali, Salim; Barrero, Carlos A.; Sacktor, Ned C.; Haughey, Norman J.; Datta, Prasun K.; Langford, Dianne; Khalili, Kamel

    2014-01-01

    Objectives Spermidine/spermine-N1-acetytransferase (SSAT) is the key enzyme in the catabolism of polyamines that are involved in regulating NMDA functioning. Over expression of SSAT leads to abnormal metabolic cycling and may disrupt NMDA receptor signaling. In fact, the HIV protein Tat induces neurotoxicity involving polyamine/NMDA receptor interactions. Thus, we investigated abnormal polyamine cycling in HIV+ participants with varying degrees of HIV-associated neurocognitive disorders. Methods Acetyl-polyamine (SSAT products) levels were assessed by HPLC in CSF from 99 HIV-infected participants (no cognitive impairment (NCI, n=25), asymptomatic neurocognitive impairment (ANI, n=25), mild cognitive and motor disorders (MCMD, n=24), and HIV-associated dementia (HAD, n=25)). Polyamine levels in brain tissues from a subset of participants (uninfected (n=3), NCI (n=3), and MNCD (n=3)) were also assessed. Human primary astrocytes expressing HIV Tat were assessed for levels of the SSAT activity. Results Activation of the polyamine catabolic enzyme, SSAT increases polyamine flux in brain and CSF of HIV infected individuals with HIV-associated neurocognitive disorders. CSF levels of acetylated polyamine increase with the degree of HAND severity as indicated by significantly increased acetylpolyamine levels in HAD participants compared to NCI and ANI (p<0.0001) and between MCMD and NCI and ANI (p<0.0001). In vitro studies suggest that the HIV protein Tat may be responsible in part for astrocyte-derived acetyl polyamine release. Interpretation Our data suggest that polyamine metabolism may play a pivotal role in the neurodegeneration process among HAND patients. Changes in polyamine flux may serve as a potential predictive diagnostic biomarker for different severities of HAND. PMID:25893137

  11. Carcinomatosis of the Meninges

    PubMed Central

    Dinsdale, Henry B.; Taghavy, Ahmad

    1964-01-01

    Some clinical and pathological features of carcinomatosis of the meninges are reviewed along with a report of four cases. This condition usually presents in middle age as a subacute meningitis with cranial nerve involvement, but the diagnostic importance of the various mental disturbances which may be encountered early in its course are noted. The acute or subacute course may reflect a widespread mechanical interference with normal cerebral metabolism, a notion which is supported by recent clinical measurements in these patients of the rate of glucose transport across the blood-brain barrier. It is probable that the route taken by tumour cells to reach the meningeal spaces is a relatively unimportant factor in determining this pattern of growth and that the intrinsic growth characteristics of the primary tumour, its nutritional needs, and gravity probably play the major roles in production of this unusual type of secondary invasion. Greater therapeutic use of irradiation for these patients is encouraged. ImagesFig. 1Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10 PMID:14118690

  12. Meningococcal meningitis outbreak control strategies.

    PubMed

    Ahlawat, S; Kumar, R; Roy, P; Varma, S; Sharma, B K

    2000-12-01

    Meningococcal meningitis has been occurring worldwide in both endemic and epidemic forms. Serogroup A accounts for majority of cases of epidemic as well as endemic Meningococcal meningitis in developing nations, whereas group C and group B causes epidemic and endemic meningococcal meningitis in developed countries. Person to person spread of N. meningitides generally occurs through inhalation of droplets of infected nasopharyngeal secretions by direct or indirect oral contact. Incubation period varies from 2 to 10 days. N. meningitides typically causes acute infective illness characterized by sequential development of upper respiratory tract infection, meningococcemia, meningitis and focal neurological deficit. Over 90 per cent cases of adult meningococcal infections have cerebrospinal meningitis, whereas in children prevalence of meningitis is much lower (50 per cent). Acute meningitis manifests with fever, severe headache, vomiting and neck stiffness. Presentations may be non-specific in infants, elderly and in patients with fulminant meningococcemia. Diagnosis is confirmed with cerebrospinal fluid analysis. Overall mortality due to meningitis is usually around 10 per cent. In meningococcal septicemia, the case fatality rate may exceed 50 per cent. Preventive strategies include vaccination, chemoprophylaxis and early detection and treatment. Mass vaccination campaign, if appropriately carried out, has been documented to halt an epidemic of meningococcal disease due to serogroup A or C. In the present review we have discussed the available evidence with regards to prevention at primary, secondary and tertiary level. Public health approach to an outbreak of meningococcal meningitis in a community or an organization is also outlined. PMID:11668937

  13. Recognising early meningitis: a missed opportunity to diagnose meningitis.

    PubMed

    Ponnampalam, Anusha; de Sousa, Paula; Carroll, Will

    2016-01-01

    There are ∼250 cases of neonatal bacterial meningitis each year in the UK. Clinical evaluation of signs and symptoms of meningitis is challenging, particularly, during the neonatal period. Although uncommon, it is recognised that bacterial meningitis can be present in a child with an apparently normal cerebrospinal fluid (CSF) initially.We report the case of a newborn baby girl who was admitted with concerns regarding 2 dusky episodes. She underwent blood tests, a lumbar puncture and was started on intravenous antibiotics. With negative cultures, normal blood results and following a significant clinical improvement, antibiotics were discontinued after 48 hours and the baby was discharged home. She re-presented to the children's emergency department 7 hours later with a history of an apnoeic episode. A second CSF sample was suggestive of bacterial meningitis. We will discuss the published literature and the potential drawbacks of lumbar punctures and ways to diagnose meningitis early. PMID:27516108

  14. Rapid Etiological Classification of Meningitis by NMR Spectroscopy Based on Metabolite Profiles and Host Response

    PubMed Central

    Himmelreich, Uwe; Malik, Richard; Kühn, Till; Daniel, Heide-Marie; Somorjai, Ray L.; Dolenko, Brion; Sorrell, Tania C.

    2009-01-01

    Bacterial meningitis is an acute disease with high mortality that is reduced by early treatment. Identification of the causative microorganism by culture is sensitive but slow. Large volumes of cerebrospinal fluid (CSF) are required to maximise sensitivity and establish a provisional diagnosis. We have utilised nuclear magnetic resonance (NMR) spectroscopy to rapidly characterise the biochemical profile of CSF from normal rats and animals with pneumococcal or cryptococcal meningitis. Use of a miniaturised capillary NMR system overcame limitations caused by small CSF volumes and low metabolite concentrations. The analysis of the complex NMR spectroscopic data by a supervised statistical classification strategy included major, minor and unidentified metabolites. Reproducible spectral profiles were generated within less than three minutes, and revealed differences in the relative amounts of glucose, lactate, citrate, amino acid residues, acetate and polyols in the three groups. Contributions from microbial metabolism and inflammatory cells were evident. The computerised statistical classification strategy is based on both major metabolites and minor, partially unidentified metabolites. This data analysis proved highly specific for diagnosis (100% specificity in the final validation set), provided those with visible blood contamination were excluded from analysis; 6–8% of samples were classified as indeterminate. This proof of principle study suggests that a rapid etiologic diagnosis of meningitis is possible without prior culture. The method can be fully automated and avoids delays due to processing and selective identification of specific pathogens that are inherent in DNA-based techniques. PMID:19390697

  15. The Meningitis Vaccine Project.

    PubMed

    LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

    2007-09-01

    Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world. PMID:17521780

  16. The meningeal lymphatic system: a route for HIV brain migration?

    PubMed

    Lamers, Susanna L; Rose, Rebecca; Ndhlovu, Lishomwa C; Nolan, David J; Salemi, Marco; Maidji, Ekaterina; Stoddart, Cheryl A; McGrath, Michael S

    2016-06-01

    Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system. PMID:26572785

  17. Multiple facets of HIV-associated renal disease

    PubMed Central

    da Silva, D.R.; Gluz, I.C.; Kurz, J.; Thomé, G.G.; Zancan, R.; Bringhenti, R.N.; Schaefer, P.G.; dos Santos, M.; Barros, E.J.G.; Veronese, F.V.

    2016-01-01

    HIV infection has a broad spectrum of renal manifestations. This study examined the clinical and histological manifestations of HIV-associated renal disease, and predictors of renal outcomes. Sixty-one (64% male, mean age 45 years) HIV patients were retrospectively evaluated. Clinical presentation and renal histopathology were assessed, as well as CD4 T-cell count and viral load. The predictive value of histological lesion, baseline CD4 cell count and viral load for end-stage renal disease (ESRD) or death were determined using the Cox regression model. The outcomes of chronic kidney disease (CKD) and ESRD or death were evaluated by baseline CD4 cell count. The percent distribution at initial clinical presentation was non-nephrotic proteinuria (54%), acute kidney injury (28%), nephrotic syndrome (23%), and chronic kidney disease (22%). Focal segmental glomerulosclerosis (28%), mainly the collapsing form (HIVAN), acute interstitial nephritis (AIN) (26%), and immune complex-mediated glomerulonephritis (ICGN) (25%) were the predominant renal histology. Baseline CD4 cell count ≥200 cells/mm3 was a protective factor against CKD (hazard ratio=0.997; 95%CI=0.994-0.999; P=0.012). At last follow-up, 64% of patients with baseline CD4 ≥200 cells/mm3 had eGFR >60 mL·min-1·(1.73 m2)-1 compared to the other 35% of patients who presented with CD4 <200 cells/mm3 (log rank=9.043, P=0.003). In conclusion, the main histological lesion of HIV-associated renal disease was HIVAN, followed by AIN and ICGN. These findings reinforce the need to biopsy HIV patients with kidney impairment and/or proteinuria. Baseline CD4 cell count ≥200 cells/mm3 was associated with better renal function after 2 years of follow-up. PMID:27007656

  18. Resident Rounds Part III: Case Report: Fatal Cryptococcal Panniculitis in a Lung Transplant Recipient.

    PubMed

    Reddy, Bobby Y; Shaigany, Sheila; Schulman, Lawrence; Grossman, Marc E

    2015-05-01

    Cryptococcal panniculitis is a rare entity previously reported in only 13 solid organ transplant (SOT) recipients. Cutaneous cryptococcosis in SOT recipients warrants extensive systemic workup and treatment as if central nervous system (CNS) disease is present. It should be included in the differential diagnosis of panniculitis in the immunocompromised host, as early diagnosis and treatment are critical. We report a fatal case of cryptococcal panniculitis in a 44-year-old lung transplant recipient. PMID:25942673

  19. Late onset of cryptococcal cervical lymphadenitis following immune reconstitution inflammatory syndrome in a patient with AIDS.

    PubMed

    Sethupathi, Meenakshi; Yoganathan, Kathir

    2015-01-01

    A 32-year-old woman was diagnosed HIV positive with disseminated cryptococcal infection in May 2006. Her initial CD4 was 7 cells/µL and she had a right supraclavicular nodal mass, which was biopsied and shown to be consistent with cryptococcal lymphadenitis. She was treated for disseminated cryptococcal infection and was started on antiretroviral medications subsequently. Two years later, she developed a left supraclavicular mass. Her CD4 count was 320 cells/µL and HIV RNA level was undetectable. Investigations and biopsy results were consistent with a late presentation of cryptococcal immune reconstitution inflammatory syndrome (IRIS). She was treated with oral corticosteroids and her symptoms resolved completely. IRIS is a recognised complication of HIV treatment and occurs in a significant percentage of patients within the first 3 months of starting antiretroviral therapy. This case report illustrates the importance of recognising late presentations of IRIS. It is vital to differentiate true cryptococcal lymphadenitis from IRIS-induced cryptococcal lymphadenitis. PMID:25564633

  20. Massive cerebral edema resulting in brain death as a complication of Cryptococcus neoformans meningitis

    PubMed Central

    Orsini, Jose; Blaak, Christa; Mahmoud, Dalia; Young-Gwang, Jeong

    2015-01-01

    Despite the widespread use of highly active antiretroviral therapy, cryptococcal meningoencephalitis has emerged as the second leading cause of infectious morbidity and mortality in HIV-infected patients worldwide. It presents usually as subacute or chronic disease but occasionally may be fulminant. Common clinical presentations included headache, fever, and depressed level of consciousness. The infection affects both the subarachnoid space and brain parenchyma, and is characterized by a paucity of inflammation and a large fungal burden in the cerebrospinal fluid at the time of diagnosis. Infection is usually lethal without treatment, thus the prompt diagnosis and therapy might improve the outcome. We report a case of brain death caused by Cryptococcus neoformans meningitis that was diagnosed based on clinical neurological examinations and supported by the absence of cerebral blood flow on brain angiography. PMID:25656669

  1. Campylobacter Fetus Meningitis in Adults

    PubMed Central

    van Samkar, Anusha; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

    2016-01-01

    Abstract The zoonotic pathogen Campylobacter fetus is a rare cause of bacterial meningitis. Little is known about the clinical characteristics, predisposing factors and outcome of C fetus meningitis in adults. We report cases of C fetus meningitis in a nationwide cohort study of adult bacterial meningitis patients in the Netherlands and performed a review of the literature. Two patients with C fetus meningitis were identified from January 2006 through May 2015. The calculated annual incidence was 0.02 per million adults. Combined with the literature, we identified 22 patients with a median age of 48 years. An immunocompromised state was present in 16 patients (73%), mostly due to alcoholism (41%) and diabetes mellitus (27%). The source of infection was identified in 13 out of 19 patients (68%), consisting of regular contact with domestic animals in 5 and working on a farm in 4. Recurrent fever and illness was reported in 4 patients (18%), requiring prolonged antibiotic treatment. Two patients died (9%) and 3 survivors (15%) had neurological sequelae. C fetus is a rare cause of bacterial meningitis and is associated with an immunocompromised state. Based on the apparent slow clinical response seen in this limited number of cases, the authors of this study recommend a prolonged course of antimicrobial therapy when C fetus is identified as a causative agent of bacterial meningitis. Cases appeared to do best with carbapenem therapy. PMID:26937916

  2. Concurrent meningitis and vivax malaria

    PubMed Central

    Santra, Tuhin; Datta, Sumana; Agrawal, Neha; Bar, Mita; Kar, Arnab; Adhikary, Apu; Ranjan, Kunal

    2015-01-01

    Malaria is an endemic infectious disease in India. It is often associated with other infective conditions but concomitant infection of malaria and meningitis are uncommon. We present a case of meningitis with vivax malaria infection in a 24-year-old lady. This case emphasizes the importance of high index of clinical suspicion to detect other infective conditions like meningitis when fever does not improve even after anti-malarial treatment in a patient of malaria before switching therapy suspecting drug resistance, which is quite common in this part of world. PMID:26985423

  3. Rheumatoid meningitis associated with infliximab

    PubMed Central

    Stroberg, Edana; Metting, Austin

    2016-01-01

    We present a patient who had rheumatoid meningitis while on infliximab, a tumor necrosis factor alpha (TNF-α) inhibitor, which initially presented as transient ischemic attacks. Although our patient had been stable on infliximab for several years, her neurologic symptoms improved when her infliximab was held due to active infection and then recurred after reinitiation of therapy. Rheumatoid meningitis is exceedingly rare; however, there have been several other reports of rheumatoid meningitis developing in patients on TNF-α inhibitor therapy. PMID:27034572

  4. Angiostrongylus cantonensis eosinophilic meningitis.

    PubMed

    Pien, F D; Pien, B C

    1999-01-01

    In the past 50 years, Angiostrongylus cantonensis, the most common cause of eosinophilic meningitis, has spread from Southeast Asia to the South Pacific, Africa, India, the Caribbean, and recently, to Australia and North America, mainly carried by cargo ship rats. Humans are accidental, "dead-end" hosts infected by eating larvae from snails, slugs, or contaminated, uncooked vegetables. These larvae migrate to the brain, spinal cord, and nerve roots, causing eosinophilia in both spinal fluid and peripheral blood. Infected patients present with severe headache, vomiting, paresthesias, weakness, and occasionally visual disturbances and extraocular muscular paralysis. Most patients have a full recovery; however, heavy infections can lead to chronic, disabling disease and even death. There is no proven treatment for this disease. In the authors' experience, corticosteroids have been helpful in severe cases to relieve intracranial pressure as well as neurologic symptoms due to inflammatory responses to migrating and eventually dying worms. PMID:10460929

  5. Considering syphilis in aseptic meningitis.

    PubMed

    Tayal, Sarup; Chadwick, David; Chawla, Girish

    2009-12-01

    Clinicians need to consider syphilis in the differential diagnosis of macular or papular rashes with neurological conditions, particularly aseptic meningitis, as early diagnosis and treatment lead to a better prognosis. PMID:20095316

  6. HIV-associated lipodystrophy: a review from a Brazilian perspective

    PubMed Central

    Alves, Marcelle D; Brites, Carlos; Sprinz, Eduardo

    2014-01-01

    The prognosis of human immunodeficiency virus (HIV)-infected individuals has dramatically improved worldwide since the introduction of highly antiretroviral therapy. Nevertheless, along with the decrease in mortality, several body modifications not initially related to HIV infection have been reported. Disorders in lipid and glucose metabolism, accompanied by body shape abnormalities and alterations in fat distribution, began to be described. A syndrome, named “HIV-associated lipodystrophy syndrome”, was coined to classify these clinical spectrum aspects. This syndrome involves not only metabolic alterations but also fat redistribution, with lipoatrophy due to subcutaneous fat loss (predominantly in the face and lower limbs) and lipohypertrophy related to central fat gain. These changes in body shape are very important to be recognized, as they are associated with worse morbidity and mortality. Self-esteem difficulties related to body alterations might lead to treatment failures due to medication adherence problems. Moreover, these alterations have been associated with an increased risk of cardiovascular events. Therefore, it is extremely important to identify this syndrome early in order to provide an even better quality of life for this population, as the clinical approach is not easy. Treatment change, medications to treat dyslipidemia, and surgical intervention are instruments to be used to try to correct these abnormalities. The aim of this study is to review clinical presentation, diagnosis, and management of body shape and metabolic complications of HIV infection from a Brazilian perspective, a medium income country with a large number of patients on antiretroviral therapy. PMID:25083134

  7. Spinal perineurial and meningeal cysts.

    PubMed

    Tarlov, I M

    1970-12-01

    Perineurial cysts may be responsible for clinical symptoms and a cure effected by their removal. They do not fill on initial myelography but may fill with Pantopaque some time, days or weeks, after Pantopaque has been instilled into the subarachnoid space. Perineurial cysts arise at the site of the posterior root ganglion. The cyst wall is composed of neural tissue. When initial myelography fails to reveal an adequate cause for the patient's symptoms and signs referable to the caudal nerve roots, then about a millilitre of Pantopaque should be left in the canal for delayed myelography which may later reveal a sacral perineurial cyst or, occasionally, a meningeal cyst. Meningeal diverticula occur proximal to the posterior root ganglia and usually fill on initial myelography. They are in free communication with the subarachnoid space and are rarely in my experience responsible for clinical symptoms. Meningeal diverticula and meningeal cysts appear to represent a continuum. Pantopaque left in the subarachnoid space may convert a meningeal diverticulum into an expanding symptomatic meningeal cyst, as in the case described. Many cases described as perineurial cysts represent abnormally long arachnoidal prolongations over nerve roots or meningeal diverticula. In general, neither of the latter is of pathological significance. Perineurial, like meningeal cysts and diverticula, may be asymptomatic. They should be operated upon only if they produce progressive or disabling symptoms or signs clearly attributable to them. When myelography must be done, and this should be done only as a preliminary to a probable necessary operation, then patient effort should be made to remove the Pantopaque. PMID:5531903

  8. Current knowledge on HIV-associated Plasmablastic Lymphoma

    PubMed Central

    Bibas, Michele; Castillo, Jorge J.

    2014-01-01

    HIV-associated PBL is an AIDS-defining cancer, classified by WHO as a distinct entity of aggressive DLBCL. To date less than 250 cases have been published, of them 17 are pediatric. The pathogenesis of this rare disease is related to immunodeficiency, chronic immune stimulation and EBV. Clinically is a rapid growing destructive disease mainly involving the oral cavity even if extraoral and extranodal sites are not infrequent. The diagnosis requires tissue mass or lymph node biopsy and core needle or fine needle biopsy is acceptable only for difficult access sites. Classically immunophenotype is CD45, CD20, CD79a negative and CD38, CD138, MUM1 positive, EBER and KI67 is >80%. Regarding the therapy, standard treatment is, usually, CHOP or CHOP-like regimens while more intensive regimens as CODOX-M/IVAC or DA-EPOCH are possible options. Use of cART is recommended during chemotherapy, keeping in mind the possible overlapping toxicities. Rituximab is not useful for this CD20 negative disease and CNS prophylaxis is mandatory. Intensification with ABMT in CR1 may be considered for fit patients. For refractory/relapsed patients, therapy is, usually, considered palliative, however, in chemo-sensitive disease, intensification + ABMT or new drugs as Bortezomib may be considered. Factors affecting outcome are achieving complete remission, PS, clinical stage, MYC, IPI score. Reported median PFS ranges between 6–7 months and median OS ranges between 11–13 months. Long term survivors are reported but mostly in pediatric patients. Finally, due to the scarcity of data on this subtype of NHL we suggest that the diagnosis and the management of HIV-positive PBL patients should be performed in specialized centers. PMID:25408850

  9. Age exacerbates HIV-associated white matter abnormalities.

    PubMed

    Seider, Talia R; Gongvatana, Assawin; Woods, Adam J; Chen, Huaihou; Porges, Eric C; Cummings, Tiffany; Correia, Stephen; Tashima, Karen; Cohen, Ronald A

    2016-04-01

    Both HIV disease and advanced age have been associated with alterations to cerebral white matter, as measured with white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and more recently with diffusion tensor imaging (DTI). This study investigates the combined effects of age and HIV serostatus on WMH and DTI measures, as well as the relationships between these white matter measures, in 88 HIV seropositive (HIV+) and 49 seronegative (HIV-) individuals aged 23-79 years. A whole-brain volumetric measure of WMH was quantified from FLAIR images using a semi-automated process, while fractional anisotropy (FA) was calculated for 15 regions of a whole-brain white matter skeleton generated using tract-based spatial statistics (TBSS). An age by HIV interaction was found indicating a significant association between WMH and older age in HIV+ participants only. Similarly, significant age by HIV interactions were found indicating stronger associations between older age and decreased FA in the posterior limbs of the internal capsules, cerebral peduncles, and anterior corona radiata in HIV+ vs. HIV- participants. The interactive effects of HIV and age were stronger with respect to whole-brain WMH than for any of the FA measures. Among HIV+ participants, greater WMH and lower anterior corona radiata FA were associated with active hepatitis C virus infection, a history of AIDS, and higher current CD4 cell count. Results indicate that age exacerbates HIV-associated abnormalities of whole-brain WMH and fronto-subcortical white matter integrity. PMID:26446690

  10. [Normal and abnormal meningeal enhancement: MRI features].

    PubMed

    Dietemann, J L; Correia Bernardo, R; Bogorin, A; Abu Eid, M; Koob, M; Nogueira, Th; Vargas, M I; Fakhoury, W; Zöllner, G

    2005-11-01

    The authors describe normal imaging of the meninges and meningeal spaces and MR (magnetic resonance) imaging findings in tumoral and nontumoral diseases. Dural or/and pial enhancement may be related to tumoral, infectious or granulomatous diseases. PMID:16269979

  11. An unusual case of meningitis

    PubMed Central

    Pond, Eric DR; El-Bailey, Sameh; Webster, Duncan

    2015-01-01

    Pasteurella multocida is a rare cause of bacterial meningitis. A 56-year-old man with several pets developed a profoundly decreased level of consciousness following left tympanomastoidectomy. Lumbar puncture produced cerebrospinal fluid with the typical findings of meningitis (low glucose, high protein, high leukocytes). Cultures from the cerebrospinal fluid and a swab of the left ear revealed Gram-negative coccobacillus identified as P multocida. The organism was sensitive to ceftriaxone, ampicillin and penicillin, and a 14-day course of intravenous penicillin was used as definitive treatment, resulting in full recovery. Although rare, P multocida should be considered as a potential cause of meningitis in patients with animal exposure, particularly in the setting of recent cranial surgery. PMID:26236360

  12. Meningococcal Disease (Bacterial Meningitis) Vaccine and Pregnancy

    MedlinePlus

    Meningococcal Disease (Bacterial meningitis) Vaccine and Pregnancy In every pregnancy, a woman starts out with a 3-5% chance of having a baby ... advice from your health care provider. What is meningitis? Meningitis is an infection of the lining that ...

  13. Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER.

    PubMed

    Holzinger, Emily R; Hulgan, Todd; Ellis, Ronald J; Samuels, David C; Ritchie, Marylyn D; Haas, David W; Kallianpur, Asha R; Bloss, Cinnamon S; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina M; McArthur, Justin C; McCutchan, J Allen; Morgello, Susan; Simpson, David M; Franklin, Donald R; Rosario, Debralee; Selph, Doug; Letendre, Scott; Grant, Igor

    2012-12-01

    HIV-associated sensory neuropathy remains an important complication of combination antiretroviral therapy and HIV infection. Mitochondrial DNA haplogroups and single nucleotide polymorphisms (SNPs) have previously been associated with symptomatic neuropathy in clinical trial participants. We examined associations between mitochondrial DNA variation and HIV-associated sensory neuropathy in CNS HIV Antiretroviral Therapy Effects Research (CHARTER). CHARTER is a USA-based longitudinal observational study of HIV-infected adults who underwent a structured interview and standardized examination. HIV-associated sensory neuropathy was determined by trained examiners as ≥1 sign (diminished vibratory and sharp-dull discrimination or ankle reflexes) bilaterally. Mitochondrial DNA sequencing was performed and haplogroups were assigned by published algorithms. Multivariable logistic regression of associations between mitochondrial DNA SNPs, haplogroups, and HIV-associated sensory neuropathy were performed. In analyses of associations of each mitochondrial DNA SNP with HIV-associated sensory neuropathy, the two most significant SNPs were at positions A12810G [odds ratio (95 % confidence interval) = 0.27 (0.11-0.65); p = 0.004] and T489C [odds ratio (95 % confidence interval) = 0.41 (0.21-0.80); p = 0.009]. These synonymous changes are known to define African haplogroup L1c and European haplogroup J, respectively. Both haplogroups were associated with decreased prevalence of HIV-associated sensory neuropathy compared with all other haplogroups [odds ratio (95 % confidence interval) = 0.29 (0.12-0.71); p = 0.007 and odds ratio (95 % confidence interval) = 0.42 (0.18-1.0); p = 0.05, respectively]. In conclusion, in this cohort of mostly combination antiretroviral therapy-treated subjects, two common mitochondrial DNA SNPs and their corresponding haplogroups were associated with a markedly decreased prevalence of HIV-associated sensory neuropathy

  14. Meningitis, clinical presentation of tetanus.

    PubMed

    Moniuszko, Anna; Zajkowska, Agata; Tumiel, Ewa; Rutkowski, Krzysztof; Czupryna, Piotr; Pancewicz, Sławomir; Rutkowski, Ryszard; Zdrodowska, Agnieszka; Zajkowska, Joanna

    2015-01-01

    Background. Tetanus is an acute disease caused by a neurotoxin produced by Clostridium tetani. Tetanus immunization has been available since the late 1930s but sporadic cases still occur, usually in incompletely vaccinated or unvaccinated individuals. Case Report. An elderly previously vaccinated female contracted tetanus following foot injury. Clinically she presented with meningitis causing diagnostic and therapeutic delays. Why Should Physician Be Aware of This? Even in developed countries the differential diagnosis of meningitis, especially in the elderly, should include tetanus. Treatment in intensive care unit is required. General population might benefit from vaccine boosters and education on this potentially fatal disease. PMID:25789186

  15. The lncRNA RZE1 Controls Cryptococcal Morphological Transition

    PubMed Central

    Yang, Ence; Wang, Linqi; Cai, James J.; Lin, Xiaorong

    2015-01-01

    In the fungal pathogen Cryptococcus neoformans, the switch from yeast to hypha is an important morphological process preceding the meiotic events during sexual development. Morphotype is also known to be associated with cryptococcal virulence potential. Previous studies identified the regulator Znf2 as a key decision maker for hypha formation and as an anti-virulence factor. By a forward genetic screen, we discovered that a long non-coding RNA (lncRNA) RZE1 functions upstream of ZNF2 in regulating yeast-to-hypha transition. We demonstrate that RZE1 functions primarily in cis and less effectively in trans. Interestingly, RZE1’s function is restricted to its native nucleus. Accordingly, RZE1 does not appear to directly affect Znf2 translation or the subcellular localization of Znf2 protein. Transcriptome analysis indicates that the loss of RZE1 reduces the transcript level of ZNF2 and Znf2’s prominent downstream targets. In addition, microscopic examination using single molecule fluorescent in situ hybridization (smFISH) indicates that the loss of RZE1 increases the ratio of ZNF2 transcripts in the nucleus versus those in the cytoplasm. Taken together, this lncRNA controls Cryptococcus yeast-to-hypha transition through regulating the key morphogenesis regulator Znf2. This is the first functional characterization of a lncRNA in a human fungal pathogen. Given the potential large number of lncRNAs in the genomes of Cryptococcus and other fungal pathogens, the findings implicate lncRNAs as an additional layer of genetic regulation during fungal development that may well contribute to the complexity in these “simple” eukaryotes. PMID:26588844

  16. Neuroimaging features of tuberculous meningitis.

    PubMed

    Sobri, M; Merican, J S; Nordiyana, M; Valarmathi, S; Ai-Edrus, S A

    2006-03-01

    Tuberculous meningitis leads to a high mortality rate. However, it responds well to chemotherapy if the treatment is started early. Neuroimaging is one of the most important initial investigations. There were 42 patients diagnosed with tuberculous meningitis in Kuala Lumpur Hospital based on clinical criteria, cerebrospinal fluid analysis and response to anti-tuberculous treatment over a 7 year period. Relevant information was obtained from patients' medical case notes and neuroimaging findings were evaluated. Male to female ratio was 3:1. The three major ethnics and the immigrant groups in Malaysia were represented in this study. The majority of the cases involved the Malays followed by immigrants, Chinese and Indians. The patients' age ranged from 18 to 62 years old with the mean age of 34.4 years. There were 95.2% (n = 40) of patients who presented with various neuroimaging abnormalities and only 2 (4.8%) patients had normal neuroimaging findings. Hydrocephalus and meningeal enhancement were the two commonest neuroimaging features. Other features include infarction, enhancing lesion, tuberculoma, abcess, oedema and calcification. Contrasted CT scan is an adequate neuroimaging tool to unmask abnormal findings in tuberculous meningitis. PMID:16708732

  17. Acute Cryptococcal Immune Reconstitution Inflammatory Syndrome in a Patient on Natalizumab

    PubMed Central

    Gundacker, Nathan D.; Jordan, Stephen J.; Jones, Benjamin A.; Drwiega, Joseph C.; Pappas, Peter G.

    2016-01-01

    Presented is the first case of acute immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcal meningoencephalitis in a patient on natalizumab for multiple sclerosis. The patient developed acute cerebral edema after initiation of amphotericin B. We propose several mechanisms that explain the acuity of IRIS in this specific patient population and suggest possible therapies. PMID:27006962

  18. Cryptococcal Neuroradiological Lesions Correlate with Severity during Cryptococcal Meningoencephalitis in HIV-Positive Patients in the HAART Era

    PubMed Central

    Charlier, Caroline; Dromer, Françoise; Lévêque, Christophe; Chartier, Loïc; Cordoliani, Yves-Sébastien; Fontanet, Arnaud; Launay, Odile; Lortholary, Olivier

    2008-01-01

    Cryptococcal meningoencephalitis has an overall global mortality rate of 20% in AIDS patients despite antifungals. There is a need for additional means of precise assessment of disease severity. We thus studied the radiological brain images available from 62 HIV-positive patients with cryptococcocal meningoencephalitis to analyse the brain lesions associated with cryptococcosis in relationship with disease severity, and the respective diagnostic contribution of magnetic resonance (MR) versus computed tomography (CT). In this retrospective multicenter analysis, two neuroradiologists blindly reviewed the brain imaging. Prospectively acquired clinical and mycological data were available at baseline and during follow-up. Baseline images were abnormal on 92% of the MR scans contrasting with 53% of the CT scans. MR/CT cryptococcosis-related lesions included mass(es) (21%/9%), dilated perivascular spaces (46%/5%) and pseudocysts (8%/4%). The presence compared to absence of cryptococcosis-related lesions was significantly associated with high serum (78% vs. 42%, p = 0.008) and CSF (81% vs. 50%, p = 0.024) antigen titers, independently of neurological abnormalities. MR detected significantly more cryptococcosis-related lesions than CT for 17 patients who had had both investigations (76% vs. 24%, p = 0.005). In conclusion, MR appears more effective than CT for the evaluation of AIDS-associated cerebral cryptococcosis. Furthermore, brain imaging is an effective tool to assess the initial disease severity in this setting. Given this, we suggest that investigation for cryptococcosis-related lesions is merited, even in the absence of neurological abnormality, if a high fungal burden is suspected on the basis of high serum and/or CSF antigen titers. PMID:18414656

  19. Cryptococcal Immune Reconstitution Inflammatory Syndrome in HIV-1–infected individuals: Literature Review and Proposed Clinical Case Definitions

    PubMed Central

    Haddow, Lewis J; Colebunders, Robert; Meintjes, Graeme; Lawn, Stephen D; Elliott, Julian H; Manabe, Yukari C; Bohjanen, Paul R; Sungkanuparph, Somnuek; Easterbrook, Philippa J; French, Martyn A; Boulware, David R

    2011-01-01

    Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) may present as a clinical deterioration or new presentation of cryptococcal disease following initiation of antiretroviral therapy (ART) and is believed to be caused by recovery of cryptococcus-specific immune responses. We have reviewed the existing literature on C-IRIS to inform the development of a consensus case definition specific for paradoxical cryptococcal IRIS in patients with known cryptococcal disease prior to ART, and a second definition for incident cases of cryptococcosis developing during ART (here termed ART-associated cryptococcosis), a proportion of which are likely to be “unmasking” C-IRIS. These structured case definitions are intended for use in future clinical, epidemiologic and immunopathologic studies of C-IRIS, harmonizing diagnostic criteria, and facilitating comparisons between studies. As with tuberculosis-associated IRIS, these proposed definitions should be regarded as preliminary until further insights into the immunopathology of IRIS permit their refinement. PMID:21029993

  20. Corticosteroids for managing tuberculous meningitis

    PubMed Central

    Prasad, Kameshwar; Singh, Mamta B; Ryan, Hannah

    2016-01-01

    Background Tuberculous meningitis is a serious form of tuberculosis (TB) that affects the meninges that cover a person's brain and spinal cord. It is associated with high death rates and with disability in people who survive. Corticosteroids have been used as an adjunct to antituberculous drugs to treat people with tuberculous meningitis, but their role has been controversial. Objectives To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register up to the 18 March 2016; CENTRAL; MEDLINE; EMBASE; LILACS; and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists. Selection criteria Randomized controlled trials that compared corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculous meningitis and included death or disability as outcome measures. Data collection and analysis We independently assessed search results and methodological quality, and extracted data from the included trials. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs) and used a fixed-effect model. We performed an intention-to-treat analysis, where we included all participants randomized to treatment in the denominator. This analysis assumes that all participants who were lost to follow-up have good outcomes. We carried out a sensitivity analysis to explore the impact of the missing data. Main results Nine trials that included 1337 participants (with 469 deaths) met the inclusion criteria. At follow-up from three to 18 months, steroids reduce deaths by almost one quarter (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence). Disabling neurological deficit is not common in survivors, and steroids may have little or no

  1. Streptococcal meningitis following myelogram procedures.

    PubMed

    Hsu, Jennifer; Jensen, Bette; Arduino, Matthew; Bergeron, Toni; Fox, Teresa; Gum, Greg; Pischke, Vera; Potts, David; Townes, John; Srinivasan, Arjun

    2007-05-01

    In September of 2004, we investigated 7 cases of post-myelography meningitis. Streptococcal species were recovered from blood or cerebrospinal fluid in all cases. Our findings suggest that droplet transmission of the oral flora of the clinician performing the procedure was the most likely source of these infections. The Centers for Disease Control and Prevention recommends the use of face masks by those performing myelograms. PMID:17464927

  2. Gallium-67 uptake in meningeal sarcoidosis

    SciTech Connect

    Ayres, J.G.; Hicks, B.H.; Maisey, M.N.

    1986-07-01

    A case of sarcoidosis limited to the central nervous system is described in which the diagnosis was suggested by high Ga-67 uptake in the cranial and spinal meninges. The diagnosis was confirmed by meningeal biopsy. Treatment with oral corticosteroids resulted in clinical improvement and marked reduction in Ga-67 uptake in the meninges. This is the first reported case of the central nervous system sarcoid diagnosed by Ga-67 imaging.

  3. Pathophysiology and Treatment of Bacterial Meningitis

    PubMed Central

    Hoffman, Olaf

    2009-01-01

    Bacterial meningitis is a medical emergency requiring immediate diagnosis and immediate treatment. Streptococcus pneumoniae and Neisseria meningitidis are the most common and most aggressive pathogens of meningitis. Emerging antibiotic resistance is an upcoming challenge. Clinical and experimental studies have established a more detailed understanding of the mechanisms resulting in brain damage, sequelae and neuropsychological deficits. We summarize the current pathophysiological concept of acute bacterial meningitis and present current treatment strategies. PMID:21180625

  4. Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa

    PubMed Central

    Rockers, Peter C.; Bonawitz, Rachael; Sriruttan, Charlotte; Glencross, Deborah K.; Cassim, Naseem; Coetzee, Lindi M.; Greene, Gregory S.; Chiller, Tom M.; Vallabhaneni, Snigdha; Long, Lawrence; van Rensburg, Craig; Govender, Nelesh P.

    2016-01-01

    countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved. PMID:27390864

  5. Toward improved anti-cryptococcal drugs: Novel molecules and repurposed drugs.

    PubMed

    Krysan, Damian J

    2015-05-01

    Cryptococcosis is one of the most important fungal infections of humans. It primarily, but not exclusively, afflicts people with compromised immune function. Cryptococcosis is most commonly caused by Cryptococcus neoformans var. grubii with C. neoformans var. neoformans and C. gatti also contributing to the disease. Cryptococcosis is primarily manifested as meningoencephalitis although pneumonia occurs frequently as well. Globally, the burden of disease is highest among those living with HIV/AIDS and is one of the most common causes of death in this patient population. Cryptococcal meningitisis almost invariably fatal if untreated. The current gold standard therapy is amphotericin B combined with 5-flucytosine. Unfortunately, this therapy has significant toxicity and is not widely available in resource-limited regions. Fluconazole, which is associated with poorer outcomes, is frequently as an alternative. Here, I present the characteristics of an ideal anti-cryptococcal agent and review recent progress toward identifying both novel and repurposed drugs as potential new therapies. PMID:25514636

  6. Japanese encephalitis virus in meningitis patients, Japan.

    PubMed

    Kuwayama, Masaru; Ito, Mikako; Takao, Shinichi; Shimazu, Yukie; Fukuda, Shinji; Miyazaki, Kazuo; Kurane, Ichiro; Takasaki, Tomohiko

    2005-03-01

    Cerebrospinal fluid specimens from 57 patients diagnosed with meningitis were tested for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified. Two products had highest homology with Nakayama strain and 2 with Ishikawa strain. Results suggest that Japanese encephalitis virus causes some aseptic meningitis in Japan. PMID:15757569

  7. Full recovery from Baylisascaris procyonis eosinophilic meningitis.

    PubMed

    Pai, Poulomi J; Blackburn, Brian G; Kazacos, Kevin R; Warrier, Rajasekharan P; Bégué, Rodolfo E

    2007-06-01

    Infection by Baylisascaris procyonis is an uncommon but devastating cause of eosinophilic meningitis. We report the first case-patient, to our knowledge, who recovered from B. procyonis eosinophilic meningitis without any recognizable neurologic deficits. The spectrum of illness for this organism may be wider than previously recognized. PMID:17553240

  8. Trimethoprim-sulfamethoxazole-induced aseptic meningitis.

    PubMed Central

    Wambulwa, Charles; Bwayo, Salome; Laiyemo, Adeyinka O.; Lombardo, Fredric

    2005-01-01

    We present a 46-year-old African-American man with AIDS who was admitted on two different occasions within three weeks for signs and symptoms of meningitis after using trimethoprim/sulfamethoxazole (TMP/SMX). TMP/SMX is primarily used for the treatment of pneumocystis carinii pneumonia prophylaxis in AIDS patients. Drug-induced aseptic meningitis (DIAM) is commonly seen with nonsteroidal anti-inflammatory drugs (NSAIDS), antibiotics (with TMP/SMX being the most frequently implicated), intravenous immunoglobulins and OKT3 antibodies. However, the implication of TMP/SMX inducing aseptic meningitis has been underreported to FDA/MEDWATCH program. This might be due to the fact that it has also been used to treat bacterial meningitis from organisms like Listeria monocytogenes, which is a common pathogen in the elderly and in infants. We reviewed the literature in an attempt to characterize the pattern and predictors of TMP/SMX-induced aseptic meningitis. PMID:16396068

  9. Towards a meningitis free world--can we eliminate meningococcal meningitis?: contribution of the meningitis patient groups.

    PubMed

    Davie, Sue; Glennie, Linda; Rowland, Kate

    2012-05-30

    Patient groups play a critical part in the fight against meningitis in all its forms. The UK has the world's three largest meningitis patient groups, which over the past 3 decades have worked tirelessly in the fight against meningitis. Within the UK, where the patient groups work to prevent or alleviate the suffering caused by meningitis and septicaemia, their work is in three areas: continued research; demonstrating burden; and awareness-raising and advocacy. The research relates to developing and improving vaccines, and to improving outcomes for forms of meningitis that are not vaccine preventable. Demonstrating burden - showing the real impact of meningitis from a human perspective - highlights the need for vaccines to prevent the disease. Lives are saved by raising awareness of signs and symptoms and of the need for fast action, whilst advocacy can bring about change to improve the quality of life of those affected by meningitis. Awareness raising and advocacy also have the wider benefit of creating a climate in which people recognise the need for vaccines to prevent this dreadful disease. In addition, the patient groups seek to influence the early introduction and uptake of vaccines as they are licensed and approved by the expert bodies, the UK body being the Joint Committee for Vaccination and Immunisation (JCVI). Each area of activity is explored, and examples given from each of the patient groups of work they have done or are doing in that area. PMID:22607905

  10. In Brief: Forecasting meningitis threats

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2008-12-01

    The University Corporation for Atmospheric Research (UCAR), in conjunction with a team of health and weather organizations, has launched a project to provide weather forecasts to medical officials in Africa to help reduce outbreaks of meningitis. The forecasts will enable local health care providers to target vaccination programs more effectively. In 2009, meteorologists with the National Center for Atmospheric Research, which is managed by UCAR, will begin issuing 14-day forecasts of atmospheric conditions in Ghana. Later, UCAR plans to work closely with health experts from several African countries to design and test a decision support system to provide health officials with useful meteorological information. ``By targeting forecasts in regions where meningitis is a threat, we may be able to help vulnerable populations. Ultimately, we hope to build on this project and provide information to public health programs battling weather-related diseases in other parts of the world,'' said Rajul Pandya, director of UCAR's Community Building Program. Funding for the project comes from a $900,000 grant from Google.org, the philanthropic arm of the Internet search company.

  11. High detection rates of cryptococcal antigen in pulmonary cryptococcosis by Eiken latex agglutination test with pronase pretreatment.

    PubMed

    Kohno, S; Yasuoka, A; Koga, H; Kaku, M; Maesaki, S; Tanaka, K; Mitsutake, K; Matsuda, H; Hara, K

    1993-08-01

    Two different kits for the detection of serum cryptococcal antigen in patients with pulmonary cryptococcosis were evaluated. The Eiken test (the Eiken Co., Tokyo), which uses pronase for pretreatment of serum, was compared with the Crypto-LA test (International Biological Laboratories, Cranbury, NJ), which did not use pronase prior to testing. Cryptococcal antigen was detected in 21 of 23 patients (91%) with the Eiken test and in only 10 of 23 patients (43%) with the Crypto-LA test (p < 0.01 by McNemar test). However, the sensitivity of two tests was identical without use of pronase, as both tests could detect as little as 10(4) cells/ml of Cryptococcus neoformans and 10 ng/ml of capsular polysaccharide of C. neoformans. In those serum specimens for which both tests were positive, titers were much higher for the Eiken test, but there was a statistically significant correlation between the two tests (coefficient correlation 0.79, p < 0.01). Cryptococcal antigen titer levels measured by the Eiken test correlated well with clinical courses. There was one false-positive reaction among 82 sera of non-cryptococcal patients. Pronase enhanced the sensitivity of the Eiken test, which appeared to be useful in patients with pulmonary cryptococcal disease, and its use may prevent unneeded lung biopsies. PMID:8264770

  12. HIV-associated tuberculosis in developing countries: clinical features, diagnosis, and treatment.

    PubMed Central

    Raviglione, M. C.; Narain, J. P.; Kochi, A.

    1992-01-01

    This article reviews the clinical aspects and diagnosis of HIV-associated tuberculosis in developing countries, and summarizes WHO's recommendations for treatment. According to WHO estimates (early 1992) over 4 million persons worldwide have been infected with HIV and tuberculosis; 95% of them are in the developing countries. Clinical features of HIV-associated pulmonary tuberculosis in adults are frequently atypical, particularly in the late stage of HIV infection, with non-cavitary disease, lower lobe infiltrates, hilar lymphadenopathy and pleural effusion. More typical post-primary tuberculosis with upper lobe infiltrates and cavitations is seen in the earlier stages of HIV infection. Extrapulmonary tuberculosis is reported more frequently, despite the difficulties in diagnosing it. WHO's recent guidelines recommend 6-month short-course chemotherapy with isoniazid, rifampicin, pyrazinamide and ethambutol for patients with HIV-associated tuberculosis. The older 12-month regimen without rifampicin is much less effective. Streptomycin should not be used, because of the risk of transmitting blood-borne pathogens through contaminated needles. Thioacetazone should be abandoned, because of severe adverse reactions observed among HIV-infected patients. The roles of preventive chemotherapy and BCG vaccination for prevention of tuberculosis are also briefly discussed. PMID:1394786

  13. Climate Change and Cerebrospinal Meningitis in the Ghanaian Meningitis Belt

    PubMed Central

    Codjoe, Samuel Nii Ardey; Nabie, Vivian Adams

    2014-01-01

    Cerebrospinal meningitis (CSM) is one of the infectious diseases likely to be affected by climate change. Although there are a few studies on the climate change-CSM nexus, none has considered perceptions of community members. However, understanding public perception in relation to a phenomenon is very significant for the design of effective communication and mitigation strategies as well as coping and adaptation strategies. This paper uses focus group discussions (FGDs) to fill this knowledge lacuna. Results show that although a few elderly participants ascribed fatal causes (disobedience to gods, ancestors, and evil spirits) to CSM infections during FGDs, majority of participants rightly linked CSM infections to dry, very hot and dusty conditions experienced during the dry season. Finally, community members use a suite of adaptation options to curb future CSM epidemics. PMID:25003550

  14. Stenotrophomonas maltophilia: rare cause of meningitis.

    PubMed

    Correia, Cátia Rodrigues; Ferreira, Sara Tavares; Nunes, Paula

    2014-08-01

    Stenotrophomonas maltophilia is a Gram-negative bacillus, which is an extremely rare cause of meningitis. To our knowledge, there are only five previous pediatrics cases. Here, we describe the case of a 4-year-old boy who developed meningitis associated with this organism, after several neurosurgical procedures and previous treatment with a broad-spectrum antibiotic. He was treated successfully with a combination of trimethoprim-sulfamethoxazole, ceftazidime and levofloxacin. Stenotrophomonas maltophilia should be considered as a potential cause of meningitis, especially among severely debilitated or immunosuppressed patients. Antimicrobial therapy is complicated by the high resistance of the organism to multiple antibiotics. PMID:25252064

  15. Chronic Meningitis: Simplifying a Diagnostic Challenge.

    PubMed

    Baldwin, Kelly; Whiting, Chris

    2016-03-01

    Chronic meningitis can be a diagnostic dilemma for even the most experienced clinician. Many times, the differential diagnosis is broad and encompasses autoimmune, neoplastic, and infectious etiologies. This review will focus on a general approach to chronic meningitis to simplify the diagnostic challenges many clinicians face. The article will also review the most common etiologies of chronic meningitis in some detail including clinical presentation, diagnostic testing, treatment, and outcomes. By using a case-based approach, we will focus on the key elements of clinical presentation and laboratory analysis that will yield the most rapid and accurate diagnosis in these complicated cases. PMID:26888190

  16. [Pasteurella multocida meningitis with cerebral abscesses].

    PubMed

    Nguefack, S; Moifo, B; Chiabi, A; Mah, E; Bogne, J-B; Fossi, M; Fru, F; Mbonda, E; Djientcheu, V-P

    2014-03-01

    Pasteurella multocida is classically responsible for local soft tissue infections secondary to dog bites or cat scratches. It can be responsible for meningitis in infants and elderly persons. We report the case history of a 5-year-old male child admitted to our pediatric unit for meningitis. Cerebrospinal fluid analysis revealed an infection with P. multocida. The suspected mode of contamination was either from the saliva of a pet dog or through an unnoticed skull fracture sustained after an accident 1 year prior to the occurrence of meningitis. In spite of the neurologic complication (cerebral abscess), the progression was favorable after drainage of the abscess, 5 weeks of parenteral treatment, and 3 weeks of oral antibiotic therapy. Meningitis due to Pasteurella sp. is rare and can lead to neurologic complications. The notion of bites or scratches can be absent and the mode of contamination is sometimes difficult to unveil. PMID:24457110

  17. Hemi-meningitis with hemophagocytic lymphohistiocytosis.

    PubMed

    Kocak, Ozan; Yarar, Coskun; Yimenicioğlu, Sevgi; Ekici, Arzu; Bör, Özcan

    2016-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare lymphoproliferative disorder. HLH may occur as a complication of Epstein-Barr virus (EBV), particularly in patients with immunodeficiencies. Herein, we describe a 16-year-old girl with neurological complications associated EBV-induced HLH. Her cerebral magnetic resonance imaging (MRI) showed contrast-enhanced axial T1-weighted images with enhancement of meningeal surface in the right hemisphere that was consistent with right hemi-meningitis. Hydrocephalus, dilated subdural spaces, delayed myelination, edema, diffuse parenchymal atrophy, calcifications, diffuse/patchy white matter abnormalities have all been previously described with HLH. To the best of our knowledge, this is the first case of hemi-meningitis associated with HLH. We suggest that clinicians should consider HLH with vascular disorders when they determine unilateral meningitis on a brain MRI. PMID:27570395

  18. Environmental Risk and Meningitis Epidemics in Africa

    PubMed Central

    Molesworth, Anna M.; Cuevas, Luis E.; Connor, Stephen J.; Morse, Andrew P.

    2003-01-01

    Epidemics of meningococcal meningitis occur in areas with particular environmental characteristics. We present evidence that the relationship between the environment and the location of these epidemics is quantifiable and propose a model based on environmental variables to identify regions at risk for meningitis epidemics. These findings, which have substantial implications for directing surveillance activities and health policy, provide a basis for monitoring the impact of climate variability and environmental change on epidemic occurrence in Africa. PMID:14609465

  19. Cryptococcal meningoencephalitis relapse after an eight-year delay: an interplay of infection and immune reconstitution.

    PubMed

    Katchanov, Juri; Blechschmidt, Cristiane; Nielsen, Kirsten; Branding, Gordian; Arastéh, Keikawus; Tintelnot, Kathrin; Meintjes, Graeme; Boulware, David R; Stocker, Hartmut

    2015-10-01

    We report a case of a symptomatic relapse of HIV-related cryptococcal meningoencephalitis eight years after the first diagnosis on the background of immune reconstitution. The findings as well as the clinical course suggests a combination of smouldering localised infection and enhanced inflammatory reaction related to immune restoration due to antiretroviral therapy. A combination of antifungal and anti-inflammatory therapy resulted in clinical and radiological improvement. Our case challenges the concept that immune reconstitution inflammatory syndrome and microbiological relapse are dichotomous entities. PMID:25505049

  20. Cryptococcal osteomyelitis: a report of 5 cases and a review of the recent literature.

    PubMed

    Medaris, Leigh Ann; Ponce, Brent; Hyde, Zane; Delgado, Dennis; Ennis, David; Lapidus, William; Larrison, Matthew; Pappas, Peter G

    2016-06-01

    Cryptococcus neoformans is a fungal pathogen associated with advanced HIV disease and other disorders associated with immune dysfunction. The pulmonary and the central nervous system are the most common manifestations of the disease. Localised osteomyelitis as the sole manifestation of extrapulmonary disease is rare. Herein, we present five cases of Cryptococcus osteomyelitis as the only manifestation of extrapulmonary disease. We also identified 84 additional cases of isolated cryptococcal osteomyelitis in the literature. Using these data, we have made some general recommendations regarding an approach to treatment of this uncommon clinical entity. PMID:26968335

  1. Pathogenesis and pathophysiology of bacterial meningitis.

    PubMed Central

    Tunkel, A R; Scheld, W M

    1993-01-01

    Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder. Images PMID:8472245

  2. Diagnostic Accuracy of Procalcitonin in Bacterial Meningitis Versus Nonbacterial Meningitis

    PubMed Central

    Wei, Ting-Ting; Hu, Zhi-De; Qin, Bao-Dong; Ma, Ning; Tang, Qing-Qin; Wang, Li-Li; Zhou, Lin; Zhong, Ren-Qian

    2016-01-01

    Abstract Several studies have investigated the diagnostic accuracy of procalcitonin (PCT) levels in blood or cerebrospinal fluid (CSF) in bacterial meningitis (BM), but the results were heterogeneous. The aim of the present study was to ascertain the diagnostic accuracy of PCT as a marker for BM detection. A systematic search of the EMBASE, Scopus, Web of Science, and PubMed databases was performed to identify studies published before December 7, 2015 investigating the diagnostic accuracy of PCT for BM. The quality of the eligible studies was assessed using the revised Quality Assessment for Studies of Diagnostic Accuracy method. The overall diagnostic accuracy of PCT detection in CSF or blood was pooled using the bivariate model. Twenty-two studies involving 2058 subjects were included in this systematic review and meta-analysis. The overall specificities and sensitivities were 0.86 and 0.80 for CSF PCT, and 0.97 and 0.95 for blood PCT, respectively. Areas under the summary receiver operating characteristic curves were 0.90 and 0.98 for CSF PCT and blood PCT, respectively. The major limitation of this systematic review and meta-analysis was the small number of studies included and the heterogeneous diagnostic thresholds adopted by eligible studies. Our meta-analysis shows that PCT is a useful biomarker for BM diagnosis. PMID:26986140

  3. Antioxidant enzyme dysfunction in monocytes and CSF of Hispanic women with HIV-associated cognitive impairment

    PubMed Central

    Velázquez, Ixane; Plaud, Marinés; Wojna, Valerie; Skolasky, Richard; Laspiur, Juliana Pérez; Meléndez, Loyda M.

    2010-01-01

    HIV-associated cognitive neurological disorders (HAND) prevail in the antiretroviral therapy era. Proteomics analysis of CSF revealed expression of Cu/Zn superoxide dismutase (Cu/Zn SOD) in Hispanic women with cognitive impairment (CI). We tested the hypothesis that there is reduced capacity of antioxidant enzymes in CI by measures of expression and activity of Cu/Zn SOD, catalase, and Se-glutathione peroxidase in HAND. Our results showed that the function of these antioxidants was decreased in the CSF and monocytes of women with CI. These findings have important implications regarding their possible contribution to oxidative stress and in the diagnosis and therapy for HAND. PMID:19101040

  4. Medical marijuana for HIV-associated sensory neuropathy: legal and ethical issues.

    PubMed

    Larriviere, Daniel G

    2014-10-01

    The number of states legalizing medical marijuana is increasing. Medical marijuana is possibly effective therapy for HIV-associated sensory neuropathy. Despite legalization at the state level, however, the current and contradictory federal drug enforcement policy creates the risk that physicians who recommend medical marijuana to their patients will lose their ability to prescribe medications. The federal-state tension has legal and ethical implications for neurologists who receive a request for medical marijuana from their patients since neurologists must strive to both relieve suffering and obey relevant laws. Recommendation of medical marijuana by neurologists to their patients is ethically permissible but is not ethically mandatory. PMID:25299291

  5. Meningitis and Climate: From Science to Practice

    NASA Technical Reports Server (NTRS)

    Perez Garcia-Pando, Carlos; Thomson, Madeleine C.; Stanton, Michelle C.; Diggle, Peter J.; Hopson, Thomas; Pandya, Rajul; Miller, Ron L.; Hugonnet, Stephane

    2014-01-01

    Meningococcal meningitis is a climate sensitive infectious disease. The regional extent of the Meningitis Belt in Africa, where the majority of epidemics occur, was originally defined by Lapeysonnie in the 1960s. A combination of climatic and environmental conditions and biological and social factors have been associated to the spatial and temporal patterns of epidemics observed since the disease first emerged in West Africa over a century ago. However, there is still a lack of knowledge and data that would allow disentangling the relative effects of the diverse risk factors upon epidemics. The Meningitis Environmental Risk Information Technologies Initiative (MERIT), a collaborative research-to-practice consortium, seeks to inform national and regional prevention and control strategies across the African Meningitis Belt through the provision of new data and tools that better determine risk factors. In particular MERIT seeks to consolidate a body of knowledge that provides evidence of the contribution of climatic and environmental factors to seasonal and year-to-year variations in meningococcal meningitis incidence at both district and national scales. Here we review recent research and practice seeking to provide useful information for the epidemic response strategy of National Ministries of Health in the Meningitis Belt of Africa. In particular the research and derived tools described in this paper have focused at "getting science into policy and practice" by engaging with practitioner communities under the umbrella of MERIT to ensure the relevance of their work to operational decision-making. We limit our focus to that of reactive vaccination for meningococcal meningitis. Important but external to our discussion is the development and implementation of the new conjugate vaccine, which specifically targets meningococcus A

  6. A pseudo-outbreak of disseminated cryptococcal disease after orthotopic heart transplantation.

    PubMed

    Kennedy, E; Vanichanan, J; Rajapreyar, I; Gonzalez, B; Nathan, S; Gregoric, I; Kar, B; Loyalka, P; Weeks, P; Chavez, V; Wanger, A; Ostrosky Zeichner, L

    2016-02-01

    Cryptococcal infection is the third most common invasive fungal infection (IFI) among solid-organ transplant (SOT) recipients and is considered an important opportunistic infection due to its significant morbidity and mortality. To determine whether a cluster of cryptococcosis in heart transplant patients was of nosocomial nature, three cases of orthotopic heart transplant recipients with postoperative disseminated cryptococcal infection were investigated and paired with an environmental survey in a tertiary care hospital. The infection prevention department conducted a multidisciplinary investigation, which did not demonstrate any evidence of health care-associated environmental exposure. Moreover, multilocus sequence typing showed that one isolate was unique and the two others, although identical, were not temporally related and belong to the most common type seen in the Southern US. Additionally, all three patients had preexisting abnormalities of the CT chest scan and various degrees of acute and chronic rejection. Reactivation was suggested in all three patients. Screening methods may be useful to identify at risk patients and trigger a prophylactic or preemptive approach. However, more data is needed. PMID:26627342

  7. Procalcitonin as a Diagnostic and Prognostic Factor for Tuberculosis Meningitis

    PubMed Central

    Kim, Jinseung; Kim, Si Eun; Park, Bong Soo; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Kim, Sung Eun

    2016-01-01

    Background and Purpose We investigated the potential role of serum procalcitonin in differentiating tuberculosis meningitis from bacterial and viral meningitis, and in predicting the prognosis of tuberculosis meningitis. Methods This was a retrospective study of 26 patients with tuberculosis meningitis. In addition, 70 patients with bacterial meningitis and 49 patients with viral meningitis were included as the disease control groups for comparison. The serum procalcitonin level was measured in all patients at admission. Differences in demographic and laboratory data, including the procalcitonin level, were analyzed among the three groups. In addition, we analyzed the predictive factors for a prognosis of tuberculosis meningitis using the Glasgow Coma Scale (GCS) at discharge, and the correlation between the level of procalcitonin and the GCS score at discharge. Results Multiple logistic regression analysis showed that a low level of procalcitonin (≤1.27 ng/mL) independently distinguished tuberculosis meningitis from bacterial meningitis. The sensitivity and specificity for distinguishing tuberculosis meningitis from bacterial meningitis were 96.2% and 62.9%, respectively. However, the level of procalcitonin in patients with tuberculosis meningitis did not differ significantly from that in patients with viral meningitis. In patients with tuberculosis meningitis, a high level of procalcitonin (>0.4 ng/mL) was a predictor of a poor prognosis, and the level of procalcitonin was negatively correlated with the GCS score at discharge (r=-0.437, p=0.026). Conclusions We found that serum procalcitonin is a useful marker for differentiating tuberculosis meningitis from bacterial meningitis and is also valuable for predicting the prognosis of tuberculosis meningitis. PMID:27165424

  8. The Causes of HIV-Associated Cardiomyopathy: A Tale of Two Worlds

    PubMed Central

    Lumsden, Rebecca H.; Bloomfield, Gerald S.

    2016-01-01

    Antiretroviral therapy (ART) has transformed the clinical profile of human immunodeficiency virus (HIV) from an acute infection with a high mortality into a treatable, chronic disease. As a result, the clinical sequelae of HIV infection are changing as patients live longer. HIV-associated cardiomyopathy (HIVAC) is a stage IV, HIV-defining illness and remains a significant cause of morbidity and mortality among HIV-infected individuals despite ART. Causes and clinical manifestations of HIVAC depend on the degree of host immunosuppression. Myocarditis from direct HIV toxicity, opportunistic infections, and nutritional deficiencies are implicated in causing HIVAC when HIV viral replication is unchecked, whereas cardiac autoimmunity, chronic inflammation, and ART cardiotoxicity contribute to HIVAC in individuals with suppressed viral loads. The initiation of ART has dramatically changed the clinical manifestation of HIVAC in high income countries from one of severe, left ventricular systolic dysfunction to a pattern of subclinical cardiac dysfunction characterized by abnormal diastolic function and strain. In low and middle income countries, however, HIVAC is the most common HIV-associated cardiovascular disease. Clear diagnostic and treatment guidelines for HIVAC are currently lacking but should be prioritized given the global burden of HIVAC. PMID:26885518

  9. HIV-associated Burkitt lymphoma in a Japanese patient with early submandibular swelling

    PubMed Central

    2013-01-01

    Background Patients infected with the human immunodeficiency virus (HIV) are at risk of developing malignancies and have an increased susceptibility to infection. HIV-associated Burkitt lymphoma (BL) is relatively rare in developed countries, but remains prevalent in developing counties and is sometimes compounded by the fact that patients may be unaware that they are HIV-positive. Case presentation A 37-year-old Japanese man was referred to our department for diagnosis and management of submandibular swelling. He was unaware that he was HIV-positive at the initial visit. Here, we describe our diagnostic approach, in which we used hematological and immunological investigations, biopsy, fluorescence-activated cell sorting and fluorescence in situ hybridization to confirm the diagnosis of HIV-associated BL. The patient has no risk factors for HIV infection, and the source of infection remains unclear. Conclusions In this case, submandibular swelling was the first clinical sign of pathology and the patient’s HIV-positive status only became evident later. It is highly likely that BL was triggered by HIV infection. PMID:24370065

  10. Prevalence and Correlates of HIV-Associated Neurocognitive Disorders (HAND) in Northwestern Nigeria

    PubMed Central

    Yakasai, Ahmad M.; Gudaji, Mustafa I.; Muhammad, Hamza; Ibrahim, Aliyu; Owolabi, Lukman F.; Ibrahim, Daiyabu A.; Babashani, Musa; Mijinyawa, Muhammad S.; Borodo, Musa M.; Ogun, Abayomi S.; Habib, Abdulrazaq G.

    2015-01-01

    HIV-associated Neurocognitive Disorders (HAND) are common among HIV-positive individuals. This study explored the prevalence and correlates of HAND in Nigeria. 80 HIV-positive and 40 HIV-negative adults selected from Aminu Kano Teaching Hospital (AKTH) received comprehensive evaluations. A multidomain neuropsychological test (MDNPT) battery assessing 7 domains was administered to the participants and their performance was combined with measures of functional status to classify impairments into various grades of HAND. Univariate and multivariate analyses were performed to identify correlates of symptomatic HAND. Among the HIV-positive individuals, 50% were highly active antiretroviral therapy-experienced (HAART+) and 50% were highly active antiretroviral therapy naive (HAART−). Symptomatic HAND was found among 40% of the HAART− individuals and 30% of the HAART+ individuals. Respective prevalence of HIV-associated dementia (HAD) was 23% and 5%, respectively (p = 0.0002). In a binary logistic regression model, only fewer years of education independently predicted symptomatic HAND [Odds Ratio (OR) = 1.2, 95% confidence interval (CI) = 1.04–1.44, p = 0.016]. The prevalence of HAND in Nigeria is high with HAD being commoner among HAART− patients. Provision of HAART and strict monitoring of patients at risk of HAND are needed to scale down the burden of the disease. PMID:26347017

  11. Prospective Memory in HIV-associated Neurocognitive Disorders (HAND): The Neuropsychological Dynamics of Time Monitoring

    PubMed Central

    Doyle, Katie L.; Loft, Shayne; Morgan, Erin E.; Weber, Erica; Cushman, Clint; Johnston, Elaine; Grant, Igor; Woods, Steven Paul

    2013-01-01

    Strategic monitoring during a delay interval is theorized to be an essential feature of time-based prospective memory (TB PM), the cognitive architecture of which is thought to rely heavily on frontostriatal systems and executive functions. This hypothesis was examined in 55 individuals with HIV-associated neurocognitive disorders (HAND) and 108 seronegative comparison participants who were administered the Memory for Intentions Screening Test (MIST), during which time monitoring (clock checking) behavior was measured. Results revealed a significant interaction between HAND group and the frequency of clock checking, in which individuals with HAND monitored checked the clock significantly less often than the comparison group across the TB PM retention intervals of the MIST. Subsequent analyses in the HAND sample revealed that the frequency of clocking checking was positively related to overall TB performance, as well as to standard clinical measures of retrospective memory and verbal fluency. These findings add support to a growing body of research elucidating TB PM’s reliance on strategic monitoring processes dependent upon intact frontostriatal systems. HIV-associated TB strategic time monitoring deficits may manifest in poorer functioning outcomes, including medication non-adherence and dependence in activities of daily living. Future research is needed to further delineate the cognitive mechanisms underlying strategic time monitoring in order to advise rehabilitation strategies for reducing HAND related TB PM deficits. PMID:23465043

  12. Characteristics and survival for HIV-associated multicentric Castleman disease in Malawi

    PubMed Central

    Gopal, Satish; Liomba, N George; Montgomery, Nathan D; Moses, Agnes; Kaimila, Bongani; Nyasosela, Richard; Chikasema, Maria; Dhungel, Bal M; Kampani, Coxcilly; Sanders, Marcia K; Krysiak, Robert; Dittmer, Dirk P; Fedoriw, Yuri

    2015-01-01

    Introduction Clinical reports of multicentric Castleman disease (MCD) from sub-Saharan Africa (SSA) are scarce despite high prevalence of HIV and Kaposi sarcoma-associated herpesvirus (KSHV). Our objective is to describe characteristics and survival for HIV-associated MCD patients in Malawi. To our knowledge, this is the first HIV-associated MCD case series from the region. Methods We describe HIV-positive patients with MCD in Lilongwe, and compare them to HIV-associated lymph node Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) patients treated at our centre. All patients were enrolled into a prospective longitudinal cohort study at a national teaching hospital and cancer referral centre serving half of Malawi's 16 million people. We included adult patients≥18 years of age with HIV-associated MCD (n=6), lymph node KS (n=5) or NHL (n=31) enrolled between 1 June 2013 and 31 January 2015. Results and discussion MCD patients had a median age of 42.4 years (range 37.2–51.8). All had diffuse lymphadenopathy and five had hepatosplenomegaly. Concurrent KS was present for one MCD patient, and four had performance status ≥3. MCD patients had lower median haemoglobin (6.4 g/dL, range 3.6–9.3) than KS (11.0 g/dL, range 9.1–12.0, p=0.011) or NHL (11.2 g/dL, range 4.5–15.1, p=0.0007). Median serum albumin was also lower for MCD (2.1 g/dL, range 1.7–3.2) than KS (3.7 g/dL, range 3.2–3.9, p=0.013) or NHL (3.4 g/dL, range 1.8–4.8, p=0.003). All six MCD patients were on antiretroviral therapy (ART) with median CD4 count 208 cells/µL (range 108–1146), and all with HIV RNA <400 copies/mL. Most KS and NHL patients were also on ART, although ART duration was longer for MCD (56.4 months, range 18.2–105.3) than KS (14.2 months, range 6.8–21.9, p=0.039) or NHL (13.8 months, range 0.2–98.8, p=0.017). Survival was poorer for MCD patients than lymph node KS or NHL. Conclusions HIV-associated MCD occurs in Malawi, is diagnosed late and is associated with high

  13. Endolymphatic sac involvement in bacterial meningitis.

    PubMed

    Møller, Martin Nue; Brandt, Christian; Østergaard, Christian; Caye-Thomasen, Per

    2015-04-01

    The commonest sequelae of bacterial meningitis are related to the inner ear. Little is known about the inner ear immune defense. Evidence suggests that the endolymphatic sac provides some protection against infection. A potential involvement of the endolymphatic sac in bacterial meningitis is largely unaccounted for, and thus the object of the present study. A well-established adult rat model of Streptococcus pneumoniae meningitis was employed. Thirty adult rats were inoculated intrathecally with Streptococcus pneumoniae and received no additional treatment. Six rats were sham-inoculated. The rats were killed when reaching terminal illness or on day 7, followed by light microscopy preparation and PAS-Alcian blue staining. The endolymphatic sac was examined for bacterial invasion and leukocyte infiltration. Neither bacteria nor leukocytes infiltrated the endolymphatic sac during the first days. Bacteria invaded the inner ear through the cochlear aquaduct. On days 5-6, the bacteria invaded the endolymphatic sac through the endolymphatic duct subsequent to invasion of the vestibular endolymphatic compartment. No evidence of direct bacterial invasion of the sac through the meninges was found. Leukocyte infiltration of the sac occurred prior to bacterial invasion. During meningitis, bacteria do not invade the endolymphatic sac through the dura, but solely through the endolymphatic duct, following the invasion of the vestibular system. Leukocyte infiltration of the sac occurs prior to, as well as concurrent with bacterial invasion. The findings support the endolymphatic sac as part of an innate immune defense system protecting the inner ear from infection. PMID:24452771

  14. [A case of recurrent aseptic meningitis induced by ergot agents].

    PubMed

    Ogawa, Tomoko; Tagawa, Asako; Hashimoto, Ritsuo; Kato, Hiroyuki

    2015-01-01

    We describe the case of a 29-year-old woman with recurrent aseptic meningitis that was caused by ergot agents. She miscarried at age 27, and the uterus constrictor methylergometrine was prescribed. Three days later, she developed aseptic meningitis and was hospitalized. Two years later, she again developed aseptic meningitis the day after she took ergotamine tartrate. In both events, her symptoms improved rapidly when the medication was stopped. The drug-induced lymphocyte stimulation test for methylergometrine yielded a value of 180%. Drug-induced meningitis is a rare form of recurrent aseptic meningitis. Many studies have reported cases of meningitis caused by non-steroidal anti-inflammatory drugs, but many other drugs can induce aseptic meningitis. To the best of our knowledge, this is the first case of aseptic meningitis induced by ergot agents. PMID:26103816

  15. Risk of Bacterial Meningitis in Children with Cochlear Implants

    MedlinePlus

    ... Information For... Media Policy Makers Risk of Bacterial Meningitis in Children with Cochlear Implants Language: English Español ( ... Compartir 2002 Study of the Risk of Bacterial Meningitis in Children with Cochlear Implants Many people have ...

  16. Evaluation and Treatment of Chronic Meningitis

    PubMed Central

    Zunt, Joseph R.

    2014-01-01

    Chronic meningitis is defined as an inflammatory cerebrospinal fluid (CSF) profile that persists for at least 1 month. The presentation often includes headache, nausea, vomiting, cranial neuropathies, symptoms of elevated intracranial pressure, or focal neurologic deficits. The most common etiologies of chronic meningitis fall into 3 broad categories: infectious, autoimmune, and neoplastic. Evaluation of the patient with suspected chronic meningitis should include a detailed history and physical examination as well as repeated CSF diagnostics, serologic studies, and biopsy of the brain or other abnormal tissue (eg, lymph node or lung), when indicated. Early identification of the etiology and rapid treatment are crucial for improving morbidity and mortality, but potential infectious and neoplastic conditions should be excluded prior to empirically starting steroids or immunosuppressive medications. PMID:25360204

  17. Postsurgical Pantoea calida meningitis: a case report

    PubMed Central

    2014-01-01

    Introduction Pantoea calida, a recently described environmental Enterobacteriaceae organism, has not yet been associated with human infection. Case presentation We report a case of postoperative meningitis caused by P. calida. After pituitary adenoma resection, a 52-year-old Caucasian woman developed febrile meningitis confirmed by cerebrospinal fluid analysis. P. calida was grown in pure culture from this fluid and was firmly identified with partial rpoB gene sequencing. She was cured by a 14-day course of meropenem. Conclusions P. calida must be added to the list of opportunistic Enterobacteriaceae pathogens responsible for postsurgical meningitis. It is easily identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PMID:24934580

  18. Meningitis after cochlear implantation in Mondini malformation.

    PubMed

    Page, E L; Eby, T L

    1997-01-01

    Although the potential for CSF leakage and subsequent meningitis after cochlear implantation in the malformed cochlea has been recognized, this complication has not been previously reported. We report a case of CSF otorhinorrhea and meningitis after minor head trauma developing 2 years after cochlear implantation in a child with Mondini malformation. Leakage of CSF was identified from the cochleostomy around the electrode of the implant, and this leak was sealed with a temporalis fascia and muscle plug. Although this complication appears to be rare, care must be taken to seal the cochleostomy in children with inner ear malformations at the initial surgery, and any episode of meningitis after surgery must be thoroughly investigated to rule out CSF leakage from the labyrinth. PMID:9018266

  19. [Purulent meningitis, caused by Corynebacterium xerosis, after spinal anesthesia].

    PubMed

    Vukmirovits, G; Todorova, R; Arányi, Z; Káli, G

    1991-12-30

    A previously healthy 25 year old sportsman is reported who developed Corynebacterium xerosis meningitis with coma and seizures after spinal anaesthesia. The adequate therapy (dexamethason, penicillin, ampicillin, mannitol, intensive care, hyperventillation) resulted in a complete recovery. To the authors' knowledge this is the first case of Corynebacterium xerosis meningitis and the first bacterial meningitis reported after spinal anaesthesia in Hungary. PMID:1766661

  20. Meningitis-Retention Syndrome as a Presentation of West Nile Virus Meningitis

    PubMed Central

    Laengvejkal, Pavis; Argueta, Erwin; Limsuwat, Chok; Nugent, Kenneth

    2013-01-01

    A 26-year-old previously healthy man presented with fever, urinary retention, nuchal rigidity, and hyperreflexia but with a clear sensorium. His initial spinal fluid results were consistent with aseptic meningitis from West Nile virus infection, and this was confirmed by serological studies on blood and cerebrospinal fluid. Computed tomography and magnetic resonance imaging studies were unremarkable. He received supportive care and urinary catheterization to prevent bladder injury from overdistension. He was discharged home without recurrence of urinary retention after five days of hospitalization. Therefore, this case report describes the first case of West Nile virus meningitis in a patient with the meningitis-retention syndrome. PMID:23983716

  1. Asymptomatic (Subclinical) Meningitis in One of Premature Triplets with Simultaneous Enteroviral Meningitis: A Case Report

    PubMed Central

    Gupta, Ashish; Tolan, Robert W.

    2011-01-01

    Most enterovirus infection in the neonate and young infant is asymptomatic, but serious disease may occur, especially if acquired perinatally. We report the first case, to our knowledge, of asymptomatic enterovirus aseptic meningitis, and of concurrent enterovirus aseptic meningitis in premature triplets. Ten-week-old, 31-week-estimated gestational age premature triplet boys were diagnosed with enterovirus aseptic meningitis on the same day. Two of the triplets developed symptoms on the day of admission, while the third remained symptom free throughout the infection. All three recovered completely and are healthy more than a decade later. PMID:23946897

  2. Meningitis-retention Syndrome; A Case Report.

    PubMed

    Ishii, Gen; Hata, Kenichi; Aoki, Soichiro; Suzuki, Masayasu; Kimura, Takahiro; Egawa, Shin

    2016-05-01

    We report a case of meningitis-retention syndrome followed by urodynamic tests. A 48-year-old man was admitted to the hospital for an undiagnosed fever with headache and urinary retention. Aseptic meningitis was suspected according to cerebrospinal fluid analyses, and urodynamic test showed an underactive detrusor, leading to inadequate contraction of the bladder on voiding in spite of a normal sensation during bladder filling. Clean intermittent self-catheterization was required temporarily, but normal urinary voiding without the need for medication was restored in 2 weeks after discharge from the hospital, when urodynamic tests showed normal contractility of the bladder during voiding. PMID:27175342

  3. Meningitis-retention Syndrome; A Case Report

    PubMed Central

    Ishii, Gen; Hata, Kenichi; Aoki, Soichiro; Suzuki, Masayasu; Kimura, Takahiro; Egawa, Shin

    2016-01-01

    We report a case of meningitis-retention syndrome followed by urodynamic tests. A 48-year-old man was admitted to the hospital for an undiagnosed fever with headache and urinary retention. Aseptic meningitis was suspected according to cerebrospinal fluid analyses, and urodynamic test showed an underactive detrusor, leading to inadequate contraction of the bladder on voiding in spite of a normal sensation during bladder filling. Clean intermittent self-catheterization was required temporarily, but normal urinary voiding without the need for medication was restored in 2 weeks after discharge from the hospital, when urodynamic tests showed normal contractility of the bladder during voiding. PMID:27175342

  4. CSF cytology versus immunocytochemistry in meningeal carcinomatosis.

    PubMed Central

    Boogerd, W; Vroom, T M; van Heerde, P; Brutel de la Rivière, G; Peterse, J L; van der Sande, J J

    1988-01-01

    CSF immunocytochemistry with monoclonal antibodies was compared with conventional cytology to determine its sensitivity in detecting malignant cells in patients with meningeal carcinomatosis. One hundred and eighteen samples were investigated. Cytology was tumour positive in 83 samples and immunocytochemistry in 85. Dissimilar results between the two diagnostic methods were noted in 12 specimens, invariably occurring in samples with a low cell count and obtained from treated patients. Combined use of the two methods led to a 9% increase of sensitivity in detecting malignant cells compared with cytology alone. It is concluded that immunocytochemistry is of minor help in the problem of false-negative cytology in meningeal carcinomatosis. PMID:2832546

  5. FDG PET in Intracranial Carcinomatous Meningitis.

    PubMed

    Heimburger, Céline; Bund, Caroline; Namer, Izzie Jacques

    2016-01-01

    A 63-year-old white man, diagnosed with pT3N2 squamous cell lung carcinoma, underwent right upper lobectomy with adjuvant radiochemotherapy. After a partial epileptic seizure, MRI revealed a solitary right frontal metastasis that was treated with surgical resection followed by stereotaxic radiotherapy. Three months later, the patient presented weight loss, weakness, and headache. He underwent a whole-body FDG PET/CT for restaging. It showed intense FDG uptakes on the brain periphery corresponding to nodular meningeal contrast enhancement on MRI leading to the diagnosis of carcinomatous meningitis, despite negative cerebrospinal fluid cytology. PMID:26447391

  6. [Bacterial meningitis in patients with sepsis syndrome].

    PubMed

    Olejnik, Z; Janeczko, J; Lipowski, D; Przyjałkowski, W; Strzelecki, R; Romanowska, B; Pogorzelska, E

    1994-01-01

    The authors discuss problems connected with diagnosis, management and treatment of bacterial meningitis among patients with the sepsis syndrome. Considering secondary organ changes bacterial meningitis belongs to the severest one and as a life-threathing sequel of sepsis demands immediate use of proper casual treatment. The authors show the therapeutic difficulties in this group of patients particularly when the etiological organism is unknown. They discuss this problems and present their own schemes of tretment. They indicate the value of passive immunotherapy and surgical removal of the primary source of infection. They emphasize final result depends on secondary organ changes, age, immunity of patient and the kind of etiological agent. PMID:7938619

  7. Depression and Apathy Among People Living with HIV: Implications for Treatment of HIV Associated Neurocognitive Disorders

    PubMed Central

    Whitehead, Nicole E.; Burrell, Larry E.; Dotson, Vonetta M.; Cook, Robert L.; Malloy, Paul; Devlin, Kathryn; Cohen, Ronald A.

    2015-01-01

    Depression and apathy are common among people living with HIV (PLWH). However, in PLWH, it is unclear whether depression and apathy are distinct conditions, which contribute to different patterns of disruption to cognitive processing and brain systems. Understanding these conditions may enable the development of prognostic indicators for HIV associated neurocognitive disorders (HAND). The present study examined substance use behavior and cognitive deficits, associated with depression and apathy, in 120 PLWH, using hierarchical regression analyses. Higher levels of depression were associated with a history of alcohol dependence and greater deficits in processing speed, motor and global cognitive functioning. Higher levels of apathy were associated with a history of cocaine dependence. It is recommended that PLWH get screened appropriately for apathy and depression, in order to receive the appropriate treatment, considering the comorbidities associated with each condition. Future research should examine the neurological correlates of apathy and depression in PLWH. PMID:25533921

  8. HIV-associated risk behaviour among drug users at drug rehabilitation centres.

    PubMed

    Fauziah, M N; Anita, S; Sha'ari, B N; Rosli, B I

    2003-06-01

    A cross-sectional study to determine the prevalence of Human Immunodeficiency Virus (HIV) and HIV-associated risk behavior was conducted in February 1998 among 6,324 drug users in 26 drug rehabilitation centres in Malaysia. The majority of respondents were males (97.3%) and Malays (77.8%), administered drugs intravenously (64.6%) and of these 65.4% shared needles. About 78.1% had sexual exposure, of which 55.1% had sex with girl friends, 31.3% with prostitutes and 4.6% with male partners. The HIV prevalence rate in the group was 12.1% and significantly high among injecting drug users (IDU); those sharing needles; those who started addiction at a young age (10-15 years); those who had sexual exposures and had sex with prostitutes. PMID:14569748

  9. Cornoid Lamella-Like Structures in HIV-Associated Epidermodysplasia Verruciformis: A Unique Histopathologic Finding

    PubMed Central

    Champagne, Courtney; Moore, Lindsey; Reule, Ross; Dyer, Jonathan A.; Rady, Peter; Tyring, Stephen K.

    2015-01-01

    Abstract: Epidermodysplasia verruciformis (EV) is an uncommon inherited skin condition with increased vulnerability to widespread infection by certain human papillomavirus types, resulting in extensive verruca plana-like papules coalescing to large confluent plaques. Since the AIDS epidemic starting in the 1980s, an acquired type of EV has been described in patients infected with human immunodeficiency virus. The histopathologic features of EV consist of papillated epidermal hyperplasia with hypergranulosis and a distinct bluish-gray color in the large human papillomavirus-infected keratinocytes in the stratum granulosum. The authors present a case of HIV-associated EV with a unique histopathologic finding of multiple cornoid lamella-like structures. To the authors' knowledge, this finding has not been previously described in the literature. PMID:26588337

  10. Developing neuroprotective strategies for treatment of HIV-associated neurocognitive dysfunction

    PubMed Central

    Rumbaugh, Jeffrey A; Steiner, Joseph; Sacktor, Ned; Nath, Avindra

    2009-01-01

    Important advances have been made in recent years in identifying the molecular mechanisms of HIV neuropathogenesis. Defining the pathways leading to HIV dementia has created an opportunity to therapeutically target many steps in the pathogenic process. HIV itself rarely infects neurons, but significant neuronal damage is caused both by viral proteins and by inflammatory mediators produced by the host in response to infection. Highly active antiretroviral therapy (HAART) does not target these mediators of neuronal damage, and the prevalence of HIV-associated neurocognitive dysfunction has actually been rising in the post-HAART era. This review will briefly summarize our current understanding of the mechanisms of HIV-induced neurological disease, and emphasize translation of this basic research into potential clinical applications. PMID:19774095

  11. Diagnosing and treating HIV-associated sensory neuropathy: a global perspective.

    PubMed

    Cherry, Catherine L; Wadley, Antonia L; Kamerman, Peter R

    2016-04-01

    HIV-associated sensory neuropathy (HIV-SN) is a common complication of HIV and remains highly prevalent even with modern HIV management strategies, causing debilitating pain in millions globally. We review HIV-SN diagnosis and management. We suggest most HIV-SN cases are easily recognized using clinical screening tools, with physician assessment and/or specialized testing prioritized for atypical cases. Management aims to prevent further nerve damage and optimize symptom control. Symptom relief is difficult and rarely complete, with a lack of proven pharmacological strategies. Work is needed to clarify optimal use of available medications. This includes understanding the marked placebo effect in HIV-SN analgesic trials and exploring 'responder phenotypes'. Limited data support nondrug strategies including hypnosis, meditation, psychology, physical activity and a positive therapeutic relationship. PMID:26988147

  12. Novel Approaches to Targeting Visceral and Hepatic Adiposities in HIV-Associated Lipodystrophy.

    PubMed

    Tien, Phyllis C

    2015-12-01

    Visceral and hepatic adiposities have been associated with both cardiovascular and liver disease and are of concern in HIV-infected persons in the modern era of combination antiretroviral therapy (ART). The development of therapeutic targets to reduce visceral and hepatic adiposities in HIV-infected persons has been slow, because of early reports that attributed the excess adiposity to specific antiretroviral drugs. Visceral adiposity was initially thought to occur as part of a protease inhibitor-induced "HIV-associated lipodystrophy syndrome." Subsequent studies show that visceral adiposity is likely a result of effective ART, recovery of health, and the normal aging process. Visceral adiposity is an established risk factor for hepatic adiposity. Identifying drug targets for non-alcoholic fatty liver disease is under active investigation. The present review summarizes the recent literature on the pathogenesis of visceral and hepatic adiposities in HIV-infected persons, current therapeutic strategies, and novel interventions in HIV-infected and uninfected persons. PMID:26493063

  13. Crofelemer, a novel antisecretory agent approved for the treatment of HIV-associated diarrhea.

    PubMed

    Yeo, Q M; Crutchley, R; Cottreau, J; Tucker, A; Garey, K W

    2013-04-01

    Secretory diarrhea has a significant impact on morbidity and mortality worldwide and may be a predominant or minor component of pathogenesis in diarrhea of various etiologies. Crofelemer is a first-in-class antidiarrheal medication with unique inhibitory mechanisms at both the cystic fibrosis transmembrane conductance regulator and the calcium-activated chloride channels which are responsible for chloride secretion and subsequent luminal hydration. The efficacy of crofelemer has been investigated in patients with HIV-associated diarrhea, diarrhea of various infectious etiologies, as well as diarrhea-predominant irritable bowel syndrome. Crofelemer was approved by the FDA in December 2012 to treat diarrhea in HIV/AIDS patients on antiretroviral therapy. Crofelemer is not absorbed in the body and well-tolerated in small trials performed to date although long-term safety data is lacking. Crofelemer may be an important addition to the currently available drugs for the management of secretory diarrhea. PMID:23616951

  14. Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications

    PubMed Central

    Tsiodras, Sotirios; Mantzoros, Christos

    2006-01-01

    Leptin and adiponectin represent two newly discovered adipose tissue derived hormones with important roles in energy homeostasis and insulin resistance. Their interrelations with the manifestations of the HIV associated metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is reviewed. A synopsis of published studies is presented and the potential role of leptin and adiponectin is discussed. We have described an association of the HIV metabolic syndrome with a state of reduced insulin sensitivity due to adiponectin deficiency. The metabolic syndrome is also accompanied by leptin deficiency in lipoatrophic subjects and possibly by a leptin resistance state in lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner similar to other leptin deficiency states may assist in the future management of such patients. PMID:17183414

  15. Loss of subcutaneous adipose tissue in HIV-associated lipodystrophy is not due to accelerated apoptosis.

    PubMed

    Mynarcik, Dennis; Wei, Lin-Xiang; Komaroff, Eugene; Ferris, Robert; McNurlan, Margaret; Gelato, Marie

    2005-01-01

    HIV-associated lipodystrophy is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue. The present study examined the rate of apoptosis in subcutaneous adipose tissue with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders. Individuals with HIV lipodystrophy were compared with HIV-infected subjects without lipodystrophy and subjects without HIV disease. Although apoptosis was observed in subjects with HIV lipodystrophy, there was no difference in the frequency of individuals with apoptosis among those with HIV lipodystrophy (10/22), those with HIV but no lipodystrophy (13/25), and subjects without HIV disease (13/27). PMID:15608525

  16. HIV-Associated Histoplasmosis Early Mortality and Incidence Trends: From Neglect to Priority

    PubMed Central

    Adenis, Antoine; Nacher, Mathieu; Hanf, Matthieu; Vantilcke, Vincent; Boukhari, Rachida; Blachet, Denis; Demar, Magalie; Aznar, Christine; Carme, Bernard; Couppie, Pierre

    2014-01-01

    Background Histoplasmosis is an endemic fungal infection in French Guiana. It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths. Diagnosis is difficult, but in the past 2 decades, it has improved in this French overseas territory which offers an interesting model of Amazonian pathogen ecology. The objectives of the present study were to describe the temporal trends of incidence and mortality indicators for HIV-associated histoplasmosis in French Guiana. Methods A retrospective study was conducted to describe early mortality rates observed in persons diagnosed with incident cases of HIV-associated Histoplasma capsulatum var. capsulatum histoplasmosis admitted in one of the three main hospitals in French Guiana between 1992 and 2011. Early mortality was defined by death occurring within 30 days after antifungal treatment initiation. Data were collected on standardized case report forms and analysed using standard statistical methods. Results There were 124 deaths (45.3%) and 46 early deaths (16.8%) among 274 patients. Three time periods of particular interest were identified: 1992–1997, 1998–2004 and 2005–2011. The two main temporal trends were: the proportion of early deaths among annual incident histoplasmosis cases significantly declined four fold (χ2, p<0.0001) and the number of annual incident histoplasmosis cases increased three fold between 1992–1997 and 1998–2004, and subsequently stabilized. Conclusion From an occasional exotic diagnosis, AIDS-related histoplasmosis became the top AIDS-defining event in French Guiana. This was accompanied by a spectacular decrease of early mortality related to histoplasmosis, consistent with North American reference center mortality rates. The present example testifies that rapid progress could be at reach if awareness increases and leads to clinical and laboratory capacity building in order to diagnose and treat this curable disease. PMID:25144374

  17. Predictors of mortality in HIV-associated hospitalizations in Portugal: a hierarchical survival model

    PubMed Central

    Dias, Sara S; Andreozzi, Valeska; Martins, Maria O; Torgal, Jorge

    2009-01-01

    Background The beneficial effects of highly active antiretroviral therapy, increasing survival and the prevention of AIDS defining illness development are well established. However, the annual Portuguese hospital mortality is still higher than expected. It is crucial to understand the hospitalization behaviour to better allocate resources. This study investigates the predictors of mortality in HIV associated hospitalizations in Portugal through a hierarchical survival model. Methods The study population consists of 12,078 adult discharges from patients with HIV infection diagnosis attended at Portuguese hospitals from 2005–2007 that were registered on the diagnosis-related groups' database. We used discharge and hospital level variables to develop a hierarchical model. The discharge level variables were: age, gender, type of admission, type of diagnoses-related group, related HIV complication, the region of the patient's residence, the number of diagnoses and procedures, the Euclidean distance from hospital to the centroid of the patient's ward, and if patient lived in the hospital's catchment area. The hospital characteristics include size and hospital classification according to the National Health System. Kaplan-Meier plots were used to examine differences in survival curves. Cox proportional hazard models with frailty were applied to identify independent predictors of hospital mortality and to calculate hazard ratios (HR). Results The Cox proportional model with frailty showed that male gender, older patient, great number of diagnoses and pneumonia increased the hazard of HIV related hospital mortality. On the other hand tuberculosis was associated with a reduced risk of death. Central hospital discharge also presents less risk of mortality. The frailty variance was small but statistically significant, indicating hazard ratio heterogeneity among hospitals that varied between 0.67 and 1.34, and resulted in two hospitals with HR different from the average risk

  18. Does the informal caregiver notice HIV associated mild cognitive impairment in people living with HIV?

    PubMed

    Murray, Kenneth J; Cummins, Denise; Batterham, Marijka; Trotter, Garry; Healey, Loretta; O'Connor, Catherine C

    2016-01-01

    HIV associated minor neurocognitive disorder (MND) may be difficult to identify as key signs and symptoms (S & S) may be due to other clinical conditions. Using a self-assessment booklet "HIV and associated MND" we recruited 123 people living with HIV (PLHIV) from three sites: two hospital HIV clinics and a sexual health clinic in Sydney, Australia. Patients may down play S & S. Caregivers may notice subtle changes. By including caregivers, we aimed to find whether the caregivers noticed S & S undetected by the PLHIV. This is a sub-study of a prospective observational multi-site study aimed to validate the usefulness of a patient self-assessment tool (HIV-associated MND booklet). Using the booklet, participants and their caregivers subsequently identified S & S of MND. Sixty-four per cent (79) did not nominate a caregiver to be contacted. Participants from 2 sites 44 (36%) nominated caregivers to be contacted. Twenty-five caregivers identified more than four S & S of MND. S & S reported most by caregivers related to participants being more tired at the end of the day (76%). Participants agreed (77%). Participants also reported that they found it more difficult to remember things such as taking medications or attending medical appointments (67%). The most agreed on symptom was the requirement for increased concentration to get the same things done (Kappa P 0.599 <0.001 and McNemar 0.289). For each question at least one caregiver identified a symptom when the PLHIV did not. Caregivers were more likely than participants to report irritability and communication difficulties. It is important to include caregivers when investigating PLHIV for MND, as caregivers may validate the experience of the patient, and may also be uniquely placed to identify S & S not otherwise identified. PMID:26489931

  19. Detecting altered connectivity patterns in HIV associated neurocognitive impairment using mutual connectivity analysis

    NASA Astrophysics Data System (ADS)

    Abidin, Anas Zainul; D'Souza, Adora M.; Nagarajan, Mahesh B.; Wismüller, Axel

    2016-03-01

    The use of functional Magnetic Resonance Imaging (fMRI) has provided interesting insights into our understanding of the brain. In clinical setups these scans have been used to detect and study changes in the brain network properties in various neurological disorders. A large percentage of subjects infected with HIV present cognitive deficits, which are known as HIV associated neurocognitive disorder (HAND). In this study we propose to use our novel technique named Mutual Connectivity Analysis (MCA) to detect differences in brain networks in subjects with and without HIV infection. Resting state functional MRI scans acquired from 10 subjects (5 HIV+ and 5 HIV-) were subject to standard preprocessing routines. Subsequently, the average time-series for each brain region of the Automated Anatomic Labeling (AAL) atlas are extracted and used with the MCA framework to obtain a graph characterizing the interactions between them. The network graphs obtained for different subjects are then compared using Network-Based Statistics (NBS), which is an approach to detect differences between graphs edges while controlling for the family-wise error rate when mass univariate testing is performed. Applying this approach on the graphs obtained yields a single network encompassing 42 nodes and 65 edges, which is significantly different between the two subject groups. Specifically connections to the regions in and around the basal ganglia are significantly decreased. Also some nodes corresponding to the posterior cingulate cortex are affected. These results are inline with our current understanding of pathophysiological mechanisms of HIV associated neurocognitive disease (HAND) and other HIV based fMRI connectivity studies. Hence, we illustrate the applicability of our novel approach with network-based statistics in a clinical case-control study to detect differences connectivity patterns.

  20. Central and peripheral markers of neurodegeneration and monocyte activation in HIV-associated neurocognitive disorders.

    PubMed

    McGuire, Jennifer L; Gill, Alexander J; Douglas, Steven D; Kolson, Dennis L

    2015-08-01

    HIV-associated neurocognitive disorders (HAND) affect up to 50 % of HIV-infected adults, independently predict HIV morbidity/mortality, and are associated with neuronal damage and monocyte activation. Cerebrospinal fluid (CSF) neurofilament subunits (NFL, pNFH) are sensitive surrogate markers of neuronal damage in several neurodegenerative diseases. In HIV, CSF NFL is elevated in individuals with and without cognitive impairment, suggesting early/persistent neuronal injury during HIV infection. Although individuals with severe cognitive impairment (HIV-associated dementia (HAD)) express higher CSF NFL levels than cognitively normal HIV-infected individuals, the relationships between severity of cognitive impairment, monocyte activation, neurofilament expression, and systemic infection are unclear. We performed a retrospective cross-sectional study of 48 HIV-infected adults with varying levels of cognitive impairment, not receiving antiretroviral therapy (ART), enrolled in the CNS Anti-Retroviral Therapy Effects Research (CHARTER) study. We quantified NFL, pNFH, and monocyte activation markers (sCD14/sCD163) in paired CSF/plasma samples. By examining subjects off ART, these correlations are not confounded by possible effects of ART on inflammation and neurodegeneration. We found that CSF NFL levels were elevated in individuals with HAD compared to cognitively normal or mildly impaired individuals with CD4+ T-lymphocyte nadirs ≤200. In addition, CSF NFL levels were significantly positively correlated to plasma HIV-1 RNA viral load and negatively correlated to plasma CD4+ T-lymphocyte count, suggesting a link between neuronal injury and systemic HIV infection. Finally, CSF NFL was significantly positively correlated with CSF pNFH, sCD163, and sCD14, demonstrating that monocyte activation within the CNS compartment is directly associated with neuronal injury at all stages of HAND. PMID:25776526

  1. Lymphocyte protein synthesis is increased with the progression of HIV-associated disease to AIDS.

    PubMed

    Caso, G; Garlick, P J; Gelato, M C; McNurlan, M A

    2001-12-01

    HIV infection has been shown to affect lymphocyte function and to reduce lymphocyte responsiveness in vitro to mitogenic stimulation, but little is known about lymphocyte metabolism in vivo and how it is affected during the course of the disease. This study investigated the metabolic activity of lymphocytes in vivo through the progression of HIV-associated disease. Lymphocyte protein synthesis was measured with L-[(2)H(5)]phenylalanine (45 mg/kg body weight) in healthy volunteers (n=7), in patients who were HIV-positive (n=7) but asymptomatic, and in patients with AIDS (n=8). The rates of lymphocyte protein synthesis [expressed as a percentage of lymphocyte protein, i.e. fractional synthesis rate (FSR)] were not altered in HIV-positive patients compared with healthy controls (7.9+/-1.28% and 9.1+/-0.53%/day respectively), but were significantly elevated in AIDS patients (14.0+/-1.16%/day; P<0.05). The serum concentration of the cytokine tumour necrosis factor-alpha (TNF-alpha) increased with the progression of the disease, and TNF-alpha levels were significantly higher in AIDS patients (6.81+/-0.88 ng/l) than in healthy controls (3.09+/-0.27 ng/l; P<0.05). Lymphocyte protein FSR was positively correlated with serum TNF-alpha concentration (r=0.55, P=0.009) and negatively correlated with CD4(+) lymphocyte count (r=-0.70, P=0.004). The elevation of lymphocyte protein synthesis in AIDS patients suggests a higher rate of turnover of lymphocytes. This may be associated with a generalized activation of the immune system, which is also reflected by the elevated serum TNF-alpha concentration in the late stages of HIV-associated disease. PMID:11724643

  2. Meningococcal Meningitis Surveillance in the African Meningitis Belt, 2004–2013

    PubMed Central

    Lingani, Clément; Bergeron-Caron, Cassi; Stuart, James M.; Fernandez, Katya; Djingarey, Mamoudou H.; Ronveaux, Olivier; Schnitzler, Johannes C.; Perea, William A.

    2015-01-01

    Background. An enhanced meningitis surveillance network was established across the meningitis belt of sub-Saharan Africa in 2003 to rapidly collect, disseminate, and use district weekly data on meningitis incidence. Following 10 years’ experience with enhanced surveillance that included the introduction of a group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), in 2010, we analyzed the data on meningitis incidence and case fatality from countries reporting to the network. Methods. After de-duplication and reconciliation, data were extracted from the surveillance bulletins and the central database held by the World Health Organization Inter-country Support Team in Burkina Faso for countries reporting consistently from 2004 through 2013 (Benin, Burkina Faso, Chad, Democratic Republic of Congo, Ghana, Côte d'Ivoire, Mali, Niger, Nigeria, Togo). Results. The 10 study countries reported 341 562 suspected and confirmed cases over the 10-year study period, with a marked peak in 2009 due to a large epidemic of group A Neisseria meningitidis (NmA) meningitis. Case fatality was lowest (5.9%) during this year. A mean of 71 and 67 districts annually crossed the alert and epidemic thresholds, respectively. The incidence rate of NmA meningitis fell >10-fold, from 0.27 per 100 000 in 2004–2010 to 0.02 per 100 000 in 2011–2013 (P < .0001). Conclusions. In addition to supporting timely outbreak response, the enhanced meningitis surveillance system provides a global overview of the epidemiology of meningitis in the region, despite limitations in data quality and completeness. This study confirms a dramatic fall in NmA incidence after the introduction of PsA-TT. PMID:26553668

  3. Tuberculous meningitis in a Filipino maid.

    PubMed

    Sheu, J J; Yuan, R Y; Lu, J J; Chung, C L; Hsu, C Y

    1999-11-01

    Tuberculous meningitis, while not uncommon in Taiwan, has not been reported among foreign workers. We report the first case of tuberculous meningitis in a 37-year-old Filipino maid in Taiwan, who presented with headache, fever and vomiting. She had been well before this episode and the small screening films of the chest radiograph obtained on her arrival in Taiwan 15 months previously, and every 6 months thereafter showed no evidence of tuberculosis. The suspicion of tuberculous meningitis was delayed until disturbance of consciousness manifested and a standard chest radiograph showed a diffuse miliary pattern in both lung fields. A cerebrospinal fluid sample that was sent for a polymerase chain reaction-based assay specific for Mycobacterium tuberculosis showed a positive result. The patient recovered with sequelae of mildly incoherent speech and urinary incontinence after antituberculous medication and short-course steroid treatment. Clinicians should be aware of the possibility of tuberculous meningitis in foreign workers with complaints of fever and headache. Because high-quality chest radiographs are a prerequisite for early detection of pulmonary tuberculosis, we recommended that standard posterior-anterior chest radiographs should be obtained as part of the routine health examination for foreign workers. PMID:10705697

  4. Citrobacter koseri meningitis: another freediving risk?

    PubMed

    Pollara, Gabriele; Savy, Lloyd; Cropley, Ian; Hopkins, Susan

    2011-01-01

    We present a rare case of meningitis caused by Citrobacter koseri in an immunocompetent adult who had recently been freediving. Middle ear pressure changes from this recreational activity, and the subsequent inflammatory response, are likely to have provided this environmental organism access to the central nervous system, and thus the ability to cause clinically significant infection. PMID:20933000

  5. Streptococcus equi subsp. zooepidemicus meningitis in Peru

    PubMed Central

    Guevara, Jose M.; Tilley, Drake H.; Briceno, Jesus A.; Zunt, Joseph R.; Montano, Silvia M.

    2013-01-01

    A 59-year-old man with a history of fever, unsteadiness, hemiparesis, motor aphasia and consciousness disturbance was hospitalized for Streptococcus equi subsp. zooepidemicus meningitis. He denied contact with farm animals, but had a practice of consuming unpasteurized goats’ cheese from an uncertain source. PMID:23105024

  6. Pathogenesis and Pathophysiology of Pneumococcal Meningitis

    PubMed Central

    Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

    2011-01-01

    Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  7. Pathogenesis and pathophysiology of pneumococcal meningitis.

    PubMed

    Mook-Kanamori, Barry B; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

    2011-07-01

    Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  8. Infective Meningitis Caused by Phialemonium curvatum

    PubMed Central

    Zou, Yueli; Bu, Hui; He, Yunying; Guo, Li

    2014-01-01

    Infections caused by rarely encountered fungal pathogens have increased in recent decades. Phialemonium species are widely distributed in the environment and are also involved in human infections, affecting both immunocompromised and immunocompetent patients. The present study describes a case of meningitis caused by Phialemonium curvatum. PMID:24850352

  9. Meninges: from protective membrane to stem cell niche

    PubMed Central

    Decimo, Ilaria; Fumagalli, Guido; Berton, Valeria; Krampera, Mauro; Bifari, Francesco

    2012-01-01

    Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction. PMID:23671802

  10. Enterovirus meningitis in Brazil, 1998-2003.

    PubMed

    Dos Santos, Gina P L; Skraba, Irene; Oliveira, Denise; Lima, Ana A F; de Melo, Maria Mabel M; Kmetzsch, Claudete I; da Costa, Eliane V; da Silva, Edson E

    2006-01-01

    Acute viral infections of the central nervous system (CNS) such as acute flaccid paralysis, meningitis, and encephalitis, are responsible for a high morbidity, particularly in children. Non-Polio enteroviruses (NPEV) are known to be responsible for over 80% of viral meningitis in which the etiologic agent is identified. In the present study, we show the frequency of enterovirus meningitis in Brazil from December 1998 to December 2003. Enterovirus were isolated from 162 (15.8%), of a total of 1,022 cerebrospinal fluid (CSF) specimens analyzed. Echovirus 30 was identified in 139 of these isolates (139/162-85.2%). Other identified enteroviruses were: Coxsackievirus B5 (3.7%), Echovirus 13 (3.7%), Echovirus 18 (3%), Echovirus 6 (1.2%), Echovirus 25 (1.2%), Echovirus 1 (0.6%), and Echovirus 4 (0.6%). Patients's age ranged from 28 days to 68 years old. The most frequent symptoms were fever (77%), headache (69.5%), vomiting (71.3%), neck stiffness (41.3%), convulsion (7.1%), and diarrhea (3.7%). Although, the majority of the patients recovered without any complication or permanent squeal, five deaths occurred. Throughout the surveillance period, five viral meningitis outbreaks were confirmed: four in the Southern Brazil and one in the Northeast Brazil. Echovirus 30 was responsible for four out of the five outbreaks while Echovirus 13 caused the fifth one. Besides the outbreaks, 734 sporadic cases were also identified during the study period and 59 of these were positive for virus isolation (8%). Echovirus 30 accounted for 70% of the isolates. Our results showed that Echovirus 30 was the most prevalent etiological agent of viral meningitis in Brazil, causing both outbreaks and sporadic cases. PMID:16299728

  11. Spectrum of imaging appearances of intracranial cryptococcal infection in HIV/AIDS patients in the anti-retroviral therapy era.

    PubMed

    Offiah, Curtis E; Naseer, Aisha

    2016-01-01

    Cryptococcus neoformans infection is the most common fungal infection of the central nervous system (CNS) in advanced human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, but remains a relatively uncommon CNS infection in both the immunocompromised and immunocompetent patient population, rendering it a somewhat elusive and frequently overlooked diagnosis. The morbidity and mortality associated with CNS cryptococcal infection can be significantly reduced by early recognition of the imaging appearances by the radiologist in order to focus and expedite clinical management and treatment. The emergence and evolution of anti-retroviral therapy have also impacted significantly on the imaging appearances, morbidity, and mortality of this neuro-infection. The constellation of varied imaging appearances associated with cryptococcal CNS infection in the HIV and AIDS population in the era of highly active anti-retroviral therapy (HAART) will be presented in this review. PMID:26564776

  12. An unusual presentation of carcinomatous meningitis.

    PubMed

    Foo, Chuan T; Burrell, Louise M; Johnson, Douglas F

    2016-08-01

    A 67-year old previously well male presented with a 1 week history of confusion on a background of 3 weeks of headache. Past history included two superficial melanomas excised 5 years ago. Treatment for meningoencephalitis was commenced based on lumbar puncture (LP) and non-contrast brain magnetic resonance imaging (MRI) results. Lack of a clinical response to antibiotics resulted in a second LP and contrast brain MRI which demonstrated hydrocephalus and leptomeningeal disease. Ongoing deterioration led to a whole-body computed tomographic and spinal MRI that showed widespread metastatic disease and extensive leptomeningeal involvement of the spinal cord. The diagnosis of metastatic melanoma with carcinomatous meningitis was made based on cytological analysis of cerebrospinal fluid. He died 2 weeks later in a palliative care facility. This case illustrates that the diagnosis of carcinomatous meningitis can be difficult to make as the heterogeneous nature of its presentation often delays the diagnosis. PMID:27574561

  13. An unusual presentation of carcinomatous meningitis

    PubMed Central

    Foo, Chuan T.; Burrell, Louise M.; Johnson, Douglas F.

    2016-01-01

    A 67-year old previously well male presented with a 1 week history of confusion on a background of 3 weeks of headache. Past history included two superficial melanomas excised 5 years ago. Treatment for meningoencephalitis was commenced based on lumbar puncture (LP) and non-contrast brain magnetic resonance imaging (MRI) results. Lack of a clinical response to antibiotics resulted in a second LP and contrast brain MRI which demonstrated hydrocephalus and leptomeningeal disease. Ongoing deterioration led to a whole-body computed tomographic and spinal MRI that showed widespread metastatic disease and extensive leptomeningeal involvement of the spinal cord. The diagnosis of metastatic melanoma with carcinomatous meningitis was made based on cytological analysis of cerebrospinal fluid. He died 2 weeks later in a palliative care facility. This case illustrates that the diagnosis of carcinomatous meningitis can be difficult to make as the heterogeneous nature of its presentation often delays the diagnosis. PMID:27574561

  14. Neurosyphilis: An Unresolved Case of Meningitis

    PubMed Central

    Ahsan, Shagufta; Burrascano, Joesph

    2015-01-01

    Neurosyphilis can cause both symptomatic and asymptomatic meningitis. However the epidemiology of modern neurosyphilis is not well defined because of the paucity of population-based data. The majority of neurosyphilis cases have been reported in HIV-infected patients. Here we present a case of early neurosyphilis/symptomatic syphilitic meningitis in a non-HIV patient who presented with rash but was mistakenly treated for early latent or secondary syphilis. Syphilis presenting with a skin rash and an extremely high RPR titer could indicate CNS infection rather than simply secondary syphilis because rash is a nonspecific manifestation of disseminated infection. Given the effectiveness of penicillin therapy, why is the rate of syphilis continuing to increase? Is it due to a failure of prevention or could it be also because of failure to diagnose and treat syphilis adequately, as in this case? PMID:26075118

  15. Meningitis C vaccine (North American vaccine).

    PubMed

    Lattanzi, Maria; Del Giudice, Giuseppe

    2002-01-01

    North American Vaccine Inc (NAVI) has launched a conjugate polysaccharide vaccinefor the prevention of meningitis caused by group C meningococcal bacteria [433475]. The vaccine is based upon conjugate technology, incorporating the serogroup C polysaccharide (CPS) of all three major serogroups. Antibody-dependent, complement-mediated activity was demonstrated in mice and non-human primates, with no detectable adverse effects [277193]. Approval was filed for in the UK in January 2000 [353305]. In July 2000, Baxter received approval for NeisVac-C in the UK, and by September 2000 the vaccine was expected to be incorporated into the NHS's immunization campaign against meningitis C [381225]. NeisVac-C will initially appear labeled from NAVI; Baxter completed its acquisition of NAVI in June 2000 [375389]. Baxter estimates the worldwide global market for the vaccine at US $600 million per year [376204]. PMID:12054072

  16. Cognitive impairment in adults with good recovery after bacterial meningitis.

    PubMed

    van de Beek, Diederik; Schmand, Ben; de Gans, Jan; Weisfelt, Martijn; Vaessen, Heleen; Dankert, Jacob; Vermeulen, Marinus

    2002-10-01

    Adults without neurologic sequelae after bacterial meningitis are supposed to live without restrictions. Neuropsychological outcome was assessed in 51 adults from a prospective cohort with good recovery, defined as Glasgow Outcome Scale score 5, after pneumococcal or meningococcal meningitis. Patients who recovered well after pneumococcal meningitis showed cognitive slowness (P=.001). A cognitive disorder was found in 27% of these patients. Patients who previously had meningococcal meningitis were not significantly different from control subjects. Scores on general health and quality of life questionnaires revealed lower scores for patients with meningitis, which were related to cognitive slowing (R, -0.46 to -0.38). In conclusion, adults surviving pneumococcal meningitis were at significant risk of neuropsychological abnormalities, even if they were clinically well recovered. PMID:12232850

  17. Testing for Meningitis in Children with Bronchiolitis

    PubMed Central

    Stefanski, Michael; Williams, Ronald; McSherry, George; Geskey, Joseph

    2014-01-01

    Viral bronchiolitis accounts for almost 20% of all-cause hospitalizations of infants (ie, children younger than age 1 year). The annual incidence of fever in viral bronchiolitis has been documented at 23% to 31%. However the incidence of concurrent serious bacterial infections is low (1%–7%), with meningitis occurring in less than 1% to 2% of cases, but lumbar puncture is performed in up to 9% of viral bronchiolitis cases. To our knowledge, no study has examined clinical factors that influence a physician’s decision to perform a lumbar puncture in the setting of viral bronchiolitis. We present a retrospective, case-control study of hospitalized infants younger than one year diagnosed with viral bronchiolitis who underwent lumbar puncture as part of an evaluation for meningitis. The objective of the study was to determine clinical factors that influence a physician’s decision to perform a lumbar puncture in the setting of viral bronchiolitis. Although the presence of apnea, cyanosis, meningeal signs, positive urine culture results, and young age were factors found to be preliminarily associated with the performance of a lumbar puncture in the setting of bronchiolitis, young age was the only significant clinical factor found after multivariable regression; no other demographic, clinical, laboratory, or radiologic variables were found to be significant. PMID:25662522

  18. Host-pathogen interactions in bacterial meningitis.

    PubMed

    Doran, Kelly S; Fulde, Marcus; Gratz, Nina; Kim, Brandon J; Nau, Roland; Prasadarao, Nemani; Schubert-Unkmeir, Alexandra; Tuomanen, Elaine I; Valentin-Weigand, Peter

    2016-02-01

    Bacterial meningitis is a devastating disease occurring worldwide with up to half of the survivors left with permanent neurological sequelae. Due to intrinsic properties of the meningeal pathogens and the host responses they induce, infection can cause relatively specific lesions and clinical syndromes that result from interference with the function of the affected nervous system tissue. Pathogenesis is based on complex host-pathogen interactions, some of which are specific for certain bacteria, whereas others are shared among different pathogens. In this review, we summarize the recent progress made in understanding the molecular and cellular events involved in these interactions. We focus on selected major pathogens, Streptococcus pneumonia, S. agalactiae (Group B Streptococcus), Neisseria meningitidis, and Escherichia coli K1, and also include a neglected zoonotic pathogen, Streptococcus suis. These neuroinvasive pathogens represent common themes of host-pathogen interactions, such as colonization and invasion of mucosal barriers, survival in the blood stream, entry into the central nervous system by translocation of the blood-brain and blood-cerebrospinal fluid barrier, and induction of meningeal inflammation, affecting pia mater, the arachnoid and subarachnoid spaces. PMID:26744349

  19. Community-acquired Acinetobacter meningitis in adults.

    PubMed

    Chang, W N; Lu, C H; Huang, C R; Chuang, Y C

    2000-01-01

    Community-acquired Acinetobacter meningitis in adults is an extremely rare infection of the central nervous system (CNS). Here we report one adult case of this rare CNS infection and review the clinical data of another seven cases reported in the English language literature. In total, eight patients (six men and two women) aged between 19 and 63 years were studied. The causative pathogen in our patient was Acinetobacter baumannii; in the other reported cases they were most likely Acinetobacter Iwoffii, Acinetobacter johnsonii, Acinetobacter junii, a genomic species 3 or 6. No underlying disease was found in seven of the eight cases and six of the eight patients acquired the infections before the age of 30 years. Fever and consciousness disturbance were the most common clinical manifestations. Waterhouse-Friderichsen syndrome (WFS) was found in two cases. Unlike the Acinetobacter strains found in nosocomial infections, the strain of Acinetobacter meningitis in the community-acquired case did not show multiple antibiotic resistance. Most adult patients with community-acquired Acinetobacter meningitis can be saved by timely therapy with appropriate antibiotics before deterioration of the systemic condition and impairment of consciousness. PMID:11139162

  20. HIV-associated wasting in the HAART era: guidelines for assessment, diagnosis, and treatment.

    PubMed

    Polsky, B; Kotler, D; Steinhart, C

    2001-08-01

    Wasting (malnutrition) and lipodystrophy are the two major nutritional alterations in human immunodeficiency virus (HIV)-infected individuals. Both wasting and lipodystrophy may involve a decrease in body fat content, while wasting-but not lipodystrophy-also includes the loss of lean body mass. Lipodystrophy has made the identification of wasting increasingly more difficult. The diagnosis of wasting depends on a definition of the condition that takes into account sex and cultural differences, as well as measurements of body cell mass. Patient management involves a concurrent, comprehensive approach designed to restore lost body cell mass and weight. The authors make recommendations for defining, diagnosing, and treating HIV-associated wasting. Specific therapies include testosterone replacement, other anabolic steroids, and recombinant human growth hormone. Other adjunctive measures, such as progressive resistance exercise and cytokine modulation, may also be utilized. Expected outcomes from effective treatment include restored body cell mass, improvement in quality of life, and reduced rates of hospitalization. Future directions for research should address the need for optimal treatment strategies. PMID:11522215

  1. An Unusual Case of Anti-GBM Antibody Elevation in HIV-Associated Nephropathy

    PubMed Central

    Makary, Raafat; Poenariu, Andreea

    2014-01-01

    Introduction. The most commonly seen glomerular disease in HIV infected patients is HIV-associated nephropathy (HIVAN); however, a multitude of other nephropathies can occur in HIV infection with an almost equal cumulative frequency. We report an unusual case of a patient with clinical and histological evidence of HIVAN in which the diagnosis was initially confounded by the finding of an elevated serum anti-glomerular basement membrane (anti-GBM) antibody. Case Presentation. We present a case of a 27-year-old African American female with a history of schizophrenia, cocaine abuse, and HIV infection who upon admission to our hospital was found to have severe acute kidney injury requiring hemodialysis. Urine studies revealed nephrotic range proteinuria and a serological workup was positive for anti-GBM antibody elevation with a value of 91 units (normal: 0–20 units). A renal biopsy revealed HIVAN with no evidence of crescentic glomerulonephritis or anti-GBM disease. Conclusion. This case highlights the need for careful interpretation of anti-GBM antibody tests in HIV infected patients with kidney disease and, in particular, the need for biopsy confirmation of the diagnosis prior to starting therapy. More research is needed to study the prognostic correlation between the degree of anti-GBM antibody elevation in HIVAN and disease severity. PMID:24995137

  2. Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND).

    PubMed

    Zayyad, Zaina; Spudich, Serena

    2015-03-01

    Early in the HIV epidemic, the central nervous system (CNS) was recognized as a target of infection and injury in the advanced stages of disease. Though the most severe forms of HIV-associated neurocognitive disorder (HAND) related to severe immunosuppression are rare in the current era of widespread combination antiretroviral therapy (cART), evidence now supports pathological involvement of the CNS throughout the course of infection. Recent work suggests that the stage for HIV neuropathogenesis may be set with initial viral entry into the CNS, followed by initiation of pathogenetic processes including neuroinflammation and neurotoxicity, and establishment of local, compartmentalized HIV replication that may reflect a tissue reservoir for HIV. Key questions still exist as to when HIV establishes local infection in the CNS, which CNS cells are the primary targets of HIV, and what mechanistic processes underlie the injury to neurons that produce clinical symptoms of HAND. Advances in these areas will provide opportunities for improved treatment of patients with established HAND, prevention of neurological disease in those with early stage infection, and understanding of HIV tissue reservoirs that will aid efforts at HIV eradication. PMID:25604237

  3. HIV alters neuronal mitochondrial fission/fusion in the brain during HIV-Associated Neurocognitive Disorders

    PubMed Central

    Fields, Jerel Adam; Serger, Elisabeth; Campos, Sofia; Divakaruni, Ajit S.; Kim, Changyoun; Smith, Kendall; Trejo, Margarita; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; Murphy, Anne N.; Ellis, Ronald J.; Letendre, Scott; Grant, Igor; Masliah, Eliezer

    2015-01-01

    HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of HIV patients, and therapies to combat HAND progression are urgently needed. HIV proteins are released from infected cells and cause neuronal damage, possibly through mitochondrial abnormalities. Altered mitochondrial fission and fusion is implicated in several neurodegenerative disorders. Here, we hypothesized that mitochondrial fission/fusion may be dysregulated in neurons during HAND. We have identified decreased mitochondrial fission protein (dynamin 1-like; DNM1L) in frontal cortex tissues of HAND donors, along with enlarged and elongated mitochondria localized to the soma of damaged neurons. Similar pathology was observed in the brains of GFAP-gp120 tg mice. In vitro, recombinant gp120 decreased total and active DNM1L levels, reduced the level of Mitotracker staining, and increased extracellular acidification rate (ECAR) in primary neurons. DNM1L knockdown enhanced the effects of gp120 as measured by reduced Mitotracker signal in the treated cells. Interestingly, overexpression of DNM1L increased the level of Mitotracker staining in primary rat neurons and reduced neuroinflammation and neurodegeneration in the GFAP-gp120-tg mice. These data suggest that mitochondrial biogenesis dynamics are shifted towards mitochondrial fusion in brains of HAND patients and this may be due to gp120-induced reduction in DNM1L activity. Promoting mitochondrial fission during HIV infection of the CNS may restore mitochondrial biogenesis and prevent neurodegeneration. PMID:26611103

  4. HIV-Associated Oral Mucosal Melanin Hyperpigmentation: A Clinical Study in a South African Population Sample

    PubMed Central

    Chandran, R.; Feller, L.; Lemmer, J.; Khammissa, R. A. G.

    2016-01-01

    Objective. The aim of the study was to determine the prevalence of HIV-associated oral mucosal melanin hyperpigmentation (HIV-OMH) in a specific population of HIV-seropositive South Africans and to analyse the associations between HIV-OMH clinical features and the demographic and immunological characteristics of the study cohort. Material and Methods. This cross-sectional study included 200 HIV-seropositive Black subjects. The collected data comprised age, gender, CD4+ T cell count, viral load, systemic disease, medications, oral site affected by HIV-OMH, extent (localized or generalized), intensity of the pigmentation (dark or light), and smoking and snuff use. Results. Overall, 18.5% of the study cohort had HIV-OMH. Twenty-two and a half percent had OMH that could not with confidence be attributed to HIV infection, and 59% did not have any OMH. There was a significant but weak association between smoking and the presence of HIV-OMH. Conclusions. The prevalence of HIV-OMH in the study population was 18.5%, the gingiva being the most commonly affected site. It appears that the CD4+ T cell count does not play any role in the biopathology of HIV-OMH. PMID:27006825

  5. HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

    PubMed Central

    Saylor, Deanna; Dickens, Alex M.; Sacktor, Ned; Haughey, Norman; Slusher, Barbara; Pletnikov, Mikhail; Mankowski, Joseph L.; Brown, Amanda; Volsky, David J.; McArthur, Justin C.

    2016-01-01

    In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies — treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism — are needed to reverse or improve HAND-related neurological dysfunction. PMID:26965674

  6. Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction

    PubMed Central

    Pitcher, Jonathan; Abt, Anna; Myers, Jaclyn; Han, Rachel; Snyder, Melissa; Graziano, Alessandro; Festa, Lindsay; Kutzler, Michele; Garcia, Fernando; Gao, Wen-Jun; Fischer-Smith, Tracy; Rappaport, Jay; Meucci, Olimpia

    2014-01-01

    Interaction of the chemokine CXCL12 with its receptor CXCR4 promotes neuronal function and survival during embryonic development and throughout adulthood. Previous studies indicated that μ-opioid agonists specifically elevate neuronal levels of the protein ferritin heavy chain (FHC), which negatively regulates CXCR4 signaling and affects the neuroprotective function of the CXCL12/CXCR4 axis. Here, we determined that CXCL12/CXCR4 activity increased dendritic spine density, and also examined FHC expression and CXCR4 status in opiate abusers and patients with HIV-associated neurocognitive disorders (HAND), which is typically exacerbated by illicit drug use. Drug abusers and HIV patients with HAND had increased levels of FHC, which correlated with reduced CXCR4 activation, within cortical neurons. We confirmed these findings in a nonhuman primate model of SIV infection with morphine administration. Transfection of a CXCR4-expressing human cell line with an iron-deficient FHC mutant confirmed that increased FHC expression deregulated CXCR4 signaling and that this function of FHC was independent of iron binding. Furthermore, examination of morphine-treated rodents and isolated neurons expressing FHC shRNA revealed that FHC contributed to morphine-induced dendritic spine loss. Together, these data implicate FHC-dependent deregulation of CXCL12/CXCR4 as a contributing factor to cognitive dysfunction in neuroAIDS. PMID:24401274

  7. Sidekick-1 is upregulated in glomeruli in HIV-associated nephropathy.

    PubMed

    Kaufman, Lewis; Hayashi, Kayo; Ross, Michael J; Ross, Michael D; Klotman, Paul E

    2004-07-01

    Infection of podocytes by HIV-1 induces unique changes in phenotype, which contribute to the pathogenesis of glomerular disease in HIV-associated nephropathy (HIVAN). The host genetic pathways altered by HIV-1 infection that are responsible for these phenotypic changes are largely unknown. For identifying such pathways, representational difference analysis was performed comparing cDNA from HIV-1 transgenic podocytes with nontransgenic controls. In this way, a gene named sidekick-1 (sdk-1) was cloned, a transmembrane protein of the Ig superfamily that is highly upregulated in HIV-1 transgenic podocytes. Sdk-1 and its ortholog, sidekick-2 (sdk-2), were recently shown to guide axonal terminals to specific synapses in developing neurons. Their presence and role in other organs, including the kidney, has not been described. The current study demonstrates developmental expression of both sdk-1 and sdk-2 and a tight spatial and temporal regulation of these genes in kidney. During nephrogenesis, sidekick expression was observed first in ureteric bud and ureteric bud-derived tissues in a pattern similar to other genes known to play important roles in branching morphogenesis. In adult murine renal tissue, sidekick proteins were seen in glomeruli at low levels, and expression of sdk-1 was greatly upregulated in diseased HIV-1 transgenic mouse kidneys. In a human HIVAN kidney biopsy, sidekick expression was increased in glomeruli in a pattern consistent with the mouse model. It is proposed that the dysregulation of sdk-1 protein may play an important role in HIVAN pathogenesis. PMID:15213259

  8. The homophilic adhesion molecule sidekick-1 contributes to augmented podocyte aggregation in HIV-associated nephropathy.

    PubMed

    Kaufman, Lewis; Yang, Guozhe; Hayashi, Kayo; Ashby, James R; Huang, Li; Ross, Michael J; Klotman, Mary E; Klotman, Paul E

    2007-05-01

    The collapsing glomerulopathy of HIV-associated nephropathy (HIVAN) is characterized by podocyte dedifferentiation and proliferation. In affected glomeruli, proliferating podocytes adhere in aggregates to form glomerular pseudocrescents and fill an enlarged Bowman's space. Previously, we reported that sidekick-1 (sdk-1), an adhesion molecule of the immunoglobulin superfamily, was highly up-regulated in HIV-1 transgenic podocytes. In the current work, we explore how sdk-1 overexpression contributes to HIVAN pathogenesis. Murine podocytes infected with HIV-1 virus expressed significantly more sdk-1 than control-infected cells. Podocytes stably transfected with an sdk-1 expression construct grew in large aggregates with a simplified morphology characterized by a disorganized actin cytoskeleton, changes similar to podocytes in HIVAN. In contrast to controls, HIV-1 infected podocytes adhered to stably transfected sdk-1 podocyte aggregates in mixing studies. Furthermore, substrate-released cell sheets of wild-type podocytes were readily dissociated by mechanical stress, whereas HIV-1 podocytes remained in aggregates. The number of HIV-1 podocyte aggregates was significantly reduced in cells expressing a short hairpin RNA (shRNA) construct specific for sdk-1 compared with cells expressing control shRNA. Finally, in a HIVAN mouse model, sdk-1 protein was detected in podocytes in collapsed glomerular tufts and in glomerular pseudocrescents. These findings suggest that sdk-1 is an important mediator of cellular adhesion in HIV-infected podocytes and may contribute to podocyte clustering that is characteristic of pseudocrescent formation in HIVAN. PMID:17307840

  9. HIV-Associated Oral Mucosal Melanin Hyperpigmentation: A Clinical Study in a South African Population Sample.

    PubMed

    Chandran, R; Feller, L; Lemmer, J; Khammissa, R A G

    2016-01-01

    Objective. The aim of the study was to determine the prevalence of HIV-associated oral mucosal melanin hyperpigmentation (HIV-OMH) in a specific population of HIV-seropositive South Africans and to analyse the associations between HIV-OMH clinical features and the demographic and immunological characteristics of the study cohort. Material and Methods. This cross-sectional study included 200 HIV-seropositive Black subjects. The collected data comprised age, gender, CD4+ T cell count, viral load, systemic disease, medications, oral site affected by HIV-OMH, extent (localized or generalized), intensity of the pigmentation (dark or light), and smoking and snuff use. Results. Overall, 18.5% of the study cohort had HIV-OMH. Twenty-two and a half percent had OMH that could not with confidence be attributed to HIV infection, and 59% did not have any OMH. There was a significant but weak association between smoking and the presence of HIV-OMH. Conclusions. The prevalence of HIV-OMH in the study population was 18.5%, the gingiva being the most commonly affected site. It appears that the CD4+ T cell count does not play any role in the biopathology of HIV-OMH. PMID:27006825

  10. Factors Related to HIV-Associated Neurocognitive Impairment Differ With Age

    PubMed Central

    Fogel, Gary B.; Lamers, Susanna L.; Levine, Andrew J.; Valdes-Sueiras, Miguel; McGrath, Michael S.; Shapshak, Paul; Singer, Elyse J.

    2014-01-01

    Over 50% of HIV-infected (HIV+) persons are expected to be over age 50 by 2015. The pathogenic effects of HIV, particularly in cases of long-term infection, may intersect with those of age-related illnesses and prolonged exposure to combined antiretroviral therapy (cART). One potential outcome is an increased prevalence of neurocognitive impairment in older HIV+ individuals, as well as an altered presentation of HIV-associated neurocognitive disorders (HAND). METHODS In this study, we employed stepwise regression to examine 24 features sometimes associated with HAND in forty older (55–73 years of age) and thirty younger (32–50 years of age) HIV+, cART-treated participants without significant central nervous system confounds. RESULTS The features most effective in generating a true assessment of the likelihood of HAND diagnosis differed between older and younger cohorts, with the younger cohort containing features associated with drug abuse that were correlated to HAND, and the older cohort containing features that were associated with lipid disorders mildly associated with HAND. CONCLUSION As the HIV-infected population grows and the demographics of the epidemic change, it is increasingly important to re-evaluate features associated with neurocognitive impairment. Here we have identified features, routinely collected in primary care settings that provide more accurate diagnostic value than a neurocognitive screening measure among younger and older HIV-individuals. PMID:25404233

  11. Genetic, transcriptomic, and epigenetic studies of HIV-associated neurocognitive disorder

    PubMed Central

    Levine, Andrew J.; Panos, Stella E.; Horvath, Steve

    2014-01-01

    The Human Genome Project, coupled with rapidly evolving high throughput technologies, has opened the possibility of identifying heretofore unknown biological processes underlying human disease. Due to the opaque nature of HIV-associated neurocognitive disorder (HAND) neuropathogenesis, the utility of such methods has gained notice among NeuroAIDS researchers. Further, the merging of genetics with other research areas has also allowed for application of relatively nascent fields, such as neuroimaging genomics and pharmacogenetics, to the context of HAND. In this review, we detail the development of genetic, transcriptomic, and epigenetic studies of HAND, beginning with early candidate gene association studies and culminating in current “omics” approaches that incorporate methods from systems biology to interpret data from multiple levels of biological functioning. Challenges with this line of investigation are discussed; including the difficulty of defining a valid phenotype for HAND. We propose that leveraging known associations between biology and pathology across multiple levels will lead to a more reliable and valid phenotype. We also discuss the difficulties of interpreting the massive and multi-tiered mountains of data produced by current high-throughput omics assays, and explore the utility of systems biology approaches in this regard. PMID:24583618

  12. The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders

    PubMed Central

    Mediouni, Sonia; Garibaldi Marcondes, Maria Cecilia; Miller, Courtney; McLaughlin, Jay P.; Valente, Susana T.

    2015-01-01

    Antiretroviral therapy has dramatically improved the lives of human immunodeficiency virus 1 (HIV-1) infected individuals. Nonetheless, HIV-associated neurocognitive disorders (HAND), which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life. The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system (CNS) and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat) in the brain. Tat is a secreted viral protein that crosses the blood–brain barrier into the CNS, where it has the ability to directly act on neurons and non-neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine (MA) abusers is high among the HIV-1-positive population compared to the general population. On the other hand, MA abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and MA use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and MA in HAND and discuss a few promising potential therapeutic developments. PMID:26557111

  13. HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment.

    PubMed

    Saylor, Deanna; Dickens, Alex M; Sacktor, Ned; Haughey, Norman; Slusher, Barbara; Pletnikov, Mikhail; Mankowski, Joseph L; Brown, Amanda; Volsky, David J; McArthur, Justin C

    2016-04-01

    In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies--treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism--are needed to reverse or improve HAND-related neurological dysfunction. PMID:26965674

  14. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy.

    PubMed

    Kopp, Jeffrey B; Nelson, George W; Sampath, Karmini; Johnson, Randall C; Genovese, Giulio; An, Ping; Friedman, David; Briggs, William; Dart, Richard; Korbet, Stephen; Mokrzycki, Michele H; Kimmel, Paul L; Limou, Sophie; Ahuja, Tejinder S; Berns, Jeffrey S; Fryc, Justyna; Simon, Eric E; Smith, Michael C; Trachtman, Howard; Michel, Donna M; Schelling, Jeffrey R; Vlahov, David; Pollak, Martin; Winkler, Cheryl A

    2011-11-01

    Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice. PMID:21997394

  15. APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy

    PubMed Central

    Nelson, George W.; Sampath, Karmini; Johnson, Randall C.; Genovese, Giulio; An, Ping; Friedman, David; Briggs, William; Dart, Richard; Korbet, Stephen; Mokrzycki, Michele H.; Kimmel, Paul L.; Limou, Sophie; Ahuja, Tejinder S.; Berns, Jeffrey S.; Fryc, Justyna; Simon, Eric E.; Smith, Michael C.; Trachtman, Howard; Michel, Donna M.; Schelling, Jeffrey R.; Vlahov, David; Pollak, Martin; Winkler, Cheryl A.

    2011-01-01

    Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice. PMID:21997394

  16. The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders.

    PubMed

    Mediouni, Sonia; Marcondes, Maria Cecilia Garibaldi; Miller, Courtney; McLaughlin, Jay P; Valente, Susana T

    2015-01-01

    Antiretroviral therapy has dramatically improved the lives of human immunodeficiency virus 1 (HIV-1) infected individuals. Nonetheless, HIV-associated neurocognitive disorders (HAND), which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life. The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system (CNS) and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat) in the brain. Tat is a secreted viral protein that crosses the blood-brain barrier into the CNS, where it has the ability to directly act on neurons and non-neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine (MA) abusers is high among the HIV-1-positive population compared to the general population. On the other hand, MA abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and MA use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and MA in HAND and discuss a few promising potential therapeutic developments. PMID:26557111

  17. Characteristics of Resting-State Functional Connectivity in HIV-Associated Neurocognitive Disorder

    PubMed Central

    Jun, Suhnyoung; Shin, Na-Young; Han, Sanghoon; Ahn, Jin Young; Ahn, Mi Young; Jeon, Yong Duk; Jung, In Young; Kim, Moo Hyun; Jeong, Woo Yong; Ku, Nam Su; Kim, June Myung; Smith, Davey M.; Choi, Jun Yong

    2016-01-01

    Background HIV-associated neurocognitive disorder (HAND) can occur in patients without prior AIDS defining illness and can be debilitating. This study aimed to evaluate the difference in the patterns of intrinsic brain activity between patients with or without HAND for deepening our understanding of HAND. Methods We evaluated 24 HIV-infected individuals, 12 with previously diagnosed HAND and 12 previously diagnosed without HAND, and 11 seronegative individuals. These individuals then underwent repeat NP testing and a functional brain MRI scan. For functional MRI analysis, seed-based analysis with bilateral precuneus cortex seed was applied. Results Among the 12 individuals with previously diagnosed HAND, 3 showed improvement of their neurocognitive function and 1 was excluded for worsening liver disease. Among the 12 patients who previously had normal neurocognitive function, 2 showed neurocognitive impairment. Overall, the HAND group, who had impaired cognitive function at the time of MRI scan, showed significant decrease of resting status functional connectivity between bilateral precuneus and prefrontal cortex (PFC) compared with nonHAND group, those who had normal neurocognitive function (Corrected P<0.05). The functional connectivity with the right inferior frontal operculum and right superior frontal gyrus was positively correlated with memory and learning ability. Conclusions This cross-sectional study found a significant difference in fMRI patterns between patients with and without HAND. Decreased functional connectivity between precuneus and PFC could be possible functional substrate for cognitive dysfunction in HIV patients, which should be characterized in a longitudinal study. PMID:27104345

  18. Adjunctive and Long-Acting Nanoformulated Antiretroviral Therapies for HIV-associated neurocognitive disorders

    PubMed Central

    Gendelman, Howard E.; Gelbard, Harris A.

    2014-01-01

    Purpose of review This review focuses on current and future strategies to modulate neuroinflammation while reducing residual viral burden in the central nervous system (CNS). This has been realized by targeted long acting antiretroviral nano- and adjunctive therapies being developed for HIV infected people. Our ultimate goal is to eliminate virus from its CNS reservoirs and, in so doing, reverse the cognitive and motor dysfunctions seen in HIV-associated neurocognitive disorders (HAND). Recent findings Herein, we highlight our laboratories development of adjunctive and nanomedicine therapies for HAND. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory pro-inflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy (ART) has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HAND. Symptoms, while reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir targeted nanoformulated ART. The translation of these inventions from animals to humans is the focus of this review. PMID:25226025

  19. Plasma HHV8 DNA predicts relapse in individuals with HIV-associated multicentric Castleman disease.

    PubMed

    Stebbing, Justin; Adams, Caroline; Sanitt, Adam; Mletzko, Salvinia; Nelson, Mark; Gazzard, Brian; Newsom-Davis, Tom; Bower, Mark

    2011-07-14

    HIV-associated multicentric Castleman disease (HIV-MCD) is a rare lymphoproliferative disorder caused by infection with human herpesvirus-8. The disease follows a relapsing and remitting clinical course, with marked systemic symptoms during an active attack, which can prove fatal. Its incidence is rising, and new data indicate the utility of the anti-CD20 monoclonal antibody rituximab at inducing remissions in both first- and second-line settings, although biomarkers associated with relapse have not been previously identified. In 52 individuals with a histologic diagnosis of HIV-MCD, we performed univariate and multivariate analyses to predict factors associated with an HIV-MCD attack. Although a younger age (< 50 years) was associated with an attack, the strongest association was observed with plasma levels of human herpesvirus-8 DNA. Rising levels predicted an attack (hazard ratio = 2.9; 95% confidence interval, 1.3-6.7), and maintenance therapy with rituximab should be considered in these individuals. PMID:21511959

  20. HIV-Associated Distal Neuropathic Pain is Associated with Smaller Total Cerebral Cortical Gray Matter

    PubMed Central

    Keltner, John R.; Fennema-Notestine, Christine; Vaida, Florin; Wang, Dongzhe; Franklin, Donald R.; Dworkin, Robert H.; Sanders, Chelsea; McCutchan, J. Allen; Archibald, Sarah L.; Miller, David J.; Kesidis, George; Cushman, Clint; Kim, Sung Min; Abramson, Ian; Taylor, Michael J.; Theilmann, Rebecca J.; Julaton, Michelle D.; Notestine, Randy J.; Corkran, Stephanie; Cherner, Mariana; Duarte, Nichole A.; Alexander, Terry; Robinson-Papp, Jessica; Gelman, Benjamin B.; Simpson, David M.; Collier, Ann C.; Marra, Christina M.; Morgello, Susan; Brown, Greg; Grant, Igor; Atkinson, J. Hampton; Jernigan, Terry L.; Ellis, Ronald J.

    2014-01-01

    Despite modern antiretroviral therapy, HIV-associated sensory neuropathy affects over 50% of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. To better understand central nervous system contributions to HIV DNP, we performed a cross-sectional analysis of structural magnetic resonance imaging (MRI) volumes in 241 HIV-infected participants from an observational multi-site cohort study at five US sites (CNS HIV Antiretroviral Treatment Effects Research Study, CHARTER). The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (R = −0.24; p = 0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance. PMID:24549970

  1. Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion

    PubMed Central

    Tenor, Jennifer L.; Oehlers, Stefan H.; Yang, Jialu L.

    2015-01-01

    ABSTRACT The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of Cryptococcus with the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute cryptococcal infections. By interrogating survival and cryptococcal burden following infection with a panel of Cryptococcus mutants, we find that virulence factors initially identified as important in causing disease in mice are also necessary for pathogenesis in zebrafish larvae. Live imaging of the cranial blood vessels of infected larvae reveals that C. neoformans is able to penetrate the zebrafish brain following intravenous infection. By studying a C. neoformans FNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a murine model of central nervous system invasion. The zebrafish-C. neoformans platform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents. PMID:26419880

  2. Long-Term Neuropsychological Sequelae in HIV-Seronegative Cryptococcal Meningoencephalitis Patients with and without Ventriculoperitoneal Shunts: A Cine MRI Study

    PubMed Central

    Lu, Cheng-Hsien; Wang, Hung-Chen; Chen, Hsiu-Ling; Tsai, Nai-Wen; Hsu, Nai-Wen; Lin, Wei-Ming; Kung, Chia-Te; Lin, Wei-Che

    2015-01-01

    Background. Hydrocephalus in cryptococcal meningoencephalitis is most commonly managed with a ventriculoperitoneal shunt. This study applied cine magnetic resonance imaging (MRI) to evaluate initial disease severity on long-term cerebrospinal fluid (CSF) flow dynamics and associated neuropsychological sequelae in cryptococcal meningoencephalitis patients with and without ventriculoperitoneal shunts. Methods. Eighteen human immunodeficiency virus-seronegative cryptococcal meningoencephalitis patients (10 with shunts versus 8 without shunts) were compared with 32 age- and sex-matched healthy volunteers. All subjects underwent complete neurologic examination and neuropsychological testing. Cine MRI was conducted to evaluate CSF flow parameters. Initial CSF laboratory analysis and imaging findings were correlated with present CSF flow parameters and neuropsychological scores. Results. Patients without shunts had higher average flow than controls, suggesting chronic hydrocephalus. Initial Evans ratios and CSF glucose levels were associated with CSF peak velocity and flow. Worsening CSF flow parameters correlated with decreased neuropsychological performance. Conclusions. CSF flow parameter differences between the cryptococcal meningoencephalitis patients both with and without ventriculoperitoneal shunts could be detected by cine MRI and correlated with acute stage disease severity and chronic stage neuropsychological results. Cine MRI is useful for assessing the chronic hydrocephalus that may lead to neuropsychological deficits in cryptococcal meningoencephalitis patients. PMID:25948879

  3. A perspective on the proposal for neurocognitive disorder criteria in DSM-5 as applied to HIV-associated neurocognitive disorders

    PubMed Central

    Goodkin, Karl; Fernandez, Francisco; Forstein, Marshall; Miller, Eric N; Becker, James T; Douaihy, Antoine; Cubano, Luis; Santos, Flavia H; Filho, Nelson Silva; Zirulnik, Jorge; Singh, Dinesh

    2011-01-01

    SUMMARY HIV-associated neurocognitive disorders remain common in the current era of effective antiretroviral therapy. However, the severity at presentation of these disorders has been reduced, and the typical manifestations have changed. A revision of the American Academy of Neurology (AAN) criteria has been made on this basis, and a revision of the analogous criteria by the American Psychiatric Association will be forthcoming in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5. This article compares the relevant sets of diagnostic criteria that will be employed. It is concluded that a greater degree of integration of the revised, HIV-specific AAN criteria for HIV-associated neurocognitive disorders with the criteria proposed for the DSM-5 would prove advantageous for research, clinical, educational and administrative purposes. PMID:22844348

  4. From Epidemic Meningitis Vaccines for Africa to the Meningitis Vaccine Project

    PubMed Central

    Aguado, M. Teresa; Jodar, Luis; Granoff, Dan; Rabinovich, Regina; Ceccarini, Costante; Perkin, Gordon W.

    2015-01-01

    Background. Polysaccharide vaccines had been used to control African meningitis epidemics for >30 years but with little or modest success, largely because of logistical problems in the implementation of reactive vaccination campaigns that are begun after epidemics are under way. After the major group A meningococcal meningitis epidemics in 1996–1997 (250 000 cases and 25 000 deaths), African ministers of health declared the prevention of meningitis a high priority and asked the World Health Organization (WHO) for help in developing better immunization strategies to eliminate meningitis epidemics in Africa. Methods. WHO accepted the challenge and created a project called Epidemic Meningitis Vaccines for Africa (EVA) that served as an organizational framework for external consultants, PATH, the US Centers for Disease Control and Prevention (CDC), and the Bill & Melinda Gates Foundation (BMGF). Consultations were initiated with major vaccine manufacturers. EVA commissioned a costing study/business plan for the development of new group A or A/C conjugate vaccines and explored the feasibility of developing these products as a public–private partnership. Representatives from African countries were consulted. They confirmed that the development of conjugate vaccines was a priority and provided information on preferred product characteristics. In parallel, a strategy for successful introduction was also anticipated and discussed. Results. The expert consultations recommended that a group A meningococcal conjugate vaccine be developed and introduced into the African meningitis belt. The results of the costing study indicated that the “cost of goods” to develop a group A – containing conjugate vaccine in the United States would be in the range of US$0.35–$1.35 per dose, depending on composition (A vs A/C), number of doses/vials, and presentation. Following an invitation from BMGF, a proposal was submitted in the spring of 2001. Conclusions. In June 2001

  5. Vascular endothelial growth factor (VEGF) is increased in serum, but not in cerebrospinal fluid in HIV associated CNS diseases.

    PubMed

    Sporer, B; Koedel, U; Paul, R; Eberle, J; Arendt, G; Pfister, H-W

    2004-02-01

    Vascular endothelial growth factor (VEGF) is a potent angiogenic and mitogenic peptide, which also induces several mediators that may play a role in HIV induced CNS damage. VEGF levels were determined in cerebrospinal fluid (CSF) and serum samples from patients with (n = 8) and without (n = 19) directly HIV associated CNS disorders and HIV negative control patients (n = 18). VEGF serum but not CSF levels were significantly increased in HIV infected patients with (381.1 (78.9) pg/ml) HIV associated CNS diseases compared with those without (120.8 (13.1) pg/ml) and HIV negative control patients (133.1(14.8) pg/ml). Serum samples from patients with untreated HIV associated encephalopathy (HIVE, n = 3) contained the highest VEGF levels (583.9 (71.5) pg/ml). In two patients VEGF serum levels were reduced during antiretroviral therapy. However, regardless of effective viral suppression, patients with HIVE still had higher levels compared with HIV infected patients without HIVE. A relevant increase of serum VEGF was not observed in patients without HIVE though high HI viral load. We conclude that HIVE is associated with increased serum VEGF levels. Further studies are warranted to elucidate the role of VEGF in HIVE. PMID:14742610

  6. An unusual and challenging case of HIV-associated primary CNS Lymphoma with Hodgkin-like morphology and HIV encephalitis.

    PubMed

    Lloyd, Isaac E; Clement, Parker W; Salzman, Karen L; Jensen, Randy L; Salama, Mohamed E; Palmer, Cheryl A

    2015-01-01

    HIV-associated primary CNS lymphomas are well-recognized, almost exclusively EBV-driven neoplasms with poor clinical prognosis. We report a challenging, atypical case of an HIV-associated lymphoproliferative disorder with unusual morphologic features reminiscent of Hodgkin Lymphoma, accompanied by HIV encephalitis. A 52-year-old male presented with acute seizures after seven months of progressive neurocognitive decline that was clinically diagnosed as progressive supranuclear palsy. Clinical work-up revealed HIV infection along with two ring-enhancing lesions in the brain on MRI, and negative CSF EBV testing. Subsequent biopsy showed well-demarcated hypercellular regions in the brain comprised of scattered Reed-Sternberg-like cells in a background of small to medium-sized lymphocytes exhibiting focal angiocentricity and geographic necrosis. The atypical cells were positive for CD20, EBV, and CD79a, and negative for CD45, GFAP, CD15, CD30, and p24. These cells were admixed with numerous CD68-positive cells. The adjacent brain showed classic features of HIV encephalitis with perivascular, CD68 and p24-positive multinucleated giant cells. This case illustrates several diagnostic pitfalls in the work-up of HIV-associated brain lesions, as well as reporting a unique histomorphology for an HIV-related primary CNS lymphoproliferative disorder. PMID:26328586

  7. Evidence for Branching in Cryptococcal Capsular Polysaccharides and Consequences on its Biological Activity

    PubMed Central

    Cordero, Radames J.B.; Frases, Susana; Guimaräes, Allan J.; Rivera, Johanna; Casadevall, Arturo

    2011-01-01

    SUMMARY The encapsulated fungus Cryptococcus neoformans is a common cause of life-threatening disease in immunocompromised individuals. Its major virulence determinant is the polysaccharide (PS) capsule. An unsolved problem in cryptococcal biology is whether the PSs composing the capsule are linear or complex branched polymers, as well as the implications of this structural composition in pathogenesis. In this study we approached the problem by combining static and dynamic light scattering, viscosity analysis, and high-resolution microscopy and correlated the findings with biological properties. Analysis of the dependence of capsular PS molecular mass and the radius of gyration provided strong evidence against a simple linear PS configuration. Shape factors calculated from light scattering measurements in solution revealed values consistent with polymer branching. Furthermore, viscosity measurements provided complementary evidence for structural branching. Electron microscopy showed PS spherical-like structures similar to other branched PS. Finally, we show that the capacity of capsular PS to interfere in complement-mediated phagocytosis, inhibit nitric oxide production by macrophage-like cells, protect against reactive oxygen species, antibody reactivity and half-life in serum were influenced by the degree of branching, providing evidence for the notion that PS branching is an important parameter in determining the biological activity of C. neoformans PS. PMID:21208301

  8. Analysis of asthma patients for cryptococcal seroreactivity in an urban German area.

    PubMed

    Grahnert, Andreas; Müller, Uwe; von Buttlar, Heiner; Treudler, Regina; Alber, Gottfried

    2015-08-01

    Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised patients but is also able to asymptomatically infect immunocompetent individuals. C. neoformans is found ubiquitously especially in urban areas where it is spread by pigeons, and fungal exposure may predispose for asthma development already at an early age, as soon as confronted with pigeon droppings. In the study presented here, we investigated the presence of specific immunoglobulin G (IgG) against C. neoformans in sera from patients suffering from asthma in comparison to a healthy control cohort, accrued from the Leipzig Research Centre for Civilization Diseases (LIFE). For serological analysis we developed a flow cytometry (FACS) based assay specific for an acapsular strain of C. neoformans to comprehensively analyze different cryptococcal serotypes. Compared with the non-asthmatic cohort, asthmatics exhibited, as expected, an elevated level of total serum immunoglobulin E (IgE), whereas the IgG seroreactivity against C. neoformans was not significantly different among the two groups (P = .118). Nevertheless, there was a trend toward increased Cryptococcus-specific IgG antibodies in the serum of asthmatics. Additionally, in male asthmatics an increased IgG-mediated seroreactivity compared to female asthmatics was found. This points to a higher prevalence of subclinical C. neoformans infection in male asthmatics and may support the hypothesis of C. neoformans as a risk factor for the development of asthma in urban areas. PMID:26026172

  9. Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort

    PubMed Central

    Gelman, Benjamin B.; Lisinicchia, Joshua G.; Morgello, Susan; Masliah, Eliezer; Commins, Deborah; Achim, Cristian L.; Fox, Howard S.; Kolson, Dennis L.; Grant, Igor; Singer, Elyse; Yiannoutsos, Constantin T.; Sherman, Seth; Gensler, Gary; Moore, David J.; Chen, Tiansheng; Soukup, Vicki M.

    2013-01-01

    Objective Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A clinico-neurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. Subjects and assays HIV gag/pol RNA and DNA copies were quantified with RT-PCR or PCR in 148 HAART-era brain specimens. Comparison to HAND, HIVE and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman’s tests respectively. Results Brain HIV RNA was higher in subjects with HAND plus HIVE vs without HAND (delta = 2.48 log10 units, n = 27 vs 36, p < 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different vs without HAND (p = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (p<0.001), but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (p<0.01), and much lower versus with HIVE (p<0.001). Conclusion Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE; while on HAART these patients could obtain added NP improvement by further reducing brain HIV. Patients not in those groups are less certain to obtain added NP benefit. PMID:23242157

  10. HIV-associated neurocognitive disorder in HIV-infected Koreans: Korean NeuroAIDS Project

    PubMed Central

    Ku, Nam Su; Lee, Youngjoon; Ahn, Jin Young; Song, Je Eun; Kim, Min Hyung; Kim, Sun Bean; Jeong, Su Jin; Hong, Kyung-Wook; Kim, Eosu; Han, Sang Hoon; Song, Joon Young; Cheong, Hee Jin; Song, Young Goo; Kim, Woo Joo; Kim, June Myung; Smith, Davey M.; Choi, Jun Yong

    2014-01-01

    Background HIV-associated neurocognitive disorder (HAND) is an independent predictor of early mortality and is associated with many difficulties in activities of daily living. We sought to determine the prevalence of and risk factors for HAND in HIV-infected Koreans. In addition, we investigated the performance of screening tools and components of neuropsychological (NP) tests for diagnosing HAND. Methods HIV-infected patients were enrolled consecutively from two different urban teaching hospitals in Seoul, South Korea between March 2012 and September 2012. Participants completed a detailed NP assessment of six cognitive domains commonly affected by HIV. The Frascati criteria were used for diagnosing HAND. Four key questions, international HIV dementia scale (IHDS) and MoCA-K were also assessed as potential tools for screening for HAND. Results Among the 194 participants, the prevalence of HAND was 26.3%. Asymptomatic neurocognitive impairment, minor neurocognitive disorder accounted for 52.9% and 47.1% of the patients with HAND, respectively. In multivariate analysis, hemoglobin levels ≤13g/dL (p=0.046) and the current use of protease inhibitor-based regimen (p=0.031) were independent risk factors for HAND. The sensitivity and specificity of IHDS were 72.6% and 60.8%, and MoCA-K were 52.9% and 73.4%, respectively. IHDS (p<0.001) and MoCA-K (p<0.001) were both useful for screening for HAND. Among NP tests, the sensitivity and specificity of the Grooved Pegboard Test were 90.2% and 72.0%, and the Wisconsin Card Sorting Test were 61.2% and 84.4%, respectively. Conclusions HAND is a prevalent comorbidity in HIV-infected Koreans. Active screening and diagnosis with useful tools, like IHDS, MoCA-K and Grooved Pegboard Test, could be used to identify this important complication. PMID:24580888

  11. Complement and HIV-I infection/ HIV-associated neurocognitive disorders

    PubMed Central

    Liu, Fengming; Dai, Shen; Gordon, Jennifer; Qin, Xuebin

    2014-01-01

    The various neurological complications associated with HIV-1 infection, specifically HIV-associated neurocognitive disorders (HAND) persist as a major public health burden worldwide. Despite the widespread use of anti-retroviral therapy, the prevalence of HAND is significantly high. HAND results from the direct effects of an HIV-1 infection as well as secondary effects of HIV-1-induced immune reaction and inflammatory response. Complement, a critical mediator of innate and acquired immunity, plays important roles in defeating many viral infections by the formation of a lytic pore or indirectly by opsonization and recruitment of phagocytes. While the role of complement in the pathogenesis of HIV-1 infection and HAND has been previously recognized for over fifteen years, it has been largely underestimated thus far. Complement can be activated through HIV-1 envelope proteins, mannose binding lectins (MBL) and anti-HIV-1 antibodies. Complement not only fights against HIV-1 infection but also enhances HIV-1 infection. Also, HIV-1 can hijack complement regulators such as CD59 and CD55 and can utilize these regulators and factor H to escape from complement attack. Normally, complement levels in brain are much lower than plasma levels and there is no or little complement deposition in brain cells. Interestingly, local production and deposition of complement are dramatically increased in HIV-1-infected brain, indicating that complement may contribute to the pathogenesis of HAND. Here, we review the current understanding of the role of complement in HIV-1 infection and HAND as well as potential therapeutic approaches targeting to the complement system for the treatment and eradications of HIV-1 infection. PMID:24639397

  12. Pathogenesis of HIV-associated pulmonary hypertension: potential role of HIV-1 Nef.

    PubMed

    Almodovar, Sharilyn; Hsue, Priscilla Y; Morelli, Julie; Huang, Laurence; Flores, Sonia C

    2011-06-01

    Infection with HIV increases the risk for lung diseases, including noninfectious pulmonary hypertension (PH). HIV-associated PH (HIV-PH) is an important lung disease in HIV-infected persons who live longer with antiretrovirals. The early stages of HIV-PH may be overlooked by healthcare providers due to nonspecific symptoms, including progressive dyspnea and nonproductive cough. HIV-PH may be detected via chest radiographs, CT scans, or electrocardiograms, but Doppler echocardiography is the most useful screening test to identify candidates for right heart catheterization. HIV-PH has a poor prognosis with high mortality; improved biomarkers to identify earlier stages of PH would benefit clinical care. The HIV-PH mechanism remains unknown, but HIV proteins such as Tat and Nef may play a role. HIV-1 Nef is a broad-spectrum adaptor protein that may affect HIV-infected and uninfected pulmonary vascular cells. Studies in macaques suggest that Nef is important in HIV-PH pathogenesis because monkeys infected with a chimeric simian immunodeficiency virus (SIV) expressing HIV-nef (SHIVnef) alleles, but not monkeys infected with the native SIV, develop pulmonary vascular remodeling. Four consistent amino acid mutations arose spontaneously in Nef passaged in the monkeys. To translate these findings to humans, one research endeavor of the Lung HIV Study focuses on the identification of HIV nef mutations in HIV-infected individuals with PH compared with HIV-infected normotensive patients. We present some of the preliminary evidence. Ongoing longitudinal studies will establish the connection between Nef mutations and the propensity for HIV-PH. PMID:21653533

  13. Tubular cell phenotype in HIV-associated nephropathy: role of phospholipid lysophosphatidic acid.

    PubMed

    Ayasolla, Kamesh R; Rai, Partab; Rahimipour, Shai; Hussain, Mohammad; Malhotra, Ashwani; Singhal, Pravin C

    2015-08-01

    Collapsing glomerulopathy and microcysts are characteristic histological features of HIV-associated nephropathy (HIVAN). We have previously reported the role of epithelial mesenchymal transition (EMT) in the development of glomerular and tubular cell phenotypes in HIVAN. Since persistent tubular cell activation of NFκB has been reported in HIVAN, we now hypothesize that HIV may be contributing to tubular cell phenotype via lysophosphatidic acid (LPA) mediated downstream signaling. Interestingly, LPA and its receptors have also been implicated in the tubular interstitial cell fibrosis (TIF) and cyst formation in autosomal dominant polycystic kidney disease (PKD). Primary human proximal tubular cells (HRPTCs) were transduced with either empty vector (EV/HRPTCs), HIV (HIV/HRPTCs) or treated with LPA (LPA/HRPTC). Immunoelectrophoresis of HIV/HRPTCs and LPA/HRPTCs displayed enhanced expression of pro-fibrotic markers: a) fibronectin (2.25 fold), b) connective tissue growth factor (CTGF; 4.8 fold), c) α-smooth muscle actin (α-SMA; 12 fold), and d) collagen I (5.7 fold). HIV enhanced tubular cell phosphorylation of ILK-1, FAK, PI3K, Akt, ERKs and P38 MAPK. HIV increased tubular cell transcriptional binding activity of NF-κB; whereas, a LPA biosynthesis inhibitor (AACOCF3), a DAG kinase inhibitor, a LPA receptor blocker (Ki16425), a NF-κB inhibitor (PDTC) and NFκB-siRNA not only displayed downregulation of a NFκB activity but also showed attenuated expression of profibrotic/EMT genes in HIV milieu. These findings suggest that LPA could be contributing to HIV-induced tubular cell phenotype via NFκB activation in HIVAN. PMID:26079546

  14. A better screening tool for HIV-associated neurocognitive disorders: is it what clinicians need?

    PubMed Central

    Brouillette, Marie-J.; Mayo, Nancy; Fellows, Lesley K.; Lebedeva, Elena; Higgins, Johanne; Overton, Edgar T.; Ances, Beau M.; Koski, Lisa

    2015-01-01

    Objective: Existing screening tools for HIV-Associated Neurocognitive Disorders (HAND) may lack the accuracy required for clinical use. We hypothesized that the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) as a screening tool for HAND might be improved with a stronger scoring methodology. Design: Two hundred HIV-positive participants aged 18–65 years completed the MoCA and a battery of neuropsychological tests. Methods: HAND diagnosis was established according to the Frascati criteria, and an NPZ-8 score was also calculated. Rasch analysis was applied to the MoCA items to create a quantitative score. Results: The optimal cut-off on the quantitative MoCA for detecting impairment as per Frascati criteria yielded a sensitivity of 0.74 and a specificity of 0.68. Overall accuracy was 0.79 (95% CI: 0.73–0.85), an improvement over standard scoring methods. However, whether cognition was quantified with the quantitative MoCA or with NPZ-8, there was substantial overlap between diagnostic categories; several individuals categorized as impaired had better overall cognitive function as assessed by NPZ-8 or quantitative MoCA than those classified as normal using standard criteria. Conclusion: Quantifying performance on MoCA items through Rasch analysis improves its accuracy as a screening tool for HAND, and demonstrates that cognition can be measured as a unidimensional construct in HIV, at least at the level of precision of bedside testing. However, the current categorical diagnostic approach to HAND is poorly aligned with summary measures of cognitive ability. Measuring cognition as a quasi-continuous construct may be more relevant than conventional HAND diagnostic categories for many clinical purposes. PMID:25291105

  15. HIV Promotes NLRP3 Inflammasome Complex Activation in Murine HIV-Associated Nephropathy.

    PubMed

    Haque, Shabirul; Lan, Xiqian; Wen, Hongxiu; Lederman, Rivka; Chawla, Amrita; Attia, Mohamed; Bongu, Ramchandra P; Husain, Mohammad; Mikulak, Joanna; Saleem, Moin A; Popik, Waldemar; Malhotra, Ashwani; Chander, Praveen N; Singhal, Pravin C

    2016-02-01

    Dysregulated growth and loss of podocytes are important features of HIV-associated nephropathy. Recently, HIV was reported to induce a new type of programed cell death, pyroptosis, in T lymphocytes through induction of Nod-like receptor protein 3 (NLRP3) inflammasome complexes. We evaluated the role of HIV in podocyte NLRP3 inflammasome formation both in vivo and in vitro. Renal cortical sections of HIV-transgenic mice (Tg26) displayed increased expression of NLRP3, ASC (a CARD protein), caspase-1, and IL-1β proteins, confirming NLRP3 inflammasome complex formation in podocytes of Tg26 mice. Renal tissues of Tg26 mice also displayed enhanced mRNA levels and protein expressions of inflammasome markers (NLRP3, ASC, and caspase-1, and IL-1β). Serum of Tg26 mice also showed elevated concentrations of IL-1β cytokine compared with FVBN mice. HIV induced pyroptosis in a dose- and time-dependent manner within podocytes, a phenotype of inflammasome activation. Caspase-1 inhibitor not only attenuated podocyte expression of caspase-1 and IL-1β but also provided protection against pyroptosis, suggesting that HIV-induced podocyte injury was mediated by caspase-1 activation. Interestingly, HIV-induced podocyte pyroptosis could be partially inhibited by Tempol (a superoxide dismutase-mimetic agent) and by glyburide (an inhibitor of potassium efflux). These findings suggest that generation of reactive oxygen species and potassium efflux contribute to HIV-induced pyroptosis and NLRP3 inflammasome activation in podocytes. PMID:26683666

  16. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder

    PubMed Central

    Marquie-Beck, J.A.; FitzSimons, C.A.; Letendre, S.L.; Ellis, R.J.; Heaton, R.K.; Wolfson, T.; Rosario, D.; Alexander, T.J.; Marra, C.; Ances, B.M.; Grant, I.

    2012-01-01

    Objective: To evaluate relationships between HIV-associated neurocognitive disorder and metabolic variables in a subgroup of HIV+ participants examined in a prospective, observational, multicenter cohort study. Methods: In a cross-sectional substudy of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort, 130 HIV+ participants provided fasting blood samples. Neurocognitive impairment (NCI) was defined by performance on neuropsychological tests adjusting for age, education, gender, and race/ethnicity. Global ratings and global deficit scores were determined. Demographics, biomarkers of HIV disease, metabolic variables, combination antiretroviral therapy (CART) history, other drug exposures, and self-reported diabetes were examined in multivariate models predicting NCI. Separate models were used for body mass index (BMI) alone (n = 90) and BMI and waist circumference (WC) together (n = 55). Results: NCI (global impairment rating ≥5) was diagnosed in 40%. In univariate analyses, age, longer duration of HIV infection, obesity, and WC, but not BMI, were associated with NCI. Self-reported diabetes was associated with NCI in the substudy and in those >55 in the entire CHARTER cohort. Multivariate logistic regression analyses demonstrated that central obesity (as measured by WC) increased the risk of NCI and that greater body mass may be protective if the deleterious effect of central obesity is accounted for. Conclusions: As in HIV-uninfected persons, central obesity, but not more generalized increases in body mass (BMI), was associated with a higher prevalence of NCI in HIV+ persons. Diabetes appeared to be associated with NCI only in older patients. Avoidance of antiretroviral drugs that induce central obesity might protect from or help to reverse neurocognitive impairment in HIV-infected persons. PMID:22330412

  17. Estimation of cerebrospinal fluid cortisol level in tuberculous meningitis

    PubMed Central

    Mahale, Rohan R.; Mehta, Anish; Uchil, Sudhir

    2015-01-01

    Background: Central nervous system (CNS) involvement in tuberculosis is around 5–10%. Of the various manifestations of CNS tuberculosis, meningitis is the most common (70–80%). Delay in diagnosis and treatment results in significant morbidity and mortality. Objective: To study the cerebrospinal fluid (CSF) cortisol levels in tubercular meningitis and compare the levels with controls. Methods: Cross-sectional, prospective, observational, hospital-based study done in 20 patients of tubercular meningitis, 20 patients of aseptic meningitis (AM) and 25 control subjects without any preexisting neurological disorders who have undergone lumbar puncture for spinal anesthesia. Results: Cortisol was detected in all 40 CSF samples of patients (100%). Mean CSF cortisol level was 8.82, 3.47 and 1.05 in tubercular meningitis, AM and controls, respectively. Mean CSF cortisol level in tubercular meningitis was significantly higher as compared to AM and controls (P < 0.0001). Conclusion: Cortisol level estimation in CSF is one of the rapid, relatively inexpensive diagnostic markers in early identification of tubercular meningitis along with CSF findings of elevated proteins, hypoglycorrhachia and lymphocytic pleocytosis. This aids in earlier institution of appropriate treatment and thereby decreasing morbidity and mortality. This is the first study on the estimation of CSF cortisol level in tuberculous meningitis. PMID:26752900

  18. Abducens Nerve Palsy and Meningitis by Rickettsia typhi

    PubMed Central

    Moy, Wai Lun; Ooi, Say Tat

    2015-01-01

    Patients with rickettsial infection may present with encephalitis or meningitis but neurologic involvement is rare in murine typhus. Here, we report two patients with Rickettsia typhi meningitis who presented with cranial neuropathy, presumably caused by two distinct disease processes. Recognition of the disease manifestations is important because rickettsial infections are potentially associated with significant morbidity. Simple effective treatments are available. PMID:25548377

  19. Meningitis in a College Student in Connecticut, 2007

    ERIC Educational Resources Information Center

    Sosa, Lynn E.; Gupta, Shaili; Juthani-Mehta, Manisha; Hadler, James L.

    2009-01-01

    The authors describe a case of aseptic meningitis in a college student that was ultimately attributed to infection with lymphocytic choriomeningitis virus (LCMV). The authors also provide a review of LCMV infection, epidemiology, and public health implications. Providers should be aware of LCMV as a cause of meningitis in college students,…

  20. Quantitative proteomics for identifying biomarkers for tuberculous meningitis

    PubMed Central

    2012-01-01

    Introduction Tuberculous meningitis is a frequent extrapulmonary disease caused by Mycobacterium tuberculosis and is associated with high mortality rates and severe neurological sequelae. In an earlier study employing DNA microarrays, we had identified genes that were differentially expressed at the transcript level in human brain tissue from cases of tuberculous meningitis. In the current study, we used a quantitative proteomics approach to discover protein biomarkers for tuberculous meningitis. Methods To compare brain tissues from confirmed cased of tuberculous meningitis with uninfected brain tissue, we carried out quantitative protein expression profiling using iTRAQ labeling and LC-MS/MS analysis of SCX fractionated peptides on Agilent’s accurate mass QTOF mass spectrometer. Results and conclusions Through this approach, we identified both known and novel differentially regulated molecules. Those described previously included signal-regulatory protein alpha (SIRPA) and protein disulfide isomerase family A, member 6 (PDIA6), which have been shown to be overexpressed at the mRNA level in tuberculous meningitis. The novel overexpressed proteins identified in our study included amphiphysin (AMPH) and neurofascin (NFASC) while ferritin light chain (FTL) was found to be downregulated in TBM. We validated amphiphysin, neurofascin and ferritin light chain using immunohistochemistry which confirmed their differential expression in tuberculous meningitis. Overall, our data provides insights into the host response in tuberculous meningitis at the molecular level in addition to providing candidate diagnostic biomarkers for tuberculous meningitis. PMID:23198679

  1. Meningococcal meningitis C in Tamil Nadu, public health perspectives.

    PubMed

    David, Kirubah Vasandhi; Pricilla, Ruby Angeline; Thomas, Beeson

    2014-01-01

    Meningococcal meningitis has rarely been reported in Tamil Nadu. We report here two children diagnosed with meningococcal meningitis in Vellore, Tamil Nadu, on May 2014. The causative strain was Neisseria meningitidis serotype C. The role of the primary care physician in early diagnosis, appropriate referral, and preventive measures of this disease to the immediate family and community is stressed. PMID:25657960

  2. Meningeal Melanocytes in the Mouse: Distribution and Dependence on Mitf

    PubMed Central

    Gudjohnsen, Stefán A. H.; Atacho, Diahann A. M.; Gesbert, Franck; Raposo, Graca; Hurbain, Ilse; Larue, Lionel; Steingrimsson, Eirikur; Petersen, Petur Henry

    2015-01-01

    Summary: Melanocytes are pigment producing cells derived from the neural crest. They are primarily found in the skin and hair follicles, but can also be found in other tissues including the eye, ear and heart. Here, we describe the distribution of pigmented cells in C57BL/6J mouse meninges, the membranes that envelope the brain. These cells contain melanosomes of all four stages of development and they depend on Microphthalmia associated transcription factor (MITF), the master regulator of melanocyte development, suggesting that they are bona-fide melanocytes. The location of these pigmented cells is consistent with the location of meningeal melanomas in humans and animal models. Significance: Here, we document and define pigmented cells in the meninges of the mouse brain and confirm that they are melanocytes. This is important for understanding the role of this cell type and for understanding primary meningeal melanoma, a rare disease that likely arises from normal meningeal melanocytes. PMID:26635543

  3. Brain Abscesses Complicating Acute Pneumococcal Meningitis During Etanercept Therapy

    PubMed Central

    Kasirye, Yusuf; Epperla, Narendranath; Manne, Janaki Ram; Bapani, Sowjanya; Garcia-Montilla, Romel J

    2012-01-01

    Brain abscess formation as a sequelae of community-acquired pneumococcal meningitis is extremely rare, accounting for less than 1% of all meningitis complications. Although metastatic seeding from a distal peripheral septic focus has been observed, this phenomenon most commonly occurs in the context of ear, nose and throat infections, post-cranial neurosurgical procedures, traumatic open cranial injury, or immunosuppression. We present the case of a man, 61 years old, on etanercept therapy for ankylosing spondylitis who developed multiple brain abscesses as a complication of pneumococcal meningitis. We believe that the predisposition to this extremely rare complication of a particularly aggressive pneumococcal meningitis was most likely due to the underlying immunosuppression resulting from etanercept therapy. As far as we know, this case is the first report linking multiple brain abscess formation in a patient with community-acquired pneumococcal meningitis with etanercept therapy. PMID:22634540

  4. A Retrospective Cohort Study of Lesion Distribution of HIV-1 Infection Patients With Cryptococcal Meningoencephalitis on MRI

    PubMed Central

    Xia, Shuang; Li, Xueqin; Shi, Yanbin; Liu, Jinxin; Zhang, Mengjie; Gu, Tenghui; Pan, Shinong; Song, Liucun; Xu, Jinsheng; Sun, Yan; Zhao, Qingxia; Lu, Zhiyan; Lu, Puxuan; Li, Hongjun

    2016-01-01

    Abstract The objective of this paper is to correlate the MRI distribution of cryptococcal meningoencephalitis in HIV-1 infection patients with CD4 T cell count and immune reconstitution effect. A large retrospective cohort study of HIV patients from multi-HIV centers in China was studied to demonstrate the MRI distribution of cryptococcal meningoencephalitis and its correlation with the different immune status. The consecutive clinical and neuroimaging data of 55 HIV-1-infected patients with cryptococcal meningoencephalitis collected at multi-HIV centers in China during the years of 2011 to 2014 was retrospectively analyzed. The enrolled patients were divided into 2 groups based on the distribution of lesions. One group of patients had their lesions at the central brain (group 1, n = 34) and the other group of patients had their lesions at the superficial brain (group 2, n = 21). We explored their MRI characterization of brain. In addition, we also compared their CD4 T cell counts and immune reconstitution effects between the 2 groups based on the imaging findings. No statistical difference was found in terms of age and gender between the 2 groups. The medians of CD4 T cell counts were 11.67 cells/mm3 (3.00–52.00 cells/mm3) in group 1 and 42.00 cells/mm3 (10.00–252.00 cells/mm3) in group 2. Statistical difference of CD4 T cell count was found between the 2 groups (P = 0.023). Thirteen patients in group 1 (13/34) and 12 patients in group 2 (12/21) received highly active antiretroviral treatment (HAART). Patients of group 2 received HAART therapy more frequently than patients of group 1 (P = 0.021). Central and superficial brain lesions detected by MR imaging in HIV-1-infected patients with cryptococcal meningoencephalitis are in correlation with the host immunity and HAART therapy. PMID:26871791

  5. Chitin Recognition via Chitotriosidase Promotes Pathologic Type-2 Helper T Cell Responses to Cryptococcal Infection

    PubMed Central

    Wiesner, Darin L.; Specht, Charles A.; Lee, Chrono K.; Smith, Kyle D.; Mukaremera, Liliane; Lee, S. Thera; Lee, Chun G.; Elias, Jack A.; Nielsen, Judith N.; Boulware, David R.; Bohjanen, Paul R.; Jenkins, Marc K.; Levitz, Stuart M.; Nielsen, Kirsten

    2015-01-01

    Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection. PMID:25764512

  6. Severe Cysticercal Meningitis: Clinical and Imaging Characteristics

    PubMed Central

    Cárdenas, Graciela; Jung, Helgi; Ríos, Camilo; Fleury, Agnes; Soto-Hernández, José Luís

    2010-01-01

    In disease-endemic areas, severe cysticercal meningitis (SCM) is characterized by intense inflammatory cerebrospinal fluid (CSF) and negative bacterial and fungal cultures. There have been no systematic studies of SCM. We characterized patients with SCM and compare them with neurocysticercosis (NC) patients with mild CSF abnormalities by conducting a nine-year retrospective review at a neurological referral center. Two groups of patients were compared: group A, those with severe CSF pleocytosis > 1,000 cells/mm3 (n = 12), and group B, those with CSF pleocytosis ≤ 1,000 cells/mm3 (n = 126). All patients had positive CSF results in an enzyme-linked immunosorbent assay for cysticercal antigens and negative CSF cultures for bacteria, fungi, and mycobacteria. Intracranial hypertension, meningeal signs, CSF hypoglycorrachia, and a longer clinical course of NC were more frequently seen in group A. It is likely that SCM often goes unrecognized. Its correct identification may reduce morbidity and risks of unnecessary surgery in patients with chronic NC and CSF shunts. PMID:20065006

  7. Ehrlichia Meningitis Mimicking Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Dredla, Brynn

    2015-01-01

    Thunderclap headache is a sudden and severe headache that can occur after an aneurysmal subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage is a medical emergency that requires prompt attention and hospitalization. Patients with thunderclap headache often undergo a noncontrast head computed tomography (CT) scan to ascertain SAH bleeding and, if the scan is negative, then undergo a lumbar puncture to look for cerebrospinal fluid (CSF) red blood cells (RBCs), which would be consistent with an aneurysmal leak. If the initial CT is negative and CSF is positive for RBCs, patients are usually admitted to the hospital for evaluation of intracranial aneurysm. We encountered a patient with thunderclap headache whose initial head CT was negative for SAH and whose CSF tested positive for RBCs. The patient was referred to our center for evaluation and management of aneurysmal SAH. However, on careful review of the patient’s medical history, serum laboratory values, and spinal fluid values, the patient was diagnosed with Ehrlichia chaffeensis meningitis. While Ehrlichia meningitis is rare, it is important to recognize the clinical clues that could help avoid formal cerebral angiography, a costly and potentially unnecessary procedure. We present how this case represented a cognitive framing bias and anchoring heuristic as well as steps that medical providers can use to prevent such cognitive errors in diagnosis. PMID:27053985

  8. Pneumococcal meningitis: development of a new animal model

    PubMed Central

    Wei, Benjamin P.C.; Shepherd, Robert K.; Robins-Browne, Roy M.; Clark, Graeme M.; O’Leary, Stephen J.

    2007-01-01

    Hypothesis The rat is a suitable animal to establish a model for the study of pneumococcal meningitis post cochlear implantation Background There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis post implantation and are based on relatively small animal numbers, making it difficult to assess the cause and effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant. Methods Eighteen non-implanted rats were infected with 1× 106 and 1 × 108 colony forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear and intraperitoneal) to examine for evidence of meningitis over 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 × 1010 CFU intraperitoneal, 3 × 108CFU middle ear, 1 × 106 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. Histological pattern of cochlear infections for each of the three different inoculating routes were examined. Results Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system either via the cochlear aqueduct or canaliculi perforantes of osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal

  9. Relationship Between Blood Concentrations of Hepcidin and Anemia Severity, Mycobacterial Burden, and Mortality Among Patients With HIV-Associated Tuberculosis

    PubMed Central

    Kerkhoff, Andrew D.; Meintjes, Graeme; Burton, Rosie; Vogt, Monica; Wood, Robin; Lawn, Stephen D.

    2016-01-01

    Background Anemia is very common in patients with human immunodeficiency virus (HIV)–associated tuberculosis, and hepcidin may be key in mediating this. We explored the relationship between blood hepcidin concentrations and anemia severity, mycobacterial burden and mortality in patients with HIV-associated tuberculosis. Methods Consecutive unselected HIV-infected adults in South Africa were systematically investigated for tuberculosis. Three groups were studied: 116 hospitalized inpatients with HIV infection and tuberculosis (hereafter, “hospitalized patients”), 58 ambulatory outpatients with HIV infection and newly diagnosed tuberculosis (hereafter, “ambulatory patients with tuberculosis”), and 58 ambulatory outpatients with HIV infection and without tuberculosis (hereafter, “ambulatory patients without tuberculosis”). Blood hepcidin concentrations were determined for all patients. Vital status at 3 months was determined, and independent predictors of mortality were identified. Results Median hepcidin concentrations were 38.8 ng/mL among hospitalized patients, 19.1 ng/mL among ambulatory patients with tuberculosis, and 5.9 ng/mL among ambulatory patients without tuberculosis (P < .001). In both groups with HIV-associated tuberculosis, hepcidin concentrations were strongly associated with greater anemia severity. Additionally, strong, graded associations were observed between hepcidin and composite indices of mycobacterial burden and dissemination. Patients dying within 3 months had significantly higher hepcidin concentrations, which independently predicted mortality. Conclusions High hepcidin concentrations were strongly associated with disseminated disease, anemia, and poor prognosis in patients with HIV-associated tuberculosis. Hepcidin may be a mechanistically important mediator underlying the high prevalence of severe anemia in these patients. PMID:26136467

  10. Use of peptide thrombopoietin receptor agonist romiplostim (Nplate) in a case of primary HIV-associated thrombocytopenia.

    PubMed

    Aslam, M Imran; Cardile, Anthony P; Crawford, George E

    2014-01-01

    Thrombocytopenia is frequently encountered in HIV-infected patients, and the predominant cause is primary HIV-associated thrombocytopenia (PHAT). Standard treatment regimens include optimization of antiretroviral therapy, intravenous immunoglobulin, anti-D, and corticosteroids. Retreatment due to the inability to sustain remission or inferior responses is common, and investigation into the safety and efficacy of alternative therapies is warranted. We describe novel and effective treatment of PHAT with the peptide thrombopoietin receptor agonist romiplostim in a patient with a minimal response to conventional therapy. PMID:24036490

  11. Dual tropism of HIV-1 envelopes derived from renal tubular epithelial cells of patients with HIV-associated nephropathy.

    PubMed

    Zerhouni-Layachi, Bouchra; Husain, Mohammad; Ross, Michael J; Marras, Daniele; Sunamoto, Masaaki; Liu, Xinyan; Klotman, Paul E; Klotman, Mary E

    2006-02-28

    The phenotype of HIV-1 gp120 envelope derived from renal epithelium and peripheral blood mononuclear cells (PBMC) of patients with HIV-associated nephropathy was investigated in vitro. Chimeric viruses were derived from kidney or blood and used to infect primary CD4+T cells, cell lines expressing single co-receptors and a renal epithelial cell line HPT-1. HIV-1 variants derived from renal epithelium were dual tropic whereas simultaneously derived viruses from PBMC were R5-tropic. Utilization of alternative co-receptors CCR3, BONZO and BOB, also differed. PMID:16470129

  12. Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam

    PubMed Central

    Lan, Nguyen Thi Ngoc; Thu, Nguyen Thi Nguyet; Barrail-Tran, Aurélie; Duc, Nguyen Hong; Lan, Nguyen Ngoc; Laureillard, Didier; Thi Xuan Lien, Truong; Borand, Laurence; Quillet, Catherine; Connolly, Catherine; Lagarde, Dominique; Pym, Alexander; Lienhardt, Christian; Dung, Nguyen Huy; Taburet, Anne-Marie; Harries, Anthony D

    2014-01-01

    Background Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. Methods This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. Results Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 – 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant

  13. Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment.

    PubMed

    Rappaport, Jay; Volsky, David J

    2015-06-01

    Combination antiretroviral therapy (ART) has altered the outcomes of HIV infection in treated populations by greatly reducing the incidence of opportunistic infections, cancer, and HIV-associated dementia. Despite these benefits, treated patients remain at high risk of chronic diseases affecting the peripheral organs and brain. Generally, these morbidities are attributed to persistence of latent HIV in resting T cells, chronic inflammation, and metabolic effects of ART. This review makes the case that monocytes/macrophages warrant attention as persistent reservoirs of HIV under ART, source of systemic and brain inflammation, and important targets for HIV eradication to control chronic HIV diseases. PMID:25933548

  14. Neutrophilic bacterial meningitis: pathology and etiologic diagnosis of fatal cases.

    PubMed

    Guarner, Jeannette; Liu, Lindy; Bhatnagar, Julu; Jones, Tara; Patel, Mitesh; DeLeon-Carnes, Marlene; Zaki, Sherif R

    2013-08-01

    The frequency of fatalities due to acute bacterial meningitis has decreased significantly due to vaccinations, early diagnoses, and treatments. We studied brain tissues of patients with fatal neutrophilic meningitis referred to the Centers for Disease Control for etiologic diagnosis from 2000-2009 to highlight aspects of the disease that may be preventable or treatable. Demographic, clinical, and laboratory data were extracted from records. Of 117 cases in the database with a diagnosis of meningitis or meningoencephalitis, 39 had neutrophilic inflammation in the meninges. Inflammatory cells infiltrated the superficial cortex in 16 of 39 (41%) cases. Bacteria were found using Gram and bacterial silver stains in 72% of cases, immunohistochemistry in 69% (including two cases where the meningococcus was found outside the meninges), and PCR in 74%. Streptococcus pneumoniae was the cause of the meningitis in 14 patients and Neisseria meningitidis in 9. In addition, Streptococcus spp. were found to be the cause in six cases, while Staphylococcus aureus, Staphylococcus spp., Enterococcus spp., and Fusobacterium were the cause of one case each. There were six cases in which no specific etiological agent could be determined. The mean age of the patients with S. pneumoniae was 39 years (range 0-65), with N. meningitidis was 19 years (range 7-51), whereas that for all others was 31 years (range 0-68). In summary, our study shows that S. pneumoniae continues to be the most frequent cause of fatal neutrophilic bacterial meningitis followed by N. meningitidis, both vaccine preventable diseases. PMID:23558577

  15. Cryptococcal infection of the femoral bone similar with pathologic features of vascular tumors: a case report and review of literature

    PubMed Central

    Chen, Juan; Liu, Shaoyan; Xiong, Zhongtang; Yang, Yuexin; Tan, Xuexian; Luo, Qiuping; Peng, Juan; Chen, Hui; Jiang, Qingping

    2015-01-01

    A rare case is presented of a 62-year-old man with primary isolated cryptococcal femoral osteomyelitis. Magnetic resonance imaging (MRI) revealed osteolytic destruction of his left femur. Biopsy was performed firstly. Under microscope, the lesion was compose of numerous large mononuclear cells, scattered multinucleated giant cells, a few lymphocytes and neutrophils, necrosis with serious artificial deformation. By immunohistochemistry (IHC), only CD31 and CD68 were positive, while CK, CK8/18, EMA, P63, CK7, CK20, PSAP, PSA, CD34 negative. It was considered a low grade vascularsarcoma, but not confirmed. Then the operation was done. Surgical specimen showed a lot of red-sphere materials in most cells cytoplasm. The Gomorra methenamine silver staining and PAS revealed the mucopolysaccharide-containing capsule of the Cryptococcus. Laboratory culture of lesion liquid grew a kind of yeast at 37°C. Cryptococcal femoral osteomyelitis was diagnosed at last. The patient is good now after the thorough debridement and anti-fungal treatment. PMID:26339432

  16. Pd@Ag Nanosheets in Combination with Amphotericin B Exert a Potent Anti-Cryptococcal Fungicidal Effect

    PubMed Central

    Wang, Guizhen; Fang, Wei; Ye, Chen; Hu, Hanhua; Fa, Zhenzong; Yi, Jiu; Liao, Wan-qing

    2016-01-01

    Silver nanoparticles have received considerable interest as new “nanoantibiotics” with the potential to kill drug-resistant microorganisms. Recently, a class of new core-shell nanostructures, Pd@Ag nanosheets (Pd@Ag NSs), were created using deposition techniques and demonstrated excellent inhibitory effects on various bacteria in vitro. In this study, we evaluated the antifungal activity of Pd@Ag NSs against common invasive fungal pathogens. Among these organisms, Cryptococcus neoformans complex species was most susceptible to Pd@Ag NSs, which exhibited potent antifungal activity against various molecular types or sources of cryptococcal strains including fluconazole-resistant isolates. The anticryptococcal activity of Pd@Ag NSs was significantly greater than fluconazole and similar to that of amphotericin B (AmB). At relatively high concentrations, Pd@Ag NSs exhibited fungicidal activity against Cryptococcus spp., which can likely be attributed to the disruption of cell integrity, intracellular protein synthesis, and energy metabolism. Intriguingly, Pd@Ag NSs also exhibited strong synergistic anti-cryptococcal fungicidal effects at low concentrations in combination with AmB but exhibited much better safety in erythrocytes than AmB, even at the minimal fungicidal concentration. Therefore, Pd@Ag NSs may be a promising adjunctive agent for treating cryptococcosis, and further investigation for clinical applications is required. PMID:27271376

  17. Neuropsychological sequelae of bacterial and viral meningitis.

    PubMed

    Schmidt, H; Heimann, B; Djukic, M; Mazurek, C; Fels, C; Wallesch, C-W; Nau, R

    2006-02-01

    Survivors of meningitis often complain about neurological and neuropsychological consequences. In this study, the extent of these sequelae was quantified and correlated to MRI findings. Neurological, neuropsychological and neuroradiological examinations were performed with adult patients younger than 70 years, 1-12 years after recovery from bacterial meningitis (BM; n = 59), or from viral meningitis (VM; n = 59). Patients with other potential causes for neuropsychological deficits (e.g. alcoholism) were carefully excluded. Patients were compared to 30 healthy subjects adjusted for age, gender and length of school education. With the exception of attention functions, both patient groups showed more frequently pathological results than the control group for all domains examined. Applying an overall cognitive sum score, patients after BM did not differ significantly in their performance from patients after VM. Separate analyses of various cognitive domains, however, revealed a higher rate of persistent disturbances in short-term and working memory after BM than after VM. Moreover, patients after BM exhibited greater impairment of executive functions. Associative learning of verbal material was also reduced. These deficits could not be ascribed to impaired alertness functions or decreased motivation in BM patients. Applying a logistic regression model, the neuropsychological outcome was related to the neurological outcome. Patients with a Glasgow Outcome Scale (GOS) of <5 had more frequently impaired test results for non-verbal learning and memory. GOS was also correlated with performance in executive functions. Brain volume was lower and ventricular volume was higher in the bacterial than in the VM group, and cerebral volume and the amount of white matter lesions of patients after BM were negatively correlated with short-term and working memory. In conclusion, patients after both BM and VM with favourable outcome showed affected learning and memory functions. More

  18. Ibuprofen-induced meningitis in mixed connective tissue disease.

    PubMed

    Hoffman, M; Gray, R G

    1982-06-01

    A young Black woman with mixed connective tissue disease (MCTD) developed an aseptic meningitis after receiving ibuprofen. The meningeal reaction, reported infrequently in systemic lupus erythematosus (SLE) and only once previously in MCTD, was characterized by a predominantly polymorphonuclear cerebrospinal fluid (CSF) pleocytosis and depression of CSF glucose. Reversible renal insufficiency also occurred. Features suggestive of a hypersensitivity reaction included pruritus, conjunctivitis, facial oedema, desquamation of the palms and soles, and subsequent near total alopecia. Meningeal signs responded rapidly to systemic corticosteroid therapy. Patients with MCTD as well as those with SLE may be at peculiar risk of developing this uncommon reaction to ibuprofen. PMID:6985377

  19. Intracranial meningeal chondrosarcoma--probable mesenchymal type.

    PubMed

    Rodda, R A; Franklin, C I

    1984-08-01

    A 12 year old girl with episodes of left hemiparesis for 9 months was found to have a large, partly calcified brain tumour which at craniotomy presented on the parasagittal and medial surfaces of the right frontal lobe. No dural or falx attachment could be found and naked eye removal of the tumour was achieved. At a second craniotomy 10 weeks later there was recurrent tumour attached to the falx and involving the sagittal sinus. She died 5 months later. Pathologically, almost all this malignant intracranial neoplasm comprised differentiated cartilaginous tumour. Although only a very small amount of undifferentiated mesenchymal tissue was found in the surgical material available for histological study, it is suggested the tumour can be regarded as a predominantly mature mesenchymal chondrosarcoma of the meninges. PMID:6593035

  20. Bacterial meningitis: a new risk factor

    PubMed Central

    Ataee, Ramezan Ali; Mehrabi-Tavana, Ali; Izadi, Morteza; Hosseini, Sayed Mohammad Javad; Ataee, Mohammad Hossein

    2011-01-01

    BACKGROUND: The purpose of this study is to discuss a possible new risk factor for the bacterial meningitis. METHODS: Cerebrospinal fluid collected from 270 patients was assayed. An enzyme immunosorbent assay for the detection of Staphylococcal enterotoxins A to E was used. RESULTS: The results indicated that the frequency of Coagulase Negative Staphylococci (CoNS) was 35 (20.46%). An important finding of this research was that the CoNS isolates produced enterotoxin C and D or enterotoxin C and E. CONCLUSIONS: This is the first report of enterotoxin-producing Coagulase Negative Staphylococci isolated from CSF patients. Therefore, these enterotoxins probably act as risk factors in the bacterial invasion into central nervous system. PMID:22091233

  1. Gemifloxacin Is Effective in Experimental Pneumococcal Meningitis

    PubMed Central

    Smirnov, A.; Wellmer, A.; Gerber, J.; Maier, K.; Henne, S.; Nau, R.

    2000-01-01

    In a rabbit model of Streptococcus pneumoniae meningitis, 5 mg of gemifloxacin mesylate (SB-265805) per kg/h reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as 10 mg of ceftriaxone per kg/h (Δlog CFU/ml/h ± standard deviation [SD], −0.25 ± 0.09 versus −0.38 ± 0.11; serum and CSF concentrations of gemifloxacin were 2.1 ± 1.4 mg/liter and 0.59 ± 0.38 mg/liter, respectively, at 24 h). Coadministration of 1 mg of dexamethasone per kg did not affect gemifloxacin serum and CSF levels (2.7 ± 1.4 mg/liter and 0.75 ± 0.34 mg/liter, respectively, at 24 h) or activity (Δlog CFU/ml/h ± SD, −0.26 ± 0.11). PMID:10681354

  2. The comorbidity of HIV-associated neurocognitive disorders and Alzheimer's disease: a foreseeable medical challenge in post-HAART era.

    PubMed

    Xu, Jiqing; Ikezu, Tsuneya

    2009-06-01

    Although the introduction of highly active antiretroviral therapy (HAART) has led to a strong reduction of HIV-associated dementia (HAD) incidence, the prevalence of minor HIV-1-associated neurocognitive disorder (HAND) is rising among AIDS patients. HAART medication has shifted neuropathology from a subacute encephalitic condition to a subtle neurodegenerative process involving synaptic and dendritic degeneration, particularly of hippocampal neurons that are spared prior to HAART medication. Considerable neuroinflammation coupled with mononuclear phagocyte activation is present in HAART-medicated brains, particularly in the hippocampus. Accumulating evidence suggests that the resultant elevated secretion of pro-inflammatory cytokines such as interferon-gamma, tumor necrosis factor-alpha, and interleukin-1beta can increase amyloid-beta peptide (Abeta) generation and reduce Abeta clearance. Recent advancements in Alzheimer's disease (AD) research identified Abeta biogenesis and clearance venues that are potentially influenced by HIV viral infection, providing new insights into beta-amyloidosis segregation in HIV patients. Our study suggests enhanced beta-amyloidosis in ART-treated HAD and HIV-associated encephalitis brains and suppression of Abeta clearance by viral infection of human primary macrophages. A growing awareness of potential convergent mechanisms leading to neurodegeneration shared by HIV and Abeta points to a significant chance of comorbidity of AD and HAND in senile HIV patients, which calls for a need of basic studies. PMID:19016329

  3. Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review

    PubMed Central

    2013-01-01

    The HIV-associated tuberculosis (TB) epidemic remains a huge challenge to public health in resource-limited settings. Reducing the nearly 0.5 million deaths that result each year has been identified as a key priority. Major progress has been made over the past 10 years in defining appropriate strategies and policy guidelines for early diagnosis and effective case management. Ascertainment of cases has been improved through a twofold strategy of provider-initiated HIV testing and counseling in TB patients and intensified TB case finding among those living with HIV. Outcomes of rifampicin-based TB treatment are greatly enhanced by concurrent co-trimoxazole prophylaxis and antiretroviral therapy (ART). ART reduces mortality across a spectrum of CD4 counts and randomized controlled trials have defined the optimum time to start ART. Good outcomes can be achieved when combining TB treatment with first-line ART, but use with second-line ART remains challenging due to pharmacokinetic drug interactions and cotoxicity. We review the frequency and spectrum of adverse drug reactions and immune reconstitution inflammatory syndrome (IRIS) resulting from combined treatment, and highlight the challenges of managing HIV-associated drug-resistant TB. PMID:24295487

  4. A Case of Tuberculous Meningitis with Tuberculoma in Nonimmunocompromised Immigrant

    PubMed Central

    Arshad, Hammad; Bihler, Eric

    2016-01-01

    We present a case of tuberculous (TB) meningitis in nonimmunocompromised immigrant worker who initially presented with headache and later with generalized tonic clonic seizures and disseminated tuberculosis. PMID:27413568

  5. Future challenges in the elimination of bacterial meningitis.

    PubMed

    Bottomley, Matthew J; Serruto, Davide; Sáfadi, Marco Aurélio Palazzi; Klugman, Keith P

    2012-05-30

    Despite the widespread implementation of several effective vaccines over the past few decades, bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Group B Streptococcus (GBS) still results in unacceptably high levels of human mortality and morbidity. A residual disease burden due to bacterial meningitis is also apparent due to a number of persistent or emerging pathogens, including Mycobacterium tuberculosis, Escherichia coli, Staphylococcus aureus, Salmonella spp. and Streptococcus suis. Here, we review the current status of bacterial meningitis caused by these pathogens, highlighting how past and present vaccination programs have attempted to counter these pathogens. We discuss how improved pathogen surveillance, implementation of current vaccines, and development of novel vaccines may be expected to further reduce bacterial meningitis and related diseases in the future. PMID:22607903

  6. Use of Intrathecal Fluorescein in Recurrent Meningitis after Cochlear Implantation

    PubMed Central

    Tandon, Swati; Singh, Satinder; Sharma, Shalabh; Lahiri, Asish K.

    2016-01-01

    Introduction: Congenital anomalies of the cochlea and labyrinth can be associated with meningitis and varying degrees of hearing loss or deafness. Despite antibiotics, meningitis remains a life threatening complication. Case Report: We report a case of recurrent meningitis following episodes of otitis media in a cochlear implantee child with bilateral vestibulocochlear malformation, due to fistula in the stapes footplate. Intrathecal fluorescin was used to identify the leak site. Conclusion: Recurrent meningitis can indicate for possible immunological or anatomical abnormalities as well for chronic parameningeal infections. Intraoperative use of intrathecal fluorescin is an ideal investigative tool to demonstrate cerebrospinal fluid (CSF) leak site in patients in whom other investigations fail to do so. PMID:27429952

  7. Cerebrospinal fluid "leaks" and meningitis following acoustic tumor surgery.

    PubMed

    Hughes, G B; Glasscock, M E; Hays, J W; Jackson, C G; Sismanis, A

    1982-01-01

    We reviewed 271 intracanalicular and cerebellopontine angle lesions removed over the past ten years, 237 by the translabyrinthine or combined approach which created a mastoid defect. The patients were divided into three groups with the following results: (1) obliteration of the mastoid defect combined with older wound closure techniques in the first 188 patients produced CSF leakage in 25% and meningitis in 16% of cases; (2) not obliterating the defect intentionaly in 16 patients produced CSF leakage in 50% and meningitis in 25% of cases; (3) obliteration of the defect combined with newer packing and closure techniques in the last 33 patients produced CSF leakage and meningitis in only 6% of cases. Four problem areas were identified: the eustachian tube, middle ear, mastoid defect, and postauricular wound. Of these, obliteration of the mastoid defect was most important in minimizing postoperative CSF wound leakage, CSF rhinorrhea, and meningitis. PMID:6806745

  8. Five Cases of Recurrent Meningitis Associated with Chronic Strongyloidiasis

    PubMed Central

    Shimasaki, Teppei; Chung, Heath; Shiiki, Soichi

    2015-01-01

    Although meningitis secondary to chronic strongyloidiasis is a rare complication, it is associated with a high mortality rate. Recurrent meningitis can occur if the underlying parasitic infection is left untreated. We report five cases of recurrent meningitis related to chronic strongyloidiasis that were associated with human T-lymphotropic virus type 1 (HTLV-1) infection. Common causative organisms are Escherichia coli, Streptococcus bovis, and Klebsiella pneumonia. One patient died during the second episode of meningitis. Three patients showed significant gastrointestinal and respiratory symptoms before developing headache and fever. In four cases, patients developed multiple recurrences even with the treatment of thiabendazol. Ivermectin seems to be a better agent compared with thiabendazol to achieve eradication of strongyloidiasis. PMID:25548379

  9. A case of postpartum Group B streptococcal meningitis

    PubMed Central

    Gayford, Kylie; McCarthy, Ana; Hague, William M

    2011-01-01

    A case of postpartum Group B streptococcal meningitis, a rare complication of an invasive infection by a common maternal commensal bacterium, which demonstrates the need to develop rapid and accurate antepartum and intrapartum screening methods for this organism.

  10. Enterococcus gallinarum meningitis in an immunocompetent host: a case report.

    PubMed

    Antonello, Vicente Sperb; Zenkner, Francis de Moura; França, Josiane; Santos, Breno Riegel

    2010-01-01

    We describe a rare case of a 53-year-old man with a long history of alcohol abuse, with Enterococcus gallinarum meningitis, an organism that rarely causes human infection and is primarily found in the gastrointestinal tract of poultry. The patient improved with high-dose ampicillin and gentamicin therapy. To our knowledge, this is the first Brazilian reported case of E. gallinarum meningitis and probably the first case described in an immunocompetent host. PMID:20464133

  11. An aseptic meningitis picture from incipient brain abscess.

    PubMed

    Singer, J I

    1992-08-01

    A preadolescent with headache and stiff neck presented for emergency department care. The presumptive diagnosis of viral meningitis was entertained on the basis of clinical examination and cerebrospinal fluid analysis. Events subsequent to his release from the department formed the stimulus for this report. It is apparent that patients with complicated sinusitis may present with a constellation of findings consistent with viral meningitis. PMID:1513739

  12. Liver metastasis of meningeal hemangiopericytoma: a study of 5 cases

    PubMed Central

    Lo, Regina C.; Suriawinata, Arief A.; Rubin, Brian P.

    2016-01-01

    Mesenchymal tumors in the liver, whether primary or metastatic, are rare. Meningeal hemangiopericytoma (HPC) is characteristically associated with delayed metastasis and the liver is one of the most common sites. Despite its consistent histological features, a pathological diagnosis of HPC in the liver is sometimes not straightforward due to its rarity and usually remote medical history of the primary meningeal tumor. In this report, the clinicopathological features of 5 cases of metastatic HPC to the liver were reviewed and described. PMID:27044772

  13. Management of meningitis due to antibiotic-resistant Acinetobacter species

    PubMed Central

    Kim, Baek-Nam; Peleg, Anton Y; Lodise, Thomas P; Lipman, Jeffrey; Li, Jian; Nation, Roger; Paterson, David L

    2009-01-01

    Acinetobacter meningitis is becoming an increasingly common clinical entity, especially in the postneurosurgical setting, with mortality from this infection exceeding 15%. Infectious Diseases Society of America guidelines for therapy of postneurosurgical meningitis recommend either ceftazidime or cefepime as empirical coverage against Gram-negative pathogens. However, assessment of the pharmacodynamics of these cephalosporins in cerebrospinal fluid suggests that recommended doses will achieve pharmacodynamic targets against fewer than 10% of contemporary acinetobacter isolates. Thus, these antibiotics are poor options for suspected acinetobacter meningitis. From in vitro and pharmacodynamic perspectives, intravenous meropenem plus intraventricular administration of an aminoglycoside may represent a superior, albeit imperfect, regimen for suspected acinetobacter meningitis. For cases of meningitis due to carbapenem-resistant acinetobacter, use of tigecycline is not recommended on pharmacodynamic grounds. The greatest clinical experience rests with use of polymyxins, although an intravenous polymyxin alone is inadvisable. Combination with an intraventricularly administered antibiotic plus removal of infected neurosurgical hardware appears the therapeutic strategy most likely to succeed in this situation. Unfortunately, limited development of new antibiotics plus the growing threat of multidrug-resistant acinetobacter is likely to increase the problems posed by acinetobacter meningitis in the future. PMID:19324297

  14. Randomized, Double-Blind, Crossover Trial of Amitriptyline for Analgesia in Painful HIV-Associated Sensory Neuropathy

    PubMed Central

    Dinat, Natalya; Marinda, Edmore; Moch, Shirra; Rice, Andrew S. C.; Kamerman, Peter R.

    2015-01-01

    We conducted a randomized, double-blind, placebo-controlled, crossover study at a single center in South Africa, to ascertain whether amitriptyline is an effective analgesic for painful HIV-associated sensory neuropathy of moderate to severe intensity in: i) antiretroviral drug naive individuals, and ii) antiretroviral drug users. 124 HIV-infected participants (antiretroviral drug naive = 62, antiretroviral drug users = 62) who met the study criteria for painful HIV-associated sensory neuropathy were randomized to once-daily oral amitriptyline (titrated to a median: interquartile range of 50: 25-50 mg) or placebo for six weeks, followed by a three-week washout period and subsequent treatment crossover. The primary outcome measure was change from baseline in worst pain intensity of the feet (measured by participant self-report using an 11-point numerical pain rating scale) after six weeks of treatment. 122 of 124 participants completed all study visits and were included in the analysis of the primary outcome. In the antiretroviral drug-naive group (n = 61) there was no significant difference in the mean change in pain score from baseline after six weeks of treatment with placebo or amitriptyline [amitriptyline: 2.8 (SD 3.3) vs. placebo: 2.8 (3.4)]. Similarly, there was no significant difference in the change in pain score after six weeks of treatment with placebo or amitriptyline in the antiretroviral drug-user group (n = 61) [amitriptyline: 2.7 (3.3) vs. placebo: 2.1 (2.8)]. Controlling for period effects and treatment order effects did not alter the outcome of the analyses. Nor did analyzing the intention-to-treat cohort (missing data interpolated using baseline observation carried forward) alter the outcome of the analyses. In summary, amitriptyline, at the doses used here, was no more effective than an inactive placebo at reducing pain intensity in individuals with painful HIV-associated sensory neuropathy of moderate to severe intensity, irrespective of whether

  15. Streptococcus pneumoniae Meningitis Presenting with Acute Urinary Retention and Emphysematous Cystitis.

    PubMed

    Mizuno, Yasushi; Doi, Asako; Endo, Akiko; Nishioka, Hiroaki

    2016-01-01

    A combination of acute urinary retention and aseptic meningitis has occasionally been described, which is referred to as meningitis-retention syndrome. In contrast, acute urinary retention has rarely been reported in bacterial meningitis. We herein report a case of Streptococcus pneumoniae meningitis presenting with acute urinary retention which led to emphysematous cystitis in an elderly woman. She presented with impaired consciousness and a distended lower abdomen. She was diagnosed with pneumococcal meningitis by lumbar puncture. Abdominal computed tomography revealed the presence of emphysematous cystitis. She completely recovered with antibiotic therapy without any complications. Acute urinary retention can occur secondary to pneumococcal meningitis. PMID:27477423

  16. HIV-associated dementia in the Dominican Republic: a consequence of stigma, domestic abuse and limited health literacy.

    PubMed

    Santoso, Laura Frances; Erkkinen, Emily E; Deb, Anindita; Adon, Carlos

    2016-01-01

    A 38-year-old Dominican woman presented at an infectious disease clinic in Santo Domingo, with subacute dementia and psychomotor slowing. Based on physical findings and laboratory results, she was diagnosed with AIDS and HIV-associated dementia (HAD). She subsequently began combined antiretroviral therapy (cART). Psychiatric complications later emerged: the patient developed suicidal ideation and her partner expressed homicidal thoughts. After extensive interviewing, it was revealed that the patient had known her HIV-positive serostatus for years. However, several factors, including HIV stigma, mental illness stigma, domestic abuse and limited health literacy, had prevented her from seeking treatment and from disclosing her status to her partner. This patient's HIV was unmanaged as a consequence of social and educational circumstance, which resulted in severe sequelae, namely HAD. Compounded barriers to care can lead to the presentation of disease complications that are rarely seen today in countries with widespread access to antiretroviral therapy. PMID:27097891

  17. Chronic loss of subcutaneous adipose tissue in HIV-associated lipodystrophy may not be associated with accelerated apoptosis.

    PubMed

    Mynarcik, Dennis; Wei, Lin-Xiang; Komaroff, Eugene; Ferris, Robert; McNurlan, Margaret; Gelato, Marie

    2005-03-01

    HIV-associated lipodystrophy (HIV-LD) is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue (SAT). The present study examined the rate of apoptosis in SAT with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders. Individuals with HIV-LD were compared with HIV-infected subjects without LD and subjects without HIV disease. Although apoptosis was observed in subjects with HIV-LD, there was no difference in the incidence of individuals with apoptosis among those with HIV-LD (10 of 22 subjects), those with HIV but no LD (13 of 25 subjects), and those without HIV disease (13 of 27 subjects). These data suggest that HIV-related chronic loss of SAT may not always be associated with increased frequency of adipocyte apoptosis. PMID:15776544

  18. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    PubMed

    Sufiawati, Irna; Tugizov, Sharof M

    2014-01-01

    Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals. PMID:24586397

  19. HIV-Associated Disruption of Tight and Adherens Junctions of Oral Epithelial Cells Facilitates HSV-1 Infection and Spread

    PubMed Central

    Sufiawati, Irna; Tugizov, Sharof M.

    2014-01-01

    Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals. PMID:24586397

  20. Novel p75 neurotrophin receptor ligand stabilizes neuronal calcium, preserves mitochondrial movement and protects against HIV associated neuropathogenesis.

    PubMed

    Meeker, Rick B; Poulton, Winona; Clary, Gillian; Schriver, Michael; Longo, Frank M

    2016-01-01

    Human immunodeficiency virus (HIV) rapidly penetrates into the brain and establishes a persistent infection of macrophages/microglia. Activation of these cells by HIV results in the secretion of soluble factors that destabilize neuronal calcium homeostasis, encourage oxidative stress and result in neural damage. This damage is thought to underlie the cognitive-motor dysfunction that develops in many HIV-infected patients. Studies have suggested that neurotrophins may protect neurons from the toxic effects of HIV-associated proteins. To better understand the pathogenic mechanisms and the neuroprotective potential of neurotrophin ligands, we evaluated neuronal damage, calcium homeostasis and mitochondrial functions after exposure of cultured rat neurons directly to HIV gp120 or to conditioned medium from human monocyte-derived macrophages treated with gp120. We then assessed the ability of a new non-peptide p75 neurotrophin receptor ligand, LM11A-31, to stabilize calcium homeostasis and prevent the development of pathology. Each toxic challenge resulted in a delayed accumulation of intracellular calcium coupled to a decrease in the rate of calcium clearance from the cell. The delayed calcium accumulation correlated with the development of focal dendritic swellings (beading), cytoskeletal damage and impaired movement of mitochondria. Addition of LM11A-31 to the cultures at nanomolar concentrations eliminated cell death, significantly reduced the pathology, suppressed the delayed accumulation of calcium and restored mitochondrial movements. The potent neuroprotection and the stabilization of calcium homeostasis indicate that LM11A-31 may have excellent potential for the treatment of HIV-associated neurodegeneration. PMID:26424436

  1. Meningococcal carriage in the African meningitis belt

    PubMed Central

    2013-01-01

    A meningococcal serogroup A polysaccharide/tetanus toxoid conjugate vaccine (PsA-TT) (MenAfriVac#x2122;) is being deployed in countries of the African meningitis belt. Experience with other polysaccharide/protein conjugate vaccines has shown that an important part of their success has been their ability to prevent the acquisition of pharyngeal carriage and hence to stop transmission and induce herd immunity. If PsA-TT is to achieve the goal of preventing epidemics, it must be able to prevent the acquisition of pharyngeal carriage as well as invasive meningococcal disease and whether PsA-TT can prevent pharyngeal carriage needs to be determined. To address this issue, a consortium (the African Meningococcal Carriage (MenAfriCar) consortium) was established in 2009 to investigate the pattern of meningococcal carriage in countries of the African meningitis belt prior to and after the introduction of PsA-TT. This article describes how the consortium was established, its objectives and the standardised field and laboratory methods that were used to achieve these objectives. The experience of the MenAfriCar consortium will help in planning future studies on the epidemiology of meningococcal carriage in countries of the African meningitis belt and elsewhere. Un vaccin conjugué contenant un polysaccharide du sérogroupe A méningococcique et une anatoxine du tétanos (PsA-TT) (MenAfriVac™) est en cours de déploiement dans les pays de la ceinture africaine de la méningite. L’ expérience avec d’ autres vaccins conjugués polysaccharide/protéine a montré qu’ une partie importante de leur succès a été leur capacité à empêcher l’ acquisition du portage pharyngé et donc à arrêter la transmission et à induire une immunité de group. Si PsA-TT doit d’ atteindre l’ objectif de prévenir les épidémies, il devrait être en mesure d’ empêcher l’ acquisition du portage pharyngé ainsi que la méningococcie invasive et le fait que PsA-TT puisse emp

  2. Diagnosis of tuberculous meningitis: challenges and promises.

    PubMed

    Philip, N; William, T; William, D V

    2015-04-01

    Tuberculosis (TB) which is caused by Mycobacterium tuberculosis infects primarily the lungs but it also affects other parts of the body. Tuberculous meningitis (TBM) is the most severe form of TB and has the highest mortality and morbidity rate compared to other forms of TB. It is common in young children and HIV-infected patients, but is also seen in adults. Despite anti-tuberculosis treatment, TBM is still a major cause of death and neurological sequelae as treatment given to the patients is often delayed. Early diagnosis is challenging due to the non-specific symptoms of TBM and the low number of tubercle bacilli in cerebrospinal fluid (CSF). Until now, there is no established diagnostic method that can rapidly detect M. tuberculosis in TBM patients with high sensitivity and specificity. The emergence of drug resistant M. tuberculosis strains further complicates the diagnosis and treatment regimen of TBM. This review summarizes challenges of the currently used diagnostic methods and the potential future use of molecular diagnostic methods for TBM. PMID:25890607

  3. Appearance of the canine meninges in subtraction magnetic resonance images.

    PubMed

    Lamb, Christopher R; Lam, Richard; Keenihan, Erin K; Frean, Stephen

    2014-01-01

    The canine meninges are not visible as discrete structures in noncontrast magnetic resonance (MR) images, and are incompletely visualized in T1-weighted, postgadolinium images, reportedly appearing as short, thin curvilinear segments with minimal enhancement. Subtraction imaging facilitates detection of enhancement of tissues, hence may increase the conspicuity of meninges. The aim of the present study was to describe qualitatively the appearance of canine meninges in subtraction MR images obtained using a dynamic technique. Images were reviewed of 10 consecutive dogs that had dynamic pre- and postgadolinium T1W imaging of the brain that was interpreted as normal, and had normal cerebrospinal fluid. Image-anatomic correlation was facilitated by dissection and histologic examination of two canine cadavers. Meningeal enhancement was relatively inconspicuous in postgadolinium T1-weighted images, but was clearly visible in subtraction images of all dogs. Enhancement was visible as faint, small-rounded foci compatible with vessels seen end on within the sulci, a series of larger rounded foci compatible with vessels of variable caliber on the dorsal aspect of the cerebral cortex, and a continuous thin zone of moderate enhancement around the brain. Superimposition of color-encoded subtraction images on pregadolinium T1- and T2-weighted images facilitated localization of the origin of enhancement, which appeared to be predominantly dural, with relatively few leptomeningeal structures visible. Dynamic subtraction MR imaging should be considered for inclusion in clinical brain MR protocols because of the possibility that its use may increase sensitivity for lesions affecting the meninges. PMID:24833219

  4. The Meninges: New Therapeutic Targets For Multiple Sclerosis

    PubMed Central

    Russi, Abigail E.; Brown, Melissa A.

    2014-01-01

    The CNS is largely comprised of non-regenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data has established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood barrier integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting of the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the blood brain barrier. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. PMID:25241937

  5. Chronic candidal meningitis: an uncommon manifestation of candidiasis.

    PubMed

    Voice, R A; Bradley, S F; Sangeorzan, J A; Kauffman, C A

    1994-07-01

    Chronic meningitis is an uncommon manifestation of candidiasis. We present the case of an elderly woman who had symptoms such as headache, malaise, and fever for 8 months and was found to have Candida albicans meningitis, and we review 17 similar cases. An underlying illness or risk factor for candidiasis was present in only 13 (72%) of the 18 patients. Headache, fever, and nuchal rigidity were the predominant clinical findings. Analysis of CSF showed either mononuclear or neutrophilic pleocytosis, an elevated protein level, and a decreased level of glucose. Only 17% of CSF smears were positive, and only 44% of initial CSF cultures yielded Candida species. In four cases, Candida species grew only after special techniques were used; in three cases, CSF cultures remained negative. The overall mortality associated with candidal meningitis was 53%, but among 12 patients who were treated and followed, the rate was 33%. In addition to acute meningitis seen with disseminated infection, Candida species can cause chronic meningitis that mimics tuberculosis and the more common fungal meningitides, such as cryptococcosis. PMID:7948559

  6. Dementia and capsular genu ischemia in patients with severe bacterial meningitis.

    PubMed

    Naito, Makoto; Johkura, Ken; Momoo, Takayuki; Nomiya, Tamaki; Kudo, Yosuke; Kuroiwa, Yoshiyuki

    2010-04-01

    Infarction in the genu of the internal capsule causes dementia that is characterized by abulia, lethargy and memory loss without obvious motor palsy (capsular genu syndrome). We found infarction or decreased cerebral blood flow in the genu of the internal capsule in 6 of 13 patients with severe bacterial meningitis. Four of these six patients developed post-meningitis dementia, characterized by abulia, lethargy, and memory loss. Of 24 patients with viral meningitis, none developed capsular genu ischemia or post-meningitis dementia. In patients with severe bacterial meningitis, capsular genu ischemia may play some role in the development of post-meningitis dementia. In patients with viral meningitis, absence of such ischemia may explain, at least in a part, the rarity of post-meningitis dementia. PMID:19838622

  7. [Successful treatment for cryptococcal meningoencephalitis complicated by cerebral salt-wasting syndrome in a patient with chronic lymphocytic leukemia: A clinical case].

    PubMed

    Potapenko, V G; Konovalenko, I B; Oksema, E V; Filippova, L N; Dulaeva, E N; Derevyannykh, N A; Krasnoruzhsky, A I; Klimovich, A V; Klimko, N N; Medvedeva, N V

    2015-01-01

    Cryptococcus neoformans is a common agent of fungal meningoencephalitis in immunocompromised patients. Cerebral salt-wasting syndrome is one of the rare causes of severe hyponatremia in patients with CNS diseases. The paper describes the first clinical case of a patient, whose onset of chronic lymphocytic leukemia was complicated by cryptococcal meningoencephalitis presenting with mental disorders and severe electrolytic imbalance. Antifungal treatment with amphotericin B and fluconazole could alleviate an infectious process and metabolic disturbances. PMID:26821425

  8. Stroke Secondary to Aseptic Meningitis After Endovascular Treatment of a Giant Aneurysm with Parent Artery Occlusion

    SciTech Connect

    Doenmez, Halil Mavili, Ertugrul Ikizceli, Tuerkan; Durak, Ahmet Candan; Kurtsoy, Ali

    2009-07-15

    Aseptic meningitis related to hydrogel-coated coils is a known complication, but it is extremely rare after platinum bare coil aseptic meningitis. Here we report the development of aseptic meningitis causing brain stem and cerebellar infarct in a patient with a giant aneurysm treated with bare platinum coils. We conclude that aneurysm size is an important factor affecting the occurrence of aseptic meningitis associated with stroke.

  9. Acute myelopathy with sudden paraplegia as the sole manifestation of meningococcal meningitis.

    PubMed

    Ibrahim, Wanis H; Elalamy, Osama R; Doiphode, Sanjay H; Mobyaed, Hassan; Darweesh, Adham

    2010-01-01

    Acute myelopathy with sudden paraplegia is a very rare manifestation of meningococcal meningitis, with only a few cases reported in the literature. In almost all previously reported cases, other clinical manifestations of meningitis, such as fever, headache, and neck stiffness preceded acute myelopathy. In this paper, we report a case of acute myelopathy with sudden paraplegia as the sole manifestation of meningococcal meningitis, in the absence of other clinical manifestations of meningitis. PMID:21483588

  10. Acute myelopathy with sudden paraplegia as the sole manifestation of meningococcal meningitis

    PubMed Central

    Ibrahim, Wanis H.; Elalamy, Osama R.; Doiphode, Sanjay H.; Mobyaed, Hassan; Darweesh, Adham

    2010-01-01

    Acute myelopathy with sudden paraplegia is a very rare manifestation of meningococcal meningitis, with only a few cases reported in the literature. In almost all previously reported cases, other clinical manifestations of meningitis, such as fever, headache, and neck stiffness preceded acute myelopathy. In this paper, we report a case of acute myelopathy with sudden paraplegia as the sole manifestation of meningococcal meningitis, in the absence of other clinical manifestations of meningitis. PMID:21483588

  11. The Evolution of the Meningitis Vaccine Project

    PubMed Central

    Tiffay, Kathleen; Jodar, Luis; Kieny, Marie-Paule; Socquet, Muriel; LaForce, F. Marc

    2015-01-01

    Background. In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Methods. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a “virtual vaccine company,” and over the next decade managed a network of public–private and public–public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. Results. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. Conclusions. The development, through a public–private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. PMID:26553666

  12. Severe cochlear dysplasia causing recurrent meningitis: a surgical lesson.

    PubMed

    Stevenson, D S; Proops, D W; Phelps, P D

    1993-08-01

    Meningitis may be the sole presenting sign of a cerebrospinal fluid (CSF) fistula of the temporal bone. An eight-year-old boy suffering from recurrent meningitis was found to have bilateral severe cochlear dysplasia. Bilateral tympanotomies were performed, planning to obliterate each vestibule. In the right ear a stapedectomy was performed, resulting in a torrential 'CSF gusher' and difficulty in packing the vestibule. CSF rhinorrhoea requiring revision surgery and two episodes of gram-negative bacterial meningitis complicated the post-operative management, resulting in a prolonged hospital stay. Subsequently, the left ear was managed in a different fashion, leaving the stapes in situ, with grafts placed to seal the oval window niche. We would recommend this alternative procedure in cases of severe cochlear dysplasia, where abnormalities of the vestibule and basal turn of the cochlea mean that performing a stapedectomy to pack the vestibule may result in a severe 'CSF gusher', by opening directly into the subarachnoid space. PMID:8409727

  13. Vaccine preventable meningitis in Malaysia: epidemiology and management.

    PubMed

    McNeil, Hannah C; Jefferies, Johanna M C; Clarke, Stuart C

    2015-06-01

    Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9-25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis. PMID:25962101

  14. Citramalic acid in cerebrospinal fluid of patients with bacterial meningitis.

    PubMed

    Perlman, S; Carr, S A

    1984-07-01

    Cerebrospinal fluid (CSF) from uninfected patients and from patients with bacterial and viral meningitis was analyzed by gas-liquid chromatography, with use of a flame ionization detector, and by gas chromatography-mass spectrometry. The resulting profiles were consistent and reproducible. Hydroxy acids were the compounds found in greatest abundance in both normal and infected CSF. Control experiments to establish the sensitivity and efficiency of the extraction and derivatization methods are also presented. Constituents of CSF from patients with bacterial meningitis differed quantitatively and qualitatively from those of CSF from uninfected patients or patients with nonbacterial infections. CSF from seven of eight patients with bacterial meningitis contained citramalic acid, a compound not previously identified in either normal or infected CSF. The implications of these findings are discussed. PMID:6145530

  15. Multiplex PCR for rapid diagnosis of tuberculous meningitis.

    PubMed

    Kusum, Sharma; Aman, Sharma; Pallab, Ray; Kumar, Sharma Shiv; Manish, Modi; Sudesh, Prabhakar; Subhash, Varma; Meera, Sharma

    2011-10-01

    Rapid and specific diagnosis of tubercular meningitis is of paramount importance to decrease morbidity and mortality. The aim of the study was to evaluate multiplex PCR using protein b, MPB 64, and IS6110 primers directed against M. tuberculosis complex for the diagnosis of tuberculous meningitis (TBM). Multiplex PCR was performed on 18 TBM confirmed cases (culture was positive), 92 clinically suspected TBM cases and 100 non-TBM (control group) patients. Multiplex PCR had a sensitivity of 94.4% for confirmed cases and specificity of 100% for confirmed TBM cases. In 92 clinically diagnosed but unconfirmed TBM cases, multiplex PCR was positive in 84.78% cases. The overall sensitivity of microscopy, culture and multiplex cases were 1.81, 16.73, and 86.63% and specificity was 100, 100, and 100% respectively. Multiplex PCR using protein b, MPB 64, and IS6110 primers has a high sensitivity and specificity in diagnosis of tubercular meningitis. PMID:21455603

  16. Probable acute disseminated encephalomyelitis due to Haemophilus influenzae meningitis.

    PubMed

    Beleza, Pedro; Ribeiro, Manuel; Pereira, João; Ferreira, Carla; Jordão, Maria José; Almeida, Fátima

    2008-05-01

    We report the case of a 17-year-old male on long-term steroid therapy for minimal lesion glomerulopathy who, after an upper respiratory infection, presented with Haemophilus influenzae type b meningitis. Twenty-four hours later he developed depression of consciousness which progressed to coma and left hemiparesis. Brain magnetic resonance imaging (MRI) revealed multiple lesions (hyperintense on T2 and slightly hypointense on Tl) involving mainly white matter suggestive of inflammation. MRI features were compatible with acute disseminated encephalomyelitis (ADEM), although a differential diagnosis included cerebritis or vasculitis, secondary to bacterial meningitis. The patient was treated with high-dose steroids which resulted in a gradual improvement followed by complete clinical recovery. We propose a diagnosis of ADEM was the best diagnosis because of the radiological features and response to steroids. The occurrence of ADEM associated with acute meningitis, however rare, represents an important diagnostic challenge for the clinician. PMID:18355336

  17. Recent advances in the pathogenesis and pathophysiology of bacterial meningitis.

    PubMed

    Quagliarello, V J; Scheld, W M

    1986-11-01

    Bacterial meningitis continues to account for worldwide morbidity and mortality despite the advent of effective bactericidal antibiotic therapy. Recent advances over the past 10 years in the development of experimental animal models as well as basic investigation into critical bacterial surface virulence factors have begun to clarify a conceptual framework for understanding the mechanism of meningitis development in humans. Basic observations regarding competing host defenses and bacterial virulence factors have supported a pathogenetic sequence of mucosal colonization with a meningeal pathogen; systemic host invasion with intravascular replication; blood brain barrier penetration and unimpeded CSF proliferation amid the impaired host defenses in the CSF milieu; and pathophysiologic sequelae including vasogenic, cytotoxic, and interstitial brain edema (and other processes) accounting for irreversible neuronal injury and death. Only through continued basic investigation into each of these pathogenetic steps will significant reductions in morbidity and mortality ensue. PMID:3535498

  18. Streptococcus salivarius meningitis and sphenoid sinus mucocele. Case report and literature review.

    PubMed

    Conte, Aristide; Chinello, Pierangelo; Civljak, Rok; Bellussi, Angelo; Noto, Pasquale; Petrosillo, Nicola

    2006-01-01

    We report a case of meningitis caused by Streptococcus salivarius in a 49-year-old woman with a previously undiagnosed cerebrospinal fluid fistula due to a sphenoid mucocele. We reviewed the literature concerning meningitis caused by this uncommon organism and to the best of our knowledge this is the first case of S. salivarius meningitis associated with sphenoid mucocele. PMID:15936084

  19. Exome Array Analysis of Susceptibility to Pneumococcal Meningitis.

    PubMed

    Kloek, Anne T; van Setten, Jessica; van der Ende, Arie; Bots, Michiel L; Asselbergs, Folkert W; Valls Serón, Mercedes; Brouwer, Matthijs C; van de Beek, Diederik; Ferwerda, Bart

    2016-01-01

    Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10(-7)). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10(-6); G allele OR 3.21 [95% CI 2.05-5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10(-5); G allele OR 0.66 [95% CI 0.54-0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10(-7)). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis. PMID:27389768

  20. Streptococcus suis Meningitis: A Systematic Review and Meta-analysis

    PubMed Central

    van Samkar, Anusha; Brouwer, Matthijs C.; Schultsz, Constance; van der Ende, Arie; van de Beek, Diederik

    2015-01-01

    Background Streptococcus suis is the most common cause of meningitis in pork consuming and pig rearing countries in South-East Asia. We performed a systematic review of studies on S. suis meningitis to define the clinical characteristics, predisposing factors and outcome. Methodology Studies published between January 1, 1980 and August 1, 2015 were identified from main literature databases and reference lists. Studies were included if they were written in West-European languages and described at least 5 adult patients with S. suis meningitis in whom at least one clinical characteristic was described. Findings We identified 913 patients with S. suis meningitis included in 24 studies between 1980 and 2015. The mean age was 49 years and 581 of 711 patients were male (82%). Exposure to pigs or pork was present in 395 of 648 patients (61%) while other predisposing factors were less common. 514 of 528 patients presented with fever (97%), 429 of 451 with headache (95%), 462 of 496 with neck stiffness (93%) and 78 of 384 patients (20%) had a skin injury in the presence of pig/pork contact. The case fatality rate was 2.9% and hearing loss was a common sequel occurring in 259 of 489 patients (53%). Treatment included dexamethasone in 157 of 300 (52%) of patients and was associated with reduced hearing loss in S. suis meningitis patients included in a randomized controlled trial. Conclusion S. suis meningitis has a clear association with pig and pork contact. Mortality is low, but hearing loss occurs frequently. Dexamethasone was shown to reduce hearing loss. PMID:26505485

  1. [A meningitis case of Brucella and tuberculosis co-infection].

    PubMed

    Karsen, Hasan; Karahocagil, Mustafa Kasim; Irmak, Hasan; Demiröz, Ali Pekcan

    2008-10-01

    Turkey is located at an endemic area for brusellosis and tuberculosis which are both important public health problems. Meningitis caused by Brucella and Mycobacterium spp. may be confused since the clinical and laboratory findings are similar. In this report, a meningitis case with Brucella and tuberculosis co-infection has been presented. A 19-years-old woman was admitted to our clinic with severe headache, fever, vomiting, meningeal irritation symptoms, confusion and diplopia. The patient was initially diagnosed as Brucella meningitis based on her history (stockbreeding, consuming raw milk products, clinical symptoms concordant to brucellosis lasting for 4-5 months), physical examination and laboratory findings of cerebrospinal fluid (CSF). Standard tube agglutination test for brucellosis was positive at 1/80 titer in CSF and at 1/640 titer in serum, whereas no growth of Brucella spp. was detected in CSF and blood cultures. Antibiotic therapy with ceftriaxone, rifampicin and doxycyclin was started, however, there was no clinical improvement and agitation and confusion of the patient continued by the end of second day of treatment. Repeated CSF examination yielded acid-fast bacteria. The patient was then diagnosed as meningitis with double etiology and the therapy was changed to ceftriaxone, streptomycin, morphozinamide, rifampicin and isoniazid for thirty days. Tuberculosis meningitis was confirmed with the growth of Mycobacterium tuberculosis on the 14th day of cultivation (BACTEC, Becton Dickinson, USA) of the CSF sample. On the 30th day of treatment she was discharged on anti-tuberculous treatment with isoniazid and rifampicin for 12 months. The follow-up of the patient on the first and third months of treatment revealed clinical and laboratory improvement. Since this was a rare case of Brucella and tuberculosis co-infection, this report emphasizes that such co-infections should be kept in mind especially in the endemic areas for tuberculosis and brucellosis

  2. Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

    PubMed Central

    Kloek, Anne T.; van Setten, Jessica; van der Ende, Arie; Bots, Michiel L.; Asselbergs, Folkert W.; Serón, Mercedes Valls; Brouwer, Matthijs C.; van de Beek, Diederik; Ferwerda, Bart

    2016-01-01

    Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10−7). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10−6; G allele OR 3.21 [95% CI 2.05–5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10−5; G allele OR 0.66 [95% CI 0.54–0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10−7). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis. PMID:27389768

  3. Bacterial meningitis as a first presentation of pituitary macroprolactinoma

    PubMed Central

    Margari, Niki

    2014-01-01

    Summary A 56-year-old man was brought to the Emergency Department after being found collapsed at his office with a reduced level of consciousness. From clinical examination and initial investigations, he was diagnosed as having bacterial meningitis and was promptly commenced on empirical i.v. antibiotics. Computed tomography of the brain revealed a parenchymal mass at the base of the skull and subsequent magnetic resonance imaging of the head 4 days later confirmed a large soft tissue mass, which extended through to the cavernous sinus. Examination of the cerebrospinal fluid (CSF) following lumbar puncture confirmed pneumococcal meningitis and antibiotics were continued for 2 weeks in total. During the admission, hormone profiling revealed a grossly elevated prolactin. When coupled with the initial results of the brain imaging, this result helped to confirm a macroprolactinoma that was invading the postnasal space. A final diagnosis of pneumococcal meningitis secondary to invading prolactinoma was made. The patient was started on cabergoline and was followed up in the outpatient clinic upon discharge. He made a full recovery from the meningitis. Over the next few months, prolactin levels returned to be normal and the prolactinoma shrank significantly in size. The patient remains on cabergoline that will most likely be continued indefinitely. Learning points Bacterial meningitis is a rare first presentation of pituitary macroprolactinoma.Patients with invasive macroprolactinoma do not always present with CSF leakage.Prompt treatment with antibiotics and a dopamine agonist is of great importance for a favourable outcome.Close monitoring of the patient for signs of raised intracranial pressure is essential in the management of macroprolactinoma.Note the risk of CSF leakage after initiation of dopamine agonist therapy irrespective of concomitant meningitis in macroprolactinoma. PMID:24963397

  4. Diagnostic Accuracy of Intracellular Mycobacterium tuberculosis Detection for Tuberculous Meningitis

    PubMed Central

    Feng, Guo-dong; Shi, Ming; Ma, Lei; Chen, Ping; Wang, Bing-ju; Zhang, Min; Chang, Xiao-lin; Su, Xiu-chu; Yang, Yi-ning; Fan, Xin-hong; Dai, Wen; Liu, Ting-ting; He, Ying; Bian, Ting; Duan, Li-xin; Li, Jin-ge; Hao, Xiao-ke; Liu, Jia-yun; Xue, Xin; Song, Yun-zhang; Wu, Hai-qin; Niu, Guo-qiang; Zhang, Li; Han, Cui-juan; Lin, Hong; Lin, Zhi-hui; Liu, Jian-jun; Jian, Qian; Zhang, Jin-she; Tian, Ye; Zhou, Bai-yu; Wang, Jing; Xue, Chang-hu; Han, Xiao-fang; Wang, Jian-feng; Wang, Shou-lian

    2014-01-01

    Rationale: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity. Objectives: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis. Methods: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6–expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients’ final diagnosis. Measurements and Main Results: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6–6.7%), compared with 82.9% (95% confidence interval, 77.4–87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8–80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4–93.8%) and 90.0% (95% confidence interval, 75.4–96.7%), respectively. Conclusions: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis. PMID:24450377

  5. Community-Acquired Bacterial Meningitis in Alcoholic Patients

    PubMed Central

    Weisfelt, Martijn; de Gans, Jan; van der Ende, Arie; van de Beek, Diederik

    2010-01-01

    Background Alcoholism is associated with susceptibility to infectious disease, particularly bacterial pneumonia. In the present study we described characteristics in alcoholic patients with bacterial meningitis and delineate the differences with findings in non-alcoholic adults with bacterial meningitis. Methods/Principal Findings This was a prospective nationwide observational cohort study including patients aged >16 years who had bacterial meningitis confirmed by culture of cerebrospinal fluid (696 episodes of bacterial meningitis occurring in 671 patients). Alcoholism was present in 27 of 686 recorded episodes of bacterial meningitis (4%) and alcoholics were more often male than non-alcoholics (82% vs 48%, P = 0.001). A higher proportion of alcoholics had underlying pneumonia (41% vs 11% P<0.001). Alcoholics were more likely to have meningitis due to infection with Streptococcus pneumoniae (70% vs 50%, P = 0.01) and Listeria monocytogenes (19% vs 4%, P = 0.005), whereas Neisseria meningitidis was more common in non-alcoholic patients (39% vs 4%, P = 0.01). A large proportion of alcoholics developed complications during clinical course (82% vs 62%, as compared with non-alcoholics; P = 0.04), often cardiorespiratory failure (52% vs 28%, as compared with non-alcoholics; P = 0.01). Alcoholic patients were at risk for unfavourable outcome (67% vs 33%, as compared with non-alcoholics; P<0.001). Conclusions/Significance Alcoholic patients are at high risk for complications resulting in high morbidity and mortality. They are especially at risk for cardiorespiratory failure due to underlying pneumonia, and therefore, aggressive supportive care may be crucial in the treatment of these patients. PMID:20161709

  6. Herpes simplex virus 2 meningitis: a retrospective cohort study.

    PubMed

    Miller, Stephanie; Mateen, Farrah J; Aksamit, Allen J

    2013-04-01

    Herpes simplex virus 2 is a leading cause of viral meningitis and the most commonly recognized infectious cause of benign, recurrent meningitis. We report a retrospective, observational cohort study of patients with herpes simplex virus type 2 (HSV-2) meningitis, confirmed by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). The terms "herpes simplex," "meningitis," or "encephalitis" were searched in the medical records system of the Mayo Clinic in Rochester, Minnesota (1995-2008). Patients were included if they had a clinical diagnosis of meningitis and HSV-2 detected by PCR in the CSF. There were 28 patients with 33 episodes identified (83 % female; mean age at presentation of meningitis 36 years, range 17-53; mean time to HSV2 detection from symptom onset 3 days, range 0-6; history of genital herpes 23 %). No patient took oral antiviral treatment at the time of presentation. Episodes were most likely to include headache (100 %), photophobia (47 %), self-reported fever (45 %), meningismus (44 %), and nausea and/or vomiting (29 %). CSF at the time of meningitis was notable for elevated protein (mean 156 g/dL, range 60-258) and white cell count (mean 504 cells/μL, range 86-1,860) with normal glucose (mean 54 mg/dL, range 32-80). Mollaret cells were never detected. Neuroimaging was most often normal (83 %) when performed, although some cases showed nonspecific (14 %) or meningeal changes (3 %). There was no consistent relationship to genital herpes. The duration of treatment with intravenous acyclovir ranged from 3 to 14 days for the first meningitic episode (daily dose range from 500 to 1,000 mg and total dose range from 500 mg q8h for 3 days to 800 mg q8h for 14 days). For subsequent episodes, the duration of treatment of intravenous acyclovir ranged from less than 1 to 14 days (total dose range from 1,390 mg for 1 day to 900 mg q8h for 10 days). The dose of valacyclovir ranged from 500 mg once daily to 500 mg four times daily. The median duration

  7. Detectability of early brain meningitis with magnetic resonance imaging

    SciTech Connect

    Runge, V.M.; Wells, J.W.; Williams, N.M.

    1995-08-01

    The ability of high-field (1.5 T) magnetic resonance imaging (MRI) to detect early brain meningitis was evaluated in a canine model. Contrast dose, timing postinjection, and imaging technique (specifically the use of magnetization transfer) were assessed. Imaging of five canines was performed at 1.5 T 24 hours after injection of Cowans staphylococcus into the cisterna magna. Two control animals also were imaged using the same protocol. Contrast doses of 0.1, 0.3, and 0.8 mmol/kg gadoteridol were compared. Scans were performed at 2, 13, and 22 minutes after an initial injection of 0.1 mmol/kg. Thirty minutes after the initial injection of contrast, a supplemental dose of 0.2 mmol/kg was given. Scans were then repeated at 2, 12, and 22 minutes after this dose was administered. A second supplemental contrast injection of 0.5 mmol/kg was given at 70 minutes, and immediate postinjection scans with and without MT were acquired. Results. In the animals receiving a cisternal injection of bacteria, the degree of meningeal enhancement was greatest at 0.8 mmol/kg, intermediate at 0.3 mmol/kg, and least at 0.1 mmol/kg. Scans in control studies did not demonstrate abnormal meningeal enhancement. High-contrast dose, MT, and acquisition of immediate postcontrast scans all resulted in statistically significant improvement. On masked film review, abnormal meningeal enhancement was noted in only 2 of 5 experimental dogs at a dose of 0.1 mmol/kg (regardless of the use of MT) compared with all animals at a dose of 0.3 mmol/kg. In 18 of 37 dogs (paired scans with and without MT), when abnormal enhancement was noted, the use of MT improved the visualization of abnormal meningeal enhancement. In early brain meningitis, high-contrast dose (0.3 mmol/kg), MT, and scanning immediately after injection improve detection of abnormal meningeal enhancement, thus facilitating the diagnosis of meningitis. Of these factors, contrast dose is the most important. 14 refs., 9 figs., 2 tabs.

  8. Group A streptococcal meningitis in a patient with palmoplantar pustulosis.

    PubMed

    Hagiya, Hideharu; Otsuka, Fumio

    2013-01-01

    A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma. The patient was diagnosed with Group A Streptococcal meningitis and promptly treated with antibiotics. Although his general condition recovered well, sensorineural hearing loss and facial palsy remained. Group A Streptococcal meningitis is a rare condition, and its typical clinical picture and epidemiological features remain poorly understood. Physicians need to be more aware of this infection, which is extremely rare but frequently causes various complications and yields a high mortality. PMID:24292762

  9. Case of Mycobacterium tuberculosis meningitis: Gram staining as a useful initial diagnostic clue for tuberculous meningitis.

    PubMed

    Kawakami, Sayoko; Kawamura, Yasuyosi; Nishiyama, Kyouhei; Hatanaka, Hiroki; Fujisaki, Ryuichi; Ono, Yasuo; Miyazawa, Yukihisa; Nishiya, Hajime

    2012-12-01

    A 32-year-old man was admitted to our hospital because of fever, headache, and loss of consciousness. Four days before admission, he had had difficulty speaking. On the day of admission, his colleague had found him to be unconscious and lying on his back. He was admitted to our hospital. The temperature at the eardrum was 35.2°C. Neurologic evaluation was negative. Computed tomography (CT) scan of the brain showed slight ventricular enlargement bilaterally. An X-ray film of the chest showed no abnormality. On the second hospital day, neck stiffness was noted. The cerebrospinal fluid (CSF) contained 870 white cells/μl, most of which were neutrophils; the glucose level in the CSF was 10 mg/dl, and the protein level was 140 mg/dl. Stained smears of the CSF, including Gram staining and India-ink preparations, disclosed no microorganisms. Capsular antigen tests for several bacteria were negative. Antimicrobial agents were started. However, by changing the microscope focus slightly while viewing Gram stains of the CSF, we could see brightened and Gram-positive bacilli that had been phagocytosed by neutrophils. This finding suggested the presence of Mycobacterium tuberculosis. Ziehl-Neelsen staining of the CSF and gastric juice revealed anti-acid bacilli. Polymerase chain reaction for M. tuberculosis in the gastric juice was positive. This case showed that Gram staining could be useful as an initial adjunct for the diagnosis of tuberculous meningitis, particularly when the CSF shows predominantly neutrocytic pleocytosis, but no other evidence of bacterial meningitis. PMID:22476652

  10. Anabolic growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting.

    PubMed

    Esposito, John G; Thomas, Scott G; Kingdon, Lori; Ezzat, Shereen

    2005-09-01

    Growth hormone (GH) treatment reverses the muscle loss allegedly responsible for diminished aerobic capacity and increased fatigue in patients with HIV-associated wasting. This study examined whether submaximal measures of physical performance can be used as objective measures of the functional impact of GH treatment-induced anabolism. We randomized 27 HIV-positive men [mean (SD) age, 43.9 (7.2) yr; body mass, 71.9 (10.4) kg; BMI, 23.1 (2.8) kg/m2] with unintentional weight loss despite antiretroviral therapy to receive GH (6 mg) or placebo in a double-blinded, placebo-controlled, cross-over trial with a 3-mo washout. Lean body mass (LBM), maximum oxygen uptake (Vo2 peak), ventilatory threshold (VeT), 6-min walk test (6MWT) distance and work, profile of mood states (POMS) fatigue and vigor scores, and Nottingham health profile (NHP) energy and physical mobility scores were measured. LBM significantly increased after 3 mo of GH treatment vs. placebo (means +/- SE, 3.7 +/- 0.6 vs. 0.3 +/- 0.4 kg; P < 0.001). VeT significantly improved (17.6 +/- 3.7 vs. -5.9 +/- 2.5%; P < 0.001), but Vo2 peak did not change significantly. 6MWT distance improved (24.9 +/- 9.7 vs. 19.9 +/- 11.6 m; P > 0.05) and 6MWT work increased significantly more after 3 mo of GH treatment (33.3 +/- 8.8 vs. 16.5 +/- 7.5 kJ; P < 0.05). POMS scores of fatigue and vigor and the NHP score of energy improved, yet the changes were not statistically significant. GH treatment improved VeT linearly to the increase in LBM (r =0.43, P = 0.037) and 6MWT work (r = 0.51, P = 0.008), and the increase in 6MWT work correlated with increase in LBM (r = 0.45, P = 0.024). Improvement in 6MWT work above the median (27.3 kJ) showed a decrease in fatigue (r = -0.62, P = 0.024). We concluded that GH treatment-induced LBM gains in HIV-associated wasting were functionally relevant, as determined by effort-independent submaximal measures of cardiopulmonary exercise testing. PMID:15886228

  11. Using Relative Humidity Forecasts to Manage Meningitis in the Sahel

    NASA Astrophysics Data System (ADS)

    Pandya, R. E.; Adams-Forgor, A.; Akweogno, P.; Awine, T.; Dalaba, M.; Dukic, V.; Dumont, A.; Hayden, M.; Hodgson, A.; Hopson, T. M.; Hugonnet, S.; Yoksas, T. C.

    2012-12-01

    Meningitis epidemics in the Sahel occur quasi-regularly and with devastating impact. In 2008, for example, eighty-eight thousand people contracted meningitis and over five thousand died. Until very recently, the protection provided by the only available vaccine was so limited and short-lived that the only practical strategy for vaccination was reactive: waiting until an epidemic occurred in the region and then vaccinating in that region to prevent the epidemic's further growth. Even with that strategy, there were still times when demand outpaced available vaccine. While a new vaccine has recently been developed that is effective and inexpensive enough to be used more broadly and proactively, it is only effective against the strain of bacteria that causes the most common kind of bacterial meningitis. As a result, there will likely be continued need for reactive vaccination strategies. It is widely known that meningitis epidemics in the Sahel occur only in the dry season. Our project investigated this relationship, and several independent lines of evidence demonstrate a robust relationship between the onset of the rainy season, as marked by weekly average relative humidity above 40%, and the end of meningitis epidemics. These lines of evidence include statistical analysis of two years of weekly meningitis and weather data across the Sahel, cross-correlation of ten years of meningitis and weather data in the Upper East region of northern Ghana, and high-resolution weather simulations of past meningitis seasons to interpolate available weather data. We also adapted two techniques that have been successfully used in public health studies: generalized additive models, which have been used to relate air quality and health, and a linearized version of the compartmental epidemics model that has been used to understand MRSA. Based on these multiple lines of evidence, average weekly relative humidity forecast two weeks in advance appears consistently and strongly related to

  12. The Risk of Meningitis Following Expanded Endoscopic Endonasal Skull Base Surgery: A Systematic Review

    PubMed Central

    Lai, Leon T.; Trooboff, Spencer; Morgan, Michael K.; Harvey, Richard J.

    2013-01-01

    Objective To examine the risk of postoperative meningitis following expanded endoscopic endonasal skull base (EESB) surgery. Setting A systematic analysis of publications identified through searches of the electronic databases from Embase (1980–July 17, 2012), Medline (1950–July 17, 2012), and references of review articles. Main Outcome Measures Incidence of meningitis following EESB surgery. Results A total of 2,444 manuscripts were selected initially, and full-text analysis produced 67 studies with extractable data. Fifty-two contained data regarding the frequency of postoperative meningitis. The overall risk of postoperative meningitis following EESB surgery was 1.8% (36 of 2,005). For those reporting a cerebrospinal fluid (CSF) leak, meningitis occurred in 13.0% (35 of 269). For those not reporting a CSF leak, meningitis occurred in 0.1% (1 of 1,736). The odds ratio for the development of meningitis in the presence of a postoperative CSF leak was 91.99 (95% confidence interval, 11.72–721.88; p < 0.01). There was no difference in reported incidence of meningitis or CSF leak between anterior and posterior cranial fossa surgery. There was one reported case of meningitis-related mortality following EESB surgery. Conclusion The evidence in skull base surgery is limited. This study demonstrates a low incidence of meningitis (1.8%) following EESB procedures. The incidence of meningitis from EESB surgery without an associated CSF leak is uncommon. PMID:24498585

  13. [Revival of old diagnostic markers in the cerebrospinal fluid for the detection of infectious meningitis].

    PubMed

    Sakushima, Ken; Yabe, Ichiro; Sasaki, Hidenao

    2012-01-01

    Bacterial meningitis and tubercular meningitis are still neurological emergencies characterized by severe mortality and morbidity. Recent studies of meta-analysis have shown the usefulness of cerebrospinal fluid (CSF) lactate and CSF adenosine deaminase (ADA) as markers for the detection of bacterial meningitis and tubercular meningitis, respectively. CSF lactate has a high sensitivity and specificity for the diagnosis of bacterial meningitis, but the sensitivity can be reduced by antibiotic pretreatment. CSF-ADA has a moderate sensitivity but a high specificity and is reliable for the diagnosis of tubercular meningitis. These old diagnostic markers can be evaluated in resource-poor settings including small general hospitals and non-specialized hospitals for infectious diseases, and they can contribute to the quick and accurate diagnosis of infectious meningitis. PMID:22260972

  14. Pituitary abscess: an unusual presentation of "aseptic meningitis".

    PubMed

    Schwartz, I D; Zalles, M C; Foster, J L; Burry, V F

    1995-01-01

    Granulomatous inflammation of the pituitary and pituitary abscesses are rare entities. These conditions are found even more rarely in the pediatric aged population. We report a case of a radiographic and clinical, sterile pituitary abscess with non-caseating granulomatous inflammation in a girl who presented with hypopituitarism, meningeal irritation, and symptoms of pituitary apoplexy. PMID:7584709

  15. Recurrent Lymphocytic Meningitis Positive for Herpes Simplex Virus Type 2

    PubMed Central

    Seppänen, Mikko; Kautiainen, Hannu; Lokki, Marja-Liisa; Lappalainen, Maija; Valtonen, Ville; Färkkilä, Markus; Kalso, Eija

    2009-01-01

    We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996–2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2–5 days after symptom onset. PMID:19624935

  16. Recurrent lymphocytic meningitis positive for herpes simplex virus type 2.

    PubMed

    Kallio-Laine, Katariina; Seppänen, Mikko; Kautiainen, Hannu; Lokki, Marja Liisa; Lappalainen, Maija; Valtonen, Ville; Färkkilä, Markus; Kalso, Eija

    2009-07-01

    We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996-2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2-5 days after symptom onset. PMID:19624935

  17. Real-time PCR for Strongyloides stercoralis-associated meningitis.

    PubMed

    Nadir, Eyal; Grossman, Tamar; Ciobotaro, Pnina; Attali, Malka; Barkan, Daniel; Bardenstein, Rita; Zimhony, Oren

    2016-03-01

    Four immunocompromised patients, immigrants from Ethiopia, presented with diverse clinical manifestations of meningitis associated with Strongyloides stercoralis dissemination as determined by identification of intestinal larvae. The cerebrospinal fluid of 3 patients was tested by a validated (for stool) real-time PCR for S. stercoralis and was found positive, establishing this association. PMID:26704620

  18. Staphylococcal meningitis following Synchromed intrathecal pump implant: a case report.

    PubMed

    Bennett, M I; Tai, Y M; Symonds, J M

    1994-02-01

    Staphylococcal meningitis associated with implantation of an intrathecal drug pump for spasticity was successfully treated by intrathecal vancomycin delivered by the same pump. This produced high CSF antibiotic levels, and the pump and catheter system did not have to be removed. We are unable to identify a similar case reported in the literature to date. PMID:8008414

  19. [Salmonella meningitis in an infant due to a pet turtle].

    PubMed

    Ricard, C; Mellentin, J; Ben Abdallah Chabchoub, R; Kingbede, P; Heuclin, T; Ramdame, A; Bouquet, A; Couttenier, F; Hendricx, S

    2015-06-01

    In humans, Salmonella most often causes self-limiting gastroenteritis, but more severe symptoms such as sepsis and meningitis can also occur and can sometimes have a fatal outcome. Even if the meningitis is not fatal, sequelae such as epilepsy, cranial nerve palsies, and hydrocephalus can occur. In the United States, it has been estimated that approximately 6% of the human cases of salmonellosis can be attributed to contact with reptiles or amphibians. The infection may take place by direct contact between reptile and human or indirectly via contact with an environment contaminated with Salmonella from a reptile. Salmonella enterica subsp. enterica serotype Vitkin is a common gut inhabitant of reptiles. Though human cases due to this organism are exceedingly rare, it may infect young infants and immunocompromised individuals with a history of intimate associations with reptiles. Gastroenteritis is the most common presentation ; others include peritonitis, meningitis and bacteremia. We report a case of meningitis caused by S. enterica subsp. enterica serotype Vitkin in a 1-month-old child due to a pet turtle. PMID:26014646

  20. Tuberculous granulomas in childhood tuberculous meningitis: radiological features and course.

    PubMed

    Ravenscroft, A; Schoeman, J F; Donald, P R

    2001-02-01

    The clinical course and serial cranial computerized tomographic (CT) findings of 202 children with tuberculous meningitis (TBM) admitted to Tygerberg Hospital between 1985 and 1994 were reviewed with regard to the incidence, CT appearance and clinical course of associated intracranial tuberculous granulomas. Thirty-four patients (16.85 per cent) had associated intracranial granulomas. Thirty-eight individual lesions were analysed and classified as meningeal, parenchymal or ependymal according to their central nervous system (CNS) location. Twenty-five patients had round to irregular, brain iso-, hypo- or hyperdense meningeal granulomas with variable degrees of enhancement and peri-lesional hypodensities. Four patients had diffusely enhancing, brain isodense, enplaque-like ependymal granulomas associated with the ventricular ependymal lining. Four patients with miliary tuberculosis and TBM showed multiple small diffusely enhancing, brain iso- or hyperdense parenchymal lesions and associated hypodensities on initial CT. Although granulomas in the meningeal and ependymal group had the propensity to paradoxically enlarge or appear on standard four-drug antituberculosis therapy, the majority resolved uneventfully. Rapid resolution of small parenchymal granulomas associated with miliary tuberculosis occurred in all cases. Most granulomas in this series were co-incidental, asymptomatic CT findings. In rare cases, the development or enlargement of a strategically located granuloma may result in complications. PMID:11245351

  1. Eggerthella lenta Bacteremia Complicated by Spondylodiscitis, Psoas Abscess, and Meningitis

    PubMed Central

    Korman, T. M.; Junckerstorff, R. K.

    2014-01-01

    Eggerthella lenta bacteremia is uncommon and generally associated with abdominal sepsis. The organism and its clinical significance have not been well characterized due to historical difficulties with identification. We report a case of severe infection in a paraplegic man complicated by psoas abscess, osteomyelitis, and meningitis and discuss treatment challenges. PMID:24430458

  2. Cytomegalovirus Meningitis in an Infant with Severe Combined Immunodeficiency.

    PubMed

    Vicetti Miguel, Claudia P; Mejias, Asuncion; Ramilo, Octavio; Ardura, Monica I; Sánchez, Pablo J

    2016-06-01

    A 35-day-old female with severe combined immunodeficiency developed cytomegalovirus (CMV) meningitis before undergoing hematopoietic stem cell transplantation. Strategies for timely diagnosis of neonates with congenital or acquired CMV infection and prevention of CMV acquisition in the era of universal newborn severe combined immunodeficiency screening are needed. PMID:26996725

  3. Prevention of bacterial meningitis: an overview of Cochrane systematic reviews.

    PubMed

    Prasad, Kameshwar; Karlupia, Neha

    2007-10-01

    Acute bacterial meningitis (ABM) is an acute inflammation of leptomeninges caused by bacteria, and has a case fatality rate of 10-30%. Prevention strategies, such as vaccination and prophylactic antibiotics, can prevent ABM and have substantial public health impact by reducing the disease burden associated with it. The aim of this paper is to summarize the main findings from Cochrane systematic reviews that have considered the evidence for measures to prevent ABM. We assessed the evidence available in the Cochrane Library. We found five Cochrane reviews focused on the prevention of ABM; three with use of vaccination and two with prophylactic antibiotics. Polysaccharide serogroup A vaccine is strongly protective for the first year, against serogroup A meningococcal meningitis in adults and children over 5 years of age. Meningococcal serogroup C conjugate (MCC) vaccine is safe and effective in infants. Haemophilus influenzae type b (Hib) vaccine is safe and effective against Hib-invasive disease at all ages. Ceftriaxone, rifampicin and ciprofloxacin are the most effective prophylactic antibiotics against Neisseria meningitidis. There is sufficient evidence to use polysaccharide serogroup A vaccine to prevent serogroup A meningococcal meningitis, MCC conjugate vaccines to prevent meningococcal C meningitis and Hib conjugate vaccine to prevent Hib infections. More studies are needed to evaluate the effects of Hib conjugate vaccine on mortality. Further, studies are required to compare the relative effectiveness of ceftriaxone, ciprofloxacin and rifampicin in chemoprophylaxis against meningococcal infection. PMID:17706408

  4. [Adult purulent meningitis caused by Streptococcus pneumoniae in Dakar, Senegal].

    PubMed

    Manga, N M; Ndour, C T; Diop, S A; Ka-Sall, R; Dia, N M; Seydi, M; Soumare, M; Diop, B M; Sow, A I; Sow, P S

    2008-12-01

    The purpose of this retrospective study was to describe epidemiological, clinical, bacteriological and outcome features of purulent meningitis caused by Streptococcus pneumoniae in adult patients hospitalized in the infectious diseases clinic of the Fann University Hospital in Dakar, Senegal from 1995 to 2004. A total of 73 cases of pneumococcal meningitis were recorded during the study period. Streptococcus pneumoniae was the second cause of purulent meningitis after meningococcal infection. Sickle-cell disease (n=3) and HIV infection (n=9) were the main underlying factors and pneumonia was the main portal of entry into the CNS (51.8%). Coma was a frequent complication (61.6%). Penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) accounted for 27.3% of isolated strains. However strains were sensitive to third-generation cephalosporin (100%) and chloramphenicol (68.2%) which were the most frequently used antibiotics. The mortality rate was 69.8% and neurological complications occurred in 13.7% of patients. The main unfavorable prognostic factors were cardiovascular collapse and/or coma at the time of admission and detection of pneumococcal strains by direct examination of CSF. The high mortality of pneumococcal meningitis in adult patients in Dakar shows the need to improve intensive care facilities and the growing incidence of PNSP underlines the requirement for better control of antibiotic prescription. PMID:19639833

  5. Pneumococcal meningitis: clinical-pathological correlations (MeninGene-Path).

    PubMed

    Engelen-Lee, Joo-Yeon; Brouwer, Matthijs C; Aronica, Eleonora; van de Beek, Diederik

    2016-01-01

    Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been treated with adjunctive dexamethasone therapy. Observed pathological processes were inflammation of medium-large arteries in 30 brains (97 %), cerebral haemorrhage in 24 (77 %), cerebritis in 24 (77 %), thrombosis in 21 (68 %), infarction in 19 (61 %) and ventriculitis in 19 (of 28 cases, 68 %). Inflammation of medium-large arteries led to obstruction of the vascular lumen in 14 (of 31 cases, 45 %). Vascular inflammation was associated with infarction and thrombosis of brain parenchymal vessels. Hippocampal dentate gyrus apoptosis between patients treated with and without dexamethasone was similar (p = 0.66); however, dexamethasone treated patients had higher total pathology score than non-dexamethasone treated patients (p = 0.003). Our study shows that vascular damage is key in the process of brain damage in pneumococcal meningitis. Data and material of this study will be made open-access for translational research in pneumococcal meningitis (MeninGene-Path). PMID:27001057

  6. Streptococcus suis toxic-shock syndrome and meningitis.

    PubMed

    Leelarasamee, A; Nilakul, C; Tien-Grim, S; Srifuengfung, S; Susaengrat, W

    1997-01-01

    Three cases with S. suis bacteremia and meningitis were reported. The first case was a 23-year-old butcher who was a regular drinker of alcohol for two years and developed streptococcal toxic-shock syndrome. The organism was transmitted to him through a minor cut in his right arm. The second cases was a 49-year-old female laborer who had been consuming locally produced alcohol for 20 years and developed fever and meningitis. Unfortunately, she succumbed in seven days despite intensive supportive and cefotaxime treatments. The third case was a 45-year-old regular alcoholic drinker and car painter who was seen at a private hospital due to contusion at his left lateral chest wall. However, fever and confusion due to meningitis was detected upon admission. Irreversible deafness developed within 48 hours of ceftriaxone therapy for meningitis. He finally recovered with deafness. S. suis was isolated from blood and cerebrospinal fluid cultures in all three cases though initially reported to be viridans group of streptococci. PMID:9078819

  7. [Systemic candidiasis with meningeal involvement in a newborn infant].

    PubMed

    Kacprzak-Bergman, I; Szychowska, Z; Rudkowski, Z

    1989-04-24

    The newborn with sepsis (E. coli) and salmonellosis was described. After treatment with broad-spectrum antibiotics it was suffered from Candida albicans (Meningitis with Hydrocephalus internus, Chorioretinitis and Ostitis). The authors difficulties connected with diagnosis and anti-fungal therapy have showed. They have punctated the necessity of combined anti-mycotic therapy. PMID:2626360

  8. One Family's Crusade To Inform the Public about Meningococcal Meningitis.

    ERIC Educational Resources Information Center

    Skowronek, Linda and Carl

    2001-01-01

    Describes meningococcal meningitis, which strikes over 100 college students yearly. Living in dormitories puts students at risk for contracting the disease. The current vaccine protects against the four main types of the infection, though it is not perfect protection. Some states have adopted legislation requiring all incoming college freshmen and…

  9. Variations of relative humidity in relation to meningitis in Africa

    NASA Astrophysics Data System (ADS)

    Seefeldt, M. W.; Hopson, T. M.

    2011-12-01

    The meningitis belt is a region covering Sub-Saharan Africa from the Sahel of West Africa eastward to western Ethiopia. The region is prone to meningitis epidemics during the dry season extending from approximately January to May, depending on the region. Relative humidity has been found to be a critical environmental factor indicating the susceptibility of a region to meningitis epidemics. This study evaluates the variation of relative humidity across West Africa over 30 dry-seasons (1979 - 2009) using the NASA-MERRA dataset. The method of self-organizing maps is employed to characterize the changes in relative humidity patterns across the region within a given dry season as well as changes over the 30 years. A general pattern of changes in relative humidity is indicated as the rainbelt retreats to the south at the onset of the dry season and then returns to the region at the end of the dry season. Within each dry season there is a unique pattern. The climatological conditions of relative humidity at the onset of the dry season provide an indication of the moisture environment for the entire dry season. Year to year variation in the relative humidity patterns are found to be gradual. Future applications involve using the results from the SOM evaluation to be used for future decisions involving prevention of meningitis epidemics.

  10. Vaccine May Reduce Incidence of Meningitis-Related Hearing Impairment.

    ERIC Educational Resources Information Center

    Smith, Dorothy

    1988-01-01

    Hearing loss as a result of meningitis, now the leading nongenetic cause of deafness in infants and young children, may be reduced by the introduction of the HiB (Hemophilus influenzae type B) vaccine. It is highly effective, relatively safe, and recommended for most children over 24 months and high risk children 18-24 months old. (VW)

  11. Streptococcus bovis septicemia and meningitis associated with chronic radiation enterocolitis

    SciTech Connect

    Jadeja, L.; Kantarjian, H.; Bolivar, R.

    1983-12-01

    We describe the first patient with simultaneous S bovis septicemia and meningitis associated with chronic radiation enterocolitis. This case underlines the value of a thorough gastrointestinal evaluation of all patients with S bovis infection, and the need for a neurologic investigation even with minor neurologic manifestations.

  12. Distinct BK polyomavirus non-coding control region (NCCR) variants in oral fluids of HIV- associated Salivary Gland Disease patients.

    PubMed

    Burger-Calderon, Raquel; Ramsey, Kathy J; Dolittle-Hall, Janet M; Seaman, William T; Jeffers-Francis, Liesl K; Tesfu, Daniel; Nickeleit, Volker; Webster-Cyriaque, Jennifer

    2016-06-01

    HIV-associated Salivary Gland Disease (HIVSGD) is among the most common salivary gland-associated complications in HIV positive individuals and was associated with the small DNA tumorvirus BK polyomavirus (BKPyV). The BKPyV non-coding control region (NCCR) is the main determinant of viral replication and rearranges readily. This study analyzed the BKPyV NCCR architecture and viral loads of 35 immunosuppressed individuals. Throatwash samples from subjects diagnosed with HIVSGD and urine samples from transplant patients were BKPyV positive and yielded BKPyV NCCR sequences. 94.7% of the BKPyV HIVSGD NCCRs carried a rearranged OPQPQQS block arrangement, suggesting a distinct architecture among this sample set. BKPyV from HIV positive individuals without HIVSGD harbored NCCR block sequences that were distinct from OPQPQQS. Cloned HIVSGD BKPyV isolates displayed active promoters and efficient replication capability in human salivary gland cells. The unique HIVSGD NCCR architecture may represent a potentially significant oral-tropic BKPyV substrain. PMID:27085139

  13. A Comparison of Five Brief Screening Tools for HIV-Associated Neurocognitive Disorders in the USA and South Africa.

    PubMed

    Joska, J A; Witten, J; Thomas, K G; Robertson, C; Casson-Crook, M; Roosa, H; Creighton, J; Lyons, J; McArthur, J; Sacktor, N C

    2016-08-01

    Screening for HIV-associated neurocognitive disorders (HAND) is important to improve clinical outcomes. We compared the diagnostic sensitivity and specificity of the mini-mental state examination, International HIV dementia scale (IHDS), Montreal cognitive assessment, Simioni symptom questionnaire and cognitive assessment tool-rapid version (CAT-rapid) to a gold standard neuropsychological battery. Antiretroviral-experienced participants from Cape Town, South Africa, and Baltimore, USA, were recruited. The sensitivity and specificity of the five tools, as well as those of the combined IHDS and CAT-rapid, were established using 2 × 2 contingency tables and ROC analysis. More than a third (65165) had symptomatic HAND. In detecting HIV-D, the CAT-Rapid had good sensitivity (94 %) and weak specificity (52 %) (cut-point ≤10), while the IHDS showed fair sensitivity (68 %) and good specificity (86 %) (cut-point ≤10). The combined IHDS and CAT-rapid showed excellent sensitivity and specificity for HIV-D at a cut-off score of ≤16 (out of 20; 89 and 82 %). No tool was adequate in screening for any HAND. The combination IHDS and CAT-rapid tool appears to be a good screener for HIV-D but is only fairly sensitive and poorly specific in screening for any HAND. Screening for milder forms of HAND continues to be a clinical challenge. PMID:26860536

  14. Investigating changes in brain network properties in HIV-associated neurocognitive disease (HAND) using mutual connectivity analysis (MCA)

    NASA Astrophysics Data System (ADS)

    Abidin, Anas Zainul; D'Souza, Adora M.; Nagarajan, Mahesh B.; Wismüller, Axel

    2016-03-01

    About 50% of subjects infected with HIV present deficits in cognitive domains, which are known collectively as HIV associated neurocognitive disorder (HAND). The underlying synaptodendritic damage can be captured using resting state functional MRI, as has been demonstrated by a few earlier studies. Such damage may induce topological changes of brain connectivity networks. We test this hypothesis by capturing the functional interdependence of 90 brain network nodes using a Mutual Connectivity Analysis (MCA) framework with non-linear time series modeling based on Generalized Radial Basis function (GRBF) neural networks. The network nodes are selected based on the regions defined in the Automated Anatomic Labeling (AAL) atlas. Each node is represented by the average time series of the voxels of that region. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We tested for differences in these properties in network graphs obtained for 10 subjects (6 male and 4 female, 5 HIV+ and 5 HIV-). Global network properties captured some differences between these subject cohorts, though significant differences were seen only with the clustering coefficient measure. Local network properties, such as local efficiency and the degree of connections, captured significant differences in regions of the frontal lobe, precentral and cingulate cortex amongst a few others. These results suggest that our method can be used to effectively capture differences occurring in brain network connectivity properties revealed by resting-state functional MRI in neurological disease states, such as HAND.

  15. Modeling HIV-associated neurocognitive disorders in mice: new approaches in the changing face of HIV neuropathogenesis.

    PubMed

    Jaeger, Laura B; Nath, Avindra

    2012-05-01

    It is well established that infection with the human immunodeficiency virus (HIV) leads to immune suppression. Less well known is the fact that long-term, progressive HIV disease is associated with the development of cognitive deficits. Since the introduction of combined antiretroviral therapy (cART), the clinical presentation of HIV infection has evolved into a chronic illness with very low levels of viral replication and chronic immune activation, with compliant affected individuals surviving for decades with a high quality of life. Despite these advances, many HIV-infected individuals develop some degree of neurodegeneration and cognitive impairment. The underlying pathophysiological mechanisms are not well understood, and there are no effective treatments. Thus, there is an unmet need for animal models that enable the study of HIV-associated neurocognitive disorders (HAND) and the testing of new therapeutic approaches to combat them. Here, we review the pros and cons of existing mouse models of HIV infection for addressing these aims and propose a detailed strategy for developing a new mouse model of HIV infection. PMID:22563057

  16. Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-05-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  17. Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients

    PubMed Central

    Xue, Xiaonan; Wang, Dan; Tamari, Roni; Lee, Jeannette Y.; Mounier, Nicolas; Kaplan, Lawrence D.; Ribera, Josep-Maria; Spina, Michele; Tirelli, Umberto; Weiss, Rudolf; Galicier, Lionel; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Oriol, Albert; Navarro, José-Tomás; Dunleavy, Kieron; Little, Richard F.; Ratner, Lee; Garcia, Olga; Morgades, Mireia; Remick, Scot C.; Noy, Ariela; Sparano, Joseph A.

    2013-01-01

    Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; “intensive regimens”: HR 0.35; P < .001) and OS (“intensive regimens”: HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable. PMID:24014242

  18. Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the mind exchange program.

    PubMed

    2013-04-01

    Many practical clinical questions regarding the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain unanswered. We sought to identify and develop practical answers to key clinical questions in HAND management. Sixty-six specialists from 30 countries provided input into the program, which was overseen by a steering committee. Fourteen questions were rated as being of greatest clinical importance. Answers were drafted by an expert group based on a comprehensive literature review. Sixty-three experts convened to determine consensus and level of evidence for the answers. Consensus was reached on all answers. For instance, good practice suggests that all HIV patients should be screened for HAND early in disease using standardized tools. Follow-up frequency depends on whether HAND is already present or whether clinical data suggest risk for developing HAND. Worsening neurocognitive impairment may trigger consideration of antiretroviral modification when other causes have been excluded. The Mind Exchange program provides practical guidance in the diagnosis, monitoring, and treatment of HAND. PMID:23175555

  19. Incidence, Clinical Spectrum, Risk Factors and Impact of HIV-Associated Immune Reconstitution Inflammatory Syndrome in South Africa

    PubMed Central

    Haddow, Lewis John; Moosa, Mahomed-Yunus Suleman; Mosam, Anisa; Moodley, Pravi; Parboosing, Raveen; Easterbrook, Philippa Jane

    2012-01-01

    before onset of advanced immunodeficiency, improved pre-ART screening for TB and cryptococcal infection, optimization of OI therapy prior to ART initiation, more intensive clinical monitoring in initial weeks of ART, and education of health care workers and patients about IRIS. PMID:23152745

  20. Care of Patients With HIV Infection: Medical Complications and Comorbidities.

    PubMed

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    Care of patients with HIV infection starts with diagnosis as soon as possible, preferably at or near the time of acute infection. Opportunistic infections, malignancies, and other conditions develop progressively over time, particularly in untreated patients. The AIDS-defining opportunistic infections most common in the United States include Pneumocystis jirovecii pneumonia, Candida esophagitis, toxoplasmic encephalitis, tuberculosis, disseminated Mycobacterium avium complex, cryptococcal meningitis, and cytomegalovirus retinitis. Specific prophylaxis regimens exist for several opportunistic infections, and effective antiretroviral therapy reduces the risk of most others. Other AIDS-defining conditions include wasting syndrome and HIV encephalopathy. AIDS-defining malignancies include Kaposi sarcoma, systemic non-Hodgkin lymphoma, primary central nervous system lymphoma, and invasive cervical cancer. Although not an AIDS-defining condition, anal cancer is common in patients with HIV infection. Other HIV-related conditions include thrombocytopenia, recurrent bacterial respiratory infections, HIV-associated nephropathy, and HIV-associated neurocognitive disorder. PMID:27092563

  1. Genetics of focal segmental glomerulosclerosis and HIV-associated collapsing glomerulopathy: the role of MYH9 genetic variation

    PubMed Central

    Winkler, Cheryl A.; Nelson, George; Oleksyk, Taras K.; Nava, M. Berenice; Kopp, Jeffrey B.

    2010-01-01

    Until recently knowledge of genetic causes of glomerular disease was limited to certain rare or uncommon inherited diseases, and to a genes, either rare or with small effect, identified in candidate gene studies. These genetic factors accounted for only a very small fraction of kidney disease. However, the striking differences in frequency of many forms of kidney disease between African Americans and European Americans, which could not be completely explained by cultural or economic factors, pointed to a large unidentified genetic influence. Since FSGS and HIV-associated collapsing glomerulopathy (HVAN) have striking racial disparities, we performed an admixture mapping study to identify contributing genetic factors. Admixture mapping identified genetic variants in the non-muscle myosin gene MYH9 as having an extreme influence on both FSGS and HIVAN, with odds ratios from 4 to 8 and attributable fractions of 70–100%. Previously identified, rare inherited MYH9 disorders point to a mechanism by which MYH9 variation disrupts the actin-myosin filaments responsible for maintaining the structure of podocytes, the cells that provide one of three filtration barriers in the glomeruli. MYH9 variation has a smaller but still highly significant effect on non-diabetic kidney disease, and a weaker but significant effect on diabetic kidney disease; it is unclear whether underlying cryptic FSGS is responsible for the MYH9 association with these diseases. The strong predicted power of MYH9 variation for disease indicates a clear role for genetic testing for these variants in personalized medicine, for assessment of genetic risk, and potentially for diagnosis. PMID:20347641

  2. Prevalence of HIV-Associated Neurocognitive Disorder (HAND) among Patients Attending a Tertiary Health Facility in Northern Nigeria

    PubMed Central

    Yusuf, Abdulkareem Jika; Hassan, Abdulaziz; Mamman, Aisha Indo; Muktar, Haruna Mohammed; Sulieman, Aishatu Maude; Baiyewu, Olusegun

    2014-01-01

    Background HIV-associated neurocognitive disorder (HAND) is a great source of morbidity in sub-Saharan African region. However, the magnitude of this problem remains largely uninvestigated despite having the largest number of population with HIV/AIDS. The aim of this study is to determine the prevalence of HAND among patients attending a tertiary health facility in Nigeria. Method We conducted a cross-sectional study among HIV-positive patients on antiretroviral therapy (ART) for at least 1 year. They were assessed using the International HIV Dementia Scale, Word Recall Test, Stick Design Test, Subjective Cognitive Complaint Questionnaire, Alcohol Use Disorder Identification Test, Drug Abuse Screening Test, Center for Epidemiological Study–Depression Scale, Instrumental Activity of Daily Living, and neurological examination. The CD4 count and viral load were determined for all the participants. A consensus diagnosis was made on each case based on the Frascati criteria. Data obtained were analyzed using “SPSS” for Windows version 15. Results A total of 418 HIV-positive patients participated in the study, of which 325 (77.8%) are females. The mean age (standard deviation) of the participants was 37.2 (9.3) years. The prevalence of HAND was 21.5% (95% confidence interval [CI] = 17.6%-25.4%), of which 9.6% were asymptomatic. The significant predictors of HAND in this study are duration of illness (odds ratio [OR] = 1.33 P < .001), detectable viral load (OR = 0.19, P < .001), CD4 count (OR = 0.99, P < .001), education (OR = 0.94, P = .011), stopping medication (OR = 3.55 P = .01), and severity of illness (OR = 1.24, P = .005). Conclusion One-fifth of the HIV-positive patients in this study had HAND. Various sociodemographic and clinical features were related to the prevalence of HAND. PMID:25331222

  3. Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder.

    PubMed

    Kim, WooJin; Zekas, Erin; Lodge, Robert; Susan-Resiga, Delia; Marcinkiewicz, Edwidge; Essalmani, Rachid; Mihara, Koichiro; Ramachandran, Rithwik; Asahchop, Eugene; Gelman, Benjamin; Cohen, Éric A; Power, Christopher; Hollenberg, Morley D; Seidah, Nabil G

    2015-11-01

    The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. PMID:26283733

  4. Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder

    PubMed Central

    Kim, WooJin; Zekas, Erin; Lodge, Robert; Susan-Resiga, Delia; Marcinkiewicz, Edwidge; Essalmani, Rachid; Mihara, Koichiro; Ramachandran, Rithwik; Asahchop, Eugene; Gelman, Benjamin; Cohen, Éric A.; Power, Christopher; Hollenberg, Morley D.

    2015-01-01

    The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. PMID:26283733

  5. HIV-1 Tat Alters Neuronal Autophagy by Modulating Autophagosome Fusion to the Lysosome: Implications for HIV-Associated Neurocognitive Disorders

    PubMed Central

    Fields, Jerel; Dumaop, Wilmar; Elueteri, Simona; Campos, Sofia; Serger, Elisabeth; Trejo, Margarita; Kosberg, Kori; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; He, Johnny J.

    2015-01-01

    Antiretroviral therapy has increased the life span of HIV+ individuals; however, HIV-associated neurocognitive disorder (HAND) occurrence is increasing in aging HIV patients. Previous studies suggest HIV infection alters autophagy function in the aging CNS and HIV-1 proteins affect autophagy in monocyte-derived cells. Despite these findings, the mechanisms leading to dysregulated autophagy in the CNS remain unclear. Here we sought to determine how HIV Tat dysregulates autophagy in neurons. Tat caused a dose-dependent decrease in autophagosome markers, microtubule-associated protein-1 light chain β II (LC3II), and sequestosome 1(SQSTM1), in a membrane-enriched fraction, suggesting Tat increases autophagic degradation. Bafilomycin A1 increased autophagosome number, LC3II, and SQSTM1 accumulation; Tat cotreatment diminished this effect. Tat had no effect when 3-methyladenine or knockdown of beclin 1 blocked early stages of autophagy. Tat increased numbers of LC3 puncta and resulted in the formation of abnormal autophagosomes in vitro. Likewise, in vivo studies in GFAP-Tat tg mice showed increased autophagosome accumulation in neurons, altered LC3II levels, and neurodegeneration. These effects were reversed by rapamycin treatment. Tat colocalized with autophagosome and lysosomal markers and enhanced the colocalization of autophagosome with lysosome markers. Furthermore, co-IP studies showed that Tat interacts with lysosomal-associated membrane protein 2A (LAMP2A) in vitro and in vivo, and LAMP2A overexpression reduces Tat-induced neurotoxicity. Hence, Tat protein may induce autophagosome and lysosome fusion through interaction with LAMP2A leading to abnormal neuronal autophagy function and dysregulated degradation of critical intracellular components. Therapies targeting Tat-mediated autophagy alterations may decrease neurodegeneration in aging patients with HAND. PMID:25653352

  6. HIV-associated anemia after 96 weeks on therapy: determinants across age ranges in Uganda and Zimbabwe.

    PubMed

    Jaganath, Devan; Walker, A Sarah; Ssali, Francis; Musiime, Victor; Kiweewa, Francis; Kityo, Cissy; Salata, Robert; Mugyenyi, Peter

    2014-06-01

    Given the detrimental effects of HIV-associated anemia on morbidity, we determined factors associated with anemia after 96 weeks of antiretroviral therapy (ART) across age groups. An HIV-positive cohort (n=3,580) of children age 5-14, reproductive age adults 18-49, and older adults ≥50 from two randomized trials in Uganda and Zimbabwe were evaluated from initiation of therapy through 96 weeks. We conducted logistic and multinomial regression to evaluate common and differential determinants for anemia at 96 weeks on therapy. Prior to initiation of ART, the prevalence of anemia (age 5-11 <10.5 g/dl, 12-14 <11 g/dl, adult females <11 g/dl, adult males <12 g/dl) was 43%, which decreased to 13% at week 96 (p<0.001). Older adults had a significantly higher likelihood of anemia compared to reproductive age adults (OR 2.60, 95% CI 1.44-4.70, p=0.002). Reproductive age females had a significantly higher odds of anemia compared to men at week 96 (OR 2.56, 95% CI 1.92-3.40, p<0.001), and particularly a greater odds for microcytic anemia compared to males in the same age group (p=0.001). Other common factors associated with anemia included low body mass index (BMI) and microcytosis; greater increases in CD4 count to week 96 were protective. Thus, while ART significantly reduced the prevalence of anemia at 96 weeks, 13% of the population continued to be anemic. Specific groups, such as reproductive age females and older adults, have a greater odds of anemia and may guide clinicians to pursue further evaluation and management. PMID:24506102

  7. Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS.

    PubMed

    Dahal, Santosh; Chitti, Sai V P; Nair, Madhavan P N; Saxena, Shailendra K

    2015-01-01

    Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection

  8. Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS

    PubMed Central

    Dahal, Santosh; Chitti, Sai V. P.; Nair, Madhavan P. N.; Saxena, Shailendra K.

    2015-01-01

    Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection

  9. Sensory, psychological, and metabolic dysfunction in HIV-associated peripheral neuropathy: A cross-sectional deep profiling study

    PubMed Central

    Phillips, Tudor J.C.; Brown, Matthew; Ramirez, Juan D.; Perkins, James; Woldeamanuel, Yohannes W.; Williams, Amanda C. de C.; Orengo, Christine; Bennett, David L.H.; Bodi, Istvan; Cox, Sarah; Maier, Christoph; Krumova, Elena K.; Rice, Andrew S.C.

    2014-01-01

    HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of HIV infection and a major source of morbidity. A cross-sectional deep profiling study examining HIV-SN was conducted in people living with HIV in a high resource setting using a battery of measures which included the following: parameters of pain and sensory symptoms (7 day pain diary, Neuropathic Pain Symptom Inventory [NPSI] and Brief Pain Inventory [BPI]), sensory innervation (structured neurological examination, quantitative sensory testing [QST] and intraepidermal nerve fibre density [IENFD]), psychological state (Pain Anxiety Symptoms Scale-20 [PASS-20], Depression Anxiety and Positive Outlook Scale [DAPOS], and Pain Catastrophizing Scale [PCS], insomnia (Insomnia Severity Index [ISI]), and quality of life (Short Form (36) Health Survey [SF-36]). The diagnostic utility of the Brief Peripheral Neuropathy Screen (BPNS), Utah Early Neuropathy Scale (UENS), and Toronto Clinical Scoring System (TCSS) were evaluated. Thirty-six healthy volunteers and 66 HIV infected participants were recruited. A novel triumvirate case definition for HIV-SN was used that required 2 out of 3 of the following: 2 or more abnormal QST findings, reduced IENFD, and signs of a peripheral neuropathy on a structured neurological examination. Of those with HIV, 42% fulfilled the case definition for HIV-SN (n = 28), of whom 75% (n = 21) reported pain. The most frequent QST abnormalities in HIV-SN were loss of function in mechanical and vibration detection. Structured clinical examination was superior to QST or IENFD in HIV-SN diagnosis. HIV-SN participants had higher plasma triglyceride, concentrations depression, anxiety and catastrophizing scores, and prevalence of insomnia than HIV participants without HIV-SN. PMID:24973717

  10. Practical Management of HIV-Associated Anemia in Resource-Limited Settings: Prospective Observational Evaluation of a New Mozambican Guideline.

    PubMed

    Brentlinger, Paula E; Silva, Wilson P; Vermund, Sten H; Valverde, Emilio; Buene, Manuel; Moon, Troy D

    2016-01-01

    Mozambique's updated guideline for management of HIV-associated anemia prompts clinicians to consider opportunistic conditions, adverse drug reactions, and untreated immunosuppression in addition to iron deficiency, intestinal helminthes, and malaria. We prospectively evaluated this guideline in rural Zambézia Province. Likely cause(s) of anemia were determined through prespecified history, physical examination, and laboratory testing. Diagnoses were "etiologic" if laboratory confirmed (sputum microscopy, blood culture, Plasmodium falciparum malaria rapid test) or "syndromic" if not. To assess hemoglobin response, we used serial point-of-care measurements. We studied 324 ambulatory, anemic (hemoglobin <10 g/dl) HIV-infected adults. Study clinicians treated nearly all [315 (97.2%)] for suspected iron deficiency and/or helminthes; 56 (17.3%) had laboratory-confirmed malaria. Other assigned diagnoses included tuberculosis [30 (9.3%)], adverse drug reactions [26 (8.0%)], and bacteremia [13 (4.1%)]. Etiologic diagnosis was achieved in 79 (24.4%). Of 169 (52.2%) subjects who improved (hemoglobin increase of ≥1 g/dl without indications for hospitalization), only 65 (38.5%) received conventional management (iron supplementation, deworming, and/or antimalarials) alone. Thirty (9.3%) died and/or were hospitalized, and 125 (38.6%) were lost to follow-up. Multivariable linear and logistic regression models described better hemoglobin responses and/or outcomes in subjects with higher CD4(+) T-lymphocyte counts, pre-enrollment antiretroviral therapy and/or co-trimoxazole prophylaxis, discontinuation of zidovudine for suspected adverse reaction, and smear-positive tuberculosis. Adverse outcomes were associated with fever, low body mass index, bacteremia, esophageal candidiasis, and low or missing CD4(+) T cell counts. In this severely resource-limited setting, successful anemia management often required interventions other than conventional presumptive treatment, thus

  11. Incidence, Carriage and Case-Carrier Ratios for Meningococcal Meningitis in the African Meningitis Belt: A Systematic Review and Meta-Analysis

    PubMed Central

    Koutangni, Thibaut; Boubacar Maïnassara, Halima; Mueller, Judith E.

    2015-01-01

    Background To facilitate the interpretation of meningococcal meningitis epidemiology in the “African meningitis belt”, we aimed at obtaining serogroup-specific pooled estimates of incidence, carriage and case-carrier ratios for meningococcal meningitis in the African meningitis belt and describe their variations across the endemic, hyperendemic and epidemic context. Methods We conducted a systematic review and meta-analysis of studies reporting serogroup-specific meningococcal meningitis monthly incidence and carriage in the same population and time period. Epidemiological contexts were defined as endemic (wet season, no epidemic), hyperendemic (dry season, no epidemic), and epidemic (dry season, epidemic). Findings Eight studies reporting a total of eighty pairs of serogroup-specific meningococcal meningitis incidence and carriage estimates were included in this review. For serogroup A, changes associated with the transition from endemic to hyperendemic incidence and from hyperendemic to epidemic incidence were 15-fold and 120-fold respectively. Changes in carriage prevalence associated with both transitions were 1-fold and 30-fold respectively. 
For serogroup W and X, the transition from endemic to hyperendemic incidence involved a 4-fold and 1•1-fold increase respectively. Increases in carriage prevalence for the later transition were 7-fold and 1•7-fold respectively. No data were available for the hyperendemic-epidemic transition for these serogroups. Our findings suggested that the regular seasonal variation in serogroup A meningococcal meningitis incidence between the rainy and the dry season could be mainly driven by seasonal change in the ratio of clinical cases to subclinical infections. In contrast appearance of epidemic incidences is related to a substantial increase in transmission and colonisation and to lesser extent with changes in the case-carrier ratio. Conclusion Seasonal change in the rate of progression to disease given carriage

  12. Congenital cerebrospinal fluid fistula through the inner ear and meningitis.

    PubMed

    Phelps, P D; Proops, D; Sellars, S; Evans, J; Michaels, L

    1993-06-01

    Congenital deformities of the labyrinth of the inner ear can be associated with a fistulous communication between the intracranial subarachnoid space and the middle ear cavity. We describe seven such cases, six confirmed by high resolution CT and one by postmortem histological section. The seven patients all presented with meningitis although a cerebrospinal fluid fistula was demonstrated at subsequent surgery or postmortem. The lesions were bilateral in three patients, unilateral in three and probably bilateral in the postmortem case although only one temporal bone was obtained. In every case there was a dilated sac instead of the normal two and a half turn cochlea on the affected side and this was confirmed at surgery. The demonstration of the basal cochlear turn is of paramount importance in any deaf child presenting with meningitis. A true Mondini deformity with a normal basal turn and some hearing is not at risk of developing a fistula. PMID:8345296

  13. How Do Meningeal Lymphatic Vessels Drain the CNS?

    PubMed

    Raper, Daniel; Louveau, Antoine; Kipnis, Jonathan

    2016-09-01

    The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood. Here, we discuss the potential differences between peripheral and CNS lymphatic vessels and examine the purported mechanisms of CNS lymphatic drainage, along with how these may fit into established patterns of CSF flow. PMID:27460561

  14. Epidemiology, Etiology, Pathogenesis, and Diagnosis of Recurrent Bacterial Meningitis

    PubMed Central

    Tebruegge, Marc; Curtis, Nigel

    2008-01-01

    Recurrent bacterial meningitis is a rare phenomenon and generally poses a considerable diagnostic challenge to the clinician. Ultimately, a structured approach and early diagnosis of any underlying pathology are crucial to prevent further episodes and improve the overall outcome for the affected individual. In this article, we are reviewing the existing literature on this topic over the last two decades, encompassing 363 cases of recurrent bacterial meningitis described in 144 publications. Of these cases, 214 (59%) were related to anatomical problems, 132 (36%) were related to immunodeficiencies, and 17 (5%) were related to parameningeal infections. The review includes a detailed discussion of the underlying pathologies and microbiological aspects as well as recommendations for appropriate diagnostic pathways for investigating this unusual entity. PMID:18625686

  15. Subarachnoid space: middle ear pathways and recurrent meningitis.

    PubMed

    Barcz, D V; Wood, R P; Stears, J; Jafek, B W; Shields, M

    1985-03-01

    Congenital bony abnormalities of the inner ear may result in a communication between the middle ear and the subarachnoid space. Patients with this anomaly often present with recurrent meningitis associated with acute otitis media or with middle ear fluid. This article presents three cases of recurrent meningitis with open middle ear--subarachnoid space connections. The first two cases involve a cerebrospinal fluid leak into the middle ear via the oval window, both patients having a Mondini-type of inner ear deformity. The pathway in the third case opened into the middle ear along the horizontal portion of the facial nerve. Computed tomography (CT) scanning with metrizamide and differential density calculations helped to identify the abnormal pathway and to confirm that the leak has been closed postoperatively. Use of the CT scanner in these cases can be helpful in planning the surgical closure and in postoperative follow-up. PMID:4039111

  16. Pneumococcal meningitis in an adolescent with fever and foot ache.

    PubMed

    Dias, Catarina; Pedrosa, Cláudia; Romariz, Jorge; Santos, Mafalda; Rodrigues, Lúcia

    2013-01-01

    Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis and Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement. PMID:23956909

  17. [A case of invasive pulmonary aspergillosis accompanied with Aspergillus meningitis].

    PubMed

    Akutsu, K; Goto, H; Sakurada, S; Ota, T; Yuasa, K; Iguchi, M; Okamura, T; Ieki, R; Kawamura, T

    1996-06-01

    A 53-year-old female was admitted to our hospital complaining of chest pain and gait disturbance. Examinations on admission showed that she was immunocompetent except the negative tuberculin test. The chest X-ray showed infiltrative shadows with old tuberculous lesions in the bilateral upper lung fields. In CT, a mass lesion was revealed in the lesion, which destructed the fifth thoracic vertebra and invaded into the epidural space. She died of meningitis on the 18th day after admission. On autopsy, it was made clear that the mass lesion was caused by Aspergillus fumigatus, and that the meningitis was the result of the invasion of the fungus into the epidural space. PMID:8741716

  18. Antibiotic therapy for bacterial meningitis in children in developing countries.

    PubMed Central

    Kumar, P.; Verma, I. C.

    1993-01-01

    We carried out a study to investigate the effectiveness of chloramphenicol alone as a treatment for bacterial meningitis. A total of 70 consecutive children aged > 3 months with bacterial meningitis, who had been admitted to the paediatric hospital of the All India Institute of Medical Sciences, were randomized to receive chloramphenicol alone or chloramphenicol + penicillin. The two groups were matched with each other. Treatment failure occurred with three (9%) patients in the chloramphenicol-alone group and with four (12.1%) patients in the combination therapy group (P > 0.05). The mean duration of intravenous therapy, the number of intravenous cannulae used per patient, and the incidence of thrombophlebitis were significantly higher for the group that received the combination therapy. Also, the cost of using chloramphenicol + penicillin was four times higher than that of chloramphenicol alone. Hence, chloramphenicol alone was as effective as chloramphenicol + penicillin and much cheaper and more convenient to use. PMID:8490981

  19. Pasteurella multocida bacterial meningitis caused by contact with pigs

    PubMed Central

    López, C.; Sanchez-Rubio, P.; Betrán, A.; Terré, R.

    2013-01-01

    Pasteurella multocida belongs to the normal flora of the respiratory and digestive tract of many animals. Animal exposure is a considerable risk factor for Pasteurella infection. P. multocida is the most common cause of local infection after an animal bite but is an unusual cause of meningitis. We present a case of bacterial meningitis by P. multocida in a 37-year-old man who worked in a pig farm and was bitten by a pig. The patient had a defect located in the lamina cribosa and this lesion could be the gateway of the infection, although in this case the infection could also be acquired through the pig bite. The bacteria was identified as P. multocida with the biochemical test API 20E (bioMérieux). In agreement with findings in the literature, the strain was susceptible in vitro to penicillin, ampicillin, cefotaxime, ceftriaxone ciprofloxacin, levofloxacin, imipenem and tetracycline. PMID:24294240

  20. Improving Decision-Making Activities for Meningitis and Malaria

    NASA Technical Reports Server (NTRS)

    Ceccato, Pietro; Trzaska, Sylwia; Garcia-Pando, Carlos Perez; Kalashnikova, Olga; del Corral, John; Cousin, Remi; Blumenthal, M. Benno; Bell, Michael; Connor, Stephen J.; Thomson, Madeleine C.

    2013-01-01

    Public health professionals are increasingly concerned about the potential impact that climate variability and change can have on infectious disease. The International Research Institute for Climate and Society (IRI) is developing new products to increase the public health community's capacity to understand, use and demand the appropriate climate data and climate information to mitigate the public health impacts of climate on infectious disease, in particular meningitis and malaria. In this paper, we present the new and improved products that have been developed for: (i) estimating dust aerosol for forecasting risks of meningitis and (ii) for monitoring temperature and rainfall and integrating them into a vectorial capacity model for forecasting risks of malaria epidemics. We also present how the products have been integrated into a knowledge system (IRI Data Library Map Room, SERVIR) to support the use of climate and environmental information in climate-sensitive health decision-making.

  1. [Salmonella enteritidis: an unusual meningitis agent in an adult patient].

    PubMed

    Metan, Gökhan; Alp, Emine; Eşel, Duygu; Aygen, Bilgehan; Sümerkan, Bülent

    2005-10-01

    Salmonella species may cause wide spectrum of infections changing from enterocolitis to sepsis. However, Salmonella meningitis in adults is a rare but important clinical condition with a high mortality rate. In this report, a 71 years old male patient with Salmonella enteritidis meningitis who was followed-up with the diagnosis of immune thrombocytopenic purpura and had been administered azothioprin and prednisolone, has been presented and similar cases in the literature have been reviewed. The cerebrospinal fluid culture yielded S. enteritidis, and the isolate was intermediate susceptible to ampicillin, susceptible to cefotaxime, trimethoprim-sulphametoxasole, ciprofloxacin and chloramphenicol. Our patient was successfully treated with ceftriaxone (2 x 2 gr i.v.) and discharged with total cure. PMID:16544553

  2. Pneumococcal Meningitis in an Adolescent with Fever and Foot Ache

    PubMed Central

    Dias, Catarina; Pedrosa, Cláudia; Romariz, Jorge; Santos, Mafalda; Rodrigues, Lúcia

    2013-01-01

    Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis and Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement. PMID:23956909

  3. Sonographic findings in bacterial meningitis in neonates and young infants.

    PubMed

    Yikilmaz, Ali; Taylor, George A

    2008-02-01

    Cranial sonography plays an important role in the initial evaluation of infants with suspected bacterial meningitis and in monitoring for complications of the disease. Echogenic widening of the brain sulci, meningeal thickening and hyperemia suggest the diagnosis in an at-risk population. Sonography can identify the presence of extra-axial fluid collections, and color Doppler sonography can be very helpful in differentiating benign enlargement of subarachnoid spaces from subdural effusions. Intraventricular debris and stranding, and an irregular and echogenic ependyma are highly suggestive findings associated with ventriculitis. Sonography can play an important role in the detection of postinfectious hydrocephalus, in the determination of the level of obstruction, and in the evaluation of intracranial compliance. Focal or diffuse parenchymal involvement can represent parenchymal involvement by cerebritis, infarction, secondary hemorrhage or early abscess. PMID:17611750

  4. [Cryptococcus meningitis in an immunocompetent child: a case report].

    PubMed

    Ndiaye, M; Hagerimana, R; Diagne, N S; Faye, M W; Sène, M S; Sow, A D; Sène-Diouf, F; Diop, A G; Ndiaye, M M

    2010-07-01

    Cryptococcus meningitis is uncommon in childhood. We report a Senegalese case of cryptococcus meningitis diagnosed in an apparently immunocompetent child. A 9-year-old boy was admitted for acute meningoencephalitis. A computerized tomography scan of the brain showed an ischemic lesion in the left caudate and study of cerebrospinal fluid (CSF) revealed cytological and biochemical abnormalities and Cryptococcus neoformans on direct exam and culture. HIV and syphilis antibodies were negative and the blood CD4 lymphocyte count was 804/mm(3). The child had no immunocompromising factors such as hematologic abnormalities, solid tumor, or undernutrition. He was treated with fluconazole intravenously, but clinical outcome was unsuccessful. The patient died after 1 month from cardiovascular and respiratory distress. PMID:20400277

  5. Improving Decision-Making Activities for Meningitis and Malaria

    NASA Astrophysics Data System (ADS)

    Ceccato, P.; Trzaska, S.; Perez, C.; Kalashnikova, O. V.; del Corral, J.; Cousin, R.; Blumenthal, M. B.; Connor, S.; Thomson, M. C.

    2012-12-01

    Public health professionals are increasingly concerned about the potential impact that climate variability and change can have on infectious disease. The International Research Institute for Climate and Society (IRI) is developing new products to increase the public health community's capacity to understand, use, and demand the appropriate climate data and climate information to mitigate the public health impacts of climate on infectious disease, in particular Meningitis and Malaria. In this paper we present the new and improved products that have been developed for monitoring dust, temperature, rainfall and vectorial capacity model for monitoring and forecasting risks of Meningitis and Malaria epidemics. We also present how the products have been integrated into a knowledge system (IRI Data Library Map room, SERVIR) to support the use of climate and environmental information in climate-sensitive health decision-making.

  6. The spectrum of primary blastomycotic meningitis: a review of central nervous system blastomycosis.

    PubMed

    Gonyea, E F

    1978-01-01

    Three cases of meningitis with initial and exclusive neurological involvement prompted a review of the clinical, cerebrospinal fluid, and pathological findings in an additional 78 patients with central nervous system blastomycosis. The first patient of the 3 had progressive cerebellar dysfunction as the result of chronic basilar meningitis. The second had a C8-T1 radiculopathy without other evidence of superior sulcus syndrome, and subsequent acute fatal meningitis. The third had aseptic, benign, self-limited meningitis followed by clinically obvious systemic blastomycosis. Diagnosis is difficult, and it is likely that other cases have been presumptively treated for tuberculous meningitis. A more aggressive approach to diagnosis is proposed that takes into account the condition of the patient, the likelihood of dissemination at necropsy, and the frequent meningeal infections that are negative on culture of lumbar CSF. PMID:655652

  7. Recurrent sterile meningitis caused by a pituitary abscess.

    PubMed

    Ford, J; Torres, L F; Cox, T; Hayward, R

    1986-10-01

    The case of a 21 year old woman who presented with recurrent sterile meningitis and bitemporal hemianopia is described. Computed tomographic scan showed a large low density ring enhancing lesion above and within the pituitary fossa which at operation and on histological examination was found to be compatible with an abscess. The visual field defect recovered completely and the scan appearances returned to normal postoperatively. PMID:3774724

  8. Recrudescence and relapse of meningococcal meningitis and septicaemia.

    PubMed

    Nielsen, P E; Thelle, T; Tvede, M

    1995-03-01

    Three cases of recrudescence and relapse of Neisseria meningitidis group B meningitis and septicaemia are reported. The recrudescence and relapses could not be explained by infectious foci, increased bacterial penicillin resistance or immunological defects. As a supplement to antibiotic treatment, all three patients received corticosteroids for the initial 2 days of treatment, and this may have contributed to the unusual course of the disease in our patient. PMID:7780262

  9. An outbreak of meningitis caused by Neisseria meningitidis Group A.

    PubMed

    Annapurna, M E; Bhave, G G; Mathur, M

    1989-03-01

    During a period of six months from September, 1985 to March, 1986, there were twenty seven cases of pyogenic meningitis due to Neisseria meningitidis Group A. Maximum number of cases could be diagnosed by antigen detection by latex agglutination test. The organism was sensitive to all commonly used antibiotics. The patients affected were mostly young adults. The mortality rate was eleven per cent. PMID:2509544

  10. [A case of Listeria monocytogenes meningitis in an immunocompetent infant].

    PubMed

    Pattarino, G; Arrigoni, S; Grazioli, R; De Palma, A; di Natale, B

    2006-08-01

    Listeria Monocytogenes meningitis is a rare affection after the neonatal period, but in immunocompromised patients. Listeria Monocytogenes is a Gram-positive, facultative intracellular bacterium frequently causing infection in pregnant women, in patients with cell-mediated immunity deficit and in the early and late stages of life. We present a case of Listeria Monocytogenes meningitis in an immunocompetent nomad 8-month-child, preceded by gastroenteritis. Although gastrointestinal symptoms may be due to intestinal infection by Listeria, the concomitant presence of other bacteric or viral enteric pathogens may have promoted bacterium intestinal translocation and generated disseminated disease. The main transmission route of infection after the neonatal period is ingestion of contaminated food. A diet history was taken after isolation of the bacterium in liquor and showed that the child was an eater of undercooked hot-dogs. Despite the frequency of clinical complication in such affection, the outcome in this patient was a complete recovery. Although the infection is extremely infrequent in healthy children, physicians should always consider Listeria as a possible etiologic agent of meningitis in pediatric patients, regardless of their age or immunological status, especially in patients living in precarious sanitary conditions, where weaning times and conditions are not respected and a suitable food cooking is not assured. PMID:17008849

  11. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis

    PubMed Central

    Grandgirard, Denis; Valente, Luca G.; Täuber, Martin G.; Leib, Stephen L.

    2016-01-01

    Streptococcus pneumoniae bacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  12. Distribution of meningeal worm (Parelaphostrongylus tenuis) in South Dakota.

    PubMed

    Jacques, Christopher N; Jenks, Jonathan A

    2004-01-01

    Heads of hunter-harvested deer (Odocoileus sp.) and elk (Cervus elaphus) were collected from meat processing plants throughout South Dakota (USA) from 1997 through 1999 to determine distribution of meningeal worm (Parelaphostrongylus tenuis) in eastern and western South Dakota. A total of 2,848 white-tailed deer (WTD) were examined for P. tenuis, of which 578 (20.3%) were infected with the parasite. Of 578 deer infected, 570 (98.6%) were harvested east of the Missouri River. Our results indicate that P. tenuis is widely distributed throughout eastern South Dakota and limited to the southcentral region of western South Dakota. Infected WTD were documented in 37 of 44 counties in eastern South Dakota and three of 22 counties in western South Dakota. No meningeal worms were found on the meninges or cranial surfaces of 215 mule deer ( Odocoileus hemionus) or 344 elk examined. These findings further define the distribution of the parasite throughout the state. We suggest that the Missouri River acts, in part, as a physical barrier to the westward expansion of P. tenuis to the grasslands of western South Dakota. PMID:15137501

  13. [Pneumococcal meningitis in the infantile population of Cantabria].

    PubMed

    Alonso Palacio, J; Madrigal Díez, V; García Fuentes, M

    1992-06-01

    A retrospective study of pneumococcal meningitis was carried out. This study included 22 cases of this illness that occurred in 17 pediatric patients in Cantabria between 1977 and 1990, inclusive. Three children suffered from recurrent meningitis. The age range of the patients was 0.3-14 years, with a mean age of 4 years. Of these cases, 77.4% occurred in the winter or spring. In 14 cases of meningitis (63.6%), corresponding to 9 patients, underlying pathology was observed: cranial fracture, occipital dermoid cyst, splenectomy, congenital cardiopathy, epilepsy and gastroduodenal "situs inversus". The isolated pneumococci were found to be resistant to penicillin and chloramphenicol in 4 cases. One patient suffered from septic shock. The outcome was complete recovery in 19 cases (86.4%), recovery with sequelae (deafness and epilepsy, respectively) in 2 cases (9.1%) and death in another 2 cases. CSF protein levels elevated above 150 mg/dl and the absence of glucose in the CSF were found to be the most useful analytical indicators of the seriousness of the illness. PMID:1497225

  14. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis.

    PubMed

    Hathaway, Lucy J; Grandgirard, Denis; Valente, Luca G; Täuber, Martin G; Leib, Stephen L

    2016-03-01

    Streptococcus pneumoniaebacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  15. Neoplastic Meningitis from Solid Tumors: New Diagnostic and Therapeutic Approaches

    PubMed Central

    Zustovich, Fable; Farina, Patrizia; Della Puppa, Alessandro; Manara, Renzo; Cecchin, Diego; Brunello, Antonella; Cappetta, Alessandro; Zagonel, Vittorina

    2011-01-01

    Neoplastic meningitis is a result of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid. This event occurs in 4%–15% of all patients with solid tumors and represents an important prognostic factor for poor survival. Neoplastic meningitis should be diagnosed in the early stages of disease to prevent important neurological deficits and to provide the most appropriate treatment. Despite new diagnostic approaches developed in recent years, such as positron emission tomography–computed tomography and new biological markers, the combination of magnetic resonance imaging without and with gadolinium enhancement and cytology still has the greatest diagnostic sensitivity. Recently, no new randomized studies comparing intrathecal (i.t.) with systemic treatment have been performed, yet there have been a few small phase II studies and case reports about new molecularly targeted substances whose successful i.t. or systemic application has been reported. Trastuzumab, gefitinib, and sorafenib are examples of possible future treatments for neoplastic meningitis, in order to better individualize therapy thus allowing better outcomes. In this review, we analyze the most recent and interesting developments on diagnostic and therapeutic approaches. PMID:21795431

  16. HIV-Associated Tuberculosis.

    PubMed

    Naidoo, Kogieleum; Naidoo, Kasavan; Padayatchi, Nesri; Abdool Karim, Quarraisha

    2011-01-01

    The intersecting HIV and Tuberculosis epidemics in countries with a high disease burden of both infections pose many challenges and opportunities. For patients infected with HIV in high TB burden countries, the diagnosis of TB, ARV drug choices in treating HIV-TB coinfected patients, when to initiate ARV treatment in relation to TB treatment, managing immune reconstitution, minimising risk of getting infected with TB and/or managing recurrent TB, minimizing airborne transmission, and infection control are key issues. In addition, given the disproportionate burden of HIV in women in these settings, sexual reproductive health issues and particular high mortality rates associated with TB during pregnancy are important. The scaleup and resource allocation to access antiretroviral treatment in these high HIV and TB settings provide a unique opportunity to strengthen both services and impact positively in meeting Millennium Development Goal 6. PMID:20871843

  17. [Neonatal meningitis. Study of 26 cases and a review of its sequelae after 5 years].

    PubMed

    Cervantes Pardo, A; Tauler Girona, M C; López Soler, C; Puche Mira, A; Casas Fernández, C; Rodríguez Costa, T

    1988-06-01

    Twenty-six cases of neonatal meningitis in term newborns are studied. Incidence, etiological features, treatment, clinical and biochemical evolution and mortality are analysed. Lief motif of this paper is the search for deficits in psychomotor growth in propositi of four and six years old, finding an important relation between neonatal bacterial meningitis and neuropsychological deficits (hyperkinesia, perceptive area impairment, reading-writing disorders, etc.) in contrast to the good evolution of lymphocytic meningitis. PMID:2461673

  18. [Nosocomial meningitis with dual agents and treatment with intraventricular gentamicin].

    PubMed

    Oztoprak, Nefise; Celebi, Güven; Baruönü, Fatma; Kalayci, Murat

    2008-07-01

    Nosocomial central nervous system infections constitute 0.4% of all nosocomial infections. The responsible pathogens of nosocomial meningitis are quite different from community-acquired meningitis with high rates of morbidity and mortality. The most important prognostic factor is the appropriate choice of pathogen-specific antibacterial therapy. In this report, a 64 years old woman with nosocomial meningitis caused by Klebsiella pneumoniae and Acinetobacter spp. after lumbar disc hernia operation, has been presented. The risk factors were detected as recent history of neurosurgical operation for three times and long term (29 days) use of external ventricular drainaige (EVD) catheter. Empirical meropenem (3 x 2 g, IV) and vancomycin (2 x 1 g, IV) therapy was initiated upon the diagnosis of nosocomial meningitis based on the clinical and laboratory findings on the postoperative fifth day. Extended-spectrum beta-lactamase (ESBL) producing K. pneumoniae (susceptible to amikacin, imipenem, meropenem, cefoxitine, ciprofloxacin, piperasillin-tazobactam and trimethoprim/sulfamethoxazole) was recovered from cerebrospinal fluid (CSF) and blood samples obtained on the same day. There was no change in the status of the patient on the eighth day of meropenem therapy, with high leukocyte number (1300/mm3) and presence of gram-negative bacilli in CSF, and ESBL positive K. pneumoniae (antibiotic susceptibility pattern same with the previous isolate) growth in CSF culture. Thereupon intravenous ciprofloxacin (3 x 400 mg) was added to the therapy and her EVD has been changed. However, ESBL positive K. pneumoniae (antibiotic susceptibility pattern same with the previous isolate) together with Acinetobacter spp. (susceptible to gentamycin, tobramycin, netilmicin, ciprofloxacin, levofloxacin and cefepime) were isolated from CSF and blood cultures obtained on the 13th day of meropenem and fifth day of ciprofloxacin therapy. Therefore intraventricular and intravenous gentamicin (15 mg

  19. Natural Products as Anti-HIV Agents and Role in HIV-Associated Neurocognitive Disorders (HAND): A Brief Overview

    PubMed Central

    Kurapati, Kesava Rao V.; Atluri, Venkata S.; Samikkannu, Thangavel; Garcia, Gabriella; Nair, Madhavan P. N.

    2016-01-01

    As the threat of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) persists to rise, effective drug treatments are required to treat the infected people. Even though combination antiretroviral therapy (cART) provides stable viral suppression, it is not devoid of undesirable side effects, especially in persons undergoing long-term treatment. The present therapy finds its limitations in the emergence of multidrug resistance and accordingly finding new drugs and novel targets is the need of the hour to treat the infected persons and further to attack HIV reservoirs in the body like brain, lymph nodes to achieve the ultimate goal of complete eradication of HIV and AIDS. Natural products such as plant-originated compounds and plant extracts have enormous potential to become drug leads with anti-HIV and neuroprotective activity. Accordingly, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action and for HIV-associated neurocognitive disorders (HAND). The basic challenge that still persists is to develop viral replication-targeted therapy using novel anti-HIV compounds with new mode of action, accepted toxicity and less resistance profile. Against this backdrop, the World Health Organization (WHO) suggested the need to evaluate ethno-medicines for the management of HIV/AIDS. Consequently, there is need to evaluate traditional medicine, particularly medicinal plants and other natural products that may yield effective and affordable therapeutic agents. Although there are a good number of reports on traditional uses of plants to treat various diseases, knowledge of herbal remedies used to manage HIV/AIDS and HAND are scanty, vague and not well documented. In this review, plant substances showing a promising action that is anti-HIV and HAND will be explored along with what they interact. Since some plant substances are also known to modulate several cellular

  20. Cerebrospinal Fluid (CSF) CD8+ T-Cells That Express Interferon-Gamma Contribute to HIV Associated Neurocognitive Disorders (HAND)

    PubMed Central

    Schrier, Rachel D.; Hong, Suzi; Crescini, Melanie; Ellis, Ronald; Pérez-Santiago, Josué; Spina, Celsa; Letendre, Scott

    2015-01-01

    Background HIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis. Methods To investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFNγ, IL-2, TNFα) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART. Results Data were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNFα, IL-2, IFNγ and CD8+T-cells: IL-2 and IFNγ. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA <103 copies/ml (p<0.0001). Specifically, CSF CD8+ T-cell IFNγ expression correlated with severity of NCI (r = 0.57, p = 0.004). Multivariable analyses indicated that CSF CD8+T-cell IFNγ and myeloid activation (CD163) contributed equally and independently to cognitive status and a composite variable produced the strongest correlation with NCI (r = 0.83, p = 0.0001). In contrast, CD8+ cytolytic activity (CD107a expression) was negatively correlated with NCI (p = 0.05) but was dependent on CD4 levels >400/μl and low CSF HIV RNA levels (<103 copies/ml). In our longitudinal analysis of 16 subjects, higher CSF CD8+IFNγ expression at baseline predicted NC decline at follow-up (p = 0.02). Severity of NCI at follow-up correlated with level of residual HIV RNA in CSF. Conclusions Presence of IFNγ expressing CD8+ T

  1. Osmotic therapies added to antibiotics for acute bacterial meningitis

    PubMed Central

    Wall, Emma CB; Ajdukiewicz, Katherine MB; Heyderman, Robert S; Garner, Paul

    2014-01-01

    Background Every day children and adults throughout the world die from acute community-acquired bacterial meningitis, particularly in low-income countries. Survivors are at risk of deafness, epilepsy and neurological disabilities. Osmotic therapies have been proposed as an adjunct to improve mortality and morbidity from bacterial meningitis. The theory is that they will attract extra-vascular fluid by osmosis and thus reduce cerebral oedema by moving excess water from the brain into the blood. The intention is to thus reduce death and improve neurological outcomes. Objectives To evaluate the effects on mortality, deafness and neurological disability of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults. Search methods We searched CENTRAL 2012, Issue 11, MEDLINE (1950 to November week 3, 2012), EMBASE (1974 to November 2012), CINAHL (1981 to November 2012), LILACS (1982 to November 2012) and registers of ongoing clinical trials (April 2012). We also searched conference abstracts and contacted researchers in the field. Selection criteria Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. Data collection and analysis Two review authors independently screened the search results and selected trials for inclusion. We collected data from each study for mortality, deafness, seizures and neurological disabilities. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. Main results Four trials were included comprising 1091 participants. All compared glycerol (a water-soluble sugar alcohol) with a control; in three trials this was a placebo, and in one a small amount of 50% dextrose. Three trials included comparators of dexamethasone alone or in combination with glycerol. As dexamethasone appeared to have no modifying effect, we aggregated results across arms where both

  2. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    PubMed Central

    Park, Yoon-Dong; Sun, Wei; Salas, Antonio; Antia, Avan; Carvajal, Cindy; Wang, Amy; Xu, Xin; Meng, Zhaojin; Zhou, Ming; Tawa, Gregory J.; Dehdashti, Jean; Zheng, Wei; Henderson, Christina M.; Zelazny, Adrian M.

    2016-01-01

    ABSTRACT Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS) screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development. PMID:27486194

  3. Clinical and laboratory features of Streptococcus salivarius meningitis: a case report and literature review.

    PubMed

    Wilson, Megan; Martin, Ryan; Walk, Seth T; Young, Carol; Grossman, Sylvia; McKean, Erin Lin; Aronoff, David M

    2012-02-01

    Streptococcus salivarius is a normal member of the human oral microbiome that is an uncommon cause of invasive infections. Meningitis is a rare but increasingly reported infection caused by S. salivarius. Despite the growing number of reported cases, a comprehensive review of the literature on S. salivarius meningitis is lacking. We sought to gain a better understanding of the clinical presentation, evaluation, management, and outcome of S. salivarius meningitis by analyzing previously reported cases. In addition to a single case reported here, 64 previously published cases of meningitis were identified for this review. The collected data confirm that most patients presented with classical signs and symptoms of bacterial meningitis with a predominance of neutrophils in the cerebrospinal fluid (CSF) and hypoglycorrhachia. The majority of cases followed iatrogenic or traumatic CSF contamination. Most cases were diagnosed by CSF culture within one day of symptom onset. There was no clear evidence of predisposing co-morbid conditions in patients with meningitis, although in most case reports, limited information was given on the medical history of each patient. Outcomes were generally favorable with antibiotic management. Clinicians should suspect S. salivarius meningitis in patients presenting acutely after medical or surgical procedures involving the meninges. PMID:21817122

  4. Clinical and Laboratory Features of Streptococcus salivarius Meningitis: A Case Report and Literature Review

    PubMed Central

    Wilson, Megan; Martin, Ryan; Walk, Seth T.; Young, Carol; Grossman, Sylvia; McKean, Erin Lin; Aronoff, David M.

    2012-01-01

    Streptococcus salivarius is a normal member of the human oral microbiome that is an uncommon cause of invasive infections. Meningitis is a rare but increasingly reported infection caused by S. salivarius. Despite the growing number of reported cases, a comprehensive review of the literature on S. salivarius meningitis is lacking. We sought to gain a better understanding of the clinical presentation, evaluation, management, and outcome of S. salivarius meningitis by analyzing previously reported cases. In addition to a single case reported here, 64 previously published cases of meningitis were identified for this review. The collected data confirm that most patients presented with classical signs and symptoms of bacterial meningitis with a predominance of neutrophils in the cerebrospinal fluid (CSF) and hypoglycorrhachia. The majority of cases followed iatrogenic or traumatic CSF contamination. Most cases were diagnosed by CSF culture within one day of symptom onset. There was no clear evidence of predisposing co-morbid conditions in patients with meningitis, although in most case reports, limited information was given on the medical history of each patient. Outcomes were generally favorable with antibiotic management. Clinicians should suspect S. salivarius meningitis in patients presenting acutely after medical or surgical procedures involving the meninges. PMID:21817122

  5. Identification of Streptococcus suis Meningitis through Population-Based Surveillance, Togo, 2010–2014

    PubMed Central

    Tall, Haoua; Njanpop-Lafourcade, Berthe-Marie; Mounkoro, Didier; Tidjani, Loukoumane; Agbenoko, Kodjo; Alassani, Issifou; Amidou, Moussa; Tamekloe, Stanislas; Laing, Kenneth G.; Witney, Adam A.; Hinds, Jason; van der Linden, Mark P.G.; Gessner, Bradford D.

    2016-01-01

    During 2010–2014, we enrolled 511 patients with suspected bacterial meningitis into surveillance in 2 districts of northern Togo. We identified 15 persons with Streptococcus suis infection; 10 had occupational contact with pigs, and 12 suffered neurologic sequelae. S. suis testing should be considered in rural areas of the African meningitis belt. PMID:27314251

  6. Identification of Streptococcus suis Meningitis through Population-Based Surveillance, Togo, 2010-2014.

    PubMed

    Tall, Haoua; Njanpop-Lafourcade, Berthe-Marie; Mounkoro, Didier; Tidjani, Loukoumane; Agbenoko, Kodjo; Alassani, Issifou; Amidou, Moussa; Tamekloe, Stanislas; Laing, Kenneth G; Witney, Adam A; Hinds, Jason; van der Linden, Mark P G; Gessner, Bradford D; Moïsi, Jennifer C

    2016-07-01

    During 2010-2014, we enrolled 511 patients with suspected bacterial meningitis into surveillance in 2 districts of northern Togo. We identified 15 persons with Streptococcus suis infection; 10 had occupational contact with pigs, and 12 suffered neurologic sequelae. S. suis testing should be considered in rural areas of the African meningitis belt. PMID:27314251

  7. Spatial dynamics of meningococcal meningitis in Niger: observed patterns in comparison with measles.

    PubMed

    Bharti, N; Broutin, H; Grais, R F; Ferrari, M J; Djibo, A; Tatem, A J; Grenfell, B T

    2012-08-01

    Throughout the African meningitis belt, meningococcal meningitis outbreaks occur only during the dry season. Measles in Niger exhibits similar seasonality, where increased population density during the dry season probably escalates measles transmission. Because meningococcal meningitis and measles are both directly transmitted, we propose that host aggregation also impacts the transmission of meningococcal meningitis. Although climate affects broad meningococcal meningitis seasonality, we focus on the less examined role of human density at a finer spatial scale. By analysing spatial patterns of suspected cases of meningococcal meningitis, we show fewer absences of suspected cases in districts along primary roads, similar to measles fadeouts in the same Nigerien metapopulation. We further show that, following periods during no suspected cases, districts with high reappearance rates of meningococcal meningitis also have high measles reintroduction rates. Despite many biological and epidemiological differences, similar seasonal and spatial patterns emerge from the dynamics of both diseases. This analysis enhances our understanding of spatial patterns and disease transmission and suggests hotspots for infection and potential target areas for meningococcal meningitis surveillance and intervention. PMID:22009033

  8. Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis

    PubMed Central

    2013-01-01

    Background Bacterial meningitis caused by Streptococcus pneumoniae leads to death in up to 30% of patients and leaves up to half of the survivors with neurological sequelae. The inflammatory host reaction initiates the induction of the kynurenine pathway and contributes to hippocampal apoptosis, a form of brain damage that is associated with learning and memory deficits in experimental paradigms. Vitamin B6 is an enzymatic cofactor in the kynurenine pathway and may thus limit the accumulation of neurotoxic metabolites and preserve the cellular energy status. The aim of this study in a pneumococcal meningitis model was to investigate the effect of vitamin B6 on hippocampal apoptosis by histomorphology, by transcriptomics and by measurement of cellular nicotine amide adenine dinucleotide content. Methods and results Eleven day old Wistar rats were infected with 1x106 cfu/ml of S. pneumoniae and randomized for treatment with vitamin B6 or saline as controls. Vitamin B6 led to a significant (p > 0.02) reduction of hippocampal apoptosis. According to functional annotation based clustering, vitamin B6 led to down-regulation of genes involved in processes of inflammatory response, while genes encoding for processes related to circadian rhythm, neuronal signaling and apoptotic cell death were mostly up-regulated. Conclusions Our results provide evidence that attenuation of apoptosis by vitamin B6 is multi-factorial including down-modulation of inflammation, up-regulation of the neuroprotective brain-derived neurotrophic factor and prevention of the exhaustion of cellular energy stores. The neuroprotective effect identifies vitamin B6 as a potential target for the development of strategies to attenuate brain injury in bacterial meningitis. PMID:23977941

  9. [Community-acquired Pseudomonas stutzeri meningitis in an immunocompetent patient].

    PubMed

    Sünbül, Mustafa; Zivalioğlu, Muammer; Taşdelen Fişgin, Nuriye

    2009-01-01

    Pseudomonas stutzeri which is an aerobic, non-fermentative gram-negative bacillus frequently found in soil, water and hospital environment, rarely leads to serious community-acquired infections. In this report a case of community-acquired meningitis due to P. stutzeri was presented. A 73-years-old male patient was admitted to the emergency department with the complaints of nausea, vomiting, headache, dizziness, difficulties in walking and speaking and loss of consciousness. There was no history of an underlying disease or immunosuppression. Physical examination revealed nuchal rigidity, however, Kernig and Brudzinski signs were negative. The cerebrospinal fluid (CSF) analysis revealed 0.4 mg/dl glucose (simultaneous blood glucose 145 mg/dl), and 618 mg/dl protein and 640 leucocyte/mm3 (90% PMNL). No bacteria were detected in Gram stained and Ehrlich-Ziehl-Neelsen stained CSF smears. Upon the diagnosis of acute bacterial meningitis, treatment with ceftriaxone and ampicillin was initiated, however, the patient died after 16 hours of hospitalization. CSF culture yielded the growth of gram-negative oxidase-positive bacteria and the isolate was identified as P. stutzeri by Vitek-2 Compact system (bioMerieux, France). The isolate was found to be sensitive to piperacillin/tazobactam, amikacin, gentamycin, ceftazidime, cefepime, ciprofloxacin, imipenem and meropenem. Since the patient was lost due to acute respiratory and cardiac failure, it was not possible to change the therapy to agent specific therapy. In conclusion, it should always be kept in mind that uncommon agents could lead to community-acquired meningitis in elderly patients and empirical treatment protocols might fail in such cases resulting in high morbidity and mortality. PMID:19334394

  10. A Five Years Study of Tuberculous Meningitis in Iran

    PubMed Central

    Hajia, Massoud; Amirzargar, Ali Akbar; Nazari, Mina; Razavi Davodi, Neda; Karami Zarandi, Morteza

    2015-01-01

    Background: Tuberculous meningitis (TBM) is a severe form of extra pulmonary tuberculosis with high mortality and morbidity rate in all age group patients specific in adults and children. The incidence and prevalence are not exactly known in Iran. In this study, we tried to evaluate the role of rapid diagnosis and to find out the highest risk group patients. Methods: Totally, 1783-suspected patients with tuberculous meningitis whose CSF specimens were admitted at Noor Pathobiology Laboratory, Tehran, Iran were enrolled in this study from January 2009 until December 2013. All specimens were checked for MTB by direct examination, culture and PCR tests, and for the adenosine deaminase (ADA). Results: Confirmed positive cases were aged from 13 to 82 yr old with mean age 46.63 yr (SD±18.84). The number of diagnosed positive MTB was different by the 3 applied protocol, 64 by PCR, 28 by culture and 33 by direct examination. Considering the result of PCR protocol the TBM was approved in 64 patients with rate of 3.59%. Two patients had other infection as well, one 56 years old with VZV and the other patient who was HIV positive was 27 years old. Increased ADA titer higher than cutoff was relevant with other results of positive samples except in two cases. Conclusion: Analysis of the results proved adults are more at risk for tuberculous meningitis than children in Iran are. It is also confirmed PCR method provide the most efficient, rapid and reliable results for these patients who are at the critical situations. PMID:26351499

  11. A Rare Case of Crowned Dens Syndrome Mimicking Aseptic Meningitis

    PubMed Central

    Takahashi, Teruyuki; Minakata, Yugo; Tamura, Masato; Takasu, Toshiaki; Murakami, Marohito

    2013-01-01

    Background Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Microcrystal-line deposition most often consists of calcium pyrophosphate dehydrate crystals and/or hydroxyapatite crystals. Case Presentation This report describes the case of an 89-year-old woman who presented with sudden onset, high fever, severe occipital headache, and neck stiffness. A laboratory examination revealed a markedly elevated white blood cell count (11,100/µl) and C-reactive protein level (23.8 mg/dl). These clinical findings suggested severe infection such as meningitis with sepsis. However, the results of blood culture, serum endotoxin, and procalcitonin were all negative, and cerebrospinal fluid studies revealed only a slight abnormality. The patient was first diagnosed with meningitis and treated with antiviral and antibiotic agents as well as non-steroidal anti-inflammatory drugs, but they only had limited effects. A cervical plain computed tomography (CT) scan and its three-dimensional (3D) reconstruction detected a remarkable crown-like calcification surrounding the odontoid process. On the basis of the CT findings, the patient was diagnosed as a severe case of CDS and was immediately treated with corticosteroids. The patient's condition drastically improved within a week after one course of corticosteroid therapy. Conclusion Some atypical symptoms of CDS are misleading and may be misdiagnosed as meningitis, as happened in our case. A CT scan, especially a 3D-CT scan, is necessary and useful for a definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for fever, headache, and cervical pain of unknown origin. PMID:23569451

  12. Place of Colistin-Rifampicin Association in the Treatment of Multidrug-Resistant Acinetobacter Baumannii Meningitis: A Case Study

    PubMed Central

    Souhail, Dahraoui; Bouchra, Belefquih; Belarj, Badia; Laila, Rar; Mohammed, Frikh; Nassirou, Oumarou Mamane; Azeddine, Ibrahimi; Haimeur, Charki; Lemnouer, Abdelhay; Elouennass, Mostafa

    2016-01-01

    Treatment of Acinetobacter baumannii meningitis is an important challenge due to the accumulation of resistance of this bacteria and low meningeal diffusion of several antimicrobial requiring use of an antimicrobial effective combination to eradicate these species. We report a case of Acinetobacter baumannii multidrug-resistant nosocomial meningitis which was successfully treated with intravenous and intrathecal colistin associated with rifampicin. PMID:27064923

  13. A Syrian patient diagnosed with meningococcal meningitis serogroup B

    PubMed Central

    Tezer, Hasan; Ozkaya-Parlakay, Aslinur; Kanik-Yuksek, Saliha; Gülhan, Belgin; Güldemir, Dilek

    2014-01-01

    Meningococcal infection is an important health problem in children, with significant mortality and morbidity. In this infection, early recognition and aggressive treatment can reduce mortality. Herein we report an 11-year-old-Syrian refugee girl living in Turkey for 3 months admitting with fever, headache, and vomiting diagnosed as meningococcal meningitis type B who was cured with intravenous ceftriaxone therapy. Infections in refugee populations constitute major importance for highlighting importance of investigation of endemic diseases in their own country and contagious diseases in their present place. PMID:25424959

  14. An uncommon cause of recurrent pyogenic meningitis: pituitary abscess

    PubMed Central

    Walia, Rama; Bhansali, Anil; Dutta, Pinaki; Shanmugasundar, G; Mukherjee, Kanchan Kumar; Upreti, Vimal; Das, Ashim

    2010-01-01

    The authors report a 36-year-old male who presented with headache and hypopituitarism, and MRI revealed a ring enhancing lesion with pituitary stalk thickening. During follow-up, he presented with recurrent pyogenic meningitis with persistence of the lesion, therefore a diagnosis of pituitary abscess was considered. He underwent trans-sphenoidal surgery (TSS) with evacuation of pus and received antibiotic treatment for the same. After this he remarkably improved and had no recurrence of symptoms. He is on levothyroxine, glucocorticoids and testosterone replacement therapy for his respective hormone deficits. PMID:22767626

  15. Treatment of lymphomatous and leukemic meningitis with liposomal encapsulated cytarabine

    PubMed Central

    Kripp, Melanie; Hofheinz, Ralf-Dieter

    2008-01-01

    Liposomal encapsulated cytarabine (DepoCyte®, Mundipharma GmbH, Limburg/Lahn, Germany) is a slow-release formulation of conventional cytarabine. It is licensed for intrathecal use in patients with lymphomatous and leukemic meningitis. DepoCyte® obtained superior response rates, improved patient quality of life and improved the time to neurological progression in a randomized albeit small clinical trial. In this review we briefly summarize the clinical data and discuss them in light of clinical problems and possible treatment scenarios. PMID:19337408

  16. From suspected Creutzfeldt-Jakob disease to confirmed histoplasma meningitis.

    PubMed

    Batra, Vivek; Khararjian, Armen; Wheat, Joseph; Zhang, Sean X; Crain, Barbara; Baras, Alexander

    2016-01-01

    A 77-year-old man with chronic obstructive lung disease who was on steroids, presented to the hospital after a fall with subacute headaches and ataxia. During the patient's hospital course, his clinical condition deteriorated with myoclonic jerks, fevers and severe encephalopathy. An extensive workup, including EEG, brain MRI and lumbar puncture, revealed possible Creutzfeldt-Jakob disease. Unfortunately, the patient failed to improve and died 12 days after admission. A brain-only autopsy revealed he had acute histoplasma meningitis with patchy superficial cerebritis. PMID:27389723

  17. Simultaneous genital ulcer and meningitis: a case of EBV infection

    PubMed Central

    Nunes, Jairo Tavares; Lopes, Leonardo da Costa; Prokopowitsch, Aleksander Snioka

    2016-01-01

    The Epstein-Barr virus (EBV) is associated with a broad spectrum of diseases, mainly because of its genomic characteristics, which result in different latency patterns in immune cells and infective mechanisms. The patient described in this report is a previously healthy young man who presented to the emergency department with clinical features consistent with meningitis and genital ulcers, which raised concern that the herpes simplex virus was the causative agent. However, the polymerase chain reaction of cerebral spinal fluid was positive for EBV. The authors highlight the importance of this infection among the differential diagnosis of central nervous system involvement and genital ulceration. PMID:27547743

  18. Partial Kluver-Bucy syndrome secondary to tubercular meningitis.

    PubMed

    Jha, Kunal Kishor; Singh, Satyajeet Kumar; Kumar, Prem; Arora, Charu Dutt

    2016-01-01

    Tubercular meningitis (TBM) is a devastating extra pulmonary manifestation of tuberculosis and demonstrates a high neurological morbidity. A rare complication of this condition is Kluver-Bucy syndrome (KBS), which is a neurobehavioral disorder characterised by hyper-sexuality, visual agnosia, bulimia, placidity, hyperorality and memory deficits caused by lesions to the amygdala. The amygdala lesions can be due to many causes, including traumatic brain injury, systemic conditions and infections such as tuberculosis. Here, we present a case of partial KBS in a patient undergoing treatment for TBM. PMID:27530874

  19. Simultaneous genital ulcer and meningitis: a case of EBV infection.

    PubMed

    Rahhal, Hassan; Nunes, Jairo Tavares; Lopes, Leonardo da Costa; Prokopowitsch, Aleksander Snioka

    2016-01-01

    The Epstein-Barr virus (EBV) is associated with a broad spectrum of diseases, mainly because of its genomic characteristics, which result in different latency patterns in immune cells and infective mechanisms. The patient described in this report is a previously healthy young man who presented to the emergency department with clinical features consistent with meningitis and genital ulcers, which raised concern that the herpes simplex virus was the causative agent. However, the polymerase chain reaction of cerebral spinal fluid was positive for EBV. The authors highlight the importance of this infection among the differential diagnosis of central nervous system involvement and genital ulceration. PMID:27547743

  20. Treatment of lymphomatous and leukemic meningitis with liposomal encapsulated cytarabine.

    PubMed

    Kripp, Melanie; Hofheinz, Ralf-Dieter

    2008-01-01

    Liposomal encapsulated cytarabine (DepoCyte, Mundipharma GmbH, Limburg/Lahn, Germany) is a slow-release formulation of conventional cytarabine. It is licensed for intrathecal use in patients with lymphomatous and leukemic meningitis. DepoCyte obtained superior response rates, improved patient quality of life and improved the time to neurological progression in a randomized albeit small clinical trial. In this review we briefly summarize the clinical data and discuss them in light of clinical problems and possible treatment scenarios. PMID:19337408

  1. Assessments for the impact of mineral dust on the meningitis incidence in West Africa

    NASA Astrophysics Data System (ADS)

    Martiny, Nadège; Chiapello, Isabelle

    2013-05-01

    Recently, mineral dust has been suspected to be one of the important environmental risk factor for meningitis epidemics in West Africa. The current study is one of the first which relies on long-term robust aerosol measurements in the Sahel region to investigate the possible impact of mineral dust on meningitis cases (incidence). Sunphotometer measurements, which allow to derive aerosol and humidity parameters, i.e., aerosol optical thickness, Angström coefficient, and precipitable water, are combined with quantitative epidemiological data in Niger and Mali over the 2004-2009 AMMA (African Monsoon Multidisciplinary Analysis) program period. We analyse how the extremely high aerosol loads in this region may influence both the calendar (onset, peaks, end) and the intensity of meningitis. We highlight three distinct periods: (i) from November to December, beginning of the dry season, humidity is weak, there is no dust and no meningitis cases; (ii) from January to April, humidity is still weak, but high dust loads occur in the atmosphere and this is the meningitis season; (iii) from May to October, humidity is high and there is no meningitis anymore, in presence of dust or not, which flow anyway in higher altitudes. More specifically, the onset of the meningitis season is tightly related to mineral dust flowing close to the surface at the very beginning of the year. During the dry, and the most dusty season period, from February to April, each meningitis peak is preceded by a dust peak, with a 0-2 week lead-time. The importance (duration, intensity) of these meningitis peaks seems to be related to that of dust, suggesting that a cumulative effect in dust events may be important for the meningitis incidence. This is not the case for humidity, confirming the special contribution of dust at this period of the year. The end of the meningitis season, in May, coincides with a change in humidity conditions related to the West African Monsoon. These results, which are

  2. Recurrent meningitis associated with complete Currarino triad in an adult--case report.

    PubMed

    Haga, Yasushi; Cho, Hiroyuki; Shinoda, Souji; Masuzawa, Toshio

    2003-10-01

    A 58-year-old woman presented with Currarino triad manifesting as recurrent meningitis. Currarino triad is a combination of a presacral mass, a congenital sacral bony abnormality, and an anorectal malformation, which is caused by dorsal-ventral patterning defects during embryonic development. She had a history of treatment for anal stenosis in her childhood. Radiographic examinations demonstrated the characteristic findings of Currarino triad and a complicated mass lesion. The diagnosis was recurrent meningitis related to the anterior sacral meningocele. Neck ligation of the meningocele was performed via a posterior transsacral approach after treatment with antibiotics. At surgery, an epidermoid cyst was observed inside the meningocele. The cyst content was aspirated. She suffered no further episodes of meningitis. The meningitis was probably part of the clinical course of Currarino triad. Radiography of the sacrum and magnetic resonance imaging are recommended for patients with meningitis of unknown origin. The early diagnosis and treatment of this condition are important. PMID:14620204

  3. Preventive immunisation could reduce the risk of meningococcal epidemics in the African meningitis belt.

    PubMed

    Chippaux, J P; Campagne, G; Djibo, S; Cissé, L; Hassane, A; Kanta, I

    1999-07-01

    Control of meningitis epidemics is based on early case detection followed by mass campaigns of immunisation. However, this strategy showed severe inadequacies during recent outbreaks in Africa. In Niamey, Niger, meningococcal vaccinations began in 1978 and detailed bacteriological and epidemiological surveillance of meningitis started in 1981. When vaccine coverage rates were higher than 50%, the prevalences of Neisseria meningitidis A meningitis were low in Niamey, although there was a concurrent epidemic in rural Niger. A massive outbreak of meningitis in Niamey in 1994-1995 followed a 6-year period during which the mean rate of vaccine coverage remained < 25%. The data indicate that, in the meningitis belt, preventive immunization should avoid a great number of deaths and be less expensive than mass immunisation campaigns performed after epidemics have begun. PMID:10690246

  4. EDA-containing fibronectin levels in the cerebrospinal fluid of children with meningitis.

    PubMed

    Pupek, Małgorzata; Jasonek, Jolanta; Kątnik-Prastowska, Iwona

    2013-01-01

    Fibronectin containing an alternatively spliced extra domain A (EDA-FN) participates in diverse biological cell functions, being also directly or indirectly engaged during an inflammatory response to brain injury and/or neuron regeneration. We analyzed FN and EDA-FN isoform levels by ELISA in 85 cerebrospinal fluid samples and 67 plasma samples obtained from children suffering from bacterial or viral meningitis and non-meningitis peripheral inflammation. We have found that the cerebrospinal level of EDA-FN was significantly lower in the bacterial meningitis group than in the viral- and non-meningitis groups. In the patients' plasma, EDA-FN was almost undetectable. The determination of fibronectin containing the EDA segment might be considered as an additional diagnostic marker of bacterial meningitis in children. PMID:23884219

  5. Factors associated with mumps meningitis and the possible impact of vaccination

    PubMed Central

    Rhie, Kyuyol; Park, Heung-Keun; Kim, Young-Soo; Park, Ji Sook; Seo, Ji-Hyun; Park, Eun Sil; Lim, Jae-Young; Park, Chan-Hoo; Woo, Hyang-Ok; Youn, Hee-Shang

    2016-01-01

    Purpose Mumps meningitis is a common complication of mumps infection; however, information on mumps meningitis in the postvaccine era is limited. The purpose of the present study was to determine factors associated with mumps meningitis and to discuss the effect of vaccination on this disease. Methods We retrospectively reviewed patients younger than 19 years with mumps, diagnosed at a university hospital in Korea between 2003 and 2013. Patients were divided into groups with and without meningitis, and the clinical features of the 2 groups were compared. Results The study enrolled 119 patients: 19 patients with meningitis and 100 patients without. Univariate analysis showed that older age (median: 15 years vs. 9.5 years, respectively), a longer interval from last vaccination (median: 10.2 years vs. 4.8 years, respectively), and febrile presentation (94.7% vs. 31.0%, respectively) were significantly associated with mumps meningitis. Sex, number of vaccination doses, bilateral parotitis, and the presence of complications other than meningitis did not differ between the 2 groups. In multivariate logistic regression analysis, age (odds ratio, 1.38; 95% confidence interval, 1.01–1.89; P=0.04) and fever (odds ratio, 30.46; 95% confidence interval, 3.27–283.61; P<0.01) remained independent factors for mumps meningitis. Conclusion Clinicians in the postvaccine era should be aware of the possibility of mumps meningitis in febrile cases of mumps in adolescents, regardless of the number of vaccination doses. To establish the role of vaccination in mumps meningitis, further studies will be necessary. PMID:26893600

  6. [Klebsiella pneumoniae meningitis associated with liver abscess: a case report].

    PubMed

    Yanagawa, T; Nakamura, H; Takei, I; Maruyama, H; Kataoka, K; Saruta, T; Kobayashi, Y

    1989-10-01

    We report a rare case of Klebsiella pneumoniae meningitis associated with liver abscess, which was successfully treated with cefotaxime (CTX), one of the third-generation cephalosporins. A 53-year-old man was admitted to Keio University Hospital on June 13, 1988, because of a fever and a headache. On June 3, he suddenly started shivering and his temperature rose to 39 degrees C. He then began to complain of polydipsia, polyuria, and a weight loss of 4 kg a week. On June 11, he developed a severe headache. Four years prior to this incident, he had been diagnosed as having diabetes after a routine medical examination, but had neglected to undergo medical treatment. On admission, laboratory data showed leukocytosis, hyperglycemia (394 mg/dl) and ketonuria (4+). A lumbar puncture yielded cloudy cerebrospinal fluid (CSF) containing 500/3 cells/mm8, of which about 70% were neutrophils. A diagnosis of diabetic ketoacidosis and purulent meningitis was made. A treatment with ampicillin (ABPC) and CTX, (12 g/day, each) was begun. On the third day, cultures of a blood specimen and CSF yielded both K. pneumoniae. The MICs of CTX to K. pneumoniae isolated from blood and CSF were both 0.05 microgram/ml. ABPC was discontinued, gentamicin was administered for 2 days, CTX was continued at the same dosage level and an administration of prednisolone 40 mg daily was begun.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2691713

  7. [Carcinomatous meningitis: The radiation therapist's point of view].

    PubMed

    Espenel, S; Vallard, A; Langrand-Escure, J; Ben Mrad, M; Méry, B; Rivoirard, R; Moriceau, G; Guy, J-B; Trone, J-C; Moncharmont, C; Wang, G; Diao, P; Bernichon, É; Chanal, É; Fournel, P; Magné, N

    2016-02-01

    Carcinomatous meningitis complicates 5 to 10% of cancers, essentially with breast cancers, lung cancers and melanomas. The incidence probably increased because of therapeutic advances in oncology. Treatment is based on external beam radiotherapy, systemic treatment, intrathecal chemotherapy and supportive care. The aim of this work was to review data on external radiation therapy and carcinomatous meningitis. There are few evidences on the subject, but it is a major topic of interest. A whole brain radiation therapy is indicated in case of brain metastases or clinical encephalitis. Focal radiation therapy is recommended on symptomatic, bulky or obstructive sites. The dose depends on performance status (20 to 40 Gy in five to 20 fractions), volume to treat and available techniques (classic fractionation or hypofractionation via stereotactic radiosurgery). The objective of radiation therapy is to improve quality of life. Association with systemic therapy improves overall survival. Administration of sequential intrathecal chemotherapy may also improve overall survival, but induces more toxicity. The use of new radiotherapy techniques and development of radiosensitizing molecules in patients with good performance status could improve survival in this frequent complication of cancer. PMID:26867467

  8. Role of Microglial Activation in the Pathophysiology of Bacterial Meningitis.

    PubMed

    Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Goularte, Jessica A; Petronilho, Fabricia; Saigal, Priyanka; Badawy, Marwa; Quevedo, João

    2016-04-01

    Bacterial meningitis is a life-threatening infection associated with cognitive impairment in many survivors. The pathogen invades the central nervous system (CNS) by penetrating through the luminal side of the cerebral endothelium, which is an integral part of the blood-brain barrier. The replication of bacteria within the subarachnoid space occurs concomitantly with the release of their compounds that are highly immunogenic. These compounds known as pathogen-associated molecular patterns (PAMPs) may lead to both an increase in the inflammatory response in the host and also microglial activation. Microglia are the resident macrophages of the CNS which, when activated, can trigger a host of immunological pathways. Classical activation increases the production of pro-inflammatory cytokines, chemokines, and reactive oxygen species, while alternative activation is implicated in the inhibition of inflammation and restoration of homeostasis. The inflammatory response from classical microglial activation can facilitate the elimination of invasive microorganisms; however, excessive or extended microglial activation can result in neuronal damage and eventually cell death. This review aims to discuss the role of microglia in the pathophysiology of bacterial meningitis as well as the process of microglial activation by PAMPs and by endogenous constituents that are normally released from damaged cells known as danger-associated molecular patterns (DAMPs). PMID:25744564

  9. Rhodotorula glutinis meningitis: a case report and review of literature.

    PubMed

    Menon, Sarala; Gupta, H R; Sequeira, R; Chavan, Shazia; Gholape, D; Amandeep, S; Bhilave, N; Chowdhary, A S

    2014-07-01

    Rhodotorula is ubiquitous saprophytic yeast belonging to phylum Basidiomycota. These encapsulated basidiomycetes are being increasingly recognised as important emerging human pathogens. There are scanty reports of meningitis caused by Rhodurorula spp in HIV infected patients. We present one such case of meningitis by Rhodutorula glutinis in HIV-infected patient. The patient also had a past history of abdominal tuberculosis. The diagnosis of Rhodotorula was confirmed by Gram staining and culture of the cerebrospinal fluid (CSF). Contamination was ruled out by repeated culturing of CSF from the same patient. Therapy with Amphotericin B showed good results. Patient was discharged from the hospital. However, in the seventh month of follow-up patient was readmitted with complaints of fever, breathlessness, altered sensorium, vomiting and succumbed to his illness. This time the CSF cultures remained negative for Rhodotorula, acid fast bacilli and other pyogenic organisms. Our last 11-year retrospective analysis of 8197 specimens received for mycological work-up showed that this is the first report of R. glutinis isolation from our institute. PMID:24589085

  10. Bilateral ophthalmic origin of the middle meningeal artery.

    PubMed

    Plas, B; Bonneville, F; Dupuy, M; Sol, J-C; Chaynes, P

    2013-01-01

    The origin of the middle meningeal artery (MMA) may vary although it can arise from the ophthalmic artery (OA) with a 0.5% prevalence. We report the exceptional bilateral asymmetric origin from the OAs that has not previously been reported in the literature. Surgeons should be aware of this variation as it could be crucial in the setting of an endovascular approach for meningeal lesions, as in our observation. A 50-year-old male underwent a preoperative cerebral digital subtracted angiography that incidentally revealed MMAs arising from the OA on both sides. In fact, the origin was asymmetric because it was complete on the right side with the anterior and posterior branches of the MMA arising from the OA, whereas it was partial on the left side, with only the anterior branch arising from the OA. The CT scan showed the absence of the foramen spinosum only on the right side. This paper discusses the unique anatomic variation in the light of MMA embryology and its different origins. Knowledge of this variation may have a practical impact in cases of cerebral embolization. PMID:24176432

  11. Meningitis in infancy in England and Wales: follow up at age 5 years

    PubMed Central

    Bedford, Helen; de Louvois, John; Halket, Susan; Peckham, Catherine; Hurley, Rosalinde; Harvey, David

    2001-01-01

    Objective To describe important sequelae occurring among a cohort of children aged 5 years who had had meningitis during the first year of life and who had been identified by a prospective national study of meningitis in infancy in England and Wales between 1985 and 1987. Design Follow up questionnaires asking about the children's health and development were sent to general practitioners and parents of the children and to parents of matched controls. The organism that caused the infection and age at infection were also recorded. Setting England and Wales. Participants General practitioners and parents of children who had had meningitis before the age of 1 year and of matched controls. Main outcome measures The prevalence of health and developmental problems and overall disability among children who had had meningitis compared with controls. Results Altogether, 1584 of 1717 (92.2%) children who had had meningitis and 1391 of 1485 (93.6%) controls were successfully followed up. Among children who survived to age 5 years 247 of 1584 (15.6%) had a disability; there was a 10-fold increase in the risk of severe or moderate disability at 5 years of age among children who had had meningitis (relative risk 10.3, 95% confidence interval 6.7 to 16.0, P<0.001). There was considerable variation in the rates of severe or moderate disability in children infected with different organisms. Conclusion The long term consequences of having meningitis during the first year of life are significant: 32 of 1717 (1.8%) children died within five years. Not only did almost a fifth of children with meningitis have a permanent, severe or moderately severe disability, but subtle deficits were also more prevalent. What is already known on this topicMeningitis in infancy is associated with important long term consequencesThere is considerable variation in outcome depending on which organism caused the infectionWhat this study addsThis follow up study of 1717 children who had meningitis in infancy

  12. Aetiological agents of cerebrospinal meningitis: a retrospective study from a teaching hospital in Ghana

    PubMed Central

    2012-01-01

    Abstracts Background Meningitis is an important cause of morbidity and mortality in low-resource settings. In sub-Saharan Africa, the meningitis belt has been characterized by particularly high and seasonal incidences of bacterial meningitis extending throughout life. Despite the progress being made in treating the condition, the mortality rates continue to be high, ranging between 2% and 30% globally. In Ghana, the mortality rate of meningitis has been estimated to range from 36% to 50%. However little information is available on the pathogens contributing to meningitis and their antimicrobial susceptibilities. Updated information is essential to adjust the recommendations for empirical treatment or prevention of meningitis which could have immense implications for local and global health. Methods We retrospectively reviewed laboratory records of all patients suspected of bacterial meningitis who underwent a lumbar puncture from January 1, 2008 to December 31, 2010. Data were retrieved from laboratory record books and double entered into a Microsoft® excel spreadsheet. Results Records of 4,955 cerebrospinal fluid samples were analysed. Of these, 163 (3.3%, 95%CI: 2.8% to 3.8%) were confirmed meningitis and 106 (2.1%, 95%CI: 1.7% to 2.6%) were probable meningitis cases. Confirmed meningitis cases were made up of 117 (71.8%) culture positive bacteria, 19 (11.7%) culture positive Cryptococcus neoformans and 27(16.6%) Gram positive bacteria with negative culture. The most prevalent bacteria was Streptococcus pneumoniae 91 (77.7%), followed by E.coli 4 (3.4%), Salmonella species 4 (3.4%), Neisseria meningitidis 3 (2.5%), Pseudomonas species 3(2.5%) and others. Pneumococcal isolates susceptibility to penicillin, chloramphenicol and ceftriaxone were 98.9% (95%CI: 94.0% to 100.0%), 83.0% (95%CI: 73.4% to 90.1%) and 100.0% (95%CI: 95.8% to 100.0%) respectively. Conclusion Streptococcus pneumoniae is an important cause of meningitis among all age groups and its

  13. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    PubMed Central

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine. PMID:26558118

  14. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    PubMed Central

    Xu, Jintao; Eastman, Alison J.; Flaczyk, Adam; Neal, Lori M.; Zhao, Guolei; Carolan, Jacob; Malachowski, Antoni N.; Stolberg, Valerie R.; Yosri, Mohammed; Chensue, Stephen W.; Curtis, Jeffrey L.; Osterholzer, John J.

    2016-01-01

    ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. PMID:27406560

  15. Proteomic Analysis of Cerebrospinal Fluid in Pneumococcal Meningitis Reveals Potential Biomarkers Associated with Survival

    PubMed Central

    Goonetilleke, Upali R.; Scarborough, Matthew; Ward, Stephen A.; Gordon, Stephen B.

    2016-01-01

    Background Patients with pneumococcal meningitis often die or have severe neurological damage despite optimal antibiotic therapy. New or improved therapy is required. The delivery of new interventions will require an improved understanding of the disease pathogenesis. Our objective was to learn more about the pathophysiology of severe meningitis through the interpretation of differences in the proteomic profile of cerebrospinal fluid (CSF) from patients with meningitis. Methods Two-dimensional polyacrylamide gel electrophoresis of CSF from normal subjects (controls, n = 10) and patients with pneumococcal meningitis (n = 20) was analyzed. Spot differences were compared and identified between controls, nonsurvivors (n = 9), and survivors (n = 11). Results Protein concentration in CSF of patients with meningitis was 4-fold higher than in CSF of control subjects (7.0 mg/mL vs 0.23 mg/mL; P < .01). A mean of 2466 discrete protein spots was present in CSF of patients with meningitis. Thirty-four protein spots were differentially expressed in CSF of nonsurvivors, compared with survivors. None of these protein spots were observed in CSF of control subjects. Conclusions Proteomic screening of CSF yields potential biomarkers capable of differentiating control subjects from nonsurvivors and survivors of meningitis. Proteins involved in the inflammatory process and central metabolism were represented in the differentially expressed protein repertoire. PMID:20608875

  16. Meninges harbor cells expressing neural precursor markers during development and adulthood

    PubMed Central

    Bifari, Francesco; Berton, Valeria; Pino, Annachiara; Kusalo, Marijana; Malpeli, Giorgio; Di Chio, Marzia; Bersan, Emanuela; Amato, Eliana; Scarpa, Aldo; Krampera, Mauro; Fumagalli, Guido; Decimo, Ilaria

    2015-01-01

    Brain and skull developments are tightly synchronized, allowing the cranial bones to dynamically adapt to the brain shape. At the brain-skull interface, meninges produce the trophic signals necessary for normal corticogenesis and bone development. Meninges harbor different cell populations, including cells forming the endosteum of the cranial vault. Recently, we and other groups have described the presence in meninges of a cell population endowed with neural differentiation potential in vitro and, after transplantation, in vivo. However, whether meninges may be a niche for neural progenitor cells during embryonic development and in adulthood remains to be determined. In this work we provide the first description of the distribution of neural precursor markers in rat meninges during development up to adulthood. We conclude that meninges share common properties with the classical neural stem cell niche, as they: (i) are a highly proliferating tissue; (ii) host cells expressing neural precursor markers such as nestin, vimentin, Sox2 and doublecortin; and (iii) are enriched in extracellular matrix components (e.g., fractones) known to bind and concentrate growth factors. This study underlines the importance of meninges as a potential niche for endogenous precursor cells during development and in adulthood. PMID:26483637

  17. Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone.

    PubMed Central

    Scheld, W M; Dacey, R G; Winn, H R; Welsh, J E; Jane, J A; Sande, M A

    1980-01-01

    Acute bacterial meningitis may be associated with increased intracranial pressure, neurological sequelae such as communicating hydrocephalus, and a slow response to antibiotic therapy. Alterations in cerebrospinal hydrodynamics are at least partially responsible for these complications. Constant, low-flow short-duration manometric infusion studies through a hollow-bore pressure monitoring device in direct continuity with the supracortical subarachnoid space were performed in rabbits with experimental meningitis. Maximal resistance to cerebrospinal fluid (CSF) outflow from the subarachnoid to vascular space was markedly increaed in acute pneumococcal meningitis when compared to control, uninfected animals (6.77 +/- 3.52 vs. 0.26 +/- 0.04 mm Hg/microliter per min, P less than 0.001). Similar elevations (8.93 +/- 4.15 mm Hg/microliter per min were found in experimental Escherichia coli meningitis. Despite eradication of viable bacteria from the CSF by penicillin therapy during the acute stage of pneumococcal meningitis, resistance remained elevated (6.07 +/- 4.68 mm Hg/microliter per min) and had not returned to normal up to 15 d later. Administration of methylprednisolone during the early stages of acute pneumococcal meningitis reduced mean peak outflow resistance towards control values (0.59 mm Hg/microliter per min) and no "rebound" effect was apparent 24 h later. These hydrodynamic alterations in experimental meningitis prevent normal CSF absorption and decrease the ability of the bran to compensate for changes in intracranial volume and pressure. PMID:6995482

  18. rmpM gene as a genetic marker for human bacterial meningitis.

    PubMed

    Dash, S K; Sharma, M; Khare, S; Kumar, A

    2012-01-01

    Meningitis is a bacterial, viral or fungal infection of the protective membrane meninges covering the brain and spinal cord. Viral and other forms of meningitis are mild and get cured within one or two week without any treatment. Whereas, bacterial meningitis can prove lethal if not being diagnosed or treated in time. Meningitis is a contagious infection and can spread from one person to another through coughing, sneezing or close contact. Usually the disease is diagnosed from cerebrospinal fluid (CSF) of the patients using culture, PCR, immunological and biochemical tests. All these methods suffer from one or more limitations. Our lab has developed a quick PCR based detection of Neisseria meningitidis (bacterial meningitis) directly from the patient CSF samples using specific primers of virulent rmpM gene. The overall analysis completes in 80 min for confirmation of the disease. Amplicon of 308 bp of rmpM gene does not show homology with other organisms and can be used as a genetic marker for human bacterial meningitis caused by Neisseria meningitidis. PMID:23273188

  19. Long-Term Effects from Bacterial Meningitis in Childhood and Adolescence on Postural Control

    PubMed Central

    Petersen, Hannes; Patel, Mitesh; Ingason, Einar F.; Einarsson, Einar J.; Haraldsson, Ásgeir; Fransson, Per-Anders

    2014-01-01

    Bacterial meningitis in childhood is associated with cognitive deficiencies, sensorimotor impairments and motor dysfunction later in life. However, the long-term effects on postural control is largely unknown, e.g., whether meningitis subjects as adults fully can utilize visual information and adaptation to enhance stability. Thirty-six subjects (20 women, mean age 19.3 years) treated in childhood or adolescence for bacterial meningitis, and 25 controls (13 women, mean age 25.1 years) performed posturography with eyes open and closed under unperturbed and perturbed standing. The meningitis subjects were screened for subjective vertigo symptoms using a questionnaire, clinically tested with headshake and head thrust test, as well as their hearing was evaluated. Meningitis subjects were significantly more unstable than controls during unperturbed (p≤0.014) and perturbed standing, though while perturbed only with eyes open in anteroposterior direction (p = 0.034) whereas in lateral direction both with eyes open and closed (p<0.001). Meningitis subjects had poorer adaption ability to balance perturbations especially with eyes open, and they frequently reported symptoms of unsteadiness (88% of the subjects) and dizziness (81%), which was found significantly correlated to objectively decreased stability. Out of the 36 subjects only 3 had unilateral hearing impairment. Hence, survivors of childhood bacterial meningitis may suffer long-term disorders affecting postural control, and would greatly benefit if these common late effects became generally known so treatments can be developed and applied. PMID:25405756

  20. Acute bacterial meningitis in adults: a hospital based study in Yemen.

    PubMed

    Abdulrab, Amin; Algobaty, Faker; Salem, Ahmed K; Mohammed, Y A K

    2010-03-01

    Acute bacterial meningitis is an important cause of mortality and morbidity with high rates of long-term neurological sequelae. To determine the clinical presentation, complications, and outcome of acute meningitis in Yemen, a retrospective study in patients 15 years or older with acute bacterial meningitis who were admitted into Al-Thawra Teaching Hospital in Sana'a from January 2006 to December 2007 was carried out. There were 121 patients with acute bacterial meningitis. Lumbar puncture was performed in 112 (92.6%). The most common pathogen was Streptococcus pneumoniae found in 47.4% of positive cultures, Neisseria meningitidis in 33.9%, and Haemophilus influenzae in 10.2%. The classical triad of acute bacterial meningitis was found in 65% of cases. The mortality rate was 22.3%, with 27 patients dying during hospitalization. S. pneumoniae had a case fatality rate of 35.7%. Frequent complications were impaired consciousness, recurrent convulsion, and chest infection, which occurred in 30.6, 16.5, and 10.7% of the patients, respectively. Risk factors for death among those with acute bacterial meningitis included older age (>or=45 years), altered mental status, chest infection, and S. pneumoniae infection. This study highlights the importance of bacterial meningitis as a serious disease of adults in Yemen and the need for effective methods to prevent its complications. PMID:20332577

  1. Frequency and Outcome of Meningitis in Pediatric Intensive Care Unit of Pakistan.

    PubMed

    Jawaid, Amna; Bano, Surriya; Haque, Anwar Ul; Arif, Khubaib

    2016-08-01

    Meningitis is a leading cause of morbidity and mortality worldwide in intensive care settings. The aim of this study was to assess the frequency and outcome in children with meningitis through a retrospective chart review done in pediatric intensive care unit of a tertiary care hospital from January 2000 to December 2014. During these 14 years, 64 patients were admitted with meningitis in pediatric intensive care unit. Out of 64, 36 were diagnosed with pyogenic meningitis, 18 patients with viral meningitis, and 10 with tuberculous meningitis. Most complications were observed in the initial 48 hours. Most common presentation was altered level of consciouness in 50 (78.1%), seizure in 38 (59.4%), and shock in 23 (35.9%) patients. Ventilatory support was required in 30 (46.9%) patients and inotropic support in 26 (40.6%). During stay in pediatric intensive care unit, there was 7.8% mortality. Although meningitis was an infrequent cause of hospitalization at the study centre, but it was an important infectious cause of mortality and morbidity in pediatric age group and associated with high neurological sequelae. PMID:27539773

  2. Serial study of clinical and CT changes in tuberculous meningitis.

    PubMed

    Ranjan, P; Kalita, J; Misra, U K

    2003-05-01

    Clinical and radiological changes in tuberculous meningitis (TBM) have been reported but there is paucity of comprehensive serial clinicoradiological follow-up. In this prospective hospital based study, we investigated serial changes in the clinical and radiological findings and their relationships over 6 months in 31 consecutive patients with TBM, diagnosed on the basis of clinical, radiological and spinal fluid criteria. We graded the severity of the TBM as I-III. Detailed clinical examination, contrast-enhanced CT and activities of daily living (ADL) assessments were made on admission, and 3 and 6 months after therapy. Further CT was carried out as required. Patients received four-drug antituberculous therapy (RHZE) and underwent a ventriculoperitoneal shunt if necessary. Outcome was defined as poor, partial or complete recovery using the Barthel index score at 6 months. The age of the patients was 6-80 years, mean 35.2 years; four were children and 13 female. Meningitis was stage I in 5, stage II in six and stage III in 20 patients. Focal weakness was present in nine, papilloedema in six and ophthalmoplegia in ten. There were ten patients who deteriorated within first 6 weeks of therapy. Mean Glasgow coma score (GCS) deteriorated from 12.5 to 11.4; the grade of meningitis increased by two stages in one patient, one stage in another, and motor deficits appeared in four and optic atrophy in four; four patients required shunt surgery. By 3 months most patients were stable. At 6 months 17 patients had complete, four partial and nine poor recovery. Initial CT was abnormal in 28 patients, revealing hydrocephalus and exudates in 15 each, infarcts in ten and tuberculomas in 13. It was repeated in ten patients who deteriorated, showing new abnormalities such as hydrocephalus in two, infarcts in four, exudates in four and granulomas in two, with worsening of the previous findings. CT at 3 and 6 months was still abnormal in most patients. At 6 months hydrocephalus had

  3. Analysis of tuberculous meningitis cases by an immunoblotting assay based on a mycobacterial antigen complex.

    PubMed Central

    Zou, Y L; Van Antwerpen, M P; Shi, G Q; Chen, Q X; Sindic, C J; Cocito, C

    1994-01-01

    Tuberculous meningitis cases were analyzed by an immunoblotting test based on Mycobacterium bovis BCG antigen complex A60. Anti-A60 immunoglobulin G (IgG) in cerebrospinal fluid (CSF) allowed early diagnosis, and concentrations decreased after recovery. In primary meningitis forms, anti-A60 IgGs were intrathecally synthesized and specific oligoclonal IgGs were present in CSF. In meningeal complications of pulmonary tuberculosis, there were matching titers of anti-A60 IgG in blood and CSF (mirror pattern). Correlation between CSF-restricted patterns and CSF pleocytosis was shown. Images PMID:7496976

  4. Eosinophilic meningitis: a case series and review of literature of Angiostrongylus cantonensis and Gnathostoma spinigerum.

    PubMed

    Shah, I; Barot, S; Madvariya, M

    2015-01-01

    Eosinophilic meningitis is defined as the presence of >10 eosinophils/μL in cerebrospinal fluid (CSF) or at least 10% eosinophils in the total CSF leukocyte count. Eosinophilic meningitis has been reported in two case series and two case reports in India till date and has not been reported in children below 15 years of age. We present two children with eosinophilic meningitis with peripheral eosinophilia and the proposed etiologic agents based on the clinical setting and their response to antihelminthic agents. PMID:25560024

  5. Quick diagnosis of human brain meningitis using omp85 gene amplicon as a genetic marker.

    PubMed

    Dash, Sandip K; Sharma, Minakshi; Khare, Shashi; Kumar, Ashok

    2013-06-01

    The usual diagnosis of life-threatening human brain bacterial meningitis are expensive, time consuming or non-confirmatory. A quick PCR based diagnosis of meningitis in cerebrospinal fluids (CSF) using specific primers of virulent Omp85 gene of Neisseria meningitidis can detect as low as 1.0 ng of genomic DNA (G-DNA) in 80 min for confirmation of bacterial meningitis caused by N. meningitidis infection. The 257 bp amplicon of Omp85 gene does not show homology with other suspected pathogens in CSF and can be used as a specific genetic marker for diagnosis of the disease. PMID:24426115

  6. Response to trabectedin treatment in a highly pretreated patient with an advanced meningeal hemangiopericytoma.

    PubMed

    Martinez-Trufero, Javier; Alfaro, Jorge; Felipo, Francesc; Alvarez, Maria; Madani, Julia; Cebollero, Ana

    2010-09-01

    Meningeal hemangiopericytoma is an uncommon and aggressive malignancy that, in contrast to meningiomas, shows a high propensity for local recurrence and the development of late extraneural metastases. The results of chemotherapy in advanced hemangiopericytoma have been disappointing, and they have been particularly poor in cases located in the meninges. We report a case of a heavily pretreated metastatic meningeal hemangiopericytoma in which fourth-line chemotherapy with trabectedin, a marine-derived antineoplastic agent effective in treating advanced soft tissue sarcomas, resulted in clinical benefit. PMID:20622667

  7. Herpes Zoster Meningitis Complicating Combined Tocilizumab and Cyclosporine Therapy for Adult-Onset Still's Disease

    PubMed Central

    Tsurukawa, Shinichiro; Iwanaga, Nozomi; Izumi, Yasumori; Shirakawa, Atsunori; Kawahara, Chieko; Shukuwa, Tetsuo; Inamoto, Miwako; Kawakami, Atsushi; Migita, Kiyoshi

    2016-01-01

    A 56-year-old female with refractory adult-onset Still's disease presented with ocular herpes zoster infection during TCZ treatment. After three days of acyclovir treatment (5 mg/kg), she developed a severe headache and high fever. Viral DNA isolation and cerebral spinal fluid abnormalities led to a herpes zoster meningitis diagnosis. Her meningitis was cured by high doses of intravenous acyclovir (10 mg/kg for 14 days). To our knowledge, this is the first report of meningeal herpes zoster infection in rheumatic diseases under TCZ treatment. PMID:27092286

  8. Herpes Zoster Meningitis Complicating Combined Tocilizumab and Cyclosporine Therapy for Adult-Onset Still's Disease.

    PubMed

    Tsurukawa, Shinichiro; Iwanaga, Nozomi; Izumi, Yasumori; Shirakawa, Atsunori; Kawahara, Chieko; Shukuwa, Tetsuo; Inamoto, Miwako; Kawakami, Atsushi; Migita, Kiyoshi

    2016-01-01

    A 56-year-old female with refractory adult-onset Still's disease presented with ocular herpes zoster infection during TCZ treatment. After three days of acyclovir treatment (5 mg/kg), she developed a severe headache and high fever. Viral DNA isolation and cerebral spinal fluid abnormalities led to a herpes zoster meningitis diagnosis. Her meningitis was cured by high doses of intravenous acyclovir (10 mg/kg for 14 days). To our knowledge, this is the first report of meningeal herpes zoster infection in rheumatic diseases under TCZ treatment. PMID:27092286

  9. Mass Media as an HIV-Prevention Strategy: Using Culturally Sensitive Messages to Reduce HIV-Associated Sexual Behavior of At-Risk African American Youth

    PubMed Central

    Sznitman, Sharon; DiClemente, Ralph; Salazar, Laura F.; Vanable, Peter A.; Carey, Michael P.; Hennessy, Michael; Brown, Larry K.; Valois, Robert F.; Stanton, Bonita F.; Fortune, Thierry; Juzang, Ivan

    2009-01-01

    The evidence base and theoretical frameworks for mass media HIV-prevention campaigns in the United States are not well-developed. We describe an intervention approach using culturally sensitive mass media messages to enhance protective beliefs and behavior of African American adolescents at risk for HIV. This approach exploits the potential that mass media messages have, not only to reach a large segment of the adolescent population and thereby support normative change, but also to engage the most vulnerable segments of this audience to reduce HIV-associated risk behaviors. The results from an ongoing HIV-prevention trial implemented in 2 medium-sized cities in the United States illustrate the effectiveness of this intervention approach. PMID:19833995

  10. Translation of HLA-HIV associations to the cellular level: HIV adapts to inflate CD8 T cell responses against Nef and HLA-adapted variant epitopes.

    PubMed

    Almeida, Coral-Ann M; Bronke, Corine; Roberts, Steven G; McKinnon, Elizabeth; Keane, Niamh M; Chopra, Abha; Kadie, Carl; Carlson, Jonathan; Haas, David W; Riddler, Sharon A; Haubrich, Richard; Heckerman, David; Mallal, Simon; John, Mina

    2011-09-01

    Strong statistical associations between polymorphisms in HIV-1 population sequences and carriage of HLA class I alleles have been widely used to identify possible sites of CD8 T cell immune selection in vivo. However, there have been few attempts to prospectively and systematically test these genetic hypotheses arising from population-based studies at a cellular, functional level. We assayed CD8 T cell epitope-specific IFN-γ responses in 290 individuals from the same cohort, which gave rise to 874 HLA-HIV associations in genetic analyses, taking into account autologous viral sequences and individual HLA genotypes. We found immunological evidence for 58% of 374 associations tested as sites of primary immune selection and identified up to 50 novel HIV-1 epitopes using this reverse-genomics approach. Many HLA-adapted epitopes elicited equivalent or higher-magnitude IFN-γ responses than did the nonadapted epitopes, particularly in Nef. At a population level, inclusion of all of the immunoreactive variant CD8 T cell epitopes in Gag, Pol, Nef, and Env suggested that HIV adaptation leads to an inflation of Nef-directed immune responses relative to other proteins. We concluded that HLA-HIV associations mark viral epitopes subject to CD8 T cell selection. These results can be used to guide functional studies of specific epitopes and escape mutations, as well as to test, train, and evaluate analytical models of viral escape and fitness. The inflation of Nef and HLA-adapted variant responses may have negative effects on natural and vaccine immunity against HIV and, therefore, has implications for diversity coverage approaches in HIV vaccine design. PMID:21821798

  11. Risk factors associated with postcraniotomy meningitis: A retrospective study.

    PubMed

    Chen, Chang-Hua; Chang, Chih-Yen; Lin, Li-Jhen; Chen, Wei Liang; Chang, Yu-Jun; Wang, Shu-Hui; Cheng, Chun-Yuan; Yen, Hua-Cheng

    2016-08-01

    Postcraniotomy meningitis (PCM) is a major challenge in neurosurgery, and changing patterns of infectious agents in PCM have been noted. The limited epidemiological data and urgent clinical needs motivated this research. We conducted this study to determine a risk assessment for PCM and the current pattern of infectious agents.We performed a retrospective case-control study of significant cases of postcraniotomy meningitis in the Changhua Christian Hospital System between January 1, 2008, and December 31, 2012. Postcraniotomy meningitis was diagnosed in 22 out of 4392 surgical patients; this data was reviewed for risk assessment.This study assessed the risk factors for postcraniotomy meningitis and found that it was more frequently seen in patients who were elderly (OR = 1.57, 95% CI = 1.32-2.98, P = 0.013), underwent emergency procedures (OR = 4.82, 95% CI = 1.50-14.53, P = 0.008), had leak of cerebrospinal fluid (OR = 4.62, 95% CI = 2.03-10.50, P = 0.012), had external ventricular drainage (OR = 4.68, 95% CI = 2.46-8.87, P = 0.006), were admitted to the intensive care unit (OR = 2.41, 95% CI = 1.53-8.08, P = 0.012), had used drain placement >72 hours (OR = 2.66, 95% CI = 1.04-4.29, P = 0.007), had surgery >4.5 hours (OR = 2.38, 95% CI = 1.39-4.05, P = 0.005), had repeat operations (OR = 2.74, 95% CI = 1.31-5.73, P = 0.018), endured trauma (OR = 5.97, 95% CI = 1.57-17.61, P = 0.007), or had 30-days mortality (OR = 5.07, 95% CI = 2.20-11.48, P = 0.001). The predominant pathogens isolated from cerebrospinal fluid were Staphylococcus aureus in 8 patients (36.7%) and Acinetobacter baumannii in 7 patients (31.8%). In our study, the mortality rate was 5.1% among all postcraniotomy patients.Accurate risk assessment, early diagnosis, and choice of appropriate antibiotics in accordance with epidemiologic information are the cornerstones of reducing

  12. A pituitary abscess masquerading as recurrent hypernatremia and aseptic meningitis.

    PubMed

    Gonzales, Michael; Marik, Paul Ellis; Khardori, Romesh K; O'Brian, John T

    2012-01-01

    Pituitary abscess is a rare condition. In the setting of multiple surgical interventions, the risk of its development increases. A 49-year-old man presented with episodes of altered mental status. He had two surgeries for a recurrent suprasellar arachnoid cyst. The second surgery was complicated by a persistent cerebrospinal fluid (CSF) leak that required two repairs following which he developed panhypopituitarism and central diabetes insipidus. Twelve months after his last surgery he was diagnosed with aseptic meningitis. This was followed by recurrent hospitalisations for severe hypernatremia blamed on poor medication compliance. He was subsequently hospitalised for the evaluation of a febrile illness. Brain MRI showed ventriculitis and enhancement of the sella. Exploratory surgery revealed a purulent collection in the sella and a mucosal graft which had been used to repair the CSF leak. After drainage of pus and replacement of the graft he recovered completely but requiring life-long hormonal replacement. PMID:22751424

  13. A pituitary abscess masquerading as recurrent hypernatremia and aseptic meningitis

    PubMed Central

    Gonzales, Michael; Marik, Paul Ellis; Khardori, Romesh K; O'Brian, John T

    2012-01-01

    Pituitary abscess is a rare condition. In the setting of multiple surgical interventions, the risk of its development increases. A 49-year-old man presented with episodes of altered mental status. He had two surgeries for a recurrent suprasellar arachnoid cyst. The second surgery was complicated by a persistent cerebrospinal fluid (CSF) leak that required two repairs following which he developed panhypopituitarism and central diabetes insipidus. Twelve months after his last surgery he was diagnosed with aseptic meningitis. This was followed by recurrent hospitalisations for severe hypernatremia blamed on poor medication compliance. He was subsequently hospitalised for the evaluation of a febrile illness. Brain MRI showed ventriculitis and enhancement of the sella. Exploratory surgery revealed a purulent collection in the sella and a mucosal graft which had been used to repair the CSF leak. After drainage of pus and replacement of the graft he recovered completely but requiring life-long hormonal replacement. PMID:22751424

  14. Salmonella berta meningitis in a term neonate.

    PubMed

    Bowe, A C; Fischer, M; Waggoner-Fountain, L A; Heinan, K C; Goodkin, H P; Zanelli, S A

    2014-10-01

    We report the case of a 37-week male infant born via spontaneous vaginal delivery who developed Salmonella berta sepsis and meningitis. The infant was born to a mother with active diarrhea and stool cultures growing S. berta. On day 3, the infant developed poor feeding, lethargy, apnea and bradycardia prompting a sepsis evaluation. Blood, stool and cerebrospinal fluid cultures were positive for S. berta. An electroencephalogram performed for posturing revealed neonatal status epilepticus. Extensive bilateral periventricular venous hemorrhagic infarctions with multiple herniations were seen on brain magnetic resonance imaging. The infant's condition continued to deteriorate despite maximal support and care was redirected towards comfort measures. PMID:25263727

  15. Recurrent pneumococcal meningitis in a splenectomised HIV-infected patient

    PubMed Central

    Morand, Philippe C; Veuillez, Veronique; Poyart, Claire; Abachin, Eric; Quesne, Gilles; Dupont, Bertrand; Berche, Patrick; Viard, Jean-Paul

    2003-01-01

    Background Streptococcus pneumoniae is a major cause of human disease, especially in pre-school children and elderly people, as well as in special risk groups such as asplenic, antibody deficient patients, or presenting disruption of natural barriers. The occurrence of pneumococcal disease has increased with the onset of the HIV epidemic and the emergence of drug-resistance. Case presentation We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination. Conclusions Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case. PMID:14613586

  16. Tuberculous radiculomyelitis complicating tuberculous meningitis: case report and review.

    PubMed

    Hernández-Albújar, S; Arribas, J R; Royo, A; González-García, J J; Peña, J M; Vázquez, J J

    2000-06-01

    Tuberculous radiculomyelitis (TBRM) is a complication of tuberculous meningitis (TBM), which has been reported rarely in the modern medical literature. We describe a case of TBRM that developed in an human immunodeficiency virus (HIV)-infected patient, despite prompt antituberculous treatment. To our knowledge, this is the second case of TBRM reported in an HIV-infected patient. We also review 74 previously reported cases of TBRM. TBRM develops at various periods after TBM, even in adequately treated patients after sterilization of the cerebrospinal fluid (CSF). The most common symptoms are subacute paraparesis, radicular pain, bladder disturbance, and subsequent paralysis. CSF evaluation usually shows an active inflammatory response with a very high protein level. MRI and CT scan are critical for diagnosis, revealing loculation and obliteration of the subarachnoid space along with linear intradural enhancement. As in other forms of paradoxical reactions to antituberculous treatment, there is evidence that steroid treatment might have a beneficial effect. PMID:10854362

  17. Risk factors associated with postcraniotomy meningitis: A retrospective study

    PubMed Central

    Chen, Chang-Hua; Chang, Chih-Yen; Lin, Li-Jhen; Chen, Wei Liang; Chang, Yu-Jun; Wang, Shu-Hui; Cheng, Chun-Yuan; Yen, Hua-Cheng

    2016-01-01

    Abstract Postcraniotomy meningitis (PCM) is a major challenge in neurosurgery, and changing patterns of infectious agents in PCM have been noted. The limited epidemiological data and urgent clinical needs motivated this research. We conducted this study to determine a risk assessment for PCM and the current pattern of infectious agents. We performed a retrospective case-control study of significant cases of postcraniotomy meningitis in the Changhua Christian Hospital System between January 1, 2008, and December 31, 2012. Postcraniotomy meningitis was diagnosed in 22 out of 4392 surgical patients; this data was reviewed for risk assessment. This study assessed the risk factors for postcraniotomy meningitis and found that it was more frequently seen in patients who were elderly (OR = 1.57, 95% CI = 1.32–2.98, P = 0.013), underwent emergency procedures (OR = 4.82, 95% CI = 1.50–14.53, P = 0.008), had leak of cerebrospinal fluid (OR = 4.62, 95% CI = 2.03–10.50, P = 0.012), had external ventricular drainage (OR = 4.68, 95% CI = 2.46–8.87, P = 0.006), were admitted to the intensive care unit (OR = 2.41, 95% CI = 1.53–8.08, P = 0.012), had used drain placement >72 hours (OR = 2.66, 95% CI = 1.04–4.29, P = 0.007), had surgery >4.5 hours (OR = 2.38, 95% CI = 1.39–4.05, P = 0.005), had repeat operations (OR = 2.74, 95% CI = 1.31–5.73, P = 0.018), endured trauma (OR = 5.97, 95% CI = 1.57–17.61, P = 0.007), or had 30-days mortality (OR = 5.07, 95% CI = 2.20–11.48, P = 0.001). The predominant pathogens isolated from cerebrospinal fluid were Staphylococcus aureus in 8 patients (36.7%) and Acinetobacter baumannii in 7 patients (31.8%). In our study, the mortality rate was 5.1% among all postcraniotomy patients. Accurate risk assessment, early diagnosis, and choice of appropriate antibiotics in accordance with epidemiologic information are

  18. Prolonged incubation period in neonatal Pasteurella multocida meningitis and bacteremia.

    PubMed

    Yamaguchi, Hiroshi; Tamura, Takuya; Abe, Michiko; Ogiwara, Shigetoshi; Sai, Shuji; Kosugiyama, Kiyotaka; Sugihara, Akemi; Nagumo, Kiyoshi; Iwata, Seido; Kinugawa, Yoshikazu

    2014-12-01

    Pasteurella multocida, often found as part of the human oral flora and in finger/toenails, also exists in many animals, especially cats, dogs, and pigs. Although rare, pasteurella infection in neonates can cause serious systemic disease, such as meningitis. In this article, a 23-day-old girl presented with decreased appetite and irritability for >2 days. Eighteen days previously her pet cat had jumped onto the left side of her head while she was sleeping. On laboratory data C-reactive protein was high, and on cerebrospinal fluid (CSF) analysis leukocyte count was extremely high, with low glucose and high protein. P. multocida grew out of the blood and CSF cultures, and she was successfully treated with antibiotics for 3 weeks. Although pasteurellosis rarely occurs, it can sometimes lead to life-threatening situations, so parents should exercise caution when having pets around their children. PMID:25521988

  19. Neisseria sicca meningitis following intracranial hemorrhage and ventriculostomy tube placement.

    PubMed

    Carter, J Elliot; Mizell, Kelly N; Evans, Tara N

    2007-12-01

    A normal component of the flora of the oropharynx, Neisseria sicca was first isolated in 1906 and has since been reported as a rare cause of various human infections including endocarditis, pneumonia, sinusitis, sepsis, and urethritis. We report the case of a 44-year-old African-American female with a history of hypertension who presented with complaints of right frontal headache, nausea, photophobia, and vomiting. A computed tomography scan of the patient's brain showed a large subarachnoid hemorrhage, and an arteriogram confirmed a large posterior communicating artery aneurysm. A ventriculostomy tube was placed, and the patient subsequently developed an elevated temperature and elevated white blood cell count. Cerebrospinal fluid studies showed elevated protein and glucose levels and cultures positive for N. sicca. This is only the seventh reported case of culture-proven meningitis related to N. sicca, and the first reported case associated with intracranial hemorrhage and ventriculostomy tube placement. PMID:17904282

  20. Suppurative meningitis: A life-threatening complication in male macroprolactinomas

    PubMed Central

    Chentli, Farida; Akkache, Lina; Daffeur, Katia; Haddad, Meriem; Azzoug, Said

    2013-01-01

    Background: Suppurative meningitis (SM) or bacterial meningitis is a life-threatening condition, which is exceptionally due to pituitary tumors (PT). Our aim was to analyze its frequency among male macroprolactinomas (MPRL) deemed to be aggressive, to report the cases we observed in our practice and describe the circumstances under which SM appeared. Materials and Methods: We retrospectively analyzed 82 male MPRL in order to look for a history of well proved SM and the circumstances under which SM appeared. We also took into account the possibility of SM relapsing. Results: Four out of 82 male MPRL had SM = 4.87%. Three consulted for SM symptoms. SM was confirmed in Infectious Diseases department, but only one had rhinorrhea. Hormonal assessment and cerebral magnetic resonance imaging pleaded for aggressive prolactinomas. After antibiotics, SM was sterilized. Then, MPRL were treated with bromocriptine, which normalized prolactin and reduced PT. SM never relapsed. The 4th case was hospitalized for a large multidirectional prolactinoma invading and/or arising from the skull base. He was operated on 3 times and then he was given Bromocriptine. After 3 months, he had rhinorrhea and then SM which was successfully treated by antibiotics. SM never relapsed after tumor reduction. Conclusion: SM was demonstrated in 4.87%. SM has revealed MPRL in 3 cases and appeared after bromocriptine intake in the 4th one. Endocrinologists should be aware of this severe condition, which can be avoided by repairing as soon as possible the bony defect secondary to aggressive tumors, unless it is clogged by fibrosis: What probably happened in our cases. PMID:24251128

  1. Surgical Treatments for Infantile Purulent Meningitis Complicated by Subdural Effusion

    PubMed Central

    Wang, Xianshu; Zhang, Xiaoru; Cao, Hongbin; Jing, Shiyuan; Yang, Zhiguo; Cheng, Zhenghai; Liu, Ye; Li, Xin; Gao, Feifei; Ji, Yuanqi

    2015-01-01

    Background Infantile purulent meningitis (PM) is a commonly severe intracranial infectious disease in infants under age 1 year. In recent years, several diagnostic and treatment methods were reported, but in these cases the neurological complications and sequel were often observed, among which subdural effusion (SE) is the most common complication in PM. Timely diagnosis and early intervention are vital for better outcomes. In this study, the surgical treatments for infantile PM complicated by SE were investigated. Material/Methods Patients who had PM complicated by SE in the Children’s Hospital of Hebei Province from June 2000 to June 2012 were retrospectively analyzed and 170 patients were enrolled in the study. Surgical treatment for each patient was adopted according to producing effusion time, leucocyte count, protein content, intracranial pressure, and bacteria culture, coupled with cranial ultrasound examination, CT, and MRI scans. Results Nearly, 15 patients were cured using serial taps, with a 50% cure rate. Seventeen out of 30 (56.6%) patients receiving subcutaneous reservoir drainage had better outcome. Nearly 80% of patients (55/69) who underwent minimally invasive trepanation and drainage were positive. Surgical procedure of minimally invasive trepanation and drainage combined with drug douche was effective in 63% of patients (19/30). In addition, 6 patients were cured with subdural-peritoneal shunt. Only 1 patient died, after the recurrence of meningitis, and the remaining 4 patients were cured by craniotomy. Conclusions For infantile PM complicated with SE, treatment needs be chosen according to the specific situation. Surgical procedure of minimally invasive trepanation and drainage is a very effective treatment in curing PM complicated by SE. The treatment was highly effective with the use of drug douche. Subdural-peritoneal shunt and craniotomy were as effective as in refractory cases. PMID:26482715

  2. Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis

    PubMed Central

    Han, Nayoung; Kim, Hannah; Min, Soo Kee; Paek, Sun-Ha; Park, Chul-Kee; Choi, Seung-Hong; Chae, U-Ri; Park, Sung-Hye

    2016-01-01

    Background: The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. Methods: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. Results: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. Conclusions: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases. PMID:26657311

  3. The 2012 Fungal Meningitis Outbreak in the United States: Connections Between Soils and Human Health

    NASA Astrophysics Data System (ADS)

    Burgess, Lynn; Brevik, Eric

    2013-04-01

    In September of 2012 the United States found itself facing a fungal meningitis outbreak that was traced back to contaminated steroid injections. The fungus Exserohilium rostratum, which is found in soil, among other locations in the environment, was identified as the main cause of the health issues created by the contaminated steroids. As of November 7, 2012 419 cases of fungal meningitis, stroke due to presumed fungal meningitis, or other central nervous system-related infections, 10 cases of peripheral joint infections, and 31 deaths linked to the contaminated steroids had been documented. However, the life cycle and soil ecology of E. rostratum is not well understood, and such knowledge would aid human health professionals in understanding the pathogenic potential of E. rostratum. Therefore, soil scientists have a role to play in developing the most effective ways to combat human health challenges such as the 2012 fungal meningitis outbreak.

  4. Meningeal involvement in Wegener granulomatosis: case report and review of the literature.

    PubMed

    Soriano, A; Lo Vullo, M; Casale, M; Quattrocchi, C C; Afeltra, A

    2012-01-01

    Wegener Granulomatosis (WG) is a multisystem autoimmune disorder characterized by necrotizing granulomatous vasculitis that most commonly involves the upper respiratory tract, lungs, and kidneys. The involvement of the central nervous system (CNS) is infrequent and can cause stroke, cranial nerve abnormalities, cerebrovascular events, seizures, and meningeal involvement. Meningeal involvement is rare and may occur due to local vasculitis, directly spread from adjacent disease in the skull base, paranasal or orbital region. We describe the case of a 20-year-old Caucasian man who was diagnosed with sinonasal WG with frontal focal meningeal involvement. A literature review on diagnosis and treatment of meningeal involvement in course of WG was carried out. The importance of an early diagnosis and treatment of localized WG has been emphasized, in order to avoid the progression to a severe form of disease, especially in younger patients and in paucisymptomatic cases. PMID:23298504

  5. Hemorrhagic and ischemic stroke secondary to herpes simplex virus type 2 meningitis and vasculopathy.

    PubMed

    Snider, Samuel B; Jacobs, Claire S; Scripko, Patricia S; Klein, Joshua P; Lyons, Jennifer L

    2014-08-01

    Herpes simplex virus type 2 (HSV-2) meningitis dogmatically is benign and self-limited in the immune competent patient. However, we describe how left untreated HSV-2 meningitis can be complicated by vasculitis and both ischemic and hemorrhagic stroke. We report a 57-year-old woman with lymphocytic meningitis complicated by ischemic stroke and intracerebral hemorrhage in the setting of vasculopathy and HSV-2 DNA detected in CSF successfully treated with acyclovir and corticosteroids. Subsequent angiographic magnetic resonance imaging revealed improvement in the vasculopathy after treatment. This case demonstrates that HSV-2 meningitis may take a less benign course and further provides the first evidence of angiographic improvement in addition to clinical improvement after definitive treatment. PMID:24806272

  6. Use of Vaccines to Prevent Meningitis in Persons with Cochlear Implants

    MedlinePlus

    ... vaccine=MPSV4 Meningococcal conjugate vaccine=MenACWY Use of Vaccines to Prevent Meningitis in Persons with Cochlear Implants ... References FACT SHEET What You Should Know Pneumococcal Vaccine Recommendations Pneumococcal Vaccination for Cochlear Implant Candidates and ...

  7. Soil Dust Aerosols and Wind as Predictors of Seasonal Meningitis Incidence in Niger

    NASA Technical Reports Server (NTRS)

    Perez Garcia Pando, Carlos; Stanton, Michelle C.; Diggle, Peter J.; Trzaska, Sylwia; Miller, Ron L.; Perlwitz, Jan P.; Baldasano, Jose M.; Cuevas, Emilio; Ceccato, Pietro; Yaka, Pascal; Thomson, Madeleine C.

    2014-01-01

    Background: Epidemics of meningococcal meningitis are concentrated in sub-Saharan Africa during the dry season, a period when the region is affected by the Harmattan, a dry and dusty northeasterly trade wind blowing from the Sahara into the Gulf of Guinea.Objectives: We examined the potential of climate-based statistical forecasting models to predict seasonal incidence of meningitis in Niger at both the national and district levels.Data and methods: We used time series of meningitis incidence from 1986 through 2006 for 38 districts in Niger. We tested models based on data that would be readily available in an operational framework, such as climate and dust, population, and the incidence of early cases before the onset of the meningitis season in January-May. Incidence was used as a proxy for immunological state.

  8. Expect the Unexpected: A Case of Isolated Eosinophilic Meningitis in Toxocariasis

    PubMed Central

    Sick, Christian; Hennerici, Michael G.

    2014-01-01

    We present the case of a young police officer suffering from headache without other neurological symptoms caused by isolated eosinophilic meningitis, which resulted from an infection with Toxocara cati, along with a discussion of the differential diagnosis. PMID:25535488

  9. Awareness of Meningococcal Disease among Travelers from the United Kingdom to the Meningitis Belt in Africa

    PubMed Central

    Goodman, Anna L.; Masuet-Aumatell, Cristina; Halbert, Jay; Zuckerman, Jane N.

    2014-01-01

    Meningococcal disease causes considerable morbidity and has a high case-fatality rate. In the United Kingdom, the meningococcal quadrivalent vaccine is recommended for travelers visiting the meningitis belt of Africa. We analyzed 302 responses to a cross-sectional study conducted in 2010 of travelers who had visited the meningitis belt recently or were shortly due to travel there. Using the results of an online questionnaire, we assessed knowledge and understanding of meningococcal disease and likelihood of uptake of meningococcal immunization before travel. Meningococcal vaccine uptake was 30.1%. Although global scores in the questionnaire did not correlate with vaccine uptake, knowledge of the meningitis belt and knowledge of certain key symptoms or signs were statistically associated with high vaccine uptake. We conclude that improved education of travelers may improve vaccine uptake before travel to the meningitis belt in Africa. PMID:24891461

  10. Detection of single bacteria - causative agents of meningitis using raman microscopy

    NASA Astrophysics Data System (ADS)

    Baikova, T. V.; Minaeva, S. A.; Sundukov, A. V.; Svistunova, T. S.; Bagratashvili, V. N.; Alushin, M. V.; Gonchukov, S. A.

    2015-03-01

    Early diagnostics of meningitis is a very topical problem as it is a fulminant disease with a high level of mortality. The progress of this disease is, as a rule, accompanied by the appearance of bacteria in the cerebrospinal fluid (CSF) composition. The examination of the CSF is well known to be the only reliable approach to the identification of meningitis. However, the traditional biochemical analyses are time consuming and not always reliable, simple, and inexpensive, whereas the optical methods are poorly developed. This work is devoted to the study of Raman spectra of several bacterial cultures which are mainly present during meningitis. Raman microscopy is a prompt and noninvasive technique capable of providing reliable information about molecular-level alterations of biological objects at their minimal quantity and size. It was shown that there are characteristic lines in Raman spectra which can be the reliable markers for determination of bacterial form of meningitis at a level of a single bacterium.

  11. Etiologies and Management of Aseptic Meningitis in Patients Admitted to an Internal Medicine Department

    PubMed Central

    Jarrin, Irène; Sellier, Pierre; Lopes, Amanda; Morgand, Marjolaine; Makovec, Tamara; Delcey, Veronique; Champion, Karine; Simoneau, Guy; Green, Andrew; Mouly, Stéphane; Bergmann, Jean-François; Lloret-Linares, Célia

    2016-01-01

    Abstract Several studies have focused on the clinical and biological characteristics of meningitis in order to distinguish between bacterial and viral meningitis in the emergency setting. However, little is known about the etiologies and outcomes of aseptic meningitis in patients admitted to Internal Medicine. The aim of the study is to describe the etiologies, characteristics, and outcomes of aseptic meningitis with or without encephalitis in adults admitted to an Internal Medicine Department. A retrospective cohort study was conducted in the Internal Medicine Department of the Lariboisière Hospital in Paris, France, from January 2009 to December 2011. Clinical and biological characteristics of aseptic meningitis were recorded. These included cerebrospinal fluid analysis, results of polymerase chain reaction testing, final diagnoses, and therapeutic management. The cohort included 180 patients fulfilling the criteria for aseptic meningitis with (n = 56) or without (n = 124) encephalitis. A definitive etiological diagnosis was established in 83 of the 180 cases. Of the cases with a definitive diagnosis, 73 were due to infectious agents, mainly enteroviruses, Herpes Simplex Virus 2, and Varicella Zoster Virus (43.4%, 16.8%, and 14.5% respectively). Inflammatory diseases were diagnosed in 7 cases. Among the 97 cases without definitive diagnoses, 26 (26.8%) remained free of treatment throughout their management whereas antiviral or antibiotic therapy was initiated in the emergency department for the remaining 71 patients. The treatment was discontinued in only 10 patients deemed to have viral meningitis upon admission to Internal Medicine. The prevalence of inflammatory diseases among patients admitted to internal medicine for aseptic meningitis is not rare (4% of overall aseptic meningitis). The PCR upon admission to the emergency department is obviously of major importance for the prompt optimization of therapy and management. However, meningitis due to

  12. HSV-1 as a novel therapy for breast cancer meningeal metastases.

    PubMed

    Kuruppu, D; Tanabe, K K

    2015-10-01

    Meningeal metastasis is a fatal complication of breast cancer that affects 5-8% of patients. When cancer cells seed in the meninges, their subsequent growth results in severe neurological complications involving the cranial nerves, cerebrum and spinal cord, limiting life expectancy to less than 4 months. The incidences of meningeal metastases increase with prolonged lifespan resulting from treatment advances for primary breast cancer and their metastases. Currently, there is no cure. Aggressive multimodal therapies such as radiation and chemotherapy (intra-cerebrospinal fluid (CSF) and systemic) are ineffective. Therapeutic agents are often quickly cleared from the CSF, while higher doses that can achieve a therapeutic response are highly toxic. The secure guarding of the subarachnoid space by the blood-brain barrier on one side and the blood-CSF barrier on the other prevents chemotherapy from reaching cancer cells in the meninges. These challenges with treating meningeal metastases highlight the urgent need for a new therapeutic modality. An ideal treatment would be an agent that avoids rapid clearance, remains within the CSF, reaches the meninges and selectively destroys tumor cells. Replication conditional oncolytic herpes simplex virus type 1 (HSV-1) may be effective in this regard. Viral oncolysis, the destruction of cancer cells by replicating virus, is under clinical investigation for cancers that are unresponsive to current therapies. It is based on the model of multiple cycles of lytic virus replication in cancer cells that amplify the injected dose. The therapeutic potential of oncolytic HSV-1 for breast cancer meningeal metastases is discussed here. HSV-1 could be a potential novel treatment for meningeal metastases that can be translated to the clinic. PMID:26384139

  13. The frequency of physical signs usually attributed to meningeal irritation in elderly patients.

    PubMed

    Puxty, J A; Fox, R A; Horan, M A

    1983-10-01

    Nuchal rigidity, which may be a sign of meningitis, was found in 35 per cent of geriatric patients on acute-care and rehabilitation wards and in 13 per cent of younger patients on an acute-care ward. It was significantly associated with cerebrovascular disease, confusion, abnormal plantar responses, and primitive reflexes. Elderly patients who have nuchal rigidity with no history of neurologic or cognitive disorders should be investigated for meningitis. PMID:6619465

  14. A rare presentation of cerebral venous sinus thrombosis associated with tubercular meningitis.

    PubMed

    Verma, Rajesh; Lalla, Rakesh; Patil, Tushar B; Tiwari, Navin

    2013-01-01

    Central nervous system (CNS) tuberculosis may manifest as meningitis, meningoencephalitis, tuberculoma, tubercular abscess, stroke due to tuberculous vasculitis and tuberculous encephalopathy. Occasionally, tubercular meningitis (TBM) can predispose to cerebral venous sinus thrombosis (CVST). We report a young man, who developed CVST as a complication of TBM. Worsening of pre-existing headache, impairment of consciousness and seizures should raise suspicion of CVST in any patient with CNS infection. Early diagnosis and appropriate clinical management are important for good outcome. PMID:23917359

  15. The relationship between prior antimicrobial prescription and meningitis: a case–control study

    PubMed Central

    Armstrong, David; Ashworth, Mark; Dregan, Alex; White, Patrick

    2016-01-01

    Background Recent research into the role of the human microbiome in maintaining health has identified the potentially harmful impact of antimicrobials. Aim The association with bacterial and viral meningitis following antimicrobial prescription during the previous year was investigated to determine whether antimicrobials have a deleterious effect on the nasopharyngeal microbiome. Design and setting A case-control study (1:4 cases to controls) was conducted examining the rate of previous antimicrobial exposure in cases of meningitis and in a matched control group. Data from a UK primary care clinical database were analysed using conditional logistic regression. Results A total of 7346 cases of meningitis were identified, 3307 (45%) viral, 1812 (25%) bacterial, and 2227 (30%) unspecified. The risks of viral (adjusted odds ratio [AOR] 2.45; 95% confidence interval [CI] = 2.24 to 2.68) or bacterial (AOR 1.98; 95% CI = 1.71 to 2.30) meningitis were both increased following antimicrobial prescription in the preceding year. Patients who received ≥4 antimicrobial prescriptions in the preceding year were at significantly increased risk of all types of meningitis (AOR 2.85; 95% CI = 2.44 to 3.34), bacterial meningitis (AOR 3.06; 95% CI = 2.26 to 4.15) and viral meningitis (AOR 3.23; 95% CI = 2.55 to 4.08) compared to their matched controls. Conclusion There was an increased risk of meningitis following antimicrobial prescription in the previous year. It is possible that this increase was due to an effect of antimicrobials on the microbiome or reflected an increased general susceptibility to infections in these patients. PMID:26965030

  16. A rare presentation of cerebral venous sinus thrombosis associated with tubercular meningitis

    PubMed Central

    Verma, Rajesh; Lalla, Rakesh; Patil, Tushar B; Tiwari, Navin

    2013-01-01

    Central nervous system (CNS) tuberculosis may manifest as meningitis, meningoencephalitis, tuberculoma, tubercular abscess, stroke due to tuberculous vasculitis and tuberculous encephalopathy. Occasionally, tubercular meningitis (TBM) can predispose to cerebral venous sinus thrombosis (CVST). We report a young man, who developed CVST as a complication of TBM. Worsening of pre-existing headache, impairment of consciousness and seizures should raise suspicion of CVST in any patient with CNS infection. Early diagnosis and appropriate clinical management are important for good outcome. PMID:23917359

  17. Tuberculous meningitis with dementia as the presenting symptom after intramedullary spinal cord tumor resection

    PubMed Central

    Kobayashi, Kazuyoshi; Imagama, Shiro; Ito, Zenya; Ando, Kei; Yagi, Hideki; Shinjo, Ryuichi; Hida, Tetsuro; Ito, Kenyu; Ishikawa, Yoshimoto; Matsuyama, Yukihiro; Ishiguro, Naoki

    2015-01-01

    ABSTRACT Early-stage TB meningitis has no specific symptoms in patients, potentially leading to delayed diagnosis and consequently worsening prognosis. The authors present the fatal case with a delayed diagnosis of tuberculous (TB) meningitis with dementia as the presenting symptom after intramedullary spinal cord tumor resection. The medical records, operative reports, and radiographical imaging studies of a single patient were retrospectively reviewed. A 77-year-old man who underwent thoracic intramedullary hemangioblastoma resection for 2 times. The postoperative course was uneventful, but 1.5 months after surgery, the patient suffered from dementia with memory loss and diminished motivation and speech in the absence of a fever. No abnormalities were detected on blood test, brain computed tomography and cerebrospinal fluid (CSF) analysis. A sputum sample was negative for Mycobacterium tuberculosis in the QuantiFERON®-TB Gold (QFT-G) In-Tube Test and the tuberculin skin test was also negative. The patient was diagnosed with senile dementia by a psychiatrist. However, the patient’s symptoms progressively worsened. Despite the absence of TB meningitis findings, we suspected TB meningitis from the patient’s history, and administered a four-drug regimen. However the patient died 29 days after admission, subsequently M. tuberculosis was detected in the CSF sample. This case is a rare case of TB meningitis initially mistaken for dementia after intramedullary spinal cord tumor resection. Symptoms of dementia after intramedullary spinal cord tumor resection should first be suspected as one of TB meningitis, even if the tests for meningitis are negative. We propose that anti-tuberculosis therapy should be immediately initiated in cases of suspected TB meningitis prior to positive identification on culture. PMID:26663944

  18. Rhodotorula mucilaginosa associacted meningitis: A subacute entity with high mortality. Case report and review

    PubMed Central

    Tsiodras, Sotirios; Papageorgiou, Sotirios; Meletiadis, Joseph; Tofas, Polydoros; Pappa, Vasiliki; Panayiotides, John; Karakitsos, Petros; Armaganidis, Apostolos; Petrikkos, George

    2014-01-01

    A fatal case of meningitis due to Rhodotorula mucilaginosa in a 28 year-old HIV-negative male with a history of Hodgkin lymphoma who underwent salvage chemotherapy is presented. Reviewing the literature we identified 13 cases with central nervous system infection due Rhodotorula spp. The disease usually occurs in HIV negative immunosupressed middle-aged males. It takes the form of subacute or chronic meningitis accompanied by fever with an overall mortality of 46.2% despite antifungal therapy. PMID:25379400

  19. Adjunctive N-acetyl-L-cysteine in treatment of murine pneumococcal meningitis.

    PubMed

    Högen, Tobias; Demel, Cornelia; Giese, Armin; Angele, Barbara; Pfister, Hans-Walter; Koedel, Uwe; Klein, Matthias

    2013-10-01

    Despite antibiotic therapy, acute and long-term complications are still frequent in pneumococcal meningitis. One important trigger of these complications is oxidative stress, and adjunctive antioxidant treatment with N-acetyl-l-cysteine was suggested to be protective in experimental pneumococcal meningitis. However, studies of effects on neurological long-term sequelae are limited. Here, we investigated the impact of adjunctive N-acetyl-l-cysteine on long-term neurological deficits in a mouse model of meningitis. C57BL/6 mice were intracisternally infected with Streptococcus pneumoniae. Eighteen hours after infection, mice were treated with a combination of ceftriaxone and placebo or ceftriaxone and N-acetyl-l-cysteine, respectively. Two weeks after infection, neurologic deficits were assessed using a clinical score, an open field test (explorative activity), a t-maze test (memory function), and auditory brain stem responses (hearing loss). Furthermore, cochlear histomorphological correlates of hearing loss were assessed. Adjunctive N-acetyl-l-cysteine reduced hearing loss after pneumococcal meningitis, but the effect was minor. There was no significant benefit of adjunctive N-acetyl-l-cysteine treatment in regard to other long-term complications of pneumococcal meningitis. Cochlear morphological correlates of meningitis-associated hearing loss were not reduced by adjunctive N-acetyl-l-cysteine. In conclusion, adjunctive therapy with N-acetyl-l-cysteine at a dosage of 300 mg/kg of body weight intraperitoneally for 4 days reduced hearing loss but not other neurologic deficits after pneumococcal meningitis in mice. These results make a clinical therapeutic benefit of N-acetyl-l-cysteine in the treatment of patients with pneumococcal meningitis questionable. PMID:23877681

  20. Successful treatment of Stenotrophomonas maltophilia meningitis in a preterm baby boy: a case report

    PubMed Central

    2009-01-01

    Introduction Stenotrophomonas maltophilia is an important cause of hospital acquired infection particularly among severely debilitated and immunosuppressed patients. Case presentation We report a case of S. maltophilia meningitis in a preterm baby boy after a neurosurgical procedure, successfully treated with trimethoprim-sulfamethoxazole and ciprofloxacin. Conclusion This organism should be considered as a potential cause of meningitis and trimethoprim-sulfamethoxazole and ciprofloxacin are a combination that is successful and safe for treating preterm infants. PMID:19830198