Epidemiology of meningitis in an HIV-infected Ugandan cohort.

PubMed

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

2015-02-01

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. © The American Society of Tropical Medicine and Hygiene.

Outcomes of HIV-positive patients with cryptococcal meningitis in the Americas.

PubMed

Crabtree Ramírez, B; Caro Vega, Y; Shepherd, B E; Le, C; Turner, M; Frola, C; Grinsztejn, B; Cortes, C; Padgett, D; Sterling, T R; McGowan, C C; Person, A

2017-10-01

Cryptococcal meningitis (CM) is associated with substantial mortality in HIV-infected patients. Optimal timing of antiretroviral therapy (ART) in persons with CM represents a clinical challenge, and the burden of CM in Latin America has not been well described. Studies suggest that early ART initiation is associated with higher mortality, but data from the Americas are scarce. HIV-infected adults in care between 1985-2014 at participating sites in the Latin America (the Caribbean, Central and South America network (CCASAnet)) and the Vanderbilt Comprehensive Care Clinic (VCCC) and who had CM were included. Survival probabilities were estimated. Risk of death when initiating ART within the first 2 weeks after CM diagnosis versus initiating between 2-8 weeks was assessed using dynamic marginal structural models adjusting for site, age, sex, year of CM, CD4 count, and route of HIV transmission. 340 patients were included (Argentina 58, Brazil 138, Chile 28, Honduras 27, Mexico 34, VCCC 55) and 142 (42%) died during the observation period. Among 151 patients with CM prior to ART 56 (37%) patients died compared to 86 (45%) of 189 with CM after ART initiation (p=0.14). Patients diagnosed with CM after ART had a higher risk of death (p=0.03, log-rank test). The probability of survival was not statistically different between patients who started ART within 2 weeks of CM (7/24, 29%) vs. those initiating between 2-8 weeks (14/53, 26%) (p=0.96), potentially due to lack of power. In this large Latin-American cohort, patients with CM had very high mortality rates, especially those diagnosed after ART initiation. This study reflects the overwhelming burden of CM in HIV-infected patients in Latin America. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings

PubMed Central

Lofgren, Sarah M; Abassi, Mahsa; Rhein, Joshua; Boulware, David R

2017-01-01

Introduction Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths. Areas covered Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent. Expert Commentary Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging. PMID:28111998

Asymptomatic cryptococcal antigen prevalence detected by lateral flow assay in hospitalised HIV-infected patients in São Paulo, Brazil.

PubMed

Vidal, José E; Toniolo, Carolina; Paulino, Adriana; Colombo, Arnaldo; Dos Anjos Martins, Marilena; da Silva Meira, Cristina; Pereira-Chioccola, Vera Lucia; Figueiredo-Mello, Claudia; Barros, Tiago; Duarte, Jequelie; Fonseca, Fernanda; Alves Cunha, Mirella; Mendes, Clara; Ribero, Taiana; Dos Santos Lazera, Marcia; Rajasingham, Radha; Boulware, David R

2016-12-01

To determine the prevalence of asymptomatic cryptococcal antigen (CRAG) using lateral flow assay (LFA) in hospitalised HIV-infected patients with CD4 counts <200 cells/μl. Hospitalised HIV-infected patients were prospectively recruited at Instituto de Infectologia Emilio Ribas, a tertiary referral hospital to HIV-infected patients serving the São Paulo State, Brazil. All patients were >18 years old without prior cryptococcal meningitis, without clinical suspicion of cryptococcal meningitis, regardless of antiretroviral (ART) status, and with CD4 counts <200 cells/μl. Serum CRAG was tested by LFA in all patients, and whole blood CRAG was tested by LFA in positive cases. We enrolled 163 participants of whom 61% were men. The duration of HIV diagnosis was a median of 8 (range, 1-29) years. 26% were antiretroviral (ART)-naïve, and 74% were ART-experienced. The median CD4 cell count was 25 (range, 1-192) cells/μl. Five patients (3.1%; 95%CI, 1.0-7.0%) were asymptomatic CRAG-positive. Positive results cases were cross-verified by performing LFA in whole blood. 3.1% of HIV-infected inpatients with CD4 <200 cells/μl without symptomatic meningitis had cryptococcal antigenemia in São Paulo, suggesting that routine CRAG screening may be beneficial in similar settings in South America. Our study reveals another targeted population for CRAG screening: hospitalised HIV-infected patients with CD4 <200 cells/μl, regardless of ART status. Whole blood CRAG LFA screening seems to be a simple strategy to prevention of symptomatic meningitis. © 2016 John Wiley & Sons Ltd.

The Epidemiology of Meningitis among Adults in a South African Province with a High HIV Prevalence, 2009-2012.

PubMed

Britz, Erika; Perovic, Olga; von Mollendorf, Claire; von Gottberg, Anne; Iyaloo, Samantha; Quan, Vanessa; Chetty, Verushka; Sriruttan, Charlotte; Ismail, Nazir A; Nanoo, Ananta; Musekiwa, Alfred; Reddy, Carl; Viljoen, Karien; Cohen, Cheryl; Govender, Nelesh P

Meningitis is a major cause of mortality in southern Africa. We aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a South African province with an 11% HIV prevalence, over 4 years. We conducted a retrospective, observational study of secondary laboratory data, extracted on all cerebrospinal fluid (CSF) specimens submitted to public-sector laboratories in Gauteng province from 2009 through 2012. We calculated cause-specific incidence rates in the general and HIV-infected populations and used Poisson regression to determine if trends were significant. We identified 11,891 (10.7%) incident cases of meningitis from 110,885 CSF specimens. Cryptococcal meningitis, tuberculous meningitis and pneumococcal meningitis accounted for 62.3% (n = 7,406), 24.6% (n = 2,928) and 10.1% (n = 1,197) of cases over the four-year period. The overall incidence (cases per 100,000 persons) of cryptococcal meningitis declined by 23% from 24.4 in 2009 to 18.7 in 2012 (p <0.001) and decreased by 19% among HIV-infected persons from 178.2 to 144.7 (p <0.001). Tuberculous meningitis decreased by 40% from 11.3 in 2009 to 6.8 in 2012 (p <0.001) and decreased by 36% among HIV-infected persons from 54.4 to 34.9 (p <0.001). Pneumococcal meningitis decreased by 41% from 4.2 in 2009 to 2.5 in 2012 (p <0.001) and decreased by 38% among HIV-infected persons from 28.0 to 17.5 (p <0.001). Among cases of other bacterial meningitis (248/11,891, 2.1%), Neisseria meningitidis (n = 93), Escherichia coli (n = 72) and Haemophilus influenzae (n = 20) were the most common organisms identified. In this high HIV-prevalence province, cryptococcal meningitis was the leading cause of laboratory-confirmed meningitis among adults. Over a 4-year period, there was a significant decrease in incidence of cryptococcal, tuberculous and pneumococcal meningitis. This coincided with expansion of the national antiretroviral treatment programme, enhanced

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

The Epidemiology of Meningitis among Adults in a South African Province with a High HIV Prevalence, 2009-2012

PubMed Central

Britz, Erika; Perovic, Olga; von Mollendorf, Claire; von Gottberg, Anne; Iyaloo, Samantha; Quan, Vanessa; Chetty, Verushka; Sriruttan, Charlotte; Ismail, Nazir A.; Nanoo, Ananta; Musekiwa, Alfred; Reddy, Carl; Viljoen, Karien; Cohen, Cheryl; Govender, Nelesh P.

2016-01-01

Introduction Meningitis is a major cause of mortality in southern Africa. We aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a South African province with an 11% HIV prevalence, over 4 years. Methods We conducted a retrospective, observational study of secondary laboratory data, extracted on all cerebrospinal fluid (CSF) specimens submitted to public-sector laboratories in Gauteng province from 2009 through 2012. We calculated cause-specific incidence rates in the general and HIV-infected populations and used Poisson regression to determine if trends were significant. Results We identified 11,891 (10.7%) incident cases of meningitis from 110,885 CSF specimens. Cryptococcal meningitis, tuberculous meningitis and pneumococcal meningitis accounted for 62.3% (n = 7,406), 24.6% (n = 2,928) and 10.1% (n = 1,197) of cases over the four-year period. The overall incidence (cases per 100,000 persons) of cryptococcal meningitis declined by 23% from 24.4 in 2009 to 18.7 in 2012 (p <0.001) and decreased by 19% among HIV-infected persons from 178.2 to 144.7 (p <0.001). Tuberculous meningitis decreased by 40% from 11.3 in 2009 to 6.8 in 2012 (p <0.001) and decreased by 36% among HIV-infected persons from 54.4 to 34.9 (p <0.001). Pneumococcal meningitis decreased by 41% from 4.2 in 2009 to 2.5 in 2012 (p <0.001) and decreased by 38% among HIV-infected persons from 28.0 to 17.5 (p <0.001). Among cases of other bacterial meningitis (248/11,891, 2.1%), Neisseria meningitidis (n = 93), Escherichia coli (n = 72) and Haemophilus influenzae (n = 20) were the most common organisms identified. Conclusions In this high HIV-prevalence province, cryptococcal meningitis was the leading cause of laboratory-confirmed meningitis among adults. Over a 4-year period, there was a significant decrease in incidence of cryptococcal, tuberculous and pneumococcal meningitis. This coincided with expansion of the national

Poor long-term outcomes for cryptococcal meningitis in rural South Africa.

PubMed

Lessells, Richard J; Mutevedzi, Portia C; Heller, Tom; Newell, Marie-Louise

2011-04-01

To explore linkage to and retention in HIV care after an episode of cryptococcal meningitis (CM) in rural South Africa. Design. A retrospective case series of adult individuals (> or = 16 years old) with laboratory-confirmed CM from January - December 2007 at Hlabisa Hospital--a district hospital in northern KwaZulu-Natal. Inpatient mortality and associated risk factors were analysed. The proportion alive and on antiretroviral therapy (ART) at 2 years was determined by linkage to the HIV treatment programme. One hundred and four individuals were identified with laboratory diagnosis of CM; 74/104 (71.2%) with complete records were included in the analysis. Inpatient mortality was high (40.5%) and was significantly associated with reduced conscious level (aHR 3.09, 95% CI 1.30 - 7.33) and absence of headache (aHR 0.33 for headache, 95% CI 0.13 - 0.87). Only 8 individuals (10.8% of all study subjects) were alive and receiving ART 2 years after the CM episode. Long-term outcomes of CM are poor in routine practice. Interventions to strengthen linkage to HIV treatment and care and continuation of secondary fluconazole prophylaxis are critical.

Rapid diagnosis of cryptococcal meningitis by use of lateral flow assay on cerebrospinal fluid samples: influence of the high-dose "hook" effect.

PubMed

Lourens, Adré; Jarvis, Joseph N; Meintjes, Graeme; Samuel, Catherine M

2014-12-01

Cryptococcal meningitis is the most frequent cause of meningitis and a major cause of mortality in HIV-infected adults in Africa. This study evaluated the performance of the lateral flow assay (LFA) on cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcal meningitis against that of existing diagnostic tests. LFA performed on 465 undiluted CSF samples had a sensitivity of 91%. When the LFA was paired with Gram staining, a sensitivity of 100% was achieved after implementation of a dilution step for samples with negative LFA results and the presence of yeasts on microscopy. Microscopy is essential for preventing the reporting of false-negative results due to the high-dose "hook" effect. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Combination Antifungal Therapy for Cryptococcal Meningitis

PubMed Central

Day, Jeremy N.; Chau, Tran T.H.; Wolbers, Marcel; Mai, Pham P.; Dung, Nguyen T.; Mai, Nguyen H.; Phu, Nguyen H.; Nghia, Ho D.; Phong, Nguyen D.; Thai, Cao Q.; Thai, Le H.; Chuong, Ly V.; Sinh, Dinh X.; Duong, Van A.; Hoang, Thu N.; Diep, Pham T.; Campbell, James I.; Sieu, Tran P.M.; Baker, Stephen G.; Chau, Nguyen V.V.; Hien, Tran T.

2014-01-01

BACKGROUND Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. METHODS We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. RESULTS A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P = 0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P = 0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P = 0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P = 0.13). amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although

Diagnostic Performance of a Multiplex PCR assay for meningitis in an HIV-infected population in Uganda

PubMed Central

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; Meya, David B; Boulware, David R

2015-01-01

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: CMV (n=2), VZV (n=2), HHV-6 (n=1), and Streptococcus pneumoniae (n=1). The FilmArray Meningitis/Encephalitis panel offers a promising platform for rapid meningitis diagnosis. PMID:26711635

Evaluation of trypan blue stain in a haemocytometer for rapid detection of cerebrospinal fluid sterility in HIV patients with cryptococcal meningitis.

PubMed

Kwizera, Richard; Akampurira, Andrew; Kandole, Tadeo K; Nielsen, Kirsten; Kambugu, Andrew; Meya, David B; Boulware, David R; Rhein, Joshua

2017-08-22

Quantitative culture is the most common method to determine the fungal burden and sterility of cerebrospinal fluid (CSF) among persons with cryptococcal meningitis. A major drawback of cultures is a long turnaround-time. Recent evidence demonstrates that live and dead Cryptococcus yeasts can be distinguished using trypan blue staining. We hypothesized that trypan blue staining combined with haemocytometer counting may provide a rapid estimation of quantitative culture count and detection of CSF sterility. To test this, we evaluated 194 CSF specimens from 96 HIV-infected participants with cryptococcal meningitis in Kampala, Uganda. Cryptococcal meningitis was diagnosed by CSF cryptococcal antigen (CRAG). We stained CSF with trypan blue and quantified yeasts using a haemocytometer. We compared the haemocytometer readings versus quantitative Cryptococcus CSF cultures. Haemocytometer counting with trypan blue staining had a sensitivity of 98% (64/65), while CSF cultures had a sensitivity of 95% (62/65) with reference to CSF CRAG for diagnostic CSF specimens. For samples that were positive in both tests, the haemocytometer had higher readings compared to culture. For diagnostic specimens, the median of log 10 transformed counts were 5.59 (n = 64, IQR = 5.09 to 6.05) for haemocytometer and 4.98 (n = 62, IQR = 3.75 to 5.79) for culture; while the overall median counts were 5.35 (n = 189, IQR = 4.78-5.84) for haemocytometer and 3.99 (n = 151, IQR = 2.59-5.14) for cultures. The percentage agreement with culture sterility was 2.4% (1/42). Counts among non-sterile follow-up specimens had a median of 5.38 (n = 86, IQR = 4.74 to 6.03) for haemocytometer and 2.89 (n = 89, IQR = 2.11 to 4.38) for culture. At diagnosis, CSF quantitative cultures correlated with haemocytometer counts (R 2  = 0.59, P < 0.001). At 7-14 days, quantitative cultures did not correlate with haemocytometer counts (R 2  = 0.43, P = 0.4). Despite a positive correlation, the

Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial

PubMed Central

Scriven, James E.; Rhein, Joshua; Hullsiek, Katherine Huppler; von Hohenberg, Maximilian; Linder, Grace; Rolfes, Melissa A.; Williams, Darlisha A.; Taseera, Kabanda; Meya, David B.; Meintjes, Graeme; Boulware, David R.

2015-01-01

Introduction. Earlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation (1–2 weeks vs 5 weeks postmeningitis diagnosis). We hypothesized this was due to ART-associated immune pathology, without clinically recognized immune reconstitution inflammatory syndrome. Methods. Three macrophage activation markers and 19 cytokines/chemokines were measured from cryopreserved cerebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial. Comparisons were made between trial arms (early vs deferred) at 1, 8, 14, and 21 days following meningitis diagnosis. Results. More participants with early ART initiation had CSF white cell count (WCC) ≥5/µL at day 14 (58% vs 40%; P = .047), after a median of 6-days ART. Differences were mainly driven by participants with CSF WCC <5/µL at meningitis diagnosis: 28% (10/36) of such persons in the early ART group had CSF WCC ≥5/µL by day 14, compared with 0% (0/27) in the deferred arm (P = .002). Furthermore, Kampala participants (the largest site) receiving early ART had higher day-14 CSF levels of interleukin-13 (P = .04), sCD14 (P = .04), sCD163 (P = .02), and CCL3/MIP-1α (P = .02), suggesting increased macrophage/microglial activation. Conclusions. Early ART initiation in cryptococcal meningitis increased CSF cellular infiltrate, macrophage/microglial activation, and T helper 2 responses within the central nervous system. This suggests that increased mortality from early ART in the COAT trial was immunologically mediated. PMID:25651842

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

Kumari, Sunita; Verma, Rajesh Kumar; Singh, Dharmendra Prasad; Yadav, Ramakant

2016-04-01

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. 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. 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. 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. 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.

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

PubMed

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.

International Collaboration between US and Thailand on a Clinical Trial of Treatment for HIV-associated Cryptococcal Meningitis

PubMed Central

Zimmer, LO; Nolen, TL; Pramanpol, S; Wallace, D; Walker, ME; Pappas, P; Chetchotisakd, P

2010-01-01

Background International clinical trials can provide scientific and logistic benefits in spite of the many challenges. Determining whether a country, especially a developing country, is an appropriate location for the research should include in-country consultation and partnering to assess its social value for the population; that treatments are relevant for the population under study; and that the research infrastructure and ethical oversight are adequate. Collaboration increases the likelihood of study success and helps ensure that benefits accrue to recruited populations and their community. Purpose This paper describes our experiences on a bi-national study and may provide guidance for those planning to engage in future collaborations. Methods A Thai and United States team collaborated to develop and implement a Phase II clinical trial for HIV-associated cryptococcal meningitis to assess safety and tolerability of combination therapy versus standard treatment. Clinical and cultural differences, regulatory hurdles and operational issues were addressed before and during the study to ensure a successful collaboration between the 2 groups. Results The international multicenter study allowed for more rapid enrollment, reduced costs to complete the study, sharing of the benefits of research, greater generalizability of results and capacity building in Thailand; quality metrics in Thailand were equivalent to or better than those in the U.S. Conclusions Conducting successful clinical trials internationally requires early and ongoing collaboration to ensure the study meets sites’ requirements and expectations, conforms to varying national regulations, adheres to data quality standards and is responsive to the health needs of studied populations. PMID:19897055

Brief Report: Geographical Variation in Prevalence of Cryptococcal Antigenemia Among HIV-Infected, Treatment-Naive Patients in Nigeria: A Multicenter Cross-Sectional Study.

PubMed

Ezeanolue, Echezona E; Nwizu, Chidi; Greene, Gregory S; Amusu, Olatilewa; Chukwuka, Chinwe; Ndembi, Nicaise; Smith, Rachel M; Chiller, Tom; Pharr, Jennifer; Kozel, Thomas R

2016-09-01

Worldwide, HIV-associated cryptococcal meningitis affects approximately 1 million persons and causes 600,000 deaths each year mostly in sub-Saharan Africa. Limited data exist on cryptococcal meningitis and antigenemia in Nigeria, and most studies are geographically restricted. We determined the prevalence of cryptococcal antigenemia (CrAg) among HIV-infected, treatment-naive individuals in Nigeria. This was a retrospective, cross-sectional study across 4 geographic regions in Nigeria. We performed CrAg testing using a lateral flow immunoassay on archived whole-blood samples collected from HIV-infected participants at US President's Emergency Plan for AIDS Relief (PEPFAR)-supported sites selected to represent the major geographical and ethnic diversity in Nigeria. Eligible samples were collected from consenting patients (>15 years) naive to antiretroviral therapy with CD4 count less than 200 cells per cubic millimeter and were stored in an -80°C freezer. A total of 2752 stored blood samples were retrospectively screened for CrAg. Most of the samples were from participants aged 30-44 years (57.6%), and 1570 (57.1%) were from women. The prevalence of CrAg positivity in specimens with CD4 <200 cells per cubic millimeter was 2.3% (95% confidence interval: 1.8% to 3.0%) and varied significantly across the 4 regions (P < 0.001). At 4.4% (3.2% to 5.9%), the South East contained the highest prevalence. The significant regional variation in CrAg prevalence found in Nigeria should be taken into consideration as plans are made to integrate routine screening into clinical care for HIV-infected patients.

Geographical Variation in Prevalence of Cryptococcal Antigenemia among HIV-infected Treatment-Naïve Patients in Nigeria: A multicenter cross-sectional study

PubMed Central

Ezeanolue, Echezona E.; Nwizu, Chidi; Greene, Gregory S.; Amusu, Olatilewa; Chukwuka, Chinwe; Ndembi, Nicaise; Smith, Rachel M.; Chiller, Tom; Pharr, Jennifer; Kozel, Thomas R

2016-01-01

Objective Worldwide, HIV-associated cryptococcal meningitis affects approximately 1 million persons and causes 600,000 deaths each year mostly in sub-Sharan Africa. Limited data exist on cryptococcal meningitis and antigenemia in Nigeria, and most studies are geographically restricted. We determined the prevalence of cryptococcal antigenemia (CrAg) among HIV-infected treatment-naïve individuals in Nigeria. Design/Methods This was a retrospective, cross-sectional study across four geographic regions in Nigeria. We performed CrAg testing using a lateral flow immunoassay on archived whole blood samples collected from HIV-infected participants at US PEPFAR-supported sites selected to represent the major geographical and ethnic diversity in Nigeria. Eligible samples were (1) stored in an -80° freezer; (2) collected from consenting patients (>15 years) naïve to antiretroviral therapy with CD4+ count less than 200 cells/mm3. Results A total of 2,752 stored blood samples were retrospectively screened for CrAg. A majority of samples were from participants aged 30 - 44 (57.6%), and 1,570 (57.1%) were from women. The prevalence of CrAg positivity in specimens with CD4 < 200 cells/mm3 was 2.3% (95% CI = 1.8%-3.0%), and varied significantly across the four regions (p < 0.001). At 4.4% (3.2%-5.9%), the South East contained the highest prevalence. Conclusion The significant regional variation in CrAg prevalence found in Nigeria should be taken into consideration as plans are made to integrate routine screening into clinical care for HIV-infected patients. PMID:27144527

Meningitis in HIV-positive patients in sub-Saharan Africa: a review

PubMed Central

Veltman, Jennifer A; Bristow, Claire C; Klausner, Jeffrey D

2014-01-01

Introduction Meningitis is one of the leading causes of death among patients living with HIV in sub-Saharan Africa. There is no widespread tracking of the incidence rates of causative agents among patients living with HIV, yet the aetiologies of meningitis are different than those of the general population. Methods We reviewed the scientific literature published in PubMed to determine the incidence rates of meningitis among hospitalized people living with HIV in sub-Saharan Africa and report our findings from seven studies across sub-Saharan Africa. Results We found high rates of cryptococcal meningitis (19–68%). Tuberculous meningitis was lower (1–36%), although some centres included possible cases as “other” meningitis; therefore, this may not be a true representation of the total cases. Pyogenic meningitis ranged from 6 to 30% and “other” meningitis ranged from 7 to 28% of all reported cases of meningitis. Mortality rates ranged from 25 to 68%. This review describes the most common aetiologies and provides practical diagnostic, treatment and prevention considerations as they apply to the individual living with HIV in sub-Saharan Africa. Conclusions Diagnosis is often limited, and wider availability of accurate and low-cost laboratory diagnostics is desperately needed for prompt diagnosis and initiation of appropriate treatment. Wider acceptance and adoption of available preventative modalities can decrease the incidence of potentially fatal central nervous system infections in African patients living with HIV. PMID:25308903

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%).

Prognostic implications of baseline anaemia and changes in haemoglobin concentrations with amphotericin B therapy for cryptococcal meningitis.

PubMed

Tugume, L; Morawski, B M; Abassi, M; Bahr, N C; Kiggundu, R; Nabeta, H W; Hullsiek, K H; Taseera, K; Musubire, A K; Schutz, C; Muzoora, C; Williams, D A; Rolfes, M A; Meintjes, G; Rhein, J; Meya, D B; Boulware, D R

2017-01-01

Anaemia represents a common toxicity with amphotericin B-based induction therapy in HIV-infected persons with cryptococcal meningitis. We sought to examine the impact of amphotericin-related anaemia on survival. We used data from Ugandan and South African trial participants to characterize the variation of haemoglobin concentrations from diagnosis to 12 weeks post-diagnosis. Anaemia severity was classified based on the haemoglobin concentration at cryptococcal meningitis diagnosis, and nadir haemoglobin values during amphotericin induction. Cox proportional hazard models were used to estimate 2- and 10-week mortality risk. We also estimated 10-week mortality risk among participants with nadir haemoglobin < 8.5 g/dL during amphotericin induction and who survived ≥ 2 weeks post-enrolment. The median haemoglobin concentration at meningitis diagnosis was 11.5 g/dL [interquartile range (IQR) 9.7-13 g/dL; n = 311] with a mean decline of 4.2 g/dL [95% confidence interval (CI) -4.6 to -3.8; P < 0.001; n = 148] from diagnosis to nadir value among participants with baseline haemoglobin ≥ 8.5 g/dL. The median haemoglobin concentration was 8.1 g/dL (IQR 6.5-9.5 g/dL) at 2 weeks, increasing to 9.4 g/dL (IQR 8.2-10.9 g/dL) by 4 weeks and continuing to increase to 12 weeks. Among participants with haemoglobin < 8.5 g/dL at diagnosis, mortality risk was elevated at 2 weeks [hazard ratio (HR) 2.7; 95% CI 1.5-4.9; P < 0.01] and 10 weeks (HR 1.8; 95% CI 1.1-2.2; P = 0.03), relative to those with haemoglobin ≥ 8.5 g/dL. New-onset anaemia occurring with amphotericin therapy did not have a statistically significant association with 10-week mortality (HR 2.0; 95% CI 0.5-9.1; P = 0.4). Amphotericin induced significant haemoglobin declines, which were mostly transient and did not impact 10-week mortality. Individuals with moderate to life-threatening anaemia at baseline had a higher mortality risk at 2 and 10 weeks post-enrolment. © 2016 British HIV Association.

Is it possible to differentiate tuberculous and cryptococcal meningitis in HIV-infected patients using only clinical and basic cerebrospinal fluid characteristics?

PubMed

Vidal, J E; Peixoto de Miranda, E J F; Gerhardt, J; Croda, M; Boulware, D R

2017-01-30

Tuberculous and cryptococcal meningitis (TBM and CM) are the most common causes of opportunistic meningitis in HIVinfected patients from resource-limited settings, and the differential diagnosis is challenging. To compare clinical and basic cerebrospinal fluid (CSF) characteristics between TBM and CM in HIV-infected patients. A retrospective analysis was conducted of clinical, radiological and laboratory records of 108 and 98 HIV-infected patients with culture-proven diagnosis of TBM and CM, respectively. The patients were admitted at a tertiary centre in São Paulo, Brazil. A logistic regression model was used to distinguish TBM from CM and derive a diagnostic index based on the adjusted odds ratio (OR) to differentiate these two diseases. In multivariate analysis, TBM was independently associated with: CSF with neutrophil predominance (odds ratio (OR) 35.81, 95% confidence interval (CI) 3.80 - 341.30, p=0.002), CSF pleocytosis (OR 9.43, 95% CI 1.30 - 68.70, p=0.027), CSF protein >1.0 g/L (OR 5.13, 95% CI 1.38 - 19.04, p=0.032) and Glasgow Coma Scale <15 (OR 3.10, 95% CI 1.03 - 9.34, p=0.044). Nausea and vomiting (OR 0.27, 95% CI 0.08 - 0.90, p=0.033) were associated with CM. Algorithm-related area under the receiver operating characteristics curve was 0.815 (95% CI 0.758 - 0.873, p<0.0001), but an accurate cut-off was not derived. Although some clinical and basic CSF characteristics appear useful in the differential diagnosis of TBM and CM in HIVinfected patients, an accurate algorithm was not identified. Optimised access to rapid, sensitive and specific laboratory tests is essential.

Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: comparison of primer sets for Cryptococcus neoformans and Cryptococcus gattii species complex.

PubMed

Martins, Marilena dos Anjos; Brighente, Kate Bastos Santos; Matos, Terezinha Aparecida de; Vidal, Jose Ernesto; Hipólito, Daise Damaris Carnietto de; Pereira-Chioccola, Vera Lucia

2015-01-01

This study evaluated the use of polymerase chain reaction for cryptococcal meningitis diagnosis in clinical samples. The sensitivity and specificity of the methodology were evaluated using eight Cryptococcus neoformans/C. gattii species complex reference strains and 165 cerebrospinal fluid samples from patients with neurological diseases divided into two groups: 96 patients with cryptococcal meningitis and AIDS; and 69 patients with other neurological opportunistic diseases (CRL/AIDS). Two primer sets were tested (CN4-CN5 and the multiplex CNa70S-CNa70A/CNb49S-CNb-49A that amplify a specific product for C. neoformans and another for C. gattii). CN4-CN5 primer set was positive in all Cryptococcus standard strains and in 94.8% in DNA samples from cryptococcal meningitis and AIDS group. With the multiplex, no 448-bp product of C. gattii was observed in the clinical samples of either group. The 695bp products of C. neoformans were observed only in 64.6% of the cryptococcal meningitis and AIDS group. This primer set was negative for two standard strains. The specificity based on the negative samples from the CTL/AIDS group was 98.5% in both primer sets. These data suggest that the CN4/CN5 primer set was highly sensitive for the identification of C. neoformans/C. gattii species complex in cerebrospinal fluid samples from patients with clinical suspicion of cryptococcal meningitis. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia

PubMed Central

Ganiem, A. Rizal; Dian, Sofiati; Indriati, Agnes; Chaidir, Lidya; Wisaksana, Rudi; Sturm, Patrick; Melchers, Willem; van der Ven, Andre; Parwati, Ida; van Crevel, Reinout

2013-01-01

Background HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis. Methodology/Principal Findings We performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia. Neuroradiology was only available for 6 patients. At time of presentation, patients mostly had newly diagnosed and advanced HIV infection (median CD4 count 22 cells/mL), with only 17.2% taking ART, and 9.4% PJP-prophylaxis. CSF PCR for T. Gondii was positive in 21 patients (32.8%). Circulating toxoplasma IgG was present in 77.2% of patients tested, including all in whom the PCR of CSF was positive for T. Gondii. Clinically, in the absence of neuroradiology, toxoplasmosis was difficult to distinguish from tuberculosis or cryptococcal meningitis, although CSF abnormalities were less pronounced. Mortality among patients with a positive CSF T. Gondii PCR was 81%, 2.16-fold higher (95% CI 1.04–4.47) compared to those with a negative PCR. Conclusions/Significance Toxoplasmosis should be considered in HIV-infected patients with clinically suspected subacute meningitis in settings where neuroradiology is not available. PMID:23326616

Monocyte Phenotype and IFN-γ-Inducible Cytokine Responses Are Associated with Cryptococcal Immune Reconstitution Inflammatory Syndrome

PubMed Central

Meya, David B.; Okurut, Samuel; Zziwa, Godfrey; Cose, Stephen; Bohjanen, Paul R.; Mayanja-Kizza, Harriet; Joloba, Moses; Boulware, David R.; Yukari Manabe, Carol; Wahl, Sharon; Janoff, Edward N.

2017-01-01

A third of adults with AIDS and cryptococcal meningitis (CM) develop immune reconstitution inflammatory syndrome (IRIS) after initiating antiretroviral therapy (ART), which is thought to result from exaggerated inflammatory antigen-specific T cell responses. The contribution of monocytes to the immunopathogenesis of cryptococcal IRIS remains unclear. We compared monocyte subset frequencies and immune responses in HIV-infected Ugandans at time of CM diagnosis (IRIS-Baseline) for those who later developed CM-IRIS, controls who did not develop CM-IRIS (Control-Baseline) at CM-IRIS (IRIS-Event), and for controls at a time point matched for ART duration (Control-Event) to understand the association of monocyte distribution and immune responses with cryptococcal IRIS. At baseline, stimulation with IFN-γ ex vivo induced a higher frequency of TNF-α- and IL-6-producing monocytes among those who later developed IRIS. Among participants who developed IRIS, ex vivo IFN-γ stimulation induced higher frequencies of activated monocytes, IL-6+, TNF-α+ classical, and IL-6+ intermediate monocytes compared with controls. In conclusion, we have demonstrated that monocyte subset phenotype and cytokine responses prior to ART are associated with and may be predictive of CM-IRIS. Larger studies to further delineate innate immunological responses and the efficacy of immunomodulatory therapies during cryptococcal IRIS are warranted. PMID:29371546

Looking for fungi in all the right places: screening for cryptococcal disease and other AIDS-related mycoses among patients with advanced HIV disease.

PubMed

Greene, Greg; Sriruttan, Charlotte; Le, Thuy; Chiller, Tom; Govender, Nelesh P

2017-03-01

As HIV treatment programmes scale up to meet the UNAIDS 90-90-90 goals, care must be taken to start antiretroviral treatment safely in patients with advanced disease (CD4 counts <200 cells/μl) who are simultaneously at risk for opportunistic infections and immune reconstitution inflammatory syndrome. Invasive fungal diseases pose a great threat at this critical time point, though the development of inexpensive and highly accurate rapid diagnostic tests has changed the approach HIV programmes are taking to reduce the high mortality associated with these opportunistic infections. This article summarizes recent advances and findings in fungal opportunistic infection diagnostics with a focus on screening to prevent cryptococcal meningitis. Cryptococcal antigen (CrAg) screening using a lateral flow assay platform is cost-effective and feasible to implement as either a laboratory reflex or point-of-care test. Recent CrAg screening pilots have elucidated the varying prevalence of cryptococcal antigenemia across geographic regions, which may aid programme planning. Evidence from recently completed clinical trials provides a strong motivation for the use of CrAg titer to refine treatment options for patients with subclinical cryptococcal disease. Although several operational barriers to programme effectiveness still need to be addressed, the utility of CrAg screening using inexpensive and accurate antigen assays has been demonstrated in real-world HIV programmes, paving the way for development and testing of other fungal opportunistic infection screening strategies and for an integrated advanced HIV disease testing package to reduce AIDS mortality and ensure safe antiretroviral treatment initiation.

Evaluation of screening and treatment of cryptococcal antigenaemia among HIV-infected persons in Soweto, South Africa.

PubMed

Govender, N P; Roy, M; Mendes, J F; Zulu, T G; Chiller, T M; Karstaedt, A S

2015-09-01

We retrospectively evaluated clinic-based screening to determine the prevalence of cryptococcal antigenaemia and management and outcome of patients with antigenaemia. Cryptococcal antigen (CrAg) screening of HIV-infected adults who attended the HIV clinic at Chris Hani Baragwanath Hospital was conducted over 19 months. Data collected from CrAg-positive patients included CD4 T-lymphocyte count at screening, prior or subsequent cryptococcal meningitis (CM), antifungal and antiretroviral treatment and outcome after at least 8 months. Of 1460 patients with no prior CM, 30 (2.1%) had a positive CrAg test. The prevalence of antigenaemia among patients with a CD4 count < 100 cells/μl and no prior CM was 2.8% (20 of 708). Of 29 evaluable CrAg-positive patients with no prior CM, 14 (48%) did not return for post-screening follow-up. Of these 14, five developed CM and one (7%) was known to be alive at follow-up. Of 15 patients who returned for follow-up, two already had evidence of nonmeningeal cryptococcosis. Overall, 11 received fluconazole, one did not and fluconazole treatment was unknown for three. Among these 15, one developed CM and 10 (67%) were known to be alive at follow-up. Overall, 18 (62%) of 29 CrAg-positive patients died or were lost to follow-up. Seven (0.5%) of 1430 CrAg-negative patients developed CM a median of 83 days post-screening (range 34 to 219 days). Loss to follow-up is the major operational issue relevant to scale-up of screen-and-treat. Patient outcomes may be improved by rapid access to CrAg results and focus on linkage to and retention in HIV care. © 2015 British HIV Association.

Meningitis - cryptococcal

MedlinePlus

... Other tests that may be done include: Blood culture Chest x-ray Cryptococcal antigen in CSF or ... the head Gram stain, other special stains, and culture of CSF Treatment Antifungal medicines are used to ...

Effect of severity of meningitis on fungicidal activity of flucytosine combined with fluconazole in a murine model of cryptococcal meningitis.

PubMed Central

Ding, J C; Bauer, M; Diamond, D M; Leal, M A; Johnson, D; Williams, B K; Thomas, A M; Najvar, L; Graybill, J R; Larsen, R A

1997-01-01

We studied the effect of the severity of meningitis on the response to therapy with fluconazole and flucytosine in a murine model of cryptococcal meningitis. Meningitis was established by intracerebral injection of Cryptococcus neoformans. The severity of meningitis was varied by delaying the onset of treatment from 3 to 7 days. Animals were sacrificed after 14 days of treatment, and the numbers of C. neoformans per gram of brain tissue were quantified. The range of effective dose combinations of fluconazole and flucytosine became progressively reduced as the severity of meningitis increased. The magnitude of treatment effect, as measured by the numbers of CFU/gram of brain tissue, was also reduced with increasing severity of meningitis. In this model, as the severity of meningitis increases, higher doses of fluconazole are required to achieve equivalent levels of activity. The combination of fluconazole and flucytosine appears to have the most-potent antifungal effects. This is most readily observed in animals with more-severe meningitis. PMID:9210691

Cryptococcal meningitis with secondary cutaneous involvement in an immunocompetent host.

PubMed

Tabassum, Saadia; Rahman, Atiya; Herekar, Fivzia; Masood, Sadia

2013-09-16

Cryptococcosis is a potentially fatal fungal disease caused by variants of Cryptococcus neoformans species.  The respiratory tract is the usual portal of entry, with a peculiar predilection to invade the central nervous system.  The skin can be secondarily involved in disseminated infection or be exceptionally involved as primary cutaneous infection by inoculation.  The disease is mostly seen in immunodeficiency states.  The diagnosis is frequently unsuspected in immunocompetent patients. We report a case of disseminated cryptococcal meningitis in an immunocompetent young adult. The cutaneous eruption prompted the accurate diagnosis.  The patient, a 20-year-old female, had fever, cough, headache and intractable vomiting for the past two months and was being managed as a case of tuberculous meningitis. Two weeks after starting antituberculous treatment she developed umbilicated papules on the head and neck region. Necessary laboratory workup identified C. neoformans in cerebrospinal fluid (CSF) and skin specimens.  The titers of cryptococcal antigen were measured in CSF and serum for diagnostic and prognostic purposes.  Anti-fungal treatment resulted in regression of the cutaneous lesions and resolution of systemic complaints. The case highlights the need for high degree of suspicion, especially in healthy young adults, in the diagnosis of cryptococcosis. The cutaneous eruptions can be the first manifestation or a diagnostic clue of enormous significance.

Neurological Sequelae of Adult Meningitis in Africa: A Systematic Literature Review

PubMed Central

Goldberg, Drew W; Mitchell, Hannah K; Jarvis, Joseph N

2018-01-01

Abstract The high human immunodeficiency virus (HIV) prevalence in sub-Saharan Africa has markedly changed the epidemiology and presentation of adult meningitis. We conducted a systematic review using PubMed, Embase, Ovid, CENTRAL, and African Index Medicus to identify studies in Africa with data on neurological outcomes in adults after meningitis. We found 22 articles meeting inclusion criteria. From 4 studies with predominately pneumococcal meningitis, a median of 19% of survivors experienced hearing loss up to 40 days. Two studies of cryptococcal meningitis evaluated 6- to 12-month outcomes; in one, 41% of survivors had global neurocognitive impairment and 20% severe impairment at 1 year, and in a second 30% of survivors had intermediate disability and 10% severe disability at 6 months. A single small study of patients with tuberculosis/HIV found marked disability in 20% (6 of 30) at 9 months. Despite the high burden of meningitis in sub-Saharan Africa, little is known about neurological outcomes of patients with HIV-associated meningitides. PMID:29322063

Compartmentalisation of innate immune responses in the central nervous system during cryptococcal meningitis/HIV co-infection

PubMed Central

NARANBHAI, Vivek; CHANG, Christina C.; DURGIAH, Raveshni; OMARJEE, Saleha; LIM, Andrew; MOOSA, Mahomed-Yunus S.; ELLIOT, Julian H.; NDUNG’U, Thumbi; LEWIN, Sharon R.; FRENCH, Martyn A.; CARR, William H.

2014-01-01

Objective The role of innate immunity in pathogenesis of cryptococcal meningitis (CM) is unclear. We hypothesised that NK cell and monocyte responses are central nervous system (CNS) compartmentalised, and altered by anti-fungal therapy and combination antiretroviral therapy (cART) during CM/HIV co-infection. Design Sub-study of a prospective cohort study of adults with CM/HIV co-infection in Durban, South Africa. Methods We used multi-parametric flow cytometry to study compartmentalisation of subsets, activation (CD69pos), CXCR3 and CX3CR1 expression and cytokine secretion of NK cells and monocytes in freshly collected blood and cerebrospinal fluid (CSF) at diagnosis (n=23), completion of anti-fungal therapy induction (n=19) and after a further 4 weeks of cART (n=9). Results Relative to blood, CSF was enriched with CD56bright (immunoregulatory) NK cells (p=0.0004). At enrolment, CXCR3 expression was more frequent amongst blood CD56bright than either blood CD56dim (p<0.0001) or CSF CD56bright (p=0.0002) NK cells. Anti-fungal therapy diminished blood (p<0.05) but not CSF CXCR3pos NK cell proportions nor CX3CR1pos NK cell proportions. CD56bright and CD56dim NK cells were more activated in CSF than blood (p<0.0001). Anti-fungal therapy induction reduced CD56dim NK cell activation in CSF (p=0.02). Activation of blood CD56bright and CD56dim NK cells was diminished following cART commencement (p<0.0001, p=0.03). Immunoregulatory NK cells in CSF tended to secrete higher levels of CXCL10 (p=0.06) and lower levels of TNF-α (p=0.06) than blood immunoregulatory NK cells. CSF was enriched with non-classical monocytes (p=0.001), but anti-fungal therapy restored proportions of classical monocytes (p=0.007). Conclusions These results highlight CNS activation, trafficking and function of NK cells and monocytes in CM/HIV and implicate immunoregulatory NK cells and pro-inflammatory monocytes as potential modulators of CM pathogenesis during HIV co-infection. PMID:24451162

Cerebro-meningeal infections in HIV-infected patients: a study of 116 cases in Libreville, Gabon.

PubMed

Ondounda, Magloire; Ilozue, Chinenye; Magne, Caroline

2016-06-01

Cerebro-meningeal pathology is common in human immunodeficiency virus (HIV) infection and the aetiology is often difficult to ascertain with certainty. To describe the major suspected and identified causes of meningeal or encephalitic syndromes in HIV infection in Libreville, Gabon. A descriptive study using clinical records of patients hospitalised in the Department of Medicine in the Military Hospital of Libreville (Gabon) between January 2006 and May 2010. Clinical features were evaluated using multivariable logistic regression to evaluate association with the outcome of a clinical improvement or death. The most frequent neurological symptoms were reduced level of consciousness (54.3%), headache (55.2%), motor deficit (38.7%), and convulsions (36.2%). Cerebral toxoplasmosis represented 64.7% of diagnoses, followed by cryptococcal neuromeningitis in 12.9% of cases. Tuberculoma was diagnosed in 4 cases and lymphoma in 2 cases. In 9.5% of cases, no aetiology was determined. Toxoplasmosis treatment led to clinical improvement in 69.3% of cases with suspected cerebral toxoplasmosis. Overall mortality was 39.7%. The diagnosis of neurological conditions in HIV positive patients is difficult, particularly in a low-resource setting. A trial of treatment for toxoplasmosis should be initiated first line with all signs of neurological pathology in a patient infected with HIV.

Immunology of Cryptococcal Infections: Developing a Rational Approach to Patient Therapy

PubMed Central

Elsegeiny, Waleed; Marr, Kieren A.; Williamson, Peter R.

2018-01-01

Cryptococcal meningoencephalitis is responsible for upwards of 15% of HIV-related deaths worldwide and is currently the most common cause of non-viral meningitis in the US, affecting both previously healthy and people with immune suppression caused by cancer chemotherapy, transplantation, and biologic therapies. Despite a continued 30–50% attributable mortality, recommended therapeutic strategies have remained largely unchanged since the 1950s. Recent murine models and human studies examining the role of the immune system in both susceptibility to the infection as well as host damage have begun to influence patient care decisions. The Damage Framework Response, originally proposed in 1999, was recently used to discuss dichotomous etiologies of host damage in cryptococcal disease. These include patients suffering microbiological damage with low host immunity (especially those immunosuppressed with HIV) and those having low (live) microbiological burden but high immune-mediated damage (HIV-related immune reconstitution syndrome and non-HIV-related postinfectious inflammatory response syndrome). Cryptococcal disease in previously healthy hosts, albeit rare, has been known for a long time. Immunophenotyping and dendritic cell-T cell signaling studies on cerebral spinal fluid of these rare patients reveal immune capacity for recognition and T-cell activation pathways including increased levels of HLA-DR and CD56. However, despite effective T-cell signals, brain biopsy and autopsy specimens demonstrated an M2 alternative macrophage polarization and poor phagocytosis of fungal cells. These studies expand the paradigm for cryptococcal disease susceptibility to include a prominent role for immune-mediated damage and suggest a need for careful individual consideration of immune activation during therapy of cryptococcal disease in diverse hosts. PMID:29670625

Immunology of Cryptococcal Infections: Developing a Rational Approach to Patient Therapy.

PubMed

Elsegeiny, Waleed; Marr, Kieren A; Williamson, Peter R

2018-01-01

Cryptococcal meningoencephalitis is responsible for upwards of 15% of HIV-related deaths worldwide and is currently the most common cause of non-viral meningitis in the US, affecting both previously healthy and people with immune suppression caused by cancer chemotherapy, transplantation, and biologic therapies. Despite a continued 30-50% attributable mortality, recommended therapeutic strategies have remained largely unchanged since the 1950s. Recent murine models and human studies examining the role of the immune system in both susceptibility to the infection as well as host damage have begun to influence patient care decisions. The Damage Framework Response, originally proposed in 1999, was recently used to discuss dichotomous etiologies of host damage in cryptococcal disease. These include patients suffering microbiological damage with low host immunity (especially those immunosuppressed with HIV) and those having low (live) microbiological burden but high immune-mediated damage (HIV-related immune reconstitution syndrome and non-HIV-related postinfectious inflammatory response syndrome). Cryptococcal disease in previously healthy hosts, albeit rare, has been known for a long time. Immunophenotyping and dendritic cell-T cell signaling studies on cerebral spinal fluid of these rare patients reveal immune capacity for recognition and T-cell activation pathways including increased levels of HLA-DR and CD56. However, despite effective T-cell signals, brain biopsy and autopsy specimens demonstrated an M2 alternative macrophage polarization and poor phagocytosis of fungal cells. These studies expand the paradigm for cryptococcal disease susceptibility to include a prominent role for immune-mediated damage and suggest a need for careful individual consideration of immune activation during therapy of cryptococcal disease in diverse hosts.

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

PubMed

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

2016-01-01

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. 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. 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. 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.

Neurological complication in HIV patients

NASA Astrophysics Data System (ADS)

Ritarwan, K.

2018-03-01

Human Immunodeficiency Virus (HIV) is neurotropic and immunotropic, making themassive destruction of both systems. Although their amount has been reduced, there is still neurological presentations and complications of HIV remain common in the era of combination antiretroviral therapy (cART). Neurological opportunistic infections (OI) occur in advanced HIV diseases such as primary cerebral lymphoma, cryptococcal meningitis, cerebral toxoplasmosis, and progressive multifocal encephalopathy. Neurological problem directly related to HIV appear at any stage in the progress of HIV disease, from AIDS-associated dementia to the aseptic meningitis of primary HIV infection observed in subjects with an immune deficiency. The replication of peripheral HIV viral is able to be controlled in the era of effective antiretroviral therapy. Non-HIV-related neurological disease such as stroke increased important as the HIV population ages.

Screening for Cryptococcal Antigenaemia in Patients Accessing an Antiretroviral Treatment Program in South Africa

PubMed Central

Jarvis, Joseph N; Lawn, Stephen D; Vogt, Monica; Bangani, Nonzwakazi; Wood, Robin; Harrison, Thomas S

2009-01-01

Background Cryptococcal meningitis is a leading cause of death in AIDS patients and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. Screening for cryptococcal antigen (CRAG) in patients enrolling in ART programs may identify those at risk of cryptococcal meningitis and permit targeted use of pre-emptive therapy. Methods In this retrospective study, CRAG was measured in stored plasma samples obtained from patients as they enrolled in a well characterised ART cohort in South Africa. The predictive value of screening for CRAG prior to ART for development of microbiologically confirmed cryptococcal meningitis or death during the first year of follow-up was determined. Results Of 707 participants with a baseline median CD4 count of 97 (IQR 46-157) cells/μL, 46 (7%) had a positive CRAG. Antigenaemia was 100% sensitive for predicting development of cryptococcal meningitis during the first year of ART and in multivariate analysis was an independent predictor of mortality (AHR 3.2, 95%CI 1.5-6.6). Most (92%) cases of cryptococcal meningitis developed in patients with a CD4 count ≤100 cells/μL. In this sub-set of patients, a CRAG titre ≥1 in 8 was 100% sensitive and 96% specific for predicting incident cryptococcal meningitis during the first year of ART in those with no previous history of the disease. Conclusions CRAG screening prior to commencing ART in patients with a CD4 count ≤100 cells/μL is highly effective at identifying those at risk of cryptococcal meningitis and death and might permit implementation of a targeted pre-emptive treatment strategy. PMID:19222372

Integrated therapy for HIV and cryptococcosis.

PubMed

Srichatrapimuk, Sirawat; Sungkanuparph, Somnuek

2016-11-29

Cryptococcosis has been one of the most common opportunistic infections and causes of mortality among HIV-infected patients, especially in resource-limited countries. Cryptococcal meningitis is the most common form of cryptococcosis. Laboratory diagnosis of cryptococcosis includes direct microscopic examination, isolation of Cryptococcus from a clinical specimen, and detection of cryptococcal antigen. Without appropriate treatment, cryptococcosis is fatal. Early diagnosis and treatment is the key to treatment success. Treatment of cryptococcosis consists of three main aspects: antifungal therapy, intracranial pressure management for cryptococcal meningitis, and restoration of immune function with antiretroviral therapy (ART). Optimal integration of these three aspects is crucial to achieving successful treatment and reducing the mortality. Antifungal therapy consists of three phases: induction, consolidation, and maintenance. A combination of two drugs, i.e. amphotericin B plus flucytosine or fluconazole, is preferred in the induction phase. Fluconazole monotherapy is recommended during consolidation and maintenance phases. In cryptococcal meningitis, intracranial pressure rises along with CSF fungal burden and is associated with morbidity and mortality. Aggressive control of intracranial pressure should be done. Management options include therapeutic lumbar puncture, lumbar drain insertion, ventriculostomy, or ventriculoperitoneal shunt. Medical treatment such as corticosteroids, mannitol, and acetazolamide are ineffective and should not be used. ART has proven to have a great impact on survival rates among HIV-infected patients with cryptococcosis. The time to start ART in HIV-infected patients with cryptococcosis has to be deferred until 5 weeks after the start of antifungal therapy. In general, any effective ART regimen is acceptable. Potential drug interactions between antiretroviral agents and amphotericin B, flucytosine, and fluconazole are minimal. Of most

Effect of fluconazole on fungicidal activity of flucytosine in murine cryptococcal meningitis.

PubMed Central

Larsen, R A; Bauer, M; Weiner, J M; Diamond, D M; Leal, M E; Ding, J C; Rinaldi, M G; Graybill, J R

1996-01-01

Both animal and in vitro studies have demonstrated that combinations of flucytosine with amphotericin B and with fluconazole have significantly improved activity against cryptococcal meningitis compared with the activity of each drug used alone. However, very few dose levels of these agents have been tested in combination. This study evaluated the efficacy of fluconazole plus flucytosine in a murine model of cryptococcal meningitis over a broad range of dose combinations (fluconazole, 0 to 40 micrograms/g of body weight per day; flucytosine, 0 to 200 micrograms/g/day). Both drugs were dissolved in drinking water, with treatment on days 2 to 11. In this highly reproducible model, fluconazole had a dramatic effect on the fungicidal activity of flucytosine. Flucytosine at dose levels of as much as 200 micrograms/g/day alone or in combination with low doses of fluconazole had minimal fungicidal activity, whereas in combination with fluconazole at 24 to 40 micrograms/g/day, flucytosine showed fungicidal activity in the range of 45 to 65% of the animals treated at doses of 40 to 100 micrograms/g/day. This striking effect of fluconazole is consistent with the results of both in vitro and clinical studies. In the clinic, the use of flucytosine is often limited by severe toxicity, while toxicity is rarely observed with fluconazole. These results suggest that when flucytosine is given with higher doses of fluconazole, the maximum therapeutic effect of the former in the clinic may be observed at dose levels that are far less than the doses commonly employed (150 micrograms/g daily). PMID:8878602

Cryptococcal cerebellitis in no-VIH patient.

PubMed

Lasso, Fabricio Andres; Zamora Bastidas, Tomas Omar; Potosí García, Jorge Andrés; Díaz Idrobo, Bairon

2017-06-30

Cryptococcosis is an opportunistic fungal infection whose etiology is Cryptococcus neofromans / C. gattii, complex which affects immunocompromised patients mainly. Meningeal infection is one of the most common presentations, but cerebellar affection is rare. Male patient with 65 old years, from an area of subtropical climate with chronic exposure to poultry, without pathological antecedents, who presented clinical picture consistent with headache, fever, seizures and altered mental status. Initially without menigeal signs or intracranial hypertension and normal neurological examination. Later, the patient developed ataxia, dysdiadochokinesia and limb loss. By lumbar punction and image of nuclear magnetic resonance (NMR) cerebellitis cryptococcal was diagnosticated. Antifungal therapy with amphotericin B and fluconazole was performed, however the patient died. The cryptococcosis has different presentations, it´s a disease whose incidence has been increasing since the advent of the HIV / AIDS pandemy, however the commitment of the encephalic parenchyma and in particular the cerebellum is considered rare. In this way we are facing the first case of cryptococcal cerebellitis in our midst.

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

Cryptococcal cerebellitis in no-VIH patient

PubMed Central

Zamora Bastidas, Tomas Omar; Potosí García, Jorge Andrés; Díaz Idrobo, Bairon

2017-01-01

Abstract Introduction: Cryptococcosis is an opportunistic fungal infection whose etiology is Cryptococcus neofromans / C. gattii, complex which affects immunocompromised patients mainly. Meningeal infection is one of the most common presentations, but cerebellar affection is rare. Case Description: Male patient with 65 old years, from an area of subtropical climate with chronic exposure to poultry, without pathological antecedents, who presented clinical picture consistent with headache, fever, seizures and altered mental status. Clinical findings and diagnostic methods: Initially without menigeal signs or intracranial hypertension and normal neurological examination. Later, the patient developed ataxia, dysdiadochokinesia and limb loss. By lumbar punction and image of nuclear magnetic resonance (NMR) cerebellitis cryptococcal was diagnosticated. Treatment: Antifungal therapy with amphotericin B and fluconazole was performed, however the patient died. Clinical Relevance: The cryptococcosis has different presentations, it´s a disease whose incidence has been increasing since the advent of the HIV / AIDS pandemy, however the commitment of the encephalic parenchyma and in particular the cerebellum is considered rare. In this way we are facing the first case of cryptococcal cerebellitis in our midst. PMID:29021643

HTLV-III: Intra-BBB IgG Synthesis and Hybridization in CSF Cells

DTIC Science & Technology

1988-02-08

toxoplasmosis , and 3 had cryptococcal meningitis. All patients had known risk factors for HIV infection: 44 were homosexual and 8 were intravenous drug abusers...disease caused by detectable CNS opportunistic pathogens, cryptococcal meningitis, and cerebral toxoplasmosis . In six instances of AIDS-associated dementia

Think fungus NOT just a crypto-meningitis in AIDS!

PubMed

Badiye, Amit; Patnaik, Mrinal; Deshpande, Alaka; Rajendran, C; Chandrashekara, K V

2012-12-01

Extrapulmonary cryptococcosis has been defined as AIDS defining illness in HIV infected people. Cryptococcal meningitis is the commonest meningitis with advanced immune deficiency. Therefore clinicians ask for tests only for detection of cryptococci which may be misleading. A prospective study of suspected fungal meningitis with CSF fungal culture is carried out. 70 ART naive cases of suspected fungal meningitis in HIV cases were subjected to CSF cytochemistry, smear exam and CSF fungal culture. The CSF culture was positive in 75.6% cases of these 21 were C. Neoformans as against 28 of Rhodotorula. In addition candida, aspergillus, geotrichum, trichosporon were isolated. Apart from c. neoformans, other fungi also cause meningitis. Each case of suspected fungal meningitis, may be subjected for CSF fungal culture for proper and adequate management. If facility for fungal culture is not available and if CSF smear shows evidence of fungal infection then standard therapy with Amphotericin may be instituted earlier to reduce mortality. This is the largest series isolating Rhodotorula from CSF in AIDS patients.

Cryptococcal infections over a 15 year period at a tertiary facility & impact of guideline management.

PubMed

Gassiep, Ian; Douglas, Joel; Emeto, Theophilus I; Crawley, Katherine; Playford, Elliott G

2018-04-17

Cryptococcosis is an invasive fungal infection caused primarily by Cryptococcus neoformans and Cryptococcus gattii species, presenting predominantly as meningoencephalitis. The aim of this study is to assess all cryptococcal infections managed at our facility from 2001-2015 to determine incidence, risk factors, and comparison of outcomes prior to and following introduction of the 2010 Infectious Disease Society of America (IDSA) guidelines. Retrospective analysis of all patients diagnosed and treated for cryptococcal infection occurring between January 2001 and December 2015. Of 102 patients diagnosed with cryptococcal infection, 97 were eligible for study inclusion. There appears to be an overall increased incidence of cryptococcosis in both transplant and non-transplant cohorts with a peak in 2015 of 6 transplant and 13 non-transplant cases. In the meningitis cohort, 38/52 (73%) of identified isolates were C. neoformans, and 14/52 (27%) were C. gattii. Notably, 14/14 (100%) of C. gattii isolates were associated with meningitis, as compared to only 38/64 (59%) C. neoformans associated with meningitis (p: 0.003). It appears that patients presenting with cough are less likely to have meningitis, 17/27 (63%), (p: 0.005). When stratifying for culture positive meningitis lumbar puncture opening pressure, the median in the culture positive cohort was 31.5 cmH2O compared with 15.5 cmH2O (p: 0.036).Multiple admissions were required prior to diagnosis in the majority of cases with only 18/72 (25%) diagnosed on 1st presentation. Post-guideline mortality has improved from 15% to 6.1% (p: 0.046). Cryptococcal infection remains relatively uncommon, but there appears to be an increasing trend in incidence. Overall mortality is relatively low and has improved since introduction of the 2010 IDSA guidelines. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Managing Advanced HIV Disease in a Public Health Approach

PubMed Central

Ford, Nathan; Meintjes, Graeme; Calmy, Alexandra; Bygrave, Helen; Migone, Chantal; Vitoria, Marco; Penazzato, Martina; Vojnov, Lara; Doherty, Meg; Asero, Patricia; Bologna, Rosa; Chakroun, Mohamed; Chambal, Lucia; Chiller, Tom; Conradie, Francesca; Eholie, Serge; Frigati, Lisa; Gibb, Diana; Goemaere, Eric; Govender, Nelesh; Grant, Alison; Kumarasamy, Nagalingeswaran; Lalloo, David; Le, Thuy; Letang, Emilio; Mbori-Ngacha, Dorothy; Mfinanga, Sayoki; Nacher, Mathieu; Ribakare, Muhayimpundu; Siegfried, Nandi; Sikwese, Kenly; Tun, Nini; Vidal, Jose E

2018-01-01

Abstract In 2017, the World Health Organization (WHO) published guidelines for the management of advanced human immunodeficiency virus (HIV) disease within a public health approach. Recent data suggest that more than a third of people starting antiretroviral therapy (ART) do so with advanced HIV disease, and an increasing number of patients re-present to care at an advanced stage of HIV disease following a period of disengagement from care. These guidelines recommend a standardized package of care for adults, adolescents, and children, based on the leading causes of morbidity and mortality: tuberculosis, severe bacterial infections, cryptococcal meningitis, toxoplasmosis, and Pneumocystis jirovecii pneumonia. A package of targeted interventions to reduce mortality and morbidity was recommended, based on results of 2 recent randomized trials that both showed a mortality reduction associated with delivery of a simplified intervention package. Taking these results and existing recommendations into consideration, WHO recommends that a package of care be offered to those presenting with advanced HIV disease; depending on age and CD4 cell count, the package may include opportunistic infection screening and prophylaxis, including fluconazole preemptive therapy for those who are cryptococcal antigen positive and without evidence of meningitis. Rapid ART initiation and intensified adherence interventions should also be proposed to everyone presenting with advanced HIV disease. PMID:29514232

Managing Advanced HIV Disease in a Public Health Approach.

PubMed

Ford, Nathan; Meintjes, Graeme; Calmy, Alexandra; Bygrave, Helen; Migone, Chantal; Vitoria, Marco; Penazzato, Martina; Vojnov, Lara; Doherty, Meg

2018-03-04

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

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

Bacterial meningitis in patients with HIV: A population-based prospective study.

PubMed

van Veen, Kiril E B; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

2016-03-01

We studied occurrence, disease course, and prognosis of community-acquired bacterial meningitis in HIV-infected adults in the Netherlands. We performed a nationwide, prospective cohort study. Patients over 16 years old with bacterial meningitis were included. Data on patient history, symptoms and signs on admission, laboratory findings, radiologic examination, treatment, and outcome were collected prospectively. For HIV-positive patients additional information was collected retrospectively. From March 2006 to December 2013, 1354 episodes of community-acquired meningitis were included in the cohort. Thirteen patients were HIV-infected (1.0%). The annual incidence of bacterial meningitis was 8.3-fold higher (95%CI 4.6-15.1, P < 0.001) among HIV-infected patients as compared to the general population (10.79 [95%CI 5.97-19.48] vs 1.29 [95%CI 1.22-1.37] per 100.000 patients per year). Predisposing factors (other than HIV), clinical symptoms and signs, ancillary investigations, causative organisms and outcome were comparable between HIV-infected and patients without HIV infection. HIV-infected patients in the Netherlands have a 8.3-fold higher risk for bacterial meningitis as compared to the general population despite cART therapy. Clinical presentation and outcome of patients with acute bacterial meningitis with and without HIV are similar. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The pattern and predictors of mortality of HIV/AIDS patients with neurologic manifestation in Ethiopia: a retrospective study

PubMed Central

2012-01-01

Background Even though the prevalence of HIV infection among the adult population in Ethiopia was estimated to be 2.2% in 2008, the studies on the pattern of neurological manifestations are rare. The aim of this retrospective study was to assess the pattern and predictors of mortality of HIV/AIDS patients with neurologic manifestations. Methods Medical records of 347 patients (age ≥13 years) admitted to Tikur Anbesa Hospital from September 2002 to August 2009 were reviewed and demographic and clinical data were collected. Results Data from 347 patients were analysed. The mean age was 34.6 years. The diagnosis of HIV was made before current admission in 33.7% and 15.6% were on antiretroviral therapy (ART). Causes of neurological manifestation were: cerebral toxoplasmosis (36.6%), tuberculous meningitis (22.5%), cryptococcal meningitis (22.2%) and bacterial meningitis (6.9%). HIV-encephalopathy, primary central nervous system (CNS) lymphoma and progressive multifocal leukoencephalopathy were rare in our patients. CD4 count was done in 64.6% and 89.7% had count below 200/mm3[mean = 95.8, median = 57] and 95.7% were stage IV. Neuroimaging was done in 38% and 56.8% had mass lesion. The overall mortality was 45% and the case-fatality rates were: tuberculous meningitis (53.8%), cryptococcal meningitis (48.1%), cerebral toxoplasmosiss (44.1%) and bacterial meningitis (33.3%). Change in sensorium and seizure were predictors of mortality. Conclusions CNS opportunistic infections were the major causes of neurological manifestations of HIV/AIDS and were associated with high mortality and morbidity. Almost all patients had advanced HIV disease at presentation. Early diagnosis of HIV, prophylaxis and treatment of opportunistic infections, timely ART, and improving laboratory services are recommended. Mortality was related to change in sensorium and seizure. PMID:22490062

HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

PubMed Central

Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

2010-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

Identification of potential metabolic biomarkers of cerebrospinal fluids that differentiate tuberculous meningitis from other types of meningitis by a metabolomics study

PubMed Central

Dai, Yi-Ning; Huang, Hai-Jun; Song, Wen-Yuan; Tong, Yong-Xi; Yang, Dan-Hong; Wang, Ming-Shan; Huang, Yi-Cheng; Chen, Mei-Juan; Zhang, Jia-Jie; Ren, Ze-Ze; Zheng, Wei; Pan, Hong-Ying

2017-01-01

Tuberculous meningitis (TBM) is caused by tuberculosis infection of of the meninges, which are the membrane systems that encircle the brain, with a high morbidity and mortality rate. It is challenging to diagnose TBM among other types of meningitis, such as viral meningitis, bacterial meningitis and cryptococcal meningitis. We aimed to identify metabolites that are differentially expressed between TBM and the other types of meningitis by a global metabolomics analysis. The cerebrospinal fluids (CSF) from 50 patients with TBM, 17 with viral meningitis, 17 with bacterial meningitis, and 16 with cryptococcal meningitis were analyzed using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS). A total of 1161 and 512 features were determined in positive and negative electrospray ionization mode, respectively. A clear separation between TBM and viral, bacterial or cryptococcal meningitis was achieved by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) analysis. Potential metabolic markers and related pathways were identified, which were mainly involved in the metabolism of amino acid, lipids and nucleosides. In summary, differential metabolic profiles of the CSF exist between TBM and other types of meningitis, and potential metabolic biomarkers were identified to differentiate TBM from other types of meningitis. PMID:29245963

Cryptococcal Meningitis Treatment Strategies Affected by the Explosive Cost of Flucytosine in the United States: A Cost-effectiveness Analysis.

PubMed

Merry, Matthew; Boulware, David R

2016-06-15

In the United States, cryptococcal meningitis causes approximately 3400 hospitalizations and approximately 330 deaths annually. The US guidelines recommend treatment with amphotericin B plus flucytosine for at least 2 weeks, followed by fluconazole for a minimum of 8 weeks. Due to generic drug manufacturer monopolization, flucytosine currently costs approximately $2000 per day in the United States, with a 2-week flucytosine treatment course costing approximately $28 000. The daily flucytosine treatment cost in the United Kingdom is approximately $22. Cost-effectiveness analysis was performed to determine the value of flucytosine relative to alternative regimens. We estimated the incremental cost-effectiveness ratio (ICER) of 3 cryptococcal induction regimens: (1) amphotericin B deoxycholate for 4 weeks; (2) amphotericin and flucytosine (100 mg/kg/day) for 2 weeks; and (3) amphotericin and fluconazole (800 mg/day) for 2 weeks. Costs of care were calculated using 2015 US prices and the medication costs. Survival estimates were derived from a randomized trial and scaled relative to published US survival data. Cost estimates were $83 227 for amphotericin monotherapy, $75 121 for amphotericin plus flucytosine, and $44 605 for amphotericin plus fluconazole. The ICER of amphotericin plus flucytosine was $23 842 per quality-adjusted life-year. Flucytosine is currently cost-effective in the United States despite a dramatic increase in price in recent years. Combination therapy with amphotericin and flucytosine is the most attractive treatment strategy for cryptococcal meningitis, though the rising price may be creating access issues that will exacerbate if the trend of profiteering continues. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

PubMed

Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

2011-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Relationship between intracranial pressure and antifungal agents levels in the CSF of patients with cryptococcal meningitis.

PubMed

Wirth, Fernanda; de Azevedo, Maria Isabel; Pilla, Carmen; Aquino, Valério Rodrigues; Neto, Gustavo Wissmann; Goldani, Luciano Zubaran

2018-04-01

The purpose of this study was to evaluate the influence of intracranial hypertension in the cerebrospinal fluid (CSF) levels of amphotericin B and fluconazole levels of patients with cryptococcal meningitis. CSF samples and intracranial pressure were obtained by means of routine punctures performed at days 1, 7, and 14 of therapy, respectively. Amphotericin B and fluconazole CSF levels were measured by HPLC method as previously described. The minimum inhibitory concentration for amphotericin B, fluconazole, 5΄flucytosine, and voriconazole of each Cryptococcus isolate was performed according to CLSI. The predominant Cryptococcus species found was C. neoformans, and the major underlying condition was AIDS. Only one CSF sample had a detectable level for amphotericin B during the 14 days of therapy. Fluconazole CSF levels progressively increased from day 1 to day 14 of therapy for most cases. Fluconazole levels in the CSF were above the minimum inhibitory concentrations (MICs) for Cryptococcus during the initial 14 days of antifungal therapy. Variations of intracranial pressure did not affect amphotericin B and fluconazole levels in the CSF. The generalized estimating correlation (GEE) and Spearman correlation test (SCT) showed no significant correlation between the amphotericin B or fluconazole concentrations in the CSF and intracranial pressure (P = .953 and P = .093, respectively for GEE test and P = .477 and P = .847, respectively, for SCT). Combination therapy of amphotericin B with fluconazole was effective in 60% of the patients considering CSF cultures were negative in 9 of 15 patients after 14 days of therapy. Further studies are necessary to evaluate the role of intracranial hypertension on the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.

Paradoxical immune reconstitution inflammatory syndrome associated with previous Cryptococcus neoformans infection in an HIV-positive patient requiring neurosurgical intervention.

PubMed

Biagetti, Carlo; Nicola, Monica; Borderi, Marco; Pavoni, Michele; Tampellini, Livia; Verucchi, Gabriella; Chiodo, Francesco

2009-04-01

Immune reconstitution inflammatory syndrome (IRIS) in HIV-1-infected patients is associated with an exaggerated inflammatory response against an opportunistic infection during highly active antiretroviral therapy. The only review on IRIS associated with Criptococcus neoformans reported 21 episodes including lymphadenitis, necrotizing pneumonitis, breast and cutaneous abscess, and cryptococcomas. To our knowledge this is the first report of IRIS associated with previous meningeal criptococcal infection which required neurosurgical intervention with placement of a ventriculo-peritoneal shunt to drain a CSF cyst formed by exclusion of the temporal horn of the right lateral ventricle. We demonstrate that this procedure is possible without complications such as cryptococcal dissemination into the peritoneum.

Cryptococcal meningitis management in Tanzania with strict schedule of serial lumber punctures using intravenous tubing sets: an operational research study.

PubMed

Meda, John; Kalluvya, Samuel; Downs, Jennifer A; Chofle, Awilly A; Seni, Jeremiah; Kidenya, Benson; Fitzgerald, Daniel W; Peck, Robert N

2014-06-01

Cryptococcal meningitis (CM) has a mortality rate of ∼70% among HIV-infected adults in low-income countries. Controlling intracranial pressure (ICP) is essential in CM, but it is difficult in low-income countries because manometers and practical ICP management protocols are lacking. As part of a continuous quality improvement project, our Tanzanian hospital initiated a new protocol for ICP management for CM. All adult inpatients with CM are included in a prospective patient registry. At the time of analysis, this registry included data from 2 years before the initiation of this new ICP management protocol and for a 9-month period after. ICP was measured at baseline and at days 3, 7, and 14 by both manometer and intravenous (IV) tubing set. All patients were given IV fluconazole according to Tanzanian treatment guidelines and were followed until 30 days after admission. Among adult inpatients with CM, 32 of 35 patients (91%) had elevated ICP on admission. Cerebrospinal fluid pressure measurements using the improvised IV tubing set demonstrated excellent agreement (r = 0.96) with manometer measurements. Compared with historical controls, the new ICP management protocol was associated with a significant reduction in 30-day mortality (16/35 [46%] vs. 48/64 [75%] in historical controls; hazard ratio = 2.1 [95% CI: 1.1 to 3.8]; P = 0.018]. Increased ICP is almost universal among HIV-infected adults admitted with CM in Tanzania. Intensive ICP management with a strict schedule of serial lumbar punctures reduced in-hospital mortality compared with historical controls. ICP measurement with IV tubing sets may be a good alternative in resource-limited health facilities where manometers are not available.

Tuberculous meningitis is associated with higher cerebrospinal HIV-1 viral loads compared to other HIV-1-associated meningitides.

PubMed

Seipone, Ikanyeng D; Singh, Ravesh; Patel, Vinod B; Singh, Avashna; Gordon, Michelle L; Muema, Daniel M; Dheda, Keertan; Ndung'u, Thumbi

2018-01-01

To gain a better understanding of the immunopathogenesis of tuberculous meningitis (TBM) and identify potential diagnostic biomarkers that may discriminate TBM from other HIV-1-associated meningitides, we assessed HIV-1 viral load levels, drug resistance patterns in antiretroviral therapy (ART)-experienced patients with persistent viremia and soluble immunological analytes in peripheral blood and cerebrospinal fluid (CSF) of HIV-1 infected patients with TBM versus other meningitides. One hundred and three matched blood and CSF samples collected from HIV-1 infected patients with TBM or other meningitides presenting at a hospital in Durban, South Africa, from January 2009 to December 2011 were studied. HIV-1 RNA and 28 soluble immunological potential biomarkers were quantified in blood plasma and CSF. Viremic samples were assessed for HIV-1 drug resistance mutations. There were 16 TBM, 46 probable TBM, 35 non-TBM patients, and six unclassifiable patients. TBM and non-TBM patients did not differ in median plasma viral load but TBM patients had significantly higher median CSF viral load than non-TBM participants (p = 0.0005). No major drug resistance mutations were detected in viremic samples. Interleukin (IL)-1β, IL-17, platelet derived growth factor (PDGF)-BB, granulocyte colony stimulating factor (G-CSF) and cathelicidin were significantly elevated in the CNS of TBM participants compared to other patients although these associations were lost after correction for false discovery. Our data suggest that TB co-infection of the CNS is associated with enhanced localized HIV-1 viral replication but none of the evaluated soluble immunological potential biomarkers could reliably distinguish TBM from other HIV-associated meningitides.

Tuberculous meningitis is associated with higher cerebrospinal HIV-1 viral loads compared to other HIV-1-associated meningitides

PubMed Central

Seipone, Ikanyeng D.; Singh, Ravesh; Patel, Vinod B.; Singh, Avashna; Gordon, Michelle L.; Muema, Daniel M.; Dheda, Keertan

2018-01-01

To gain a better understanding of the immunopathogenesis of tuberculous meningitis (TBM) and identify potential diagnostic biomarkers that may discriminate TBM from other HIV-1-associated meningitides, we assessed HIV-1 viral load levels, drug resistance patterns in antiretroviral therapy (ART)-experienced patients with persistent viremia and soluble immunological analytes in peripheral blood and cerebrospinal fluid (CSF) of HIV-1 infected patients with TBM versus other meningitides. One hundred and three matched blood and CSF samples collected from HIV-1 infected patients with TBM or other meningitides presenting at a hospital in Durban, South Africa, from January 2009 to December 2011 were studied. HIV-1 RNA and 28 soluble immunological potential biomarkers were quantified in blood plasma and CSF. Viremic samples were assessed for HIV-1 drug resistance mutations. There were 16 TBM, 46 probable TBM, 35 non-TBM patients, and six unclassifiable patients. TBM and non-TBM patients did not differ in median plasma viral load but TBM patients had significantly higher median CSF viral load than non-TBM participants (p = 0.0005). No major drug resistance mutations were detected in viremic samples. Interleukin (IL)-1β, IL-17, platelet derived growth factor (PDGF)-BB, granulocyte colony stimulating factor (G-CSF) and cathelicidin were significantly elevated in the CNS of TBM participants compared to other patients although these associations were lost after correction for false discovery. Our data suggest that TB co-infection of the CNS is associated with enhanced localized HIV-1 viral replication but none of the evaluated soluble immunological potential biomarkers could reliably distinguish TBM from other HIV-associated meningitides. PMID:29394269

Cryptococcal antigen screening by lay cadres using a rapid test at the point of care: A feasibility study in rural Lesotho.

PubMed

Rick, Fernanda; Niyibizi, Aline Aurore; Shroufi, Amir; Onami, Kazumi; Steele, Sarah-Jane; Kuleile, Malehlohonolo; Muleya, Innocent; Chiller, Tom; Walker, Tiffany; Van Cutsem, Gilles

2017-01-01

Cryptococcal meningitis is one of the leading causes of death among people with HIV in Africa, primarily due to delayed presentation, poor availability and high cost of treatment. Routine cryptococcal antigen (CrAg) screening of patients with a CD4 count less than 100 cells/mm3, followed by pre-emptive therapy if positive, might reduce mortality in high prevalence settings. Using the cryptococcal antigen (CrAg) lateral flow assay (LFA), screening is possible at the point of care (POC). However, critical shortages of health staff may limit adoption. This study investigates the feasibility of lay counsellors conducting CrAg LFA screening in rural primary care clinics in Lesotho. From May 2014 to June 2015, individuals who tested positive for HIV were tested for CD4 count and those with CD4 <100 cells/mm3 were screened with CrAg LFA. All tests were performed by lay counsellors. CrAg-positive asymptomatic patients received fluconazole, while symptomatic patients were referred to hospital. Lay counsellors were trained and supervised by a laboratory technician and counsellor activity supervisor. Additionally, nurses and doctors were trained on CrAg screening and appropriate treatment. During the study period, 1,388 people were newly diagnosed with HIV, of whom 129 (9%) presented with a CD4 count <100 cells/mm3. Of these, 128 (99%) were screened with CrAg LFA and 14/128 (11%) tested positive. Twelve of the 14 (86%) were asymptomatic, and received outpatient fluconazole. All commenced ART with a median time to initiation of 15.5 days [IQR: 14-22]. Of the asymptomatic patients, nine (75%) remained asymptomatic after a median time of 5 months [IQR; 3-6] of follow up. One (8%) became co-infected with tuberculosis and died and two were transferred out. The two patients with symptomatic cryptococcal meningitis (CM) were referred to hospital, where they later died. CrAg LFA screening by lay counsellors followed by pre-emptive fluconazole treatment for asymptomatic cases, or

Cryptococcal antigen screening by lay cadres using a rapid test at the point of care: A feasibility study in rural Lesotho

PubMed Central

Rick, Fernanda; Niyibizi, Aline Aurore; Shroufi, Amir; Onami, Kazumi; Steele, Sarah-Jane; Kuleile, Malehlohonolo; Muleya, Innocent; Chiller, Tom; Walker, Tiffany; Van Cutsem, Gilles

2017-01-01

Introduction Cryptococcal meningitis is one of the leading causes of death among people with HIV in Africa, primarily due to delayed presentation, poor availability and high cost of treatment. Routine cryptococcal antigen (CrAg) screening of patients with a CD4 count less than 100 cells/mm3, followed by pre-emptive therapy if positive, might reduce mortality in high prevalence settings. Using the cryptococcal antigen (CrAg) lateral flow assay (LFA), screening is possible at the point of care (POC). However, critical shortages of health staff may limit adoption. This study investigates the feasibility of lay counsellors conducting CrAg LFA screening in rural primary care clinics in Lesotho. Methods From May 2014 to June 2015, individuals who tested positive for HIV were tested for CD4 count and those with CD4 <100 cells/mm3 were screened with CrAg LFA. All tests were performed by lay counsellors. CrAg-positive asymptomatic patients received fluconazole, while symptomatic patients were referred to hospital. Lay counsellors were trained and supervised by a laboratory technician and counsellor activity supervisor. Additionally, nurses and doctors were trained on CrAg screening and appropriate treatment. Results During the study period, 1,388 people were newly diagnosed with HIV, of whom 129 (9%) presented with a CD4 count <100 cells/mm3. Of these, 128 (99%) were screened with CrAg LFA and 14/128 (11%) tested positive. Twelve of the 14 (86%) were asymptomatic, and received outpatient fluconazole. All commenced ART with a median time to initiation of 15.5 days [IQR: 14–22]. Of the asymptomatic patients, nine (75%) remained asymptomatic after a median time of 5 months [IQR; 3–6] of follow up. One (8%) became co-infected with tuberculosis and died and two were transferred out. The two patients with symptomatic cryptococcal meningitis (CM) were referred to hospital, where they later died. Conclusions CrAg LFA screening by lay counsellors followed by pre

Repurposing and Reformulation of the Antiparasitic Agent Flubendazole for Treatment of Cryptococcal Meningoencephalitis, a Neglected Fungal Disease

PubMed Central

Nixon, Gemma L.; McEntee, Laura; Johnson, Adam; Farrington, Nicola; Whalley, Sarah; Livermore, Joanne; Natal, Cristien; Washbourn, Gina; Bibby, Jaclyn; Berry, Neil; Lestner, Jodi; Truong, Megan; Owen, Andrew; Lalloo, David; Charles, Ian

2018-01-01

ABSTRACT Current therapeutic options for cryptococcal meningitis are limited by toxicity, global supply, and emergence of resistance. There is an urgent need to develop additional antifungal agents that are fungicidal within the central nervous system and preferably orally bioavailable. The benzimidazoles have broad-spectrum antiparasitic activity but also have in vitro antifungal activity that includes Cryptococcus neoformans. Flubendazole (a benzimidazole) has been reformulated by Janssen Pharmaceutica as an amorphous solid drug nanodispersion to develop an orally bioavailable medicine for the treatment of neglected tropical diseases such as onchocerciasis. We investigated the in vitro activity, the structure-activity-relationships, and both in vitro and in vivo pharmacodynamics of flubendazole for cryptococcal meningitis. Flubendazole has potent in vitro activity against Cryptococcus neoformans, with a modal MIC of 0.125 mg/liter using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. Computer models provided an insight into the residues responsible for the binding of flubendazole to cryptococcal β-tubulin. Rapid fungicidal activity was evident in a hollow-fiber infection model of cryptococcal meningitis. The solid drug nanodispersion was orally bioavailable in mice with higher drug exposure in the cerebrum. The maximal dose of flubendazole (12 mg/kg of body weight/day) orally resulted in an ∼2 log10CFU/g reduction in fungal burden compared with that in vehicle-treated controls. Flubendazole was orally bioavailable in rabbits, but there were no quantifiable drug concentrations in the cerebrospinal fluid (CSF) or cerebrum and no antifungal activity was demonstrated in either CSF or cerebrum. These studies provide evidence for the further study and development of the benzimidazole scaffold for the treatment of cryptococcal meningitis. PMID:29311092

Detection of herpes viruses in the cerebrospinal fluid of adults with suspected viral meningitis in Malawi.

PubMed

Benjamin, L A; Kelly, M; Cohen, D; Neuhann, F; Galbraith, S; Mallewa, M; Hopkins, M; Hart, I J; Guiver, M; Lalloo, D G; Heyderman, R S; Solomon, T

2013-02-01

We looked for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively), varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) DNA in Malawian adults with clinically suspected meningitis. We collected cerebrospinal fluid (CSF) from consecutive adults admitted with clinically suspected meningitis to Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, for a period of 3 months. Those with proven bacterial or fungal meningitis were excluded. Real-time polymerase chain reaction (PCR) was performed on the CSF for HSV-1 and HSV-2, VZV, EBV and CMV DNA. A total of 183 patients presented with clinically suspected meningitis. Of these, 59 (32 %) had proven meningitis (bacterial, tuberculous or cryptococcal), 39 (21 %) had normal CSF and 14 (8 %) had aseptic meningitis. For the latter group, a herpes virus was detected in 9 (64 %): 7 (50 %) had EBV and 2 (14 %) had CMV, all were human immunodeficiency virus (HIV)-positive. HSV-2 and VZV were not detected. Amongst those with a normal CSF, 8 (21 %) had a detectable herpes virus, of which 7 (88 %) were HIV-positive. The spectrum of causes of herpes viral meningitis in this African population is different to that in Western industrialised settings, with EBV being frequently detected in the CSF. The significance of this needs further investigation.

Rapid Clinical Score for the Diagnosis of Tuberculous Meningitis: A Retrospective Cohort Study

PubMed Central

Jipa, Raluca; Olaru, Ioana D.; Manea, Eliza; Merisor, Simona; Hristea, Adriana

2017-01-01

Objective: The aim of our study was to retrospectively validate a previously described rapid clinical score (RCS) in distinguishing tuberculous meningitis (TBM) from viral meningitis (VM) in people who are at increased risk of tuberculosis, as well as from cryptococcal meningitis (CM) in HIV-infected patients. Methods: We performed a retrospective study of patients admitted with a diagnosis of aseptic meningitis between January 2012 and December 2015, to a referral hospital for infectious diseases. The variables included in RCS were duration of symptoms before admission, neurological stage, cerebrospinal fluid (CSF) to blood glucose ratio, and CSF protein. We included in this retrospective study 31 patients with definite or probable TBM including 14 HIV-infected patients, 62 HIV-noninfected patients with VM, and 18 HIV-infected patients with CM. Results: The sensitivity of RCS to distinguish TBM from VM was 96.7%, with a specificity of 81.1% and the area under the receiver operating characteristic (ROC) curve was 0.949 (0.90–0.99). When all four criteria from the RCS were present, the specificity increased at 100%. In HIV-infected patients, the sensitivity and specificity of RCS in differentiating TBM from CM were 86.6% and 27.7%, respectively, and the area under the ROC curve was 0.669 (0.48–0.85). Conclusion: This easy-to-use RCS was found to be helpful in differentiating TBM from VM, with a better sensitivity than molecular amplification techniques and a relatively good specificity. However, the RCS was not useful to differentiate between TBM and CM in HIV-infected patients. PMID:29184338

HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam.

PubMed

Thao, Vu P; Le, Thuy; Török, Estee M; Yen, Nguyen T B; Chau, Tran T H; Jurriaans, Suzanne; van Doorn, H Rogier; van Doorn, Rogier H; de Jong, Menno D; Farrar, Jeremy J; Dunstan, Sarah J

2012-01-01

Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled trial of immediate versus deferred ART in individuals with HIV-associated tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations were identified by population sequencing of the HIV pol gene and were defined based on 2009 WHO surveillance drug resistance mutations (SDRMs). We successfully sequenced 219/220 plasma samples of subjects prior to ART; 218 were subtype CRF01_AE and 1 was subtype B. SDRMs were identified in 14/219 (6.4%) subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A), 1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors. After 6 months of ART, eight subjects developed protocol-defined virological failure. HIVDR mutations were identified in 5/8 subjects. All five had mutations with high-level resistance to NNRTIs and three had mutations with high-level resistance to NRTIs. Due to a high early mortality rate (58%), the effect of pre-existing HIVDR mutations on treatment outcome could not be accurately assessed. The prevalence of WHO SDRMs in ART-naive individuals with HIV-associated tuberculous meningitis in HCMC from 2005-2008 is 6.4%. The SDRMs identified conferred resistance to NRTIs and/or NNRTIs, reflecting the standard first-line ART regimens in Vietnam.

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.

A Retrospective Cohort Study of Lesion Distribution of HIV-1 Infection Patients With Cryptococcal Meningoencephalitis on MRI: Correlation With Immunity and Immune Reconstitution.

PubMed

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

2016-02-01

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/mm (3.00-52.00 cells/mm) in group 1 and 42.00 cells/mm (10.00-252.00 cells/mm) 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.

Postpartum cryptococcal pulmonary lesion incidentally discovered during a pulmonary-embolism evaluation of a 28-year-old caucasian woman.

PubMed

Kaplan, Alesia; Berntson, Daniel G; Ferrieri, Patricia

2015-01-01

We report a case of localized pulmonary cryptococcal infection in a 28-year-old Caucasian woman who was 1 month postpartum at the time of her arrival at the hospital. The patient reported right-side chest pain; on further work up, she was found to have an incidental pulmonary lesion of the left lower lung lobe. Surgical pathology examination and microbiology studies revealed localized cryptococcal infection. Cases of cryptococcal pneumonia in pregnant women and in the postpartum period have been described in the literature. However, cryptococcal infections are usually associated with various immunocompromised states, including human immunodeficiency virus (HIV) infection. Because pregnancy is associated with physiological immunosuppression, cryptococcal pneumonia should be considered in pregnant women, or women in the postpartum period, who have respiratory symptoms. Copyright© by the American Society for Clinical Pathology (ASCP).

Case report: false negative serum cryptococcal latex agglutination test in a patient with disseminated cryptococcal disease.

PubMed

Navabi, Nazlee; Montebatsi, Milton; Scott, Michelle; Gluckman, Stephen J; Reid, Michael J A

2015-01-01

A case of false-negative serum latex agglutination cryptococcal antigen (CRAG) test in a 45-year-old HIV-positive male with Cryptococcus-positive culture is described. The patient was presented to a hospital in Botswana, with breathlessness and a diffuse papular rash. His CD4 count was 25 cells/μL. Despite the suspicion for disseminated cryptococcal disease, an initial serum CRAG latex test was negative. Results of subsequent Indian ink staining, culture of cerebrospinal fluid and skin scrapings, and serum lateral flow immunoassay (LFA) were all positive for Cryptococcus neoformans. There are several possible explanations for the false-negative CRAG latex test. Given the positive LFA result, we speculate that disease may have been caused by Cryptococcus gattii, which is estimated to be responsible for between 15% and 30% of all cryptococcal diseases in Botswana. Reduced sensitivity of CRAG latex assays for detecting C gattii may lead to underdiagnosis of cryptococcal infection. © The Author(s) 2014.

[A case of both cryptococcal pneumonia and meningitis with idiopathic CD4+T-lymphocytopenia followed up over a long time].

PubMed

Anzai, Fumio; Yamamoto, Akito; Tannai, Noriyuki; Abe, Hideki; Tsuchiya, Kayoko; Kusajima, Kenji; Shimoide, Hisao; Nunomura, Maki

2009-07-01

A 62-year-old man had felt cold-like symptoms for 2 months. He visited a clinic for a health check in late July 1998 and chest X-ray film showed an infiltrative shadow in the left middle and lower lung fields. Next day he had a fever of 38.3 degrees C and felt breathless. Six days thereafter he had a cough, thick head and felt fatigue. Chest X-ray films showed other infiltrative shadows in the bilateral upper lung fields. He worked in a race track and was exposed to pigeons and seabirds at that time. Culture of sputum grew Cryptococcus neoformans. He was admitted and was treated with intravenous antifungal drugs. Cerebrospinal fluid examination revealed positive Indian ink stain for C. neoformans. The CD4 + T-lymphocyte count and CD8 + T-lymphocyte count were 143.4 cells/mm3 and 1288.8 cells/mm3 respectively, but without HIV infection. Cryptococcal pneumonia and meningitis with Idiopathic CD4 + T-lymphocytopenia was diagnosed. After induction therapy, the symptoms improved but abnormal shadows remained on chest X-ray films. Maintenance therapy has been continued at doses of 200 mg/day of fluconazole for 10 years. He has had no symptoms, but the abnormal X-ray shadow has persisted and the CD4 count has remained low during the same period.

[Causes of lymphocytic meningitis in people with HIV admitted to the Infectious Disease department of Conakry].

PubMed

Traoré, F A; Cissoko, Y; Tounkara, T M; Sako, F B; Mouelle, A D; Kpami, D O; Traoré, M; Doumbouya, M

2015-01-01

The advent of HIV infection has significantly changed the distribution of the causes of lymphocytic meningitis. The objective of this study was to identify these causes among persons with HIV hospitalized in the infectious disease department of the CHU of Conakry. This retrospective study examined hospital records of patients with HIV infection admitted for lymphocytic meningitis over a 10-year period. Of the 8649 hospitalizations in the department during the study period, 3167 patients had HIV infection, and 85 of the latter were diagnosed with lymphocytic meningitis. Slightly more than half were male (sex ratio M/F = 1.1). Their mean age was 32 years. Of these 85 patients, 73 were positive for HIV-1 only and 12 for HIV1+2. A CD4 count was performed only in 13/85 patients and averaged 140 cells/mm3. The main causes associated with lymphocytic meningitis were cryptococcosis (58%), toxoplasmosis (5%), and tuberculosis (2%). Streptococcus pneumoniae, Neisseria meningitidis, and Hæmophilus influenzae were also identified in 16% of cases. In 18% of cases no microbe was identified. The overall lethality rate was 68%; it reached 100% for tuberculous meningitis and for the cases without any identified cause and was 75%-76% for the patients with toxoplasmosis and cryptococcosis. The survival rate was 100% for all bacterial causes. A cause for lymphocytic meningitis was identified in more than 81% of the patients in our series, and the most common microbe was Cryptococcus neoformans. A better microbiological technical platform and improved accessibility to treatment would enable us to provide more relevant results and treatment.

Clinical presentation and aetiologies of acute or complicated headache among HIV-seropositive patients in a Ugandan clinic.

PubMed

Katwere, Michael; Kambugu, Andrew; Piloya, Theresa; Wong, Matthew; Hendel-Paterson, Brett; Sande, Merle A; Ronald, Allan; Katabira, Elly; Were, Edward M; Menten, Joris; Colebunders, Robert

2009-09-19

We set out to define the relative prevalence and common presentations of the various aetiologies of headache within an ambulant HIV-seropositive adult population in Kampala, Uganda. We conducted a prospective study of adult HIV-1-seropositive ambulatory patients consecutively presenting with new onset headaches. Patients were classified as focal-febrile, focal-afebrile, non-focal-febrile or non-focal-afebrile, depending on presence or absence of fever and localizing neurological signs. Further management followed along a pre-defined diagnostic algorithm to an endpoint of a diagnosis. We assessed outcomes during four months of follow up. One hundred and eighty patients were enrolled (72% women). Most subjects presented at WHO clinical stages III and IV of HIV disease, with a median Karnofsky performance rating of 70% (IQR 60-80).The most common diagnoses were cryptococcal meningitis (28%, n = 50) and bacterial sinusitis (31%, n = 56). Less frequent diagnoses included cerebral toxoplasmosis (4%, n = 7), and tuberculous meningitis (4%, n = 7). Thirty-two (18%) had other diagnoses (malaria, bacteraemia, etc.). No aetiology could be elucidated in 28 persons (15%). Overall mortality was 13.3% (24 of 180) after four months of follow up. Those without an established headache aetiology had good clinical outcomes, with only one death (4% mortality), and 86% were ambulatory at four months. In an African HIV-infected ambulatory population presenting with new onset headache, aetiology was found in at least 70%. Cryptococcal meningitis and sinusitis accounted for more than half of the cases.

Amphotericin B Colloidal Dispersion Combined with Flucytosine with or without Fluconazole for Treatment of Murine Cryptococcal Meningitis

PubMed Central

Diamond, DeAnn M.; Bauer, Madeline; Daniel, Barbra E.; Leal, Mary Ann E.; Johnson, Debra; Williams, Byron K.; Thomas, Ann M.; Ding, James C.; Najvar, Laura; Graybill, J. Richard; Larsen, Robert A.

1998-01-01

Studies with animals and in vitro studies have demonstrated that flucytosine plus amphotericin B or fluconazole has significantly improved mycologic activity against meningitis caused by Cryptococcus neoformans compared to the activity of amphotericin B or fluconazole used alone. However, few doses have been tested in combination. This study evaluated the antifungal efficacy of amphotericin B colloidal dispersion (ABCD) combined with flucytosine with and without fluconazole in a murine model of cryptococcal meningitis. The following dosages were tested: ABCD at 0 to 12.5 mg/kg of body weight given intravenously 3 days/week, flucytosine at 0 to 110 mg/kg/day, and fluconazole at 0 to 50 mg/kg/day. Meningitis was established in male BALB/c mice by intracerebral injection of C. neoformans. Treatment with flucytosine with or without fluconazole dissolved in the sole source of drinking water was started on day 2; animals were sacrificed at 16 days, and the numbers of fungal colonies in the brain were quantified. A survival rate of 100% was achieved with ABCD plus flucytosine without fluconazole; however, the addition of fluconazole was required to prevent weight loss (P < 0.00001) and to achieve the maximum antifungal effect (P < 0.00001). The only region of dose combinations for which the 99% confidence intervals were less than 100 CFU/g of brain was defined by ABCD at 5.0 to 7.5 mg/kg combined with flucytosine at 20 to 60 mg/kg/day and fluconazole at 30 to 40 mg/kg/day. The triple combination of ABCD plus flucytosine and fluconazole was necessary to achieve the greatest antifungal activity. PMID:9517927

Reproducibility of CSF quantitative culture methods for estimating rate of clearance in cryptococcal meningitis.

PubMed

Dyal, Jonathan; Akampurira, Andrew; Rhein, Joshua; Morawski, Bozena M; Kiggundu, Reuben; Nabeta, Henry W; Musubire, Abdu K; Bahr, Nathan C; Williams, Darlisha A; Bicanic, Tihana; Larsen, Robert A; Meya, David B; Boulware, David R

2016-05-01

Quantitative cerebrospinal fluid (CSF) cultures provide a measure of disease severity in cryptococcal meningitis. The fungal clearance rate by quantitative cultures has become a primary endpoint for phase II clinical trials. This study determined the inter-assay accuracy of three different quantitative culture methodologies. Among 91 participants with meningitis symptoms in Kampala, Uganda, during August-November 2013, 305 CSF samples were prospectively collected from patients at multiple time points during treatment. Samples were simultaneously cultured by three methods: (1) St. George's 100 mcl input volume of CSF with five 1:10 serial dilutions, (2) AIDS Clinical Trials Group (ACTG) method using 1000, 100, 10 mcl input volumes, and two 1:100 dilutions with 100 and 10 mcl input volume per dilution on seven agar plates; and (3) 10 mcl calibrated loop of undiluted and 1:100 diluted CSF (loop). Quantitative culture values did not statistically differ between St. George-ACTG methods (P= .09) but did for St. George-10 mcl loop (P< .001). Repeated measures pairwise correlation between any of the methods was high (r≥0.88). For detecting sterility, the ACTG-method had the highest negative predictive value of 97% (91% St. George, 60% loop), but the ACTG-method had occasional (∼10%) difficulties in quantification due to colony clumping. For CSF clearance rate, St. George-ACTG methods did not differ overall (mean -0.05 ± 0.07 log10CFU/ml/day;P= .14) on a group level; however, individual-level clearance varied. The St. George and ACTG quantitative CSF culture methods produced comparable but not identical results. Quantitative cultures can inform treatment management strategies. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Challenges in diagnosis and management of Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings.

PubMed

Musubire, A K; Meya, B D; Mayanja-Kizza, H; Lukande, R; Wiesner, L D; Bohjanen, P; R Boulware, R D

2012-06-01

In many resource-limited settings, cryptococcal meningitis (CM) contributes up to 20% of all deaths with further complications due to Immune Reconstitution Inflammatory Syndrome (IRIS). We present a case report on a patient who developed CM-IRIS and then subsequent CM-relapse with a fluconazole-resistant organism and then later CM-IRIS once again, manifesting as cystic cryptococcomas, hydrocephalus, and sterile CSF. In this case we, demonstrate that CM-IRIS and persistent low level cryptococcal infection are not mutually exclusive phenomena. The management of IRIS with corticosteroids may increase the risk of culture positive CM-relapse which may further increase the risk of recurrent IRIS and resulting complications including death. We also highlight the role of imaging and fluconazole resistance testing in patients with recurrent meningitis and the importance of CSF cultures in guiding treatment decisions.

Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease.

PubMed

Garvey, L; Winston, A; Walsh, J; Post, F; Porter, K; Gazzard, B; Fisher, M; Leen, C; Pillay, D; Hill, T; Johnson, M; Gilson, R; Anderson, J; Easterbrook, P; Bansi, L; Orkin, C; Ainsworth, J; Palfreeman, A; Gompels, M; Phillips, A N; Sabin, C A

2011-02-22

The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death. Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.

Antiretroviral therapy CNS penetration and HIV-1–associated CNS disease

PubMed Central

Winston, A.; Walsh, J.; Post, F.; Porter, K.; Gazzard, B.; Fisher, M.; Leen, C.; Pillay, D.; Hill, T.; Johnson, M.; Gilson, R.; Anderson, J.; Easterbrook, P.; Bansi, L.; Orkin, C.; Ainsworth, J.; Palfreeman, A.; Gompels, M.; Phillips, A.N.; Sabin, C.A.

2011-01-01

Objective: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5–8) in 1996–1997 to 9 (8–10) in 2000–2001 and subsequently declined to 6 (7–8) in 2006–2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤4, and less frequently in those with scores ≥10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤4 were independently associated with increased risk of death. Conclusion: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. PMID:21339496

Frequency of HIV infection amongst children with disseminated tuberculosis and tuberculous meningitis in Aligarh (North India) - a low HIV prevalence area.

PubMed

Ramzan, Mohammad; Ali, Syed Manazir; Malik, Abida; Zaka-ur-Rab, Zeeba; Shahab, Tabassum

2009-09-01

To determine frequency of HIV in children with disseminated tuberculosis and tuberculous meningitis in a low HIV prevalence area, and to study clinical profile of those found HIV positive. Cross-sectional, descriptive study. Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India from February 2005 to January 2008. The study was conducted on 215 children under 14 years of age with either disseminated tuberculosis or tuberculous meningitis. HIV infection was diagnosed in accordance with WHO strategy II. In children younger than 18 months, the strategy (to cut down costs) was to screen first by HIV antibody testing and subject only positive cases to virological tests. Parents of HIV positive children were also tested for HIV and counselled. The clinical profile of HIV positive patients was noted. The frequency of HIV was 5.12%, while that in cases of disseminated tuberculosis was much higher (22%). No case with isolated tuberculous meningitis was HIV positive. The majority (45.45%) of patients with HIV were between 1-5 years of age. The mode of infection in 7 (63.63%) cases was parent to child transmission. Loss of weight, prolonged fever, pallor, hepato-splenomegaly and oral candidiasis were the commonest clinical manifestations among HIV positive patients. Clinically directed selective HIV screening in cases of disseminated tuberculosis can pickup undiagnosed cases of the same in areas with low prevalence of HIV infection.

Feasibility and Acceptability of Cryptococcal Antigen Screening and Prevalence of Cryptocococcemia in Patients Attending a Resource-Limited HIV/AIDS Clinic in Malawi.

PubMed

Chipungu, Chifundo; Veltman, Jennifer A; Jansen, Perry; Chiliko, Peter; Lossa, Christina; Namarika, Dan; Benner, Blake; Hoffman, Risa M; Bristow, Claire C; Klausner, Jeffrey D

2015-01-01

The World Health Organization (WHO) recommends screening patients living with AIDS to detect and treat early cryptococcal infection. The authors evaluated a cryptococcal antigen (CrAg) screening and treatment program at an HIV/AIDS clinic in Malawi. Eligible patients were of age >18 years, had a CD4 count <100 cells/µL or WHO clinical HIV/AIDS stage III or IV. Of 552 patients who presented for care, 113 were eligible, and all (100%) agreed to CrAg screening. Of them, 2 (1.8%; 95% confidence interval [CI]: 0-4.2%) patients were CrAg positive. Among those with CD4 count <100 cells/µL or WHO stage IV, the CrAg prevalence was 3.5% (95% CI: 0-8.4%) and 5.0% (95% CI: 0-15%), respectively. A CrAg screening program was acceptable to new patients in a Malawian HIV/AIDS clinic. The CrAg prevalence for patients with CD4 count < 100 cells/µL and WHO stage IV was consistent with cost-effectiveness estimates. CrAg screening and treatment programs for patients living with AIDS should be expanded. © The Author(s) 2015.

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

Larson, Bruce A; 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

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.

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

Pharmacokinetics and Pharmacodynamics of Fluconazole for Cryptococcal Meningoencephalitis: Implications for Antifungal Therapy and In Vitro Susceptibility Breakpoints

PubMed Central

Sudan, Ajay; Livermore, Joanne; Howard, Susan J.; Al-Nakeeb, Zaid; Sharp, Andrew; Goodwin, Joanne; Gregson, Lea; Warn, Peter A.; Felton, Tim W.; Perfect, John R.; Harrison, Thomas S.

2013-01-01

Fluconazole is frequently the only antifungal agent that is available for induction therapy for cryptococcal meningitis. There is relatively little understanding of the pharmacokinetics and pharmacodynamics (PK-PD) of fluconazole in this setting. PK-PD relationships were estimated with 4 clinical isolates of Cryptococcus neoformans. MICs were determined using Clinical and Laboratory Standards Institute (CLSI) methodology. A nonimmunosuppressed murine model of cryptococcal meningitis was used. Mice received two different doses of fluconazole (125 mg/kg of body weight/day and 250 mg/kg of body weight/day) orally for 9 days; a control group of mice was not given fluconazole. Fluconazole concentrations in plasma and in the cerebrum were determined using high-performance liquid chromatography (HPLC). The cryptococcal density in the brain was estimated using quantitative cultures. A mathematical model was fitted to the PK-PD data. The experimental results were extrapolated to humans (bridging study). The PK were linear. A dose-dependent decline in fungal burden was observed, with near-maximal activity evident with dosages of 250 mg/kg/day. The MIC was important for understanding the exposure-response relationships. The mean AUC/MIC ratio associated with stasis was 389. The results of the bridging study suggested that only 66.7% of patients receiving 1,200 mg/kg would achieve or exceed an AUC/MIC ratio of 389. The potential breakpoints for fluconazole against Cryptococcus neoformans follow: susceptible, ≤2 mg/liter; resistant, >2 mg/liter. Fluconazole may be an inferior agent for induction therapy because many patients cannot achieve the pharmacodynamic target. Clinical breakpoints are likely to be significantly lower than epidemiological cutoff values. The MIC may guide the appropriate use of fluconazole. If fluconazole is the only option for induction therapy, then the highest possible dose should be used. PMID:23571544

Clinical and Microbiological Features of HIV-Associated Tuberculous Meningitis in Vietnamese Adults

PubMed Central

Torok, M. Estee; Chau, Tran Thi Hong; Mai, Pham Phuong; Phong, Nguyen Duy; Dung, Nguyen Thi; Chuong, Ly Van; Lee, Sue J.; Caws, M.; de Jong, Menno D.; Hien, Tran Tinh; Farrar, Jeremy J.

2008-01-01

Methods The aim of this prospective, observational cohort study was to determine the clinical and microbiological features, outcome, and baseline variables predictive of death, in Vietnamese adults with HIV-associated tuberculous meningitis (TBM). 58 patients were admitted to the Hospital for Tropical Diseases in Ho Chi Minh City and underwent routine clinical and laboratory assessments. Treatment was with standard antituberculous therapy and adjunctive dexamethasone; antiretroviral therapy was not routinely available. Patients were followed up until the end of TB treatment or death. Results The median symptom duration was 11 days (range 2–90 days), 21.8% had a past history of TB, and 41.4% had severe (grade 3) TBM. The median CD4 count was 32 cells/mm3. CSF findings were as follows: median leucocyte count 438×109cells/l (63% neutrophils), 69% smear positive and 87.9% culture positive. TB drug resistance rates were high (13% mono-resistance 32.6% poly-resistance 8.7% multidrug resistance). 17% patients developed further AIDS-defining illnesses. 67.2% died (median time to death 20 days). Three baseline variables were predictive of death by multivariate analysis: increased TBM grade [adjusted hazard ratio (AHR) 1.73, 95% CI 1.08–2.76, p = 0.02], lower serum sodium (AHR 0.93, 95% CI 0.89 to 0.98, p = 0.002) and decreased CSF lymphocyte percentage (AHR 0.98, 95% CI 0.97 to 0.99, p = 0.003). Conclusions HIV-associated TBM is devastating disease with a dismal prognosis. CSF findings included CSF neutrophil predominance, high rates of smear and culture positivity, and high rates of antituberculous drug resistance. Three baseline variables were independently associated with death: increased TBM grade; low serum sodium and decreased CSF lymphocyte percentage. PMID:18350135

Cost-effective Diagnostic Checklists for Meningitis in Resource Limited Settings

PubMed Central

Durski, Kara N.; Kuntz, Karen M.; Yasukawa, Kosuke; Virnig, Beth A.; Meya, David B.; Boulware, David R.

2013-01-01

Background Checklists can standardize patient care, reduce errors, and improve health outcomes. For meningitis in resource-limited settings, with high patient loads and limited financial resources, CNS diagnostic algorithms may be useful to guide diagnosis and treatment. However, the cost-effectiveness of such algorithms is unknown. Methods We used decision analysis methodology to evaluate the costs, diagnostic yield, and cost-effectiveness of diagnostic strategies for adults with suspected meningitis in resource limited settings with moderate/high HIV prevalence. We considered three strategies: 1) comprehensive “shotgun” approach of utilizing all routine tests; 2) “stepwise” strategy with tests performed in a specific order with additional TB diagnostics; 3) “minimalist” strategy of sequential ordering of high-yield tests only. Each strategy resulted in one of four meningitis diagnoses: bacterial (4%), cryptococcal (59%), TB (8%), or other (aseptic) meningitis (29%). In model development, we utilized prevalence data from two Ugandan sites and published data on test performance. We validated the strategies with data from Malawi, South Africa, and Zimbabwe. Results The current comprehensive testing strategy resulted in 93.3% correct meningitis diagnoses costing $32.00/patient. A stepwise strategy had 93.8% correct diagnoses costing an average of $9.72/patient, and a minimalist strategy had 91.1% correct diagnoses costing an average of $6.17/patient. The incremental cost effectiveness ratio was $133 per additional correct diagnosis for the stepwise over minimalist strategy. Conclusions Through strategically choosing the order and type of testing coupled with disease prevalence rates, algorithms can deliver more care more efficiently. The algorithms presented herein are generalizable to East Africa and Southern Africa. PMID:23466647

TB Meningitis in HIV-Positive Patients in Europe and Argentina: Clinical Outcome and Factors Associated with Mortality

PubMed Central

Efsen, Anne Marie W.; Panteleev, Alexander M.; Grint, Daniel; Podlekareva, Daria N.; Vassilenko, Anna; Rakhmanova, Aza; Zeltina, Indra; Losso, Marcelo H.; Miller, Robert F.; Caylá, Joan; Post, Frank A.; Miro, Jose M.; Bruyand, Mathias; Lundgren, Jens D.; Mocroft, Amanda; Kirk, Ole

2013-01-01

Objectives. The study aimed at describing characteristics and outcome of tuberculous meningitis (TBM) in HIV-positive patients and comparing these parameters with those of extrapulmonary TB (TBEP) and pulmonary TB (TBP). Methods. Kaplan-Meier estimation and Poisson regression models were used to assess the mortality following TB diagnosis and to evaluate potential prognostic factors for the 3 groups of TB patients separately. Results. A total of 100 patients with TBM, 601 with TBEP, and 371 TBP were included. Patients with TBM had lower CD4 cell counts and only 17.0% received antiretroviral therapy (ART) at TB diagnosis. The cumulative probability of death at 12 months following TB was 51.2% for TBM (95% CI 41.4–61.6%), 12.3% for TBP (8.9–15.7%), and 19.4% for TBEP (16.1–22.6) (P < 0.0001; log-rank test). For TBM, factors associated with a poorer prognosis were not being on ART (adjusted incidence rate ratio (aIRR) 4.00 (1.72–9.09), a prior AIDS diagnosis (aIRR = 4.82 (2.61–8.92)), and receiving care in Eastern Europe (aIRR = 5.41 (2.58–11.34))). Conclusions. TBM among HIV-positive patients was associated with a high mortality rate, especially for patients from Eastern Europe and patients with advanced HIV-infection, which urgently calls for public health interventions to improve both TB and HIV aspects of patient management. PMID:24699884

Cryptococcal breast abscess in an HIV-positive patient: arguments for reviewing the definition of immune reconstitution inflammatory syndrome.

PubMed

Haddow, Lewis J; Sahid, Faieza; Moosa, Mahomed-Yunus S

2008-07-01

Atypical manifestations of Cryptococcus neoformans disease have been reported in patients with HIV-1 infection as part of the spectrum of the immune reconstitution inflammatory syndrome (IRIS). We describe a cryptococcal breast abscess in a patient presenting after 11 months of highly active antiretroviral therapy (HAART). The arguments for and against the case being a novel manifestation of IRIS are discussed. The potential hazards of using CD4 count as a surrogate marker of IRIS and the danger of misdiagnosing IRIS as failure of HAART are highlighted.

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

Cryptococcal infections in two patients receiving ibrutinib therapy for chronic lymphocytic leukemia.

PubMed

Stankowicz, Matthew; Banaszynski, Megan; Crawford, Russell

2018-01-01

Cryptococcal infections are responsible for significant morbidity and mortality in immunocompromised patients. Reports of these infections in patients on small molecular kinase inhibitors have not been widely reported in clinical trials. We describe one case of cryptococcal meningoencephalitis and one case of cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic lymphocytic leukemia. Despite different sites of cryptococcal infection, both patients had similar presentations of acute illness. Patient 1 was worked up for health care-associated pneumonia, as well as acute sinusitis prior to the diagnosis of cryptococcal meningoencephalitis. He also had a more complex past medical history than patient 2. Patient 2 developed atrial fibrillation from ibrutinib prior to admission for presumed health care-associated pneumonia. Cryptococcal antigen testing was done sooner in this patient due to patient receiving high-dose steroids for the treatment of underlying hemolytic anemia. We conclude that patients who develop acute illness while receiving ibrutinib should be considered for cryptococcal antigen testing.

[Cryptococcus neoformans meningitis in children and adolescents infected with HIV].

PubMed

Quian, Jorge; Gutiérrez, Stella; González, Virginia; Sánchez, Mercedes; Abayian, Marina; Baccino, Fernando

2012-10-01

Three cases of meningitis due to criptococcus in children infected with HIV are reported. All patients had severe immunodeficiency. The first case occurred before antiretroviral therapy. The second case had poor adherence to treatment. The third case is a teenager with prolonged fever, who did not have a clear source of transmission of HIV and was immunodeficient at the time of diagnosis. Examination of cerebrospinal fluid with India ink dye was essential for making the diagnosis in all three cases. The disease course was adequate in all three patients despite flucytosine not being available.

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

Tuberculous meningitis in patients infected with the human immunodeficiency virus.

PubMed

Berenguer, J; Moreno, S; Laguna, F; Vicente, T; Adrados, M; Ortega, A; González-LaHoz, J; Bouza, E

1992-03-05

Tuberculosis is a frequent complication of human immunodeficiency virus (HIV) infection. We describe the clinical manifestations and outcomes of tuberculous meningitis in patients with HIV infection, and compare them with those in non-HIV-infected patients. We reviewed the records from 1985 through 1990 at two large referral hospitals in Madrid for patients who had Mycobacterium tuberculosis isolated from cerebrospinal fluid. Of 2205 patients with tuberculosis, 455 (21 percent) also had HIV infection, of whom 45 had M. tuberculosis isolated from the cerebrospinal fluid. Of the 37 HIV-infected patients with tuberculous meningitis for whom records were available, 24 (65 percent) had clinical or radiologic evidence of extrameningeal tuberculosis at the time of admission. In 18 of 26 patients (69 percent), a CT scan of the head was abnormal. In most patients, analysis of cerebrospinal fluid showed pleocytosis (median white-cell count, 0.234 x 10(9) per liter) and hypoglycorrhachia (median glucose level, 1.3 mmol per liter), but in 43 percent (15 of 35), the level of protein in cerebrospinal fluid was normal. In four patients with HIV infection, tuberculosis was only discovered after their deaths. Of the 33 patients who received antituberculous treatment, 7 died (in-hospital mortality, 21 percent). Illness lasting more than 14 days before admission and a CD4+ cell count of less than 0.2 x 10(9) per liter (200 per cubic millimeter) were associated with a poor prognosis. Comparison with tuberculous meningitis in patients without HIV infection showed that the presentation, clinical manifestations, cerebrospinal fluid findings, and mortality were generally similar in the two groups. However, of the 1750 patients without HIV infection, only 2 percent (38 patients) had tuberculous meningitis, as compared with 10 percent of the HIV-infected patients (P less than 0.001). HIV-infected patients with tuberculosis are at increased risk for meningitis, but infection with HIV does

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

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. © 2016 Blackwell Verlag GmbH.

The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis

PubMed Central

Chen, Yuan; Toffaletti, Dena L.; Tenor, Jennifer L.; Litvintseva, Anastasia P.; Fang, Charles; Mitchell, Thomas G.; McDonald, Tami R.; Nielsen, Kirsten; Boulware, David R.; Bicanic, Tihana; Perfect, John R.

2014-01-01

ABSTRACT Cryptococcus neoformans is the leading cause of fungal meningitis worldwide. Previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of the C. neoformans transcriptome in the human host has not been attempted. Here, we extracted RNA from yeast cells taken directly from the cerebrospinal fluid (CSF) of two AIDS patients with cryptococcal meningitis prior to antifungal therapy. The patients were infected with strains of C. neoformans var. grubii of molecular type VNI and VNII. Using RNA-seq, we compared the transcriptional profiles of these strains under three environmental conditions (in vivo CSF, ex vivo CSF, and yeast extract-peptone-dextrose [YPD]). Although we identified a number of differentially expressed genes, single nucleotide variants, and novel genes that were unique to each strain, the overall expression patterns of the two strains were similar under the same environmental conditions. Specifically, yeast cells obtained directly from each patient’s CSF were more metabolically active than cells that were incubated ex vivo in CSF. Compared with growth in YPD, some genes were identified as significantly upregulated in both in vivo and ex vivo CSF, and they were associated with genes previously recognized for contributing to pathogenicity. For example, genes with known stress response functions, such as RIM101, ENA1, and CFO1, were regulated similarly in the two clinical strains. Conversely, many genes that were differentially regulated between the two strains appeared to be transporters. These findings establish a platform for further studies of how this yeast survives and produces disease. PMID:24496797

Managing cryptococcosis in the immunocompromised host.

PubMed

Jarvis, Joseph N; Dromer, Francoise; Harrison, Thomas S; Lortholary, Olivier

2008-12-01

Expanding access to antiretroviral treatment has dramatically improved the long-term prognosis of patients with HIV-associated cryptococcal disease who survive the acute infection. However, the incidence and acute mortality of HIV-associated cryptococcal meningitis remain high. In this context, this review summarizes urgently needed recent work aimed at improving the acute management of cryptococcal infection in immunocompromised hosts. Studies have started to optimize antifungal regimens and address the complications of raised cerebrospinal fluid pressure and cryptococcal immune reconstitution syndrome. Amphotericin B at 1 mg/kg per day has been shown to be more rapidly fungicidal than the standard dose of 0.7 mg/kg per day, and new data support the importance of combination therapy with flucytosine. Amphotericin B and fluconazole at 800 mg is an alternative combination that appears superior to amphotericin B alone. At a dosage of 400 mg per day, fluconazole alone is much less rapidly fungicidal than amphotericin B and is associated with the development of secondary resistance. Recent findings support the use of rapidly fungicidal initial antifungal therapy with amphotericin B-based combination treatment. Where amphotericin B treatment is not yet feasible, studies are needed to optimize oral regimens. Based on accumulating data on rate of clearance of infection, the most promising new regimens in terms of fungicidal activity and safety could be selected for clinical endpoint trials.

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis.

PubMed

Ford, Nathan; Shubber, Zara; Jarvis, Joseph N; Chiller, Tom; Greene, Greg; Migone, Chantal; Vitoria, Marco; Doherty, Meg; Meintjes, Graeme

2018-03-04

Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%-7.3%; 54 studies) among patients with CD4 count ≤100 cells/µL and 2.0% (95% CI, 1.2%-2.7%; 21 studies) among patients with CD4 count 101-200 cells/µL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%-22.2%) of the CrAg-positive cases identified at ≤200 cells/µL (n = 11823) were identified among individuals with a CD4 count 101-200 cells/µL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%-15.5%]) compared with outpatients (6.3% [95% CI, 5.3%-7.4%]). The findings of this review support current recommendations to screen all PLHIV who have a CD4 count ≤100 cells/µL for CrAg and suggest that screening may be considered at CD4 cell count ≤200 cells/µL.

Diagnostic scoring system for tuberculous meningitis among adult patients with non-suppurative and non-bacterial meningitis.

PubMed

Chusri, Sarunyou; Hortiwakul, Thanaporn; Sathaporn, Natthaka; Charernmak, Boonsri; Phengmak, Manthana; Jitpiboon, Walailuk; Geater, Alan Frederick

2018-04-25

Tuberculous meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis. The definite diagnosis of this disease is difficult and can result in delayed treatment. Conventional culture yields low sensitivity while high-sensitivity diagnostic techniques are costly and unpractical. Adenosine deaminase (ADA) is used to diagnose several settings of extra-pulmonary tuberculosis but it is limited in TBM especially among HIV-infected patients. We retrospectively reviewed the data of patients with non-suppurative meningitis and compared the patient data with TBM and other causes including carcinomatous, lymphomatous, lymphocytic and fungal meningitis. We found that HIV infection, diabetes mellitus, duration of symptoms <14 days, radiologic findings of hydrocephalus, and CSF ADA level >10 IU were associated with TBM. The scoring system based on these parameters and their coefficients in the final model achieved an area under the receiver operating characteristic curve of 0.95,625. The indices were HIV infection = 5, diabetes mellitus = 3, duration of symptoms <14 days = 5, hydrocephalus = 4, and ADA in CSF >10 IU = 5. Based on the assumed costs of the patients with false negative and false positive, an appropriate cut off value of 10 was selected and the sensitivity was 92% and specificity was 89%. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Molecular diagnosis of central nervous system opportunistic infections and mortality in HIV-infected adults in Central China.

PubMed

Yang, Rongrong; Zhang, Hong; Xiong, Yong; Gui, Xien; Zhang, Yongxi; Deng, Liping; Gao, Shicheng; Luo, Mingqi; Hou, Wei; Guo, Deyin

2017-01-01

CSF PCR is the standard diagnostic technique used in resource-rich settings to detect pathogens of the CNS infection. However, it is not currently used for routine CSF testing in China. Knowledge of CNS opportunistic infections among people living with HIV in China is limited. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time polymerase chain reaction (PCR). Cryptococcal meningitis accounted for 63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive, 12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1 (1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high GCS score tended to have a lower mortality rate, whereas patients with multiple pathogens infection, seizures or intracranial hypertension showed higher odds of death. CNS OIs are frequent and multiple pathogens often coexist in CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve the diagnosis of AIDS related OIs in resource-limited developing countries, but the cost-efficacy remains to be further evaluated.

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis

PubMed Central

Ford, Nathan; Shubber, Zara; Jarvis, Joseph N; Chiller, Tom; Greene, Greg; Migone, Chantal; Vitoria, Marco; Doherty, Meg; Meintjes, Graeme

2018-01-01

Abstract Background Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Results Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%–7.3%; 54 studies) among patients with CD4 count ≤100 cells/µL and 2.0% (95% CI, 1.2%–2.7%; 21 studies) among patients with CD4 count 101–200 cells/µL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%–22.2%) of the CrAg-positive cases identified at ≤200 cells/µL (n = 11823) were identified among individuals with a CD4 count 101–200 cells/µL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%–15.5%]) compared with outpatients (6.3% [95% CI, 5.3%–7.4%]). Conclusions The findings of this review support current recommendations to screen all PLHIV who have a CD4 count ≤100 cells/µL for CrAg and suggest that screening may be considered at CD4 cell count ≤200 cells/µL. PMID:29514236

Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib.

PubMed

Okamoto, Koh; Proia, Laurie A; Demarais, Patricia L

2016-01-01

Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. It acts by inhibiting Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor critical for B-cell survival and proliferation. Ibrutinib use has not been associated previously with cryptococcal disease. However, recent evidence suggested that treatments aimed at blocking the function of Bruton's tyrosine kinase could pose a higher risk for cryptococcal infection in a mice model. Here, we report the first case of disseminated cryptococcal disease in a patient with CLL treated with ibrutinib. When evaluating possible infection in CLL patients receiving ibrutinib, cryptococcal disease, which could be life threatening if overlooked, could be considered.

In vitro antifungal susceptibility profiles of Cryptococcus species isolated from HIV-associated cryptococcal meningitis patients in Zimbabwe.

PubMed

Nyazika, Tinashe K; Herkert, Patricia F; Hagen, Ferry; Mateveke, Kudzanai; Robertson, Valerie J; Meis, Jacques F

2016-11-01

Cryptococcus neoformans is the leading cause of cryptococcosis in HIV-infected subjects worldwide. Treatment of cryptococcosis is based on amphotericin B, flucytosine, and fluconazole. In Zimbabwe, little is known about antifungal susceptibility of Cryptococcus. Sixty-eight genotyped Cryptococcus isolates were tested for antifungal profiles. Amphotericin B, isavuconazole, and voriconazole showed higher activity than other triazoles. Fluconazole and flucytosine were less effective, with geometric mean MICs of 2.24 and 2.67mg/L for C. neoformans AFLP1/VNI, 1.38 and 1.53mg/L for C. neoformans AFLP1A/VNB/VNII and AFLP1B/VNII, and 1.85 and 0.68mg/L for Cryptococcus tetragattii, respectively. A significant difference between flucytosine geometric mean MICs of C. neoformans and C. tetragattii was observed (P=0.0002). The majority of isolates (n=66/68; 97.1%) had a wild-type MIC phenotype of all antifungal agents. This study demonstrates a favorable situation with respect to the tested antifungals agents. Continued surveillance of antifungal susceptibility profiles is important due to the high burden of cryptococcosis in Africa. Copyright © 2016 Elsevier Inc. All rights reserved.

[Causes of death in patients with HIV infection in two Tunisian medical centers].

PubMed

Chelli, Jihène; Bellazreg, Foued; Aouem, Abir; Hattab, Zouhour; Mesmia, Hèla; Lasfar, Nadia Ben; Hachfi, Wissem; Masmoudi, Tasnim; Chakroun, Mohamed; Letaief, Amel

2016-01-01

Antiretroviral tritherapy has contributed to a considerable reduction in HIV-related mortality. The causes of death are dominated by opportunistic infections in developing countries and by cardiovascular diseases and cancer in developed countries. To determine the causes and risk factors associated with death in HIV-infected patients in two Tunisian medical centers. cross-sectional study of HIV-infected patients over 15 years treated at Sousse and Monastir medical centers between 2000 and 2014. Death was considered related to HIV if its primary cause was AIDS-defining illness or if it was due to an opportunistic infection of unknown etiology with CD4 < 50 cells/mm 3 ; it was considered unrelated to HIV if its primary cause wasn't an AIDS defining illness or if it was due to an unknown cause if no information was available. Two hundred thirteen patients, 130 men (61%) and 83 women (39%), average age 40 ± 11 years were enrolled in the study. Fifty four patients died, the mortality rate was 5.4/100 patients/year. Annual mortality rate decreased from 5.8% in 2000-2003 to 2.3% in 2012-2014. Survival was 72% at 5 years and 67% at 10 years. Death events were associated with HIV in 70.4% of cases. The leading causes of death were pneumocystis carinii pneumonia and cryptococcal meningitis in 6 cases (11%) each. Mortality risk factors were a personal history of opportunistic infections, duration of antiretroviral therapy < 12 months and smoking. Strengthening screening, early initiation of antiretroviral therapy and fight against tobacco are needed to reduce mortality in patients infected with HIV in Tunisia.

Comparison of biotyping methods as alternative identification tools to molecular typing of pathogenic Cryptococcus species in sub-Saharan Africa

PubMed Central

Nyazika, Tinashe K.; Robertson, Valerie J.; Nherera, Brenda; Mapondera, Prichard T.; Meis, Jacques F.; Hagen, Ferry

2015-01-01

Summary Cryptococcal meningitis is the leading fungal infection and AIDS defining opportunistic illness in patients with late stage HIV infection, particularly in South-East Asia and sub-Saharan Africa. Given the high mortality, clinical differences and the extensive ecological niche of Cryptococcus neoformans and Cryptococcus gattii species complexes, there is need for laboratories in sub-Sahara African countries to adopt new and alternative reliable diagnostic algorithms that rapidly identify and distinguish these species. We biotyped 74 and then amplified fragment length polymorphism (AFLP) genotyped 66 Cryptococcus isolates from a cohort of patients with HIV-associated cryptococcal meningitis. Cryptococcus gattii sensu lato was isolated at a prevalence of 16.7% (n = 11/66) and C. neoformans sensu stricto was responsible for 83.3% (n = 55/66) of the infections. l-Canavanine glycine bromothymol blue, yeast-carbon-base-d-proline-d-tryptophan and creatinine dextrose bromothymol blue thymine were able to distinguish pathogenic C. gattii sensu lato from C. neoformans sensu stricto species when compared with amplified fragment length polymorphism genotyping. This study demonstrates high C. gattii sensu lato prevalence in Zimbabwe. In addition, biotyping methods can be used as alternative diagnostic tools to molecular typing in resource-limited areas for differentiating pathogenic Cryptococcus species. PMID:26661484

Comparison of biotyping methods as alternative identification tools to molecular typing of pathogenic Cryptococcus species in sub-Saharan Africa.

PubMed

Nyazika, Tinashe K; Robertson, Valerie J; Nherera, Brenda; Mapondera, Prichard T; Meis, Jacques F; Hagen, Ferry

2016-03-01

Cryptococcal meningitis is the leading fungal infection and AIDS defining opportunistic illness in patients with late stage HIV infection, particularly in South-East Asia and sub-Saharan Africa. Given the high mortality, clinical differences and the extensive ecological niche of Cryptococcus neoformans and Cryptococcus gattii species complexes, there is need for laboratories in sub-Sahara African countries to adopt new and alternative reliable diagnostic algorithms that rapidly identify and distinguish these species. We biotyped 74 and then amplified fragment length polymorphism (AFLP) genotyped 66 Cryptococcus isolates from a cohort of patients with HIV-associated cryptococcal meningitis. C. gattii sensu lato was isolated at a prevalence of 16.7% (n = 11/66) and C. neoformans sensu stricto was responsible for 83.3% (n = 55/66) of the infections. l-Canavanine glycine bromothymol blue, yeast-carbon-base-d-proline-d-tryptophan and creatinine dextrose bromothymol blue thymine were able to distinguish pathogenic C. gattii sensu lato from C. neoformans sensu stricto species when compared with AFLP genotyping. This study demonstrates high C. gattii sensu lato prevalence in Zimbabwe. In addition, biotyping methods can be used as alternative diagnostic tools to molecular typing in resource-limited areas for differentiating pathogenic Cryptococcus species. © 2015 Blackwell Verlag GmbH.

Estimated Prevalence of Cryptococcus Antigenemia (CrAg) among HIV-Infected Adults with Advanced Immunosuppression in Namibia Justifies Routine Screening and Preemptive Treatment.

PubMed

Sawadogo, Souleymane; Makumbi, Boniface; Purfield, Anne; Ndjavera, Christophine; Mutandi, Gram; Maher, Andrew; Kaindjee-Tjituka, Francina; Kaplan, Jonathan E; Park, Benjamin J; Lowrance, David W

2016-01-01

Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naïve adults with a CD4+ count <100 cells/μL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routine screening strategies. The study design was cross-sectional. De-identified plasma specimens collected for routine CD4+ testing from HIV-infected adults enrolled in HIV care at 181 public health facilities from November 2013 to January 2014 were identified at the national reference laboratory. Remnant plasma from specimens with CD4+ counts <200 cells/μL were sampled and tested for CrAg using the IMMY® Lateral Flow Assay. CrAg prevalence was estimated and assessed for associations with age, sex, and CD4+ count. A total of 825 specimens were tested for CrAg. The median (IQR) age of patients from whom specimens were collected was 38 (32-46) years, 45.9% were female and 62.9% of the specimens had CD4 <100 cells/μL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4+ counts of CD4+<100 cells/μL and 100-200 cells/μL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/μL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/μL 50-200 (2.2%). This is the first study to estimate CrAg prevalence among HIV-infected patients in Namibia. CrAg prevalence of ≥3.0% among patients with CD4+<100 cells/μL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4+<100 cells/μL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in Namibia now recommend routine screening for CrAg.

False-positive cryptococcal antigen test associated with use of BBL Port-a-Cul transport vials.

PubMed

Wilson, Deborah A; Sholtis, Mary; Parshall, Sharon; Hall, Gerri S; Procop, Gary W

2011-02-01

A total of 52 residual CSF and serum specimens, which were originally negative with the Cryptococcal Antigen Latex Agglutination System (CALAS), were shown to become falsely positive after placement in BBL Port-A-Cul anaerobic transport vials. This transport device, although excellent for specimen transportation for subsequent culture, should not be used if cryptococcal antigen testing is needed.

Mollaret meningitis: case report with a familial association.

PubMed

Jones, Christopher W; Snyder, Graham E

2011-09-01

Mollaret meningitis is a syndrome characterized by recurrent bouts of meningitis that occur over a period of several years in an affected patient. Also known as recurrent lymphocytic meningitis, this entity involves repeated episodes of headache, stiff neck, fever, and cerebrospinal fluid pleocytosis. Herpes simplex virus type 2 is the most frequently implicated causative agent, and treatment involves the use of antiviral medications. We describe a case of Mollaret meningitis in a 47-year-old man who presented to the emergency department with his eighth episode of meningitis during a period of 20 years. Cerebrospinal fluid polymerase chain reaction testing for herpes simplex virus type 2 was positive, and further testing excluded other common viral, bacterial, and inflammatory causes of meningeal irritation. The patient's family history was significant for a brother who also had multiple episodes of aseptic meningitis during a period of several years. This represents the first published report of a possible familial association involving Mollaret meningitis. It is likely that Mollaret meningitis is underrecognized among emergency physicians, and improved recognition of this entity may limit unwarranted antibiotic use and shorten or eliminate unnecessary hospital admission.

False-Positive Cryptococcal Antigen Test Associated with Use of BBL Port-A-Cul Transport Vials▿

PubMed Central

Wilson, Deborah A.; Sholtis, Mary; Parshall, Sharon; Hall, Gerri S.; Procop, Gary W.

2011-01-01

A total of 52 residual CSF and serum specimens, which were originally negative with the Cryptococcal Antigen Latex Agglutination System (CALAS), were shown to become falsely positive after placement in BBL Port-A-Cul anaerobic transport vials. This transport device, although excellent for specimen transportation for subsequent culture, should not be used if cryptococcal antigen testing is needed. PMID:21159939

Update on bacterial meningitis: epidemiology, trials and genetic association studies.

PubMed

Kasanmoentalib, E Soemirien; Brouwer, Matthijs C; van de Beek, Diederik

2013-06-01

Bacterial meningitis is a life-threatening disease that continues to inflict a heavy toll. We reviewed recent advances in vaccination, randomized studies on treatment, and genetic association studies in bacterial meningitis. The incidence of bacterial meningitis has decreased after implementation of vaccines, and further implementation of existing conjugate vaccines particularly in low-income countries is expected to reduce the global disease burden. Several randomized studies have been performed recently in this field. Clinical studies showed that short duration (5 days) of antibiotic treatment is as effective as longer duration treatment in low-income countries, and that dexamethasone decreases death and neurological sequelae in high-income countries. Ongoing trials will further define the role of paracetamol, glycerol and hypothermia in bacterial meningitis. Genetic association studies identified pathophysiological mechanisms that could be counteracted in experimental meningitis, providing promising leads for future treatments. Conjugate vaccines have reduced the burden of bacterial meningitis in high-income countries, but implementation of available vaccines in low-income countries is necessary to reduce disease burden worldwide. Adjunctive dexamethasone therapy has beneficial effects in patients with bacterial meningitis but only in high-income countries. Genetic association studies may reveal targets for new treatment strategies.

Cryptococcal meningitis in an immunocompetent child: a case report and literature review.

PubMed

Othman, Norlijah; Abdullah, Nor Atiqah Ng; Wahab, Zubaidah Abdul

2004-12-01

An immunocompetent 5 year-old girl presented with pyrexia of unknown origin associated with headache. Initial investigations showed leukocytosis and an increased erythrocyte sedimentation rate. A Widal-Weil Felix test, blood film for malarial parasites, mycoplasma IgM antibody, cultures from blood and urine, full blood picture, Mantoux test, and chest x-ray were all negative. A lumbar puncture was done as part of a work-up for pyrexia of unknown origin. Cryptococcus neoformans was seen on India ink examination and confirmed on culture. She was treated with 10 weeks of intravenous amphotericin B and 8 weeks of fluconazole. Further immunological tests did not reveal any defect in the cell-mediated immune system. C. neoformans meningitis may present with non-specific symptoms and should be considered in a work-up for pyrexia of unknown origin.

Epidemiology of infectious meningitis in the State of Amazonas, Brazil.

PubMed

Saraiva, Maria das Graças Gomes; Santos, Eyde Cristianne Saraiva; Saraceni, Valéria; Rocha, Lívia Laura dos Santos; Monte, Rossicléia Lins; Albuquerque, Bernardino Cláudio de; Bastos, Michele de Souza; Santos, Marcelo Cordeiro dos; Monteiro, Wuelton Marcelo; Mourão, Maria Paula Gomes; Guerra, Marcus Vinitius de Farias; Lacerda, Marcus Vinícius Guimarães de

2015-01-01

In the State of Amazonas, particularly in the capital Manaus, meningitis has affected populations of different cultures and social strata over the years. Bacterial meningitis is caused by several different species and represents a major issue of public health importance. The present study reports the meningitis case numbers with different etiologies in Amazonas from January 1976 to December 2012. Since the 1970s, the (currently named) Tropical Medicine Foundation of Doutor Heitor Vieira Dourado [Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD)] has remained a reference center in Amazonas for the treatment of meningitis through the diagnosis and notification of cases and the confirmation of such cases using specific laboratory tests. The foundation has achieved coverage of over 90% of the state medical records for many years. Between 1990 and 2012, meningitis cases caused by Haemophilus influenzae decreased with the introduction of the H. influenzae vaccine. Meningococcal disease previously had a higher frequency of serogroup B disease, but starting in 2008, the detection of serogroup C increased gradually and has outpaced the detection of serogroup B. Recently, surveillance has improved the etiological definition of viral meningitis at FMT-HVD, with enteroviruses, Epstein-Barr virus (EBV) and varicella zoster virus (VZV) prevailing in this group of pathogens. With the advent of acquired immunodeficiency syndrome (AIDS), cryptococcal meningitis has become an important disease in Amazonas. Additionally, infectious meningitis is an important burden in the State of Amazonas. Changes in the epidemiological profile for the different etiology-defined cases are the result of continuous epidemiological surveillance and laboratory capacity improvements and control measures, such as Haemophilus influenzae vaccination.

Community-Acquired Meningitis in Older Adults: Clinical Features, Etiology, and Prognostic Factors

PubMed Central

Wang, Amy Y.; Machicado, Jorge D.; Khoury, Nabil T.; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

2014-01-01

Background Bacterial meningitis in older adults is a well-studied and serious disease, but few studies have investigated the epidemiology and outcomes of community-acquired meningitis in older adults. Methods We conducted a retrospective study of 619 adults in Houston, Texas, with community-acquired meningitis hospitalized between January 1, 2005, and January 1, 2010. Patients were categorized as older if age ≥65 (N=54) and younger if age 18–64 (N=565). An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Older patients consisted of 8.7% (54/619) of the total cohort and had higher rates of comorbidities, abnormal neurological and laboratory findings, abnormalities on computed tomography and magnetic resonance imaging of the head and adverse clinical outcomes (ACO) (p<0.05). The majority of patients (65.8%) had meningitis of unknown etiology. Bacterial meningitis was an infrequent cause (7.4%). Of the known causes, bacterial meningitis and West Nile virus were more common in older patients. In contrast, younger patients more frequently had cryptococcal and viral meningitis. On logistic regression, female gender was predictive of a poor outcome in the older patients, whereas abnormal neurologic exam, fever, and CSF glucose <45mg/dLwere significant poor prognostic factors in younger patients (p<0.05). Conclusion Most cases of community-acquired meningitis are of unknown origin. Older patients are more likely to have bacterial meningitis and West Nile virus infection when a cause can be identified. They also have more neurologic abnormalities, laboratory and imaging abnormalities, as well as adverse clinical outcomes. PMID:25370434

Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America

PubMed Central

Perfect, John R.; Dismukes, William E.; Dromer, Francoise; Goldman, David L.; Graybill, John R.; Hamill, Richard J.; Harrison, Thomas S.; Larsen, Robert A.; Lortholary, Olivier; Nguyen, Minh-Hong; Pappas, Peter G.; Powderly, William G.; Singh, Nina; Sobel, Jack D.; Sorrell, Tania C.

2018-01-01

Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)–infected individuals, (2) organ transplant recipients, and (3) non–HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary crypto-coccosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and crypto-coccomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients. PMID:20047480

Comparison of Scrub Typhus Meningitis with Acute Bacterial Meningitis and Tuberculous Meningitis.

PubMed

Kakarlapudi, Svas Raju; Chacko, Anila; Samuel, Prasanna; Verghese, Valsan Philip; Rose, Winsley

2018-01-15

To compare scrub typhus meningitis with bacterial and tuberculous meningitis. Children aged <15 years admitted with meningitis were screened and those who fit criteria for diagnosis of scrub typhus meningitis (n=48), bacterial meningitis (n=44) and tuberculous meningitis (n=31) were included for analysis. Clinical features, investigations and outcomes were compared between the three types of meningitis. Mean age, duration of fever at presentation, presence of headache and, altered sensorium and presence of hepatomegaly/splenomegaly were statistically significantly different between the groups. Scrub typhus had statistically significant thrombocytopenia, shorter hospital stay and a better neurological and mortality outcome. Sub-acute presentation of meningitis in older age group children, and good outcome is associated with scrub typhus when compared to bacterial and tuberculous meningitis.

Incidence of tuberculosis meningitis in a high HIV prevalence setting: time-series analysis from 2006 to 2011.

PubMed

Chaya, S; Dangor, Z; Solomon, F; Nzenze, S A; Izu, A; Madhi, S A

2016-11-01

This study was undertaken at a tertiary hospital in Soweto, a peri-urban low-middle income setting. Mycobacterium tuberculosis meningitis (TBM) is a severe manifestation of extra-pulmonary tuberculosis. To describe the incidence, mortality and clinical features of TBM in human immunodeficiency virus (HIV) infected and non-infected children in South Africa from 2006 to 2011. A retrospective, cross-sectional descriptive study. Electronic databases and individual patient records of all children with a discharge diagnosis of TBM were reviewed to yield incidence rate ratios (IRR) in HIV-infected and non-infected children. Clinical, laboratory and radiological characteristics were compared between HIV-infected and non-infected children with TBM. Overall TBM incidence per 100 000 population in 2006 was 6.9 (95%CI 4.4-10.3) and 9.8 (95%CI 6.9-13.6) in 2009, but had subsequently declined to 3.1 (95%CI 1.6-5.5) by 2011. There was a significant reduction in the IRR of TBM among HIV-infected children (IRR 0.916, P = 0.036). The overall case fatality ratio was 6.7%. Clinical features, cerebrospinal fluid and computed tomography brain findings were similar in HIV-infected and non-infected children. TBM incidence decreased over the study period from 2006 to 2011, and was temporally associated with an increase in the uptake of antiretroviral treatment in HIV-infected individuals.

Molecular epidemiology reveals genetic diversity among 363 isolates of the Cryptococcus neoformans and Cryptococcus gattii species complex in 61 Ivorian HIV-positive patients.

PubMed

Kassi, Fulgence K; Drakulovski, Pascal; Bellet, Virginie; Krasteva, Donika; Gatchitch, François; Doumbia, Adama; Kouakou, Gisèle A; Delaporte, Eric; Reynes, Jacques; Mallié, Michèle; Menan, Hervé I E; Bertout, Sebastien

2016-12-01

Cryptococcal meningitis is a severe opportunistic infection in HIV-infected patients. In Ivory Coast, despite the availability of antiretroviral treatment (ART), this infection is still prevalent. The study investigates the genetic diversity of 363 clinical isolates of Cryptococcus from 61 Ivorian HIV-positive patients, the occurrence of mixed infections and the in vitro antifungal susceptibility of the isolates. Serotyping was performed via LAC1 and CAP64 gene amplification. Genotyping was performed using the phage M13 core (GACA) 4 and (GTG) 5 primers and restriction fragment length polymorphism analysis of the URA5 gene. By PCR fingerprinting, the presence of the three serotypes were demonstrated among the 363 isolates in the population studied: A (n=318; 87.6%), AD (n=40; 11%) and B (n=4; 1.1%). Using PCR fingerprinting with primers M13 (GACA) 4 and (GTG) 5 , we grouped the isolates into 56 molecular subtypes. We observed a high frequency (39.3%) of mixed infections, with up to two different genotypes per sample. None of the isolates were resistant to amphotericin B. Only 0.3% and 1.1% of the isolates were resistant to fluconazole and flucytosine respectively. This study revealed the high genetic diversity among Cryptococcus isolates, the occurrence of mixed infections and a high antifungal susceptibility for the majority of Ivorian cryptococcal isolates. © 2016 Blackwell Verlag GmbH.

Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis.

PubMed

Choi, Jiwoon; Kim, Se Hoon

2018-01-01

Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4-11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.

Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis

PubMed Central

Choi, Jiwoon; Kim, Se Hoon

2018-01-01

Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4–11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small. PMID:29069886

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

Hypoglycorrhachia in Adults with Community-Acquired Meningitis: Etiologies and Prognostic Significance

PubMed Central

Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

2015-01-01

Study objectives Hypoglycorrhachia (CSF glucose < 45mg/dL) has been identified as a prognostic factor in patients with meningitis. We analyzed the differential diagnosis of hypoglycorrhachia and its clinical significance. Methods Retrospective study of 620 adult patients with community acquired meningitis [CSF WBC >5 cells/mm3, absence of a CSF shunt or recent neurosurgical procedure (< 1 month)] at 8 Memorial Hermann Hospitals in Houston, TX from January, 2005 to December, 2010. An adverse clinical outcome was defined as a Glasgow outcome scale of 4 or less. Results Out of 620 patients with meningitis, 116 (19%) had hypoglycorrachia. Etiologies of hypoglycorrhachia were idiopathic (40), bacterial (27), cryptococcal (26), viral (15), and tuberculous (4). Patients with hypoglycorrachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status and focal neurological deficits compared to those patients without hypoglycorrachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions and abnormal cranial imaging (p<005). Furthermore, patients with hypoglycorrachia had more adverse clinical outcomes [26 out of 116 (22.4%) vs. 45 out of 504 (8.9%)] (p< 0.001). Conclusion Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. PMID:26299186

Some clinical aspects of HIV infection in Africa.

PubMed

Harries, A

1991-07-01

WHO has estimated the cumulative number of AIDS cases in Africa to have grown from 2978 (1986) to 81,019 (1990). The actual numbers are probably much higher due to under reporting, under diagnosis, and delays in notification. Pathogenicity and clinical features of HIV 2, found mainly in west Africa, are similar to those of HIV 1. 2nd generation HIV-ELISA tests can check for both viruses' antigens. These and other ELISA tests can be used to rapidly identify HIV, but clinical criteria alone can usually determine an accurate diagnosis. In developed countries, AZT (zidovudine) shows some promise of stemming the onset of AIDS in asymptomatic patients. Other promising antiretrovirus drugs are being developed, but are all too expensive for Africa. Almost 33% of HIV positive patients in Africa also have tuberculosis (TB) and, up to 1988, around 40% of TB patients tested HIV positive. In Uganda, Zambia, and Malawi the percentages ranged from 50-65% in TB patients. HIV positive TB patients have a substantial higher mortality than HIV negative TB patients. In some areas of Africa, 66% of AIDS patients have chronic, watery diarrhea and weight loss. The most common pathogens include Cryptosporidium and Isopora belli. Cryptosporidium does not respond to treatment, so there is a concern of a hospital based outbreak in AIDS patients. Cytomegalovirus also causes gastrointestinal illness in African AIDS patients as well as pulmonary disease. Toxoplasma and Cryptococcus often attack the central nervous system of AIDS patients. Oral fluconazole can provide some initial relief from cryptococcal meningitis. Bacteremia is also common. Little evidence exists to suggest an important interaction between HIV and traditional tropical diseases. Unlike Western nations, pneumocystosis and Mycobacterium avium intracellular are uncommon in Africa.

Spectrum of clinical disease in a series of 135 hospitalised HIV-infected patients from north India

PubMed Central

Sharma, SK; Kadhiravan, Tamilarasu; Banga, Amit; Goyal, Tarun; Bhatia, Indrish; Saha, PK

2004-01-01

Background Literature on the spectrum of opportunistic disease in human immunodeficiency virus (HIV)-infected patients from developing countries is sparse. The objective of this study was to document the spectrum and determine the frequency of various opportunistic infections (OIs) and non-infectious opportunistic diseases, in hospitalised HIV-infected patients from north India. Methods One hundred and thirty five consecutive, HIV-infected patients (age 34 ± 10 years, females 17%) admitted to a tertiary care hospital in north India, for the evaluation and management of an OI or HIV-related disorder between January 2000 and July 2003, were studied. Results Fever (71%) and weight loss (65%) were the commonest presenting symptoms. Heterosexual transmission was the commonest mode of HIV-acquisition. Tuberculosis (TB) was the commonest OI (71%) followed by candidiasis (39.3%), Pneumocystis jiroveci pneumonia (PCP) (7.4%), cryptococcal meningitis and cerebral toxoplasmosis (3.7% each). Most of the cases of TB were disseminated (64%). Apart from other well-recognised OIs, two patients had visceral leishmaniasis. Two cases of HIV-associated lymphoma were encountered. CD4+ cell counts were done in 109 patients. Majority of the patients (82.6%) had CD4+ counts <200 cells/μL. Fifty patients (46%) had CD4+ counts <50 cells/μL. Only 50 patients (37%) received antiretroviral therapy. Twenty one patients (16%) died during hospital stay. All but one deaths were due to TB (16 patients; 76%) and PCP (4 patients; 19%). Conclusions A wide spectrum of disease, including both OIs and non-infectious opportunistic diseases, is seen in hospitalised HIV-infected patients from north India. Tuberculosis remains the most common OI and is the commonest cause of death in these patients. PMID:15555069

Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous Meningitis.

PubMed

Thuong, Nguyen T T; Heemskerk, Dorothee; Tram, Trinh T B; Thao, Le T P; Ramakrishnan, Lalita; Ha, Vu T N; Bang, Nguyen D; Chau, Tran T H; Lan, Nguyen H; Caws, Maxine; Dunstan, Sarah J; Chau, Nguyen V V; Wolbers, Marcel; Mai, Nguyen T H; Thwaites, Guy E

2017-04-01

Tuberculous meningitis (TBM) is the most devastating form of tuberculosis, yet very little is known about the pathophysiology. We hypothesized that the genotype of leukotriene A4 hydrolase (encoded by LTA4H), which determines inflammatory eicosanoid expression, influences intracerebral inflammation, and predicts survival from TBM. We characterized the pretreatment clinical and intracerebral inflammatory phenotype and 9-month survival of 764 adults with TBM. All were genotyped for single-nucleotide polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal fluid (CSF) leukocyte and cytokine concentrations. LTA4H genotype predicted survival of human immunodeficiency virus (HIV)-uninfected patients, with TT-genotype patients significantly more likely to survive TBM than CC-genotype patients, according to Cox regression analysis (univariate P = .040 and multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF proinflammatory cytokine concentrations, with intermediate and lower concentrations in those with CT and CC genotypes. Increased CSF cytokine concentrations correlated with more-severe disease, but patients with low CSF leukocytes and cytokine concentrations were more likely to die from TBM. HIV infection independently predicted death due to TBM (hazard ratio, 3.94; 95% confidence interval, 2.79-5.56) and was associated with globally increased CSF cytokine concentrations, independent of LTA4H genotype. LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from TBM. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Establishing a cost-per-result of laboratory-based, reflex Cryptococcal antigenaemia screening (CrAg) in HIV+ patients with CD4 counts less than 100 cells/μl using a Lateral Flow Assay (LFA) at a typical busy CD4 laboratory in South Africa.

PubMed

Cassim, Naseem; Schnippel, Kathryn; Coetzee, Lindi Marie; Glencross, Deborah Kim

2017-01-01

Cryptococcal meningitis is a major cause of mortality and morbidity in countries with high HIV prevalence, primarily affecting patients whose CD4 are < = 100 cells/μl. Routine Cryptococcal Antigen (CrAg) screening is thus recommended in the South African HIV treatment guidelines for all patients with CD4 counts < = 100 cells/μl, followed by pre-emptive anti-fungal therapy where CrAg results are positive. A laboratory-based reflexed CrAg screening approach, using a Lateral Flow Assay (LFA) on remnant EDTA CD4 blood samples, was piloted at three CD4 laboratories. This study aimed to assess the cost-per-result of laboratory-based reflexed CrAg screening at one pilot CD4 referral laboratory. CD4 test volumes from 2014 were extracted to estimate percentage of CD4 < = 100 cells/μl. Daily average volumes were derived, assuming 12 months per/year and 21.73 working days per/month. Costing analyses were undertaken using Microsoft Excel and Stata with a provider prospective. The cost-per-result was estimated using a bottom-up method, inclusive of test kits and consumables (reagents), laboratory equipment and technical effort costs. The ZAR/$ exchange of 14.696/$1 was used, where applicable. One-way sensitivity analyses on the cost-per-result were conducted for possible error rates (3%- 8%, reductions or increases in reagent costs as well as test volumes (ranging from -60% to +60%). The pilot CD4 laboratory performed 267000 CD4 tests in 2014; ~ 9.3% (27500) reported CD4< = 100 cells/μl, equivalent to 106 CrAg tests performed daily. A batch of 30-tests could be performed in 1.6 hours, including preparation and analysis time. A cost-per-result of $4.28 was reported, with reagents contributing $3.11 (72.8%), while technical effort and laboratory equipment overheads contributed $1.17 (27.2%) and $0.03 (<1%) respectively. One-way sensitivity analyses including increasing or decreasing test volumes by 60% revealed a cost-per-result range of $3.84 to $6.03. A cost-per-result of

Prediction of Outcome From Adult Bacterial Meningitis in a High-HIV-Seroprevalence, Resource-Poor Setting Using the Malawi Adult Meningitis Score (MAMS).

PubMed

Wall, Emma C; Mukaka, Mavuto; Scarborough, Matthew; Ajdukiewicz, Katherine M A; Cartwright, Katharine E; Nyirenda, Mulinda; Denis, Brigitte; Allain, Theresa J; Faragher, Brian; Lalloo, David G; Heyderman, Robert S

2017-02-15

Acute bacterial meningitis (ABM) in adults residing in resource-poor countries is associated with mortality rates >50%. To improve outcome, interventional trials and standardized clinical algorithms are urgently required. To optimize these processes, we developed and validated an outcome prediction tool to identify ABM patients at greatest risk of death. We derived a nomogram using mortality predictors derived from a logistic regression model of a discovery database of adult Malawian patients with ABM (n = 523 [65%] cerebrospinal fluid [CSF] culture positive). We validated the nomogram internally using a bootstrap procedure and subsequently used the nomogram scores to further interpret the effects of adjunctive dexamethasone and glycerol using clinical trial data from Malawi. ABM mortality at 6-week follow-up was 54%. Five of 15 variables tested were strongly associated with poor outcome (CSF culture positivity, CSF white blood cell count, hemoglobin, Glasgow Coma Scale, and pulse rate), and were used in the derivation of the Malawi Adult Meningitis Score (MAMS) nomogram. The C-index (area under the curve) was 0.76 (95% confidence interval, .71-.80) and calibration was good (Hosmer-Lemeshow C-statistic = 5.48, df = 8, P = .705). Harmful effects of adjunctive glycerol were observed in groups with relatively low predicted risk of poor outcome (25%-50% risk): Case Fatality Rate of 21% in the placebo group and 52% in the glycerol group (P < .001). This effect was not seen with adjunctive dexamethasone. MAMS provides a novel tool for predicting prognosis and improving interpretation of ABM clinical trials by risk stratification in resource-poor settings. Whether MAMS can be applied to non-HIV-endemic countries requires further evaluation. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Cryptococcal Meningoencephalitis Relapse after an 8 Year Delay: An Interplay of Infection and Immune Reconstitution?

PubMed Central

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

2016-01-01

We report a case of a symptomatic relapse of HIV-related cryptococcal meningoencephalitis 8 years after the first diagnosis on the background of immune reconstitution. The findings as well as the clinical course suggests a combination of smouldering localized 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

Human Meningitis-Associated Escherichia coli.

PubMed

Kim, Kwang Sik

2016-05-01

Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Our incomplete knowledge of its pathogenesis contributes to such mortality and morbidity. Recent reports of E. coli strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. Studies using in vitro and in vivo models of the blood-brain barrier have shown that E. coli meningitis follows a high degree of bacteremia and invasion of the blood-brain barrier. E. coli invasion of the blood-brain barrier, the essential step in the development of E. coli meningitis, requires specific microbial and host factors as well as microbe- and host-specific signaling molecules. Blockade of such microbial and host factors contributing to E. coli invasion of the blood-brain barrier is shown to be efficient in preventing E. coli penetration into the brain. The basis for requiring a high degree of bacteremia for E. coli penetration of the blood-brain barrier, however, remains unclear. Continued investigation on the microbial and host factors contributing to a high degree of bacteremia and E. coli invasion of the blood-brain barrier is likely to identify new targets for prevention and therapy of E. coli meningitis.

Validation of Thwaites Index for diagnosing tuberculous meningitis in a Colombian population.

PubMed

Saavedra, Juan Sebastián; Urrego, Sebastián; Toro, María Eugenia; Uribe, Carlos Santiago; García, Jenny; Hernández, Olga; Arango, Juan Carlos; Pérez, Ángela Beatriz; Franco, Andrés; Vélez, Isabel Cristina; Del Corral, Helena

2016-11-15

To determine the diagnostic accuracy of Thwaites Index (TI) in a Colombian population to distinguish meningeal tuberculosis (MTB) from bacterial meningitis (BM) and from non-tuberculous meningitis. Exploratory analyses were conducted to assess the TI's validity for patients with human immunodeficiency virus (HIV) and children above six-years-old. The study included 527 patients, the TI was calculated and results compared with those of a reference standard established by expert neurologists. Sensitivity, specificity, area under the curve of receiver-operator characteristics (AUC-ROC) and likelihood ratios were calculated. The AUC-ROC to distinguish MTB from non-tuberculous meningitis was 0.72 (95% CI: 0.67-0.77) for HIV negative adults. AUC-ROC was 0.62 (95% CI: 0.50-0.74) for HIV positive adults and 0.83 (95% CI: 0.68-0.97) for children. For distinguishing MTB from BM the AUC-ROC was 0.78 (95% CI: 0.73-0.83); furthermore, the AUC-ROC was 0.57 (95% CI: 0.31-0.83) for HIV positive adults and 0.86 (95% CI: 0.73-0.99) for children. The TI was sensitive but not specific when used to distinguish MTB from BM in HIV negative adults. In HIV positive adults the index had low diagnostic accuracy. Moreover, the TI showed discrimination capability for children over 6years; however, research with larger samples is required in these. Copyright © 2016 Elsevier B.V. All rights reserved.

Herpes simplex virus type 2-associated recurrent aseptic meningitis (Mollaret's meningitis) with a recurrence after 11-year interval: a case report.

PubMed

Nakamura, Yoshitsugu; Nakajima, Hideto; Kano, Yosuke; Unoda, Kiichi; Ishida, Shimon; Kimura, Fumiharu

2016-11-29

A 55-year-old woman was diagnosed with aseptic meningitis at the age of 43 and 44. She developed sudden fever and headache, and she showed nuchal rigidity. Cerebrospinal fluid examination revealed pleocytosis (cell count 208/mm 3 ) and was positive for herpes simplex virus type 2 (HSV-2) DNA by PCR. Acyclovir was started on the first day of admission, and she was complete recovery. Preserved cerebrospinal fluid specimen from aseptic meningitis at the age of 44 was also positive for HSV-2 DNA by PCR. She was diagnosed with HSV-2 associated recurrent aseptic meningitis (Mollaret's meningitis) with a recurrence after 11-year interval. She repeatedly relapsed genital herpes after 44 years old and she was treated with valacyclovir whenever genital herpes relapses. But she showed no genital herpes at the onset of meningitis. Because HSV-2 is one of the most significant causes of recurrent meningitis, we would like to stress that HSV-2 infection and antiviral therapy should always be kept in mind for a recurrent meningitis case.

Human Meningitis-Associated Escherichia coli

PubMed Central

KIM, KWANG SIK

2016-01-01

E. coli is the most common Gram-negative bacillary organism causing meningitis and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Our incomplete knowledge of its pathogenesis contributes to such mortality and morbidity. Recent reports of E. coli strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. Studies using in vitro and in vivo models of the blood-brain barrier have shown that E. coli meningitis follows a high-degree of bacteremia and invasion of the blood-brain barrier. E. coli invasion of the blood-brain barrier, the essentials step in the development of E. coli meningitis, requires specific microbial and host factors as well as microbe- and host-specific signaling molecules. Blockade of such microbial and host factors contributing to E. coli invasion of the blood-brain barrier is shown to be efficient in preventing E. coli penetration into the brain. The basis for requiring a high-degree of bacteremia for E. coli penetration of the blood-brain barrier, however, remains unclear. Continued investigation on the microbial and host factors contributing to a high-degree of bacteremia and E. coli invasion of the blood-brain barrier is likely to identify new targets for prevention and therapy of E. coli meningitis. PMID:27223820

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.

Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them?

PubMed

Parkes-Ratanshi, R; Achan, B; Kwizera, R; Kambugu, A; Meya, D; Denning, D W

2015-10-01

The HIV epidemic in Uganda has highlighted Cryptococcus and Candida infections as important opportunistic fungal infections. However, the burden of other fungal diseases is not well described. We aimed to estimate the burden of fungal infections in Uganda. All epidemiological papers of fungal diseases in Uganda were reviewed. Where there is no Ugandan data, global or East African data were used. Recurrent vaginal candidiasis is estimated to occur in 375 540 Uganda women per year; Candida in pregnant women affects up to 651,600 women per year. There are around 45,000 HIV-related oral and oesophageal candidosis cases per year. There are up to 3000 cases per year of post-TB chronic pulmonary aspergillosis. There are an estimated 40,392 people with asthma-related fungal conditions. An estimated 1,300,000 cases of tinea capitis occur in school children yearly in Uganda. There are approximately 800 HIV-positive adults with Pneumocystis jirovecii pneumonia (PJP) annually and up to 42 000 children with PJP per year. There are an estimated 4000 cryptococcal cases annually. There are an estimated 2.5 million fungal infections per year in Uganda. Cryptococcus and PJP cause around 28,000 deaths in adults and children per year. We propose replicating the model of research around cryptococcal disease to investigate and development management strategies for other fungal diseases in Uganda. © 2015 Blackwell Verlag GmbH.

Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance.

PubMed

Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

2015-10-01

Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has been identified as a prognostic factor in patients with meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study. This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1 month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005 to December 2010. An adverse clinical outcome was defined as a Glasgow outcome scale score of ≤ 4. Out of 620 patients with meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore, patients with hypoglycorrhachia had more adverse clinical outcomes (26/116 (22.4%) vs. 45/504 (8.9%); p<0.001). Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Integrating Clinical Services for HIV, Tuberculosis, and Cryptococcal Disease in the Developing World: A Step Forward with 2 Novel Diagnostic Tests

PubMed Central

Vijayan, Tara; Klausner, Jeffrey D.

2014-01-01

The success of antiretroviral therapy (ART) programs in the developing world is limited by the lack of adequate diagnostic tests to screen for life-threatening opportunistic infections such as tuberculosis (TB) and cryptococcal disease. Furthermore, there is an increasing need for implementation research in measuring the effectiveness of currently available rapid diagnostic tests. The recently developed lateral flow assays for both cryptococcal disease and TB have the potential to improve care and greatly reduce the time to initiation of ART among individuals who need it the most. However, we caution that the data on feasibility and effectiveness of these assays are limited and such research agendas must be prioritized. PMID:24065780

Cryptococcal necrotizing fasciitis in a patient after renal transplantation--a case report.

PubMed

Yoneda, T; Itami, Y; Hirayama, A; Saka, T; Yoshida, K; Fujimoto, K

2014-01-01

A 50-year-old man, who had received an ABO-incompatible living related preemptive renal transplantation 1 year before, presented with painful lesions on both lower extremities and fever. At first, bacterial cellulitis was suspected and antibiotic therapy was initiated, but it was not effective. The serum cryptococcal antigen titer was 1:4,098, and pathologic examination of debrided tissue and wound pus culture revealed cryptococcal necrotizing fasciitis. Liposomal amphotericin B and fluconazole were started, and repeated debridement and skin grafting were performed. Because his graft function deteriorated because of antibody-mediated rejection and polyoma viral nephropathy, hemodialysis was induced on day 9 of hospitalization. During the treatment, he suffered repeated urinary tract infections, which were treated with antibiotics, and cytomegalovirus retinopathy, which was treated with ganciclovir. His cryptococcal necrotizing fasciitis was successfully cured by the combination of antimicrobial treatment and surgical procedures. He could walk with a cane and was discharged on day 298 of hospitalization. Cryptococcal necrotizing fasciitis in renal transplant recipients is so rare that only 14 cases have been reported. The mortality is not very high, but the prognosis of the patient is complicated by worsening of the cryptococcal infection of the central nervous system (CNS). Early detection and treatment to prevent spreading to other sites, especially the CNS or disseminated disease, is very important in cases of cryptococcal necrotizing fasciitis. Copyright © 2014 Elsevier Inc. All rights reserved.

Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection.

PubMed

Hagberg, Lars; Cinque, Paola; Gisslen, Magnus; Brew, Bruce J; Spudich, Serena; Bestetti, Arabella; Price, Richard W; Fuchs, Dietmar

2010-06-03

HIV-1 invades the central nervous system (CNS) in the context of acute infection, persists thereafter in the absence of treatment, and leads to chronic intrathecal immunoactivation that can be measured by the macrophage activation marker, neopterin, in cerebrospinal fluid (CSF). In this review we describe our experience with CSF neopterin measurements in 382 untreated HIV-infected patients across the spectrum of immunosuppression and HIV-related neurological diseases, in 73 untreated AIDS patients with opportunistic CNS infections, and in 233 treated patients.In untreated patients, CSF neopterin concentrations are almost always elevated and increase progressively as immunosuppression worsens and blood CD4 cell counts fall. However, patients with HIV dementia exhibit particularly high CSF neopterin concentrations, above those of patients without neurological disease, though patients with CNS opportunistic infections, including CMV encephalitis and cryptococcal meningitis, also exhibit high levels of CSF neopterin. Combination antiretroviral therapy, with its potent effect on CNS HIV infection and CSF HIV RNA, mitigates both intrathecal immunoactivation and lowers CSF neopterin. However, despite suppression of plasma and CSF HIV RNA to below the detection limits of clinical assays (<50 copies HIV RNA/mL), CSF neopterin often remains mildly elevated, indicating persistent low-level intrathecal immune activation and raising the important questions of whether this elevation is driven by continued CNS infection and whether it causes continued indolent CNS injury.Although nonspecific, CSF neopterin can serve as a useful biomarker in the diagnosis of HIV dementia in the setting of confounding conditions, in monitoring the CNS inflammatory effects of antiretroviral treatment, and give valuable information to the cause of ongoing brain injury.

Bacterial meningitis and Haemophilus influenzae type b conjugate vaccine, Malawi.

PubMed

McCormick, David W; Molyneux, Elizabeth M

2011-04-01

A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997-2009), and pneumococcus was the most common etiologic agent (57% in 2009).

Maternal and perinatal factors associated with subsequent meningococcal, Haemophilus or enteroviral meningitis in children: database study.

PubMed

Goldacre, M J; Wotton, C J; Maisonneuve, J J

2014-02-01

We used a database of 248 659 births, with follow-up to subsequent disease, in the Oxford record linkage archive (1979-1999) to study the influence of family, maternal, and perinatal factors on subsequent hospital admission for meningococcal, Haemophilus, and enteroviral meningitis in the children. In this summary, we report key findings that were significant in multivariate analysis. Meningococcal meningitis was significantly associated with maternal smoking [odds ratio (OR) 2·1, 95% confidence interval (CI) 1·2-3·7]. Haemophilus meningitis was associated with having older siblings (e.g. second child compared to first-born, OR 3·3, 95% CI 2·0-5·6). Enteroviral meningitis was associated with low birth weight (OR 2·2, 95% CI 1·3-3·6) and male sex (OR 1·7, 95% CI 1·2-2·3). The mothers of six of the 312 children with enteroviral meningitis had previously had enteroviral meningitis themselves. We concluded that several maternal characteristics influence the risk of these types of meningitis.

Multilocus Sequence Typing of Serially Collected Isolates of Cryptococcus from HIV-Infected Patients in South Africa

PubMed Central

Van Wyk, Marelize; Govender, Nelesh P.; Litvintseva, Anastasia P.

2014-01-01

Patients with cryptococcal meningitis in sub-Saharan Africa frequently relapse following treatment. The natural history and etiology of these recurrent episodes warrant investigation. Here, we used multilocus sequence typing (MLST) to compare the molecular genotypes of strains of Cryptococcus neoformans and Cryptococcus gattii isolated from serial episodes of cryptococcal meningitis that were separated by at least 110 days. The most common MLST genotypes among the isolates were the dominant global clinical genotypes (M5 and M4) of molecular type VNI, as well as the VNI genotypes apparently restricted to southern Africa. In addition, there was considerable genetic diversity among these South African isolates, as 15% of the patients had unique genotypes. Eleven percent of the patients were reinfected with a genetically different strain following their initial diagnosis and treatment. However, the majority of serial episodes (89%) were caused by strains with the same genotype as the original strain. These results indicate that serial episodes of cryptococcosis in South Africa are frequently associated with persistence or relapse of the original infection. Using a reference broth microdilution method, we found that the serial isolates of 11% of the patients infected with strains of C. neoformans var. grubii with identical genotypes exhibited ≥4-fold increases in the MICs to fluconazole. Therefore, these recurrent episodes may have been precipitated by inadequate induction or consolidation of antifungal treatment and occasionally may have been due to increased resistance to fluconazole, which may have developed during the chronic infection. PMID:24648562

Bacterial Meningitis and Haemophilus influenzae Type b Conjugate Vaccine, Malawi

PubMed Central

Molyneux, Elizabeth M.

2011-01-01

A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997–2009), and pneumococcus was the most common etiologic agent (57% in 2009). PMID:21470461

Estimating the cost-per-result of a national reflexed Cryptococcal antigenaemia screening program: Forecasting the impact of potential HIV guideline changes and treatment goals.

PubMed

Cassim, Naseem; Coetzee, Lindi Marie; Schnippel, Kathryn; Glencross, Deborah Kim

2017-01-01

During 2016, the National Health Laboratory Service (NHLS) introduced laboratory-based reflexed Cryptococcal antigen (CrAg) screening to detect early Cryptococcal disease in immunosuppressed HIV+ patients with a confirmed CD4 count of 100 cells/μl or less. The aim of this study was to assess cost-per-result of a national screening program across different tiers of laboratory service, with variable daily CrAg test volumes. The impact of potential ART treatment guideline and treatment target changes on CrAg volumes, platform choice and laboratory workflow are considered. CD4 data (with counts < = 100 cells/μl) from the fiscal year 2015/16 were extracted from the NHLS Corporate Date Warehouse and used to project anticipated daily CrAg testing volumes with appropriately-matched CrAg testing platforms allocated at each of 52 NHLS CD4 laboratories. A cost-per-result was calculated for four scenarios, including the existing service status quo (Scenario-I), and three other settings (as Scenarios II-IV) which were based on information from recent antiretroviral (ART) guidelines, District Health Information System (DHIS) data and UNAIDS 90/90/90 HIV/AIDS treatment targets. Scenario-II forecast CD4 testing offered only to new ART initiates recorded at DHIS. Scenario-III projected all patients notified as HIV+, but not yet on ART (recorded at DHIS) and Scenario-IV forecast CrAg screening in 90% of estimated HIV+ patients across South Africa (also DHIS). Stata was used to assess daily CrAg volumes at the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles across 52 CD4-laboratories. Daily volumes were used to determine technical effort/ operator staff costs (% full time equivalent) and cost-per-result for all scenarios. Daily volumes ranged between 3 and 64 samples for Scenario-I at the 5th and 95th percentile. Similarly, daily volumes ranges of 1-12, 2-45 and 5-100 CrAg-directed samples were noted for Scenario's II, III and IV respectively. A cut-off of 30 CrAg tests per

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

[Tuberculous meningitis with atypical presentation in a patient with human immunodeficiency virus infection].

PubMed

López, M T; Lluch, M; Fernández-Solá, J; Coca, A; Urbano-Márquez, A

1992-04-11

A 32 years old male patient is described with infection by the human immunodeficiency virus (HIV) on stage IV C1 and with positive Ag p24 who developed tuberculous meningitis of atypical presentation. A persistent liquoral neutrophilia and low adenosindeaminase values were observed in cerebrospinal fluid of purulent appearance. The patient responded badly to tuberculostatic treatment and died. In the antibiogram carried out resistance to Mycobacterium tuberculosis was observed to rifampicine and isoniazide, two of the five drugs the patient had received. The peculiarities of the clinical form of presentation similar to purulent bacterian meningitis are discussed, and the possible influence of HIV infection and the antibiotic multiresistance observed in the bad evolution of the tuberculous meningitis which the patient developed.

Successful Treatment of Disseminated Cryptococcal Infection in a Pediatric Acute Lymphoblastic Leukemia Patient During Induction

PubMed Central

Heath, Jessica L.; Yin, Dwight E.; Wechsler, Daniel S.; Turner, David A.

2015-01-01

Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between anti-fungal and anti-neoplastic therapy. This balance is particularly important early in the course of leukemia, since both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy. PMID:22258349

Cryptococcal meningoencephalitis in patients with mantle cell lymphoma on ibrutinib.

PubMed

Sun, Kai; Kasparian, Saro; Iyer, Swaminathan; Pingali, Sai Ravi

2018-01-01

Ibrutinib, a Bruton's tyrosine kinase inhibitor, has been increasingly widely used in relapsed and refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia [1, 2]. With its use becoming more common, there have been emerging case reports of opportunistic infections like cryptococcal infections [3-8]. These infections in patients receiving ibrutinib were mostly reported in patients with chronic lymphocytic leukaemia, who have poor immune reconstitution. Here, we report two cases of cryptococcal meningoencephalitis in patients with MCL on ibrutinib.

In vitro and in vivo effect of PD-1/PD-L1 blockade on microglia/macrophage activation and T cell subset balance in cryptococcal meningitis.

PubMed

Che, Yuan-Mei; Zhang, Yi; Li, Ming; Li, Xiao-Peng; Zhang, Lun-Li

2018-04-01

This study aimed to investigate the PD-1/ PD-L1 signaling pathway and its effects the activation of microglia/macrophage and balancing T cell subsets in cryptococcal meningitis (CM). A total of 126 CM patients and 126 healthy individuals were recruited for the study. The CM patients were treated with amphotericin B (AmB). Seventy five C57BL/6 mice were grouped into the normal control, CM model, CM + AmB, sham, and CM + PD-1 antibodies (Ab) groups. CD4 + and CD8 + T cells as well as microglia/macrophages were analyzed by means of flow cytometry. Ionized calcium-binding adaptor molecule 1 (Ibal) expression was detected using western blotting and immunohistochemistry techniques. And the expression of Rab5 and Rab11 were detected using an immunofluorescence assay. Both PD-1 and PD-L1 mRNA and protein expression among the mice in the study were evaluated by qRT-PCR and western blotting methods. Compared to the CM model group, the CM + AmB and CM + PD-1 Ab groups exhibited increased levels of Th1 cytokines and chemokines expression, and reduced levels of Th2 cytokines expressions. Elevated cell purity and viability of CD4 + T cell were recorded as well as increases in microglia, however, there were reductions in the number of CD8 + T cells. Depleted expressions of Ibal, Rab5, and Rab11 as well as reduced mRNA expressions of PD-1 and PD-L1 in CD4 + , microglia, and macrophage cells. The findings suggested that suppression of the PD-1/PD-L1 signaling pathway restricts the proliferation of CM by down-regulating the expressions of Th2 cells and suppressing microglia and macrophage activation. © 2017 Wiley Periodicals, Inc.

Zoonotic bacterial meningitis in human adults.

PubMed

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

2016-09-13

To describe the epidemiology, etiology, clinical characteristics, treatment, outcome, and prevention of zoonotic bacterial meningitis in human adults. We identified 16 zoonotic bacteria causing meningitis in adults. Zoonotic bacterial meningitis is uncommon compared to bacterial meningitis caused by human pathogens, and the incidence has a strong regional distribution. Zoonotic bacterial meningitis is mainly associated with animal contact, consumption of animal products, and an immunocompromised state of the patient. In a high proportion of zoonotic bacterial meningitis cases, CSF analysis showed only a mildly elevated leukocyte count. The recommended antibiotic therapy differs per pathogen, and the overall mortality is low. Zoonotic bacterial meningitis is uncommon but is associated with specific complications. The suspicion should be raised in patients with bacterial meningitis who have recreational or professional contact with animals and in patients living in regions endemic for specific zoonotic pathogens. An immunocompromised state is associated with a worse prognosis. Identification of risk factors and underlying disease is necessary to improve treatment. © 2016 American Academy of Neurology.

Infections in patients undergoing craniotomy: risk factors associated with post-craniotomy meningitis.

PubMed

Kourbeti, Irene S; Vakis, Antonis F; Ziakas, Panayiotis; Karabetsos, Dimitris; Potolidis, Evangelos; Christou, Silvana; Samonis, George

2015-05-01

OBJECT The authors performed a prospective study to define the prevalence and microbiological characteristics of infections in patients undergoing craniotomy and to clarify the risk factors for post-craniotomy meningitis. METHODS Patients older than 18 years who underwent nonstereotactic craniotomies between January 2006 and December 2008 were included. Demographic, clinical, laboratory, and microbiological data were systemically recorded. Patient characteristics, craniotomy type, and pre- and postoperative variables were evaluated as risk factors for meningitis RESULTS Three hundred thirty-four procedures were analyzed (65.6% involving male patients). Traumatic brain injury was the most common reason for craniotomy. Almost 40% of the patients developed at least 1 infection. Ventilator-associated pneumonia (VAP) was the most common infection recorded (22.5%) and Acinetobacter spp. were isolated in 44% of the cases. Meningitis was encountered in 16 procedures (4.8%), and CSF cultures were positive for microbial growth in 100% of these cases. Gram-negative pathogens (Acinetobacter spp., Klebsiella spp., Pseudomonas aeruginosa, Enterobacter cloaceae, Proteus mirabilis) represented 88% of the pathogens. Acinetobacter and Klebsiella spp. demonstrated a high percentage of resistance in several antibiotic classes. In multivariate analysis, the risk for meningitis was independently associated with perioperative steroid use (OR 11.55, p = 0.005), CSF leak (OR 48.03, p < 0.001), and ventricular drainage (OR 70.52, p < 0.001). CONCLUSIONS Device-related postoperative communication between the CSF and the environment, CSF leak, and perioperative steroid use were defined as risk factors for meningitis in this study. Ventilator-associated pneumonia was the most common infection overall. The offending pathogens presented a high level of resistance to several antibiotics.

Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis

PubMed Central

Goonetilleke, U. R.; Scarborough, M.; Ward, S. A.; Hussain, S.; Kadioglu, A.; Gordon, S. B.

2012-01-01

ABSTRACT Pneumococcal meningitis can lead to death or serious neurological sequelae as a result of the host inflammatory response. We investigated the association between host response protein expression and outcome in patients with pneumococcal meningitis. Cerebrospinal fluid (CSF) was obtained from 80 patients with pneumococcal meningitis (40 nonsurvivors and 40 survivors) and 10 normal controls. Candidate proteins were analyzed for an association with survival. Complement C3 levels were 5-fold lower in nonsurvivors than in survivors (P < 0.05). This C3 reduction was not associated with lower levels in serum, indicating a compartmentalized CSF response. Transferrin levels were significantly higher in CSF (but not serum) from nonsurvivors than in CSF from survivors, suggestive of blood-brain barrier damage. Classical apoptosis proteins caspase 3 and apoptosis-inducing factor were not present in CSF. Expression of creatine kinase BB in clinically infected CSF suggested neuronal necrosis, but there was no clear association between level of expression and clinical outcome. Increased blood-brain barrier permeability and complement C3 depletion may have a role in determining outcome from bacterial meningitis. Therapeutic use of citicoline or caspase inhibitors is unlikely to have beneficial effects in patients with meningitis. PMID:22415003

Meningitis caused by Rhodotorula mucilaginosa in human immunodeficiency virus seropositive patient

PubMed Central

Baradkar, V. P.; Kumar, S.

2008-01-01

Rhodotorula species may be responsible for systemic infection in immunocompromised patients. Meningitis by Rhodotorula species in human immunodeficiency virus (HIV) infected persons has been reported previously. We report a case of meningitis caused by Rhodotorula mucilaginosa in a 36-year-old HIV seropositive male patient who presented with fever, altered sensorium and features of meningeal irritation i.e. neck rigidity. The Cerebrospinal fluid (CSF) cell counts were high, showing 150 cells/mm3, with 60% lymphocytes and 40% polymorphs, and protein content of 100 mg%; glucose was 60 mg%. The diagnosis was confirmed by culture on Sabouraud's Dextrose agar. The patient was treated successfully with intensive Amphotericin B (1 mg/kg), for two weeks, followed by oral Itraconazole (400 mg daily), for a period of two months. The patient was started on anti retroviral therapy. He did not show any relapse of the symptoms when the last follow up was done six months after the date of discharge. PMID:19893682

Performance of nested RT-PCR on CSF for tuberculous meningitis diagnosis in HIV-infected patients.

PubMed

Gualberto, F A S; Gonçalves, M G; Fukasawa, L O; Santos, A M Ramos Dos; Sacchi, C T; Harrison, L H; Boulware, D R; Vidal, J E

2017-10-01

Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.

Genetic Variation in the β2-Adrenocepter Gene Is Associated with Susceptibility to Bacterial Meningitis in Adults

PubMed Central

Adriani, Kirsten S.; Brouwer, Matthijs C.; Baas, Frank; Zwinderman, Aeilko H.; van der Ende, Arie; van de Beek, Diederik

2012-01-01

Recently, the biased β2-adrenoceptor/β-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the β2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective genetic association study we genotyped 542 patients with CSF culture proven community acquired bacterial meningitis and 376 matched controls for 2 functional single nucleotide polymorphisms in the β2-adrenoceptor gene (ADRB2). Furthermore, we analyzed if the use of non-selective beta-blockers, which bind to the β2-adrenoceptor, influenced the risk of bacterial meningitis. We identified a functional polymorphism in ADRB2 (rs1042714) to be associated with an increased risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI] 1.04–1.76; p = 0.026). The association remained significant after correction for age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95% CI 1.12–2.07; p = 0.007). For meningococcal meningitis the difference in genotype frequencies between patients and controls was similar to that in pneumococcal meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60–3.38; p = 0.72). Patients with bacterial meningitis had a lower frequency of non-selective beta-blockers use compared to the age matched population (0.9% vs. 1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88–4.39]; p = 0.09). In conclusion, we identified an association between a genetic variant in the β2-adrenoceptor and increased susceptibility to bacterial meningitis. The potential benefit of pharmacological treatment targeting the β2-adrenoceptor to prevent bacterial meningitis in the general population or patients with bacteraemia should be further studied in both experimental studies and observational cohorts. PMID:22624056

Molecular identification of enteroviruses associated with aseptic meningitis in children from India.

PubMed

Kumar, Arvind; Shukla, Deepti; Kumar, Rashmi; Idris, Mohammad Z; Jauhari, Prashant; Srivastava, Shalini; Dhole, Tapan N

2013-01-01

We identified and characterized enteroviruses associated with aseptic meningitis in children between April 2009 and March 2010. Enterovirus RNA was detected in 51 (45.5 %) of 112 CSF samples. Molecular typing by RT-PCR and sequencing of a partial VP1 region revealed the predominance of echovirus (ECV) 32 (n = 20), followed by ECV 11 (n = 10), ECV 13 and ECV 14 (n = 5 each), coxsackievirus (CV) B3 and CV B6 (n = 3 each), CV A2, CV A10 and ECV 30 (n = 1 each). Phylogenetic analysis of ECV 32 showed 0 to 4 % sequence divergence among strains of the present study and 20-23 % from the prototype Puerto Rico strain at the nucleotide level. This is the first report of ECV 32 associated with an aseptic meningitis epidemic and identification of seven different enterovirus serotypes (CV A2, CV A10, CV B3, CV B6, ECV 13, ECV 14 and ECV 32) in meningitis cases from India.

Community-acquired bacterial meningitis.

PubMed

van de Beek, Diederik; Brouwer, Matthijs; Hasbun, Rodrigo; Koedel, Uwe; Whitney, Cynthia G; Wijdicks, Eelco

2016-11-03

Meningitis is an inflammation of the meninges and subarachnoid space that can also involve the brain cortex and parenchyma. It can be acquired spontaneously in the community - community-acquired bacterial meningitis - or in the hospital as a complication of invasive procedures or head trauma (nosocomial bacterial meningitis). Despite advances in treatment and vaccinations, community-acquired bacterial meningitis remains one of the most important infectious diseases worldwide. Streptococcus pneumoniae and Neisseria meningitidis are the most common causative bacteria and are associated with high mortality and morbidity; vaccines targeting these organisms, which have designs similar to the successful vaccine that targets Haemophilus influenzae type b meningitis, are now being used in many routine vaccination programmes. Experimental and genetic association studies have increased our knowledge about the pathogenesis of bacterial meningitis. Early antibiotic treatment improves the outcome, but the growing emergence of drug resistance as well as shifts in the distribution of serotypes and groups are fuelling further development of new vaccines and treatment strategies. Corticosteroids were found to be beneficial in high-income countries depending on the bacterial species. Further improvements in the outcome are likely to come from dampening the host inflammatory response and implementing preventive measures, especially the development of new vaccines.

Meningitis

MedlinePlus

... and spinal cord. This covering is called the meninges. Causes The most common causes of meningitis are ... Kernig's sign of meningitis Lumbar puncture (spinal tap) Meninges of the brain Meninges of the spine Haemophilus ...

Genomic epidemiology of Cryptococcus yeasts identifies adaptation to environmental niches underpinning infection across an African HIV/AIDS cohort.

PubMed

Vanhove, Mathieu; Beale, Mathew A; Rhodes, Johanna; Chanda, Duncan; Lakhi, Shabir; Kwenda, Geoffrey; Molloy, Sile; Karunaharan, Natasha; Stone, Neil; Harrison, Thomas S; Bicanic, Tihana; Fisher, Matthew C

2017-04-01

Emerging infections caused by fungi have become a widely recognized global phenomenon and are causing an increasing burden of disease. Genomic techniques are providing new insights into the structure of fungal populations, revealing hitherto undescribed fine-scale adaptations to environments and hosts that govern their emergence as infections. Cryptococcal meningitis is a neglected tropical disease that is responsible for a large proportion of AIDS-related deaths across Africa; however, the ecological determinants that underlie a patient's risk of infection remain largely unexplored. Here, we use genome sequencing and ecological genomics to decipher the evolutionary ecology of the aetiological agents of cryptococcal meningitis, Cryptococcus neoformans and Cryptococcus gattii, across the central African country of Zambia. We show that the occurrence of these two pathogens is differentially associated with biotic (macroecological) and abiotic (physical) factors across two key African ecoregions, Central Miombo woodlands and Zambezi Mopane woodlands. We show that speciation of Cryptococcus has resulted in adaptation to occupy different ecological niches, with C. neoformans found to occupy Zambezi Mopane woodlands and C. gattii primarily recovered from Central Miombo woodlands. Genome sequencing shows that C. neoformans causes 95% of human infections in this region, of which over three-quarters belonged to the globalized lineage VNI. We show that VNI infections are largely associated with urbanized populations in Zambia. Conversely, the majority of C. neoformans isolates recovered in the environment belong to the genetically diverse African-endemic lineage VNB, and we show hitherto unmapped levels of genomic diversity within this lineage. Our results reveal the complex evolutionary ecology that underpins the reservoirs of infection for this, and likely other, deadly pathogenic fungi. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

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

Associations among habitat characteristics and meningeal worm prevalence in eastern South Dakota, USA

USGS Publications Warehouse

Jacques, Christopher N.; Jenks, Jonathan A.; Klaver, Robert W.; Dubay, Shelli A.

2017-01-01

Few studies have evaluated how wetland and forest characteristics influence the prevalence of meningeal worm (Parelaphostrongylus tenuis) infection of deer throughout the grassland biome of central North America. We used previously collected, county-level prevalence data to evaluate associations between habitat characteristics and probability of meningeal worm infection in white-tailed deer (Odocoileus virginianus) across eastern South Dakota, US. The highest-ranked binomial regression model for detecting probability of meningeal worm infection was spring temperature + summer precipitation + percent wetland; weight of evidence (wi=0.71) favored this model over alternative models, though predictive capability was low (Receiver operating characteristic=0.62). Probability of meningeal worm infection increased by 1.3- and 1.6-fold for each 1-cm and 1-C increase in summer precipitation and spring temperature, respectively. Similarly, probability of infection increased 1.2-fold for each 1% increase in wetland habitat. Our findings highlight the importance of wetland habitat in predicting meningeal worm infection across eastern South Dakota. Future research is warranted to evaluate the relationships between climatic conditions (e.g., drought, wet cycles) and deer habitat selection in maintaining P. tenuis along the western boundary of the parasite.

Intracerebral Hemorrhages in Adults with Community Associated Bacterial Meningitis in Adults: Should We Reconsider Anticoagulant Therapy?

PubMed Central

Mook-Kanamori, Barry B.; Fritz, Daan; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

2012-01-01

Objective To study the incidence, clinical presentation and outcome of intracranial hemorrhagic complications in adult patients with community associated bacterial meningitis. Methods Nationwide prospective cohort study from all hospitals in the Netherlands, from 1 March 2006, through 31 December 2010. Results Of the 860 episodes of bacterial meningitis that were included, 24 were diagnosed with intracranial hemorrhagic complications: 8 upon presentation and 16 during clinical course. Clinical presentation between patients with or without intracranial hemorrhage was similar. Causative bacteria were Streptococcus pneumoniae in 16 patients (67%), Staphylococcus aureus in 5 (21%), Pseudomonas aeruginosa and Listeria monocytogenes both in 1 patient (4%). Occurrence of intracranial hemorrhage was associated with death (63% vs. 15%, P<0.001) and unfavorable outcome (94% vs. 34%, P<0.001). The use of anticoagulants on admission was associated with a higher incidence of intracranial hemorrhages (odds ratio 5.84, 95% confidence interval 2.17–15.76). Conclusion Intracranial hemorrhage is a rare but devastating complication in patients with community-associated bacterial meningitis. Since anticoagulant therapy use is associated with increased risk for intracranial hemorrhage, physicians may consider reversing or temporarily discontinuing anticoagulation in patients with bacterial meningitis. PMID:23028898

Meningitis

MedlinePlus

... are caused by viruses ( viral meningitis ) or bacteria ( bacterial meningitis ). Fungi and other organisms can also cause infectious ... can spread through the body to cause meningitis. Bacterial meningitis is a more severe form of the infection. ...

Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population.

PubMed

Wang, X H; Shi, H P; Li, F J

2016-07-25

We determined whether two common single nucleotide polymorphisms (SNPs) in the Toll-like receptor 9 gene (TLR9) (TLR9+2848 rs352140 and TLR9-1237 rs5743836) influenced susceptibility to bacterial meningitis in a Chinese population. The study comprised 126 patients with bacterial meningitis and 252 control subjects, all of whom were recruited from the Tuberculosis Hospital of Shanxi Province. Genotyping of TLR9+2848 rs352140 and TLR9-1237 rs5743836 was performed by polymerase chain reaction coupled with restriction fragment length polymorphism. Using logistic regression analysis, we found that individuals with the AA genotype were associated with an increased risk of bacterial meningitis compared with those with the GG genotype (OR = 0.43, 95%CI = 0.19-0.95; P = 0.03). In a recessive model, the AA genotype was correlated with an elevated risk of bacterial meningitis compared with the GG+GA genotype (OR = 0.49, 95%CI = 0.22-0.99; P = 0.04). However, no significant differences were observed in the association between the TLR9-1237 rs5743836 polymorphism and the risk of bacterial meningitis in the codominant, dominant, or recessive models. In conclusion, the results of our study suggest an association between the TLR9+2848 polymorphism and a reduced risk of bacterial meningitis in the codominant and recessive models.

Streptococcus bovis septicemia and meningitis associated with chronic radiation enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

Cognitive outcome in adults after bacterial meningitis

PubMed Central

Hoogman, Martine; van de Beek, Diederik; Weisfelt, Martijn; de Gans, Jan; Schmand, Ben

2007-01-01

Objective To evaluate cognitive outcome in adult survivors of bacterial meningitis. Methods Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. Results Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self‐reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar. Conclusions Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment. PMID:17353256

Optic neuritis following aseptic meningitis associated with modified measles: a case report.

PubMed

Nakajima, Nobuhito; Ueda, Masayuki; Yamazaki, Mineo; Takahashi, Toshiyuki; Katayama, Yasuo

2013-01-01

In this study, we report the case of a 35-year-old woman with modified measles complicated by aseptic meningitis and subsequent optic neuritis. Although her initial manifestations were only flu-like symptoms without any Koplik's spots or skin rashes, virological testing confirmed an acute measles infection. Subsequently, right optic neuritis appeared after aseptic meningitis and was completely resolved following steroid pulse therapy. In general, modified measles is believed to be associated with mild symptoms and few neurological complications; however, our present observations demonstrated that modified measles can cause rapid neurological complications.

Bacterial meningitis among children under the age of 2 years in a high human immunodeficiency virus prevalence area after Haemophilus influenzae type b vaccine introduction.

PubMed

Nansera, Denis; Max, Irama; Annet, Kisakye; Gessner, Bradford D

2012-04-01

The aim of this study was to describe bacterial causes of meningitis among children < 2 years in a high human immunodeficiency virus (HIV) prevalence area after introduction of routine Haemophilus influenzae type b vaccination. Data collected between April 2003 and December 2008 were extracted from a surveillance database and medical records of children < 2 years admitted in Mbarara Hospital, Uganda with suspected bacterial meningitis. HIV infection was confirmed using rapid tests and polymerase chain reaction and bacterial meningitis by using cerebrospinal fluid culture. Between April 2003 and December 2008, 1464 children under 5 years were admitted with suspected bacterial meningitis of which 1235 (84.4%) had cerebrospinal fluid collected; 894 (72.4%) of these samples were from children < 2 years. Of the 894 samples, 64 (7.2%) grew an organism including Streptococcus pneumoniae (26; 41%), Salmonella species (20; 31%), H. influenzae (6; 9%) and coliforms (7; 11%), and five (8%) grew contaminants that are all coagulase negative Staphylococcus. Of the 894 children, 468 (52.3%) were tested for HIV; 16.7% were positive. Fifty-one children had a pathogenic isolate and a treatment outcome, and 23 (45%) died; 13 (56.6%) deaths were due to S. pneumoniae, eight (34.8%) were due to Salmonella spp., one (4.3%) was due to H. influenzae and one (4.3%) was due to coliforms. HIV infection was associated with a threefold increase in mortality, increased likelihood of a bacterial isolate and decreased likelihood of malaria parasitaemia. Following H. influenzae type b vaccine introduction, S. pneumoniae and Salmonella spp. are the major causes of bacterial meningitis among children < 2 years in Uganda. Pneumococcal conjugate vaccines and reduction in mother to child transmission of HIV could reduce the observed mortality. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

First report of two cases of cryptococcosis in Tripoli, Libya, infected with Cryptococcus neoformans isolates present in the urban area.

PubMed

Ellabib, M S; Krema, Z A; Allafi, A A; Cogliati, M

2017-09-01

Cryptococcosis is a potentially fatal fungal disease caused by the basidiomycetes yeasts Cryptococcus neoformans and C. gattii with high predilection to invade the central nervous system mainly in immunocompromised hosts. Skin can be secondarily involved in disseminated infection or be exceptionally involved as primary cutaneous infection by inoculation with contaminated materials. We report the first two Libyan cases of cryptococcal meningitis in HIV patients, in which one of them presented a secondary cutaneous involvement due to systemic dissemination. The first patient was a 17-year-old female, had fever, cough, headache and intractable vomiting as well as itchy water bumps on her skin and upper limbs. The cutaneous eruption prompted the accurate diagnosis. Cultures were positive for C. neoformans in both cerebrospinal fluid and skin specimens, as well as cryptococcal antigen was detected in serum. The isolate was identified, by molecular analysis, as C. neoformans AD-hybrid belonging to molecular type VNIII and mating type αAAα, the same genotype found for some environmental isolates recovered from olive trees in Tripoli. The second patient was a 36-years-old male with a long history of HIV on irregular treatment. Cryptococcal antigen in serum was positive and cultures yielded the growth of C. neoformans var. grubii, molecular type VNI and mating type αA. Both patients did not respond adequately to treatment and died of impaired central nervous system function and respiratory failure, respectively. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Persistence of Pneumolysin in the Cerebrospinal Fluid of Patients With Pneumococcal Meningitis Is Associated With Mortality

PubMed Central

Wall, Emma C.; Hussain, Samia; Goonetilleke, Upali R. S.; Gritzfeld, Jenna; Scarborough, Matthew; Kadioglu, Aras

2012-01-01

Poor prognosis in Pneumococcal meningitis may be associated with high pneumolysin levels in cerebrospinal fluid (CSF). In patient samples we showed that pneumolysin levels in CSF remained high after 48 hours in nonsurvivors of meningitis compared with survivors. Selective antipneumolysin treatment may present a novel therapeutic option. PMID:22238165

Association of treatment for bacterial meningitis with the development of sequelae.

PubMed

Theodoridou, Kalliopi; Vasilopoulou, Vasiliki A; Katsiaflaka, Anna; Theodoridou, Maria N; Roka, Violeta; Rachiotis, George; Hadjichristodoulou, Christos S

2013-09-01

Bacterial meningitis continues to be a serious, often disabling infectious disease. The aim of this study was to assess the possibility that treatment influences the development of sequelae in childhood bacterial meningitis. Two thousand four hundred and seventy-seven patients aged 1 month to 14 years with acute bacterial meningitis over a 32-year period were enrolled in the study. Data were collected prospectively from the Meningitis Registry of a tertiary university teaching hospital in Athens, Greece. Treatment was evaluated through univariate and multivariate analysis with regard to sequelae: seizure disorder, severe hearing loss, ventriculitis, and hydrocephalus. According to the multinomial logistic regression analysis, there was evidence that penicillin, an all-time classic antibiotic, had a protective effect on the occurrence of ventriculitis (odds ratio (OR) 0.17, 95% confidence interval (CI) 0.05-0.60), while patients treated with chloramphenicol had an elevated risk of ventriculitis (OR 17.77 95% CI 4.36-72.41) and seizure disorder (OR 4.72, 95% CI 1.12-19.96). Cephalosporins were related to an increased risk of hydrocephalus (OR 5.24, 95% CI 1.05-26.29) and ventriculitis (OR 5.72, 95% CI 1.27-25.76). The use of trimethoprim/sulfamethoxazole increased the probability of seizure disorder (OR 3.26, 95% CI 1.08-9.84) and ventriculitis (OR 8.60, 95% CI 2.97-24.91). Hydrocortisone was associated with a rise in hydrocephalus (OR 5.44, 95% CI 1.23-23.45), while a protective effect of dexamethasone (OR 0.82, 95% CI 0.18-3.79) was not statistically significant. Current study findings suggest that the type of antimicrobial treatment for childhood bacterial meningitis may influence in either a positive or a negative way the development of neurological sequelae. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Neurological sequelae of bacterial meningitis.

PubMed

Lucas, Marjolein J; Brouwer, Matthijs C; van de Beek, Diederik

2016-07-01

We reported on occurrence and impact of neurological sequelae after bacterial meningitis. We reviewed occurrence of neurological sequelae in children and adults after pneumococcal and meningococcal meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Adults with pneumococcal meningitis have the highest risk of developing focal neurological deficits, which are most commonly caused by cerebral infarction, but can also be due to cerebritis, subdural empyema, cerebral abscess or intracerebral bleeding. Focal deficits may improve during clinical course and even after discharge, but a proportion of patients will have persisting focal neurological deficits that often interfere in patient's daily life. Hearing loss occurs in a high proportion of patients with pneumococcal meningitis and has been associated with co-existing otitis. Children and adults recovering from bacterial meningitis without apparent neurological deficits are at risk for long-term cognitive deficits. Early identification of neurological sequelae is important for children to prevent additional developmental delay, and for adults to achieve successful return in society after the disease. Neurological sequelae occur in a substantial amount of patients following bacterial meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Group A streptococcus meningitis in children.

PubMed

de Almeida Torres, Rosângela Stadnick Lauth; Fedalto, Luiz Ernesto; de Almeida Torres, Rômulo Francisco; Steer, Andrew C; Smeesters, Pierre Robert

2013-02-01

To characterize the epidemiologic burden and the molecular determinants of group A streptococcal (GAS) meningitis among the pediatric population of the state of Paraná, Brazil. Clinical and epidemiologic data were gathered by a compulsory notification system during the period 2003 to 2011. Bacterial identification, antibiotic resistance profile, emm-typing, pulsed-field gel electrophoresis typing and virulence profile were analyzed by a central reference laboratory. A review of published pediatric cases of GAS meningitis from the last 45 years was undertaken and compared with the Brazilian series. The incidence of GAS meningitis among the pediatric population was 0.06 cases per 100,000 children per year and was associated with a case fatality rate of 43%. Neonatal age and the presence of an associated toxic shock syndrome were identified as risk factors for death. A distant focus of infection was present in more than half of the patients in the literature and in 36% in the Brazilian case series. A high diversity of emm-types was associated with GAS meningitis in Brazil. No single virulence determinant could be associated with death. GAS meningitis is associated with high mortality and with a high diversity of GAS emm-types and virulence determinants in Brazil.

Meningitis

MedlinePlus

... around. Even more protection is given by the meninges (say: muh-NIN-jeez), which are the membranes ... disease involving inflammation (swelling), or irritation, of the meninges. There are different kinds of meningitis, but most ...

Molecular types of Cryptococcus gattii/Cryptococcus neoformans species complex from clinical and environmental sources in Nairobi, Kenya.

PubMed

Kangogo, Mourine; Bader, Oliver; Boga, Hamadi; Wanyoike, Wanjiru; Folba, Claudia; Worasilchai, Navaporn; Weig, Michael; Groß, Uwe; Bii, Christine C

2015-11-01

Cryptococcal meningitis infections cause high mortality rates among HIV-infected patients in Sub-Saharan Africa. The high incidences of cryptococcal infections may be attributed to common environmental sources which, if identified, could lead to institution of appropriate control strategies. To determine the genotypes of Cryptococcus gattii/C. neoformans- species complex from Nairobi, Kenya, 123 clinical and environmental isolates were characterised. Typing was done using orotidine monophosphate pyrophosphorylase (URA5) gene restriction fragment length polymorphism (URA5-RFLP). The majority of the isolates [105/123; 85.4%] were C. neoformans genotype (AFLPI/VNI) and 1.6% AFLP1A/VNB/VNII, whereas (13%) were C. gattii (AFLP4/VGI). This is the first report on the genotypes of C. gattii/C. neoformans species complex from clinical and environmental sources in Nairobi, Kenya and the isolation of C. gattii genotype AFLP4/VGI from the environment in Kenya. © 2015 Blackwell Verlag GmbH.

Meningitis

MedlinePlus

... nose or mouth and travels to the brain. Bacterial meningitis is rare, but can be deadly. It usually ... meningococcal infections are the most common causes of bacterial meningitis. Anyone can get meningitis, but it is more ...

Treatment of bacterial meningitis: an update.

PubMed

Shin, Seon Hee; Kim, Kwang Sik

2012-10-01

The introduction of protein conjugate vaccines for Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (S. pneumoniae) and Neisseria meningitidis (N. menigitidis) has changed the epidemiology of bacterial meningitis. Bacterial meningitis continues to be an important cause of mortality and morbidity, and our incomplete knowledge of its pathogenesis and emergence of antimicrobial resistant bacteria contribute to such mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis. This article gives an overview on optimal treatment strategies of bacterial meningitis, along with considerations of new insights on epidemiology, clinical and laboratory findings supportive of bacterial meningitis, chemoprophylaxis, selection of initial antimicrobial agents for suspected bacterial meningitis, antimicrobial resistance and utility of new antibiotics, status on anti-inflammatory agents and adjunctive therapy, and pathogenesis of bacterial meningitis. Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood-brain barrier (BBB), with efficacy in cerebrospinal fluid (CSF). Several new antibiotics have been introduced for the treatment of meningitis caused by resistant bacteria, but their use in human studies has been limited. More complete understanding of the microbial and host interactions that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.

Steroids in bacterial meningitis: yes.

PubMed

Benninger, Felix; Steiner, Israel

2013-02-01

Bacterial meningitis is an infectious condition associated with severe morbidity and mortality, even with rapid diagnosis and appropriate antibiotic therapy. Despite decrease in the rate of bacterial meningitis brought about by vaccination programs against Haemophilus influenzae type-B and Streptococcus pneumonia, the incidence of meningitis is still unacceptably high and acute treatment remains the mainstay of therapy. The infection is accompanied by intense inflammatory response, which may carry deleterious effects upon the tissue. This led to the possibility of adjuvant corticosteroid therapy, as an anti-inflammatory agent, in bacterial meningitis. The debate focuses on the rational and evidence supporting and refuting such an approach.

Bacterial meningitis - principles of antimicrobial treatment.

PubMed

Jawień, Miroslaw; Garlicki, Aleksander M

2013-01-01

Bacterial meningitis is associated with significant morbidity and mortality despite the availability of effective antimicrobial therapy. The management approach to patients with suspected or proven bacterial meningitis includes emergent cerebrospinal fluid analysis and initiation of appropriate antimicrobial and adjunctive therapies. The choice of empirical antimicrobial therapy is based on the patient's age and underlying disease status; once the infecting pathogen is isolated, antimicrobial therapy can be modified for optimal treatment. Successful treatment of bacterial meningitis requires the knowledge on epidemiology including prevalence of antimicrobial resistant pathogens, pathogenesis of meningitis, pharmacokinetics and pharmacodynamics of antimicrobial agents. The emergence of antibiotic-resistant bacterial strains in recent years has necessitated the development of new strategies for empiric antimicrobial therapy for bacterial meningitis.

Total antioxidant/oxidant status in meningism and meningitis.

PubMed

Aycicek, Ali; Iscan, Akin; Erel, Ozcan; Akcali, Mustafa; Selek, Sahbettin

2006-12-01

The objective of this study was to investigate the antioxidant/oxidant status of serum and cerebrospinal fluid in children with meningismus and acute bacterial meningitis. Twenty-three children (age range, 0.75 to 9 years) with fever and meningeal signs that required analysis of the cerebrospinal fluid, but no cytologic or biochemical evidence of meningitis in their serum and cerebrospinal fluid, constituted the meningismus group. Thirty-one children (age range, 0.5 to 10 years) with acute bacterial meningitis constituted the meningitis group. Twenty-nine healthy children (age range, 0.5 to 11 years) were recruited as control subjects. Antioxidant status (ascorbic acid, albumin, thiol, uric acid, total bilirubin, total antioxidant capacity, catalase and ceruloplasmin concentrations) and oxidant status (lipid hydroperoxide and total oxidant status) were measured. The serum antioxidant status was lower, and oxidant status levels higher in both meningitis and meningismus subjects than in the control children (P < 0.001). Cerebrospinal fluid oxidant status was lower in the meningitis group than in the meningismus group (P < 0.05). These results indicate that serum antioxidant status was lower, and serum oxidant status was higher in children in the meningismus and meningitis groups, whereas cerebrospinal fluid oxidant status was higher in the meningismus group than in the meningitis group.

Evaluation of a Cryptococcal antigen Lateral Flow Assay in serum and cerebrospinal fluid for rapid diagnosis of cryptococcosis in Colombia.

PubMed

Cáceres, Diego H; Zuluaga, Alejandra; Tabares, Ángela M; Chiller, Tom; González, Ángel; Gómez, Beatriz L

2017-12-21

A Lateral Flow Assay to detect cryptococcal antigen (CrAg® LFA) in serum and cerebrospinal fluid for the rapid diagnosis of cryptococcosis was evaluated. A retrospective validation was performed. Sensitivity and specificity of the CrAg® LFA was 100%. High concordance (kappa index=1.0) between Cryptococcal Antigen Latex Agglutination System (CALAS®) and CrAg® LFA was observed. CrAg® LFA showed higher analytical sensitivity for detecting low concentrations of cryptococcal antigen.

Evaluation of a Cryptococcal antigen Lateral Flow Assay in serum and cerebrospinal fluid for rapid diagnosis of cryptococcosis in Colombia

PubMed Central

Cáceres, Diego H.; Zuluaga, Alejandra; Tabares, Ángela M.; Chiller, Tom; González, Ángel; Gómez, Beatriz L.

2017-01-01

ABSTRACT A Lateral Flow Assay to detect cryptococcal antigen (CrAg® LFA) in serum and cerebrospinal fluid for the rapid diagnosis of cryptococcosis was evaluated. A retrospective validation was performed. Sensitivity and specificity of the CrAg® LFA was 100%. High concordance (kappa index=1.0) between Cryptococcal Antigen Latex Agglutination System (CALAS®) and CrAg® LFA was observed. CrAg® LFA showed higher analytical sensitivity for detecting low concentrations of cryptococcal antigen. PMID:29267584

Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

PubMed

Cho, Bum-Joo; Kim, Ji-Soo; Hwang, Jeong-Min

2013-12-01

A 55-year-old woman presented with diplopia following painful skin eruptions on the right upper extremity. On presentation, she was found to have 35 prism diopters of esotropia and an abduction limitation in the left eye. Two weeks later, she developed blepharoptosis and anisocoria with a smaller pupil in the right eye, which increased in the darkness. Cerebrospinal fluid analysis showed pleocytosis and a positive result for immunoglobulin G antibody to varicella zoster virus. She was diagnosed to have zoster meningitis with Horner's syndrome and contralateral abducens nerve palsy. After intravenous antiviral and steroid treatments, the vesicular eruptions and abducens nerve palsy improved. Horner's syndrome and diplopia resolved after six months. Here we present the first report of Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity?

PubMed

Tanriverdi, F; De Bellis, A; Teksahin, H; Alp, E; Bizzarro, A; Sinisi, A A; Bellastella, G; Paglionico, V A; Bellastella, A; Unluhizarci, K; Doganay, M; Kelestimur, F

2012-12-01

Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months

Recurrent Meningitis.

PubMed

Rosenberg, Jon; Galen, Benjamin T

2017-07-01

Recurrent meningitis is a rare clinical scenario that can be self-limiting or life threatening depending on the underlying etiology. This review describes the causes, risk factors, treatment, and prognosis for recurrent meningitis. As a general overview of a broad topic, the aim of this review is to provide clinicians with a comprehensive differential diagnosis to aide in the evaluation and management of a patient with recurrent meningitis. New developments related to understanding the pathophysiology of recurrent meningitis are as scarce as studies evaluating the treatment and prevention of this rare disorder. A trial evaluating oral valacyclovir suppression after HSV-2 meningitis did not demonstrate a benefit in preventing recurrences. The data on prophylactic antibiotics after basilar skull fractures do not support their use. Intrathecal trastuzumab has shown promise in treating leptomeningeal carcinomatosis from HER-2 positive breast cancer. Monoclonal antibodies used to treat cancer and autoimmune diseases are new potential causes of drug-induced aseptic meningitis. Despite their potential for causing recurrent meningitis, the clinical entities reviewed herein are not frequently discussed together given that they are a heterogeneous collection of unrelated, rare diseases. Epidemiologic data on recurrent meningitis are lacking. The syndrome of recurrent benign lymphocytic meningitis described by Mollaret in 1944 was later found to be closely related to HSV-2 reactivation, but HSV-2 is by no means the only etiology of recurrent aseptic meningitis. While the mainstay of treatment for recurrent meningitis is supportive care, it is paramount to ensure that reversible and treatable causes have been addressed for further prevention.

Endocarditis in adults with bacterial meningitis.

PubMed

Lucas, Marjolein J; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

2013-05-21

Endocarditis may precede or complicate bacterial meningitis, but the incidence and impact of endocarditis in bacterial meningitis are unknown. We assessed the incidence and clinical characteristics of patients with meningitis and endocarditis from a nationwide cohort study of adults with community-acquired bacterial meningitis in the Netherlands from 2006 to 2012. Endocarditis was identified in 24 of 1025 episodes (2%) of bacterial meningitis. Cultures yielded Streptococcus pneumoniae in 13 patients, Staphylococcus aureus in 8 patients, and Streptococcus agalactiae, Streptococcus pyogenes, and Streptococcus salivarius in 1 patient each. Clues leading to the diagnosis of endocarditis were cardiac murmurs, persistent or recurrent fever, a history of heart valve disease, and S aureus as the causative pathogen of bacterial meningitis. Treatment consisted of prolonged antibiotic therapy in all patients and surgical valve replacement in 10 patients (42%). Two patients were treated with oral anticoagulants, and both developed life-threatening intracerebral hemorrhage. Systemic (70%) and neurological (54%) complications occurred frequently, leading to a high proportion of patients with unfavorable outcome (63%). Seven of 24 patients (29%) with meningitis and endocarditis died. Endocarditis is an uncommon coexisting condition in bacterial meningitis but is associated with a high rate of unfavorable outcome.

Mannose-binding lectin-associated serine protease 2 (MASP-2) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

PubMed

Kasanmoentalib, E Soemirien; Valls Seron, Mercedes; Ferwerda, Bart; Tanck, Michael W; Zwinderman, Aeilko H; Baas, Frank; van der Ende, Arie; Brouwer, Matthijs C; van de Beek, Diederik

2017-01-03

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the pro-inflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. We investigated mannose-binding lectin-associated serine protease (MASP-2) levels in cerebrospinal fluid (CSF) samples derived from the diagnostic lumbar puncture, which was available for 307 of 792 pneumococcal meningitis episodes included in our prospective nationwide cohort study (39%), and the association between these levels and clinical outcome. Subsequently, we studied the role of MASP-2 in our experimental pneumococcal meningitis mouse model using Masp2 -/- mice and evaluated the potential of adjuvant treatment with MASP-2-specific monoclonal antibodies in wild-type (WT) mice. MASP-2 levels in cerebrospinal fluid of patients with bacterial meningitis were correlated with poor functional outcome. Consistent with these human data, Masp2-deficient mice with pneumococcal meningitis had lower cytokine levels and increased survival compared to WT mice. Adjuvant treatment with MASP-2-specific monoclonal antibodies led to reduced complement activation and decreased disease severity. MASP-2 contributes to poor disease outcome in human and mice with pneumococcal meningitis. MASP-2-specific monoclonal antibodies can be used to attenuate the inflammatory response in pneumococcal meningitis.

Herpes simplex virus type 2-associated recurrent aseptic (Mollaret's) meningitis in genitourinary medicine clinic: a case report.

PubMed

Abou-Foul, Ahmad K; Buhary, Thajunisha M; Gayed, Sedki L

2014-01-01

Cases of idiopathic recurrent benign aseptic meningitis were first described by Mollaret. Today, herpes simplex virus (HSV) is considered the cause of most cases of Mollaret's meningitis. A 40-year-old male was referred to our genitourinary medicine clinic with recurrent genital herpetic lesions. He had HSV-2-positive genital ulcers 8 years earlier. One year after the first infection, he developed severe recurrent attacks of headache associated with meningitis symptoms. The results of all radiological and biochemical tests were normal, but the patient reported a correlation between his attacks and genital herpes flare-ups. We diagnosed the patient with Mollaret's meningitis and started him on continuous suppressive acyclovir therapy, which resulted in marked clinical improvement. Mollaret's meningitis is a rare form of idiopathic recurrent aseptic meningitis that has a sudden onset, short duration, and spontaneous remission with unpredictable recurrence. We believe that the presence of concurrent or recurrent mucocutaneous herpetic lesions can aid its diagnosis, prior to which, affected patients usually have many unnecessary investigations and treatments. Therefore, detailed sexual history should be sought in all patients with aseptic meningitis, and clinicians should also ask about history of recurrent headaches in all patients with recurrent herpetic anogenital lesions. Continuous suppressive acyclovir therapy may reduce the frequency and severity of attacks and can dramatically improve lifestyle.

Bacterial Meningitis

MedlinePlus

... Links Vaccine Schedules Preteen & Teen Vaccines Meningococcal Disease Sepsis Bacterial Meningitis Language: English (US) Español (Spanish) Recommend ... can also be associated with another serious illness, sepsis . Sepsis is the body’s overwhelming and life-threatening ...

Viral Meningitis

MedlinePlus

... Links Vaccine Schedules Preteen & Teen Vaccines Meningococcal Disease Sepsis Viral Meningitis Language: English (US) Español (Spanish) Recommend ... can also be associated with another serious illness, sepsis . Sepsis is the body’s overwhelming and life-threatening ...

Community-acquired bacterial meningitis.

PubMed

Costerus, Joost M; Brouwer, Matthijs C; Bijlsma, Merijn W; van de Beek, Diederik

2017-02-01

Bacterial meningitis is a medical emergency and is associated with a high disease burden. We reviewed recent progress in the management of patients with community-acquired bacterial meningitis. The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns. Delay in diagnosis and treatment remain major concerns in the management of acute bacterial meningitis. European Society of Clinical Microbiology and Infectious Diseases guidelines strive for a door-to-antibiotic-time less than 1 h. Polymerase chain reaction (PCR) has emerged as an important diagnostic tool to identify the causative organism. Point-of-care tests using fast multiplex PCR have been developed, but additional value has not been proven. Although anecdotal observations advocate pressure-based management, a randomized controlled trial will need to be performed first to determine efficacy and safety of such an aggressive treatment approach. Adjunctive dexamethasone remains the only adjunctive therapy with proven efficacy. The incidence of bacterial meningitis has been decreasing after the implementation of effective vaccines. Treatment should be administered as soon as possible and time to treatment should not exceed 1 h.

Meningitis - H. influenzae

MedlinePlus

H. influenzae meningitis; H. flu meningitis; Haemophilus influenzae type b meningitis ... H. influenzae meningitis is caused by Haemophilus influenzae type b bacteria. This illness is not the same ...

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. © 2014 Blackwell Verlag GmbH.

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

Prophagic DNA Fragments in Streptococcus agalactiae Strains and Association with Neonatal Meningitis

PubMed Central

van der Mee-Marquet, Nathalie; Domelier, Anne-Sophie; Mereghetti, Laurent; Lanotte, Philippe; Rosenau, Agnès; van Leeuwen, Willem; Quentin, Roland

2006-01-01

We identified—by randomly amplified polymorphic DNA (RAPD) analysis at the population level followed by DNA differential display, cloning, and sequencing—three prophage DNA fragments (F5, F7, and F10) in Streptococcus agalactiae that displayed significant sequence similarity to the DNA of S. agalactiae and Streptococcus pyogenes. The F5 sequence aligned with a prophagic gene encoding the large subunit of a terminase, F7 aligned with a phage-associated cell wall hydrolase and a phage-associated lysin, and F10 aligned with a transcriptional regulator (ArpU family) and a phage-associated endonuclease. We first determined the prevalence of F5, F7, and F10 by PCR in a collection of 109 strains isolated in the 1980s and divided into two populations: one with a high risk of causing meningitis (HR group) and the other with a lower risk of causing meningitis (LR group). These fragments were significantly more prevalent in the HR group than in the LR group (P < 0.001). Our findings suggest that lysogeny has increased the ability of some S. agalactiae strains to invade the neonatal brain endothelium. We then determined the prevalence of F5, F7, and F10 by PCR in a collection of 40 strains recently isolated from neonatal meningitis cases for comparison with the cerebrospinal fluid (CSF) strains isolated in the 1980s. The prevalence of the three prophage DNA fragments was similar in these two populations isolated 15 years apart. We suggest that the prophage DNA fragments identified have remained stable in many CSF S. agalactiae strains, possibly due to their importance in virulence or fitness. PMID:16517893

Varicella zoster meningitis in a pregnant woman with acquired immunodeficiency syndrome.

PubMed

Jayakrishnan, Asha; Vrees, Roxanne; Anderson, Brenna

2008-10-01

Between 6000 and 7000 women in the United States infected with human immunodeficiency virus (HIV) give birth annually. It is well known that HIV-related immunosuppression significantly increases the risk for acquiring opportunistic infections (OIs). However, there is limited information regarding the relationship of pregnancy in the setting of HIV/AIDS infection, subsequent development of OIs, and maternal and fetal outcomes. A pregnant 36-year-old woman with AIDS was diagnosed with varicella zoster meningitis. Weight-based therapy with acyclovir was initiated with clinical improvement in symptoms. Care of a pregnant HIV-infected patient with an OI poses a unique diagnostic and therapeutic challenge for clinicians. Early diagnosis and initiation of appropriate treatment may provide an opportunity to improve both maternal and fetal outcomes.

Improved outcome of bacterial meningitis associated with use of corticosteroid treatment.

PubMed

Baunbæk-Knudsen, Gertrud; Sølling, Mette; Farre, Annette; Benfield, Thomas; Brandt, Christian T

2016-04-01

Background The aim of this study was to evaluate the clinical outcome of patients with bacterial meningitis following the introduction of dexamethasone treatment in Denmark. Methods Adult patients with bacterial meningitis, admitted from 2003-2010 to two different university hospitals, were included retrospectively. Data at clinical presentation, Glasgow outcome scale (GOS), cerebrospinal fluid and blood biochemistry were collected. Relative risk (RR) with 95% confidence interval (CI) was computed by Cox proportional hazard regression analysis. Results One hundred and forty-seven patients were included in the study. The population had a median age of 62 years and 31% had an immunosuppressive co-morbidity. Eighty-nine patients had an unfavourable outcome (GOS score = 1-4). Adjuvant treatment with corticosteroids (RR = 0.48; 95% CI = 0.30-0.76) was associated with a favourable outcome (GOS score = 5), while altered mental status (RR = 2.36; 95% CI = 1.17-4.78) and age (RR = 1.03; 95% CI = 1.01-1.04) per year increment was associated with an unfavourable outcome. Adjuvant corticosteroid treatment did not affect short- or long-term survival. Short-term mortality was influenced by age (RR = 1.06; 95% CI = 1.04-1.09). Long-term mortality was influenced by age (RR = 1.06; 95% CI = 1.03-1.08) and female sex (RR = 1.81; 95% CI = 1.05-3.14). Conclusion This study indicated that adjuvant corticosteroid treatment in acute bacterial meningitis improves the outcome and can safely be administered in an elderly population with high levels of immunosuppressive co-morbidity.

[Bacterial meningitis].

PubMed

Brouwer, M C; van de Beek, D

2012-05-01

Bacterial meningitis is a severe disease which affects 35.000 Europeans each year and has a mortality rate of about 20%. During the past 25 years the epidemiology of bacterial meningitis has changed significantly due to the implementation of vaccination against Haemophilus influenzae, Neisseria meningtidis group C and Streptococcus pneumoniae. Due to these vaccines, meningitis is now predominantly a disease occurring in adults, caused especially by Streptococcus pneumoniae, while it was formerly a child disease which was largely caused by Haemophilus influenzae. Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients. The only way to diagnose or exclude bacterial meningitis is by performing low-threshold cerebrospinal fluid examination with a suspicion of bacterial meningitis. The treatment consists of the prescription of antibiotics and dexamethasone.

[Simultaneous meningitis caused by Candida and tuberculosis as manifestation of AIDS].

PubMed

Arias Gómez, M; Requena Caballero, I; Lema Devesa, C; Suárez Dono, J; Llovo Martínez, J; Martino, V

2001-09-01

Opportunistic germs meningoencephalitis plays an important role within neurologic pathology in aids. Treponema pallidum and Mycobacterium tuberculosis among bacteries, Cryptococcus neoformans in fungus group, Toxoplasma gondii in protozoos group and Papovavirus JC in virus one are the most frequently implicated germs. Sometimes infections are mixed. We present a simultaneous meningitis case produced by Candida albicans and Mycobacterium tuberculosis that coursed with neutrophilic pleocytosis in CSF and normal glucose CSF levels, consisting the clinical debut of aids. Repeated CSF examinations are the diagnostic clue owing, as in our case, instauration of early treatment. Present case of simultaneous tuberculous and candidiasic meningitis is the first one described in a HIV positive patient.

Meningitis (For Parents)

MedlinePlus

... or sneezes on someone who isn't infected. Bacterial Meningitis Bacterial meningitis is rare, but is usually serious and ... not treated right away. In some cases of bacterial meningitis, the bacteria spread to the meninges from ...

The changing profile of pediatric meningitis at a referral centre in Cape Town, South Africa.

PubMed

Wolzak, Nena Katrina; Cooke, Melissa Louise; Orth, Heidi; van Toorn, Ronald

2012-12-01

Pediatric meningitis remains a common cause of childhood morbidity and mortality in developing countries. Knowledge of the causative organisms in a region is of importance in guiding empiric antibiotic regimes and immunization schedules assisting decisions on primary health-care interventions. This retrospective review of 557 meningitis cases represents a third pediatric survey conducted over a 3-year period (January 2007 to December 2009) at the same institution and after an interval of 14 years. Cases were identified using cerebrospinal fluid results. Demographic and laboratory variables were collected and meningitis was classified as aseptic/viral, bacterial, septic, tuberculous meningitis (TBM) or fungal. The commonest form of bacterial meningitis was TBM diagnosed in 22% (n = 126) of children. Streptococcus pneumoniae 4% (n = 23) and Klebsiella pneumoniae 3% (n = 17) were the next commonest causes of bacterial meningitis diagnosed. Haemophilus influenzae meningitis occurred in <1% (n = 3) of cases with a median age of 3 months. Aseptic meningitis remains the commonest category. Human immunodeficiency virus (HIV) testing was requested in 43% (n = 241) of cases; 8% (n = 46) were positive. TBM remains the commonest cause of pediatric bacterial meningitis in the Western Cape. It is concerning that the percentage of TBM cases out of the total study population has more than doubled compared with that in previous surveys. The low prevalence and young age of H. influenzae meningitis cases confirm the benefits derived from H. influenzae type b (Hib) vaccination.

Molecular characterization of echovirus 30-associated outbreak of aseptic meningitis in Korea in 2008.

PubMed

Choi, Young Jin; Park, Kwi Sung; Baek, Kyoung Ah; Jung, Eun Hye; Nam, Hae Seon; Kim, Yong Bae; Park, Joon Soo

2010-03-01

Evaluation of the primary etiologic agents that cause aseptic meningitis outbreaks may provide valuable information regarding the prevention and management of aseptic meningitis. In Korea, an outbreak of aseptic meningitis caused by echovirus type 30 (E30) occurred from May to October in 2008. In order to determine the etiologic agent, CSF and/or stool specimens from 140 children hospitalized for aseptic meningitis at Soonchunhyang University Cheonan Hospital between June and October of 2008 were tested for virus isolation and identification. E30 accounted for 61.7% (37 cases) and echovirus 6 accounted for 21.7% (13 cases) of all the human enteroviruses (HEVs) isolates (60 cases in total). For the molecular characterization of the isolates, the VP1 gene sequence of 18 Korean E30 isolates was compared pairwise using the MegAlign with 34 reference strains from the GenBank database. The pairwise comparison of the nucleotide sequences of the VP1 genes demonstrated that the sequences of the Korean strains differed from those of lineage groups A, B, C, D, E, F and G. Reconstruction of the phylogenetic tree based on the complete VP1 nucleotide sequences resulted in a monophyletic tree, with eight clustered lineage groups. All Korean isolates were segregated from other lineage groups, thus suggesting that the Korean strains were a distinct lineage of E30, and a probable cause of this outbreak. This manuscript is the first report, to the best of our knowledge, of the molecular characteristics of E30 strains associated with an aseptic meningitis outbreak in Korea, and their respective phylogenetic relationships.

Definite (microbiologically confirmed) tuberculous meningitis: predictors and prognostic impact.

PubMed

Jha, Sneh Kumar; Garg, Ravindra Kumar; Jain, Amita; Malhotra, Hardeep Singh; Verma, Rajesh; Sharma, Praveen Kumar

2015-12-01

Microbiological confirmation cannot be obtained in approximately two-third patients with tuberculous meningitis. In this study, we sought to identify epidemiological, clinical, cerebrospinal fluid, and imaging parameters that could indicate the possibility of microbiological confirmation among patients with suspected tuberculous meningitis. In this prospective observational study, patients with tuberculous meningitis were evaluated for clinical, laboratory (cerebrospinal fluid microscopy, culture, and polymerase chain reaction), and neuroimaging parameters. All patients received anti-tuberculosis drugs and corticosteroids. The patients were followed for a period of 6 months. Among 118 cases of tuberculous meningitis, there were 43 (36 %) definite (microbiologically confirmed) cases, 59 (50 %) probable and 16 (14 %) possible cases. Among 43 definite cases, tuberculosis polymerase chain reaction (PCR) was positive in 42 (35 %) patients, culture was positive in 1 case and microscopy, after Ziehl-Neelsen staining, was positive in 3 cases. Three factors, modified Barthel index score at admission ≤12 (p = 0.008), cerebrospinal fluid total cell count >100/mm(3) (p = 0.016), and basal exudates on imaging (p = 0.015), were significantly associated with definite tuberculous meningitis. Among 20 patients who died within 6 months, 13 belonged to definite tuberculous meningitis group (p < 0.001). Stage III tuberculous meningitis (p = 0.004), baseline-modified Barthel index score ≤12 (p = 0.013), and positive tuberculosis PCR (p = 0.007) were independently associated with poor outcome on multivariate analysis. Severe disability, cerebrospinal fluid cells >100 mm(3), and basal exudates are significantly related to the presence of microbiologically confirmed definite tuberculous meningitis. Microbiologically confirmed tuberculous meningitis is associated with poorer outcome.

Healthcare-Associated Meningitis or Ventriculitis in Older Adults.

PubMed

Srihawan, Chanunya; Habib, Onaizah; Salazar, Lucrecia; Hasbun, Rodrigo

2017-12-01

Healthcare-associated meningitis or ventriculitis (HCAMV) is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Older adults are at higher risk of adverse outcomes in community-acquired meningitis but studies of HCAMV are lacking. Therefore, we perform the study to define the differences in clinical outcomes between older and younger adults with HCAMV. Retrospective study. A large tertiary care hospital in Houston, Texas, from July 2003 to November 2014. Adults with a diagnosis of HCAMV (N = 160) aged ≥65 (n = 35), aged 18-64 (n = 125). Demographic characteristics, clinical presentation, laboratory results, treatments, and outcomes (Glasgow Outcome Scale). Older adults had more comorbidities and CSF abnormalities [pleocytosis, high cerebrospinal fluid (CSF) protein, low CSF glucose) and were more likely to have altered mental status than younger adults (P < .05). An adverse clinical outcome was seen in 142 participants (89%) (death (n = 18, 11%), persistent vegetative state (n = 26, 16%), severe disability (n = 68, 43%), moderate disability (n = 30, 19%). There was no difference in adverse outcomes between older (97%) and younger (86%) adults (P = .13). On logistic regression analysis, abnormal neurological examination (adjusted odds ratio (aOR) = 7.13, 95% confidence interval (CI) = 2.15-23.63, P = .001) and mechanical ventilation (aOR = 11.03, 95% CI = 1.35-90.51, P = .02) were associated with adverse clinical outcomes. Older adults with HCAMV have more comorbidities and CSF abnormalities and are more likely to have altered mental status than younger adults but have similar high rates of adverse clinical outcomes. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Isolation of Cryptococcus laurentii from Canada Goose guano in rural upstate New York.

PubMed

Filion, Tera; Kidd, Sarah; Aguirre, Karen

2006-11-01

Cryptococcus neoformans and Cryptococcus gattii are etiologic agents of cryptococcal pneumonia and meningitis, potentially lethal syndromes associated with AIDS. A related species, Cryptococcus laurentii, has recently been implicated in several cases of human disease. Guano from Canada Goose (Branta canadensis), an organism that lives closely beside man and inhabits recreational space in rural and suburban areas, might be a significant environmental reservoir of Cryptococcus organisms in non-urban areas. Cryptococcal organisms were isolated from Canada Goose guano from a site in rural northern New York, with identification based upon colony and microscopic morphology, ability to metabolize L: -Dopa to melanin, and positive reaction with a commercial anti-cryptococcal capsular polysaccharide latex bead agglutination test. DNA sequences from five positive isolates were identical to each other, and identical to the ITS1-5.8S-ITS2 sequences of C. laurentii strain CBS7140 (Accession AY315665) across a 511 bp sequence. All five isolates of C. laurentii possess three of the known virulence factors common to cryptococcal organisms that cause human disease: capsule, ability to grow at 37 degrees C, and laccase activity.

Mechanisms of Dendritic Cell Lysosomal Killing of Cryptococcus

NASA Astrophysics Data System (ADS)

Hole, Camaron R.; Bui, Hoang; Wormley, Floyd L.; Wozniak, Karen L.

2012-10-01

Cryptococcus neoformans is an opportunistic pulmonary fungal pathogen that disseminates to the CNS causing fatal meningitis in immunocompromised patients. Dendritic cells (DCs) phagocytose C. neoformans following inhalation. Following uptake, cryptococci translocate to the DC lysosomal compartment and are killed by oxidative and non-oxidative mechanisms. DC lysosomal extracts kill cryptococci in vitro; however, the means of antifungal activity remain unknown. Our studies determined non-oxidative antifungal activity by DC lysosomal extract. We examined DC lysosomal killing of cryptococcal strains, anti-fungal activity of purified lysosomal enzymes, and mechanisms of killing against C. neoformans. Results confirmed DC lysosome fungicidal activity against all cryptococcal serotypes. Purified lysosomal enzymes, specifically cathepsin B, inhibited cryptococcal growth. Interestingly, cathepsin B combined with its enzymatic inhibitors led to enhanced cryptococcal killing. Electron microscopy revealed structural changes and ruptured cryptococcal cell walls following treatment. Finally, additional studies demonstrated that osmotic lysis was responsible for cryptococcal death.

HIV-Associated Neurocognitive Disorder (HAND)

PubMed Central

Clifford, David B.; Ances, Beau M.

2014-01-01

Summary Neurological involvement in HIV is commonly associated with cognitive impairment. While severe and progressive neurocognitive impairment has become rare in HIV clinics in the era of potent antiretroviral therapy, a majority of HIV patients worldwide perform below expectations on formal neurocognitive tests. Co-morbid conditions contribute to impairment, but they are insufficient to explain the frequency of impairment encountered. HIV disease markers like current viral load and CD4 counts are no longer strongly associated with ongoing impairment on therapy, while cardiovascular disease markers and inflammatory markers appear more closely associated. Novel cerebrospinal fluid and neuroimaging biomarkers are needed to detect and follow impairment. Ongoing research to optimize HIV therapy within the central nervous system, and potentially to intervene in downstream mechanisms of neurotoxicity remain important avenues of future investigation. Ultimately, the full control of virus in the brain is a necessary step in the goal of HIV eradication. Weekly searches of English language publications referring to HIV neurocognitive impairment, HIV neuropathy, HIV myelopathy, HIV dementia, and HIV from 1988 to August 2013 were performed. In addition, the authors’ own files were manually searched. PMID:24156898

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

Tuberculous meningitis: a uniform case definition for use in clinical research.

PubMed

Marais, Suzaan; Thwaites, Guy; Schoeman, Johan F; Török, M Estée; Misra, Usha K; Prasad, Kameshwar; Donald, Peter R; Wilkinson, Robert J; Marais, Ben J

2010-11-01

Tuberculous meningitis causes substantial mortality and morbidity in children and adults. More research is urgently needed to better understand the pathogenesis of disease and to improve its clinical management and outcome. A major stumbling block is the absence of standardised diagnostic criteria. The different case definitions used in various studies makes comparison of research findings difficult, prevents the best use of existing data, and limits the management of disease. To address this problem, a 3-day tuberculous meningitis workshop took place in Cape Town, South Africa, and was attended by 41 international participants experienced in the research or management of tuberculous meningitis. During the meeting, diagnostic criteria were assessed and discussed, after which a writing committee was appointed to finalise a consensus case definition for tuberculous meningitis for use in future clinical research. We present the consensus case definition together with the rationale behind the recommendations. This case definition is applicable irrespective of the patient's age, HIV infection status, or the resources available in the research setting. Consistent use of the proposed case definition will aid comparison of studies, improve scientific communication, and ultimately improve care. Copyright © 2010 Elsevier Ltd. All rights reserved.

Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies.

PubMed

Correa, Néstor; Covarrubias, Cristian; Rodas, Paula I; Hermosilla, Germán; Olate, Verónica R; Valdés, Cristián; Meyer, Wieland; Magne, Fabien; Tapia, Cecilia V

2017-01-01

conclude that human melanin is more active than the two fungal melanins against Cryptococcus. Although some physico-chemical differences were found, they do not explain the differences in the antifungal activity against Cryptococcus of human and cryptococcal melanins. More detailed studies on the structure should be considered to associate structure and antifungal activity.

Community-acquired Serratia marcescens meningitis.

PubMed

Peeters, A; Vandercam, B; Sindic, C J; Hantson, P; Mahieu, P

1997-11-01

Serratia marcescens is an unusual cause of community-acquired meningitis in adults. We report a case of S. marcescens meningitis occurring 29 years after a head injury and preceded by 3 years of intermittent nasal discharge of cerebrospinal fluid (CSF). One month before admission, the patient had received treatment with cefadroxil. This case illustrates the risk of Gram-negative bacillary meningitis in patients with a CSF leak when they are treated with antibiotics. When patients have a chronic clear nasal discharge, one should look for a past medical history of head injury before prescribing antibiotics. In the presence of a fistula, any antibiotherapy may lead to the selection of resistant organisms which may be difficult to treat. Due to the high risk of meningitis and the fact that spontaneous closure in delayed CSF rhinorrhoea is unlikely, surgical repair of any associated fistulae is mandatory.

Bacterial meningitis.

PubMed

Heckenberg, Sebastiaan G B; Brouwer, Matthijs C; van de Beek, Diederik

2014-01-01

Bacterial meningitis is a neurologic emergency. Vaccination against common pathogens has decreased the burden of disease. Early diagnosis and rapid initiation of empiric antimicrobial and adjunctive therapy are vital. Therapy should be initiated as soon as blood cultures have been obtained, preceding any imaging studies. Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, and an altered level of consciousness but signs may be scarce in children, in the elderly, and in meningococcal disease. Host genetic factors are major determinants of susceptibility to meningococcal and pneumococcal disease. Dexamethasone therapy has been implemented as adjunctive treatment of adults with pneumococcal meningitis. Adequate and prompt treatment of bacterial meningitis is critical to outcome. In this chapter we review the epidemiology, pathophysiology, and management of bacterial meningitis. © 2014 Elsevier B.V. All rights reserved.

Evaluation of a Public-sector, Provider-initiated Cryptococcal Antigen Screening and Treatment Program, Western Cape, South Africa

PubMed Central

Smith, Mariette; Smith, Rachel; Osler, Meg; Kelly, Nicola; Cross, Anna; Boulle, Andrew; Meintjes, Graeme; Govender, Nelesh P.

2016-01-01

Background Screening for serum cryptococcal antigen (CrAg) may identify those at risk for disseminated cryptococcal disease (DCD), and pre-emptive fluconazole treatment may prevent progression to DCD. In August 2012, the Western Cape Province (WC), South Africa, adopted provider-initiated CrAg screening. We evaluated the implementation and effectiveness of this large-scale public-sector program during its first year, September 1, 2012—August 31, 2013. Methods We used data from the South African National Health Laboratory Service, WC provincial HIV program, and nationwide surveillance data for DCD. We assessed the proportion of eligible patients screened for CrAg (CrAg test done within 30 days of CD4 date) and the prevalence of CrAg positivity. Incidence of DCD among those screened was compared with those not screened. Results Of 4,395 eligible patients, 26.6% (n=1170) were screened. The proportion of patients screened increased from 15.9% in September 2012 to 36.6% in August 2013. The prevalence of positive serum CrAg was 2.1%. Treatment data were available for 13 of 24 CrAg-positive patients; nine of 13 were treated with fluconazole. Nine (0.8%) incident cases of DCD occurred among the 1170 patients who were screened for CrAg vs. 49 (1.5%) incident cases among the 3225 patients not screened (p=0.07). Conclusions Relatively few eligible patients were screened under the WC provider-initiated CrAg screening program. Unscreened patients were nearly twice as likely to develop DCD. CrAg screening can reduce the burden of DCD, but needs to be implemented well. To improve screening rates, countries should consider laboratory-based reflexive screening when possible. PMID:26926942

First report of urease activity in the novel systemic fungal pathogen Emergomyces africanus: a comparison with the neurotrope Cryptococcus neoformans.

PubMed

Lerm, Barbra; Kenyon, Chris; Schwartz, Ilan S; Kroukamp, Heinrich; de Witt, Riaan; Govender, Nelesh P; de Hoog, G Sybren; Botha, Alfred

2017-11-01

Cryptococcus neoformans is an opportunistic pathogen responsible for the AIDS-defining illness, cryptococcal meningitis. During the disease process, entry of cryptococcal cells into the brain is facilitated by virulence factors that include urease enzyme activity. A novel species of an Emmonsia-like fungus, recently named Emergomyces africanus, was identified as a cause of disseminated mycosis in HIV-infected persons in South Africa. However, in contrast to C. neoformans, the enzymes produced by this fungus, some of which may be involved in pathogenesis, have not been described. Using a clinical isolate of C. neoformans as a reference, the study aim was to confirm, characterise and quantify urease activity in E. africanus clinical isolates. Urease activity was tested using Christensen's urea agar, after which the presence of a urease gene in the genome of E. africanus was confirmed using gene sequence analysis. Subsequent evaluation of colorimetric enzyme assay data, using Michaelis-Menten enzyme kinetics, revealed similarities between the substrate affinity of the urease enzyme produced by E. africanus (Km ca. 26.0 mM) and that of C. neoformans (Km ca. 20.6 mM). However, the addition of 2.5 g/l urea to the culture medium stimulated urease activity of E. africanus, whereas nutrient limitation notably increased cryptococcal urease activity. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The burden of serious fungal diseases in Russia.

PubMed

Klimko, N; Kozlova, Y; Khostelidi, S; Shadrivova, O; Borzova, Y; Burygina, E; Vasilieva, N; Denning, D W

2015-10-01

The incidence and prevalence of fungal infections in Russia is unknown. We estimated the burden of fungal infections in Russia according to the methodology of the LIFE program (www.LIFE-worldwide.org). The total number of patients with serious and chronic mycoses in Russia in 2011 was three million. Most of these patients (2,607,494) had superficial fungal infections (recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis with HIV infection and tinea capitis). Invasive and chronic fungal infections (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia) affected 69,331 patients. The total number of adults with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation was 406,082. © 2015 Blackwell Verlag GmbH.

Hearing loss diagnosis followed by meningitis in Danish children, 1995-2004.

PubMed

Parner, Erik T; Reefhuis, Jennita; Schendel, Diana; Thomsen, Janus L; Ovesen, Therese; Thorsen, Poul

2007-03-01

A higher risk of meningitis associated with cochlear implants may be explained in part by a generally higher risk of meningitis in children with severe to profound hearing loss. We investigated whether children with hearing loss have an increased risk of meningitis. A historical cohort study of all children born in Denmark between January 1, 1995, and December 31, 2004, was conducted. The cohort was selected through the Danish Medical Birth Registry, and information on hearing loss and meningitis was obtained from the National Hospital Registry. We identified 39 children with both hearing loss and meningitis. Of these children, five were diagnosed first with hearing loss and later with meningitis. The relative risk of meningitis in the group of children with a hearing loss diagnosis, as compared with the non-hearing loss group, was 5.0 (95% CI, 2.0 to 12.0). The study provides evidence for an association between hearing loss and the development of meningitis. Parents and health care providers of children with hearing loss should be more alert for possible signs and symptoms of meningitis, and vaccination should be considered.

Vitamin D was not associated with survival or cerebrospinal fluid cathelicidin levels in children with bacterial meningitis.

PubMed

Savonius, Okko; Pelkonen, Tuula; Roine, Irmeli; Viljakainen, Heli; Andersson, Sture; Fernandez, Josefina; Peltola, Heikki; Helve, Otto

2018-05-11

Vitamin D deficiency impairs the immunological system and has been associated with worse outcomes of infectious diseases, but its role in bacterial meningitis remains unknown. We investigated whether serum 25-hydroxyvitamin D concentrations related to disease outcomes and to cerebrospinal fluid cathelicidin concentrations in childhood bacterial meningitis. All consecutively enrolled patients in a clinical trial on childhood bacterial meningitis in Latin America in 1996-2003 were considered and 142 children, with a median age of seven months who had a confirmed bacterial aetiology and frozen serum available for further analyses, were included in the present study. Serum 25-hydroxyvitamin D concentrations were determined with a chemiluminescence immunoassay analyser, while cerebrospinal fluid cathelicidin was measured by enzyme-linked immunosorbent assay. The median serum 25-hydroxyvitamin D concentration was 96 (range 19-251) nmol/L. No relationship was found with patient survival, but children with any neurological sequelae had lower serum 25-hydroxyvitamin D levels than children without sequelae. Serum 25-hydroxyvitamin D was unrelated to cathelicidin concentrations in cerebrospinal fluid. Although serum 25-hydroxyvitamin D in children with bacterial meningitis was not associated with survival or cerebrospinal fluid cathelicidin concentrations, its relationship with more detailed disease outcomes warrants further study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hydrocephalus in herpes simplex type 2 meningitis.

PubMed

Yap, Elaine; Ellis-Pegler, Rod

2006-08-01

A 34-year-old woman presented to hospital with symptoms of meningitis, later confirmed to be due to herpes simplex virus type 2. She developed hydrocephalus on day 2 of her admission. We describe the first case of hydrocephalus associated with herpes simplex type 2 meningitis in an adult.

Corticosteroids for acute bacterial meningitis.

PubMed

Brouwer, Matthijs C; McIntyre, Peter; Prasad, Kameshwar; van de Beek, Diederik

2013-06-04

In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response. To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis. We searched CENTRAL 2012, Issue 12, MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), Web of Science (2010 to January 2013), CINAHL (2010 to January 2013) and LILACS (2010 to January 2013). Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis. We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality. Twenty-five studies involving 4121 participants were included. Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) orNeisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.In high-income countries

Validation of the bacterial meningitis score in adults presenting to the ED with meningitis.

PubMed

McArthur, Robert; Edlow, Jonathan A; Nigrovic, Lise E

2016-07-01

The Bacterial Meningitis Score classifies children with meningitis and none of the following high-risk predictors at very low risk for bacterial meningitis: positive cerebrospinal fluid (CSF) Gram stain, CSF protein ≥80mg/dL, CSF absolute neutrophil count (ANC) ≥1000 cells/mm(3), peripheral ANC ≥10,000 cells/mm(3), and seizure at or prior to presentation. Although extensively validated in children, the Bacterial Meningitis Score has not been rigorously evaluated in adults. We performed a single-center cross-sectional retrospective study of adults presenting to the emergency department between 2003 and 2013 with meningitis (defined by CSF white blood cell count ≥10 cells/mm(3)). We defined a case of bacterial meningitis with either a positive CSF or blood culture. We report the performance of the Bacterial Meningitis Score in the study population. We identified 441 eligible patients of which, 4 (1%) had bacterial meningitis. The Bacterial Meningitis Score had a sensitivity of 100% [95% confidence interval (CI) 40%-100%], specificity 51% (95% CI, 46%-56%) and negative predictive value of 100% (95% CI, 98%-100%). None of the low risk adults had bacterial meningitis. If Bacterial Meningitis Score had been applied prospectively, the hospital admission rate would have dropped from 84% to 49% without missing any patients with bacterial meningitis. The Bacterial Meningitis Score accurately identified patients at low risk for bacterial meningitis and could assist clinical decision-making for adults with meningitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Meningitis - pneumococcal

MedlinePlus

Pneumococcal meningitis is caused by Streptococcus pneumoniae bacteria (also called pneumococcus, or S pneumoniae ). This type of bacteria is the most common cause of bacterial meningitis in adults. ...

Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies

PubMed Central

Correa, Néstor; Covarrubias, Cristian; Rodas, Paula I.; Hermosilla, Germán; Olate, Verónica R.; Valdés, Cristián; Meyer, Wieland; Magne, Fabien; Tapia, Cecilia V.

2017-01-01

extracts. We conclude that human melanin is more active than the two fungal melanins against Cryptococcus. Although some physico-chemical differences were found, they do not explain the differences in the antifungal activity against Cryptococcus of human and cryptococcal melanins. More detailed studies on the structure should be considered to associate structure and antifungal activity. PMID:28744276

HIV proviral DNA associated with decreased neuropsychological function.

PubMed

Shiramizu, Bruce; Paul, Robert; Williams, Andrew; Shikuma, Cecilia; Watters, Michael; Grove, John; Valcour, Victor

2007-01-01

The authors previously found a strong association between elevated HIV proviral DNA (HIV DNA) and a diagnosis of HIV-1-associated dementia (HAD) vs. normal cognition. It is unclear whether HIV DNA globally affects the diagnosis of HAD or whether the effect is limited to individual neuropsychological deficits. This exploratory study examined baseline HIV DNA and its association with individual neuropsychological deficits. HIV DNA was significantly associated with baseline neuropsychological deficits independent of age, ethnicity, IQ, and plasma HIV-1 RNA levels. However, HIV DNA did not predict future changes in neuropsychological deficits. The data suggest that HIV DNA and neuropsychological deficits may co-vary over time.

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.

HIV-1-Associated Atherosclerosis: Unraveling the Missing Link.

PubMed

Kearns, Alison; Gordon, Jennifer; Burdo, Tricia H; Qin, Xuebin

2017-06-27

Cardiovascular disease, including atherosclerosis and atherosclerosis-associated complications, is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV) patients in the post-antiretroviral therapy era. HIV alone accelerates atherosclerosis. Antiretroviral therapy; HIV-associated comorbidities, such as dyslipidemia, drug abuse, and opportunistic infections; and lifestyle are risk factors for HIV-associated atherosclerosis. However, our current understanding of HIV-associated atherogenesis is very limited and has largely been obtained from clinical observation. There is a pressing need to experimentally unravel the missing link between HIV and atherosclerosis. Understanding these mechanisms will help to better develop and design novel therapeutic interventions for the treatment of HIV-associated cardiovascular disease. HIV mainly infects T cells and macrophages resulting in the induction of oxidative and endoplasmic reticulum stress, the formation of the inflammasome, and the dysregulation of autophagy. These mechanisms may contribute to HIV-associated atherogenesis. In this review, we will summarize our current understanding and propose potential mechanisms of HIV-associated atherosclerosis. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Cryptococcal meningitis as a diagnostic problem in a patient with SLE--case report].

PubMed

Bosnić, Dubravka; Cerovec, Mislav; Anić, Branimir; Mayer, Miroslav; Sentić, Mirna; Baresić, Marko; Markeljević, Jasenka; Cikes, Nada

2008-01-01

Systemic erythematosus lupus (SLE) is a disease with wide range of clinical manifestations, signs and symptoms. Disease outcome depends mostly on the affection of kidneys and central nervous system by the disease. Very important cause of death in patients with SLE is infection. Infections are very common among these patients due to aggressive immunosuppressive treatment that is needed for the disease inflammatory activity control. In this case report we have presented a patient with SLE who initially had severe renal affection, but also complications of immunosuppressive therapy that was administered. Even though the disease was accidentally diagnosed, it had a severe clinical progress. Because of lupus nephropathy, in the early phase of the disease we administered aggressive immunosuppressive therapy (combined parenteral therapy of glucocorticoides and cyclophosphamide). As an outcome of the combined effect of disease and immunosuppressive agents used in the treatment of the disease, the patient had increased infective diathesis (repeated infections caused by S. enteritidis--urinary infections and sepsis). During one of the disease flares the patient was hospitalized an opportunistic infection developed. It was meningitis caused by C. neoformans. This opportunistic mycosis infection presented with clinically totally nonspecific signs and symptoms of CNS affection. Therefore, we suspected affection of CNS with SLE. Even though all diagnostic procedures were made on time and that adequate antifungal and supportive agents were applied very early after the infection onset, the outcome was fatal. Because of infective diathesis in patients with SLE, which present with common and opportunistic infections, and due to high mortality rates caused by these infections, we have tried to emphasise the importance of taking adequate specimens early after infection outcome for these rare infective agents like C. neophormans. In recent medical literature are dominant cases reported

Meningitis in children in Fiji: etiology, epidemiology, and neurological sequelae.

PubMed

Biaukula, Viema Lewagalu; Tikoduadua, Lisi; Azzopardi, Kristy; Seduadua, Anna; Temple, Beth; Richmond, Peter; Robins-Browne, Roy; Mulholland, Edward Kim; Russell, Fiona Mary

2012-04-01

To describe the etiology, epidemiology, neurological sequelae, and quality of life of children aged 1 month to less than 5 years admitted with meningitis to the Colonial War Memorial Hospital (CWMH), Suva, Fiji. Over a 3-year period, all eligible children with suspected meningitis admitted to CWMH had blood drawn for culture. Of these children, those for whom is was possible were tested for a four-fold rise in antibody titers to Haemophilus influenzae type b (Hib) and pneumococcal surface adhesin A (PsaA). Cerebrospinal fluid (CSF) was taken for bacteriological culture and antigen testing. CSF was also tested by PCR for Streptococcus species, Neisseria meningitidis, Hib, Mycobacterium tuberculosis, and enterovirus. Pneumococcal isolates were serotyped using multiplex-PCR reverse-line blot hybridization. Following discharge, cases underwent a neurological assessment, audiometry, and quality of life assessment (Pediatric Quality of Life Inventory (PedsQL) tool). There were 70 meningitis cases. Meningitis was more common in indigenous Fijian than Indo-Fijian children. Enterovirus was the most common etiological agent and appeared to be outbreak-associated. Streptococcus pneumoniae was the most common bacterial cause of meningitis with an annual incidence of 9.9 per 100 000 under 5 years old (95% confidence interval 4.9-17.7) and a case fatality rate of 36%. With the exception of deafness, neurological sequelae were more frequent in cases of bacterial meningitis than in viral meningitis (18.5% vs. 0%, p=0.04). Quality of life at follow-up was significantly lower in patients with bacterial meningitis than in those with viral meningitis (p=0.003) or meningitis of unknown etiology (p=0.004). During the study period an outbreak of enterovirus occurred making it the most common etiological agent identified. However in the absence of this outbreak, S. pneumoniae was the most common cause of childhood meningitis in Fiji. Bacterial meningitis is associated with serious

Sequelae due to bacterial meningitis among African children: a systematic literature review

PubMed Central

Ramakrishnan, Meenakshi; Ulland, Aaron J; Steinhardt, Laura C; Moïsi, Jennifer C; Were, Fred; Levine, Orin S

2009-01-01

Background African children have some of the highest rates of bacterial meningitis in the world. Bacterial meningitis in Africa is associated with high case fatality and frequent neuropsychological sequelae. The objective of this study is to present a comprehensive review of data on bacterial meningitis sequelae in children from the African continent. Methods We conducted a systematic literature search to identify studies from Africa focusing on children aged between 1 month to 15 years with laboratory-confirmed bacterial meningitis. We extracted data on neuropsychological sequelae (hearing loss, vision loss, cognitive delay, speech/language disorder, behavioural problems, motor delay/impairment, and seizures) and mortality, by pathogen. Results A total of 37 articles were included in the final analysis representing 21 African countries and 6,029 children with confirmed meningitis. In these studies, nearly one fifth of bacterial meningitis survivors experienced in-hospital sequelae (median = 18%, interquartile range (IQR) = 13% to 27%). About a quarter of children surviving pneumococcal meningitis and Haemophilus influenzae type b (Hib) meningitis had neuropsychological sequelae by the time of hospital discharge, a risk higher than in meningococcal meningitis cases (median = 7%). The highest in-hospital case fatality ratios observed were for pneumococcal meningitis (median = 35%) and Hib meningitis (median = 25%) compared to meningococcal meningitis (median = 4%). The 10 post-discharge studies of children surviving bacterial meningitis were of varying quality. In these studies, 10% of children followed-up post discharge died (range = 0% to 18%) and a quarter of survivors had neuropsychological sequelae (range = 3% to 47%) during an average follow-up period of 3 to 60 months. Conclusion Bacterial meningitis in Africa is associated with high mortality and risk of neuropsychological sequelae. Pneumococcal and Hib meningitis kill approximately one third of affected

Long-term outcomes of a transmastoid lateral semicircular canal approach to congenital CSF otorrhea in children associated with recurrent meningitis and severe inner ear malformation.

PubMed

Wang, Jie; Li, Yongxin; Chen, Shubin; Hao, Xinping

2016-08-01

To investigate the long-term effectiveness of transmastoid lateral semicircular canal approach (TMLSCCA) to repair cerebrospinal fluid (CSF) leakage in children associated with recurrent meningitis and severe congenital inner malformation. A retrospective study was conducted in a university hospital, academic medical center. Fifteen children with recurrent meningitis, secondary to severe congenital inner ear malformation, were included in the study. All of them had CSF associated otorrhea and treated using TLSCCA to repair CSF otorrhea by packing the vestibule with muscle and fascia. Observation of the status of postoperative CSF leakage, recurrence of meningitis and complication were conducted. None of the cases had recurrent meningitis and CSF leakage after their TLSCCA procedure in the follow-up period of 1-8.5 years. One case presented with transient facial nerve paralysis and completely recovered 3 months later. TLSCCA for CSF otorrhea in children with recurrent meningitis secondary to congenital inner ear malformation is an alternative approach that offers some advantages. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cerebrospinal fluid monocytes in bacterial meningitis, viral meningitis, and neuroborreliosis.

PubMed

Martinot, M; Greigert, V; Souply, L; Rosolen, B; De Briel, D; Mohseni Zadeh, M; Kaiser, J-D

2018-04-05

Cerebrospinal fluid (CSF) leukocytes analysis is commonly used to diagnose meningitis and to differentiate bacterial from viral meningitis. Interpreting CSF monocytes can be difficult for physicians, especially in France where lymphocytes and monocytes results are sometimes pooled. We assessed SF monocytes in patients presenting with microbiologically confirmed meningitis (CSF leukocyte count>10/mm 3 for adults or >30/mm 3 for children<2 months), i.e. bacterial meningitis (BM), viral meningitis (VM), and neuroborreliosis (NB). Two-hundred patients (82 BM, 86 VM, and 32 NB) were included. The proportions of monocytes were higher in VM (median 8%; range 0-57%) than in BM (median 5%; range 0-60%, P=0.03) or NB (median 5%; range 0-53%, P=0.46), with a high value overlap between conditions. CSF monocytes should not be used to discriminate BM from VM and NB because of value overlaps. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Different meningitis-causing bacteria induce distinct inflammatory responses on interaction with cells of the human meninges.

PubMed

Fowler, Mark I; Weller, Roy O; Heckels, John E; Christodoulides, Myron

2004-06-01

The interactions of bacterial pathogens with cells of the human leptomeninges are critical events in the progression of meningitis. An in vitro model based on the culture of human meningioma cells was used to investigate the interactions of the meningeal pathogens Escherichia coli K1, Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. A rank order of association with meningioma cells was observed, with N. meningitidis showing the highest levels of adherence, followed by E. coli, S. pneumoniae and H. influenzae. Neisseria meningitidis and H. influenzae did not invade meningioma cells or induce cell death, but induced a concentration-dependent secretion of inflammatory mediators. Neisseria meningitidis induced higher levels of IL-6, MCP-1, RANTES and GM-CSF than H. influenzae, but there was no significant difference in the levels of IL-8 induced by both pathogens. Streptococcus pneumoniae was also unable to invade meningioma cells, but low concentrations of bacteria failed to stimulate cytokine secretion. However, higher concentrations of pneumococci led to cell death. By contrast, only E. coli K1 invaded meningioma cells directly and induced rapid cell death before an inflammatory response could be induced. These data demonstrate that the interactions of different bacterial pathogens with human meningeal cells are distinct, and suggest that different intervention strategies may be needed in order to prevent the morbidity and mortality associated with bacterial meningitis.

Bacterial meningitis in diabetes patients: a population-based prospective study

PubMed Central

van Veen, Kiril E. B.; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

2016-01-01

Diabetes mellitus is associated with increased infection rates. We studied clinical features and outcome of community-acquired bacterial meningitis in diabetes patients. Patients were selected from a nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 2006 to October 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were prospectively collected. A total of 183 of 1447 episodes (13%) occurred in diabetes patients. The incidence of bacterial meningitis in diabetes patients was 3.15 per 100,000 patients per year and the risk of acquiring bacterial meningitis was 2.2-fold higher for diabetes patients. S. pneumoniae was the causative organism in 139 of 183 episodes (76%) and L. monocytogenes in 11 of 183 episodes (6%). Outcome was unfavourable in 82 of 183 episodes (45%) and in 43 of 183 episodes (23%) the patient died. Diabetes was associated with death with an odds ratio of 1.63 (95% CI 1.12–2.37, P = 0.011), which remained after adjusting for known predictors of death in a multivariable analysis (OR 1.98 [95% CI 1.13–3.48], P = 0.017). In conclusion, diabetes is associated with a 2-fold higher risk of acquiring bacterial meningitis. Diabetes is a strong independent risk factor for death in community-acquired adult bacterial meningitis. PMID:27845429

Bacterial meningitis in diabetes patients: a population-based prospective study.

PubMed

van Veen, Kiril E B; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

2016-11-15

Diabetes mellitus is associated with increased infection rates. We studied clinical features and outcome of community-acquired bacterial meningitis in diabetes patients. Patients were selected from a nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 2006 to October 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were prospectively collected. A total of 183 of 1447 episodes (13%) occurred in diabetes patients. The incidence of bacterial meningitis in diabetes patients was 3.15 per 100,000 patients per year and the risk of acquiring bacterial meningitis was 2.2-fold higher for diabetes patients. S. pneumoniae was the causative organism in 139 of 183 episodes (76%) and L. monocytogenes in 11 of 183 episodes (6%). Outcome was unfavourable in 82 of 183 episodes (45%) and in 43 of 183 episodes (23%) the patient died. Diabetes was associated with death with an odds ratio of 1.63 (95% CI 1.12-2.37, P = 0.011), which remained after adjusting for known predictors of death in a multivariable analysis (OR 1.98 [95% CI 1.13-3.48], P = 0.017). In conclusion, diabetes is associated with a 2-fold higher risk of acquiring bacterial meningitis. Diabetes is a strong independent risk factor for death in community-acquired adult bacterial meningitis.

HIV- and AIDS-associated cancers.

PubMed

Carr, Ellen R

2013-04-01

One of the most significant world epidemics in history, HIV/AIDS, has been a research priority since its discovery in 1981. This review article provides an update on HIV/AIDS, with a specific focus on the diagnosis and care of patients with HIV- and AIDS-associated cancers.

Listeria monocytogenes empyema in an HIV infected patient

PubMed Central

Marron, A.; Roson, B.; Mascaro, J.; Carratala, J.

1997-01-01

Listeriosis in HIV infected patients is uncommon and usually presents as meningitis or bacteraemia. Pleural fluid infections caused by this organism are extremely rare. A case is described of empyema caused by Listeria monocytogenes in an HIV infected patient that was successfully treated with medical treatment only. 




 PMID:9337838

Meningitis - staphylococcal

MedlinePlus

... system and peripheral nervous system References Nath A. Meningitis: bacterial, viral, and other. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ... D, Scheld WM. Acute meningitis. In: Bennett JE, Dolin R, Blaser MJ, eds. ...

Corticosteroids for acute bacterial meningitis.

PubMed

Brouwer, Matthijs C; McIntyre, Peter; Prasad, Kameshwar; van de Beek, Diederik

2015-09-12

In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response. To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis. We searched CENTRAL (2015, Issue 1), MEDLINE (1966 to January week 4, 2015), EMBASE (1974 to February 2015), Web of Science (2010 to February 2015), CINAHL (2010 to February 2015) and LILACS (2010 to February 2015). Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis. We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality. We included 25 studies involving 4121 participants (2511 children and 1517 adults; 93 mixed population). Four studies were of high quality with no risk of bias, 14 of medium quality and seven of low quality, indicating a moderate risk of bias for the total analysis. Nine studies were performed in low-income countries and 16 in high-income countries.Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P value = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P value = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in

Hiv-associated nephropathy occurring before HIV antibody seroconversion.

PubMed

Levin, M L; Palella, F; Shah, S; Lerma, E; Butter, J; Kanwar, Y S

2001-05-01

It currently is thought that human immunodeficiency virus-associated nephropathy (HIVAN) occurs late in the course of HIV infection. Although HIVAN may be the presenting manifestation of acquired immunodeficiency syndrome (AIDS), it usually occurs after a prolonged period of viral infection often associated with high levels of HIV viremia. The patient described here developed HIVAN as a manifestation of acute retroviral syndrome. A 41-year-old black man presented with nephrotic range proteinuria, renal insufficiency, and acute gastrointestinal and pulmonary symptoms. He recently had been treated for primary syphilis. Two HIV serologic tests, performed 3 months apart, were negative. Renal biopsy was consistent with HIVAN. After the biopsy, the patient was discovered to have more than 700,000 viral copies per mL in his blood. CD4(+) count was greater than 500/mm(3). Six weeks later, enzyme-linked immunosorbent assay and Western blot analyses for HIV antibody became positive. HIVAN can occur early in the course of HIV infection, even during acute infection before seroconversion, and prolonged exposure to virus is not necessary for this renal involvement to occur in the susceptible host.

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

Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome.

PubMed

Pomar, Virginia; Benito, Natividad; López-Contreras, Joaquin; Coll, Pere; Gurguí, Mercedes; Domingo, Pere

2013-09-30

Spontaneous meningitis caused by gram-negative bacilli in adult patients is uncommon and poorly characterized. Our objective is to describe and compare the characteristics and the outcome of adult patients with spontaneous gram-negative bacilli meningitis (GNBM) and spontaneous meningitis due to other pathogens. Prospective single hospital-based observational cohort study conducted between 1982 and 2006 in a university tertiary hospital in Barcelona (Spain). The Main Outcome Measure: In-hospital mortality. Gram-negative bacilli meningitis was diagnosed in 40 (7%) of 544 episodes of spontaneous acute bacterial meningitis. The most common pathogens were Escherichia coli and Pseudomonas species. On admission, characteristics associated with spontaneous gram-negative bacilli meningitis by multivariate modeling were advanced age, history of cancer, nosocomial acquisition of infection, urinary tract infection as distant focus of infection, absence of rash, hypotension, and a high cerebrospinal fluid white-cell count. Nine (23%) episodes were acquired in the hospital and they were most commonly caused by Pseudomonas. The in-hospital mortality rate was 53%. The mortality rate was higher among patients with Gram-negative bacillary meningitis than among those with other bacterial meningitis and their risk of death was twenty times higher than among patients infected with Neisseria meningitidis (odds ratio 20.47; 95% confidence interval 4.03-103.93; p<0.001). Gram-negative bacilli cause 9% of spontaneous bacterial meningitis of known etiology in adults. Characteristics associated with GNBM include advanced age, history of cancer, nosocomial acquisition, and urinary tract infection as distant focus of infection. The mortality rate is higher among patients with gram-negative bacillary meningitis than among those with other bacterial meningitides.

Meningitis Caused by Rhodotorula mucilaginosa in HIV-Infected Patient: A Case Report and Review of the Literature.

PubMed

Mohd Nor, Fadzilah; Tan, Lian Huat; Na, Shi Ling; Ng, Kee Peng

2015-08-01

Rhodotorula species are increasingly being identified as a cause of fungal infection in the central nervous system, especially in patients with compromised immunity. The diagnosis could easily be missed due to low index of suspicion, as cryptococcus meningitis and cerebral toxoplasmosis are more common amongst immunocompromised hosts. To date, there are six cases of Rhodotorula-related meningitis reported, and three are associated with human immunodeficiency virus infection. In this report, a case of a Malaysian male with underlying human immunodeficiency virus infection who developed Rhodotorula mucilaginosa meningitis is presented. High-grade fever and severe headaches were the complaints presented in three previous case reports. India ink and nigrosin stainings were performed in the two previous reports and both revealed positive results. R. mucilaginosa were isolated from the culture of the patient's cerebrospinal fluid in all three previous reports. Predominant lymphocyte infiltration in the cerebrospinal fluid examination was documented in two reports. CD4 counts were above 100/µl in two previously published reports, while another report documented CD4 count as 56/µl. Amphotericin B and itraconazole are identified to be the first line of antifungal used and as the maintenance therapy, respectively. The possibility of relapse cannot be excluded as it was reported in the first report. It was also revealed that the current case has almost similar clinical presentation and therapeutic outcome as compared to the published reports, but some differences in diagnostic details were to be highlighted.

Herpes simplex virus type 2 (Mollaret's) meningitis: a case report.

PubMed

Abu Khattab, Mohammed; Al Soub, Hussam; Al Maslamani, Mona; Al Khuwaiter, Jameela; El Deeb, Yasser

2009-11-01

Mollaret's meningitis is an unusual and under-appreciated syndrome of benign, recurrent aseptic meningitis. The available literature indicates that the causative agent is herpes simplex virus type 2 (HSV-2) in the majority of cases and much less frequently herpes simplex virus type 1 (HSV-1). We report the case of a 49-year-old Indian female who had four attacks of recurrent lymphocytic meningitis (Mollaret's meningitis) occurring over a 7-year period. The diagnosis of herpes simplex meningitis was made at the time of the fourth episode by a positive PCR for herpes simplex virus infection in the cerebrospinal fluid. During the first three episodes, the patient was treated with anti-tuberculous drugs and antibiotics for bacterial meningitis; however for the last episode, once the diagnosis of herpes simplex meningitis was confirmed, only symptomatic treatment was given. No long-term suppressive therapy was given and no recurrence has been experienced so far. Mollaret's meningitis should be suspected in all cases of recurrent lymphocytic meningitis. Early diagnosis may prevent prolonged hospital admissions, unnecessary investigations, and exposure to unnecessary medications, with the associated considerable costs. Treatment with acyclovir may be beneficial in decreasing the severity and duration of attacks and in preventing further episodes. [Au?1].

Human parasitic meningitis caused by Angiostrongylus cantonensis infection in Taiwan.

PubMed

Tsai, Hung-Chin; Chen, Yao-Shen; Yen, Chuan-Min

2013-06-01

The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophilic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection.

Oral microbiome in HIV-associated periodontitis.

PubMed

Noguera-Julian, Marc; Guillén, Yolanda; Peterson, Jessica; Reznik, David; Harris, Erica V; Joseph, Sandeep J; Rivera, Javier; Kannanganat, Sunil; Amara, Rama; Nguyen, Minh Ly; Mutembo, Simon; Paredes, Roger; Read, Timothy D; Marconi, Vincent C

2017-03-01

HIV-associated periodontal diseases (PD) could serve as a source of chronic inflammation. Here, we sought to characterize the oral microbial signatures of HIV+ and HIV- individuals at different levels of PD severity.This cross-sectional study included both HIV+ and HIV- patients with varying degrees of PD. Two tooth, 2 cheek, and 1 saliva samples were obtained for microbiome analysis. Mothur/SILVADB were used to classify sequences. R/Bioconductor (Vegan, PhyloSeq, and DESeq2) was employed to assess overall microbiome structure differences and differential abundance of bacterial genera between groups. Polychromatic flow cytometry was used to assess immune activation in CD4 and CD8 cell populations.Around 250 cheek, tooth, and saliva samples from 50 participants (40 HIV+ and 10 HIV-) were included. Severity of PD was classified clinically as None/Mild (N), Moderate (M), and Severe (S) with 18 (36%), 16 (32%), and 16 (32%) participants in each category, respectively. Globally, ordination analysis demonstrated clustering by anatomic site (R2 = 0.25, P < 0.001). HIV status and PD severity showed a statistically significant impact on microbiome composition but only accounted for a combined 2% of variation. HIV+ samples were enriched in genera Abiotrophia, Neisseria, Kingella, and unclassified Neisseriaceae and depleted in Leptotrichia and Selenomonas. The Neisseria genus was consistently enriched in HIV+ participants regardless of sampling site and PD level. Immune markers were altered in HIV+ participants but did not show association with the oral microbiome.HIV-associated changes in oral microbiome result in subtle microbial signatures along different stages of PD that are common in independent oral anatomic sites.

Meninges in cancer imaging.

PubMed

Mahendru, G; Chong, V

2009-10-02

Primary malignant tumours arising from the meninges are distinctly uncommon, and when they occur, they are usually sarcomas. In contrast, metastatic meningeal involvement is increasingly seen as advances in cancer therapy have changed the natural history of malignant disease and prolonged the life span of cancer patients. The meninges can either be infiltrated by contiguous extension of primary tumours of the central nervous system, paranasal sinuses and skull base origin or can be diffusely infiltrated from haematogenous dissemination from distant primary malignancies. Imaging in these patients provides crucial information in planning management. This article reviews the pertinent anatomy that underlies imaging findings, discusses the mechanism of meningeal metastasis and highlights different imaging patterns of meningeal carcinomatosis and the pitfalls.

Etiology of Acute Bacterial Meningitis in Iran: a Systematic Review.

PubMed

Ghotaslou, Reza; Yeganeh-Sefidan, Fatemeh; Salahi-Eshlaqi, Behnaz; Ebrahimzadeh-Leylabadlo, Hamed

2015-08-01

Acute bacterial meningitis (ABM) is one of the most severe infectious diseases, causing neurologic sequel, and a case fatality rate of 20-30%. The aim of this paper was to summarize the main causes of ABM in Iran. We searched the data for relevant articles using meningitis, etiology, and Iran as search terms. We found 23 papers for inclusion in the review that focused specifically on the ABM, addressing etiology and acute meningitis. Finally, during the 23 years, a total of 18163 cases were recorded, and 1074 cases of which met the criteria for bacterial meningitis. The most common agent associated with bacterial meningitis was S. pneumoniae, followed by H. influenzae, Enterobacter spp., N. meningitidis, and group B streptococcus. The total incidence of ABM during 1991 to 2002 was higher than during 2003-2013. S. pneumoniae still remains a main cause of bacterial meningitis. For improved outcomes, studies are needed to further clarify the etiology of meningitis in Iran, explore simple, accurate, and practical diagnostic tools as PCR, and investigate the most appropriate specific and supportive interventions to manage and prevent meningitis as vaccination.

The risk of aseptic meningitis associated with the Leningrad-Zagreb mumps vaccine strain following mass vaccination with measles-mumps-rubella vaccine, Rio Grande do Sul, Brazil, 1997.

PubMed

da Silveira, Claudio Marcos; Kmetzsch, Claudete Iris; Mohrdieck, Renate; Sperb, Alethea Fagundes; Prevots, D Rebecca

2002-10-01

Few data are available on the risk of aseptic meningitis following vaccination with the Leningrad-Zagreb (L-Z) strain of mumps vaccine. In 1997 the mumps vaccine was introduced into the state of Rio Grande do Sul in Brazil through mass vaccination with mumps-measles-rubella (MMR), targeting children aged 1-11 years. Five municipalities used exclusively MMR vaccine containing the L-Z strain of mumps. An outbreak of aseptic meningitis was observed shortly after the mass campaign. To estimate the risk of aseptic meningitis associated with this strain, we analysed vaccination and meningitis case surveillance data from the selected municipalities. A case of vaccine-associated aseptic meningitis was defined as one with a pleocytosis of 10-1,500 leukocytes/ml and occurring within 15-35 days after vaccine receipt. We estimated a risk of 2.9 cases per 10,000 doses of L-Z administered, equivalent to 1 case per 3,390 doses administered. The overall risk of aseptic meningitis following the campaign was increased 12.2-fold (95% CI: 6.0-24.7) compared with the same period in 1995-1996. Following the mass campaign, the incidence of mumps declined 93% during 1998-2000. Vaccination with the L-Z strain of mumps vaccine as part of a mass campaign was associated with a significantly increased risk of aseptic meningitis. Decisions about type of mumps vaccine and mumps vaccination strategies must consider vaccine safety issues in addition to other criteria.

Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens.

PubMed

Shikano, Hiroaki; Ohnishi, Hidenori; Fukutomi, Hisashi; Ito, Kimiko; Morimoto, Masahiro; Teramoto, Takahide; Aoki, Mitsuhiro; Nishihori, Takezumi; Akeda, Yukihiro; Oishi, Kazunori; Fukao, Toshiyuki

2015-12-01

Mondini dysplasia is rare, but has an important association with recurrent bacterial meningitis. We herein describe the case of a 3-year-old girl with unilateral sensorineural hearing loss who presented with three independent episodes of bacterial meningitis within 8 months. Temporal bone computed tomography indicated the characteristic features of Mondini dysplasia in the right inner ear. This was treated by surgical closure of the inner ear defect via oval window and additional vaccination was administered. Appropriate vaccination might prevent the recurrent bacterial meningitis associated with Mondini dysplasia. © 2015 Japan Pediatric Society.

[Acute care of patients with bacterial meningitis].

PubMed

Stetefeld, H R; Dohmen, C

2016-04-01

Bacterial meningitis is a life-threatening emergency that is still associated with high mortality and poor outcome. The purpose of this article is to provide a review of clinical presentation, diagnostic procedure, therapy, and prognosis in bacterial meningitis. Prognostic factors which could be influenced positively are identified and a focused procedure in the emergency setting and for the treatment of complications are provided. This work is based on a literature search (PubMed, guidelines) and personal experience (standard operating procedures, SOP). Despite improved health care, bacterial meningitis is still associated with high mortality and poor neurological outcome, which has remained largely unaltered during recent decades. Diagnosis and, more importantly, effective therapy of bacterial meningitis are often delayed, having an immediate negative influence on clinical outcome. Neurological and nonneurological complications often necessitate intensive care and may occur rapidly or in the further course of the disease. Immediate initiation of effective therapy is crucial to positively influence mortality and neurological outcome. Antibiotics should be administered within 30 min after admission. To achieve this, a focused and well-organized procedure in the emergency setting is necessary. Because of intra- and extracranial complications, patients need to be treated on intensive care units including neurological expertise and interdisciplinary support.

A comparison of neonatal Gram-negative rod and Gram-positive cocci meningitis.

PubMed

Smith, P B; Cotten, C M; Garges, H P; Tiffany, K F; Lenfestey, R W; Moody, M A; Li, J S; Benjamin, D K

2006-02-01

Neonatal meningitis is an illness with potentially devastating consequences. Early identification of potential risk factors for Gram-negative rod (GNR) infections versus Gram-positive cocci (GPC) infection prior to obtaining final culture results is of value in order to appropriately guide expirical therapy. We sought to compare laboratory and clinical parameters of GNR and GPC meningitis in a cohort of term and premature infants. We evaluated lumbar punctures from neonates cared for at 150 neonatal intensive care units managed by the Pediatrix Medical Group Inc. We compared cerebrospinal fluid (CSF) parameters (white blood cell count, red blood cell count, glucose, and protein), demographics, and outcomes between infants with GNR and GPC meningitis. CSF cultures positive with coagulase-negative staphylococci were excluded. We identified 77 infants with GNR and 86 with GPC meningitis. There were no differences in gestational age, birth weight, infant sex, race, or rate of Caesarean section. GNR meningitis was more often diagnosed after the third postnatal day and was associated with higher white blood cell and red blood cell counts. GNR meningitis diagnosed in the first 3 days of life was associated with antepartum antibiotic exposure. No difference was noted in either CSF protein or glucose levels. After correcting for gestational age, there was no observed difference in mortality between infants infected with GNR or GPC. Compared to GPC meningitis, GNR meningitis was associated with several aspects of the clinical history and laboratory findings including older age of presentation, antepartum exposure to antibiotics, and elevated CSF white blood cell and red blood cell counts.

A Hypereosinophilic Syndrome Associated with HIV Infection

DTIC Science & Technology

1992-01-01

et al, however, were very similar to that of ours and suggests a relationship (6). Eosinophilic folliculitis is a papular eruption which occurs in HIV...patients with moderate to advanced HIV infection (14). The dermatopathology of eosinophilic folliculitis is primarily characterized by follicular...Berger TG. HIV-associated eosinophilic folliculitis : A unique dermatosis associated with advanced HIV infection. Arch Derm 1991; 127: 206 15. Ray TL

Meninges in cancer imaging

PubMed Central

Chong, V.

2009-01-01

Abstract Primary malignant tumours arising from the meninges are distinctly uncommon, and when they occur, they are usually sarcomas. In contrast, metastatic meningeal involvement is increasingly seen as advances in cancer therapy have changed the natural history of malignant disease and prolonged the life span of cancer patients. The meninges can either be infiltrated by contiguous extension of primary tumours of the central nervous system, paranasal sinuses and skull base origin or can be diffusely infiltrated from haematogenous dissemination from distant primary malignancies. Imaging in these patients provides crucial information in planning management. This article reviews the pertinent anatomy that underlies imaging findings, discusses the mechanism of meningeal metastasis and highlights different imaging patterns of meningeal carcinomatosis and the pitfalls. PMID:19965290

Serratia marcescens meningitis: epidemiology, prognostic factors and treatment outcomes.

PubMed

Wu, Yen-Mu; Hsu, Po-Chang; Yang, Chien-Chang; Chang, Hong-Jyun; Ye, Jung-Jr; Huang, Ching-Tai; Lee, Ming-Hsun

2013-08-01

Serratia marcescens is a rare pathogen of central nervous system infections. This study was to investigate the epidemiology, prognostic factors, and treatment outcomes of S. marcescens meningitis. This retrospective analysis included 33 patients with culture-proven S. marcescens meningitis hospitalized between January 2000 and June 2011. Of the 33 patients enrolled, only one did not receive neurosurgery before the onset of S. marcescens meningitis. Patients with S. marcescens meningitis had higher ratios of brain solid tumors (54.5%) and neurosurgery (97.0%) with a mortality rate of 15.2%. The mean interval between the first neurosurgical procedure and the diagnosis of meningitis was 17.1 days (range, 4-51 days). Only one third-generation cephalosporin-resistant S. marcescens isolate was recovered from the patients' cerebrospinal fluid (CSF) specimens. Compared with the favorable outcome group (n = 20), the unfavorable outcome group (n = 13) had a higher percentage of brain solid tumors, more intensive care unit stays, and higher Sequential Organ Failure Assessment score, CSF lactate and serum C-reactive protein concentrations at diagnosis of meningitis. Under the multiple regression analysis, CSF lactate concentration ≥2-fold the upper limit of normal (ULN) was independently associated with unfavorable outcomes (odds ratio, 7.20; 95% confidence interval, 1.08-47.96; p = 0.041). S. marcescens meningitis is highly associated with neurosurgical procedures for brain solid tumors. CSF lactate concentration ≥2x ULN may predict an unfavorable outcome. Its mortality is not high and empiric treatment with parenteral third-generation cephalosporins may have a satisfactory clinical response. Copyright © 2012. Published by Elsevier B.V.

Two cases of bacterial meningitis accompanied by thalidomide therapy in patients with multiple myeloma: is thalidomide associated with bacterial meningitis?

PubMed

Pasa, Semir; Altintas, Abdullah; Cil, Timucin; Ustun, Cemal; Bayan, Kadim; Danis, Ramazan; Urakci, Zuhat; Tuzun, Yekta; Ayyildiz, Orhan

2009-01-01

Morbidity and mortality in multiple myeloma is often attributed to life-threatening infections. A defect in humoral immunity has been proposed for the predisposition to bacterial infections. Most of the infections are of bacterial origin, and the most serious are septicemia, meningitis, and pneumonia. Thalidomide is a drug with pleiotropic effects. The immunomodulatory effects of thalidomide are at least partially mediated through its ability to down-regulate the pathogenic over-production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a cytokine that plays a central role in the regulation of the host immune and inflammatory response to infection. In the central nervous system, TNF-alpha is involved in induction of a fever response and triggers the release of other cytokines, and may also influence transport of compounds into the brain, leading to cerebrospinal fluid leukocytosis, increased protein influx, and lactate accumulation. Thalidomide has been shown to down-regulate the production of TNF-alpha. On the other hand, knowledge of the effects of thalidomide on granulocyte functions is limited. Thalidomide has been shown to attenuate neutrophil adhesion and chemotaxis. We present herein two cases of Streptococcus pneumoniae bacterial meningitis that developed soon after the initiation of thalidomide treatment, and discuss the effect of thalidomide on the immune system. Although, it is not clear whether thalidomide caused the development of the bacterial infections and meningitis, or what its pathogenetic mechanisms are, physicians should be alert for signs and symptoms of meningitis in patients with multiple myeloma who are treated with thalidomide, especially those in neutropenic states.

Unrecognised ventriculitis/meningitis presenting as hydrocephalus in infancy.

PubMed

Udani, Vrajesh; Udani, Soonu; Merani, Rohan; Bavdekar, Manisha

2003-09-01

Infantile hydrocephalus due to unrecognized neonatal-onset meningitis/ventriculitis, was studied retrospectively using 1991-1998 chart review. Seventy two patients with hydrocephalus were reviewed. Thirteen infants had hydrocephalus associated with active meningitis/ventriculitis which had remained unrecognized. Active meningitis/ventriculitis was confirmed by the finding of an abnormal lumbar and ventricular CSF with or without positive culture. All had perinatal risk factors and 10/13 had been given antibiotics in the postnatal period. 6/13 infants appeared to be well. The most common presentation was increasing head size. All lumbar and ventricular CSFs were abnormal and 10/13 had positive cultures as well. Imaging revealed hydrocephalus in all. The infants were treated with antibiotics for a mean of 32.8 days before VP shunting. 7/11 were severely disabled. Unrecognized active meningitis/ventriculitis is an important cause of infantile hydrocephalus.

Clinical prediction rule for differentiating tuberculous from viral meningitis.

PubMed

Hristea, A; Olaru, I D; Baicus, C; Moroti, R; Arama, V; Ion, M

2012-06-01

The Professor Dr Matei Bals National Institute of Infectious Diseases, Bucharest, Romania. To create a prediction rule to enable clinicians to differentiate patients with tuberculous meningitis (TBM) from those with viral meningitis. We retrospectively analysed patients admitted to a tertiary care facility between 2001 and 2011 with viral meningitis and TBM. Patients were defined as having TBM according to a recently published consensus definition, and as viral meningitis if a viral aetiology was confirmed, or after ruling out bacterial, fungal and non-infectious causes of meningitis. We identified 433 patients with viral meningitis and 101 TBM patients and compared their clinical and laboratory features. Multivariable analysis showed a statistically significant association between TBM and the following variables: duration of symptoms before admission of ≥5 days, presence of neurological impairment (altered consciousness, seizures, mild focal signs, multiple cranial nerve palsies, dense hemiplegia or paraparesis), cerebrospinal fluid/blood glucose ratio < 0.5 and cerebrospinal fluid protein level > 100 mg/dl. We propose a diagnostic score based on the coefficients derived from the logistic regression model with a sensitivity and specificity for TBM of respectively 92% and 94%. Our study suggests that easily available clinical and laboratory data are very useful for differentiating TBM from other causes of meningitis.

Six months therapy for tuberculous meningitis

PubMed Central

Jullien, Sophie; Ryan, Hannah; Modi, Manish; Bhatia, Rohit

2016-01-01

/915 (0.8%) with longer), with only one death attributed to relapse in each group. Overall, the proportion of participants who died was higher in the cohorts treated for longer than six months (447/1423 (31.4%) versus 58/458 (12.7%)). However, most deaths occurred during the first six months in both treatment cohorts, which suggested that the difference in death rate was not directly related to duration of ATT but was due to confounding. Clinical cure was higher in the group of cohorts treated for six months (408/458 (89.1%) versus longer than six months (984/1336 (73.7%)), consistent with the observations for deaths. Few participants defaulted from treatment with six months treatment (4/370 (1.1%)) versus longer treatment (8/355 (2.3%)), and adherence was not well reported. Authors' conclusions In all cohorts most deaths occurred in the first six months; and relapse was uncommon in all participants irrespective of the regimen. Further inferences are probably inappropriate given this is observational data and confounding is likely. These data are almost all from participants who are HIV-negative, and thus the inferences will not apply to the efficacy and safety of the six months regimens in HIV-positive people. Well-designed RCTs, or large prospective cohort studies, comparing six months with longer treatment regimens with long follow-up periods established at initiation of ATT are needed to resolve the uncertainty regarding the safety and efficacy of six months regimens for TBM. Six months therapy for patients with tuberculous meningitis What is tuberculous meningitis and why is the duration of treatment important? Tuberculous meningitis (TBM) is a severe form of tuberculosis, which affects the membranes that cover the brain and spine. It is associated with high rates of death and disability. While there are standardized international recommendations for treating people with pulmonary tuberculosis (tuberculosis of the lungs) for six months with antituberculous therapy

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

Chickenpox complicated by pneumococcal meningitis: a rare coinfection.

PubMed

Rebahi, H; Mouaffak, Y; Soraa, N; Younous, S

2014-11-01

Bacterial complications, particularly skin superinfections, are common during chickenpox. However, reports of acute bacterial meningitis associated with chickenpox are unusual and amount to only a very few observations. For the most part, they are caused by Neisseria meningitidis or Streptococcus pyogenes. We report an infrequent occurrence of pneumococcal meningitis 2 days after the onset of a chickenpox rash in a 7-year-old previously healthy boy. Based on data from the literature, we attempt to understand the possible mechanisms resulting in bacterial complications, particularly meningitis, during chickenpox and to determine the means to prevent it. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A 15-year retrospective analysis of prognostic factors in childhood bacterial meningitis.

PubMed

Wee, Liang Yi Justin; Tanugroho, Raymond Reinaldo; Thoon, Koh Cheng; Chong, Chia Yin; Choong, Chew Thye; Krishnamoorthy, Subramania; Maiwald, Matthias; Tee, Nancy Wen Sim; Tan, Natalie Woon Hui

2016-01-01

This retrospective chart review aimed to identify factors in childhood bacterial meningitis that predicted disease severity and long-term outcome. The study included 112 episodes of microbiologically confirmed bacterial meningitis in children aged three days to 15 years who were admitted to a Singapore hospital from 1998 to 2013. The mortality rate was 6%, and 44% required intensive care unit (ICU) admission. Predictive factors associated with ICU admission included pneumococcal meningitis, with an odds ratio (OR) of 5.2 and 95% confidence interval (CI) of 1.5-18.2, leukopenia (OR 5.6, 95% CI 1.7-17.9) and a cerebrospinal fluid (CSF):serum glucose ratio <0.25 (OR 4.5, 95% CI 1.4-14.4). An initial CSF white blood cell count >1000/mm(3) (OR 0.26, 95% CI 0.086-0.76) was negatively associated with ICU admission. Five years after meningitis, 32% had residual sequelae, and the associated prognostic factors were Haemophilus influenzae type b (Hib) meningitis (OR 29.5, 95% CI 2-429), seizures during their inpatient stay (OR 10.6, 95% CI 1.9-60.2) and septic shock (OR 8.4, 95% CI 1.1-62.1). As mortality was low in this bacterial meningitis study, ICU admission was used as a marker of disease severity. These findings underscore the importance of the pneumococcal and Hib meningitis vaccines. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Campylobacter fetus meningitis associated with eating habits of raw meat and raw liver in a healthy patient: A case report and literature review.

PubMed

Ishihara, Ayaka; Hashimoto, Etaro; Ishioka, Haruhiko; Kobayashi, Hiroyuki; Gomi, Harumi

2018-01-01

Meningitis caused by the zoonotic pathogen Campylobacter fetus in immunocompetent adults is rare. We report a 48-year-old Japanese woman with no underlying disease who was found to have meningitis caused by C. fetus . Both C. fetus subsp. fetus and C. fetus subsp. venerealis were isolated from the cerebrospinal fluid culture. The mode of infection in our patient was considered to be associated with the consumption of raw beef and raw cattle liver on a regular basis. Public awareness and education to avoid the consumption of raw or undercooked meat might help prevent C. fetus meningitis.

Association Between Internalized HIV-Related Stigma and HIV Care Visit Adherence.

PubMed

Rice, Whitney S; Crockett, Kaylee B; Mugavero, Michael J; Raper, James L; Atkins, Ghislaine C; Turan, Bulent

2017-12-15

Internalized HIV-related stigma acts as a barrier to antiretroviral therapy (ART) adherence, but its effects on other HIV care continuum outcomes are unclear. Among 196 HIV clinic patients in Birmingham, AL, we assessed internalized HIV-related stigma and depressive symptom severity using validated multi-item scales and assessed ART adherence using a validated single-item measure. HIV visit adherence (attended out of total scheduled visits) was calculated using data from clinic records. Using covariate-adjusted regression analysis, we investigated the association between internalized stigma and visit adherence. Using path analytic methods with bootstrapping, we tested the mediating role of depressive symptoms in the association between internalized stigma and visit adherence and the mediating role of visit adherence in the association between internalized stigma and ART adherence. Higher internalized stigma was associated with lower visit adherence (B = -0.04, P = 0.04). Black (versus white) race and depressive symptoms were other significant predictors within this model. Mediation analysis yielded no indirect effect through depression in the association between internalized stigma and visit adherence (B = -0.18, SE = 0.11, 95% confidence interval: -0.44 to -0.02) in the whole sample. Supplemental mediated moderation analyses revealed gender-specific effects. Additionally, the effect of internalized stigma on suboptimal ART adherence was mediated by lower visit adherence (B = -0.18, SE = 0.11, 95% confidence interval: -0.44 to -0.02). Results highlight the importance of internalized HIV stigma to multiple and sequential HIV care continuum outcomes. Also, findings suggest multiple intervention targets, including addressing internalized stigma directly, reducing depressive symptoms, and promoting consistent engagement in care.

Differential diagnosis of scrub typhus meningitis from tuberculous meningitis using clinical and laboratory features.

PubMed

Valappil, Ashraf V; Thiruvoth, Sohanlal; Peedikayil, Jabir M; Raghunath, Praveenkumar; Thekkedath, Manojan

2017-12-01

The involvement of the central nervous system in the form of meningitis or meningoencephalitis is common in scrub typhus and is an important differential diagnosis of other lymphocytic meningitis like tuberculous meningitis (TBM). The aim of this study was to identify the clinical and laboratory parameters that may be helpful in differentiating scrub typhus meningitis from TBM. We compared of the clinical and laboratory features of 57 patients admitted with scrub typhus meningitis or TBM during a 3-year period. Patients who had abnormal cerebrospinal fluid (CSF) and positive scrub typhus enzyme-linked immunosorbent assay serology (n=28) were included in the scrub typhus meningitis group, while the TBM group included those who satisfied the consensus diagnostic criteria of TBM (n=29). Compared with the TBM group, the mean duration of symptoms was less in patients with scrub typhus meningitis, who also had a lower magnitude of neurological deficits, such as altered mental status and cranial nerve and motor deficits. Patients with scrub typhus meningitis had a lower CSF white blood-cell count (WBC) than the TBM group (130.8±213 195±175 cells/mm 3 , P=0.002), lower CSF protein elevation (125±120 vs. 195.2±108.2mg/dl, P=0.002), and higher CSF sugar (70.1±32.4 vs. 48.7±23.4mg/dl, P=0.006). Features predictive of the diagnosis of scrub typhus meningitis included the absence of neurological impairment at presentation, blood serum glutamic-oxaloacetic transaminase>40 international units (IU)/L, serum glutamic-pyruvic transaminase>60 IU/L, total blood leukocyte count>10,000/mm 3 , CSF protein<100mg/dl, CSF sugar>50mg/dl, CSF WBC<100 cells/mm 3 . All patients with scrub typhus meningitis recovered completely following doxycycline therapy CONCLUSIONS: This study suggests that, clinical features, including duration of fever, neurological deficits at presentation and laboratory parameters such as CSF pleocytosis,CSF protein elevation, CSF sugar levels and liver enzyme

Complement deficiency predisposes for meningitis due to nongroupable meningococci and Neisseria-related bacteria.

PubMed

Fijen, C A; Kuijper, E J; Tjia, H G; Daha, M R; Dankert, J

1994-05-01

Nongroupable meningococci or bacteria related to the genus Neisseria rarely cause meningitis. Complement deficiency has been identified as a major predisposing factor for meningococcal disease. To assess whether patients with meningitis due to such strains have a complement deficiency, we studied 12 persons. Six patients had meningitis due to nongroupable strains of meningococci, and six patients had meningitis due to Moraxella species or Acinetobacter species. Inherited complement component C7 or C8 deficiency was found in two persons who had had meningitis due to nongroupable meningococci, and one C8-deficient person had had meningitis caused by Moraxella osloensis. Hypocomplementemia resulting from CSF drain-associated shunt nephritis was found in one person with meningitis due to Moraxella nonliquefaciens and in one person with meningitis due to Acinetobacter lwoffi. This rather high frequency of inherited or acquired complement deficiencies among patients with meningitis due to nongroupable meningococci, Moraxella species, and Acinetobacter species justifies the recommendation that such patients must be studied for complement deficiency.

Trends in, and factors associated with, HIV infection amongst tuberculosis patients in the era of anti-retroviral therapy: a retrospective study in England, Wales and Northern Ireland.

PubMed

Winter, Joanne R; Stagg, Helen R; Smith, Colette J; Lalor, Maeve K; Davidson, Jennifer A; Brown, Alison E; Brown, James; Zenner, Dominik; Lipman, Marc; Pozniak, Anton; Abubakar, Ibrahim; Delpech, Valerie

2018-06-07

HIV increases the progression of latent tuberculosis (TB) infection to active disease and contributed to increased TB in the UK until 2004. We describe temporal trends in HIV infection amongst patients with TB and identify factors associated with HIV infection. We used national surveillance data of all TB cases reported in England, Wales and Northern Ireland from 2000 to 2014 and determined HIV status through record linkage to national HIV surveillance. We used logistic regression to identify associations between HIV and demographic, clinical and social factors. There were 106,829 cases of TB in adults (≥ 15 years) reported from 2000 to 2014. The number and proportion of TB patients infected with HIV decreased from 543/6782 (8.0%) in 2004 to 205/6461 (3.2%) in 2014. The proportion of patients diagnosed with HIV > 91 days prior to their TB diagnosis increased from 33.5% in 2000 to 60.2% in 2013. HIV infection was highest in people of black African ethnicity from countries with high HIV prevalence (32.3%), patients who misused drugs (8.1%) and patients with miliary or meningeal TB (17.2%). There has been an overall decrease in TB-HIV co-infection and a decline in the proportion of patients diagnosed simultaneously with both infections. However, high rates of HIV remain in some sub-populations of patients with TB, particularly black Africans born in countries with high HIV prevalence and people with a history of drug misuse. Whilst the current policy of testing all patients diagnosed with TB for HIV infection is important in ensuring appropriate management of TB patients, many of these TB cases would be preventable if HIV could be diagnosed before TB develops. Improving screening for both latent TB and HIV and ensuring early treatment of HIV in these populations could help prevent these TB cases. British HIV Association guidelines on latent TB testing for people with HIV from sub-Saharan Africa remain relevant, and latent TB screening for people with HIV with

The middle meningeal artery: from clinics to fossils.

PubMed

Bruner, Emiliano; Sherkat, Shahram

2008-11-01

Although research today ranges from molecular to universe scale, many issues regarding gross anatomy remain totally neglected. Within the framework of the endocranial morphogenesis and evolution, understanding the role and variation of the middle meningeal artery relies upon the very limited, scattered, and descriptive information available. The meninges are supplied by branches originating from both the internal and external carotid arteries, often converging in the same networks and hence raising questions on the homology and embryogenesis of these vessels. The middle meningeal artery is often ligated during craniotomies, with no apparent impairment of the cerebral functional processes. The exact physiological role of this extended vascular system, together with the adaptations and selective pressure associated with its evolutionary characterization, have generally been ignored. Anthropologists have made many attempts to quantify and qualify the differences and variation between and within human and nonhuman primates, with scarce results due to the blurry morphology of the vascular networks. Living apes and humans probably have meningeal vessels originating from different embryogenetic processes, further hampering easy phylogenetic comparisons. Generally, monkeys and apes display a larger component derived from the internal carotid artery and its ophthalmic branch. The fossil endocasts partially show the traces of the middle meningeal vessels, allowing some hypotheses on the evolution of these structures. In contrast with modern humans, some extinct groups show a dominance of the posterior branch over the anterior one. The most interesting features are associated with the variation of the middle branch, which supplies the parietal areas. In any case, the most striking difference between the modern and non-modern humans regard the definite increase in the number and complexity of the anastomoses and reticulation in the former. This may be either the simple result

Molecular typing of enteroviruses associated with viral meningitis in Cyprus, 2000-2002.

PubMed

Richter, Jan; Koptides, Dana; Tryfonos, Christina; Christodoulou, Christina

2006-08-01

Human enteroviruses are responsible for a wide spectrum of clinical diseases affecting many different organ systems. Although infection is usually asymptomatic, infections of the central nervous system manifested as meningitis or encephalitis can pose a serious public health problem, especially during outbreaks. In this study, samples from 218 patients diagnosed with enteroviral meningitis between January 2000 and December 2002 were analysed in order to assess the epidemiology of human enteroviruses as a cause of viral meningitis in Cyprus. A new typing strategy, based on partial sequencing of the 5' non-coding region (5'NCR), prediction of type, and selection of type-specific primers for sensitive VP1 PCR amplification, was developed. As clustering in the 5'NCR was concordant with clustering in the VP1 region, quick and reliable typing by VP1 sequencing was achieved without virus isolation in cell culture. The most frequent enterovirus serotypes identified were Human echovirus 30 (55.5%), Human echovirus 13 (15.1%), Human echovirus 6 (13.8%) and Human echovirus 9 (8.3%). Human coxsackieviruses B2, B1 and B5, Human echovirus 4, Human enterovirus 71 and Human coxsackievirus A6 represented rather rare serotypes. This is the first molecular epidemiological study of enterovirus meningitis in Cyprus. Serotype distribution corresponded basically with observations in other European countries, suggesting the spread of enteroviruses by tourism.

Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

PubMed Central

Woehrl, Bianca; Brouwer, Matthijs C.; Murr, Carmen; Heckenberg, Sebastiaan G.B.; Baas, Frank; Pfister, Hans W.; Zwinderman, Aeilko H.; Morgan, B. Paul; Barnum, Scott R.; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

2011-01-01

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis. PMID:21926466

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

Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles Protects Mice against Cryptococcosis in a Manner Dependent upon Mouse Strain and Cryptococcal Species.

PubMed

Specht, Charles A; Lee, Chrono K; Huang, Haibin; Hester, Maureen M; Liu, Jianhua; Luckie, Bridget A; Torres Santana, Melanie A; Mirza, Zeynep; Khoshkenar, Payam; Abraham, Ambily; Shen, Zu T; Lodge, Jennifer K; Akalin, Ali; Homan, Jane; Ostroff, Gary R; Levitz, Stuart M

2017-11-28

Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs) as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus -derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly expressed in Escherichia coli , purified, and loaded into GPs. Three mouse strains (C57BL/6, BALB/c, and DR4) were then vaccinated with the antigen-laden GPs, following which they received a pulmonary challenge with virulent C. neoformans and C. gattii strains. Four candidate vaccines (GP-Cda1, GP-Cda2, GP-Cda3, and GP-Sod1) afforded a significant survival advantage in at least one mouse model; some vaccine combinations provided added protection over that seen with either antigen alone. Vaccine-mediated protection against C. neoformans did not necessarily predict protection against C. gattii Vaccinated mice developed pulmonary inflammatory responses that effectively contained the infection; many surviving mice developed sterilizing immunity. Predicted T helper cell epitopes differed between mouse strains and in the degree to which they matched epitopes predicted in humans. Thus, we have discovered cryptococcal proteins that make promising candidate vaccine antigens. Protection varied depending on the mouse strain and cryptococcal species, suggesting that a successful human subunit vaccine will need to contain multiple antigens, including ones that are species specific. IMPORTANCE The encapsulated fungi Cryptococcus neoformans and Cryptococcus gattii are responsible for nearly 200,000 deaths annually, mostly in immunocompromised individuals. An

[Fahr syndrome discovered following a bacterial meningitis].

PubMed

Sbai, H; Smail, L; Hamdani, S; Essatara, Y; Harrandou, M; Khatouf, M; Kanjaa, N

2008-05-01

Fahr's disease refers to a rare syndrome characterized by symmetrical and bilateral intracranial calcifications. The basal ganglia and dentate nucleus are the most common site of involvement and most cases present extrapyramidal symptoms. This disease is mostly associated with a phosphocalcic metabolism disorder, especially to hypoparathyroidism. The authors report a case of Fahr syndrome (FS) discovered when a young patient with hypocalcemia and bacterial meningitis had a cerebral CT scan disclosing intracerebral calcifications. She fully recovered after both meningitis and hypocalcemia were treated.

Oral microbiome in HIV-associated periodontitis

PubMed Central

Noguera-Julian, Marc; Guillén, Yolanda; Peterson, Jessica; Reznik, David; Harris, Erica V.; Joseph, Sandeep J.; Rivera, Javier; Kannanganat, Sunil; Amara, Rama; Nguyen, Minh Ly; Mutembo, Simon; Paredes, Roger; Read, Timothy D.; Marconi, Vincent C.

2017-01-01

Abstract HIV-associated periodontal diseases (PD) could serve as a source of chronic inflammation. Here, we sought to characterize the oral microbial signatures of HIV+ and HIV– individuals at different levels of PD severity. This cross-sectional study included both HIV+ and HIV– patients with varying degrees of PD. Two tooth, 2 cheek, and 1 saliva samples were obtained for microbiome analysis. Mothur/SILVADB were used to classify sequences. R/Bioconductor (Vegan, PhyloSeq, and DESeq2) was employed to assess overall microbiome structure differences and differential abundance of bacterial genera between groups. Polychromatic flow cytometry was used to assess immune activation in CD4 and CD8 cell populations. Around 250 cheek, tooth, and saliva samples from 50 participants (40 HIV+ and 10 HIV–) were included. Severity of PD was classified clinically as None/Mild (N), Moderate (M), and Severe (S) with 18 (36%), 16 (32%), and 16 (32%) participants in each category, respectively. Globally, ordination analysis demonstrated clustering by anatomic site (R2 = 0.25, P < 0.001). HIV status and PD severity showed a statistically significant impact on microbiome composition but only accounted for a combined 2% of variation. HIV+ samples were enriched in genera Abiotrophia, Neisseria, Kingella, and unclassified Neisseriaceae and depleted in Leptotrichia and Selenomonas. The Neisseria genus was consistently enriched in HIV+ participants regardless of sampling site and PD level. Immune markers were altered in HIV+ participants but did not show association with the oral microbiome. HIV-associated changes in oral microbiome result in subtle microbial signatures along different stages of PD that are common in independent oral anatomic sites. PMID:28328799

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

Detection of Significant Pneumococcal Meningitis Biomarkers by Ego Network.

PubMed

Wang, Qian; Lou, Zhifeng; Zhai, Liansuo; Zhao, Haibin

2017-06-01

To identify significant biomarkers for detection of pneumococcal meningitis based on ego network. Based on the gene expression data of pneumococcal meningitis and global protein-protein interactions (PPIs) data recruited from open access databases, the authors constructed a differential co-expression network (DCN) to identify pneumococcal meningitis biomarkers in a network view. Here EgoNet algorithm was employed to screen the significant ego networks that could accurately distinguish pneumococcal meningitis from healthy controls, by sequentially seeking ego genes, searching candidate ego networks, refinement of candidate ego networks and significance analysis to identify ego networks. Finally, the functional inference of the ego networks was performed to identify significant pathways for pneumococcal meningitis. By differential co-expression analysis, the authors constructed the DCN that covered 1809 genes and 3689 interactions. From the DCN, a total of 90 ego genes were identified. Starting from these ego genes, three significant ego networks (Module 19, Module 70 and Module 71) that could predict clinical outcomes for pneumococcal meningitis were identified by EgoNet algorithm, and the corresponding ego genes were GMNN, MAD2L1 and TPX2, respectively. Pathway analysis showed that these three ego networks were related to CDT1 association with the CDC6:ORC:origin complex, inactivation of APC/C via direct inhibition of the APC/C complex pathway, and DNA strand elongation, respectively. The authors successfully screened three significant ego modules which could accurately predict the clinical outcomes for pneumococcal meningitis and might play important roles in host response to pathogen infection in pneumococcal meningitis.

Pediatric bacterial meningitis in French Guiana.

PubMed

Elenga, N; Sicard, S; Cuadro-Alvarez, E; Long, L; Njuieyon, F; Martin, E; Kom-Tchameni, R; Balcaen, J; Moreau, B; Boukhari, R

2015-01-01

Controlling vaccine-preventable infectious diseases is a public health priority in French Guiana but there is currently no epidemiological data on pediatric bacterial meningitis in this overseas department. Our aim was to describe data related to pediatric bacterial meningitis in French Guiana and compare it with that of metropolitan France. We conducted a multicenter retrospective study from 2000 to 2010 to describe the clinical picture, biological data, epidemiology, and outcome of pediatric bacterial meningitis case patients in French Guiana. The median age of bacterial meningitis patients was 6months [0-15] and the sex ratio 1.06. We observed a total of 60 bacterial meningitis case patients. Most presented with pneumococcal meningitis (24 patients; 40%); 11 with Haemophilus influenzae type b meningitis (23%), five with group B streptococcal meningitis (8.5%), and five others (8.5%) with staphylococcal meningitis (three patients presented with coagulase-negative staphylococci and two with Staphylococcus aureus). Only one patient presented with group B meningococcal meningitis, an 18-month-old infant. We recorded 14 deaths (overall case fatality: 23%); eight were due to Streptococcus pneumoniae (case fatality: 33%). The overall sequelae rate was 28%. It was 32% for patients presenting with pneumococcal meningitis. We observed that 38% of children who had never been vaccinated were infected by a vaccine-preventable bacterium. We observed many differences in the distribution of the bacteria and in the patients' prognosis when comparing the French Guiana data with that of metropolitan France. Improving vaccination coverage would decrease the incidence of H. influenzae meningitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Meningitis - gram-negative

MedlinePlus

... system and peripheral nervous system References Nath A. Meningitis: bacterial, viral, and other. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ... D, Scheld WM. Acute meningitis. In: Bennett JE, Dolin R, Blaser MJ, eds. ...

Arterial stiffness in HIV-infected youth and associations with HIV-related variables.

PubMed

Eckard, Allison Ross; Raggi, Paolo; Ruff, Joshua H; O'Riordan, Mary Ann; Rosebush, Julia C; Labbato, Danielle; Daniels, Julie E; Uribe-Leitz, Monika; Longenecker, Christopher T; McComsey, Grace A

2017-10-03

Children and young adults infected with HIV are at elevated risk for cardiovascular disease (CVD). However, scarce data exist on the utility of non-invasive methods to diagnose subclinical CVD, such as pulse wave velocity (PWV), a non-invasive measure of arterial stiffness. The objectives of this study were to assess the relationship of carotid-femoral PWV with subclinical atherosclerosis measured by carotid intima-media thickness (IMT), compare measurements to healthy controls, and evaluate variables associated with PWV in HIV-infected youth. One hundred and one 8-25 year-old subjects on stable antiretroviral therapy with low-level viremia or an undetectable HIV-1 RNA were enrolled, along with 86 healthy controls similar in age, sex and race. There was no significant difference in PWV between groups (median (Q1, Q3): 5.7 (5.2, 6.3) vs 5.7 (4.9, 6.5) m/s; P = 0.81). Among the HIV-infected subjects, PWV was positively correlated with both internal carotid artery (R = 0.31, P = 0.02) and carotid bulb IMT (R = 0.29, P = 0.01). In multivariable regression, only current alcohol consumption and systolic blood pressure were independently associated with PWV in the HIV-infected group (where current alcohol consumption and higher systolic blood pressure were associated with higher PWV); whereas, age, body mass index, and current marijuana use were associated with PWV in healthy controls. In this study of PWV in HIV-infected youth, measures of arterial stiffness were not different between subjects and controls. However, in HIV-infected youth, there was a significant association between PWV and carotid IMT, as well as between PWV and current alcohol consumption. Thus, PWV may have potential as a useful, non-invasive method to assess CVD risk in HIV-infected youth, but further investigation is needed.

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

PubMed

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

2015-11-15

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. 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. 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. In June 2001, BMGF awarded a grant of US$70 million to create the Meningitis

Advances in Meningeal Immunity.

PubMed

Rua, Rejane; McGavern, Dorian B

2018-06-01

The central nervous system (CNS) is an immunologically specialized tissue protected by a blood-brain barrier. The CNS parenchyma is enveloped by a series of overlapping membranes that are collectively referred to as the meninges. The meninges provide an additional CNS barrier, harbor a diverse array of resident immune cells, and serve as a crucial interface with the periphery. Recent studies have significantly advanced our understanding of meningeal immunity, demonstrating how a complex immune landscape influences CNS functions under steady-state and inflammatory conditions. The location and activation state of meningeal immune cells can profoundly influence CNS homeostasis and contribute to neurological disorders, but these cells are also well equipped to protect the CNS from pathogens. In this review, we discuss advances in our understanding of the meningeal immune repertoire and provide insights into how this CNS barrier operates immunologically under conditions ranging from neurocognition to inflammatory diseases. Published by Elsevier Ltd.

Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.

PubMed

Brouwer, Matthijs C; Tunkel, Allan R; van de Beek, Diederik

2010-07-01

The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the important etiological agents and populations at risk to ascertain public health measures and ensure appropriate management. In this review, we describe the changing epidemiology of bacterial meningitis in the United States and throughout the world by reviewing the global changes in etiological agents followed by specific microorganism data on the impact of the development and widespread use of conjugate vaccines. We provide recommendations for empirical antimicrobial and adjunctive treatments for clinical subgroups and review available laboratory methods in making the etiological diagnosis of bacterial meningitis. Finally, we summarize risk factors, clinical features, and microbiological diagnostics for the specific bacteria causing this disease.

Neuropathogenesis of HIV-associated neurocognitive disorders: roles for immune activation, HIV blipping and viral tropism.

PubMed

Chen, Maria F; Gill, Alexander J; Kolson, Dennis L

2014-11-01

The purpose of this study is to discuss why HIV-associated neurocognitive disorders (HAND) persist despite apparently effective HIV suppression by highly active antiretroviral therapy (ART). As many as 50% of HIV-infected individuals suffer from HAND despite ART suppression of HIV replication to apparently undetectable levels in most treated individuals. Prior to ART, HIV-associated dementia (HAD), the severest form of HAND, affected nearly 20% of infected individuals; HAD now affects only nearly 2% of ART-treated persons, although less severe HAND forms persist. Recent studies link persistent immune activation, inflammation and viral escape/blipping in ART-treated individuals, as well as comorbid conditions, to HIV disease progression and increased HAND risk. Despite sustained HIV suppression in most ART-treated individuals, indicated by routine plasma monitoring and occasional cerebrospinal fluid (CSF) monitoring, 'blips' of HIV replication are often detected with more frequent monitoring, thus challenging the concept of viral suppression. Although the causes of HIV blipping are unclear, CSF HIV blipping associates with neuroinflammation and, possibly, central nervous system (CNS) injury. The current theory that macrophage-tropic HIV strains within the CNS predominate in driving HAND and these associated factors is now also challenged. Protection of the CNS by ART is incomplete, probably due to combined effects of incomplete HIV suppression, persistent immune activation and host comorbidity factors. Adjunctive therapies to ART are necessary for more effective protection.

Imaging Features of the Brain, Cerebral Vessels and Spine in Pediatric Tuberculous Meningitis with Associated Hydrocephalus

PubMed Central

Rohlwink, Ursula K; Kilborn, Tracy; Wieselthaler, Nicky; Banderker, Ebrahim; Zwane, Eugene; Figaji, Anthony A.

2016-01-01

Background Pediatric tuberculous meningitis leads to high rates of mortality and morbidity. Prompt diagnosis and initiation of treatment are challenging; imaging findings play a key role in establishing the presumptive diagnosis. General brain imaging findings are well reported; however, specific data on cerebral vascular and spinal involvement in children are sparse. Methods This prospective cohort study examined admission and follow up computed tomography brain scans and magnetic resonance imaging scans of the brain, cerebral vessels (magnetic resonance angiogram) and spine at 3 weeks in children treated for tuberculous meningitis with hydrocephalus (inclusion criteria). Exclusion criteria were no hydrocephalus on admission, treatment of hydrocephalus or commencement of anti-TB treatment before study enrolment. Imaging findings were examined in association with outcome at 6 months. Results Forty-four patients (median age 3.3 [0.3-13.1] years) with definite (54%) or probable tuberculous meningitis were enrolled. Good clinical outcome was reported in 72%; the mortality rate was 16%. Infarcts were reported in 66% of patients and were predictive of poor outcome. Magnetic resonance angiogram abnormalities were reported in 55% of patients. Delayed tuberculomas developed in 11% of patients (after starting treatment). Spinal pathology was more common than expected, occurring in 76% of patients. Exudate in the spinal canal increased the difficulty of lumbar puncture and correlated with high cerebrospinal fluid protein content. Conclusion Tuberculous meningitis involves extensive pathology in the central nervous system. Severe infarction was predictive of poor outcome although this was not the case for angiographic abnormalities. Spinal disease occurs commonly and has important implications for diagnosis and treatment. Comprehensive imaging of the brain, spine and cerebral vessels adds insight into disease pathophysiology. PMID:27213261

Low Diversity Cryptococcus neoformans Variety grubii Multilocus Sequence Types from Thailand Are Consistent with an Ancestral African Origin

PubMed Central

Simwami, Sitali P.; Khayhan, Kantarawee; Henk, Daniel A.; Aanensen, David M.; Boekhout, Teun; Hagen, Ferry; Brouwer, Annemarie E.; Harrison, Thomas S.; Donnelly, Christl A.; Fisher, Matthew C.

2011-01-01

The global burden of HIV-associated cryptococcal meningitis is estimated at nearly one million cases per year, causing up to a third of all AIDS-related deaths. Molecular epidemiology constitutes the main methodology for understanding the factors underpinning the emergence of this understudied, yet increasingly important, group of pathogenic fungi. Cryptococcus species are notable in the degree that virulence differs amongst lineages, and highly-virulent emerging lineages are changing patterns of human disease both temporally and spatially. Cryptococcus neoformans variety grubii (Cng, serotype A) constitutes the most ubiquitous cause of cryptococcal meningitis worldwide, however patterns of molecular diversity are understudied across some regions experiencing significant burdens of disease. We compared 183 clinical and environmental isolates of Cng from one such region, Thailand, Southeast Asia, against a global MLST database of 77 Cng isolates. Population genetic analyses showed that Thailand isolates from 11 provinces were highly homogenous, consisting of the same genetic background (globally known as VNI) and exhibiting only ten nearly identical sequence types (STs), with three (STs 44, 45 and 46) dominating our sample. This population contains significantly less diversity when compared against the global population of Cng, specifically Africa. Genetic diversity in Cng was significantly subdivided at the continental level with nearly half (47%) of the global STs unique to a genetically diverse and recombining population in Botswana. These patterns of diversity, when combined with evidence from haplotypic networks and coalescent analyses of global populations, are highly suggestive of an expansion of the Cng VNI clade out of Africa, leading to a limited number of genotypes founding the Asian populations. Divergence time testing estimates the time to the most common ancestor between the African and Asian populations to be 6,920 years ago (95% HPD 122.96 - 27

Low diversity Cryptococcus neoformans variety grubii multilocus sequence types from Thailand are consistent with an ancestral African origin.

PubMed

Simwami, Sitali P; Khayhan, Kantarawee; Henk, Daniel A; Aanensen, David M; Boekhout, Teun; Hagen, Ferry; Brouwer, Annemarie E; Harrison, Thomas S; Donnelly, Christl A; Fisher, Matthew C

2011-04-01

The global burden of HIV-associated cryptococcal meningitis is estimated at nearly one million cases per year, causing up to a third of all AIDS-related deaths. Molecular epidemiology constitutes the main methodology for understanding the factors underpinning the emergence of this understudied, yet increasingly important, group of pathogenic fungi. Cryptococcus species are notable in the degree that virulence differs amongst lineages, and highly-virulent emerging lineages are changing patterns of human disease both temporally and spatially. Cryptococcus neoformans variety grubii (Cng, serotype A) constitutes the most ubiquitous cause of cryptococcal meningitis worldwide, however patterns of molecular diversity are understudied across some regions experiencing significant burdens of disease. We compared 183 clinical and environmental isolates of Cng from one such region, Thailand, Southeast Asia, against a global MLST database of 77 Cng isolates. Population genetic analyses showed that Thailand isolates from 11 provinces were highly homogenous, consisting of the same genetic background (globally known as VNI) and exhibiting only ten nearly identical sequence types (STs), with three (STs 44, 45 and 46) dominating our sample. This population contains significantly less diversity when compared against the global population of Cng, specifically Africa. Genetic diversity in Cng was significantly subdivided at the continental level with nearly half (47%) of the global STs unique to a genetically diverse and recombining population in Botswana. These patterns of diversity, when combined with evidence from haplotypic networks and coalescent analyses of global populations, are highly suggestive of an expansion of the Cng VNI clade out of Africa, leading to a limited number of genotypes founding the Asian populations. Divergence time testing estimates the time to the most common ancestor between the African and Asian populations to be 6,920 years ago (95% HPD 122.96 - 27

[Clinical, epidemiological, and etiological studies of adult aseptic meningitis: a report of 12 cases of herpes simplex meningitis, and a comparison with cases of herpes simplex encephalitis].

PubMed

Himeno, Takahiro; Shiga, Yuji; Takeshima, Shinichi; Tachiyama, Keisuke; Kamimura, Teppei; Kono, Ryuhei; Takemaru, Makoto; Takeshita, Jun; Shimoe, Yutaka; Kuriyama, Masaru

2018-01-26

We treated 437 cases of adult aseptic meningitis and 12 cases (including 2 recurrent patients; age, 31.8 ± 8.9 years; 7 females) of herpes simplex meningitis from 2004 to 2016. The incidence rate of adult herpes simplex meningitis in the cases with aseptic meningitis was 2.7%. One patient was admitted during treatment of genital herpes, but no association was observed between genital herpes and herpes simplex meningitis in the other cases. The diagnoses were confirmed in all cases as the cerebrospinal fluid (CSF) was positive for herpes simplex virus (HSV)-DNA. For diagnosis confirmation, the DNA test was useful after 2-7 days following initial disease onset. Among other types of aseptic meningitis, the patients with herpes simplex meningitis showed relatively high white blood cell counts and relatively high CSF protein and high CSF cell counts. CSF cells showed mononuclear cell dominance from the initial stage of the disease. During same period, we also experienced 12 cases of herpes simplex encephalitis and 21 cases of non-hepatic acute limbic encephalitis. Notably, the patients with herpes simplex meningitis were younger and their CSF protein and cells counts were higher than those of the patients with herpes simplex encephalitis.

Aseptic meningitis and viral myelitis.

PubMed

Irani, David N

2008-08-01

Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.

HIV-associated malignancies in children.

PubMed

Singh, Elvira; Naidu, Gita; Davies, Mary-Ann; Bohlius, Julia

2017-01-01

HIV-infected children are at an increased risk of developing cancer. Many of the cancers in HIV-infected children are linked to immunosuppression and oncogenic coinfections. Worldwide most HIV-infected children live in sub-Saharan Africa, but cancer data for this population are scarce. In this article, we review the current literature on the epidemiology and prevention of cancer in HIV-infected children. Combined antiretroviral therapy (cART) reduces the risk of developing cancer in HIV-infected children. Cancer risk remains increased in children who start cART at older ages or more advanced immunosuppression as compared with children who start cART at younger age and with mild immunosuppression. Starting cART before severe immunosuppression develops is key to prevent cancer in HIV-infected children but most children in low-income countries start cART at severe immunosuppression levels. Vaccination against high-risk variants of human papillomavirus may protect again human papillomavirus-associated cancer later in life. However, tailoring of human papillomavirus vaccination guidelines for HIV-infected children and young women awaits answers to determine the best vaccination strategies. Better data on the short-term and long-term risks of developing cancer and the effects of preventive measures in HIV-infected children from regions with high burden of HIV/AIDS are urgently needed.

Differential gene expression in HIV/SIV-associated and spontaneous lymphomas

PubMed Central

2005-01-01

Diffuse large B-cell lymphoma (DLBCL) is more prevalent and more often fatal in HIV-infected patients and SIV-infected monkeys compared to immune-competent individuals. Molecular, biological, and immunological data indicate that virus-associated lymphomagenesis is similar in both infected hosts. To find genes specifically overexpressed in HIV/SIV-associated and non-HIV/SIV-associated DLBCL we compared gene expression profiles of HIV/SIV-related and non-HIV-related lymphomas using subtractive hybridization and Northern blot analysis. Our experimental approach allowed us to detect two genes (a-myb and pub) upregulated solely in HIV/SIV-associated DLBCLs potentially involved in virus-specific lymphomagenesis in human and monkey. Downregulation of the pub gene was observed in all non-HIV-associated lymphomas investigated. In addition, we have found genes upregulated in both non-HIV- and HIV-associated lymphomas. Among those were genes both with known (set, ND4, SMG-1) and unknown functions. In summary, we have demonstrated that simultaneous transcriptional upregulation of at least two genes (a-myb and pub) was specific for AIDS-associated lymphomas. PMID:16239949

Current questions in HIV-associated lung cancer.

PubMed

Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

2013-09-01

In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

Meningococcal Two-Partner Secretion Systems and Their Association with Outcome in Patients with Meningitis

PubMed Central

Piet, Jurgen R.; van Ulsen, Peter; ur Rahman, Sadeeq; Bovenkerk, Sandra; Bentley, Stephen D.

2016-01-01

Two-partner secretion (TPS) systems export large TpsA proteins to the surface and extracellular milieu. In meningococci, three different TPS systems exist, and of these, TPS system 2 (TPS2) and TPS3 can be detected by the host's immune system. We evaluated the distribution of TPS systems among clinical isolates from two prospective cohort studies comprising 373 patients with meningococcal meningitis. TPS system 1 was present in 91% of isolates, and system 2 and/or 3 was present in 67%. The TPS system distribution was related to clonal complexes. Infection with strains with TPS2 and/or TPS3 resulted in less severe disease and better outcomes than infection with strains without these systems. Using whole-blood stimulation experiments, we found no differences in the host cytokine response between patients infected with TPS system 2 and 3 knockout strains and patients infected with a wild-type strain. In conclusion, meningococcal TPS system 2 and/or 3 is associated with disease severity and outcome in patients with meningitis. PMID:27324486

Epidemiology, Diagnosis, and Antimicrobial Treatment of Acute Bacterial Meningitis

PubMed Central

Brouwer, Matthijs C.; Tunkel, Allan R.; van de Beek, Diederik

2010-01-01

Summary: The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the important etiological agents and populations at risk to ascertain public health measures and ensure appropriate management. In this review, we describe the changing epidemiology of bacterial meningitis in the United States and throughout the world by reviewing the global changes in etiological agents followed by specific microorganism data on the impact of the development and widespread use of conjugate vaccines. We provide recommendations for empirical antimicrobial and adjunctive treatments for clinical subgroups and review available laboratory methods in making the etiological diagnosis of bacterial meningitis. Finally, we summarize risk factors, clinical features, and microbiological diagnostics for the specific bacteria causing this disease. PMID:20610819

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.

Clinical findings and management of patients with meningitis with an emphasis on Haemophilus influenzae meningitis in rural Tanzania.

PubMed

Storz, Corinna; Schutz, Cornelia; Tluway, Anthony; Matuja, William; Schmutzhard, Erich; Winkler, Andrea S

2016-07-15

The spectrum of meningitis pathogens differs depending on the age of patients and the geographic region, amongst other. Although meningitis vaccination programs have led to the reduction of incidence rates, an imbalance between low- and high-income countries still exists. In a hospital-based study in rural northern Tanzania, we consecutively recruited patients with confirmed meningitis and described their clinical and laboratory characteristics. A total of 136 patients with meningitis were included. Fever (85%), meningism (63%) and impairment of consciousness (33%) were the most frequent clinical symptoms/signs. Nearly 10% of all patients tested were positive for malaria. The majority of the patients with bacterial meningitis (39%), especially those under 5years of age, were confirmed to be infected with Haemophilus influenzae (26%), Streptococcus pneumoniae (19%) and Neisseria meningitidis (15%). Haemophilus influenzae represented the dominant causative organism in children under 2years of age. Our study emphasizes the importance of recognizing warning symptoms like fever, meningism and impairment of consciousness, implementing laboratory tests to determine responsible pathogens and evaluating differential diagnoses in patients with meningitis in sub-Saharan Africa. It also shows that Haemophilus influenza meningitis is still an important cause for meningitis in the young, most probabaly due to lack of appropriate vaccination coverage. Copyright © 2016 Elsevier B.V. All rights reserved.

Intensified treatment with high dose Rifampicin and Levofloxacin compared to standard treatment for adult patients with Tuberculous Meningitis (TBM-IT): protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin. Methods/Design A randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment plus an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30

Intensified treatment with high dose rifampicin and levofloxacin compared to standard treatment for adult patients with tuberculous meningitis (TBM-IT): protocol for a randomized controlled trial.

PubMed

Heemskerk, Dorothee; Day, Jeremy; Chau, Tran Thi Hong; Dung, Nguyen Huy; Yen, Nguyen Thi Bich; Bang, Nguyen Duc; Merson, Laura; Olliaro, Piero; Pouplin, Thomas; Caws, Maxine; Wolbers, Marcel; Farrar, Jeremy

2011-02-02

Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin. A randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment plus an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30% in the two arms

The costs of providing antiretroviral therapy services to HIV-infected individuals presenting with advanced HIV disease at public health centres in Dar es Salaam, Tanzania: Findings from a randomised trial evaluating different health care strategies.

PubMed

Kimaro, Godfather Dickson; Mfinanga, Sayoki; Simms, Victoria; Kivuyo, Sokoine; Bottomley, Christian; Hawkins, Neil; Harrison, Thomas S; Jaffar, Shabbar; Guinness, Lorna

2017-01-01

Understanding the costs associated with health care delivery strategies is essential for planning. There are few data on health service resources used by patients and their associated costs within antiretroviral (ART) programmes in Africa. The study was nested within a large trial, which evaluated screening for cryptococcal meningitis and tuberculosis and a short initial period of home-based adherence support for patients initiating ART with advanced HIV disease in Tanzania and Zambia. The economic evaluation was done in Tanzania alone. We estimated costs of providing routine ART services from the health service provider's perspective using a micro-costing approach. Incremental costs for the different novel components of service delivery were also estimated. All costs were converted into US dollars (US$) and based on 2012 prices. Of 870 individuals enrolled in Tanzania, 434 were enrolled in the intervention arm and 436 in the standard care/control arm. Overall, the median (IQR) age and CD4 cell count at enrolment were 38 [31, 44] years and 52 [20, 89] cells/mm3, respectively. The mean per patient costs over the first three months and over a one year period of follow up following ART initiation in the standard care arm were US$ 107 (95%CI 101-112) and US$ 265 (95%CI 254-275) respectively. ART drugs, clinic visits and hospital admission constituted 50%, 19%, and 19% of the total cost per patient year, while diagnostic tests and non-ART drugs (co-trimoxazole) accounted for 10% and 2% of total per patient year costs. The incremental costs of the intervention to the health service over the first three months was US$ 59 (p<0.001; 95%CI 52-67) and over a one year period was US$ 67(p<0.001; 95%CI 50-83). This is equivalent to an increase of 55% (95%CI 51%-59%) in the mean cost of care over the first three months, and 25% (95%CI 20%-30%) increase over one year of follow up.

Psychological Factors Associated With Painful Versus Non-Painful HIV-Associated Sensory Neuropathy.

PubMed

Pillay, Prinisha; Wadley, Antonia L; Cherry, Catherine L; Karstaedt, Alan S; Kamerman, Peter R

2018-05-01

HIV-associated sensory neuropathy (HIV-SN) is a common, and frequently painful complication of HIV, but factors that determine the presence of pain are unresolved. We investigated: (i) if psychological factors associated with painful (n = 125) versus non-painful HIV-SN (n = 72), and (ii) if pain and psychological factors affected quality of life (QoL). We assessed anxiety and depression using the Hopkins Symptoms Checklist-25. Pain catastrophizing and QoL were assessed using the Pain Catastrophizing Scale and Euroqol-5D, respectively. Presence of neuropathy was detected using the Brief Neuropathy Screening Tool, and pain was characterised using the Wisconsin Brief Pain Questionnaire. Overall, there was a high burden of pain, depression and anxiety in the cohort. None of the psychological variables associated with having painful HIV-SN. Greater depressive symptoms and presence of pain were independently associated with lower QoL. In those participants with painful HIV-SN, greater depressive symptom scores were associated with increased pain intensity. In conclusion, in a cohort with high background levels of psychological dysfunction, psychological factors do not predict the presence of pain, but both depression and presence of pain are associated with poor quality of life.

The role of pneumolysin in pneumococcal pneumonia and meningitis.

PubMed

Hirst, R A; Kadioglu, A; O'callaghan, C; Andrew, P W

2004-11-01

Diseases caused by Streptococcus pneumoniae include pneumonia, septicaemia and meningitis. All these are associated with high morbidity and mortality. The pneumococcus can colonize the nasopharynx, and this can be a prelude to bronchopneumonia and invasion of the vasculature space. Proliferation in the blood can result in a breach of the blood-brain barrier and entry into the cerebrospinal fluid (CSF) where the bacteria cause inflammation of the meningeal membranes resulting in meningitis. The infected host may develop septicaemia and/or meningitis secondary to bronchopneumonia. Also septicaemia is a common precursor of meningitis. The mechanisms surrounding the sequence of infection are unknown, but will be dependent on the properties of both the host and bacterium. Treatment of these diseases with antibiotics leads to clearance of the bacteria from the infected tissues, but the bacteriolytic nature of antibiotics leads to an acute release of bacterial toxins and thus after antibiotic therapy the patients can be left with organ-specific deficits. One of the main toxins released from pneumococci is the membrane pore forming toxin pneumolysin. Here we review the extensive studies on the role of pneumolysin in the pathogenesis of pneumococcal diseases.

Association of regional body composition with bone mineral density in HIV-infected and HIV-uninfected women: women's interagency HIV study.

PubMed

Sharma, Anjali; Tian, Fang; Yin, Michael T; Keller, Marla J; Cohen, Mardge; Tien, Phyllis C

2012-12-01

To understand how regional body composition affects bone mineral density (BMD) in HIV-infected and HIV-uninfected women. Dual energy x-ray absorptiometry was used to measure regional lean and fat mass and BMD at lumbar spine (LS), total hip (TH), and femoral neck (FN) in 318 HIV-infected and 122 HIV-uninfected Women's Interagency HIV Study participants at baseline and 2 and 5 years later. Total lean and fat mass were measured using bioimpedance analysis. Multivariate marginal linear regression models assessed the association of HIV status and body composition on BMD change. Compared with HIV-uninfected women, HIV-infected women were older (44 vs. 37 years), more likely to be Hepatitis C virus-infected (32% vs. 14%), and postmenopausal (26% vs. 3%) and had lower baseline total fat mass, trunk fat, and leg fat. In multivariate models, increased total lean mass was independently associated with increased BMD at LS, TH, and FN, and total fat mass was associated with increased BMD at TH and FN (all P < 0.05). When total fat was replaced in multivariate models with trunk fat and leg fat, increased trunk fat (and not leg fat) was associated with increased TH and FN BMD (P < 0.001). Total fat and lean mass are strong independent predictors of TH and FN BMD, and lean mass was associated with greater LS BMD. Regardless of HIV status, greater trunk fat (and not leg fat) was associated with increased TH and FN BMD, suggesting that weight-bearing fat may be a more important predictor of BMD in the hip.

Risk factors for community-acquired bacterial meningitis.

PubMed

Lundbo, Lene Fogt; Benfield, Thomas

2017-06-01

Bacterial meningitis is a significant burden of disease and mortality in all age groups worldwide despite the development of effective conjugated vaccines. The pathogenesis of bacterial meningitis is based on complex and incompletely understood host-pathogen interactions. Some of these are pathogen-specific, while some are shared between different bacteria. We searched the database PubMed to identify host risk factors for bacterial meningitis caused by the pathogens Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b, because they are three most common causative bacteria beyond the neonatal period. We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults. As conjugated vaccines are available for these infections, it is of utmost importance to identify high risk patients to be able to prevent invasive disease.

Dual-mixed HIV-1 Coreceptor Tropism and HIV-Associated Neurocognitive Deficits

PubMed Central

Morris, Sheldon R.; Woods, Steven Paul; Deutsch, Reena; Little, Susan J.; Wagner, Gabriel; Morgan, Erin E.; Heaton, Robert K.; Letendre, Scott L.; Grant, Igor; Smith, Davey M.

2014-01-01

Background HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described. Methods This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to 4 sequential neurocognitive assessments over a median of 160 days (IQR 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count and problematic methamphetamine use. Results Six subjects (8.3%) had dual mixed tropism (DM) at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR 7.2–12.2). There were 44 (61.1%) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio 4.4, 95% CI 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier, 95% CI 1.0–1.2). Conclusion This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND. PMID:24078557

Dual-mixed HIV-1 coreceptor tropism and HIV-associated neurocognitive deficits.

PubMed

Morris, Sheldon R; Woods, Steven Paul; Deutsch, Reena; Little, Susan J; Wagner, Gabriel; Morgan, Erin E; Heaton, Robert K; Letendre, Scott L; Grant, Igor; Smith, Davey M

2013-10-01

HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described. This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to four sequential neurocognitive assessments over a median of 160 days (IQR, 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count, and problematic methamphetamine use. Six subjects (8.3 %) had DM at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR, 7.2–12.2). There were 44 (61.1 %) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio, 4.4; 95 % CI, 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier; 95 % CI, 1.0–1.2). This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together, these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND.

Aseptic Meningitis and Viral Myelitis

PubMed Central

Irani, David N.

2008-01-01

SYNOPSIS Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system (CNS), respectively. Indeed, the number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal CNS infections, on the other hand, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with non-infectious disorders that cause acute flaccid paralysis (AFP). This chapter will review some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus will be placed on the diseases caused by enteroviruses (EVs), which as a group account for the vast majority of all aseptic meningitis cases as well as many focal infections of the spinal cord. PMID:18657719

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

Tuberculous meningitis is a major cause of mortality and morbidity in adults with central nervous system infections in Kota Kinabalu, Sabah, Malaysia: an observational study.

PubMed

Lee, Heng Gee; William, Timothy; Menon, Jayaram; Ralph, Anna P; Ooi, Eng Eong; Hou, Yan'an; Sessions, October; Yeo, Tsin Wen

2016-06-16

Central nervous system (CNS) infections are a significant contributor to morbidity and mortality globally. However, most published studies have been conducted in developed countries where the epidemiology and aetiology differ significantly from less developed areas. Additionally, there may be regional differences due to variation in the socio-economic levels, public health services and vaccination policies. Currently, no prospective studies have been conducted in Sabah, East Malaysia to define the epidemiology and aetiology of CNS infections. A better understanding of these is essential for the development of local guidelines for diagnosis and management. We conducted a prospective observational cohort study in patients aged 12 years and older with suspected central nervous system infections at Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia between February 2012 and March 2013. Cerebrospinal fluid was sent for microscopy, biochemistry, bacterial and mycobacterial cultures, Mycobacterium tuberculosis polymerase chain reaction (PCR), and multiplex and MassCode PCR for various viral and bacterial pathogens. A total of 84 patients with clinically suspected meningitis and encephalitis were enrolled. An aetiological agent was confirmed in 37/84 (44 %) of the patients. The most common diagnoses were tuberculous meningitis (TBM) (41/84, 48.8 %) and cryptococcal meningoencephalitis (14/84, 16.6 %). Mycobacterium tuberculosis was confirmed in 13/41 (31.7 %) clinically diagnosed TBM patients by cerebrospinal fluid PCR or culture. The acute case fatality rate during hospital admission was 16/84 (19 %) in all patients, 4/43 (9 %) in non-TBM, and 12/41 (29 %) in TBM patients respectively (p = 0.02). TBM is the most common cause of CNS infection in patients aged 12 years or older in Kota Kinabalu, Sabah, Malaysia and is associated with high mortality and morbidity. Further studies are required to improve the management and outcome of TBM.

[Clinical, epidemiological and etiological studies of adult aseptic meningitis: Report of 13 cases with mumps meningitis].

PubMed

Takeshima, Shinichi; Yoshimoto, Takeshi; Shiga, Yuji; Kanaya, Yuhei; Neshige, Shuichiro; Himeno, Takahiro; Kono, Ryuhei; Takamatsu, Kazuhiro; Shimoe, Yutaka; Kuriyama, Masaru

2015-01-01

We experienced 13 cases (29.8 ± 7.0 years) of mumps meningitis and 365 cases of adult aseptic meningitis during 11 years from 2004 to 2014. A small epidemic of mumps occurred for 3-4 years, and the incidence rate of adult mumps meningitis coincided with the epidemic without seasonal fluctuation. Parotitis was observed in 8 of the 13 mumps meningitis patients (61.5%) and orchitis in 2 of 7 male patients (28.6%). There were no differences in clinical manifestations, laboratory findings, and outcome between patients with adult mumps meningitis and those with echovirus 9 meningitis (9 patients), except for the low frequency of nausea/vomiting and a high percentage of mononuclear cells of the cerebrospinal fluid in those with mumps. Eight patients had contact with persons with mumps before the symptomatic stage of meningitis. Only one patient had received mumps vaccination in childhood. On the basis of the values of the anti-mumps IgM and IgG antibodies, we speculated primary infection and the re-infection of mumps in 6 and 2 patients, respectively. Moreover, second vaccine failure was suggested in the vaccinated patient.

USE OF SCORE AND CEREBROSPINAL FLUID LACTATE DOSAGE IN DIFFERENTIAL DIAGNOSIS OF BACTERIAL AND ASEPTIC MENINGITIS.

PubMed

Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

2017-01-01

To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis. Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis. Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100). 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS.

Epidemiology of community-acquired bacterial meningitis.

PubMed

Brouwer, Matthijs C; van de Beek, Diederik

2018-02-01

The epidemiology of bacterial meningitis has been dynamic in the past 30 years following introduction of conjugated vaccines against Haemophilus influenzae type B, Streptococcus pneumoniae and Neisseria meningitidis. The purpose of this review is to describe recent developments in bacterial meningitis epidemiology. The incidence of bacterial meningitis in Western countries (Finland, Netherlands, and the United States) gradually declined by 3-4% per year to 0.7-0.9 per 100 000 per year in the past 10-20 years. In African countries (Burkina Faso and Malawi), incidence rates are still substantially higher at 10-40 per 100 000 persons per year. Introduction of pneumococcal conjugate vaccines have not consistently decreased overall pneumococcal meningitis incidence because of serotype replacement. Following the introduction of serogroup A and C meningococcal vaccines, the incidence of meningococcal meningitis because of these serogroups strongly decreased. Novel outbreaks in the African meningitis belt by serogroup C and increased incidence of serogroup W in the United Kingdom and the Netherlands were observed recently. Bacterial meningitis remains an important infectious disease, despite a gradual decline in incidence after large-scale vaccination campaigns. Further development of vaccines with broader coverage is important, as is continuous surveillance of bacterial meningitis cases.

Acute bacterial and viral meningitis.

PubMed

Bartt, Russell

2012-12-01

Most cases of acute meningitis are infectious and result from a potentially wide range of bacterial and viral pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Acute meningitis is infectious in most cases and caused by a potentially wide range of bacterial and viral pathogens. Shifts in the epidemiology of bacterial pathogens have been influenced by changes in vaccines and their implementation. Seasonal and environmental changes influence the likely viral and rickettsial pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Pertinent testing and treatment can vary with the clinical presentation, season, and possible exposures. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute meningitis.

[Diagnosis, prophylaxis and treatment of central nervous system involvement by non-Hodgkin lymphoma in HIV-infected patients].

PubMed

Miralles, Pilar; Berenguer, Juan; Ribera, Josep-Maria

2010-09-18

With the widespread use of highly active antiretroviral therapy (HAART) the incidence of systemic non-Hodgkin lymphoma (NHL) in patients infected with the Human Immunodeficiency Virus (HIV) has declined. HAART has also modified the clinical manifestations of these tumors, with a lower frequency of involvement of the central nervous system (CNS). Currently, the frequency of meningeal involvement at the time of diagnosis of NHL in HIV-infected patients varies between 3% and 5%. These figures are similar to those observed among immunocompetent hosts. The diagnosis of meningeal lymphoma relies in clinical findings, imaging techniques, and cerebrospinal fluid (CSF) examination. Flow cytometry is a diagnostic technique with a higher sensitivity and specificity than conventional cytology for the diagnosis of meningeal lymphoma. However, flow cytometry is not yet considered to be the gold standard for this purpose. Until recently, most experts recommended neuromeningeal prophylaxis for all HIV-infected patients with aggressive NHL. However, at present this prophylaxis is recommended only in patients with higher risk of CNS relapse according to different sites of involvement, stage and histological subtype. There are different regimens of prophylaxis and treatment for meningeal lymphoma. The drugs most commonly used for this purpose are methotrexate and cytosine arabinoside. However, there are other alternatives such as liposomal cytosine arabinoside that requires fewer spinal taps for drug administration and whose results are very promising. In summary, in the context of an effective HAART, HIV infected patients with NHL have a frequency of CNS involvement by lymphoma similar to that found among immunocompetent hosts. Consequently, indications and regimens for CNS prophylaxis in HIV-infected patients with NHL should not be different than those employed in the general population. Universal CNS prophylaxis should be reserved for the few patients unable to receive an

Relationship between tuberculous otomastoiditis and tuberculous meningitis.

PubMed

Sonmez, G; Turhan, V; Senol, M G; Ozturk, E; Sildiroglu, H O; Mutlu, H

2008-09-01

The aim of this study was to determine the correlation between tuberculous meningitis and tuberculous otomastoiditis. Meningeal involvement sites were investigated by magnetic resonance imaging in 32 patients (21 males, 11 females) who had previously been diagnosed with tuberculous meningitis. Clinical and laboratory findings and responses to anti-tuberculous treatment were evaluated, and the presence of concomitant tuberculous otomastoiditis was also investigated. The meningeal involvement site was unilateral (in the sylvian fissure and the perimesencephalic cistern) in 28 patients (87.5 per cent), and bilateral and widespread in four patients (12.5 per cent). Tuberculous otomastoiditis was found in 11 of the patients with tuberculous meningitis (34.3 per cent). Otomastoiditis was on the same side as the meningeal involvement in nine of these 11 patients. Bilateral otomastoiditis with meningeal involvement was observed in two patients. Tuberculous meningitis is frequently accompanied by otomastoiditis, although the exact causal relationship between the two conditions is unclear. Since meningitis is a serious clinical condition, concomitant otomastoiditis generally remains unrecognised. Tuberculosis should be considered in the differential diagnosis of patients with otitis or otomastoiditis who do not respond to antibiotic therapy.

Surgical management of bacterial meningitis.

PubMed Central

Humphreys, R. P.

1975-01-01

A variety of associated lesions may require the neurosurgeon's assistance in the management of bacterial meningitis. As treatment of this infection of the central nervous system proceeds, the surgeon will have to decide about the concurrent or subsequent operative treatment of congenital dysraphic states, paraneural infections, compound fractures or penetrating wounds of thecranium or spine, or infected bypass shunts for cerebrospinal fluid (CSF). In patients with intractable meningitic infections the surgeon may have to insert a ventricular drainage-irrigation system to permit adequate perfusion of the CSF pathways with antibiotic. Hydrocephalus or subdural effusions complicating meningitis may bring the patient to the surgeon long after the infection has been cured. This paper examines these problems and outlines the current principles of management. Images FIG. 1 FIG. 2 PMID:1098760

Borrelia burgdorferi adhere to blood vessels in the dura mater and are associated with increased meningeal T cells during murine disseminated borreliosis

PubMed Central

Divan, Ali; Casselli, Timothy; Narayanan, S. Anand; Mukherjee, Sanjib; Zawieja, David C.; Watt, John A.

2018-01-01

Borrelia burgdorferi, the causative agent of Lyme disease, is a vector-borne bacterial infection that is transmitted through the bite of an infected tick. If not treated with antibiotics during the early stages of infection, disseminated infection can spread to the central nervous system (CNS). In non-human primates (NHPs) it has been demonstrated that the leptomeninges are among the tissues colonized by B. burgdorferi spirochetes. Although the NHP model parallels aspects of human borreliosis, a small rodent model would be ideal to study the trafficking of spirochetes and immune cells into the CNS. Here we show that during early and late disseminated infection, B. burgdorferi infects the meninges of intradermally infected mice, and is associated with concurrent increases in meningeal T cells. We found that the dura mater was consistently culture positive for spirochetes in transcardially perfused mice, independent of the strain of B. burgdorferi used. Within the dura mater, spirochetes were preferentially located in vascular regions, but were also present in perivascular, and extravascular regions, as late as 75 days post-infection. At the same end-point, we observed significant increases in the number of CD3+ T cells within the pia and dura mater, as compared to controls. Flow cytometric analysis of leukocytes isolated from the dura mater revealed that CD3+ cell populations were comprised of both CD4 and CD8 T cells. Overall, our data demonstrate that similarly to infection in peripheral tissues, spirochetes adhere to the dura mater during disseminated infection, and are associated with increases in the number of meningeal T cells. Collectively, our results demonstrate that there are aspects of B. burgdorferi meningeal infection that can be modelled in laboratory mice, suggesting that mice may be useful for elucidating mechanisms of meningeal pathogenesis by B. burgdorferi. PMID:29723263

Meninges-derived cues control axon guidance.

PubMed

Suter, Tracey A C S; DeLoughery, Zachary J; Jaworski, Alexander

2017-10-01

The axons of developing neurons travel long distances along stereotyped pathways under the direction of extracellular cues sensed by the axonal growth cone. Guidance cues are either secreted proteins that diffuse freely or bind the extracellular matrix, or membrane-anchored proteins. Different populations of axons express distinct sets of receptors for guidance cues, which results in differential responses to specific ligands. The full repertoire of axon guidance cues and receptors and the identity of the tissues producing these cues remain to be elucidated. The meninges are connective tissue layers enveloping the vertebrate brain and spinal cord that serve to protect the central nervous system (CNS). The meninges also instruct nervous system development by regulating the generation and migration of neural progenitors, but it has not been determined whether they help guide axons to their targets. Here, we investigate a possible role for the meninges in neuronal wiring. Using mouse neural tissue explants, we show that developing spinal cord meninges produce secreted attractive and repulsive cues that can guide multiple types of axons in vitro. We find that motor and sensory neurons, which project axons across the CNS-peripheral nervous system (PNS) boundary, are attracted by meninges. Conversely, axons of both ipsi- and contralaterally projecting dorsal spinal cord interneurons are repelled by meninges. The responses of these axonal populations to the meninges are consistent with their trajectories relative to meninges in vivo, suggesting that meningeal guidance factors contribute to nervous system wiring and control which axons are able to traverse the CNS-PNS boundary. Copyright © 2017 Elsevier Inc. All rights reserved.

Herpes simplex virus type 2 recurrent meningitis (Mollaret's meningitis): a consideration for the recurrent pathogenesis.

PubMed

Sato, Rumi; Ayabe, Mitsuyoshi; Shoji, Hiroshi; Ichiyama, Takashi; Saito, Yumiko; Hondo, Ryo; Eizuru, Yoshito

2005-11-01

We report a 44-year-old Japanese woman with herpes simplex virus (HSV) type 2 recurrent meningitis (Mollaret's meningitis). The diagnosis was confirmed by nested polymerase chain reaction in her cerebrospinal fluid, but the patient's conventional HSV antibodies by complement fixation, neutralizing test or enzyme immunoassay showed low titres with low lymphoproliferative response. Several similar cases are discussed. Although the reason for the recurrent pathogenesis is uncertain, our report suggests that the low immune response including immune evasion may be involved in the pathogenesis of HSV type 2 recurrent meningitis. For this patient, long-term suppressive and patient-initiated therapies were conducted to prevent the recurrence of meningitis.

Amount of HIV DNA in Peripheral Blood Mononuclear Cells is Proportional to the Severity of HIV-1-Associated Neurocognitive Disorders

PubMed Central

Shiramizu, Bruce; Williams, Andrew E.; Shikuma, Cecilia; Valcour, Victor

2009-01-01

Human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells was previously associated with neuropsychological function. By including individuals encompassing the full range of HIV-1-associated neurocognitive disorders, this study reports results from subjects with normal cognition, minor cognitive motor disorder, and HIV-1-associated dementia. Individuals with normal cognition had relatively low HIV DNA levels compared to those with minor cognitive motor disorder and HIV-1-associated dementia. Neuropsychological deficits were significantly associated with entry HIV DNA in all domains. These findings demonstrate for the first time that the severity of HIV-1-associated neurocognitive disorders is proportional to the amount of circulating HIV DNA. PMID:19359454

HIV-1 Reservoir Association with Immune Activation.

PubMed

Vallejo, Alejandro

2015-09-01

In this issue of EBioMedicine, Ruggiero and colleagues describe immune activation biomarkers associated with the size of the HIV reservoir in a carefully designed cross-sectional study. The cohort consists of a homogeneous sample of HIV-1-infected patients with long-term plasma HIV-1 RNA suppression under antiretroviral treatment (ART). It is crucial to explore the potential utility of biomarkers that are easier (less labor intensive, less expensive) to measure than integrated HIV DNA load, in order to quickly and accurately quantify cellular reservoirs of HIV.

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

PubMed Central

2016-01-01

SUMMARY The HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle. PMID:27357278

USE OF SCORE AND CEREBROSPINAL FLUID LACTATE DOSAGE IN DIFFERENTIAL DIAGNOSIS OF BACTERIAL AND ASEPTIC MENINGITIS

PubMed Central

Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

2017-01-01

ABSTRACT Objective: To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis. Methods: Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis. Results: Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100). Conclusions: 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS. PMID:29185620

The association of C-reactive protein with subclinical cardiovascular disease in HIV-infected and HIV-uninfected women.

PubMed

Moran, Caitlin A; Sheth, Anandi N; Mehta, C Christina; Hanna, David B; Gustafson, Deborah R; Plankey, Michael W; Mack, Wendy J; Tien, Phyllis C; French, Audrey L; Golub, Elizabeth T; Quyyumi, Arshed; Kaplan, Robert C; Ofotokun, Ighovwerha

2018-05-15

HIV is a cardiovascular disease (CVD) risk factor. However, CVD risk is often underestimated in HIV-infected women. C-reactive protein (CRP) may improve CVD prediction in this population. We examined the association of baseline plasma CRP with subclinical CVD in women with and without HIV. Retrospective cohort study. A total of 572 HIV-infected and 211 HIV-uninfected women enrolled in the Women's Interagency HIV Study underwent serial high-resolution B-mode carotid artery ultrasonography between 2004 and 2013 to assess carotid intima-media thickness (CIMT) and focal carotid artery plaques. We used multivariable linear and logistic regression models to assess the association of baseline high (≥3 mg/l) high-sensitivity (hs) CRP with baseline CIMT and focal plaques, and used multivariable linear and Poisson regression models for the associations of high hsCRP with CIMT change and focal plaque progression. We stratified our analyses by HIV status. Median (interquartile range) hsCRP was 2.2 mg/l (0.8-5.3) in HIV-infected, and 3.2 mg/l (0.9-7.7) in HIV-uninfected, women (P = 0.005). There was no statistically significant association of hsCRP with baseline CIMT [adjusted mean difference -3.5 μm (95% confidence interval:-19.0 to 12.1)] or focal plaques [adjusted odds ratio: 1.31 (0.67-2.67)], and no statistically significant association of hsCRP with CIMT change [adjusted mean difference 11.4 μm (-2.3 to 25.1)]. However, hsCRP at least 3 mg/l was positively associated with focal plaque progression in HIV-uninfected [adjusted rate ratio: 5.97 (1.46-24.43)], but not in HIV-infected [adjusted rate ratio: 0.81 (0.47-1.42)] women (P = 0.042 for interaction). In our cohort of women with similar CVD risk factors, higher baseline hsCRP is positively associated with carotid plaque progression in HIV-uninfected, but not HIV-infected, women, suggesting that subclinical CVD pathogenesis may be different HIV-infected women.

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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Viral meningitis and encephalitis.

PubMed

Tuppeny, Misti

2013-09-01

Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Meninges: from protective membrane to stem cell niche.

PubMed

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.

Pasteurella multocida meningitis in an adult: case report.

PubMed

Armstrong, G R; Sen, R A; Wilkinson, J

2000-03-01

Pasteurella multocida is known to form part of the normal flora in the nasopharynx or gastrointestinal tract in many domestic and wild animals. Most human P multocida infections are soft tissue infections caused by dog or cat bites. Less commonly this bacterium is associated with infections affecting other organ systems of man. A case of fatal P multocida meningitis discovered at the necropsy of a 52 year old man is described. P multocida is an unusual causative agent of meningitis which tends to affect those at the extremes of age.

The bacterial meningitis score to distinguish bacterial from aseptic meningitis in children from Sao Paulo, Brazil.

PubMed

Mekitarian Filho, Eduardo; Horita, Sérgio Massaru; Gilio, Alfredo Elias; Alves, Anna Cláudia Dominguez; Nigrovic, Lise E

2013-09-01

In a retrospective cohort of 494 children with meningitis in Sao Paulo, Brazil, the Bacterial Meningitis Score identified all the children with bacterial meningitis (sensitivity 100%, 95% confidence interval: 92-100% and negative predictive value 100%, 95% confidence interval: 98-100%). Addition of cerebrospinal fluid lactate to the score did not improve clinical prediction rule performance.

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation

PubMed Central

Choe, Youngshik; Siegenthaler, Julie A.; Pleasure, Samuel J.

2012-01-01

Summary The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. Using mice with either meningeal overgrowth or selective loss of meninges, we’ve identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonizes the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. PMID:22365545

Hyperglycemia in bacterial meningitis: a prospective cohort study

PubMed Central

2009-01-01

Background Hyperglycemia has been associated with unfavorable outcome in several disorders, but few data are available in bacterial meningitis. We assessed the incidence and significance of hyperglycemia in adults with bacterial meningitis. Methods We collected data prospectively between October 1998 and April 2002, on 696 episodes of community-acquired bacterial meningitis, confirmed by culture of CSF in patients >16 years. Patients were dichotomized according to blood glucose level on admission. A cutoff random non-fasting blood glucose level of 7.8 mmol/L (140 mg/dL) was used to define hyperglycemia, and a cutoff random non-fasting blood glucose level of 11.1 mmol/L (200 mg/dL) was used to define severe hyperglycemia. Unfavorable outcome was defined on the Glasgow outcome scale as a score <5. We also evaluated characteristics of patients with a preadmission diagnosis of diabetes mellitus. Results 69% of patients were hyperglycemic and 25% severely hyperglycemic on admission. Compared with non-hyperglycemic patients, hyperglycemia was related with advanced age (median, 55 yrs vs. 44 yrs, P < 0.0001), preadmission diagnosis of diabetes (9% vs. 3%, P = 0.005), and distant focus of infection (37% vs. 28%, P = 0.02). They were more often admitted in coma (16% vs. 8%; P = 0.004) and with pneumococcal meningitis (55% vs. 42%, P = 0.007). These differences remained significant after exclusion of patients with known diabetes. Hyperglycemia was related with unfavorable outcome in a univariate analysis but this relation did not remain robust in a multivariate analysis. Factors predictive for neurologic compromise were related with higher blood glucose levels, whereas factors predictive for systemic compromise were related with lower blood glucose levels. Only a minority of severely hyperglycemic patients were known diabetics (19%). The vast majority of these known diabetic patients had meningitis due to Streptococcus pneumoniae (67%) or Listeria monocytogenes (13%) and

[Neuropsychiatric sequelae of viral meningitis in adults].

PubMed

Damsgaard, Jesper; Hjerrild, Simon; Renvillard, Signe Groth; Leutscher, Peter Derek Christian

2011-10-10

Viral meningitis is considered to be a benign illness with only mild symptoms. In contrast to viral encephalitis and bacterial meningitis, the prognosis is usually good. However, retrospective studies have demonstrated that patients suffering from viral meningitis may experience cognitive impairment following the acute course of infection. Larger controlled studies are needed to elucidate the potential neuropsychiatric adverse outcome of viral meningitis.

A novel immune-to-CNS communication pathway: cells of the meninges surrounding the spinal cord CSF space produce proinflammatory cytokines in response to an inflammatory stimulus.

PubMed

Wieseler-Frank, Julie; Jekich, Brian M; Mahoney, John H; Bland, Sondra T; Maier, Steven F; Watkins, Linda R

2007-07-01

Pain is enhanced in response to elevations of proinflammatory cytokines in spinal cerebrospinal fluid (CSF), following either intrathecal injection of these cytokines or intrathecal immune challenge with HIV-1 gp120 that induces cytokine release. Spinal cord glia have been assumed to be the source of endogenous proinflammatory cytokines that enhance pain. However, assuming that spinal cord glia are the sole source of CSF cytokines may be an underestimate, as the cellular composition of the meninges surrounding the spinal cord CSF space includes several cell types known to produce proinflammatory cytokines. The present experiments provide the first investigation of the immunocompetent nature of the spinal cord meninges. Here, we explore whether rat meninges are responsive to intrathecal gp120. These studies demonstrate that: (a) intrathecal gp120 upregulates meningeal gene expression of proinflammatory signals, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin 6 (IL-6), and inducible nitric oxide synthase (iNOS), and (b) intrathecal gp120 induces meningeal release of TNF-alpha, IL-1beta, and IL-6. In addition, stimulation of isolated meninges in vitro with gp120 induced the release of TNF-alpha and IL-1beta, indicating that the resident cells of the meninges are able to respond without immune cell recruitment. Taken together, these data document that the meninges are responsive to immunogenic stimuli in the CSF and that the meninges may be a source of immune products detected in CSF. The ability of the meninges to release to proinflammatory signals suggests a potential role in the modulation of pain.

A case of group A streptococcal meningitis in an adult

PubMed Central

Pattullo, Andrew LS; Bow, Eric J

1993-01-01

Group A streptococci are an important cause of soft tissue infections but have rarely been reported as the cause of pyogenic meningitis since the advent of antibiotics. A case of group A streptococcal meningitis in an adult is presented along with a review of similar cases reported in the literature. This case serves to illustrate the virulent nature of this pathogen in infections of the meninges, the potential for associated complications, and the need for rapid diagnosis and appropriate treatment. The source of infection in this and many other cases in the literature is the upper respiratory tract. The case presented responded well to antibiotics but resulted in permanent auditory-vestibular dysfunction. PMID:22346453

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

The meninges: new therapeutic targets for multiple sclerosis.

PubMed

Russi, Abigail E; Brown, Melissa A

2015-02-01

The central nervous system (CNS) largely comprises nonregenerating 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 have 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-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting 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 BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Side effects associated with anti-HIV drugs.

PubMed

Highleyman, L

1998-04-01

Many side effects are associated with the use of anti-HIV drugs, impacting the development of drug resistance and the quality of life for HIV-patients. Concern about side effects is a primary factor in deterring people from beginning HIV therapy. Frequency and severity of side effects vary greatly, but they are frequently more common and severe in people who are taking a new drug or who have advanced HIV disease. Information on side effects comes largely from clinical trials; however, many side effects are not discovered until the drug has been approved and used by larger numbers of people. Side effects vary from serious toxicities that require stopping treatment to uncomfortable or annoying side effects that interfere with daily life. A table categorizes the four major side effects (nausea, fever, skin rash, and fatigue) and divides them into grades that describe their intensity. A chart lists the side effects associated with specific anti-HIV drugs. Suggestions for managing side effects are included.

Cryptococcal nasopharyngeal polypoid mass in a cat

PubMed Central

Javard, Romain; Alexander, Kate; Girard, Christiane; Dunn, Marilyn

2015-01-01

Case summary An indoor 9-year-old castrated male domestic cat was referred with a 4 month history of increased upper airway noise. Computed tomography revealed a nasopharyngeal polypoid mass, which was removed endoscopically with basket forceps. Histopathology was compatible with a polypoid granulomatous pharyngitis with Cryptococcus-like organisms. This was supported by a positive serum latex cryptococcal antigen agglutination test (LCAT). Minimal inflammation of the nasal tissue was noted on histopathology, with no evidence of fungus. Following endoscopic removal of the mass, the patient was treated with systemic antifungal medication (itraconazole). One year after diagnosis, the LCAT titer was negative and the cat remained free of clinical signs. Relevance and novel information This case report emphasizes the importance of considering Cryptococcus species as a potential etiology in cats presented with signs of nasopharyngeal obstruction with an isolated nasopharyngeal polypoid mass, even if kept indoors. PMID:28491377

Listeria monocytogenes meningitis in the Netherlands, 1985-2014: A nationwide surveillance study.

PubMed

Koopmans, Merel M; Bijlsma, Merijn W; Brouwer, Matthijs C; van de Beek, Diederik; van der Ende, Arie

2017-07-01

Listeria monocytogenes can cause sepsis and meningitis. We report national surveillance data on L. monocytogenes meningitis in the Netherlands, describing incidence changes, genetic epidemiology and fatality rate. We analyzed data from the Netherlands Reference Laboratory of Bacterial Meningitis for cases of L. monocytogenes meningitis. Strains were assessed by serotyping and bacterial population structure by multi-locus sequence typing. A total of 375 cases of Listeria meningitis were identified between 1985 and 2014. Peak incidence rates were observed in neonates (0.61 per 100,000 live births) and older adults (peak at 87 year; 0.53 cases per 100,000 population of the same age). Neonatal listerial meningitis decreased 17-fold from 1.95 per 100,000 live births between 1985 and 1989, to 0.11 per 100,000 live births between 2010 and 2014. Overall case fatality rate was 31%, in a multivariate analysis older age and concomitant bacteremia were associated with mortality (both p < 0.01). Clonal complexes (CC) CC1, CC2 and CC3 decreased over time from respectively 32% to 12%, 33% to 9% and 10% to 2% (all p < 0.001), while CC6 increased from 2% to 26% (p < 0.001). The incidence of neonatal listerial meningitis has declined over the past 25 years. The genotype CC6 has become the predominant genotype in listerial meningitis in the Netherlands. Mortality of listeria meningitis has remained high. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adjunctive dexamethasone therapy in unconfirmed bacterial meningitis in resource limited settings: is it a risk worth taking?

PubMed

Gudina, Esayas Kebede; Tesfaye, Markos; Adane, Aynishet; Lemma, Kinfe; Shibiru, Tamiru; Wieser, Andreas; Pfister, Hans-Walter; Klein, Matthias

2016-08-26

Bacterial meningitis is associated with significant morbidity and mortality despite advances in medical care. The main objective of this study was to assess the association of adjunctive dexamethasone treatment with discharge outcome of patients treated as bacterial meningitis in low income setting. A retrospective study was conducted at four teaching hospitals across Ethiopia. Patients of age 14 years and older treated as cases of bacterial meningitis between January 1, 2011 and April 30, 2015 were included in this study. Information regarding sociodemographic data, clinical presentations, laboratory data, treatments given and status at hospital discharge were retrieved from patients' medical records using a structured questionnaire. Predefined outcome variables at discharge were analysed using descriptive statistics. Multivariable logistic regression was used to identify factors independently associated with poor outcome. A total of 425 patients treated with the presumptive clinical diagnosis of bacterial meningitis were included in this study (lumbar puncture done in 56 %; only 19 % had CSF findings compatible with bacterial meningitis, and only 3 % had proven etiology). The overall in hospital mortality rate was 20.2 %. Impaired consciousness, aspiration pneumonia, and cranial nerve palsy at admission were independently associated with increased mortality. Adjuvant dexamethasone, which was used in 50.4 % of patients, was associated with increased in-hospital mortality (AOR = 3.38; 95 % CI 1.87-6.12, p < 0.001) and low Glasgow outcome scale (GOS) at discharge (AOR = 4.46 (95 % CI 1.98-10.08). This association between dexamethasone and unfavorable outcome was found to be more pronounced in suspected but unproven cases and in those without CSF alterations compatible with bacterial meningitis. Most patients treated for suspected bacterial meningitis did not receive proper diagnostic workup. Adjuvant dexamethasone use in clinically suspected but

Group A streptococcal meningitis: emm type distribution and theoretical vaccine coverage in children.

PubMed

Tuerlinckx, David; Gueulette, Emmanuelle; Loens, Katherine; Goossens, Herman; Smeesters, Pierre Robert

2016-06-01

As group A Streptococcus (GAS) meningitis is seldom reported in children, emm-type distribution data are scare. We report eight cases of GAS meningitis in Belgium (2008-2013) and compare molecular characteristics of our strains with a further 55 cases previously reported with their corresponding emm-types. emm1 type was the most frequent (24%) followed by emm6 (11%), emm12 (11%) and emm3 (6%). Together these four emm-types accounted for 52% of the cases, while the rest of the cases are due to 24 different emm-types. These 28 emm-types associated with GAS meningitis belonged to 16 different emm-clusters suggesting that there is no propensity for particular emm-types or emm-cluster to cause meningitis. Theoretical coverage of the 30-valent vaccine candidate would be 77.8% (49/63 isolates) among children with GAS meningitis.

Predictors of Acute Bacterial Meningitis in Children from a Malaria-Endemic Area of Papua New Guinea

PubMed Central

Laman, Moses; Manning, Laurens; Greenhill, Andrew R.; Mare, Trevor; Michael, Audrey; Shem, Silas; Vince, John; Lagani, William; Hwaiwhanje, Ilomo; Siba, Peter M.; Mueller, Ivo; Davis, Timothy M. E.

2012-01-01

Predictors of acute bacterial meningitis (ABM) were assessed in 554 children in Papua New Guinea 0.2–10 years of age who were hospitalized with culture-proven meningitis, probable meningitis, or non-meningitic illness investigated by lumbar puncture. Forty-seven (8.5%) had proven meningitis and 36 (6.5%) had probable meningitis. Neck stiffness, Kernig’s and Brudzinski’s signs and, in children < 18 months of age, a bulging fontanel had positive likelihood ratios (LRs) ≥ 4.3 for proven/probable ABM. Multiple seizures and deep coma were less predictive (LR = 1.5–2.1). Single seizures and malaria parasitemia had low LRs (≤ 0.5). In logistic regression including clinical variables, Kernig’s sign and deep coma were positively associated with ABM, and a single seizure was negatively associated (P ≤ 0.01). In models including microscopy, neck stiffness and deep coma were positively associated with ABM and parasitemia was negatively associated with ABM (P ≤ 0.04). In young children, a bulging fontanel added to the model (P < 0.001). Simple clinical features predict ABM in children in Papua New Guinea but malaria microscopy augments diagnostic precision. PMID:22302856

Clinical, epidemiological and etiological studies of adult aseptic meningitis: Report of 11 cases with varicella zoster virus meningitis.

PubMed

Takeshima, Shinichi; Shiga, Yuji; Himeno, Takahiro; Tachiyama, Keisuke; Kamimura, Teppei; Kono, Ryuhei; Takemaru, Makoto; Takeshita, Jun; Shimoe, Yutaka; Kuriyama, Masaru

2017-09-30

We treated 11 cases (52.7 ± 14.9 years, all male) with varicella zoster virus (VZV) meningitis and 437 cases with adult aseptic meningitis from 2004 to 2016. The incidence rate of adult VZV meningitis in the cases with aseptic meningitis was 2.5%. Herpes zoster infections are reported to have occurred frequently in summer and autumn. VZV meningitis also occurred frequently in the similar seasons, in our patients. The diagnoses were confirmed in 9 cases with positive VZV-DNA in the cerebrospinal fluid and in 2 cases with high VZV-IgG indexes (> 2.0). For diagnosis confirmation, the former test was useful for cases within a week of disease onset, and the latter index was useful for cases after a week of disease onset. Zoster preceded the meningitis in 8 cases, while the meningitis preceded zoster in 1 case, and 2 cases did not have zoster (zoster sine herpete). Two patients were carriers of the hepatitis B virus, 1 patient was administered an influenza vaccine 4 days before the onset of meningitis, and 1 patient was orally administered prednisolone for 2 years, for treatment. Their immunological activities might have been suppressed. The neurological complications included trigeminal neuralgia, facial palsy (Ramsay Hunt syndrome), glossopharyngeal neuralgia, and Elsberg syndrome. Because the diseases in some patients can become severe, they require careful treatment.

Meninges of the brain (image)

MedlinePlus

... covered by connective tissue layers collectively called the meninges. Consisting of the pia mater (closest to the ... the dura mater (farthest from the CNS), the meninges also support blood vessels and contain cerebrospinal fluid. ...

Meninges of the spine (image)

MedlinePlus

... by 3 connective tissue layers collectively called the meninges. Consisting of the pia mater (closest to the ... the dura mater (farthest from the CNS), the meninges also support blood vessels and contain cerebrospinal fluid. ...

[Clinical outcome and prognosis of neonatal bacterial meningitis].

PubMed

Ben Hamouda, H; Ben Haj Khalifa, A; Hamza, M A; Ayadi, A; Soua, H; Khedher, M; Sfar, M T

2013-09-01

To study the epidemiological, clinical, and bacteriological aspects as well as the outcome of neonatal bacterial meningitis and analyze the factors of poor prognosis of this condition. We report a retrospective analysis of 44 cases of neonatal bacterial meningitis hospitalized in the pediatric unit of Tahar Sfar Hospital in Mahdia, Tunisia, between January 1996 and December 2010. Inclusion criteria were infants less than 29 days of age who were hospitalized for bacterial meningitis diagnosed on either the presence of bacteria in cerebrospinal fluid or with more than 50 cells/mm(3), predominance of neutrophils, and the protein level greater than 1.2g/l. Clinical data were obtained through the analysis of patient files. Statistical analysis was based on the Chi(2) test, and P-values less than 0.05 were considered statistically significant. The incidence of neonatal bacterial meningitis was 0.49 per 1000 live births. The patients were premature in 20.4 % and low birth weight in 13.6 % of cases. The clinical presentation was not specific for most cases. The main signs at admission were hyperthermia (43.2 %), refusal to nurse (20.4 %), seizures (18.2 %), and respiratory distress (13.6 %). The cerebrospinal fluid culture was positive in 36.4 % of cases. The group B streptococcus was the most frequently isolated (62.5 %) followed by Escherichia coli (12.5 %). The association of cefotaxime-ampicillin-gentamicin was used as the first treatment in all cases. Ofloxacin was associated with initial antibiotic therapy during the first 5 days in 20.4 % of cases. The mortality rate was 15.9 % and the rate of neurological sequelae in survivors was 21.6 %. Prematurity, low birth weight, shock, respiratory distress, and pleocytosis of less than 500 cells/mm(3) were the main factors of a poor prognosis. The addition of ofloxacin to the initial antibiotic therapy was associated with a decreased rate of neurological sequelae in survivors (11 % vs. 25 %, P=0.042). This study emphasizes

[HIV-associated myelopathy: an uncommon indicator of AIDS].

PubMed

Konaté, A; Ceballos, P; Rivière, S; Faucherre, V; Ciurana, A J; Le Quellec, A

2001-10-01

Spinal cord lesions are an uncommon mode of discovering acquired immunodeficiency syndrome because they usually appear at a later stage. We report a 58-year-old patient who had a spastic paraparesia and sphincter dysfunction. The spinal cord magnetic resonance imaging showed spontaneous hypersignals on T2-weighted images at the cervical and thoracic levels, enhanced with gadolinium, and without swelling. No cause was found. The HIV serology was positive and allowed us to consider an HIV-associated myelopathy. The antiretroviral therapy led to functional recovery. An HIV serology is suggested whenever an unexplained intramedullary lesion is discovered. Indeed, the diagnosis of HIV-associated myelopathy implies a specific therapeutic approach.

Effect of vaccines on bacterial meningitis worldwide.

PubMed

McIntyre, Peter B; O'Brien, Katherine L; Greenwood, Brian; van de Beek, Diederik

2012-11-10

Three bacteria--Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis--account for most acute bacterial meningitis. Measurement of the effect of protein-polysaccharide conjugate vaccines is most reliable for H influenzae meningitis because one serotype and one age group account for more than 90% of cases and the incidence has been best measured in high-income countries where these vaccines have been used longest. Pneumococcal and meningococcal meningitis are caused by diverse serotypes and have a wide age distribution; measurement of their incidence is complicated by epidemics and scarcity of surveillance, especially in low-income countries. Near elimination of H influenzae meningitis has been documented after vaccine introduction. Despite greater than 90% reductions in disease attributable to vaccine serotypes, all-age pneumococcal meningitis has decreased by around 25%, with little data from low-income settings. Near elimination of serogroup C meningococcal meningitis has been documented in several high-income countries, boding well for the effect of a new serogroup A meningococcal conjugate vaccine in the African meningitis belt. Copyright © 2012 Elsevier Ltd. All rights reserved.

HIV/AIDS and contraceptive use: factors associated with contraceptive use among sexually active HIV-positive women in Kenya.

PubMed

Magadi, Monica A; Magadi, Winnie A

2017-03-01

With increased availability of antiretroviral therapy and improved survival for people living with HIV, more HIV-positive women are leading full reproductive lives. However, HIV-positive women have special contraceptive needs/concerns. This paper examines the individual and community-level HIV/AIDS factors associated with contraceptive use and compares predictors of contraceptive uptake between HIV-positive and HIV-negative women in Kenya. The study is based on secondary analysis of cross-sectional data of a sample of 9132 sexually active women of reproductive age from the Kenya Demographic and Health Surveys collected in 2003 and 2008. Multilevel logistic regression models are used to examine individual and contextual community-level factors associated with current contraceptive use. The study provides evidence of lower contraceptive uptake among women living in high HIV-prevalence communities. It further reveals striking differences in factors associated with contraceptive uptake between HIV-positive and HIV-negative women. Education and the desire to stop childbearing are strongly associated with contraceptive uptake among uninfected women, but both factors are not significant among HIV-positive women for whom wealth is the most important factor. While HIV-negative women in the richest wealth quintile are about twice as likely to use contraceptives as their counterparts of similar characteristics in the poorest quintile, this gap is about sevenfold among HIV-positive women. These findings suggest that having the desire and relevant knowledge to use contraceptives does not necessarily translate into expected contraceptive behavior for HIV-positive women in Kenya and that poor HIV-positive women may be particularly in need of increased access to contraceptive services. • Study provides evidence of lower contraceptive uptake among women living in high HIV-prevalence communities in Kenya. • Results reveal striking differences in factors associated with

Bacterial invasion of the inner ear in association with pneumococcal meningitis.

PubMed

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

2014-06-01

To examine the pathways of bacterial invasion and subsequent spreading in the inner ear during pneumococcal meningitis. A well-established adult rat model of Streptococcus pneumoniae meningitis was used. Thirty rats were inoculated intrathecally with S. pneumoniae serotype 1, 3 or 9 V and received no additional treatment. The rats were sacrificed when reaching terminal illness or on Day 7 and then prepared for serial sectioning and PAS-Alcian blue staining for light microscopy. During the first few days after inoculation, bacteria invade the inner ear through the cochlear aqueduct, into the scala tympani of the cochlea (perilymphatic space). From here, bacteria spreads apically toward the helicotrema and subsequently basally through the scala vestibuli, toward the vestibule and the vestibular system. When the bacteria after 5 to 6 days had reached scala vestibuli of the basal turn of the cochlea, hematogenous spreading occurred to the spiral ligament and into the cochlear endolymph, subsequently to the vestibular endolymph. We found no evidence of alternative routes for bacterial invasion in the inner ear. Several internal barriers to bacterial spreading were found within the inner ear. Bacterial elimination was evidenced by engulfment by macrophages within the inner ear. From the meninges, pneumococci invade the inner ear through the cochlear aqueduct during the first days of infection, whereas hematogenous invasion via the spiral ligament capillary bed occur at later stages. Although internal barriers exist within the inner ear, the spreading of bacteria occurs via the natural pathways of the fluid compartments. Bacterial elimination occurs by local macrophage engulfment.

Neurological disorders in HIV-infected children in India.

PubMed

Gupta, S; Shah, D M; Shah, I

2009-09-01

There are few studies of HIV-related neurological disorders from centres in low-income countries where facilities are available for detailed investigation. Records of all patients attending the paediatric HIV outpatient department at B. J. Wadia Hospital for Children, Mumbai between April 2000 and March 2008 were reviewed. Of 668 HIV-infected patients, 48 (7.2%) had neurological manifestations and are included in this study. Twenty-six (54.2%) children had HIV encephalopathy. Other causes of neurological manifestations include febrile convulsion in five (10.4%), bacterial meningitis in three (6.3%), epilepsy in two (4.2%), tuberculous meningitis and progressive multi-focal encephalopathy in two (4.2%) each and toxoplasmosis, vasculitis, acute demyelinating encephalomyelitis, anti-phospholipid antibody syndrome, Down's syndrome, birth asphyxia, herpes simplex encephalopathy and mitochondrial encephalopathy in one (2.1%) each. Mean (SD) age at presentation was 4.36 (3.38) years with a range of 2 months to 15 years. The common subtle neurological manifestations were abnormal deep tendon reflexes and extensor plantar reflexes. The common symptomatic manifestations were delayed milestones in 21 children (43.8%) and seizures in 19 (39.6%). Seizures were more common in males (54%) than in females (25%) (p=0.038). In children <5 years, delayed milestones was the most common manifestation while focal neurological deficits were more common in older children. Of the 13 children who received HAART, nine (60.23%) improved. Early diagnosis of neurological disorders in HIV-infected children is important for appropriate investigation and management, especially the introduction of HAART.

Factors related to HIV-associated neurocognitive impairment differ with age.

PubMed

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

2015-02-01

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 (HANDs). In this study, we employed stepwise regression to examine 24 features sometimes associated with HAND in 40 older (55-73 years of age) and 30 younger (32-50 years of age) HIV+, cART-treated participants without significant central nervous system confounds. 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. 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.

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

PubMed

Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

2012-02-23

The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.

Primary meningeal rhabdomyosarcoma.

PubMed

Palta, Manisha; Riedel, Richard F; Vredenburgh, James J; Cummings, Thomas J; Green, Scott; Chang, Zheng; Kirkpatrick, John P

2011-01-01

Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.

Post-traumatic stress is associated with verbal learning, memory, and psychomotor speed in HIV-infected and HIV-uninfected women.

PubMed

Rubin, Leah H; Pyra, Maria; Cook, Judith A; Weber, Kathleen M; Cohen, Mardge H; Martin, Eileen; Valcour, Victor; Milam, Joel; Anastos, Kathryn; Young, Mary A; Alden, Christine; Gustafson, Deborah R; Maki, Pauline M

2016-04-01

The prevalence of post-traumatic stress disorder (PTSD) is higher among HIV-infected (HIV+) women compared with HIV-uninfected (HIV-) women, and deficits in episodic memory are a common feature of both PTSD and HIV infection. We investigated the association between a probable PTSD diagnosis using the PTSD Checklist-Civilian (PCL-C) version and verbal learning and memory using the Hopkins Verbal Learning Test in 1004 HIV+ and 496 at-risk HIV- women. HIV infection was not associated with a probable PTSD diagnosis (17% HIV+, 16% HIV-; p = 0.49) but was associated with lower verbal learning (p < 0.01) and memory scores (p < 0.01). Irrespective of HIV status, a probable PTSD diagnosis was associated with poorer performance in verbal learning (p < 0.01) and memory (p < 0.01) and psychomotor speed (p < 0.001). The particular pattern of cognitive correlates of probable PTSD varied depending on exposure to sexual abuse and/or violence, with exposure to either being associated with a greater number of cognitive domains and a worse cognitive profile. A statistical interaction between HIV serostatus and PTSD was observed on the fine motor skills domain (p = 0.03). Among women with probable PTSD, HIV- women performed worse than HIV+ women on fine motor skills (p = 0.01), but among women without probable PTSD, there was no significant difference in performance between the groups (p = 0.59). These findings underscore the importance of considering mental health factors as correlates to cognitive deficits in women with HIV.

Applying the HIV-associated neurocognitive disorder diagnostic criteria to HIV-infected youth

PubMed Central

Phillips, Nicole; Joska, John A.; Paul, Robert; Donald, Kirsten A.; Stein, Dan J.; Thomas, Kevin G.F.

2016-01-01

Objective: The aim of this study was to apply the HIV-associated neurocognitive disorders (HAND) criteria for diagnosing HAND in HIV-infected adults, in a cohort of HIV-infected youth to thus establish whether this system is able to detect a spectrum of neurocognitive disorders (ND) in HIV-infected youth. Methods: We used a comprehensive pediatric neurocognitive battery, an assessment of functional competence, and the American Academy of Neurology system for diagnosing ND in a cross-sectional study of HIV-infected youth (n = 86) and HIV-negative controls (n = 34) to establish whether this system could detect a spectrum of ND in HIV-infected youth (6–16 years). Results: Compared to a well-matched control group of HIV-negative youth, HIV-infected youth performed significantly more poorly on tests of Verbal IQ, Full Scale IQ, processing speed, finger tapping, verbal memory, expressive language, cognitive flexibility, and inhibition. HIV-infected youth were also more likely to have impaired total competence on the Child Behavior Checklist. Using the criteria for HAND, we found that 45.35% of the 86 HIV-infected youth could be diagnosed with an ND. Furthermore, youth with HIV encephalopathy (HIVE) were 9.4 times more likely to have a diagnosis of a major ND compared to HIV-infected youth without HIVE. Conclusions: The HAND criterion designed for adults was able to identify youth with important functional cognitive impairments who do not fit criteria for HIVE and would therefore not have been identified otherwise. This has major clinical implications regarding the importance of managing HIV-infected youth. PMID:27206720

Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention.

PubMed

Mount, Hillary R; Boyle, Sean D

2017-09-01

The etiologies of meningitis range in severity from benign and self-limited to life-threatening with potentially severe morbidity. Bacterial meningitis is a medical emergency that requires prompt recognition and treatment. Mortality remains high despite the introduction of vaccinations for common pathogens that have reduced the incidence of meningitis worldwide. Aseptic meningitis is the most common form of meningitis with an annual incidence of 7.6 per 100,000 adults. Most cases of aseptic meningitis are viral and require supportive care. Viral meningitis is generally self-limited with a good prognosis. Examination maneuvers such as Kernig sign or Brudzinski sign may not be useful to differentiate bacterial from aseptic meningitis because of variable sensitivity and specificity. Because clinical findings are also unreliable, the diagnosis relies on the examination of cerebrospinal fluid obtained from lumbar puncture. Delayed initiation of antibiotics can worsen mortality. Treatment should be started promptly in cases where transfer, imaging, or lumbar puncture may slow a definitive diagnosis. Empiric antibiotics should be directed toward the most likely pathogens and should be adjusted by patient age and risk factors. Dexamethasone should be administered to children and adults with suspected bacterial meningitis before or at the time of initiation of antibiotics. Vaccination against the most common pathogens that cause bacterial meningitis is recommended. Chemoprophylaxis of close contacts is helpful in preventing additional infections.

Anatomy of the Spinal Meninges.

PubMed

Sakka, Laurent; Gabrillargues, Jean; Coll, Guillaume

2016-06-01

The spinal meninges have received less attention than the cranial meninges in the literature, although several points remain debatable and poorly understood, like their phylogenesis, their development, and their interactions with the spinal cord. Their constancy among the chordates shows their crucial importance in central nervous system homeostasis and suggests a role far beyond mechanical protection of the neuraxis. This work provides an extensive study of the spinal meninges, from an overview of their phylogenesis and embryology to a descriptive and topographic anatomy with clinical implications. It examines their involvement in spinal cord development, functioning, and repair. This work is a review of the literature using PubMed as a search engine on Medline. The stages followed by the meninges along the phylogenesis could not be easily compared with their development in vertebrates for methodological aspects and convergence processes throughout evolution. The distinction between arachnoid and pia mater appeared controversial. Several points of descriptive anatomy remain debatable: the functional organization of the arterial network, and the venous and lymphatic drainages, considered differently by classical anatomic and neuroradiological approaches. Spinal meninges are involved in neurodevelopment and neurorepair producing neural stem cells and morphogens, in cerebrospinal fluid dynamics and neuraxis functioning by the synthesis of active molecules, and the elimination of waste products of central nervous system metabolism. The spinal meninges should be considered as dynamic functional formations evolving over a lifetime, with ultrastructural features and functional interactions with the neuraxis remaining not fully understood.

HIV-negative partnered men's attitudes toward using an in-home rapid HIV test and associated factors among a sample of US HIV-Negative and HIV-discordant male couples.

PubMed

Mitchell, Jason W; Sullivan, Patrick S

2015-03-01

Many men who have sex with men acquire HIV while in a same-sex relationship. Studies with gay male couples have demonstrated that relationship characteristics and testing behaviors are important to examine for HIV prevention. Recently, an in-home rapid HIV test (HT) has become available for purchase in the United States. However, HIV-negative partnered men's attitudes toward using an HT and whether characteristics of their relationship affect their use of HTs remain largely unknown. This information is relevant for the development of HIV prevention interventions targeting at-risk HIV-negative and HIV-discordant male couples. To assess HIV-negative partnered men's attitudes and associated factors toward using an HT, a cross-sectional Internet-based survey was used to collect dyadic data from a national sample of 275 HIV-negative and 58 HIV-discordant gay male couples. Multivariate multilevel modeling was used to identify behavioral and relationship factors associated with 631 HIV-negative partnered men's attitudes toward using an HT. HIV-negative partnered men were "very likely" to use an HT. More positive attitudes toward using an HT were associated with being in a relationship of mixed or nonwhite race and with one or both men recently having had sex with a casual male partner. Less positive attitudes toward using an HT were associated with both partners being well educated, with greater resources (investment size) in the relationship, and with one or both men having a primary care provider. These findings may be used to help improve testing rates via promotion of HTs among gay male couples.

Tat-functionalized liposomes for the treatment of meningitis: an in vitro study

PubMed Central

Bartomeu Garcia, Caterina; Shi, Di; Webster, Thomas J

2017-01-01

Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47–57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat47–57), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7–3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood–brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis

Inflammasome activation mediates inflammation and outcome in humans and mice with pneumococcal meningitis

PubMed Central

2013-01-01

Background Inflammasomes are multi-protein intracellular signaling complexes that have recently been hypothesized to play a role in the regulation of the inflammation response. We studied associations between inflammasome-associated cytokines IL-1β and IL-18 in cerebrospinal fluid (CSF) of patients with bacterial meningitis and clinical outcome, and pneumococcal serotype. In a murine model of pneumococcal meningitis we examined the pathophysiological roles of two inflammasome proteins, NLRP3 (Nod-like receptor protein-3) and adaptor protein ASC (apoptosis-associated speck-like protein). Methods In a nationwide prospective cohort study, CSF cytokine levels were measured and related to clinical outcome and pneumococcal serotype. In a murine model of pneumococcal meningitis using Streptococcus pneumoniae serotype 3, we examined bacterial titers, cytokine profiles and brain histology at 6 and 30 hours after inoculation in wild-type (WT), Asc and Nlrp3 deficient mice. Results In patients with bacterial meningitis, CSF levels of inflammasome associated cytokines IL-1β and IL-18 were related to complications, and unfavorable disease outcome. CSF levels of IL-1β were associated with pneumococcal serotype (p<0.001). In our animal model, Asc and Nlrp3 deficient mice had decreased systemic inflammatory responses and bacterial outgrowth as compared to WT mice. Differences between Asc−/− and WT mice appeared sooner after bacterial inoculation and were more widespread (lower pro-inflammatory cytokine levels in both blood and brain homogenate) than in Nlrp3-/-mice. Nlrp3 deficiency was associated with an increase of cerebral neutrophil infiltration and cerebral hemorrhages when compared to WT controls. Conclusions Our results implicate an important role for inflammasome proteins NLRP3 and ASC in the regulation of the systemic inflammatory response and the development of cerebral damage during pneumococcal meningitis, which may dependent on the pneumococcal serotype. PMID

Associations between the legal context of HIV, perceived social capital, and HIV antiretroviral adherence in North America.

PubMed

Phillips, J Craig; Webel, Allison; Rose, Carol Dawson; Corless, Inge B; Sullivan, Kathleen M; Voss, Joachim; Wantland, Dean; Nokes, Kathleen; Brion, John; Chen, Wei-Ti; Iipinge, Scholastika; Eller, Lucille Sanzero; Tyer-Viola, Lynda; Rivero-Méndez, Marta; Nicholas, Patrice K; Johnson, Mallory O; Maryland, Mary; Kemppainen, Jeanne; Portillo, Carmen J; Chaiphibalsarisdi, Puangtip; Kirksey, Kenn M; Sefcik, Elizabeth; Reid, Paula; Cuca, Yvette; Huang, Emily; Holzemer, William L

2013-08-08

Human rights approaches to manage HIV and efforts to decriminalize HIV exposure/transmission globally offer hope to persons living with HIV (PLWH). However, among vulnerable populations of PLWH, substantial human rights and structural challenges (disadvantage and injustice that results from everyday practices of a well-intentioned liberal society) must be addressed. These challenges span all ecosocial context levels and in North America (Canada and the United States) can include prosecution for HIV nondisclosure and HIV exposure/transmission. Our aims were to: 1) Determine if there were associations between the social structural factor of criminalization of HIV exposure/transmission, the individual factor of perceived social capital (resources to support one's life chances and overcome life's challenges), and HIV antiretroviral therapy (ART) adherence among PLWH and 2) describe the nature of associations between the social structural factor of criminalization of HIV exposure/transmission, the individual factor of perceived social capital, and HIV ART adherence among PLWH. We used ecosocial theory and social epidemiology to guide our study. HIV related criminal law data were obtained from published literature. Perceived social capital and HIV ART adherence data were collected from adult PLWH. Correlation and logistic regression were used to identify and characterize observed associations. Among a sample of adult PLWH (n = 1873), significant positive associations were observed between perceived social capital, HIV disclosure required by law, and self-reported HIV ART adherence. We observed that PLWH who have higher levels of perceived social capital and who live in areas where HIV disclosure is required by law reported better average adherence. In contrast, PLWH who live in areas where HIV transmission/exposure is a crime reported lower 30-day medication adherence. Among our North American participants, being of older age, of White or Hispanic ancestry, and having

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2013-07-01

SUBTITLE 5a. CONTRACT NUMBER Viral Oncolytic Therapeutics for Neoplastic Meningitis 5b. GRANT NUMBER W81XWH-11-1-0388 5c. PROGRAM ELEMENT NUMBER... viral and cellular kinetics with bioluminescence and PET are being written up for publication. 15. SUBJECT TERMS Neoplastic meningitis , mouse...model of meningeal metastases, breast cancer, bioluminescence, MRI, viral oncolysis, HSV- 1. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

National Institute on Drug Abuse symposium report: drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV-associated dementia.

PubMed

Purohit, Vishnudutt; Rapaka, Rao; Frankenheim, Jerry; Avila, Albert; Sorensen, Roger; Rutter, Joni

2013-04-01

The National Institute on Drug Abuse organized a symposium on drugs of abuse, dopamine, and HIV-associated neurocognitive disorders (HAND)/HIV-associated dementia (HAD) in Rockville, Maryland, October 4, 2011. The purpose of this symposium was to evaluate the potential role of dopamine in the potentiation of HAND/HAD by drugs of abuse. A summary of the symposium has been presented in this report.

Macrophage secretome from women with HIV-associated neurocognitive disorders.

PubMed

Colon, Krystal; Perez-Laspiur, Juliana; Quiles, Raymond; Rodriguez, Yolanda; Wojna, Valerie; Shaffer, Scott A; Leszyk, John; Skolasky, Richard L; Melendez, Loyda M

2016-02-01

Thirty to 50% of HIV patients develop HIV-associated neurocognitive disorders (HANDs) despite combined antiretroviral therapy. HIV-1-infected macrophages release viral and cellular proteins that induce neuronal degeneration and death. We hypothesize that changes in the macrophage secretome of HIV-1 seropositive patients with HAND may dissect proteins related to neurotoxicity. Monocyte-derived macrophages (MDMs) were isolated from the peripheral blood of 12 HIV+ and four HIV- women characterized for neurocognitive function. Serum-free MDM supernatants were collected for protein isolation and quantification with iTRAQ® labeling. Protein identification was performed using a LTQ Orbitrap Velos mass spectrometer and validated in MDM supernatants and in plasma using ELISA. Three proteins were different between normal cognition (NC) and asymptomatic neurocognitive disorders (ANI), six between NC and HIV-associated dementia (HAD), and six between NC and HAD. Among these, S100A9 was decreased in plasma from patients with ANI, and metalloproteinase 9 was decreased in the plasma of all HIV+ patients regardless of cognitive status, and was significantly reduced in supernatant of MDM isolated from patients with ANI. S100A9 and metalloproteinase 9 have been associated with inflammation and cognitive impairment, and therefore represent potential targets for HAND treatment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The association of perceived stress and verbal memory is greater in HIV-infected versus HIV-uninfected women.

PubMed

Rubin, Leah H; Cook, Judith A; Weber, Kathleen M; Cohen, Mardge H; Martin, Eileen; Valcour, Victor; Milam, Joel; Anastos, Kathryn; Young, Mary A; Alden, Christine; Gustafson, Deborah R; Maki, Pauline M

2015-08-01

In contrast to findings from cohorts comprised primarily of HIV-infected men, verbal memory deficits are the largest cognitive deficit found in HIV-infected women from the Women's Interagency HIV Study (WIHS), and this deficit is not explained by depressive symptoms or substance abuse. HIV-infected women may be at greater risk for verbal memory deficits due to a higher prevalence of cognitive risk factors such as high psychosocial stress and lower socioeconomic status. Here, we investigate the association between perceived stress using the Perceived Stress Scale (PSS-10) and verbal memory performance using the Hopkins Verbal Learning Test (HVLT) in 1009 HIV-infected and 496 at-risk HIV-uninfected WIHS participants. Participants completed a comprehensive neuropsychological test battery which yielded seven cognitive domain scores, including a primary outcome of verbal memory. HIV infection was not associated with a higher prevalence of high perceived stress (i.e., PSS-10 score in the top tertile) but was associated with worse performance on verbal learning (p < 0.01) and memory (p < 0.001), as well as attention (p = 0.02). Regardless of HIV status, high stress was associated with poorer performance in those cognitive domains (p's < 0.05) as well as processing speed (p = 0.01) and executive function (p < 0.01). A significant HIV by stress interaction was found only for the verbal memory domain (p = 0.02); among HIV-infected women only, high stress was associated with lower performance (p's < 0.001). That association was driven by the delayed verbal memory measure in particular. These findings suggest that high levels of perceived stress contribute to the deficits in verbal memory observed in WIHS women.

Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.

PubMed

Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Anema, Aranka; Klein, Marina B; Brassard, Paul

2018-05-01

Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

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

Detection of acute childhood meningitis by PCR, culture and agglutination tests in Tabriz, Iran.

PubMed

Ghotaslou, Reza; Farajnia, Safar; Yeganeh, Fatemeh; Abdoli-Oskouei, Shahram; Ahangarzadeh Rezaee, Mohammad; Barzegar, Mohammad

2012-01-01

Meningitis is one of the hazardous and life threatening infections and is associated with mortality and morbidity. The aim of this study was to determine etiological agents of childhood bacterial meningitis. The culture, Gram staining, agglutination and PCR assays were used to examine CSF specimens from 277 patients with presumed bacterial meningitis for the occurrence of 4 most common infectious agents consist of N. meningitis, H. influnsae, S. pneumoniae and S. agalactiae between 2008 and 2009 at different wards of the Children Hospital of Tabriz. The mean age of patients was 35 ± 2 (Mean ± SEM) month, (minimum 11 days maximum 14 years), of all cases 59.6% male and 40.4% female. Overall the diagnosis was confirmed with a CSF culture in 11/277 (3.97%), by agglutination test in 14/277 (5.05%). The isolated bacteria included S. pneumoniae 5 cases, H. influnsae 2 cases, N. meningitis 3 cases and P. aeroginusae 1 case. A positive PCR assay allowed us to diagnose bacterial meningitis in 19 patients (6.8%). In the present study, we found PCR to be a useful and sensitive method for the detection of bacterial DNA in the CSF samples from suspected meningitis patients. Furthermore, to maximize management of meningitis cases, a combination of culture and PCR is necessary.

Characterization of HIV-associated Hodgkin's lymphoma in HIV-infected patients: a single-center experience.

PubMed

Ruiz, Marco; Parsons, Christopher; Cole, John

2012-01-01

Although the incidence and prevalence of AIDS-defining malignancies has decreased in the era of highly active antiretroviral therapy (HAART), the incidence and prevalence of Hodgkin's lymphoma (HL) in the HIV-infected population continues to rise. Compared with the general population, HIV-infected patients exhibit a 5-10-fold increased risk for developing HL. A retrospective review of charts and electronic records from 2000-2010 at the HIV outpatient clinic (HOP)-Louisiana State University in New Orleans was conducted, and pathologically confirmed cases of HIV-HL were identified within this cohort. We found a prevalence of 6.3 cases per 1,000 patients per year of HIV-HL over a period of 10 years in our HIV outpatient clinic. The mean absolute CD4 count before treatment was 284 cells/mm(3) and after treatment was 194 cells/mm(3). The average time from the diagnosis of HIV infection to the diagnosis of HIV-HL was 7.6 years. The most common histopathologic type was mixed cellularity followed by lymphocytic predominance. The majority of patients had 6 cycles delivered. In terms of HL staging 87% presented with advanced stages (III B or IV). To the best of our knowledge 5 out of the 14 patients remain alive. Patients in our cohort were older than most patients identified in other cohorts. All of our patients had coexisting chronic illnesses associated with inflammation, as well as detectable HIV viral loads and CD4 count >200, suggesting a role for both HIV- and non-HIV-associated inflammation in HIV-HL pathogenesis in this population. The role of HIV virus and other oncogenic viruses (EBV, HPV, and others) in the pathogenesis of Hodgkin's lymphoma in this group of patients needs to be elucidated.

Relevance of intracranial hypertension control in the management of Cryptococcus neoformans meningitis related to AIDS.

PubMed

de Vedia, L; Arechavala, A; Calderón, M I; Maiolo, E; Rodríguez, A; Lista, N; Di Virgilio, E; Cisneros, J C; Prieto, R

2013-12-01

To evaluate the relationship between intracranial hyperpressure (HICP) and mortality in patients with cryptococcal meningitis related to AIDS (CMRA). This was an observational retrospective study. Patients were treated according to the Infectious Diseases Society of America recommendations during the evaluation period (days 0, 3, 5 and after hospitalization). High intracranial pressure (HICP) was defined as ICP values of C250 mm H20. The correlation between HICP and mortality at each of the three time points considered was investigated. Statistical analysis on the descriptive parameters and on the probability of a "death" event (odds ratio, OR) at each of those three time points was performed using the statistical software program Epidata. Eighty patients were included in this study, of whom 53 (66.25 %) were male. The average age of the patients was 37.5 ± 8.1 (range 22–55) years. The median CD4?lymphocyte cell count was 35 (range 0–367) cells/ml. Among the entire patient cohort, 53 patients had a favorable outcome, and the mortality rate was 33.75 %. At baseline (day 0), 57 subjects (71.5 %) presented HICP, and these patients had a higher mortality rate than those with a normal ICP, but the difference did not reach statistical significance[OR 1.65, 95 % confidence interval (CI) 0.56–4.84]. On day 3, 41 of the patients presented HICP, and HICP at this timepoint was significantly associated with an increased risk of mortality (OR 4.35, 95 % CI 1.56–12.09). On day 5, 35(43.5 %) patients presented HICP, and HCIP at this time point was also significantly associated with higher mortality (OR 7.23, 95 % CI 2.53–20.14). The results of this study confirm an association between HICP and mortality in patients with CMRA and indicate that the control of ICP during the first 5 days of hospitalization is more important than managing HICP only at baseline.

The relationship between prior antimicrobial prescription and meningitis: a case-control study.

PubMed

Armstrong, David; Ashworth, Mark; Dregan, Alex; White, Patrick

2016-04-01

Recent research into the role of the human microbiome in maintaining health has identified the potentially harmful impact of antimicrobials. 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. 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. 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. 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. © British Journal of General Practice 2016.

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

[Pneumococcal meningitis revealing dysplasia of the bony labyrinth in an infant].

PubMed

Louaib, D; François, M; Coderc, E; Dieu, S; Nathanson, M; Narcy, P; Gaudelus, J

1996-03-01

Dysplasias of the bony labyrinth are frequently associated with cerebrospinal fluid fistula and are usually discovered because of recurrent meningitis. A 1 year-old infant was admitted for a pneumococcal meningitis which appeared 2 days after the occurrence of a clear otorrhea from the right ear. The same organism was isolated from the otorrhea fluid, which also contained cerebrospinal fluid as confirmed cytochemically. The meningitis rapidly resolved with antibiotic treatment. Auditory brain stem responses were abolished from the right ear. CT of the temporal bones showed a pseudo-Mondini type labyrinth dysplasia at the right ear and Mondini type dysplasia at the left one. A translabyrinthine cerebrospinal fluid fistula was discovered by surgical exploration of the right ear, occurring through a perforation in the stapedial foot plate. The leak was cured by packing the vestibule and obturating both oval and round windows. Three years after the operation, the child did not experience any further episode of otorrhea or meningitis. Features suggesting a translabyrinthine fistula, especially otorrhea and deafness, should be systematically searched in any child with bacterial meningitis. Closure of these fistulas can prevent severe infectious recurrences.

Meningitis following cochlear implantation: pathomechanisms, clinical symptoms, conservative and surgical treatments.

PubMed

Arnold, W; Bredberg, G; Gstöttner, W; Helms, J; Hildmann, H; Kiratzidis, T; Müller, J; Ramsden, R T; Roland, P; Walterspiel, J N

2002-01-01

Pneumococcal otogenic meningitis is a rare postsurgical complication that can develop following stapedectomy or after cochlear implantation. The bacterial infection can be fatal in some instances. A recent increase in the incidence of otogenic meningitis among cochlear implant wearers is of concern. The majority of meningitis cases are associated with a 2-component electrode manufactured by one cochlear implant company. The device with the added 'positioner' component has been withdrawn from the market (FDA Public Health Web Notification: Cochlear Implant Recipients may be at Greater Risk for Meningitis, Updated: August 29, 2002, www.fda.gov/cdrh/safety/cochlear.html). Not all cases have been subsequent to otitis media and symptoms have developed from less than 24 h up to a few years after implantation. The purpose of this paper is to review and discuss the pathogenesis, pathology/bacteriology and to elaborate on some clinical features of otogenic meningitis in implanted children and adults. Essential aspects of surgery, electrode design, and cochleostomy seal are discussed. Conclusions are drawn from the available data and recommendations are made for good practice in cochlear implantation and follow-up. Copyright 2002 S. Karger AG, Basel

Pleocytosis is not fully responsible for low CSF glucose in meningitis.

PubMed

Baud, Maxime O; Vitt, Jeffrey R; Robbins, Nathaniel M; Wabl, Rafael; Wilson, Michael R; Chow, Felicia C; Gelfand, Jeffrey M; Josephson, S Andrew; Miller, Steve

2018-01-01

The mechanism of hypoglycorrhachia-low CSF glucose-in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels. We retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis. We found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial ( R 2 = 36%, p < 0.001) and repeated CSF sampling ( R 2 = 46%, p < 0.001). Hypoglycorrhachia (<40 mg/dL) was observed in 50.1% of microbial cases, but only 9.6% of aseptic cases, most of which were neurosarcoidosis. Absolute CSF glucose and CSF-to-serum glucose ratios had similar low sensitivity and moderate-to-high specificity in diagnosing microbial meningitis at thresholds commonly used. The main driver of hypoglycorrhachia appears to be a combination of microbial meningitis with moderate to high degrees of CSF inflammation and proteins, suggesting that the presence of microorganisms capable of catabolizing glucose is a determinant of hypoglycorrhachia in meningitis. A major notable exception is neurosarcoidosis. Low CSF glucose and CSF-to-serum glucose ratios are useful markers for the diagnosis of microbial meningitis.

Prevalence and cost of HIV-associated weight loss in a managed care population.

PubMed

Siddiqui, Javeed; Phillips, Amy L; Freedland, Eric S; Sklar, Ami R; Darkow, Theodore; Harley, Carolyn R

2009-05-01

To estimate the prevalence of HIV-associated weight loss among HIV patients in a US managed care population, and compare demographic and clinical characteristics of HIV patients with and without evidence of HIV-associated weight loss. A retrospective observational study was conducted using a large, geographically diverse US managed care population to identify commercial enrollees with HIV/AIDS from 1/1/2005-7/31/2007, based on a combination of HIV/AIDS diagnosis codes or antiretroviral treatment. HIV-associated weight loss status was defined according to an algorithm combining evidence for weight loss-associated conditions, anorexia symptoms, and various treatments for weight loss or wasting. Among HIV patients continuously enrolled in the health plan for one year, patient demographics, treatments, and comorbidities were compared between patients with and without evidence for weight loss. A total of 22,535 patients with HIV/AIDS were identified, including 2098 who met the criteria for weight loss (estimated prevalence 9.3%; 95% CI: 8.9% - 9.7%). Among 12,187 continuously enrolled patients with HIV, 1006 (8.3%) had evidence of HIV-associated weight loss. Patients with HIV-associated weight loss were older (44.1 vs. 42.6 years), and more men had HIV-associated weight loss than women (8.8% vs. 5.3%). A number of comorbidities were more common among patients with HIV-associated weight loss. On average, these patients also had more ambulatory (24.0 vs. 13.4), ER (1.4 vs. 0.8), and inpatient visits (0.5 vs. 0.1). Total annual health care costs for patients with HIV-associated weight loss were more than double (mean $45,686 vs. $19,960) the costs for HIV patients without weight loss. Despite the availability of effective antiretroviral therapy, weight loss remains a problem among patients with HIV. Based on this analysis, almost 1 in 10 managed care patients with HIV have evidence of HIV-associated weight loss. These patients tend to have more comorbidities, use more