Browsing by Subject "Meningitis"
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- ItemOpen AccessAdult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases(BioMed Central Ltd, 2010) Jarvis, Joseph; Meintjes, Graeme; Williams, Anthony; Brown, Yolande; Crede, Tom; Harrison, ThomasBACKGROUND: The presentation and causes of adult meningitis in South Africa have changed substantially as a result of HIV. Knowledge of aetiology and laboratory findings in patients presenting with meningitis are important in guiding management. We performed a retrospective study to determine these findings in a setting of high HIV and TB prevalence in Cape Town. METHODS: Patients undergoing lumbar punctures between 1st January 2006 and 31st December 2008 at a public sector referral hospital were studied. Cases were classified by microbiological diagnosis, or in the absence of definitive microbiology as 1) normal CSF (neutrophils [less than or equal to] 1 x 106/L, lymphocytes [less than or equal to] 5 x 106/L, protein [less than or equal to] 0.5 g/dL, glucose [greater than or equal to]1.5 mmol/L), 2) minor abnormalities (neutrophils 2-5, lymphocytes 6-20, protein 0.51-1.0, glucose 1.0-1.49) or 3) markedly abnormal (neutrophils>5, lymphocytes>20, protein>1.0, glucose<1.0). RESULTS: 5578 LPs were performed on 4549 patients, representing 4961 clinical episodes. Of these, 2293 had normal CSF and 931 had minor abnormalities and no aetiology identified. Of the remaining 1737, microbiological diagnoses were obtained in 820 (47%). Cryptococcus accounted for 63% (514) of microbiological diagnoses, TB for 28% (227), bacterial meningitis for 8% (68). Of the remaining 917 who had marked abnormalities, the majority (59%) had a sterile lymphocytic CSF. Of note 16% (81) patients with confirmed Cryptococcus, 5% (12) with TB and 4% (3) with bacterial meningitis had normal CSF cell-counts and biochemistry. CONCLUSIONS: Cryptococcal and tuberculous meningitis are now the commonest causes of adult meningitis in this setting. TB meningitis is probably underdiagnosed by laboratory investigation, as evidence by the large numbers presenting with sterile lymphocytic markedly abnormal CSFs.
- ItemOpen AccessComparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting(Public Library of Science, 2010) Patel, Vinod B; Singh, Ravesh; Connolly, Cathy; Kasprowicz, Victoria; Zumla, Allimudin; Ndungu, Thumbi; Dheda, KeertanBackground/Objective: The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF). METHODS: Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM. RESULTS: Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4<200 vs. >200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98). CONCLUSIONS: Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression.
- ItemOpen AccessDiagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study(Public Library of Science, 2013) Patel, Vinod B; Theron, Grant; Lenders, Laura; Matinyena, Brian; Connolly, Cathy; Singh, Ravesh; Coovadia, Yacoob; Ndung'u, Thumbi; Dheda, KeertanBackground: Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM. Methods and Findings: 235 South-African patients with a meningeal-like illness were categorised as having definite (culture or Amplicor PCR positive), probable (anti-TBM treatment initiated but microbiological confirmation lacking), or non-TBM. Xpert MTB/RIF accuracy was evaluated using 1 ml of uncentrifuged and, when available, 3 ml of centrifuged cerebrospinal fluid (CSF). To evaluate the incremental value of MTB/RIF over a clinically based diagnosis, test accuracy was compared to a clinical score (CS) derived using basic clinical and laboratory information. Of 204 evaluable patients (of whom 87% were HIV-infected), 59 had definite TBM, 64 probable TBM, and 81 non-TBM. Overall sensitivity and specificity (95% CI) were 62% (48%–75%) and 95% (87%–99%), respectively. The sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy (62% versus 12%; p = 0.001) and significantly better than that of the CS (62% versus 30%; p = 0.001; C statistic 85% [79%–92%]). Xpert MTB/RIF sensitivity was higher when centrifuged versus uncentrifuged samples were used (82% [62%–94%] versus 47% [31%–61%]; p = 0.004). The combination of CS and Xpert MTB/RIF (Xpert MTB/RIF performed if CS<8) performed as well as Xpert MTB/RIF alone but with a ∼10% reduction in test usage. This overall pattern of results remained unchanged when the definite and probable TBM groups were combined. Xpert MTB/RIF was not useful in identifying TBM among HIV-uninfected individuals, although the sample was small. There was no evidence of PCR inhibition, and the limit of detection was ∼80 colony forming units per millilitre. Study limitations included a predominantly HIV-infected cohort and the limited number of culture-positive CSF samples. Conclusions: Xpert MTB/RIF may be a good rule-in test for the diagnosis of TBM in HIV-infected individuals from a tuberculosis-endemic setting, particularly when a centrifuged CSF pellet is used. Further studies are required to confirm these findings in different settings.
- ItemOpen AccessExploring the audiological management of young children (0-6 years) diagnosed with bacterial meningitis(2019) Tromp, Nikki; Ramma, Lebogang; Hlayisi, Vera-GeneveyBackground. Internationally, infectious diseases remain the greatest cause of morbidity among young children. Infectious disease burden is particularly high in low-to-mid income countries (LMIC). South Africa has a high prevalence of bacterial meningitis (BM), especially in children under the age of five. BM is also one of the commonest causes of acquired hearing loss in children. Given the fluctuating and transient nature of BM-related hearing loss, there is a need for an effective audiological protocol to facilitate timeous and appropriate audiological management. There is currently no universally accepted protocol for the audiological referral and management of children diagnosed with BM. Consequently, there is a need for an evidence-based protocol that will ensure timely referral and audiological testing of all children diagnosed with BM. Early identification of BM-related hearing loss in children will allow for timeous, appropriate audiological management and associated benefits, such as an option for placement in mainstream schooling. Objectives. This study aimed to explore the audiological management of children diagnosed with BM at a tertiary hospital in the Western Cape, South Africa, with reference to: patterns of referral for audiological assessment following a diagnosis of BM; current audiological protocols for the management of children diagnosed with BM. It was anticipated that this study would generate evidence that could potentially be used to develop appropriate protocols for the audiological management of children diagnosed with BM in LMICs, specifically South Africa. Methods. A retrospective record review was conducted using patient folders of children between 0 and 6 years who were treated for BM between May 2016 and May 2018. Data collection took place at Red Cross War Memorial Children's Hospital, which has a paediatric infectious diseases unit and an audiology department. Demographic and audiological data were recorded on a self-developed data abstraction form and data were analysed descriptively. Results. A total of 291 patient folders were accessed for review in this study. Of those, 40 (13.7%) met the inclusion criteria for the study and were selected for review. The majority of excluded folders were for patients not referred for audiological testing post-BM diagnosis. For those children referred to audiology, average referral time was 15 days (SD = 24 days) and each patient attended an average of only 2 audiology appointments. Otoacoustic emissions testing and tympanometry were the most commonly performed audiological tests in all children. BM-related hearing loss developed in 2/19 of these patients. All patients who were diagnosed with BM-related hearing loss were subsequently fitted with hearing aids – one of whom was fitted unilaterally with a hearing aid and the other, a cochlear implant candidate, was lost to follow-up. Conclusions. The key challenge experienced in this study was low referral rates to audiology (16%), which was followed by poor adherence to follow-up appointments – both of which were found to impede effective audiological management. Effective management and prevention of BM-related hearing loss pose challenges in LMICs. This study highlights the need for a well-defined referral pathway and an evidence-based protocol for the audiological management of children with BM within the South African health care setting. If this could be achieved, the early identification of hearing loss in these children has the potential to provide them with developmental, scholastic, and working opportunities in line with those of children with normal hearing.
- ItemOpen AccessManagement of HIV-associated cryptococcal disease in South Africa(2014) Govender, N P; Dlamini, SIn routine-care settings, the 10-week mortality associated with cryptococcal meningitis (CM) is high, even with prompt, appropriate antifungal treatment and correctly timed initiation of antiretroviral therapy (ART). While early diagnosis of HIV infection and initiation of ART prior to the development of AIDS is the most important way to reduce the incidence of CM, a cryptococcal antigenaemia screen-and-treat intervention has the potential to reduce mortality by identifying patients prior to onset of CM. Antifungal treatment for HIV-associated CM is divided into three phases over a minimum period of 1 year: (i) a 2-week induction phase, including intravenous amphotericin B deoxycholate as a backbone; (ii) an 8-week consolidation phase with fluconazole 400 mg daily; and (iii) a maintenance phase with fluconazole 200 mg daily. Amphotericin B should be paired with another antifungal agent to maximise cerebrospinal fluid fungal clearance. World Health Organization guidelines emphasise that patients receiving amphotericin B-containing regimens should have access to a 'minimum package of toxicity prevention, monitoring and management to minimise the serious amphotericin B-related toxicities particularly hypokalaemia and nephrotoxicity'. Raised intracranial pressure is a serious and often fatal complication of CM, which requires good pressure management with repeat lumbar punctures. ART should be initiated 4 - 6 weeks after starting antifungal therapy. In many cases, relapse CM among South African patients occurs because of suboptimal adherence to secondary prophylaxis with fluconazole and/or the antifungal not being prescribed.
- ItemOpen AccessPresentation and outcome of tuberculous meningitis in a high HIV prevalence setting(Public Library of Science, 2011) Marais, Suzaan; Pepper, Dominique J; Schutz, Charlotte; Wilkinson, Robert J; Meintjes, GraemeBACKGROUND: Mycobacterium tuberculosis is a common, devastating cause of meningitis in HIV-infected persons. Due to international rollout programs, access to antiretroviral therapy (ART) is increasing globally. Starting patients with HIV-associated tuberculous meningitis (TBM) on ART during tuberculosis (TB) treatment may increase survival in these patients. We undertook this study to describe causes of meningitis at a secondary-level hospital in a high HIV/TB co-infection setting and to determine predictors of mortality in patients with TBM. METHODS: A retrospective review of cerebrospinal fluid findings and clinical records over a six-month period (March 2009-August 2009). Definite, probable and possible TBM were diagnosed according to published case definitions. RESULTS: TBM was diagnosed in 120/211 patients (57%) with meningitis. In 106 HIV-infected patients with TBM, six-month all-cause mortality was lower in those who received antiretroviral therapy (ART) during TB treatment; hazard ratio = 0.30 (95% CI = 0.08-0.82). Factors associated with inpatient mortality in HIV-infected patients were 1) low CD4 + count at presentation; adjusted odds ratio (AOR) = 1.4 (95% confidence interval [CI] = 1.03-1.96) per 50 cells/µL drop in CD4 + count and, 2) higher British Medical Research Council TBM disease grade (2 or 3 versus 1); AOR = 4.8 (95% CI = 1.45-15.87). Interpretation Starting ART prior to or during TB treatment may be associated with lower mortality in patients with HIV-associated TBM. Advanced HIV and worse stage of TBM disease predict in-hospital mortality in patients presenting with TBM.
- ItemOpen AccessReliability and diagnostic performance of CT imaging criteria in the diagnosis of tuberculous meningitis(Public Library of Science, 2012) Botha, Hugo; Ackerman, Christelle; Candy, Sally; Carr, Jonathan A; Griffith-Richards, Stephanie; Bateman, Kathleen JIntroduction Abnormalities on CT imaging may contribute to the diagnosis of tuberculous meningitis (TBM). Recently, an expert consensus case definition (CCD) and set of imaging criteria for diagnosing basal meningeal enhancement (BME) have been proposed. This study aimed to evaluate the sensitivity, specificity and reliability of these in a prospective cohort of adult meningitis patients. METHODS: Initial diagnoses were based on the CCD, classifying patients into: ‘Definite TBM’ (microbiological confirmation), ‘Probable TBM’ (diagnostic score ≥10), ‘Possible TBM’ (diagnostic score 6-9), ‘Not TBM’ (confirmation of an alternative diagnosis) or ‘Uncertain’ (diagnostic score of <6). CT images were evaluated independently on two occasions by four experienced reviewers. Intra-rater and inter-rater agreement were calculated using the kappa statistic. Sensitivities and specificities were calculated using both ‘Definite TBM’ and either ‘Definite TBM’ or ‘Probable TBM’ as gold standards. RESULTS: CT scan criteria for BME had good intra-rater agreement (κ range 0.35-0.78) and fair to moderate inter-rater agreement (κ range 0.20-0.52). Intra- and inter-rater agreement on the CCD components were good to fair (κ = ranges 0.47-0.81 and 0.21-0.63). Using ‘Definite TBM’ as a gold standard, the criteria for BME were very specific (61.5%-100%), but insensitive (5.9%-29.4%). Similarly, the imaging components of the CCD were highly specific (69.2-100%) but lacked sensitivity (0-56.7%). Similar values were found when using ‘Definite TBM’ or ‘Probable TBM’ as a gold standard. DISCUSSION: The fair to moderate inter-rater agreement and poor sensitivities of the criteria for BME suggest that little reliance should be placed in these features in isolation. While the presence of the CCD criteria of acute infarction or tuberculoma(s) appears useful as rule-in criteria, their absence is of little help in excluding TBM. The CCD and criteria for BME, as well as any new criteria, need to be standardized and validated in prospective cohort studies.
- ItemOpen AccessStreptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008(Public Library of Science, 2015) Cohen, Cheryl; Naidoo, Nireshni; Meiring, Susan; de Gouveia, Linda; van Mollendorf, Claire; Walaza, Sibongile; Naicker, Preneshni; Madhi, Shabir A; Feldman, Charles; Klugman, Keith P; Dawood, Halima; von Gottberg, Anne; GERMS-SABACKGROUND: An association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa. METHODS: IPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003-2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent. RESULTS: Among 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1-3.5) and 19F (OR 2.9, 95%CI 1.4-6.1) vs. serotype 4; increasing age (25-44 years, OR 1.8, 95%CI 1.0-3.0; 45-64 years, OR 3.6, 95%CI 2.0-6.4; ≥65 years, OR 5.2, 95%CI 1.9-14.1; vs. 15-24 years); meningitis (OR 4.1, 95%CI 3.0-5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0-2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases. CONCLUSION: Mortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.
- ItemOpen AccessThe utility of CSF PCR in central nervous system Varicella zoster infection in HIV(2015) Stanley, Alan Michael; Bryer, Alan; Bateman, KathleenAims: To assess the clinical and cerebrospinal fluid characteristics, and the role of tuberculous meningitis (TBM) as a confounder, in a cohort of HIV positive individuals with positive varicella zoster virus (VZV) positive cerebrospinal fluid PCR. Methods: Patients in the NHLS database at Groote Schuur Hospital with positive CSF VZV PCR who were also HIV co-infected and whose folders were available for clinical review were reviewed. Clinical and biochemical data were collected. Patients were divided into two groups based an accepted case definition for TBM. Differences between groups were assessed using Mann-Whitney U or Chi squared tests as appropriate. Results: There were 437 for VZV PCR over three years. Of these 98 were positive and, after exclusions, 31 HIV positive patients were included for further analysis. Median age was 31 and median CD4 count was 146 cells/mm³. 11 (35%) had meningitis and 8 (25%) had encephalitis. 13 (42%) met the case definition for TBM. Patients with CNS varicella were frequently confused whereas those with TBM presented sub-acutely. There were no differences in CSF characteristics. Additional organisms were detected 6 (19%) patients. 4 (13%) patients died in hospital. CSF TB culture was requested in 24 (77%) patients and extra CNS samples were sent in only 4 patients. Conclusion: The clinical and CSF presentation of CNS Varicella and TBM overlap and in this cohort patients were under investigated for TB. In settings of high TB prevalence the possibility of false positive PCR or incidental varicella reactivation should be considered.