Yacoob Coovadia

Clinical and mycological predictors of cryptococcosis-associated immune reconstitution inflammatory syndrome.

Objective:HIV-infected patients with treated cryptococcal meningitis are at risk for further neurological deterioration after commencing combination antiretroviral therapy (cART), mostly because of cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). Identifying predictors of C-IRIS could enable risk stratification. Design:Prospective, longitudinal cohort study for 24 weeks. Setting:Durban, South Africa. Participants:One hundred and thirty HIV-infected patients with first cryptococcal meningitis episode Intervention:Antifungal therapy (amphotericin 1 mg/kg median 14 days, followed by consolidation and maintenance fluconazole) and cART (commenced median of 18 days from cryptococcal meningitis diagnosis). Main outcome measure:Clinical, blood, and cerebrospinal fluid (CSF) markers associated with C-IRIS before and during cART and clinical significance of CSF cryptococcal culture negativity pre-cART commencement. Results:Of 106 patients commencing cART, 27 (25.5%) developed C-IRIS, 16 (15.1%) neurological deterioration-not C-IRIS, and 63 (59.4%) no neurological deterioration. On multivariable analysis, C-IRIS was associated with persistent CSF cryptococcal growth [hazard ratio (HR) 0.27, P = 0.026] and lower CSF protein (HR 0.53, P = 0.059) prior to cART and lower CD4+ T-cell increases (HR 0.99, P = 0.026) but not change in HIV viral load during cART. Using survival analysis, patients with a negative cryptococcal culture pre-cART commencement (n = 51; 48.1%) experienced fewer episodes of neurological deterioration, C-IRIS, and cryptococcal relapse/persistence than patients with culture positivity (n = 55; 51.9%, HR 0.33, 0.33, and 0.12 and P = 0.0003, 0.0042, and 0.0004, respectively). Conclusion:Persistent CSF cryptococcal growth at cART initiation and poor CD4+ T-cell increases on cART are strong predictors of C-IRIS. Approaches aimed at achieving CSF culture negativity prior to cART should be evaluated as a strategy to reduce rates of C-IRIS.

Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population.

RATIONALE Current tools for the rapid diagnosis of tuberculous meningitis (TBM) are suboptimal. We evaluated the clinical utility of a quantitative RD-1 IFN-gamma T-cell enzyme-linked immunospot (ELISPOT) assay (T-SPOT.TB), using cerebrospinal fluid cells for the rapid immunodiagnosis of TBM. OBJECTIVES To evaluate the diagnostic utility of the RD1 antigen- specific ELISPOT assay for the diagnosis of tuberculous meningitis. METHODS The ELISPOT assay was evaluated in 150 patients with suspected TBM who were categorized as definite-TBM, probable-TBM, and non-TBM. Culture or polymerase chain reaction positivity for Mycobacerium tuberculosis served as the reference standard. To determine the diagnostic value of the ELISPOT assay, a clinical prediction rule was derived from baseline clinical and laboratory parameters using a multivariable regression model. MEASUREMENTS AND MAIN RESULTS A total of 140 patients (81% HIV-infected; median CD4 count, 160 cells/mm(3)) were included in the final analysis. When comparing the definite-TBM (n = 38) and non-TBM groups (n = 48), the ELISPOT assay (cut point of > or =228 spot-forming cells per 1 million mononuclear cells) was a useful rule-in test: sensitivity 58% (95% confidence interval [CI], 41-74); specificity 94% (95% CI, 83-99). However, ELISPOT outcomes improved when other rapid tests were concurrently used to exclude bacterial (Gram stain) and cryptococcal meningitis (latex-agglutination test) within the non-TBM group. Using this approach, the ELISPOT assay (cut point of > or =46 spot-forming cells) was an excellent rule-in test: sensitivity 82% (95% CI, 66-92); specificity 100% (95% CI, 78-100); positive predictive value, 100% (95% CI, 89-100); negative predictive value, 68% (95% CI, 45-86); area under the curve, 0.90. The ELISPOT assay had incremental diagnostic value compared with the clinical prediction rule. CONCLUSIONS The RD-1 ELISPOT assay, using cerebrospinal fluid mononuclear cells and in conjunction with other rapid confirmatory tests (Gram stain and cryptococcal latex-agglutination test), is an accurate rapid rule-in test for TBM in a TB and HIV endemic setting.

An Outbreak of Foodborne Salmonellosis in Rural KwaZulu-Natal, South Africa

BACKGROUND Salmonella enterica serotype Enteritidis is a universally recognized cause of foodborne disease. In South Africa, outbreaks of foodborne disease are generally under reported. We investigated the etiology of acute gastroenteritis in 216 patients who presented to a rural hospital in KwaZulu-Natal, South Africa, after consuming a meal at a school function. MATERIALS AND METHODS Stool specimens from 37 patients, as well as two food samples, were available for microbiological investigation. Similarity between isolates was investigated using phenotypic and genotypic techniques. Phenotypic investigations included morphological, biochemical, and antibiogram profiling. Genotypic relatedness was determined with pulsed-field gel electrophoresis analysis. The available epidemiological data were also described. RESULTS Salmonella Enteritidis was isolated from 18 patients and 1 food sample. Isolates were phenotypically and genotypically indistinguishable. Epidemiological data suggest a point-source outbreak with a possibility of continued transmission. CONCLUSIONS The results suggest a foodborne Salmonella Enteritidis outbreak due to contaminated food served at the school function. Epidemiological investigations continue to be extremely difficult in rural areas.

Synthesis and Antitubercular Activity of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium Chlorides

A series of 2‐(substituted phenyl/benzyl‐amino)‐6‐(4‐chlorophenyl)‐5‐(methoxycarbonyl)‐4‐methyl‐3,6‐dihydropyrimidin‐1‐ium chlorides 7–13 and 15 was synthesized in their hydrochloride salt form. The title compounds were characterized by FT‐IR, NMR (1H and 13C) and elemental analysis. They were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, multidrug resistance tuberculosis and extensively drug resistance tuberculosis by agar diffusion method and tested for the cytotoxic action on peripheral blood mononuclear cells by MTT assay. Among all the tested compounds in the series, compounds 7 and 11 emerged as promising antitubercular agents at 16 μg/mL against multidrug resistance tuberculosis and over 64 μg/mL against extensively drug resistance tuberculosis. The conformational features and supramolecular assembly of the promising compounds 7 and 11 were determined by single crystal X‐ray study.

Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa: a cross-sectional study.

BackgroundThe yield of mycobacterial blood cultures for multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) among drug-resistant TB suspects has not been described.MethodsWe performed a retrospective, cross-sectional analysis to determine the yield of mycobacterial blood cultures for MDR-TB and XDR-TB among patients suspected of drug-resistant TB from rural South Africa. Secondary outcomes included risk factors of Mycobacterium tuberculosis bacteremia and the additive yield of mycobacterial blood cultures compared to sputum culture.ResultsFrom 9/1/2006 to 12/31/2008, 130 patients suspected of drug-resistant TB were evaluated with mycobacterial blood culture. Each patient had a single mycobacterial blood culture with 41 (32%) positive for M. tuberculosis, of which 20 (49%) were XDR-TB and 8 (20%) were MDR-TB. One hundred fourteen (88%) patients were known to be HIV-infected. Patients on antiretroviral therapy were significantly less likely to have a positive blood culture for M. tuberculosis (p = 0.002). The diagnosis of MDR or XDR-TB was made by blood culture alone in 12 patients.ConclusionsMycobacterial blood cultures provided an additive yield for diagnosis of drug-resistant TB in patients with HIV from rural South Africa. The use of mycobacterial blood cultures should be considered in all patients suspected of drug-resistant TB in similar settings.

An investigation of the frequency of bacteraemia following dental extraction, tooth brushing and chewing.

Abstract We conducted a study to determine the frequency of bacteraemias following dental extraction and common oral procedures, namely tooth brushing and chewing, and the relationship between bacteraemia and oral health in black patients. Positive blood cultures were detected in 29.6% of patients after dental extraction, in 10.8% of patients after tooth brushing and in no patients after chewing. No relationship between the state of oral health, which was assessed using the plaque and gingival indices, and the incidence of bacteraemia was found. The duration of bacteraemia was less than 15 minutes. One patient had a positive blood culture prior to dental extraction; his oral health status was poor. Our study confirmed that bacteraemia occurs after tooth brushing.

Intravenous glucose preparation as the source of an outbreak of extended-spectrum β-lactamase-producing Klebsiella pneumoniae infections in the neonatal unit of a regional hospital in KwaZulu-Natal : original article

In the last week of May 2005, staff at Mahatma Gandhi Memorial Hospital in KwaZulu-Natal realised that many babies in the high-care nursery ward had bloodstream infections involving Klebsiella pneumoniae bacteria. Attempts to identify a common source of infection failed. The ward was therefore closed and new babies needing high care were admitted to another empty ward. Despite this, babies still became infected. This resulted in a request for assistance from the Department of Medical Microbiology of the Nelson R Mandela School of Medicine. A search for common factors through case history studies of the 26 infected babies showed that blood cultures of the babies remained positive despite the administration of appropriate antibiotics. Different options that could explain this were investigated. The organism was found in intravenous glucose preparations used for multiple dosing. Unopened vials of the same medication were sterile. The nursery was found to lack proper hand-wash facilities and to be overcrowded and understaffed. Reinforcement of hand hygiene and a ban on the multiple dosing of medicines stopped the outbreak. In conclusion, this outbreak resulted from a combination of factors among which lack of hand hygiene and multiple dosing of an intravenous glucose preparation were most significant.

Emergence of azole-resistant Candida parapsilosis causing bloodstream infection: results from laboratory-based sentinel surveillance in South Africa

OBJECTIVES To compare Candida species distribution and antifungal susceptibility at South African public- and private-sector hospitals. METHODS From February 2009 through to August 2010, laboratory-based surveillance for candidaemia was undertaken at 11 public-sector hospitals and >85 private-sector hospitals across South Africa. A case was defined as a patient of any age admitted to a sentinel hospital with isolation of Candida species from blood culture. Viable isolates were identified and tested for antifungal susceptibility at a reference laboratory. Demographic and limited clinical data were abstracted from laboratory records. RESULTS In total, 2172 cases of candidaemia were detected. Among patients with available data, almost two-thirds were critically ill (719/1138, 63%). On multivariable analysis, neonates [adjusted OR (aOR), 2.2; 95% CI, 1.5-3.1; P < 0.001] and patients diagnosed in Gauteng province (aOR, 1.9; 95% CI, 1.3-2.7; P < 0.001) or in the private sector (aOR, 1.9; 95% CI, 1.2-3.2; P = 0.008) were significantly more likely to be infected with Candida parapsilosis than any other Candida species. Of 531 C. parapsilosis isolates, only 199 (37%) were susceptible to fluconazole and voriconazole; 44% (123/282) of fluconazole-resistant isolates were voriconazole cross-resistant. Factors associated with fluconazole non-susceptible C. parapsilosis infection on multivariable analysis included diagnosis in Gauteng province (aOR, 4.2; 95% CI, 2.7-6.7; P < 0.001), an ICU (aOR, 2.3; 95% CI, 1.5-3.6; P < 0.001) or the private sector (aOR, 2.2; 95% CI, 1.4-3.5; P < 0.001). CONCLUSIONS The dominance of triazole non-susceptible C. parapsilosis limits the choice of antifungal agents for management of candidaemia among critically ill neonates, children and adults in resource-limited South African hospitals.

Extensively drug-resistant Mycobacterium tuberculosis from aspirates, Rural South Africa.

The yield from aspirating lymph nodes and pleural fluid for diagnosing extensively drug-resistant (XDR) tuberculosis is unknown. Mycobacterium tuberculosis was cultured from lymph node or pleural fluid aspirates of 21 patients; 7 (33%) cultures grew XDR M. tuberculosis. Additive diagnostic yield for XDR M. tuberculosis was found in parallel culture of sputum and fluid aspirate.

Risk factors predicting complications in blood culture-proven typhoid fever in adults.

To create a prognostic model for complications of blood culture-proven typhoid fever in adults (]15 y old), a retrospective cohort was assembled though review of the medical records of the hospitalized patients treated for typhoid fever over a 3-y period ending January 1995. Of the 59 patients included, 21 (35.6%) developed various complications of typhoid fever. No patient included died. Four baseline variables (abdominal pain, systolic blood pressure B100 mmHg, hypoalbuminaemia B32 g/l and laboratory evidence of disseminated intravascular coagulation) were independently associated with complications and were used to create a prognostic model. The prediction accuracy of the model was determined using the concordance index (c-index). The results (c-index, 0.915 [95% CI, 89.0–93.0]) showed that the model predicted complications significantly better than chance. The model stratified patients into 3 prognostic stages: low risk for complications (0%; stage I), intermediate risk (42.9%; stage II) and high risk (92.3%; stage III) (p=0.001). If validated in other settings, it will help clinicians in predicting complications in patients with blood culture-proven typhoid fever on admission.To create a prognostic model for complications of blood culture-proven typhoid fever in adults (> or = 15 y old), a retrospective cohort was assembled though review of the medical records of the hospitalized patients treated for typhoid fever over a 3-y period ending January 1995. Of the 59 patients included, 21 (35.6%) developed various complications of typhoid fever. No patient included died. Four baseline variables (abdominal pain, systolic blood pressure < 100 mmHg, hypoalbuminaemia < 32 g/l and laboratory evidence of disseminated intravascular coagulation) were independently associated with complications and were used to create a prognostic model. The prediction accuracy of the model was determined using the concordance index (c-index). The results (c-index, 0.915 [95%, CI, 89.0-93.0]) showed that the model predicted complications significantly better than chance. The model stratified patients into 3 prognostic stages: low risk for complications (0%; stage I), intermediate risk (42.9%; stage II) and high risk (92.3%; stage III) (p = 0.001). If validated in other settings, it will help clinicians in predicting complications in patients with blood culture-proven typhoid fever on admission.