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Biomedical subjects

L Blumberg

Publications and source records attributed to L Blumberg.

At least 19 recordsLinked to original sources

Rapid indication of multidrug-resistant tuberculosis from liquid cultures using FASTPlaqueTB-RIF, a manual phage-based test.

SETTING: A Mycobacteriology Reference Laboratory in Johannesburg, South Africa. OBJECTIVE: To determine the ability of FASTPlaqueTB-RIF, a rapid bacteriophage-based test, to correctly identify rifampicin susceptibility in clinical strains of Mycobacterium tuberculosis after growth in the Bactec 460 semi-automated liquid culture system. DESIGN: A comparative study of FASTPlaqueTB-RIF and conventional drug susceptibility methods, with selection bias to include sufficient rifampicin-resistant strains. RESULTS: Rifampicin susceptibility results were available for 133 strains of M. tuberculosis. Using the Bactec 460 method, 42 of these strains were rifampicin-resistant and 91 strains were rifampicin-susceptible. A further one strain was found to have a mutation in the rpoB gene which was strongly indicative of rifampicin resistance. Sensitivity, specificity and overall accuracy for the FASTPlaqueTB-RIF were respectively 100%, 98.8% and 99.2% for detection of rifampicin resistance; 95.3% (41/43) of the rifampicin-resistant strains were also resistant to isoniazid (multidrug-resistant). CONCLUSION: FASTPlaqueTB-RIF offers performance comparable to the Bactec 460 method, with results available within 2 days and without the need for specialised equipment. This makes FASTPlaqueTB-RIF a rapid test for rifampicin resistance suitable for widespread application. A combination of the FAST-PlaqueTB-RIF test with semi-automated liquid culture reduces the time required to report susceptibility results, enabling rapid and appropriate management of patients with MDR-TB. Rifampicin resistance was a good predictor of multidrug resistance in this population.

Antibiotics, Antitubercular↗

Utility of blood cultures and incidence of mycobacteremia in patients with suspected tuberculosis in a South African infectious disease referral hospital.

SETTING: A 500-bed government referral institution for patients with tuberculosis and other infectious diseases in Gauteng, South Africa. OBJECTIVES: To assess the usefulness of BACTEC blood cultures over and above that of other microbiological methods for the diagnosis of tuberculosis in patients who are suspected of suffering from tuberculosis. DESIGN: Mycobacterial blood cultures were obtained from patients presenting with symptoms suspicious of tuberculosis and where there was no clinical evidence of other infectious etiologies, and from patients who had failed tuberculosis treatment. RESULTS: Sixteen (22%) of 71 patients included in the study were positive for Mycobacterium tuberculosis on blood culture, while seven (10%) were positive for M. avium complex (MAC). Twelve (75%) of the patients with tuberculosis and positive blood cultures were however also positive for acid-fast bacilli on sputum smears and eight (50%) were initially diagnosed clinically and radiographically as localized pulmonary tuberculosis. Blood cultures positive for mycobacteria were only found among patients with human immunodeficiency virus infection (HIV). CONCLUSIONS: Bacteremia with M. tuberculosis complex was detected in HIV-infected patients with suspected tuberculosis, even in patients presenting with localized pulmonary infection on initial clinical assessment. Among patients with suspected tuberculosis, blood cultures were useful in diagnosing unsuspected MAC disease, but did not add to the diagnostic yield of conventional tests for tuberculosis used routinely, namely sputum microscopy and culture, or occasional biopsy specimens.

AIDS-Related Opportunistic Infections↗

Evaluation of FASTPlaqueTB-RIF, a rapid, manual test for the determination of rifampicin resistance from Mycobacterium tuberculosis cultures.

SETTING: Two Mycobacteriology Reference Laboratories in Johannesburg (Laboratory 1) and Cape Town (Laboratory 2), South Africa. OBJECTIVE: To determine the ability of the FASTPlaqueTB-RIF test to correctly identify rifampicin susceptibility on strains of Mycobacterium tuberculosis cultured on solid media. DESIGN: A comparative study of FASTPlaqueTB-RIF and conventional drug susceptibility methods, with selection bias to include sufficient rifampicin resistant strains. RESULTS: Rifampicin susceptibility results were available for 191 strains of M. tuberculosis. Eighty-one strains were found to be rifampicin resistant and 110 strains were rifampicin susceptible by conventional methods. The sensitivity, specificity and overall accuracy for the FASTPlaqueTB-RIF were 100%, 97% and 98% at Laboratory 1, and 100%, 94% and 97% at Laboratory 2. CONCLUSION: FASTPlaqueTB-RIF offers a performance comparable to the gold standard proportion methods of rifampicin susceptibility testing, as well as the advantage of the speed of results that the newer methods deliver, without the need for specialised equipment. This makes FASTPlaqueTB-RIF a rapid test for rifampicin resistance suitable for widespread application.

Africa, Southern↗

Characterisation of the pncA gene in Mycobacterium tuberculosis isolates from Gauteng, South Africa.

SETTING: The use of pyrazinamide (PZA) is important for the treatment of Mycobacterium tuberculosis as it is bactericidal to semi-dormant mycobacteria that are not affected by other drugs. The incidence of resistance to PZA and other drugs used in the treatment of M. tuberculosis is increasing in South Africa. OBJECTIVE: To characterise the pncA gene of M. tuberculosis isolates from Gauteng, South Africa, and to develop a rapid diagnostic method. DESIGN: The pncA gene and the putative regulatory gene were characterised by sequence analysis in a total of six PZA susceptible and 15 resistant isolates. The association with classical PZA susceptibility testing and PZase activity was determined. RESULTS: All PZA-resistant isolates were PZase negative as well as resistant to at least one other anti-tuberculosis drugs. Mutations were identified throughout the length of the pncA gene in 10/15 PZA-resistant isolates. Five lacked PZase activity, but the wild type pncA sequence was present. In all six PZase-positive strains, a PZA-susceptible pattern was obtained on BACTEC and the wild type pncA sequence was present. CONCLUSION: Sequencing is an effective means to identify mutations in the pncA gene in M. tuberculosis and therefore resistance to PZA. The fact that some PZA-resistant M. tuberculosis isolates lack mutations in the pncA gene suggests that alternative mechanisms for drug resistance exist. In PZase negative strains with no genetic changes which are resistant to 100 microg/ml and susceptible to 300 microg/ml, 300 microg/ml may be a more reliable breakpoint.

Africa, Southern↗

A comparison of outbreak- and nonoutbreak-related multidrug-resistant tuberculosis among human immunodeficiency virus-infected patients in a South African hospital.

Nosocomial multidrug-resistant tuberculosis (MDR-TB) in human immunodeficiency virus (HIV)-infected people is recognized in Europe and America. We report the first such outbreak in South Africa. Six hospitalized women, identified by DNA fingerprinting, were infected with an outbreak strain of MDR-TB while receiving treatment for drug-susceptible tuberculosis. The putative source case was identified as an HIV-positive woman who underwent prolonged hospitalization for chronic cavitary tuberculosis. Compared with other HIV-positive patients in the hospital, outbreak patients were more immunocompromised, had fewer cavitary lung changes, and were less likely to have been treated before. They had high fevers, infiltrative patterns on chest radiographs, and a mean survival of 43 days. When individual isolation is not possible, separating highly immunocompromised patients with first-time tuberculosis from previously treated patients with cavitary lesions and from those with established drug resistance may reduce nosocomial transmission.

AIDS-Related Opportunistic Infections↗

Nontuberculous mycobacteria: defining disease in a prospective cohort of South African miners.

A gold mining work force was followed prospectively over 1 yr for sputum nontuberculous mycobacterial (NTM) isolates. NTM were isolated from 118 men, of whom 32 (27%) met the American Thoracic Society (ATS) case-definitions for pulmonary NTM disease (23 M. kansasii, seven M. scrofulaceum, one M. avium, and one M. abscessus). Determining isolate significance was difficult because most men had been started on presumptive TB treatment before isolate identification (70%). Histologic criteria were considered inappropriate for this high M. tuberculosis incidence population, particularly for patients who had stabilized on presumptive TB treatment. Among men not meeting case-definitions, indicators of disease were significantly more prevalent for M. kansasii than for M. fortuitum, the local laboratory contaminant (ORs: 6.5 for cough, 7. 2 for smear-positivity, 36.0 for radiologic changes, and 14.3 for presumptive TB treatment), suggesting underdiagnosis of M. kansasii disease. Of 53 men with definite or possible M. kansasii disease, 18 (34%) were HIV-positive. HIV-associated M. kansasii disease occurred at an early stage of immunosuppression (median CD4 count, 381 x 10(6)/L) with a good outcome (83% cured after 12 mo of treatment). ATS case-definitions for NTM disease are difficult to apply in this population, and treatment decisions should be guided by the pathogenic potential of the isolate.

Adult↗

Acute HIV seroconversion illness presenting as African viral haemorrhagic fever.

BACKGROUND: Both human immunodeficiency virus type 1 (HIV-1) and African viral haemorrhagic fever (VHF) viruses cause similar symptoms in acutely infected individuals and must be included in the differential diagnosis in areas where HIV-1 and VHF viruses both occur. OBJECTIVES: To determine the cause of an acute illness in a patient at risk of exposure to both HIV-1 and African VHF viruses. RESULTS: Serological examination revealed the presence of high levels of the p24 core antigen of HIV-1 in the absence of antibodies to HIV-1 in a specimen collected during the acute stage of the infection. On follow-up, the antigen enzyme-linked immunosorbent assay (ELISA) became negative while the antibody ELISA and confirmatory Western blot for HIV-1 became positive. CONCLUSIONS: Acute HIV seroconversion illness may have protean manifestations and, in the more severe forms, may cause diagnostic dilemmas, particularly in regions where African VHFs occur.

Journal Article↗

Predictors of mortality in severe malaria: a two year experience in a non-endemic area.

Management of severe malaria is an increasing problem worldwide. This paper reviews the pathophysiology and management documenting two years' experience of admissions of severe malaria to an ICU in a non-endemic area. Clinical and laboratory features of severe malaria were analysed for predictors of mortality Twenty-eight patients had clinical or laboratory features compatible with the WHO criteria for severe malaria and, despite treatment with intravenous quinine and supportive ICU care, mortality was 28.5% (8/28). The three pregnant patients died with 100% foetal mortality and the four paediatric patients survived. Of the non-survivors, 8/8 developed ARDS (defined by worst ALI score > 2.5), 7/8 developed shock requiring inotropic support and 7/8 developed acute renal failure requiring CVVHD. Admission haemoglobin, platelet count, parasite count, and lowest Glasgow Coma Score in the first 24 hours were shown not to be predictors of mortality.

Acute Kidney Injury↗