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•Epigenetic modifications alter gene expression patterns in patients with MDR TB and HIV-1 co-infection and HIV-1 positive.•Expression of HAT, HDAC, PtkAand PtpAgenes were substantially increased in HIV-1 infected than MDR TB-HIV co-infected.•Differential gene expression can be employed to produce new therapies and vaccines capable of eliminating co-infections.

ABSTRACTSouth Africa implemented Xpert MTB/RIF as the initial diagnostic test for pulmonary tuberculosis (TB). Xpert MTB/RIF's accuracy for diagnosing extrapulmonary tuberculosis (EPTB) was investigated. EPTB specimens (n= 7,916) from hospitalized patients received over a 6-month period at a high-throughput TB referral laboratory in Johannesburg were investigated. Large-volume specimens were centrifuged, tissue biopsy specimens homogenized, and all specimens checked for growth of contaminating bacteria on blood agar. Contaminated samples received NALC-NaOH (N-acetyl-l-cysteine–sodium hydroxide) decontamination prior to liquid culture. Residual specimens (volumes > 1 ml) after inoculation of culture (n= 1,175) were tested using the Xpert MTB/RIF sputum protocol. Using culture as the reference, Xpert MTB/RIF's overall sensitivity was 59% (95% confidence interval [95% CI], 53% to 65%) and specificity was 92% (CI, 90% to 94%), with the highest sensitivities of 91% (95% CI, 78% to 97%) for pus, 80% (95% CI, 56% to 94%) for lymph node aspirates, and 51% (95% CI, 44% to 58%) for fluids (ascitic, 59%; pleural, 47%). A difference in sensitivities was noticed between specimens classified as having a thick (87% [95% CI, 76% to 94%]) versus clear (watery) (48% [95% CI, 36% to 61%]) appearance. This was unchanged with traces of blood (52% [95% CI, 44% to 60%]) or precentrifugation (57% [95% CI, 28% to 82%]) among clear specimens. Xpert MTB/RIF generated an additional 124 specimen results that were contaminated by Mycobacterial Growth Indicator Tubes (MGIT; 10.5%) and diagnosed rifampin (RIF) resistance earlier (9.6% [25/260]). Xpert MTB/RIF's performance on EPTB specimens provides very promising results and should be considered for incorporation into national TB guidelines. Xpert MTB/RIF is less affected by contaminating bacteria and reduces laboratory labor and diagnostic delay compared to traditional methods.

ABSTRACTNumerous reports have documented isolated transmission events or clonal outbreaks of multidrug-resistant Mycobacterium tuberculosisstrains, but knowledge of their epidemic spread remains limited. In this study, we evaluated drug resistance, strain diversity, and clustering rates in patients diagnosed with multidrug-resistant (MDR) tuberculosis (TB) at the National Health Laboratory Service (NHLS) Central TB Laboratory in Johannesburg, South Africa, between March 2004 and December 2007. Phenotypic drug susceptibility testing was done using the indirect proportion method, while each isolate was genotyped using a combination of spoligotyping and 12-MIRU typing (12-locus multiple interspersed repetitive unit typing). Isolates from 434 MDR-TB patients were evaluated, of which 238 (54.8%) were resistant to four first-line drugs (isoniazid, rifampin, ethambutol, and streptomycin). Spoligotyping identified 56 different strains and 28 clusters of variable size (2 to 71 cases per cluster) with a clustering rate of 87.1%. Ten clusters included 337 (77.6%) of all cases, with strains of the Beijing genotype being most prevalent (16.4%). Combined analysis of spoligotyping and 12-MIRU typing increased the discriminatory power (Hunter Gaston discriminatory index [HGDI] = 0.962) and reduced the clustering rate to 66.8%. Resolution of Beijing genotype strains was further enhanced with the 24-MIRU-VNTR (variable-number tandem repeat) typing method by identifying 15 subclusters and 19 unique strains from twelve 12-MIRU clusters. High levels of clustering among a variety of strains suggest a true epidemic spread of MDR-TB in the study setting, emphasizing the urgency of early diagnosis and effective treatment to reduce transmission within this community.

ABSTRACTRecent cases of infections caused by glycopeptide-resistant enterococci (GRE) have highlighted the emergence of these organisms in the Republic of South Africa. During May 1998 we conducted a prevalence study in four hospitals in Johannesburg and obtained 184 rectal swabs from patients identified as being at high risk for GRE colonization. Twenty enterococcal isolates showing various glycopeptide resistance genotypes were recovered: 3 Enterococcus faecium vanAisolates, 10 E. faecium vanBisolates, 6 E. gallinarum vanC1isolates, and 1 E. avium vanAisolate. Macrorestriction analysis was used to demonstrate the clonal spread of GRE strains within hospitals. Evidence also demonstrated the likely persistence of the original E. faecium vanAisolate associated with the first confirmed death contributed to by GRE infection in South Africa in March 1997.

•Despite advanced diagnostic approaches for Mtb, sub-Saharan Africa with high HIV and TB co-infections continues to suffer.•Epigenetic mechanisms can be used in such co-infections to bypass host’s immune responses.•Epigenetic modifications in the expression profile of different genes in MDR TB-HIV co-infection patients was studied.•Modulation in gene expression can be used for diagnostic, drug and vaccine development in MDR TB-HIV co-infection patients.