Genotyping and drug resistance patterns of M. tuberculosis strains in Pakistan

<p>Abstract</p> <p>Background</p> <p>The incidence of tuberculosis in Pakistan is 181/100,000 population. However, information about transmission and geographical prevalence of <it>Mycobacterium tuberculosis </it>strains and their evolutionary genetics as well as drug resistance remains limited. Our objective was to determine the clonal composition, evolutionary genetics and drug resistance of <it>M. tuberculosis </it>isolates from different regions of the country.</p> <p>Methods</p> <p><it>M. tuberculosis </it>strains isolated (2003–2005) from specimens submitted to the laboratory through collection units nationwide were included. Drug susceptibility was performed and strains were spoligotyped.</p> <p>Results</p> <p>Of 926 <it>M. tuberculosis </it>strains studied, 721(78%) were grouped into 59 "shared types", while 205 (22%) were identified as "Orphan" spoligotypes. Amongst the predominant genotypes 61% were Central Asian strains (CAS ; including CAS1, CAS sub-families and Orphan Pak clusters), 4% East African-Indian (EAI), 3% Beijing, 2% poorly defined TB strains (T), 2% Haarlem and LAM (0.2). Also TbD1 analysis (<it>M. tuberculosis </it>specific deletion 1) confirmed that CAS1 was of "modern" origin while EAI isolates belonged to "ancestral" strain types.</p> <p>Prevalence of CAS1 clade was significantly higher in Punjab (P < 0.01, Pearsons Chi-square test) as compared with Sindh, North West Frontier Province and Balochistan provinces. Forty six percent of isolates were sensitive to five first line antibiotics tested, 45% were Rifampicin resistant, 50% isoniazid resistant. MDR was significantly associated with Beijing strains (P = 0.01, Pearsons Chi-square test) and EAI (P = 0.001, Pearsons Chi-square test), but not with CAS family.</p> <p>Conclusion</p> <p>Our results show variation of prevalent <it>M. tuberculosis </it>strain with greater association of CAS1 with the Punjab province. The fact that the prevalent CAS genotype was not associated with drug resistance is encouraging. It further suggests a more effective treatment and control programme should be successful in reducing the tuberculosis burden in Pakistan.</p

Postprandial hyperglycaemia: Red herring or red flag?

Several studies have suggested that postprandial rather than fasting hyperglycaemia may be a major determinant of cardiovascular risk. This article reviews the importance of postprandial hyperglycaemia and explores the benefits and risks of managing postprandial hyperglycaemia aggressively in order to prevent diabetes-related complications

Severe asymptomatic non-alcoholic fatty liver disease in routine diabetes care; a multi-disciplinary team approach to diagnosis and management.

OBJECTIVES: To prospectively use a non-invasive algorithm to identify asymptomatic, advanced non-alcoholic fatty liver disease (NAFLD) in a secondary care diabetes clinic and to determine the short-term effect of a multi-disciplinary team (MDT) approach in a liver clinic. RESEARCH DESIGN AND METHODS: NAFLD Fibrosis Score (NFS) was calculated in 64 asymptomatic patients with type 2 diabetes. Advanced fibrosis was identified using transient elastography and confirmed with liver biopsy. In a subsequent retrospective study, 95 patients newly referred to the NAFLD MDT clinic were investigated and the impact of the MDT approach assessed. RESULTS: 25/64 (39.0%) of patients with diabetes had a low NFS (&lt;-1.455). 39/64 (61.0%) patients had a high or indeterminate NFS and were referred for review in the NAFLD MDT clinic, of which 23/39 attended for assessment. 19/23 (82.6%) were diagnosed with NAFLD, of which 6/19 (31.6%) patients had a positive transient elastography (≥8 kPa). Liver biopsy confirmed advanced fibrosis in 5/6 cases, with moderate fibrosis in 1 case. In the retrospective study, 65/95 (68.4%) new referrals to the NAFLD MDT clinic had a diagnosis of NAFLD. Over a median 98 days (IQR 70-182) follow-up, there was a significant improvement in weight (-0.8 kg; P = 0.024), total cholesterol (-0.2 mmol/L; P = 0.044), ALT (alanine transmaminase, -12.5 IU/L; P &lt; 0.001) and GGT (gammu-glutamyl transferase, -13.0 IU/L; P &lt; 0.0001). 7/28 (25%) of patients with diabetes achieved &gt;5% weight loss. CONCLUSIONS: A significant proportion of asymptomatic patients attending type 2 diabetes clinics have undiagnosed advanced NAFLD fibrosis. An MDT approach to NAFLD results in short-term improvements in metabolic and liver parameters