Aakash Roy

Tuberculosis and Diabetes Mellitus: A Double Whammy for the Developing Nations

With one-third of the estimated global population having tuberculosis and 10 million new cases added yearly, tuberculosis remains a persistent global public health problem requiring urgent attention. India has the highest tuberculosis burden (2.1 million new cases and 280,000 deaths annually) with the second largest diabetic population of the world. Nearly 40-50% adult population in India have tuberculosis infection; primary infection reactivates to clinical disease in 5-10% individuals, rest remaining latent. Conversion from latent to active disease is mainly due to underlying immunodeficiency states, diabetes being a pre-eminent cause. Tuberculosis and diabetes interact with each other at multiple levels. Diabetes triples the risk of tuberculosis. An estimated 15% of adult TB worldwide is attributed to diabetes. India and China together account for >40% of all diabetes associated tuberculosis cases; diabetes accounts for 14.8% of overall pulmonary and 20.2% smearpositive tuberculosis. Diabetic tuberculosis patients on anti-tubercular treatment (ATT) remain contagious longer than non-diabetics on ATT. Tuberculosis itself can lead to impaired glucose tolerance and overt diabetes. Moreover, certain anti-tubercular drugs interact with oral anti-diabetics, making diabetes control difficult. Development of universal, cost effective bi-directional screening methods for tuberculosis in diabetics and viceversa could improve outcome of both diseases. However, universal screening for diabetes alone is not feasible in developing nations; additional screening for tuberculosis or bi-directional screening would be an extra burden. Certain measures, based on context of local health systems and availability of resources can be adopted: (i) tuberculosis surveillance among diabetics in regions with medium to high tuberculosis burden; (ii) assessing costeffectiveness of universal tuberculosis screening in all diabetics; (iii) establishing dedicated referral system for diabetics with suspected tuberculosis to specialized centers; (iv) screening tuberculosis patients for diabetes at the start of ATT; (v) research in developing more effective treatment strategies for concurrent tuberculosis and diabetes.

Management of Hepatitis C in the Indian Context: An Update

Hepatitis C, a leading cause of chronic liver disease globally, is caused by Hepatitis C Virus (HCV), a hepatotropic RNA virus. HCV infection starts with an acute infection, mostly subclinical, which ultimately leads to chronic hepatitis in about 80% of the infected cases. HCV is classified into 6 major genotypes and numerous subtypes. The global prevalence of HCV infection is about 1.6% with a majority of these infections being in adults. There is widespread heterogeneity in the prevalence of different genotypes of HCV in different geographical regions of the world. While genotype 1 is the most common worldwide, different regions of the world report variations in the prevalence of the other genotypes. Genotype 3 is the commonest genotype in India, but there is a wide variation in the distribution of the other genotypes in different parts of the country; genotype 6, a comparatively rarer genotype, has been reported frequently from the northeast part of India. With the introduction of new oral drugs, the Directly Acting Antivirals (DAA), the management protocols of hepatitis C has undergone dramatic transformation, with a paradigm shift towards an all-oral interferon-free regimen. However, developing countries like India still face a challenge with respect to accessibility and affordability of such newer regimens. Furthermore, the differences in genotypic distributions in India, with a higher prevalence of genotype 3, which is more difficult to treat, makes the situation even more challenging. As newer antivirals are being universally used to manage HCV infection, economically weaker countries like India should incorporate these changes in treatment guidelines soon. However, till substantial evidence on the efficacy of the newer regimens is accrued in the Indian population, and issues on cost and accessibility are addressed, it may not yet be prudent enough to altogether discard the existing conventional modes of HCV therapy.

Frequency of Cyp2c93* allele in patients with type 2 diabetes mellitus on sulfonylurea therapy -

Background: Sulfonylureas are mainstay of pharmacotherapy for type 2 diabetes mellitus (T2DM). Individual variability exists in pharmacokinetic and pharmacodynamic responses adverse effects to sulfonylurea. Objective: To determine frequency of cytochrome P450 2C9 mutant allele CYP2C93*, in T2DM patients on sulfonylurea therapy, and to ascertain the frequency of adverse drug reactions (ADR) with respect to particular allelic distribution. Materials and Methods: A hospital-based prospective observational study was carried out in a tertiary-care teaching hospital. Study included 136 T2DM patients on sulfonylurea therapy (83 with ≥1 ADR and 53 without ADR). DNA was isolated from the blood samples taken from all 136 patients by DNA isolation. PCR-RFLP (restriction fragment length polymorphism) technique was used for detection of CYP2C93* (Ile359Leu) allele and the wild type allele CYP2C91* by digestion with restriction enzyme. Data were analyzed using Statistical Package for Social Survey (SPSS) for Windows, version 16.0 and Microsoft Excel to determine descriptive statistics. Result: Allele CYP2C93* was detected in 11 patients. All alleles negative for the nucleotide substitutions at position 42614 (*3) were presumed to be wild type CYP2C9*1. Among the patients with CYP2C93* allele 11 patients experienced hypoglycemia and one patient experienced acute visual disturbances. No CYP2C93* was detected in the subjects without ADR. Conclusion: In our study CYP2C93* was identified in 11 patients experiencing hypoglycaemia and in one patient experiencing acute visual disturbances. In view of the existence of such polymorphisms and its effects on sulfonylurea therapy further studies are required to assess the magnitude of such problems in T2DM.

Lupus Pneumonitis Masquerading as Pulmonary Tuberculosis A Case Study

Introduction: Systemic Lupus erythematosus (SLE) is characterized by production of antibodies against various cellular antigens derived from nucleus, cytoplasm and cell membrane. Pulmonary manifestations of SLE can include a wide spectrum of diseases such as pleuritis, pneumonia, pulmonary embolism, pneumothorax and pulmonary haemorrhage. Acute lupus pneumonitis may mimic tuberculosis or other acute infectious pneumonia and the incidence varies from 0.9% to 11.7%. We report a case of lupus pneumonitis in a case of SLE mimicking pulmonary tuberculosis. Case: An 18 year old girl presented with history cough with expectoration with occasional haemoptysis. She also had history of fever, swelling of hands and feet along with hair loss. On examination she was febrile and dyspneic, with moderate to severe anaemia, tachycardia, tachypnoea, and coarse crepitations over the chest. Sputum for acid fast bacilli, bacterial culture and fungal stains were negative. She was initially treated with broad spectrum antibiotics and then empirically with anti-tubercular therapy (ATT). However, as she failed to respond to ATT, further evaluation was done. Anti-nuclear antibodies and ds DNA were strongly positive. Urine analysis showed nephrotic range proteinuria. High resolution computed tomogram of the chest showed bilateral ground glassing suggestive of lupus pneumonitis (LP). A diagnosis of SLE with LP was made and the patient was put on corticosteroids which led to a dramatic response. Conclusion: SLE has a wide facade of presentations. Keeping this in mind, even in countries where tuberculosis is endemic, the differential diagnosis of SLE and LP should always be considered even where the clinical features and chest X-rays findings are suggestive of pulmonary tuberculosis.