Prasanta Kumar Bhattacharya

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.

Scrub typhus meningoencephalitis, a diagnostic challenge for clinicians: A hospital based study from North-East India

Central nervous system (CNS) involvement is a known complication of scrub typhus which range from mild meningitis to frank meninigoencephalitis. Aims and objectives: To study the clinical feature, laboratory parameters and response to treatment of scrub typhus meningitis/meningoencephalitis. Methods and Materials: This is a hospital based prospective observational study from North Eastern India. Diagnosis was based on clinical features and positive serological test (Weils Felix test and IgM antibody card test). Results: 13 patients of scrub typhus with features of meningitis/meningoencephalitis were included. The mean duration of fever before presentation was 5.61±3.08 days and 4 (30.76 %) patients had eschar. Altered sensorium, headache, seizure and meningeal sign were present in 13 (100%), 13 (100%), 6 (46.15%) and 10 (76.92%) patients respectively. Mean CSF protein, glucose and Adenosine deaminase was 152.16±16.88mg/dl, 55.23±21.7mg/dl, and 16.98±7.37U/L respectively. Mean total count of CSF leukocyte and lymphocyte percentage was 46.07±131 cell/cumm and 98.66±3.09% respectively. Tablet doxycycline with or without injection azithromycin was used and that shows good response 15.38% of patients died and all of them had multi organ dysfunction. Conclusion: Meningoencephalitis is a common manifestation of scrub typhus and diagnosis requires high degree of clinical suspicion which if diagnosed early and specific treatment started, patients usually recover completely with few complications.

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.

SLE and Tuberculosis: A Case Series and Review of Literature

Systemic Lupus Erythematosus (SLE) and Tuberculosis (TB) are intricately related with an increase in the risk of TB in SLE. Primary mechanisms pertaining to the increased susceptibility for TB are the inherent immunodeficient state of SLE and use of immunosuppressant agents in the treatment of SLE. We report a case series of five female patients of SLE with TB who presented between January 2015 and December 2015 in a tertiary care teaching hospital in North Eastern India. All the patients were young to middle aged females having SLE with or without lupus nephritis who were on immunosuppressive therapy with corticosteroids, mycophenolate mofetil or cyclophosphamide. Two of the cases had sputum positive pulmonary tuberculosis while rest had Extra-Pulmonary TB (EPTB). The response to anti-tubercular therapy led to clinical improvement in all the cases except one who had an adverse outcome. Our series further substantiates the increased risk of TB in SLE thus, prompting further research towards better management of these two disease entities in conjunction.

A Rare Case of Pulmonary Lymphangitic Carcinomatosis in a Young Adult with Carcinoma Stomach

Pulmonary Lymphangitic Carcinomatosis (PLC) occurs in about 6-8% of patients with lung metastasis and may rarely develop in the course of gastric cancer representing a complication due to diffuse metastasis in the lymphatics of the lungs. A 29-year-old female, admitted with difficulty in breathing and productive cough for one week, was initially evaluated for respiratory tract infection. During evaluation of associated anaemia an upper gastrointestinal endoscopy showed large ulcerative growth in the lesser curvature of the stomach suggestive of carcinoma. A High Resolution Computed Tomographic (HRCT) scan of the lungs was done for evaluation of the pulmonary opacities on chest x-ray which showed nodular thickening of interlobular septa with peribronchial cuffing and fissural thickening. The biopsy of the gastric ulcer was suggestive of poorly differentiated malignancy. With the cumulative results of the investigations a diagnosis of poorly differentiated carcinoma of stomach with pulmonary metastasis as lymphangitic carcinomatosis was made. PLC is an extremely rare manifestation of metastatic gastric cancer. Though associated with an extremely poor prognosis, advanced gastric cancer in younger patients presenting with symptoms and signs of respiratory disease should alert the physician of a possible diagnosis of PLC.

Acute Pancreatitis in a Patient with Complicated Falciparum Malaria.

Malaria is one of the most common protozoan diseases, especially in tropical countries. The clinical manifestation of malaria, especially falciparum malaria varies from mild acute febrile illness to life threatening severe systemic complications involving one or more organ systems. We would like to report a case of complicated falciparum malaria involving cerebral, renal, hepatic system along with acute pancreatitis. The patient was successfully treated with anti malarial and other supportive treatment. To the best of our knowledge there are very few reports of acute pancreatitis due to malaria. Falciparum malaria therefore should be added to the list of infectious agents causing acute pancreatitis especially in areas where malaria is endemic.

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.