A study to evaluate the hepatoprotective effect of N- acetylcysteine on anti tuberculosis drug induced hepatotoxicity and quality of life.

BACKGROUND: Drug induced liver injury (DILI) is a serious adverse effect caused by first-line anti-TB (ATT) drugs, limiting the TB-treatment. The tissue inflammation induced by free radical burst and poor dietary intake in TB induces oxidative stress, which was proposed as one of the mechanisms responsible for ATT induced DILI. N-acetylcysteine (NAC) exerts a hepato-protective effect by enhancing the cellular antioxidant defense mechanism. There are few studies evaluating the effect of NAC on ATT induced DILI in Indian-population. METHODS: This is a prospective, randomized, double-blind, placebo-controlled, parallel-group study. Thirty-eight newly diagnosed TB patients on first-line ATT with normal liver function test (LFT) were recruited and randomized to receive either NAC 600 mg tablet or placebo twice daily for 4 weeks and followed-up for next 4 weeks. LFT [AST, ALT, ALP and Total bilirubin] was assessed at baseline, 2, 4 and 8 weeks. Oxidative-stress biomarkers [Malondialdehyde (MDA), Nitric Oxide (NO), Glutathione (GSH)] and quality of life (QOL) by SF-36 questionnaire were assessed at baseline, 4 and 8 weeks. Adverse Drug Reactions (ADRs) were monitored at every visit. Compliance was assessed by pill-count method. RESULTS: Baseline characteristics were homogenous among both the groups. In the NAC group, there was significant reduction in ALT (p < 0.01), ALP (p < 0.01), total bilirubin (p < 0.001) at 4 weeks compared to baseline. AST, MDA and NO showed a reduction of 19%, 21.6% and 5.5% respectively from baseline and GSH at showed an increase of 2.6% from baseline at 4 weeks in the NAC group, however these were not statistically significant. These effects in LFT and oxidative biomarkers persisted even at the end of 8 weeks. Significant improvement from baseline in QOL was observed in both the groups (p < 0.05). Between group analysis showed, significant reduction in ALT (p < 0.05) and AST (p < 0.05) in NAC group at 4 weeks, whereas bilirubin, MDA, NO and GSH showed improvement at 4 weeks compared to placebo in NAC group, however it was not statistically significant. This improvement in the LFT and oxidative biomarkers continued even at the end of 8 weeks. Itching and rashes were the most common ADRs, with similar incidence in both the groups. Compliance to treatment was good in both the groups. CONCLUSION: Significant improvement in liver function parameters is suggestive of hepatoprotective effect of NAC. This observed effect at 4 weeks was found to be persistent at 8 weeks, which signifies prolonged hepato-protective effect of NAC. Long duration studies with large sample size are required for further confirmation of hepato-protective action of NAC.

Delayed onset renal failure in a patient on tenofovir based antiretroviral regimen.

Tenofovir is recommended as one of the first line agents in combination with other antiretroviral drugs for management of human immunodeficiency virus (HIV). It is known to cause renal failure after exposure for a median duration of 5 months. We report tenofovir induced adverse drug reaction in a 56-year-old female patient who was diagnosed to have HIV 1 infection since 10 years. The combination antiretroviral treatment included tenofovir, emtricitabine and ritonavir/lopinavir regimen since the last 6 years. She presented with recent onset renal failure and renal biopsy showed interstitial nephritis which could probably attributable to tenofovir.

Outbreak of scrub typhus in Andhra Pradesh--experience at a tertiary care hospital.

AIM: To describe the clinical features, laboratory manifestations, complications in patients diagnosed with scrub typhus at a tertiary care hospital in south India. MATERIAL AND METHODS: All cases of acute onset fever diagnosed to have scrub typhus August 2011 to December 2012 were analysed. Cases of scrub typhus confirmed by the well felix test with a titre of 1 in 80 or more and a positive immunochromatography test were studied. RESULTS: 176 confirmed cases of scrub typhus were studied over a period of 18 months. Majority (96%) of patients are from rural background. Farmers constituted 60% of the patients. Most common symptoms were due to the involvement of respiratory tract in the form of cough in 94 (53%) patients followed by breathlessness in 84 (47.7%). Signs of consolidation were seen in 80 (45.5%). Central nervous system involvement in the form of altered sensorium was seen in 43 (24.4%) and seizures in 11 (6.3%) patients. Eshcar was seen in 23 (13%) patients. Transaminases were elevated in 153 (86%) patients, serum alkaline phosphatase in 110 (62.5%) patients. Renal failure was seen in 49 (27.8%) cases and respiratory failure was seen in 11 (6.2%). Eight (4.5%) patients died in our study. CONCLUSION: Scrub typhus should be suspected in patients with rural background with fever and multi system involvement. The predominant symptoms were cough and breathlessness. Central nervous system abnormalities in the form of altered sensorium was seen in 43 (24.4%). Most common laboratory abnormality noted in our patients with scrub typhus was elevated liver enzymes which were seen in 153 (86%) cases.

A rare presentation of progressive disseminated histoplasmosis in an immunocompetent patient from a non-endemic region.

Histoplasmosis is an important systemic fungal infection in endemic areas. In India, the disease has been reported from several parts of the country, most cases being from eastern India considered to be endemic for the disease. There have been very few cases reported from the state of Andhra Pradesh, in the southern part of India. We report a case of progressive disseminated histoplasmosis presenting with bleeding manifestations in an immune competent patient from the state of Andhra Pradesh.

Immune reconstitution and inflammatory syndrome due to disseminated tuberculosis in a case of human immunodeficiency virus 2 infection.

We present a case of human immunodeficiency virus 2 (HIV- 2) infection with acquired immune deficiency syndrome with immune reconstitution and inflammatory syndrome due to disseminated tuberculosis. We address here the drug interactions between antiretroviral therapy and antituberculous treatment (ATT), choice of ATT, and duration of ATT when rifampicin is omitted as in our case. Though this problem is encountered rarely, we felt that it is important to report the issue to counter drug resistance in tuberculosis and HIV.

Emergence of dengue virus type 4 (genotype I) in India.

Dengue is an emerging arboviral disease and currently poses the greatest arboviral threat to human health. In recent decades, there has been a substantial increase in dengue outbreaks in many parts of the world including India. We performed an in-depth investigation of a major dengue outbreak in Andhra Pradesh, southern India in 2007 by serology, virus isolation, RT-PCR and genotyping. The results revealed an unusual emergence of dengue virus type 4 (DENV-4) along with the prevailing DENV-3. Phylogenetic analysis based on complete envelope gene of 182 globally diverse DENV-4 isolates demonstrated the involvement of a unique clade of genotype I of DENV-4 in the outbreak. This study also demonstrated a clear shift in the dominant serotype from DENV-3 to DENV-4 in India. This is the first report regarding the molecular characterization of Indian isolates of DENV-4, which has the potential to be involved in future outbreaks.

Methyl ethyl ketone peroxide ingestion: a rare cause of corrosive chemical poisoning.

Methyl ethyl ketone peroxide, commonly used in the lamination industry, is a highly inflammable substance. Ingestion of methyl ethyl ketone peroxide is associated with a high morbidity and mortality. It can cause injury to the gastrointestinal tract on ingestion, leading to gangrene or perforation. Gastric lavage is contraindicated as it is a highly corrosive substance. We report a patient with poisoning due to methyl ethyl ketone peroxide who presented with upper gastrointestinal bleeding, and developed gangrene of the bowel and died of septicaemia and multiorgan failure.

Clinical features and molecular diagnosis of Chikungunya fever from South India.

An epidemic of Chikungunya fever of unprecedented magnitude occurred in many parts of India in early 2006 after an interval of 33 years, and there has been a resurgence in some parts of South India since June 2007. The article highlights clinical manifestations of infection and various molecular tests that were used for diagnoses of Chikungunya virus infection. Of particular interest is the real-time loop-mediated isothermal amplification (RT LAMP) assay, which is rapid and cost-effective and can be adopted at ill-equipped laboratories. Clinical symptoms were characterized by a triad of fever, rash, and severe rheumatic manifestations. RT LAMP identified 20 additional Chikungunya virus-positive cases, compared with reverse-transcriptase polymerase chain reaction. Chikungunya virus was isolated from 20 randomly selected samples. Genotyping of the virus isolates revealed that the East Central South African genotype of Chikungunya virus was the etiologic agent of this epidemic. Molecular diagnosis is an important tool to identify such new vectorborne viral illnesses.