Tumour necrosis factor-alpha and nitric oxide response in different categories of tuberculosis patients.

OBJECTIVE: To compare the magnitude of tumour necrosis factor alpha (TNF-α) and nitric oxide (NO) response in different categories of active tuberculosis (TB) patients by ex vivo experiment. DESIGN: New, relapsed (recurrent), miliary and pleural effusion TB cases were recruited with matched healthy controls. TNF-α and NO were measured from the culture supernatant of peripheral blood monocytes derived from cases and controls with and without challenge with live Mycobacterium tuberculosis H37Rv. RESULTS: TNF-α and NO production varied significantly among the different categories of TB patients. The magnitude was highest among patients with pleural effusion and lowest in miliary TB cases. In between, progressive decreases in response were noted in new and relapse cases. Overall, positive correlations between TNF-α and NO were noted among the diseased and healthy groups. CONCLUSION: Distinct TNF-α and NO levels appear to be associated with different clinical forms of TB and might help to assess prognosis and contribute to a better understanding of underlying immunopathological mechanisms.

Clinicopathological study of gall bladder carcinoma with special reference to gallstones: our 8-year experience from eastern India.

Gallbladder carcinoma (GBC) is the commonest cancer of the biliary tree and the most frequent cause of death from biliary malignancies. The incidence of GBC shows prominent geographic, age, race, and gender-related differences and is 4-7 times higher in patients with gallstones. This prompted us to study the clinicopathological aspects of the disease and the incidence of gallstones in gallbladder carcinoma patients, in this part of India. In this, combined retrospective (Jan 2004-March 2010) and prospective study (April 2010-Dec 2011) of eight years, 198 patients of gallbladder carcinoma (50 males and 148 females), (range 28-82 years; mean 55 years) were studied. Most of the patients were poor and presented with abdominal pain and mass, with abnormal lab parameters. Gallstones were present in 86% of patients. Surgical exploration was performed in 130, with gallbladder resection in 60 (including 7 incidental GBC). Adenocarcinoma (87.7%) was the commonest histological type. The study indicates that GBC is common in our scenario. It is a disease of elderly females, has a strong association with gallstones and every cholecystectomy specimen should be examined histopathologically.

In vitro activity of gentamicin and amikacin against Salmonella enterica serovar Typhi: a search for a treatment regimen for typhoid fever.

The emergence of Salmonella enterica serovar Typhi isolates resistant to ciprofloxacin and 3rd-generation cephalosporins is a concern for physicians in developing countries. This study assessed the in vitro activity of gentamicin and amikacin against 464 S. entenca serovar Typhi isolates obtained from blood of patients clinically suspected of enteric fever who attended the Calcutta School of Tropical Medicine from 1991 to 2003. The isolates were sensitive to gentamicin and amikacin, showing minimum inhibitory concentrations 0.01-4 microg/mL and 0.005-3.5 microg/mL respectively. Both agents showed bactericidal activity at concentrations of 2 microg/mL after incubation for 6 hours. Aminoglycoside antibiotics such as gentamicin and amikacin may thus be introduced as a treatment regimen for typhoid fever.

In vitro activity of gentamicin and amikacin against Salmonella enterica serovar Typhi: a search for a treatment regimen for typhoid fever

The emergence of Salmonella enterica serovar Typhi isolates resistant to ciprofloxacin and 3rd-generation cephalosporins is a concern for physicians in developing countries. This study assessed the in vitro activity of gentamicin and amikacin against 464 S. enterica serovar Typhi isolates obtained from blood of patients clinically suspected of enteric fever who attended the Calcutta School of Tropical Medicine from 1991 to 2003. The isolates were sensitive to gentamicin and amikacin, showing minimum inhibitory concentrations 0.01-4 microg/mL and 0.005-3.5 microg/mL respectively. Both agents showed bactericidal activity at concentrations of 2 microg/mL after incubation for 6 hours. Aminoglycoside antibiotics such as gentamicin and amikacin may thus be introduced as a treatment regimen for typhoid fever

Restoration of impaired free radical generation and proinflammatory cytokines by MCP-1 in mycobacterial pathogenesis.

Mycobacterium tuberculosis exerts its pathogenic effects mainly via its cell wall glycolipid called Mannosylated Lipoarabinomannan (Man-LAM), which subverts the cellular inflammatory responses by the suppression of superoxide anion generation in earlier hours, and nitric oxide (NO) generation at later hours of pathogenic invasion. In this paper, we have shown the prophylactic effect of C-C chemokines, both in vitro and in vivo. Exogenous administration of C-C chemokines, particularly monocyte chemoattractant protein (MCP)-1, led to the induction of superoxide anion generation via the restoration of impaired protein kinase C (PKC) signalling in Man-LAM-treated macrophages. Monocyte chemoattractant protein-1 could also potently induce NO generation by upregulation of the proinflammatory cytokines tumour necrosis factor-alpha and interleukin-12 from Man-LAM-treated macrophages accompanied by inhibition of anti-inflammatory responses. Our in vivo observations clearly exhibited effective restoration of impaired PKC signalling as well as proinflammatory cytokine expression by MCP-1 in Man-LAM treated as well as M. tuberculosis H37Rv-infected C57BL/6 mice. We also observed, as direct evidence, that MCP-1 induced a significant reduction of the number of viable tubercle bacilli in the lungs and spleen of infected mice. Collectively, our findings strongly suggest the effectiveness of MCP-1 as a potent immunoprophylactic tool for controlling the mycobacterial establishment within the host.

Antibiotic resistance of Salmonella enterica serovar Paratyphi A in India: emerging and reemerging problem.

BACKGROUND: Antibiotic resistance pattern and R-plasmid of Salmonella enterica serovar Paratyphi A isolates from Kolkata, India are not well documented. AIMS: To determine the trend of antibiotic resistance of S. paratyphi A isolates. SETTINGS AND DESIGN: A retrospective study was carried out using blood culture isolates of S. paratyphi A (1991 to 2005) obtained from patients of enteric fever from Asansol and Kolkata and its suburbs (India). MATERIALS AND METHODS: Antibiotic susceptibility pattern, using seven antibiotics, for the isolates was determined following agar dilution and disk diffusion methods. Transferability of multidrug resistance to ampicillin (Am), chloramphenicol (Chl), cotrimoxazole (Cot) and tetracycline (Tet) among the isolates was determined by in vitro conjugation. The multi-drug resistant (MDR) and antibiotic susceptible S. paratyphi A strains and the trans-conjugants were screened for the presence of plasmid. STATISTICAL ANALYSIS USED: The t test was used to compare the difference between mean minimum inhibitory concentration values of ciprofloxacin (Cp) for nalidixic acid (Nx)-resistant and Nalidixic acid (Nx)-susceptible isolates. RESULTS: Among 13 outbreak causing isolates in 1991, 9 (69.23%) showed AmChlCotTet-resistance, while 4 (30.77%) Cot-resistance only. During 1992-1994, all 13 isolates were susceptible to Am, Chl, Cot and Tet. During 1995-2005, isolates demonstrated different resistance patterns and emergence of nalidixic acid (Nx)-resistance. A transferable plasmid conferring AmChlCotTet-resistance was detected among MDR isolates. All the isolates were susceptible to ceftriaxone (Ctx) and ciprofloxacin (Cp). Association between Nalidixic acid (Nx)-resistance and reduced susceptibility to ciprofloxacin (Cp) among 59 S. paratyphi A isolates was noticed (P < 0.001). CONCLUSION: Vigilance for R-plasmid and surveillance of antibiotic susceptibility among S. paratyphi A isolates in and around Kolkata, India, are mandatory in order to combat antibiotic resistance of the isolates in this part of the world.

Reduced minimum inhibitory concentration of chloramphenicol for Salmonella enterica serovar typhi.

BACKGROUND: Ciprofloxacin replaced chloramphenicol (C), the best choice of antibiotic in the treatment of enteric fever, when C-resistant enteric fever emerged and caused outbreaks in different parts of the world. C-sensitive S. enterica serovar Typhi emerged again due to withdrawal of the antibiotic pressure. AIMS: To assess the in vitro efficacy of C against Salmonella enterica serovar Typhi isolates (1991-2003). MATERIAL AND METHODS: A total of 464 blood culture isolates of S. enterica serovar Typhi were subjected to C susceptibility by disc diffusion and agar dilution methods using Mueller-Hinton agar. The antibiotic susceptibility of S. enterica serovar Typhi isolates obtained in the year 2002 and 2003 was determined using ampicillin, cotrimoxazole, ciprofloxacin, nalidixic acid, ceftriaxone and cefotaxime, in addition to C. Escherichia coli strain ATCC 25922 was used as the control. Changes in C sensitivity of the isolates were analyzed using chi2 test with Yates correction. RESULTS AND CONCLUSIONS: All the isolates of 1991 were C-resistant with minimum inhibitory concentration values (MICs) of 2000-5000 mg/ml. In the following years decrease in frequency of C resistance was noticed: 1992 (50%), 1993 (32%), 1994 (27%) and 1995 (05%). The isolates of 1996-99 and 2001 were 100% C-sensitive. In 2000, sensitivity was also high (79%). The strains isolated in the year 2002 and 2003, showing reduced susceptibility of ciprofloxacin, were nalidixic acid resistant, but sensitive to the third-generation cephalosporins (ceftriaxone and cefotaxime). The MICs for C-sensitive isolates (1991-2003) ranged 0.1-5 mg/ml. Results suggest the necessity for re-evaluation of C therapy in typhoid fever.

Cases of human immunodeficiency virus infection and tuberculosis--early experiences of different aspects.

An outpatients department based survey conducted in Calcutta amongst 1349 established cases of tuberculosis (TB) revealed 0.67% human immunodeficiency virus (HIV) infected cases. Those affected by HIV and TB did not show any deviation from epidemiological pattern of HIV infection in India. All contracted HIV infection by heterosexual route, mostly from Bombay (47.8%) followed by West Bengal (30.4%). In follow-up study of a cohort of 36 HIV seropositives over 3 years, 10(27.7%) developed TB. Of the 23 HIV infected cases with TB, lesions were mostly pulmonary (n = 18, 78.3%) followed by pleural effusion (n = 3;13%). Low incidence of Mycobacterium avium (intracelluarae) complex and tuberculous lymphadenopathy one case each and 52.2% positivity with 14.5 mm mean induration diameter in intradermal test with one TU PPD-RT23 are deviations from previous reports. Low incidence of cough (43.5%), marked weight loss (100%) and fever (100%) were the cardinal clinical features. TB infection on pattern suggestive of reactivation of dormant pulmonary lesions lower rate (11%) of treatment failure and infection caused by organisms other than Mycobacterium tuberculosis were other findings of the study. Importance of serosurveillance to unearth more TB cases amongst HIV infected cases for early treatment and isoniazid prophylaxis is stressed upon.

In vitro efficacy of ciprofloxacin alone and in combination with amoxycillin against Salmonella typhi isolates.

Combined effect of ciprofloxacin (Ci) and amoxycillin (Ax) has been studied in vitro against 12 clinical isolates of S. typhi that showed Ci minimum inhibitory concentration (MIC) of > or =1 microg/ml. By agar dilution method, MIC values of Ax were 10-16 microg/ml for 11 isolates and 0.5 microg/ml for the remaining one isolate. The isolates, when treated with Ci and Ax in combination, showed fractional inhibitory concentration (FIC) of 0.004-0.256 microg/ml for Ci. FIC of Ax ranged from 6-10 microg/ml, except for a single isolate that showed Ax FIC of 0.25 microg/ml. Thus Ci was more efficacious in combination with Ax against S. typhi than Ci alone. The antibiotic combination exhibited an additive effect for all the isolates showing FIC index 0.504-0.832.

Drug use among the urban poor in Kolkata: behaviour and environment correlates of low HIV infection.

BACKGROUND: HIV infection in injecting drug users (IDUs) has worked as a driving force for further spread of the virus in other population groups. Major metropolitan cities such as Mumbai, Kolkota, Chennai and Delhi have seen a diffusion of injecting drug use within the last decade. The prevalence of HIV infection among injectors ranges from 2% to 30%. Identifying effective interventional elements that have kept the prevalence of HIV low for the past 7 years among IDUs of Kolkata is thus of public health importance. METHODS: A purposive sample of opioid/opiate users was studied. Primary and secondary data on drug users, law-enforcement environment, records at drug treatment centres, jail admission data related to the 'Narcotic Drug and Psychotropic Substance Act' and interventions in other risk groups were collected. Laboratory tests for HIV, hepatitis B surface antigen and syphilis were done on consenting IDUs (n=129) and non-IDUs (n=120). For univariate and multivariate analysis, IDUs were taken as cases and non-IDUs as controls. RESULT: Of the IDUs, 2% were positive for HIV. No non-IDU was HIV-positive. Significantly more non-IDUs (10% v. 4%, p=0.05) were positive for syphilis. Sharing injection equipment within the past 6 months was reported by 71% of IDUs; sharing partners were stable and ranged from 1 to 3. More IDUs compared to non-IDUs reported being in touch with intervention programmes. The police has been tolerant to needle-syringe exchange and oral sublingual buprenorphine substitution conducted in Kolkata. Unlike in the early 1990s, non-IDUs did not switch to injecting during non-availability of brown sugar in the latter half of the 1990s and instead sought tratment. The availability of high quality heroin (>20%-50%) was low and the proportion of moderate quality heroin (>10%-20%) went up during these times due to increased police seizures. No intervention exists in jails despite the fact that a large number of drug users spend time in jail. CONCLUSION: Stable and few injection equipment-sharing partners of IDUs, launching of early targeted interventions among IDUs and sex workers in the city, police tolerance to harm reduction activities and preference of non-IDUs for detoxification during heroin draught periods have kept HIV prevalence at a low level among drug users of Kolkata for the past 7 years. immediate launching of interventions for drug users in jails seems necessary. Similar multi-pronged strategies with targeted and environmental intervention could work in other settings as well.

R-factor in Proteus vulgaris from ulcerative disease of fish, Channa punctatus.

A Proteus vulgaris isolated from external ulcers of the fresh water fish Channa punctatus showed multidrug resistance and heavy metal tolerance. The isolate from the ulcer showed resistance to chloramphenicol (Ch), nalidixic acid (Nx), streptomycin (Str) and tetracycline (Tet) with minimum inhibitory concentration (MIC) values of 750, 150, 75 and 125 microg/ml, respectively. The isolate showed growth in medium containing cadmium (Cd2+), up to a concentration of 2.5 mM indicating its heavy metal tolerance. Resistance to Ch, Str, Tet and Cd2+ of the isolate was lost after plasmid curing. Presence of plasmid DNA in the wild type and its absence in the cured P. vulgaris suggested that the resistance were plasmid mediated.

Chromosome aberration analysis in radiotherapy patients and simulated partial body exposures: biological dosimetry for non-uniform exposures.

Chromosome aberration analysis was carried out in peripheral blood lymphocytes of cancer patients following radiotherapy of lungs, cervix and spine. Radiotherapy in the pelvic region involving large doses (6 Gy) showed an overdispersed distribution of dicentrics. However, when the doses were fractionated (three fractions of 2 Gy) distribution was found to be near Poisson. Spine irradiation covering almost all the lymphocytes pools, indicated a Poisson distribution. The data show that depending on the sites of exposure, the distribution of dicentrics in cells varies and hence there is a non-uniform distribution of lymphocytes in the body. The average dose to the lymphocytes was found to be one sixth of the partial body dose. Based on the non-Poisson distribution of aberrations, the fraction of lymphocytes irradiated, mean dose to the fraction and part of the body exposed was calculated in a case of acute 6 Gy pelvic irradiation. The fraction of cells irradiated was calculated to be 4.11% and the portion of the body exposed was approximately 16.8%. The dose to the irradiated fraction was found to be 5.4 Gy, which is in agreement with the given dose of 6 Gy. In simulated exposures the u values increased systematically with the decrease in fraction of irradiated cells and the calculated dose to the fraction was also in good agreement with the true dose.

Interferon-alpha in the treatment of acute prolonged hepatitis B virus infection.

OBJECTIVE: Acute hepatitis B virus (HBV) infection is a self-limiting disease which usually recovers within 4-12 weeks. At the present moment, there is no specific treatment of acute HBV infection. This study investigates the efficacy of interferon-alpha (IFN) therapy in acute prolonged HBV infection to prevent its progression into chronic stage. METHODS: We enrolled a total number of 54 patients for the study in the span of 8 years. Group A patients (n = 20) received IFN-alpha 5 million units (MU) subcutaneously (s.c.) thrice a week for 12 weeks and Group B patients (n = 34) were placed on placebo therapy as control for 12 weeks, with a follow-up for one year. RESULTS: Seroconversion (disappearance of HBsAg, HBeAg, serum HBV DNA and appearance of anti-HBe) in Group A occurred in 16 patients (80%) within 24 weeks of illness, whereas in Group B seroconversion was observed only in 18 patients (53%) within 24 weeks. During follow-up upto one year, two more patients showed seroconversion in Group A but none in Group B. While on treatment no casualty was reported in Group A but one patient died of hepatic coma in Group B. Our observation revealed that in acute prolonged (> 12 weeks but < 24 weeks) hepatitis B, spontaneous seroconversion rate was 53% but with moderate dose of IFN therapy (5 MU, s.c., thrice weekly) from 12 weeks onwards, the seroconversion rate came out to be 80% (upto 24 weeks) which increased upto 90% when followed-up for one year. CONCLUSIONS: IFN-alpha treatment in acute prolonged (> 12 weeks) HBV infection is safe and may prevent its progression to the chronic stage.

Is PGL-1 also present in Leishmania donovani promastigotes?

A soluble antigen complex (SAC) derived from the ruptured promastigotes of Leishmania donovani parasites (LD-SAC) was used for complement fixation test (CFT) in leprosy Cases of tuberculoid and borderline tuberculoid leprosy, post-kala azar dermal leishmaniasis (TT, BT, PKDL) and control sera gave negative CFT. Smear-positive cases of borderline (BB, BL) and lepromatous (LL) leprosy and drug-resisting cases of pulmonary tuberculosis gave positive CFT; smear-negative cases of LL leprosy sera also gave positive CFT. Sera of smear-negative inactive LL patients contained only PGL-1 and PDIM antigens for a long time after they become inactive. Therefore, the positive CFT in inactive LL makes us suspect whether PGL-1 is present in LD promastigotes.

Community based survey of STD/HIV infection among commercial sex-workers in Calcutta (India). Part-III: Clinical findings of sexually transmitted diseases (STD).

On physical examination of 418 sex workers, 202 (48.32 per cent) were found to have vaginal discharge, which was found to be most common among younger age class. Endocervical pus, genital ulcer, and swelling of inguinal lymph glands were observed in 13.16, 6.22 and 1.91 per cent of the sex workers respectively. Clinically 16.51, 15.31, 11.96 and 4.78 per cent were found to suffer from candidiasis, trichomoniasis, cervicitis and syphilis respectively.

Community based survey of STD/HIV infection among commercial sex workers in Calcutta (India). Part-IV: Sexually transmitted diseases and related risk factors.

Community based survey on a sample of commercial sex workers in one red light area of Calcutta, was carried out to determine prevalence of sexually transmitted diseases (STD) including HIV infection and related risk factors. An alarmingly high prevalence of STDs (80.56 per cent) but low HIV-seropositivity (1.13 per cent) was observed. Candida albicans, Neisseria gonorrhoeae and Trichomonas vaginalis were detected in 23.24, 13.24 and 11.11 per cent of genital specimens respectively. BY TPHA test 62.97 per cent of the sera were reactive for Treponema pallidum. Duration in the profession of sex workers was found to have an association with seropositivity for syphilis. Prevalence of HIV infection might be low at present, but conditions were highly favourable for rapid spread of infection.