Diabetes mellitus and human immunodeficiency virus (HIV) infection in people with tuberculosis in Odisha, India.

BACKGROUND: Modelling studies have indicated that approximately 20% of all tuberculosis (TB) cases may suffer from diabetes mellitus (DM). DM increases the risk of developing active TB disease by 2-3 times. People living with HIV (PLHIV) are more likely to develop TB disease, and TB is a leading cause of hospitalization and death among PLHIV. Despite the substantial burden of DM and HIV in India, few studies have evaluated the prevalence of DM and HIV among active cases of TB, and its impact on the treatment outcome for TB. This study evaluated the burden of HIV and DM in TB cases from Odisha during 2019, and its impact on the TB treatment outcome. METHODS: The study utilized data on TB patients of Odisha during 2019, from the NIKSHAY portal, the health management information system (HMIS) of TB in India. This is a retrospective observational registry-based cohort study, which evaluated a linkage between socio-demographic predictors, clinical diagnostic and treatment predictors, time of treatment predictors, and co-morbidity with TB. Data were retrieved electronically in Microsoft-Excel and analysis was done using STATA 16 (StataCorp. 2019, College Station, TX: StataCorp LLC). RESULTS: Data for 47,831 TB cases of Odisha as study population was extracted from the Nikshay application for the year 2019. The highest prevalence (31.1%, 14,863/47,831) of TB was observed among young participants aged 15-30 years, whereas the prevalence was least among children <14 years (4.4%, 2124/47,831). Males had a higher prevalence of TB (66.7%, 31,878/47,831). Of the 47,831 TB cases included in the study, 7.6% (3659/47,831) had diabetes mellitus (DM), along with TB. 1.2% (571/47,831) had HIV along with TB, while only 0.08% (37/47,831) had both DM and HIV along with TB. 88.2% (3148/3569) of cases with DM and TB had a favorable outcome, compared to 82.3% (449/541) of cases with HIV and TB. People with TB who did not have DM had a significantly higher favorable outcome (OR 1.6, 95% CI 1.5-1.8) compared to those with TB and DM. Similarly, TB cases who did not have HIV infection had a significantly higher favorable outcome (OR 2.4, 95% CI 1.9-3.0) compared to those with TB and HIV. CONCLUSION: Our study showed that presence of DM and/or HIV in TB patients had an impact on the TB treatment outcome. There is a crucial need to prevent comorbidities such as DM and HIV from occurring and to prioritize early diagnosis and management of these conditions.

Impact of cartridge-based nucleic acid amplification test (CBNAAT) introduction on the detection of pulmonary and extra-pulmonary tuberculosis in Bhubaneswar, Odisha.

Background: Compared to conventional microscopy, the cartridge-based nucleic acid amplification test (CBNAAT, Xpert MTB/RIF, Cepheid, USA) has the dual advantage of higher sensitivity to detect Mycobacterium tuberculosis (M. tb), and the ability to detect rifampicin resistance. Aim: To evaluate the impact of the CBNAAT on the detection of pulmonary and extra-pulmonary tuberculosis from private and public healthcare facilities in Bhubaneswar, Odisha. Materials and Methods: The study included specimens received between June 2015 to February 2017 from public and private health sectors for tuberculosis diagnosis at a national reference laboratory for tuberculosis in Bhubaneswar, where the CBNAAT was initiated in February 2016. We retrospectively collected the patients' socio-demographic characteristics from their test request form, CBNAAT results from the CBNAAT register and PMDT culture and drug susceptibility testing (DST) register and validated the data by comparing the patient details and test results from the CBNAAT software. Results: From June 2015 to January 2016, 106 samples were received from Bhubaneswar at the reference laboratory, of which there were zero referrals from the private sector and zero referrals of extra-pulmonary tuberculosis (TB) samples. After initiation of the CBNAAT, from February 2016 to February 2017, 1262 specimens were received, of which 55.2% (696/1262), 17.8% (225/1262), 17.2% (217/1262), and 9.8% (124/1262) were from government hospitals and medical colleges, private hospitals, private practitioners, and district TB centers, respectively. Conclusion: The availability of TB diagnostics at public sector facilities to patients from private sectors and the rollout of the CBNAAT increased the referral of patients from private health facilities and the referral of paucibacillary non-sputum samples.

Recurrence of pulmonary tuberculosis in India: Findings from the 2019-2021 nationwide community-based TB prevalence survey.

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.

Prevalence and factors associated with tuberculosis infection in India.

BACKGROUND: The risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection. METHODS: Individuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub-analysis. TB infection was defined as positive by QFT-Plus (value >0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated. RESULTS: Of the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 -25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29-1.73), being male (aRR:1.26; 95%CI: 1.18-1.34), residing in urban location (aRR:1.58; 95%CI: 1.03-2.43) and past history of TB (aRR:1.49; 95%CI: 1.26-1.76). CONCLUSION: About one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India.

Pleural tuberculosis in Bhubaneswar, Odisha, during 2016 to 2022.

We conducted a retrospective study to evaluate the burden of tuberculosis and rifampicin resistance in patients with pleural effusion in Bhubaneswar, Odisha, during February 2016, to December 2022, using cartridge-based nucleic acid amplification test (CBNAAT, Xpert MTB/RIF). Of the 1370 pleural fluid samples tested at the National Reference Laboratory for tuberculosis, 3.8% (52/1370) were positive for M.tuberculosis. Rifampicin resistance was detected in 3.8% (2/52) samples. The positivity was 5% in 2016, increased to 7.5% in 2020, and was 4.4% in 2022. The positivity varied across age groups, ranging from 1.5% in patients aged >60 years to 6.1% in 15-30 years.

Pattern of InhA and KatG mutations in isoniazid mono resistant Mycobacterium tuberculosis isolates from Odisha.

We conducted a retrospective analysis of the line probe assay (LPA) data during January to December 2019, from 8 districts of Odisha. The prevalence of Hr-TB (isoniazid resistance only) was 1.53% (50/3272) with a range of 0-3.4% in the 8 districts. Of the 50 Hr-TB strains, katG mutation and inhA mutations were seen in 74% (37/50) and 26% (13/50) strains respectively. S315T1 and C15T were common mutations in katG and inhA respectively. Since these mutations are closely related to high- or low degree resistance to INH, it has therapeutic implications.

Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India, June-July 2021: A population-based cross-sectional study.

BACKGROUND: India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March-June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs). METHODS AND FINDINGS: We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6-9 years, 5,798 (20%) were aged 10-17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey. CONCLUSIONS: Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June-July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.

Mycobacterium mageritense causing surgical site infection: Case report from Odisha, India.

A 66-year female presented to the outpatient department (Medicine) of a tertiary care hospital with history of a recurrent sinus with multiple openings after a laparoscopic cholecystectomy surgery one and half years back. The excised tissue from sinus was sent for histopathology showed multiple non-caseating granulomas and was cultured for Mycobacterium. The growth from culture was identified as Mycobacterium mageritense by Line probe assay (LPA). The wound healed after ofloxacin and doxycycline was given for a period of two months. This case focuses the importance of proper diagnosis and treatment of chronic surgical infections keeping in mind the NTM.

SARS-CoV-2 seroprevalence among the general population and healthcare workers in India, December 2020-January 2021.

BACKGROUND: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May-June 2020 and 7.1% in August-September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. METHODS: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. RESULTS: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0-25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5-27.8%). CONCLUSIONS: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020.

SARS-CoV-2 antibody seroprevalence in India, August-September, 2020: findings from the second nationwide household serosurvey.

BACKGROUND: The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34-1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. METHODS: We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys. FINDINGS: Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8-7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2-8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case. INTERPRETATION: Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country. FUNDING: Indian Council of Medical Research.

Evaluation of 'TBDetect' sputum microscopy kit for improved detection of Mycobacterium tuberculosis: a multi-centric validation study.

OBJECTIVES: The present study aimed to evaluate the performance of the 'TBDetect' kit-based bio-safe fluorescent microscopy filter (BioFM-Filter) microscopy in comparison with direct smear microscopy and culture for the detection of pulmonary tuberculosis (TB) in a multi-centric setting in India. METHODS: The TBDetect kit enables sputum concentration through filtration using the BioFM-Filter for improved and bio-safe smear microscopy. We evaluated the performance of the TBDetect kit in a six-site multi-centric validation study on sputum collected from 2086 presumptive TB patients. RESULTS: The combined positivity of TBDetect microscopy performed on these sputum samples was 20% (n = 417/2086) vs 16.1% of light-emitting diode fluorescence microscopy (LED-FM, n = 337/2086) and 16% of Ziehl Neelsen (ZN) smear microscopy (n = 333/2086). The increment in positivity of TBDetect over both LED-FM and ZN smears was significant (p < 0.001). The overall sensitivity of TBDetect for six sites was ~55% (202/367, 95% confidence interval (CI): 50, 60%) vs 52% (191/367, 95% CI: 47, 57%) for LED-FM (p 0.14) and 50.9% (187/367, 95% CI: 46, 56%) for ZN smear (p < 0.05), using Mycobacterium Growth Indicator Tube culture (MGIT, n = 1949, culture positive, n = 367) as the reference standard. A bio-safety evaluation at six sites confirmed efficient sputum disinfection by TBDetect; 99.95% samples (1873/1874) were sterile after 42 days of incubation. Scientists and technicians at the study sites indicated the ease of use and convenience of TBDetect microscopy during feedback. CONCLUSIONS: TBDetect added value to the smear microscopy test due to its improved performance, convenience and user safety. These findings indicate that equipment-free TBDetect technology has the potential to improve TB diagnosis in basic laboratory settings by leveraging on the existing nationwide network of designated microscopy centres and primary healthcare centres.

Prevalence of SARS-CoV-2 infection in India: Findings from the national serosurvey, May-June 2020.

BACKGROUND & OBJECTIVES: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. METHODS: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. RESULTS: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. INTERPRETATION & CONCLUSIONS: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.

Prevalence, risk factors and health seeking behaviour of pulmonary tuberculosis in four tribal dominated districts of Odisha: Comparison with studies in other regions of India.

AIM: To determine the prevalence of pulmonary tuberculosis, socio-cultural practices and health seeking behaviour of tribal people in four districts of Odisha. METHODOLOGY: This was an action research study with qualitative and quantitative design following a sequential approach implemented in a 4-phased manner. It was carried out in the 6 selected villages from July,2015 to June,2017. The screening for active TB among chest symptomatics is followed as per the guidelines of the (RNTCP) Revised National Tuberculosis Control Program in India. RESULTS: In all, 1455 households were surveyed in the 6 tribal dominated villages of 4 districts, namely Balangir, Dhenkanal, Kandhamal and Mayurbhanj. Total population of the villages was 6681. Based on the eligibility, 5144 (97.7%) individuals were screened. About 139 (2.3%) could not be screened due to non-availability in their households during day time. Out of the screened individuals (5144), 126 chest symptomatics were identified. Sputum samples were collected from them and sent to the National Reference Laboratory, RMRC, Bhubaneswar using public transport and maintaining cold chain. Out of 126 chest symptomatics, 35 patients were found to be having active TB disease and 18 were culture positive. The prevalence of pulmonary TB is 0.68%. The risk factors seemed to be ignorance about TB symptoms, addiction to alcoholic drinks, difficulty reaching the health facilities owing to the long distances, lack of communication and transport. In addition, other morbidities like Malaria, diabetes, hypertension, malnutrition, etc. were observed in the tribes of the study sites. CONCLUSION: TB control programs need further strengthening in the tribal dominated regions. This study is the first of its kind in this State.

Mouse Bone Marrow Sca-1+ CD44+ Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway.

Mycobacterium tuberculosis primarily infects lung macrophages. However, a recent study showed that M. tuberculosis also infects and persists in a dormant form inside bone marrow mesenchymal stem cells (BM-MSCs) even after successful antibiotic therapy. However, the mechanism(s) by which M. tuberculosis survives in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. Here, we studied the fate of virulent and avirulent mycobacteria in Sca-1+ CD44+ BM-MSCs. We found that BM-MSCs were able to kill avirulent Mycobacterium smegmatis and Mycobacterium bovis BCG but not the pathogenic species M. tuberculosis Further mechanistic studies revealed that pathogenic M. tuberculosis dampens the antibacterial response of BM-MSCs by downregulating the expression of the cationic antimicrobial peptide cathelicidin. In contrast, avirulent mycobacteria were effectively killed by inducing the Toll-like receptor 2/4 (TLR2/4) pathway-dependent expression of cathelicidin, while small interfering RNA (siRNA)-mediated cathelicidin silencing increased the survival of M. bovis BCG in BM-MSCs. We also showed that M. bovis BCG infection caused increased expression levels of MyD88, phospho-interleukin-1 receptor-associated kinase 4 (pIRAK-4), and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Further downstream investigations demonstrated that IRAK-4-p38 activation increased the nuclear translocation of NF-κB, which subsequently induced the expression of cathelicidin and the cytokine interleukin-1ß (IL-1ß), resulting in the decreased survival of M. bovis BCG. On the other hand, inhibition of TLR2/4, pIRAK-4, p38, and NF-κB nuclear translocation decreased cathelicidin and IL-1ß expression levels and therefore increased the survival of avirulent mycobacteria. This is the first report that demonstrates that virulent mycobacteria manipulate the TLR2/4-MyD88-IRAK-4-p38-NF-κB-Camp-IL-1ß pathway to survive inside bone marrow stem cells.

First Line Anti-TB Drug Resistance in an Urban Area of Odisha, India.

INTRODUCTION: Drug resistance is a major cause for increasing the global burden of Tuberculosis (TB). However in countries with larger geographical areas and different climatic conditions like India the prevalence of drug resistance varies from place to place. Information on anti-TB drug resistance patterns particularly among newly diagnosed cases is crucial for planning an effective TB control program. AIM: To determine the prevalence of resistance against first line anti-TB drugs and Multi Drug Resistance (MDR) in Mycobacterium tuberculosis isolates. MATERIALS AND METHODS: The prospective study was carried out in National Reference Laboratory (NRL) of Regional Medical Research Centre (RMRC), Bhubaneswar. During this period from January to September 2014, sputum specimens were collected from 850 suspected pulmonary TB patients attending Designated Microscopy Center (DMC) of Capital Hospital, Bhubaneswar, Odisha. Sputum specimens were subjected to Acid Fast Bacilli (AFB) smear microscopy and further processed for isolation on solid Lowenstein Jensen (LJ) medium. Drug Susceptibility Testing (DST) on isolates with first line anti-TB drugs was performed as per Revised National Tuberculosis Control Programe (RNTCP) guidelines. RESULTS: Out of all the 850 suspected pulmonary TB patients subjected to AFB microscopy and solid LJ culture, isolation of Mycobacterium tuberculosis was successful only in 161 (117 new and 44 previously treated) pulmonary TB patients. On DST by the RNTCP approved proportion method, prevalence of MDR- TB among 0.85% new and 4.54% previously treated cases was observed. Prevalence of mono resistance to streptomycin, isoniazid, rifampicin and ethambutol observed among new and previously treated cases were 3.41%, 2.56%, 0, 0.85% and 2.27%, 13.6%, 2.27%, 0 respectively. Only one patient from each category showed resistance to both streptomycin and isoniazid in previously treated as well as in new case. CONCLUSION: The study reports an unchanged low level of MDR-TB prevalence among new cases in an urban area of Odisha over a decade. This could be due to the success of Directly Observed Treatment Short-course (DOTS) in effective treatment of drug-susceptible TB in the state and non-transmission from primary Drug Resistance (DR) TB cases.

Delay in diagnosis among pulmonary tuberculosis patients of Rayagada District, Odisha, India.

BACKGROUND: India accounts for more than one-fifth of the world's tuberculosis (TB) burden. In spite of efforts taken by the Revised National Tuberculosis Control Programme, tribal areas of the state of Odisha report a high TB incidence over the years. One of the reasons could be delay in reporting to health facilities by the symptomatic patients. During such delays an active case may infect numerous susceptible people thereby contributing to the perpetuation of the infection. The delay in diagnosis may be as long as 2-3months and even more in hard-to-reach areas. OBJECTIVE: The present study aims to find out the extent of delay in diagnosis among pulmonary TB patients of a tribal dominated district that may help in planning effective control strategies for similar situations. METHODS: The information on delay in diagnosis is part of a cross-sectional drug resistance study carried out from June 2011 to May, 2013 in 20 Designated Microscopy Centres (DMCs) of Rayagada district of Odisha, India. Out of 634 smear positive pulmonary TB patients enrolled in this study, information on health seeking by the patients were available for 580 patients. The patients included had clinical signs and symptoms suggestive of pulmonary TB (cough, chest pain, and hemoptysis), with/without radiological evidence. Patients found smear positive by Ziehl-Neelsen microscopy were requested to take part in the study and accordingly a written questionnaire including history of: TB treatment; symptoms experienced by the patient and duration of suffering; and radiological examination was completed. The delay in diagnosis at the DMCs due to delay in health seeking by the symptomatic TB patients was evident as only 5.2% patients reported within 2weeks and 62.6% up to 1month of onset of symptoms. RESULTS: The delay in health seeking by the patients was not differentiated by sex or resistance profile, although more men attended the DMC for diagnosis. The present study is the first of its kind to report diagnostic delay of TB among smear-positive TB patients of Rayagada, a tribal-dominated district of Odisha, India and it reveals an extremely long diagnostic delay of TB in this area. We found that 12.9% of patients had a delay exceeding 2months, and 50% of them had high sputum grade. This is a serious concern due to the fact that each of these patients dispenses up to 3500 bacilli in each cough, and may infect 10-15 people each year, eventually creating a public health problem. CONCLUSION: Poor awareness of patients about the disease and limited access to health care are the bottom-line in apparent diagnostic delay of TB patients. This substantial patient delay to diagnosis is a major contributing factor for increasing transmission of TB in tribal districts of Odisha. Increased awareness of the disease is crucial in improving health-seeking behavior in these areas.

Platinum-Mediated Activation of Coordinated Organonitriles by Telluroethers in Tetrahydrofuran: Isolation, Structural Characterization, and Density Functional Theory Analysis of Intermediate Complexes.

The reactions of [PtCl2(NCR)2] with telluroethers (ArAr'Te) in organic solvents have been investigated. The reactions in dichloromethane yield [PtCl2(TeArAr')2], while those in tetrahydrofuran (THF) give different products depending on the steric demands of the aryl groups on tellurium, the molarity of the reactants, and the reaction conditions. The reactions between [PtCl2(PhCN)2] and TeArAr' in 1:1 molar ratio at room temperature in THF yield several products, like [PtCl2(TeArAr')2] (Ar/Ar' = Ph/Ph, o-tol/Mes, Mes/Mes), [PtCl2(PhCN){NC(O)Ph[TeMes(o-tol)]}], and [PtCl2{NC(O)Ph(TeMes2)}2]. The reaction with TeMes2 in refluxing THF gave [PtCl2{NC(Ph)C4H7O}{NC(O)Ph(TeMes2)}] and [PtCl(TeMes2){Te(Mes)CH2C6H2Me2}], depending on the duration of heating. Reaction of [PtCl2(PhCN)2] with TeArMes afforded [PtCl2(TeArMes)2] (Ar = Ph, o-tol, and Mes), the formation of which decreased with increasing steric demand of the Ar group, together with [PtCl2{NC(O)Ph(TeArMes)}2]. The telluroether in the latter binds to nitrogen, and tellurium exists in the formal oxidation state of +4 (from XPS). The tellurium in these complexes exhibits secondary interactions with platinum (J((195)Pt-(125)Te) = 309-347 Hz) and with the carbonyl oxygen. These complexes slowly dissociate in solution to give [PtCl2(TeMesAr){NC(O)Ph(TeMesAr)}], finally leading to the formation of [PtCl2(TeMesAr)2]. Molecular structures of trans-[PtCl2(PhCN){NC(O)Ph[TeMes(o-tol)]}], trans-[PtCl2{NC(O)Ph(TeMes2)}2], trans-[PtCl2{NC(Ph)C4H7O}{NC(O)Ph(TeMes2)}], trans-[PtCl2{NC(O)Ph[TeMes(o-tol)]}2], trans-[PtCl2(TeMes2){NC(O)Ph(TeMes2)}], trans-[PtCl2{NC(O)Me(TeMes2)}2], and [PtCl(Te-o-tol){NC(O)Ph}2] have been unambiguously established by single-crystal X-ray diffraction analyses. Density functional theory calculations for some of the complexes were performed, and geometrical parameters are in good agreement with the values obtained from X-ray analyses.

Cyclopalladation of telluro ether ligands: synthesis, reactivity and structural characterization.

Treatment of [PdCl2(PhCN)2] with diaryl telluride in 1 : 2 molar ratio gave mononuclear palladium complexes, trans-[PdCl2(TeR2)2] () (R = Mes () (Mes = 2,4,6-trimethylphenyl), Ph (), o-tol () (o-tol = ortho-tolyl)). Reaction of [PdCl2(TeMes2)2] with one equivalent of [PdCl2(PhCN)2] or Na2PdCl4 with TeRR' afforded chloro-bridged binuclear complexes, [Pd2(µ-Cl)2Cl2(TeRR')2] () (R/R' = Mes/Mes (); Mes/Ph (); Ph/Ph ()). A toluene-methanol solution of trans-[PdCl2(TeMes2)2] on refluxing for 30 minutes yielded a binuclear cyclopalladated complex, [Pd2(µ-Cl)2{CH2C6H2(4,6-Me2)TeMes)}2] (). When the refluxing was prolonged, a mononuclear complex cis-[PdCl2{MesTeCH2C6H2(4,6-Me2)TeMes}] () was isolated. Treatment of palladium acetate with TeMes2 afforded an acetato-bridged analogue of , [Pd2(µ-OAc)2{CH2C6H2(4,6-Me2)TeMes}2] () together with a very minor component, a tetranuclear complex, [Pd(µ-OAc)(µ-TeMes)]4 (). This reaction with unsymmetrical tellurides, MesTeR, also gave cyclopalladated complexes [Pd2(µ-OAc)2{CH2C6H2(4,6-Me2)TeR}2] (R = o-tol () and Ph ()) in which 2-methyl of the mesityl group of the telluride was exclusively metallated. The complex trans-[PdCl2(TeMes2)2] on refluxing in xylene gave palladium telluride, Pd7Te3. These complexes were characterized by elemental analyses, IR and NMR ((1)H, (13)C and (125)Te) spectroscopy. The molecular structures of trans-[PdCl2(TeMes2)2] (), [Pd2(µ-Cl)2Cl2(TeMes2)2]·2acetone (·2acetone), cis-[PdCl2{MesTeCH2C6H2(4,6-Me2)TeMes}] (), [Pd2(µ-OAc)2{CH2C6H2(4,6-Me2)TeMes)}2]·toluene (·toluene), [Pd2(µ-OAc)2{CH2C6H2(4,6-Me2)Tetol-o}2] () and [Pd(µ-OAc)(µ-TeMes)]4 () were established by single crystal X-ray diffraction analyses. The mononuclear complex was isolated in two polymorphic forms each with the trans configuration.

Transportation of sputum samples in cetylpyridinium chloride for drug resistance studies from remote areas of Odisha, India.

INTRODUCTION: Antimicrobial susceptibility testing of Mycobacterium tuberculosis is required for successful treatment of patients, mainly in retreatment cases which necessitate isolation of mycobacteria from sputum samples within 24-48 hours. In situations where transportation of sputum is required, the use of cetylpyridinium chloride (CPC) effectively sustains the viability of mycobacteria up to two weeks. METHODOLOGY: Sputum samples were collected from pulmonary TB patients attending designated microscopy centres (DMC), stored in CPC solution and transported to a culture drug susceptibility testing laboratory using overnight bus transport facilities. For culture, the sputum specimens were processed and inoculated in Lowenstein- Jensen (LJ) medium. Growth on LJ was identified by colony morphology, growth rate and biochemical tests, and transit time was calculated as the time taken from the date of sample collection to the inoculation date. RESULTS: Out of the 816 sputum samples collected in CPC, 691 (84.7%) yielded M. tuberculosis, 97 (11.9%) yielded no growth, 21(2.6%) grew contaminants and 7 (0.8%) were nontuberculous mycobacteria. CPC containing sputum samples processed within two weeks showed 88.6% culture positivity, while positivity was significantly affected beyond two weeks. CONCLUSIONS: CPC is cheap, easy to use, inhibits the growth of other organisms and can effectively be used to transport sputum specimens within two weeks from hard to reach areas to central locations without compromising culture positivity. Bus transport services can also help in reducing delay and the cost of transportation from remote areas.