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India has the highest burden of Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) worldwide. Innovative technology is the need of the hour to identify these cases that remain either undiagnosed or inadequately diagnosed due to the unavailability of appropriate tools at primary healthcare settings. We developed and evaluated 3 kits, namely ‘TB Detect’ (containing BioFM-Filter device), ‘TB Concentration and Transport’ (containing Trans-Filter device) and ‘TB DNA Extraction’ kits. These kits enable bio-safe equipment-free concentration of sputum on filters and improved fluorescence microscopy at primary healthcare centres, ambient temperature transport of dried inactivated sputum filters to central laboratories and molecular detection of drug resistance by PCR and DNA sequencing (Mol-DST). In a 2-site evaluation (n = 1190 sputum specimens) on presumptive TB patients, BioFM-Filter smear exhibited a significant increase in positivity of 7% and 4% over ZN smear and LED-FM smear (p<0.05), respectively and an increment in smear grade status (1+ or 2+ to 3+) of 16% over ZN smear and 20% over LED-FM smear. The sensitivity of Mol-DST in presumptive MDR-TB and XDR-TB cases (n = 148) was 90% for Rifampicin (95% confidence interval [CI], 78–96%), 84% for Isoniazid (95% CI, 72–92%), 83% for Fluoroquinolones (95% CI, 66–93%) and 75% for Aminoglycosides (95% CI, 35–97%), using phenotypic DST as the reference standard. Test specificity was 88–93% and concordance was ~89–92% (κ value 0.8–0.9). The patient-friendly kits described here address several of the existing challenges and are designed to provide ‘Universal Access’ to rapid TB diagnosis, including drug-resistant disease. Their utility was demonstrated by application to sputum at 2 sites in India. Our findings pave the way for larger studies in different point-of-care settings, including high-density urban areas and remote geographical locations. [ABSTRACT FROM AUTHOR]

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In countries like India, diseases in plants are a major concern in the agricultural sector. Crop loss due to diseases led to reduction in the quality and quantity of agricultural products. This also leads to economic losses. Hence, timely monitoring of plants is necessary. But monitoring diseases in large fields is a difficult task. To overcome this problem, effective management strategies should be taken to control diseases in plants. It can be done by acquiring data for disease identification and automation of the recognition of diseases. Deep learning is of great use in this area using the principles of object detection. In this paper, we are using YOLOv3 (you only look once) to determine the diseases in plants, based on the symptoms seen on the leaves. The advantage of using YOLOv3 is that multiple diseases can be detected on the image of a single leaf. An important feature of YOLOv3 is that it can detect small disease spots seen on the leaves. Here, we are concentrating on the bacterial spot disease seen on the bell pepper plant. The identification results show a mean average precision of 90%. [ABSTRACT FROM AUTHOR]

Rice is a staple food for roughly half of the world's population. Some farmers prefer rice cultivation to other crops because rice can thrive in a wide range of environments. Several studies have found that about 70% of India's population relies on agriculture in some way and that agribusiness accounts for about 17% of India's GDP. In India, rice is one of the most important crops, but it is vulnerable to a number of diseases throughout the growing process. Farmers' manual identification of these diseases is highly inaccurate due to their lack of medical expertise. Recent advances in deep learning models show that automatic image recognition systems can be extremely useful in such situations. In this paper, we propose a suitable and effective system for predicting diseases in rice leaves using a number of different deep learning techniques. Images of rice leaf diseases were gathered and processed to fulfil the algorithmic requirements. Initially, features were extracted by using 32 pre-trained models, and then we classified the images of rice leaf diseases such as bacterial blight, blast, and brown spot with numerous machine learning and ensemble learning classifiers and compared the results. The proposed procedure works better than other methods that are currently used. It achieves 90–91% identification accuracy and other performance parameters such as precision, Recall Rate, F1-score, Matthews Coefficient, and Kappa Statistics on a normal data set. Even after the segmentation process, the value reaches 93–94% for model EfficientNetV2B3 with ET and HGB classifiers. The proposed model efficiently recognises rice leaf diseases with an accuracy of 94%. The experimental results show that the proposed procedure is valid and effective for identifying rice diseases. [ABSTRACT FROM AUTHOR]

Background: Infections by multidrug‐resistant organisms (MDRO) are a major hurdle in hematopoietic stem‐cell transplants (HSCTs). Conditioning regimens lead to mucosal barrier injury, which in‐turn leads to transmigration of gut bacteria and sepsis. Pre‐transplant stool and throat surveillance cultures can guide empirical antibiotic policy during the neutropenic period. In this paper, we document colonization with MDRO in pre‐transplant surveillance cultures and the correlation with bloodstream infections in HSCT patients and analyze transplant outcomes with respect to these infections. Methods: A single‐center, retrospective study on HSCT was performed between January 2021 and December 2021. The incidence of bacterial infections, percentage of MDROs, correlation with pre‐transplant stool/throat surveillance cultures, and their impact on overall 100‐day and post‐100‐day to 6‐month post‐transplant survival were analyzed. Results: Sixty‐four patients were included in the study. Pre‐transplant stool surveillance cultures were positive for MDRO in 85.9% of patients. Almost half (48.5%) of the isolates were positive for carbapenemase‐producing genes (mainly New Delhi metallo‐beta‐lactamase‐1 [NDM‐1] and oxacillinase‐48 [OXA‐48]). Eighteen patients (18/64, 28%) had a positive blood culture for MDRO in the peri‐engraftment neutropenic period. Correlation between surveillance and blood cultures was seen in 61% (11/18) of patients. All‐cause mortality was 14.1% (9/64) and 25% (16/64) in patients at 100 days and 6 months post‐HSCT, respectively. The 100‐day and post‐100‐day all‐cause mortality rates were higher in patients with Gram‐negative MDRO bloodstream infections (p <.012 and <.008, respectively). Conclusion: MDRO infections can adversely affect HSCT outcomes. Pre‐transplant stool and throat surveillance cultures may guide empirical antibiotic policy and lead to favorable transplant outcomes. [ABSTRACT FROM AUTHOR]

This paper presents a pioneer study on the microbial diversity and antibacterial potential of hive bees (Apiscerana and A.mellifera) honey collected from Himachal Pradesh. In total, 26 bacteria (14 from A.cerana and 12 from A.mellifera) but no fungal isolate were recovered. Bee species and locations comparison in terms of bacterial load (log CFU/g) revealed maximum loads of 3.74 and 3.99 in the honey from A.cerana and Mandi location, respectively. The most prevalent strains (HC3, HC5, HC6, HC8 and HM2) were identified (16S rRNA ribotyping) as Staphylococcushaemolyticus (MT742636), "Bacillussubtilis subsp. stecoris" (MT742637), Bacillussafensis subsp. safensis (MT742638), "Bacilluszanthoxyli" (MT742639) and Bacillussafensis subsp. safensis (MT938911). The apiary honey displayed good to excellent inhibitory activity against Escherichiacoli ATCC1041 whereas, fair to good against Bacillussubtilis ATCC6633, Pseudomonasaeruginosa ATCC10662, Salmonellatyphi NCTC786 and Klebsiellapneumoniae ATCC13883, highlighting its use as a therapeutic agent. Furthermore, it can be effective in minimizing numerous side effects associated with the consumption of synthetic drugs for treating bacterial infections thereby signifying the role of honey as a healthier substitute for synthetic drugs. [ABSTRACT FROM AUTHOR]

Background Information on the average and incremental costs of implementing alternative strategies for treating young infants 0-59 days old in primary health facilities with signs of possible serious bacterial infection (PSBI) when a referral is not feasible is limited but valuable for policymakers. Methods Direct activity costs were calculated for outpatient treatment of PSBI and pneumonia in two districts of India: Palwal, Haryana and Lucknow, Uttar Pradesh. These included costs of staff time and consumables for initial assessment, classification, and referrals; recommended treatment of fast breathing (oral amoxicillin for seven days) and PSBI (injection gentamicin and oral amoxicillin for seven days); and daily assessments. Indirect operational costs included staff training; staff time cost for general management, supervision, and coordination; referral transport; and communication. Results The average cost per young infant treated for recommended and acceptable treatment for PSBI was 16 US dollars (US$) (95% CI=US$15.4-16.3) in 2018-19 and US$18.5 in 2022 (adjusted for inflation) when all direct and indirect operational costs were considered. The average cost of recommended treatment for pneumonia was US$10.1 (95% CI=US$9.7-10.6) or US$11.7 in 2022, per treated young infant. The incremental cost 2018-2019 for supplies, medicines, and operations (excluding staff time costs) per infant treated for PSBI was US$6.1 and US$4.3 and for pneumonia was US$3.5 and US$2.2 in Palwal and Lucknow, respectively. Operation and administrative costs were 25% in Palwal and 12% in Lucknow of the total PSBI treatment costs. The average cost per live birth for treating PSBI in each population was US$5 in Palwal and US$3 in Lucknow. Higher operation costs for social mobilisation activities in Palwal led to the empowerment of families and timely care-seeking. Conclusions Costs of treatment of PSBI with the recommended regimen in an outpatient setting, when a referral is not feasible, are under US$20 per treated child and must be budgeted to reduce deaths from neonatal sepsis. The investment must be made in activities that lead to successful identification, prompt care seeking, timely initiation of treatment and follow-up. [ABSTRACT FROM AUTHOR]

Background: From time immemorial ethnic people of Purulia district of West Bengal are well acquainted with different plant resources for the treatment of various skin diseases including 'carbuncle' and others skin diseases. Carbuncle, caused by the methicillin resistant Staphylococcus aureus is of major concern in this part of India, mostly dominated by tribes like Majhi, Munda, Santal, Birhor, Ho and Rajwar etc. Hot climate, overcrowded households, improper sanitation, very poor economic background and frequent burn accidents are of major issues for spreading of these bacterial infections. Objective: Present authors are trying to summarize these ethno-medicinal knowledge of the local, conservative traditional healers by using structured questionnaires given to them and are trying to analyze these information from scientific perspective. Materials and Methods: Plant samples were collected from March 2014 to May 2016, mostly during their flowering stage and a total of 62 people, both male (84%) and female (16%) were interviewed. Informant consensus factor, fidelity level and use value were calculated. Results: Fifty-nine herbal plants belongs to 35 families were recorded for the cure of various skin diseases, among which 10 plants are used individually during medication whereas 9 polyherbal formulations were used in various combinations during treatment. Five species of the families Moraceae and Asteraceae was found to be the most common medicinal plants, among which 44.89% are herbaceous in habit. Leaves (55.55%) are the most common plant part for their use. Conclusion: Therefore, the present paper has been written to document this rapidly vanishing huge knowledge of folklore which should be digitally conserved for futuristic approach on medicinal plants in India. [ABSTRACT FROM AUTHOR]

Background: Migrant labourers living in the slums of urban and industrial patches across India make up a key sub-population so far controlling Tuberculosis (TB) in the country is concerned. This is because many TB patients from these communities- remain under reached by the Revised National Tuberculosis Control Programme (RNTCP) of India. This marginalized community usually seeks early-stage healthcare from “friendly neighbourhood” non-formal health providers (NFHPs). Because, RNTCP has limited capacity to involve the NFHPs, an implementation research project was conceived, whereby an external partner would engage with the NFHPs to enable them to identify early TB symptomatics from this key sub-population who would be then tested using Xpert MTB/RIF technology. Diagnosed TB cases among them would be referred promptly to RNTCP for treatment. This paper aimed to describe the project and its impact. Methods: Adopting a quasi-experimental before-after design, four RNTCP units from two major urban-industrial areas of Odisha were selected for intervention, which spanned five quarters and covered 151,400 people, of which 30% were slum-dwelling migrants. Two similar units comprised the control population. The hypothesis was, reaching the under reached in the intervention area through NFHPs would increase TB notification from these traditionally under-notifying units. RNTCP notification data during intervention was compared with pre-intervention era, adjusted for contemporaneous changes in control population Results: The project detected 488 Xpert+ TB cases, of whom 466 were administered RNTCP treatment. This translated into notification of additional 198 new bacteriologically positive cases to RNTCP, a 30% notification surge, after adjustment for 2% decline in control. This meant an average quarterly increase in notification of 41.20(20.08, 62.31; p<0.001) cases. The increase was immediate, evident from the rise in level in the time series analysis by 50.42(10.28, 90.55; p = 0.02) cases. Conclusion: Engagement with NFHPs contributed to an increase in TB notification to RNTCP from key under reached, slum-dwelling migrant populations. [ABSTRACT FROM AUTHOR]

Background: Even though cholera has existed for centuries and many parts of the country have sporadic, endemic and epidemic cholera, it is still an under-recognized health problem in India. A Cholera Expert Group in the country was established to gather evidence and to prepare a road map for control of cholera in India. This paper identifies cholera burden hotspots and factors associated with an increased risk of the disease. Methodology/Principle findings: We acquired district level data on cholera case reports of 2010–2015 from the Integrated Disease Surveillance Program. Socioeconomic characteristics and coverage of water and sanitation was obtained from the 2011 census. Spatial analysis was performed to identify cholera hotspots, and a zero-inflated Poisson regression was employed to identify the factors associated with cholera and predicted case count in the district. 27,615 cholera cases were reported during the 6-year period. Twenty-four of 36 states of India reported cholera during these years, and 13 states were classified as endemic. Of 641 districts, 78 districts in 15 states were identified as “hotspots” based on the reported cases. On the other hand, 111 districts in nine states were identified as “hotspots” from model-based predicted number of cases. The risk for cholera in a district was negatively associated with the coverage of literate persons, households using treated water source and owning mobile telephone, and positively associated with the coverage of poor sanitation and drainage conditions and urbanization level in the district. Conclusions/Significance: The study reaffirms that cholera continues to occur throughout a large part of India and identifies the burden hotspots and risk factors. Policymakers may use the findings of the article to develop a roadmap for prevention and control of cholera in India. [ABSTRACT FROM AUTHOR]

Rice is among the oldest crops of the world which feeds about half of the world's population. The most significant bacterial disease impacting the rice production is bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae (Xoo). Ten Xoo isolates collected from different rice growing regions of India were characterized morphologically and their reaction to different biochemical tests. Xoo isolates were gram negative, showed positive reaction for potassium hydroxide test and catalase production. The isolates TLG2 and AP showed strong oxidase activity. All the isolates except those from Telangana state showed tolerance to 5 per cent sodium chloride. None of the isolates were able to utilize sorbitol, mannitol and malonate as carbohydrate source for their growth whereas all of them were able to grow at 37 °C. Among all the isolates, KA showed highest swarming ability along with exopolysaccharide and xanthomonadin production. The results indicate that there exists variation in physiological characters among the Xoo isolates and this may have impact on their virulence and survival. [ABSTRACT FROM AUTHOR]

Linseed (Linumusitatissimum L.), commonly known as flaxseed, is an important crop in India due to its high industrial, nutritive, and medicinal value. However, the productivity of linseed in India is relatively low despite ranking second in terms of cultivation area. One of the major factors contributing to low productivity is the incidence of various diseases. Fungal diseases are particularly damaging to the crop, often causing significant losses ranging from 80 to 100 percent during epidemics. Rust (Melampsora liniErenb), wilt (Fusariumoxysporumf.sp. lini), powdery mildew [Oidiumlini, Leviellulataurica (Lev.)] are the major ones. The minor diseases are macrophomina/rhizoctonia wilt/collar rot, sclerotium stem rot, Pythium damping-off, Botrytis rot, Anthracnose and dreschlera blight. The number of seed borne mycoflora are more. Bacterial disease has been reported was aster yellow and among virus Oat blue dwarf virus has been reported. Among the pests associated with linseed, nematodes such as Rotylenchusreniformis, Tylenchorhynchusbrevidens, Meloidogyne incognita, M. hapla, andPratylenchus species have been reported to cause damage to the roots. Additionally, the phanerogamic parasite Cuscuta, commonly known as dodder, can become a serious problem in certain areas where it infests linseed crops. [ABSTRACT FROM AUTHOR]

Behind the statistics forecasting millions of deaths associated with antimicrobial resistance (AMR) is an even greater burden of morbidity leaving many people with long-term chronic illnesses and disability. Despite growing recognition of the importance of inter-sectoral and inter-disciplinary knowledge in forming responses to address this global health threat, there remains a paucity of social science research to understand the social burdens of AMR. In this qualitative study we explore the experiences of people living with chronic AMR infections, their interactions with health providers and therapeutic quests for care, and the effects upon their lives and that of their families and caregivers. Our analysis reveals that the resistant infections impacted not only the physical health but also the mental health of the sufferers and their caregivers, causing major disruptions to their social and work lives. Most undertook arduous treatment regimes – of powerful antibiotics with debilitating side effects, combined a range of other complementary and alternate therapies, including travel to seek treatment overseas. Further, we question the notion of 'AMR survivorship' currently being promoted as part of a public education campaign by the World Health Organisation and whether people with the diverse AMR experience really self-identify as 'survivors' of a biosocial group. [ABSTRACT FROM AUTHOR]

A rare incidence of multiple bacterial infections was reported in Litopenaeus vannamei grow‐out ponds in India. The pathogenic organisms identified are Aeromonas veronii, Bacillus flexus, Kurthia gibsonii, Shewanella decolorationis, Bacillus cereus and Shewanella amazonensis. The infected shrimp showed various clinical and morphological changes such as mucus secretion in the hepatopancreas, bacterial spots in the carapace, red or pink discoloration of abdomen with black stripes and highly melanized body. The Histological studies of the hepatopancreas revealed bacterial plaque in the lumen, inflammatory response, necrosis of connective tissue and lipid droplets. The histology of stomach detected degradation of spongy connective tissue, hypertrophied nucleus and the abdomen showed bacterial plaques in the gaps of the muscle fibre. Histochemically, both gram‐positive and gram‐negative bacteria's were identified in the hepatopancreas and the presence of mucus in the lumen of hepatopancreatic microtubules was confirmed by Alcian blue staining. The electron microscopic studies of the infected shrimp showed multiple bacterial infections and cellular responses like phagocytosis in the hepatopancreas, using transmission electron microscope and scanning electron microscopic confirmed the presence of bacillus and coccobacillus‐shaped bacteria in carapace. [ABSTRACT FROM AUTHOR]

A plant growth-promoting rhizobacterial strain B6 was isolated from a Cowpea rhizosphere soil in the Vellodu village of Dindugul district, Tamil Nadu, India. It could be identified as Pseudomonas aeruginosa VRKK1 through biochemical and 16S rDNA gene sequencing. The plant growth promoting behaviour already exhibited by this strain, further its bioactive metabolite extracted using chloroform. Crude extract and column purification study reveals that the idea of using this biometabolite against Xanthomonas campestris. F4 and F5 fractions showed 41 and 40 mm zone of inhibition which confirmed the broad spectrum antibacterial activity. Further this biometabolite analytically characterized and found to be as octadecanoic acid 2-oxo methyl ester. The identified biometabolite checked for the reduction of bacterial blight disease in cowpea with the disease severity percentage of 40.24% compared to control and induced plants. [ABSTRACT FROM AUTHOR]

Background: Government of India and the World Health Organization have guidelines for outpatient management of young infants 0–59 days with signs of Possible Serious Bacterial Infection (PSBI), when referral is not feasible. Implementation research was conducted to identify facilitators and barriers to operationalizing these guidelines. Methods: Himachal Pradesh government implemented the guidelines in program settings supported by Centre for Health Research and Development, Society for Applied Studies. The strategy included community sensitization, skill enhancement of Accredited Social Health Activists (ASHA), Auxiliary Nurse Midwives (ANMs) and Medical Officers (MOs) to identify PSBI and treat when referral was not feasible. The research team collected information on facilitators and barriers. A technical support unit provided training and oversight. Findings: Among 1997 live births from June 2017 to January 2019, we identified 160 cases of PSBI in young infants resulting in a coverage of 80%, assuming an incidence of 10%. Of these,29(18.1%) had signs of critical illness (CI), 92 (57.5%) had clinical severe infection (CSI), 5 (3.1%)had severe pneumonia (only fast breathing in young infants 0–6 days), while 34 (21%) had pneumonia (only fast breathing in young infants 7–59 days). Hospital referral was accepted by 48/160 (30%), whereas 112/160 (70%) were treated with the simplified treatment regimens at primary level facilities. Of the 29 infants with CI, 18 (62%) accepted referral; 26 (90%) recovered while 3 (10%) who had accepted referral, died. Of the 92 infants who had CSI, 86 (93%) recovered, 65 (71%) received simplified treatment and one infant who had accepted referral, died. All the five infants who had severe pneumonia, recovered; 3 (60%) had received simplified treatment. Of the 34 pneumonia cases, 33 received simplified treatment of which 5 (15%) failed treatment; two out of these 5 died. Overall, 6/160 infants died (case-fatality-rate 3.4%); 2 in the simplified treatment (case-fatality-rate 1.8%) and 4 in the hospital group (case-fatality-rate 8.3%). Delayed identification and care-seeking by families and health system weaknesses like manpower gaps and interrupted supplies were challenges in implementation. Conclusions: Implementation of the guidelines in program settings is possible and acceptable. Scaling up would require creating community awareness, early identification and appropriate care-seeking, strengthening ASHA home-visitation program, building skills and confidence of MOs and ANMs, uninterrupted supplies and a dependable referral system. [ABSTRACT FROM AUTHOR]

Purpose: Intracameral antibiotic in cataract surgery has shown level I evidence as prophylaxis for postoperative endophthalmitis. Not much is known if one should also use topical antibiotics after intracameral injection. The purpose of the study was to determine efficacy of intracameral antibiotic with and without postoperative topical antibiotic in reducing the incidence of acute endophthalmitis after cataract surgery in rural India.Methods: A.prospective comparative, non-randomized interventional study was designed in 15 rural centres in India. The study recruited 40,006 patients (n = 42,466 eyes), who underwent cataract surgery (phacoemulsification/small incision cataract surgery), and received intracameral antibiotic (cefuroxime/moxifloxacin). Postoperative topical antibiotic prescription was left to the choice of the treating physician, but they were encouraged not to use it in uneventful surgeries. Primary outcome measure was occurrence of acute clinical endophthalmitis within 6 weeks of surgery. Statistical analysis was done using STATA software v13.1 (StataCorp, Texas); P value of <0.05 was considered statistically significant.Results: In the study, 17,932 (42%) eyes received intracameral cefuroxime (ICC) and 24,534 (58%) eyes received intracameral moxifloxacin (ICM). Topical antibiotic was not prescribed to 17,855 (42%) eyes - 5723 (32%) eyes in ICC group and 12,132 (68%) eyes in ICM group. Acute clinical endophthalmitis occurred in 15 (0.035%) eyes - 1 / 3515 (0.028%) eyes and 1 / 2231 (0.045%) eyes that received and did not receive topical antibiotic, respectively. The difference in occurrence of endophthalmitis with/without topical antibiotics in each group (ICC: 0.016% and 0.017%; P = 0.958; ICM: 0.040% and 0.058%; P = 0.538) was not significant (P = 0.376).Conclusion: Supplementing intracameral antibiotic with topical antibiotic postoperatively did not impact the occurrence of acute post cataract surgery endophthalmitis in rural India. [ABSTRACT FROM AUTHOR]

Background A cluster of 15 acute skin and soft tissue infections (SSTIs), including two cases of necrotizing fasciitis, reported in July 2018 from Kalwala village, led us to investigate and describe their epidemiology and to provide recommendations. Methods Cases, defined as localized painful swelling and redness in Kalwala residents from 1 December 2017 to 20 August 2018, were identified from hospital records and house-to-house surveys. We conducted an unmatched case-control study to identify risk factors for severity. We cultured wound samples and environmental samples from wound-dressing stations. Results We identified 36 cases (median age: 55 [range 17–80] y; 78% male), village attack rate 1% (36/4337) and no deaths. In 34 cases (94%), lower limbs were involved. Lymphatic filariasis (LF) was a common predisposing condition (67%). Comorbidities (diabetes or hypertension) (OR=9; 95% CI 2.0 to 41.1), poor limb hygiene (OR=16; 95% CI 2.8 to 95.3) and poor health-seeking behavior (OR=5; 95% CI 1.6 to 30.8) were associated with severity. All seven wound samples and 8/11 samples from wound-dressing stations showed atypical polymicrobial growth (Pseudomonas, Proteus, Klebsiella, Escherichia coli and Clostridium). Conclusion The outbreak of SSTIs among older males with LF was due to secondary bacterial infections and severity was associated with comorbidities, poor hygiene and health-seeking behavior, and likely contamination during wound-dressing. The LF elimination program managers was alerted, programmatic interventions were scaled up, home/facility-based morbidity and comorbidity management was facilitated and the outbreak was rapidly contained. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis. It is classified as an acid-fast bacillus (AFB) because it retains stain after being treated with an acidic solution. Mycobacterium tuberculosis is a gram-positive aerobic rod-shaped bacterium with a length of 1 to 4 micrometers. Mismanagement of anti-tuberculosis drugs approved for the treatment of TB increased drug-resistant Mycobacterium tuberculosis. Consequently, treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis patientsis an enormous task for emerging and underdeveloped countries Therefore, medicinal plant-based drugs willbe one of the safest options for the treatment of multidrug resistant TB, Hence in present study we haveevaluated the drug potential of Sida acuta Burm.f., Abelmoschus esculentus (Linn.) Moech, Adhatoda vasicaNees and Azadizachata indica A. Juss. These are well-known annual plants, distributed throughout India, andtraditionally used by tribal communities in treatment for tuberculosis. The prepared powder from all theselected plants were used for the solvent based extraction using Soxhlet extractor with different solvents. The anti-tubercular potential assessment, all the extracts of water and methanol were applied on the ATCCculture of Mycobacterium smegmatis (ATCC 607, Lot 114-26-4). In this study we have reported anti-tubercular potential in methonolic extract of leaves of the Adhatoda vasica Nees. This study provided thebaseline data for the drug development against Mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

Leprosy is a bacterial infection causing severe disfigurement of the affected individual. It is considered as an ancient disease affecting humanity since thousands of years and also has tremendous stigma associated with it. It is known as a neglected tropical disease. In spite of all the efforts, the disease remains a major healthcare distress in many underdeveloped and developing countries like India and Brazil. Thus, to understand the disease and implement various strategies successfully, one need to understand the epidemiological aspect of the disease along with various operational factors influencing the epidemiological data. Thus, the present paper describes the various epidemiological facts and figures of leprosy along with the suggestions and measures to tackle this global ailment. [ABSTRACT FROM AUTHOR]

Purpose: Intracameral antibiotics are known to reduce the incidence of acute endophthalmitis. Various drugs are available for intracameral use. This prospective study was carried out to compare the efficacies of intracameral cefuroxime and moxifloxacin prophylaxis in reducing the incidence of acute endophthalmitis after cataract surgery in rural India.Methods: This was a prospective, nonrandomized, comparative, interventional study. Between October 2016 and March 2018, 15 eye care facilities spread over four Indian states were preselected to use either of the intracameral antibiotics, cefuroxime or moxifloxacin, following cataract surgery (phacoemulsification or manual small incision cataract surgery, SICS). The main outcome measure was the occurrence of acute clinical endophthalmitis within six weeks of the surgery. This was compared with the earlier rate of endophthalmitis in the same locations.Results: The study was done in 42,466 eyes. Of the total, 42.2% received intracameral cefuroxime and 57.8% received intracameral moxifloxacin. SICS was performed more often. Clinical acute endophthalmitis occurred in 15 eyes. This accounted to a 72.22% reduction, from the earlier 0.126% to 0.035%, of postcataract surgery acute endophthalmitis. The reduction in the incidence of endophthalmitis after intracameral cefuroxime was 0.017% and that after intracameral moxifloxacin was 0.049%. With either intracameral antibiotics, the reduction in incidence was statistically significant (P < 0.001), but not between the molecules. Intracameral cefuroxime showed 66.67% reduction and intracameral moxifloxacin showed 74.74% reduction.Conclusion: A 3.6-fold decrease in postcataract surgery endophthalmitis was observed upon the use of intracameral antibiotics in rural India. Both intracameral cefuroxime and moxifloxacin proved efficacious. [ABSTRACT FROM AUTHOR]

Background: Fever is a cause for concern for both parents and the treating pediatrician and a common reason for antibiotic overuse. However, the proportion of children hospitalized for fever with serious bacterial infection (SBI) is uncertain. We aimed to evaluate the epidemiological, clinical, hematological, and biochemical risks for SBI among the children admitted with fever.Method: This prospective study was conducted in a rural teaching hospital in India on consecutive children, aged 3 months-12 years, presenting with fever 100 °F (37.7 °C) or higher. The presence of SBI was confirmed with one of the following criteria: (a) a positive blood culture; (b) roentgenographically confirmed pneumonia with high titres of C-reactive protein; (c) a culture-confirmed urinary tract infection; (d) enteric fever diagnosed clinically in addition to either a positive blood culture or high Widal titers; and (e) meningitis diagnosed clinically in addition to either a positive blood culture or cerebrospinal fluid culture. A predefined questionnaire was filled.Results: A total of 302 children were included in the study, out of which 47% (95% CI 41.4-52.7%) presented with SBI. The factors associated with confirmed SBI in bivariate analysis were history of previous hospitalization, history of chronic illness, history of medication in the previous 1 week, a partially immunized child, history of common cold, moderate-grade fever, toxic look, significant lymphadenopathy, absence of BCG scar, delayed development, irritability, breathlessness, respiratory distress, poor feeding, significant weight loss, suspected urinary tract infection, hyponatremia, hypokalemia, and abnormal leucocyte count. The final generalized logistic regression model revealed partially immunized child (RR 4.26), breathlessness (RR 1.80), weight loss (RR 2.28), and suspected urinary tract infection (RR 1.95) as risk factors for the increased risk of SBI.Conclusion: The study identified multiple risk factors for SBI. Pediatricians can be made aware of these risk factors. Further studies are warranted to identify age-specific risk factors for SBI because most clinicians depend on clinical signs and symptoms to identify SBI. [ABSTRACT FROM AUTHOR]

Background: Prioritizing zoonotic diseases is one of the emerging tasks for developing multi-sectoral collaboration within One Health. Globally, many efforts have been made to prioritize zoonotic diseases at national levels, especially in low resource settings. Prioritization of zoonoses has been conducted in different countries at different levels (i.e. national, regional and local) for different purposes. India has also initiated prioritization of zoonotic diseases at the national level. However, in a country like India with wide climatic variations, different animal-human and vector densities, it is important to look at these zoonotic conditions in local settings too. The present study aims to determine which zoonoses should be prioritized for collaboration between stakeholders in the Indian city of Ahmedabad. Methods: The present study followed a participatory research method, entailing a stakeholder workshop for prioritizing zoonotic diseases in Ahmedabad. It was carried out through a facilitated consultative process involving 19 experts in zoonoses from the human and animal health systems during a one-day workshop in September 2018. To prioritize the zoonotic diseases, the One Health Zoonotic Disease Prioritization (OHZDP) tool of the U.S. Centers for Disease Control and Prevention was adopted. The Analytical Hierarchical Process (AHP) and decision-tree analysis were used to rank the diseases. Results: Out of 38 listed zoonotic diseases, 14 were selected for prioritization. These were scored and weighed against five criteria: severity of disease in humans, potential for epidemic and/or pandemic, availability of prevention and/or control strategies, burden of animal disease existing inter-sectoral collaboration. The top five diseases that have been prioritized for Ahmedabad are Rabies, Brucellosis, Avian Influenza (H5N1), Influenza A (H1N1) and Crimean-Congo Hemorrhagic Fever. Sensitivity analysis did not indicate significant changes in zoonotic disease prioritization based on criteria weights. Conclusion: Prioritization of zoonotic diseases at the local level is essential for development of effective One Health strategies. This type of participatory disease prioritization workshop is highly recommended and can be replicated in other Indian cities, as well as in other low and middle-income countries. [ABSTRACT FROM AUTHOR]

The East African Indian (EAI) and Central Asian (CAS) lineages of Mycobacterium tuberculosis complex (MTBC) mainly infect tuberculosis (TB) patients in the eastern hemisphere which contains many of the 22 high TB burden countries including China and India. We investigated if phylogeographical, epidemiological and demographical characteristics for these 2 lineages differed in SITVIT2 database. Genotyping results and associated data (age, sex, HIV serology, drug resistance) on EAI and CAS lineages (n = 10,974 strains) were extracted. Phylogenetic and Bayesian, and other statistical analyses were used to compare isolates. The male/female sex ratio was 907/433 (2.09) for the EAI group vs. 881/544 (1.62) for CAS (p-value<0.002). The proportion of younger patients aged 0–20 yrs. with CAS lineage was significantly higher than for EAI lineage (18.07% vs. 10.85%, p-value<0.0001). The proportion of multidrug resistant and extensively drug resistant TB among CAS group (30.63% and 1.03%, respectively) was significantly higher than in the EAI group (12.14% and 0.29%, respectively; p-value<0.0001). Lastly, the proportion of HIV+ patients was 20.34% among the EAI group vs. 3.46% in the CAS group (p-value<0.0001). This remarkable split observed between various parameters for these 2 lineages was further corroborated by their geographic distribution profile (EAI being predominantly found in Eastern-Coast of Africa, South-India and Southeast Asia, while CAS was predominantly found in Afghanistan, Pakistan, North India, Nepal, Middle-east, Libya, Sudan, Ethiopia, Kenya and Tanzania). Some geo-specificities were highlighted. This study demonstrated a remarkable cleavage for aforementioned characteristics of EAI and CAS lineages, showing a North-South divide along the tropic of cancer in Eastern hemisphere–mainly in Asia, and partly prolonged along the horn of Africa. Such studies would be helpful to better comprehend prevailing TB epidemic in context of its historical spread and evolutionary features, and provide clues to better treatment and patient-care in countries and regions concerned by these lineages. [ABSTRACT FROM AUTHOR]

This open-label study assessed the safety and immunogenicity of two doses (14 days apart) of an indigenously manufactured, killed, bivalent (Vibrio cholerae O1 and O139), whole-cell oral cholera vaccine (SHANCHOL; Shantha Biotechnics) in healthy adults (n = 100) and children (n = 100) in a cholera endemic area (Vellore, South India) to fulfill post-licensure regulatory requirements and post-World Health Organization (WHO) prequalification commitments. Safety and reactogenicity were assessed, and seroconversion rates (i.e. proportion of participants with a ≥ 4-fold rise from baseline in serum vibriocidal antibody titers against V. cholerae O1 Inaba, O1 Ogawa and O139, respectively) were determined 14 days after each vaccine dose. No serious adverse events were reported during the study. Commonly reported solicited adverse events were headache and general ill feeling. Seroconversion rates after the first and second dose in adults were 67.7% and 55.2%, respectively, against O1 Inaba; 47.9% and 45.8% against O1 Ogawa; and 19.8% and 20.8% against O139. In children, seroconversion rates after the first and second dose were 80.2% and 68.8%, respectively, against O1 Inaba; 72.9% and 67.7% against O1 Ogawa; and 26.0% and 18.8% against O139. The geometric mean titers against O1 Inaba, O1 Ogawa, and O139 in both adults and children were significantly higher after each vaccine dose compared to baseline titers (P < 0.001; for both age groups after each dose versus baseline). The seroconversion rates for O1 Inaba, O1 Ogawa, and O139 in both age groups were similar to those in previous studies with the vaccine. In conclusion, the killed, bivalent, whole-cell oral cholera vaccine has a good safety and reactogenicity profile, and is immunogenic in healthy adults and children. Trial Registration: ClinicalTrials.gov ; CTRI/2012/01/002354. [ABSTRACT FROM AUTHOR]

Background: Private providers dominate health care in India and provide most tuberculosis (TB) care. Yet efforts to engage private providers were viewed as unsustainably expensive. Three private provider engagement pilots were implemented in Patna, Mumbai and Mehsana in 2014 based on the recommendations in the National Strategic Plan for TB Control, 2012–17. These pilots sought to improve diagnosis and treatment of TB and increase case notifications by offering free drugs and diagnostics for patients who sought care among private providers, and monetary incentives for providers in one of the pilots. As these pilots demonstrated much higher levels of effectiveness than previously documented, we sought to understand program implementation costs and predict costs for their national scale-up. Methods and findings: We developed a common cost structure across these three pilots comprising fixed and variable cost components. We conducted a retrospective, activity-based costing analysis using programmatic data and qualitative interviews with the respective program managers. We estimated the average recurring costs per TB case at different levels of program scale for the three pilots. We used these cost estimates to calculate the budget required for a national scale up of such pilots. The average cost per privately-notified TB case for Patna, Mumbai and Mehsana was estimated to be US$95, US$110 and US$50, respectively, in May 2016 when these pilots were estimated to cover 50%, 36% and 100% of the total private TB patients, respectively. For Patna and Mumbai pilots, the average cost per case at full scale, i.e. 100% coverage of private TB patients, was projected to be US$91 and US$101, respectively. In comparison, the national TB program’s budget for 2015 averages out to $150 per notified TB case. The total annual additional budget for a national scale up of these pilots was estimated to be US$267 million. Conclusions: As India seeks to eliminate TB, extensive national engagement of private providers will be required. The cost per privately-notified TB case from these pilots is comparable to that already being spent by the public sector and to the projected cost per privately-notified TB case required to achieve national scale-up of these pilots. With additional funds expected to execute against national TB elimination commitments, the scale-up costs of these operationally viable and effective private provider engagement pilots are likely to be financially viable. [ABSTRACT FROM AUTHOR]

Background: Outreach and promotion programs are essential to ensuring uptake of new public health interventions and guidelines. We assessed the costs and operation dynamics of outreach and promotion efforts for up front Xpert MTB/RIF (Xpert) testing for pediatric presumptive tuberculosis (TB) patients in four major Indian cities. Methods: Xpert test costs were assessed as weighted average per-test costs based on the daily workload dynamics matched by test volume specific Xpert unit cost at each study site. Costs of outreach programs to recruit health providers to refer pediatric patients for Xpert testing were assessed as cost per referral for each quarter based on total program costs and referral data. All costs were assessed in the health service provider’s perspective and expressed in 2015 USD. Results: Weighted average per-test costs ranged from $14.71 to $17.81 at the four laboratories assessed. Differences between laboratories were associated with unused testing capacity and/or frequencies of overtime work to cope with increasing demand and same-day testing requirements. Outreach activities generated between 825 and 2,065 Xpert testing referrals on average each quarter across the four study sites, translating into $0.63 to $2.55 per patient referred. Overall outreach costs per referral decreased with time, stabilizing at an average cost of $1.10, and demonstrated a clear association with increased referrals. Conclusions: Xpert test and outreach program costs within and across study sites were mainly driven by the dynamics of Xpert testing demand resulting from the combined outreach activities. However, these increases in demand required considerable overtime work resulting in additional costs and operational challenges at the study laboratories. Therefore, careful laboratory operational adjustment should be evaluated at target areas in parallel to the anticipated demand from the Xpert referral outreach program scale-up in other Indian regions. [ABSTRACT FROM AUTHOR]

Background: India has the highest burden of tuberculosis (TB). Although most patients with TB in India seek care from the private sector, there is limited evidence on quality of TB care or its correlates. Following our validation study on the standardized patient (SP) method for TB, we utilized SPs to examine quality of adult TB care among health providers with different qualifications in 2 Indian cities.Methods and Findings: During 2014-2017, pilot programs engaged the private health sector to improve TB management in Mumbai and Patna. Nested within these projects, to obtain representative, baseline measures of quality of TB care at the city level, we recruited 24 adults to be SPs. They were trained to portray 4 TB "case scenarios" representing various stages of disease and diagnostic progression. Between November 2014 and August 2015, the SPs visited representatively sampled private providers stratified by qualification: (1) allopathic providers with Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees or higher and (2) non-MBBS providers with alternative medicine, minimal, or no qualifications. Our main outcome was case-specific correct management benchmarked against the Standards for TB Care in India (STCI). Using ANOVA, we assessed variation in correct management and quality outcomes across (a) cities, (b) qualifications, and (c) case scenarios. Additionally, 2 micro-experiments identified sources of variation: first, quality in the presence of diagnostic test results certainty and second, provider consistency for different patients presenting the same case. A total of 2,652 SP-provider interactions across 1,203 health facilities were analyzed. Based on our sampling strategy and after removing 50 micro-experiment interactions, 2,602 interactions were weighted for city-representative interpretation. After weighting, the 473 Patna providers receiving SPs represent 3,179 eligible providers in Patna; in Mumbai, the 730 providers represent 7,115 eligible providers. Correct management was observed in 959 out of 2,602 interactions (37%; 35% weighted; 95% CI 32%-37%), primarily from referrals and ordering chest X-rays (CXRs). Unnecessary medicines were given to nearly all SPs, and antibiotic use was common. Anti-TB drugs were prescribed in 118 interactions (4.5%; 5% weighted), of which 45 were given in the case in which such treatment is considered correct management. MBBS and more qualified providers had higher odds of correctly managing cases than non-MBBS providers (odds ratio [OR] 2.80; 95% CI 2.05-3.82; p < 0.0001). Mumbai non-MBBS providers had higher odds of correct management than non-MBBS in Patna (OR 1.79; 95% CI 1.06-3.03), and MBBS providers' quality of care did not vary between cities (OR 1.15; 95% CI 0.79-1.68; p = 0.4642). In the micro-experiments, improving diagnostic certainty had a positive effect on correct management but not across all quality dimensions. Also, providers delivered idiosyncratically consistent care, repeating all observed actions, including mistakes, approximately 75% of the time. The SP method has limitations: it cannot account for patient mix or care-management practices reflecting more than one patient-provider interaction.Conclusions: Quality of TB care is suboptimal and variable in urban India's private health sector. Addressing this is critical for India's plans to end TB by 2025. For the first time, we have rich measures on representative levels of care quality from 2 cities, which can inform private-sector TB interventions and quality-improvement efforts. [ABSTRACT FROM AUTHOR]

Background: Evidence supports the integration of prevention and management for tuberculosis (TB) with non-communicable diseases (NCDs). Bi-directional screening for TB and diabetes mellitus (DM) is already implemented in India, a country with a dual burden of TB and NCDs. However, very limited programmatic data are available on the feasibility of adding other NCDs and their risk factors in such screening programme. Objective: To assess the yield, feasibility, and acceptability of a two-stage integrated screening for NCDs and risk factors for NCDs among patients with TB ≥20 years and treated in DOTS centres of two medical colleges in Delhi, between October 2016 and March 2017. Methods: It was a mixed-methods, triangulation study with a quantitative component (cross-sectional study using questionnaires, anthropometric measurements and records review) and a qualitative component (descriptive study using interview data). Results: Amongst 403 patients screened, the prevalence of hypertension was 7% (n = 28) with 20 new cases detected and 8% for DM (n = 32) with 6 new cases diagnosed. The number needed to screen to find a new case was 20 and 63 for hypertension and DM respectively. The most frequent NCD-risk factors were inadequate vegetable (80%) and fruits (72%) intake, alcohol use (34%), use of smokeless tobacco (33%) and smoking (32%). Clustering of four or more risk factors was associated with increasing age and male sex (p<0.05). Both patients and health providers considered the screening relevant and acceptable. However, waiting time and costs involved in blood tests were considered as bothersome by the patients, while health providers perceived increased workload, inadequate medical supplies and inadequate skills and knowledge as key challenges in implementation of the screening. Conclusion: Integrating screening for NCDs and their risk factors in the existing TB programme produces high yield and it is feasible and acceptable by patients and health providers provided the challenges are overcome. [ABSTRACT FROM AUTHOR]

Purpose: To report Enterococcus faecalis endophthalmitis (EFE) in children and its comparison with adults.Methods: Retrospective study of 19 children up to 18 years age, undergoing vitrectomy for EFE at a referral eye center from January 1995 to December 2015. The results were compared to 18 adults with EFE.Results: The mean age was 7.4 ± 3.06 years. Post-traumatic EFE was seen in 17 (89.4%) children (p < 0.05) versus postoperative EFE seen in 12 (66%) adults. Broomstick 9 (52.9%) and hypodermic needle injury 6 (35.2%) were common associations. "Optimum functional outcome" was achieved in 12 (63.1%) eyes of children and 5 (27.7%) eyes of adults (p = 0.03). Sealed and Zone II wounds, lens, and needle injuries had good outcome whereas intervention after 3 days and retinal detachment had poor outcomes (p < 0.05). The was no correlation with the Ocular Trauma Score.Conclusion: EFE in children is rare; seen with broom stick and needle injuries, if managed early recovers optimum vision. [ABSTRACT FROM AUTHOR]

Background: Worldwide, acute bacterial meningitis is a major cause of high morbidity and mortality among under five children, particularly in settings where vaccination for H. influenzae type b, S. pneumoniae and N. meningitidis is yet to be introduced in the national immunization programs. Estimation of disease burden of bacterial meningitis associated with these pathogens can guide the policy makers to consider inclusion of these newer vaccines in the immunization programs. A network of hospital based sentinel surveillance was established to generate baseline data on the burden of bacterial meningitis among children aged less than 5 years in India and to provide a platform for impact assessment following introduction of the Pentavalent and Pneumococcal Conjugate Vaccines (PCV). Methods: During surveillance carried out in select hospitals across India in 2012–2013, information regarding demographics, immunization history, clinical history, treatment details and laboratory investigations viz. CSF biochemistry, culture, latex agglutination and PCR was collected from children aged 1 to 59 months admitted with suspected bacterial meningitis. Results: A total of 3104 suspected meningitis cases were enrolled from 19,670 children admitted with fever at the surveillance hospitals. Of these, 257 cases were confirmed as cases of meningitis. They were due to S. pneumoniae (82.9%), H. influenzae type b (14.4%) and N. meningitidis (2.7%). Highest prevalence (55.3%) was observed among children 1 to 11 months. Antimicrobial susceptibility testing revealed considerable resistance among S. pneumoniae isolates against commonly used antibiotics such as cotrimoxazole, erythromycin, penicillin, and cefotaxime. More commonly prevalent serotypes of S. pneumoniae in circulation included 6B, 14, 6A and 19F. More than 90% of serotypes identified were covered by Pneumococcal Conjugate Vaccine 13. Conclusions: We observed that S. pneumoniae was the commonest cause of bacterial meningitis in hospitalized children under five years of age in India. Continued surveillance is expected to provide valuable information and trends in future, to take an informed decision on introduction of pneumococcal vaccination in Universal Immunization Programme in India and will also eventually help in post-vaccination impact evaluation. [ABSTRACT FROM AUTHOR]

Background: Rising non-communicable diseases (NCDs) coupled with increasing injuries have resulted in a significant increase in health spending in India. While out-of-pocket expenditure remains the major source of health care financing in India (two-thirds of the total health spending), the financial burden varies enormously across diseases and by the economic well-being of the households. Though prior studies have examined the variation in disease pattern, little is known about the financial risk to the families by type of diseases in India. In this context, the present study examines disease-specific out-of-pocket expenditure (OOPE), catastrophic health expenditure (CHE) and distress health financing. Methods and materials: Unit data from the 71st round of the National Sample Survey Organization (2014) was used for this study. OOPE is defined as health spending on hospitalization net of reimbursement, and CHE is defined as household health spending exceeding 10% of household consumption expenditure. Distress health financing is defined as a situation when a household has to borrow money or sell their property/assets or when it gets contributions from friends/relatives to meet its health care expenses. OOPE was estimated for 16 selected diseases and across three broad categories- communicable diseases, NCDs and injuries. Multivariate logistic regression was used to understand the determinants of distress financing and CHE. Results: Mean OOPE on hospitalization was INR 19,210 and was the highest for cancer (INR 57,232) followed by heart diseases (INR 40,947). About 28% of the households incurred CHE and faced distress financing. Among all the diseases, cancer caused the highest CHE (79%) and distress financing (43%). More than one-third of the inpatients reported distressed financing for heart diseases, neurological disorders, genito urinary problems, musculoskeletal diseases, gastro-intestinal problems and injuries. The likelihood of incurring distress financing was 3.2 times higher for those hospitalized for cancer (OR 3.23; 95% CI: 2.62–3.99) and 2.6 times for tuberculosis patients (OR 2.61; 95% CI: 2.06–3.31). A large proportion of households who had reported distress financing also incurred CHE. Recommendations: Free treatment for cancer and heart diseases is recommended for the vulnerable sections of the society. Risk-pooling and social security mechanisms based on contributions from both households as well as the central and state governments can reduce the financial burden of diseases and avert households from distress health financing. [ABSTRACT FROM AUTHOR]

Background: In a study conducted in Bhopal district (a setting with facility for molecular drug susceptibility testing (DST)) located in central India in 2014–15, we found high levels of pre-diagnosis attrition among patients with presumptive multi drug-resistant tuberculosis (MDR-TB)–meaning TB patients who were eligible for DST, were not being tested. Objectives: In this study, we explored the health care provider perspectives into barriers and suggested solutions for improving DST. Methods: This was a descriptive qualitative study. One to one interviews (n = 10) and focus group discussions (n = 2) with experienced key informants involved in programmatic management of DR-TB were conducted in April 2017. Manual descriptive thematic analysis was performed. Results: The key barriers reported were a) lack of or delay in identification of patients eligible for DST because of using treatment register as the source for identifying patients b) lack of assured specimen transport after patient identification and c) lack of tracking. Extra pulmonary TB patients were not getting identified as eligible for DST. Solutions suggested by the health care providers were i) generation of unique identifier at identification in designated microscopy center (DMC), immediate intimation of unique identifier to district and regular monitoring by senior TB laboratory and senior treatment supervisors of patients eligible for DST that were missed; ii) documentation of unique identifier at each step of cascade; iii) use of human carriers/couriers to transport specimen from DMCs especially in rural areas; and iv) routine entry of all presumptive extra-pulmonary TB specimen, as far as possible, in DMC laboratory register. Conclusion: Lack of assured specimen transport and lack of accountability for tracking patient after identification and referral were the key barriers. The identification of patients eligible for DST among microbiologically confirmed TB at the time of diagnosis and among clinically confirmed TB at the time of treatment initiation is the key. Use of unique identifier at identification and its use to ensure cohort wise tracking has to be complemented with specimen transport support and prompt feedback to the DMC. The study has implications to improve detection of MDR-TB among diagnosed/notified TB patients. [ABSTRACT FROM AUTHOR]

Background: Globally, India has the world’s highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP. Objective: To evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment. Methods: This is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics. Results: In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92–125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202–381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed doses in intensive phase (IP) and continuation phase (CP); cavitary disease; prior treatment episodes characterized by re-treatment regimen taken twice, longer duration and more episodes of treatment; any weight loss during treatment; males and additional resistance to first line drugs (Ethambutol, Streptomycin). In a subgroup of 104 MDR-TB patients, 62 (59.6%) had Ofloxacin resistance among whom only 25.8% had treatment success, half of the success (54.8%) seen in Ofloxacin sensitive patients. Baseline susceptibility to Ofloxacin (HR 2.04) and Kanamycin (HR 4.55) significantly doubled and quadrupled the chances for culture conversion respectively while baseline susceptibility to Ofloxacin (AOR 0.37) also significantly reduced the odds of unfavorable treatment outcomes (p value ≤0.05) in multinomial logistic regression model. Conclusion: India’s initial MDR-TB patients’ cohort treated under the RNTCP experienced poor treatment outcomes. To address the factors associated with poor treatment outcomes revealed in our study, a systematic multi-pronged approach would be needed. A series of policies and interventions have been developed to address these factors to improve DR-TB treatment outcomes and are being scaled-up in India. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) patients face substantial delays prior to treatment initiation, and out of pocket (OOP) expenditures often surpass the economic productivity of the household. We evaluated the pre-diagnostic cost and health seeking behaviour of new adult pulmonary TB patients registered at Primary Health Centres (PHCs) in Vellore district, Tamil Nadu, India. Methods: This descriptive study, part of a randomised controlled trial conducted in three rural Tuberculosis Units from Dec 2012 to Dec 2015, collected data on number of health facilities, dates of visits prior to the initiation of anti-tuberculosis treatment, and direct OOP medical costs associated with TB diagnosis. Logistic regression analysis examined the factors associated with delays in treatment initiation and OOP expenditures. Results: Of 880 TB patients interviewed, 34.7% presented to public health facilities and 65% patients sought private health facilities as their first point of care. The average monthly individual income was $77.79 (SD 57.14). About 69% incurred some pre-treatment costs at an average of $39.74. Overall, patients experienced a median of 6 days (3–11 IQR) of time to treatment initiation and 21 days (10–30 IQR) of health systems delay. Age ≤ 40 years (aOR: 1.73; CI: 1.22–2.44), diabetes (aOR: 1.63; CI: 1.08–2.44) and first visit to a private health facility (aOR: 17.2; CI: 11.1–26.4) were associated with higher direct OOP medical costs, while age ≤ 40 years (aOR: 0.64; CI: 0.48–0.85) and first visit to private health facility (aOR: 1.79, CI: 1.34–2.39) were associated with health systems delay. Conclusion: The majority of rural TB patients registering at PHCs visited private health facilities first and incurred substantial direct OOP medical costs and delays prior to diagnosis and anti-tuberculosis treatment initiation. This study highlights the need for PHCs to be made as the preferred choice for first point of contact, to combat TB more efficiently. [ABSTRACT FROM AUTHOR]

Objective: Tuberculosis (TB) is a major source of mortality in urban India, with many structural challenges to optimal care delivery. In the government TB program in Chennai, India’s fourth most populous city, there is a 49% gap between the official number of smear-positive TB patients diagnosed and the official number registered in TB treatment within the city in 2014. We hypothesize that this “urban registration gap” is partly due to rural patients temporarily visiting the city for diagnostic evaluation. Methods: We collected data for one month (May 2015) from 22 government designated microscopy centers (DMCs) in Chennai where 90% of smear-positive TB patients are diagnosed and coded patient addresses by location. We also analyzed the distribution of chest symptomatics (i.e., patients screened for TB because of pulmonary symptoms) and diagnosed smear-positive TB patients for all of Chennai’s 54 DMCs in 2014. Results: At 22 DMCs in May 2015, 565 of 3,543 (15.9%) chest symptomatics and 71 of 412 (17.2%) diagnosed smear-positive patients had an address outside of Chennai. At the city’s four high patient volume DMCs, 54 of 270 (20.0%) smear-positive patients lived out-of-city. At one of these high-volume DMCs, 31 of 59 (52.5%) smear-positive patients lived out-of-city. Out of 6,135 smear-positive patients diagnosed in Chennai in 2014, 3,498 (57%) were diagnosed at the four high-volume DMCs. The 32 DMCs with the lowest patient volume diagnosed 10% of all smear-positive patients. Conclusions: TB case detection in Chennai is centralized, with four high-volume DMCs making most diagnoses. One-sixth of patients are from outside the city, most of whom get evaluated at these high-volume DMCs. This calls for better coordination between high-volume city DMCs and rural TB units where many patients may take TB treatment. Patient mobility only partly explains Chennai’s urban registration gap, suggesting that pretreatment loss to follow-up of patients who live within the city may also be a major problem. [ABSTRACT FROM AUTHOR]

Antibiotics to treat healthcare-associated infections (HCAIs) contribute to a substantial proportion of drug expenditure in intensive care units (ICUs). Our study aimed to determine the common HCAIs in our hospital ICU, to assess the antibiotics prescribed and the mean antibiotic cost per HCAI. All adult patients, admitted to the ICU over a 1-year period, were included in the study. HCAIs were determined according to CDC definition. The incidence of HCAIs in the ICU was 16%. Ventilator associated pneumonia (50%) was the most common HCAI, followed by urinary tract infection (35.6%). The total cost of antibiotic treatment for HCAIs in ICU over a 1-year period was approximately Rs. 2 million (US$32,000); the mean antibiotic cost per HCAI was calculated as Rs. 17,000 (US$255). HCAIs in the ICU thus put a significant economic burden on the patient and the healthcare network and should be prevented by implementing recommended infection control guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Vaccinating a buffer of individuals around a case (ring vaccination) has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE) of oral cholera vaccines (OCVs) for such a strategy.Methods and Findings: This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals' vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5-11 times higher than that among the cohort not exposed to cholera cases. The risk gradually diminished with an increase in distance and time. The overall and indirect VE measured between 8 and 28 d after exposure to a cholera index case during the first 2 y was 91% (95% CI 62%-98%) and 93% (95% CI 44%-99%), respectively. VE persisted for 5 y after vaccination and was similar whether the index case was a young child (<5 y) or was older. Of note, this study was a reanalysis of a cholera vaccine trial that used two doses; thus, a limitation of the study relates to the assumption that a single dose, if administered quickly, will induce a similar level of total and indirect protection over the short term as did two doses.Conclusions: These findings suggest that high-level protection can be achieved if individuals living close to cholera cases are living in a high coverage ring. Since this was an observational study including participants who had received two doses of vaccine (or placebo) in the clinical trial, further studies are needed to determine whether a ring vaccination strategy, in which vaccine is given quickly to those living close to a case, is feasible and effective.Trial Registration: ClinicalTrials.gov NCT00289224. [ABSTRACT FROM AUTHOR]

Background: Neonatal mortality continues to be a significant problem in the Indian setting, especially in very low birth weight (VLBW) neonates. Selenium (Se) has been shown to possess antioxidant properties, and some recent studies have shown a reduction in the sepsis-attributable neonatal mortality with its use. India is a Se-deficient country. Blood Se concentrations in newborns are lower than those of their mothers and lower still in preterm infants.Objective: To evaluate the efficacy of Se in preventing the first episode of late-onset sepsis in VLBW preterm neonates.Methods: Ninety neonates weighing <1500 g and period of gestation <32 weeks, asymptomatic at birth and admitted to the neonatal intensive-care unit (NICU) in the first 12 h of birth with no maternal risk factors for sepsis were analyzed in the study. Se or placebo was supplemented orally once daily from 1st to 28th day of life to the test (n = 45) or control (n = 45) groups, respectively, followed by daily clinical assessment for signs or symptoms of sepsis in the hospital and weekly after discharge.Results: Preterm VLBW neonates (mean birth weight 1464.22 ± 50.14 g and mean gestational age 221.75 ± 4 days) are Se deficient at birth, with mean (SD) Se levels 31.1 ± 14.8 µg/l. Se supplementation at 10 µg/day increased serum Se levels significantly (63.9 ± 13.9 µg/l on Day 28 in Se vs. 40.9 ± 17.3 on Day 28 in placebo; p < 0.01). The incidence of the first episode of culture-proven late-onset sepsis was significantly lower in the Se than in the placebo group. [0/45 (0%) in Se vs. 6/45 (13.3%) in placebo; p = 0.033]. The incidence of probable sepsis was found to be significantly lower in the Se group [7/45 (15.55%)] than in the placebo [16/45 (35.55%)]; p = 0.02. The total incidence of any late-onset sepsis (i.e. culture-proven plus probable sepsis) was also significantly reduced by Se supplementation. [7/45 (15.55%) in Se vs. 22/45 (48.88%) in placebo; p = 0.001].Conclusion: Preterm VLBW neonates are Se deficient at birth. Se supplementation at 10 µg/day resulted in getting the Se levels into the acceptable normal level and reduced the incidence of the first episode of late-onset sepsis in these neonates. [ABSTRACT FROM AUTHOR]

Background: Typhoid is an important public health challenge for India, especially with the spread of antimicrobial resistance. The decision about whether to introduce a public vaccination programme needs to be based on an understanding of disease burden and the age-groups and geographic areas at risk. Methods: We searched Medline and Web of Science databases for studies reporting the incidence or prevalence of typhoid and paratyphoid fever confirmed by culture and/or serology, conducted in India and published between 1950 and 2015. We used binomial and Poisson mixed-effects meta-regression models to estimate prevalence and incidence from hospital and community studies, and to identify risk-factors. Results: We identified 791 titles and abstracts, and included 37 studies of typhoid and 18 studies of paratyphoid in the systematic review and meta-analysis. The estimated prevalence of laboratory-confirmed typhoid and paratyphoid among individuals with fever across all hospital studies was 9.7% (95% CI: 5.7–16.0%) and 0.9% (0.5–1.7%) respectively. There was significant heterogeneity among studies (p-values<0.001). Typhoid was more likely to be detected among clinically suspected cases or during outbreaks and showed a significant decline in prevalence over time (odds ratio for each yearly increase in study date was 0.96 (0.92–0.99) in the multivariate meta-regression model). Paratyphoid did not show any trend over time and there was no clear association with risk-factors. Incidence of typhoid and paratyphoid was reported in 3 and 2 community cohort studies respectively (in Kolkata and Delhi, or Kolkata alone). Pooled estimates of incidence were 377 (178–801) and 105 (74–148) per 100,000 person years respectively, with significant heterogeneity between locations for typhoid (p<0.001). Children 2–4 years old had the highest incidence. Conclusions: Typhoid remains a significant burden in India, particularly among young children, despite apparent declines in prevalence. Infant immunisation with newly-licensed conjugate vaccines could address this challenge. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis remains a major public health challenge for India. Various studies have documented different levels of TB and multi-drug resistant (MDR) TB among diverse groups of the population. In view of renewed targets set under the End TB strategy by 2035, there is an urgent need for TB diagnosis to be strengthened. Drawing on data from a recent, multisite study, we address key questions for TB diagnosis amongst symptomatics presenting for care: are there subgroups of patients that are more likely than others, to be positive for TB? In turn, amongst these positive cases, are there factors—apart from treatment history—that may be predictive for multi-drug resistance? Methods: We used data from a multi-centric prospective demonstration study, conducted from March 2012 to December 2013 in 18 sub-district level TB programme units (TUs) in India and covering a population of 8.8 million. In place of standard diagnostic tests, upfront Xpert MTB/RIF testing was offered to all presumptive TB symptomatics. Here, using data from this study, we used logistic regression to identify association between risk factors and TB and Rifampicin-Resistant TB among symptomatics enrolled in the study. Results: We find that male gender; history of TB treatment; and adult age compared with either children or the elderly are risk factors associated with high TB detection amongst symptomatics, across the TUs. While treatment history is found be a significant risk factor for rifampicin-resistant TB, elderly (65+ yrs) people have significantly lower risk than other age groups. However, pediatric TB cases have no less risk of rifampicin resistance as compared with adults (OR 1.23 (95% C.I. 0.85–1.76)). Similarly, risk of rifampicin resistance among both the genders was the same. These patterns applied across the study sites involved. Notably in Mumbai, amongst those patients with microbiological confirmation of TB, female patients showed a higher risk of having MDR-TB than male patients. Conclusion: Our results cast fresh light on the characteristics of symptomatics presenting for care who are most likely to be microbiologically positive for TB, and for rifampicin resistance. The challenges posed by TB control are complex and multifactorial: evidence from diverse sources, including retrospective studies such as that addressed here, can be invaluable in informing future strategies to accelerate declines in TB burden. [ABSTRACT FROM AUTHOR]

Background: Newer molecular diagnostics have brought paradigm shift in early diagnosis of tuberculosis [TB]. WHO recommended use of GeneXpert MTB/RIF [Xpert] for Extra-pulmonary [EP] TB; critics have since questioned its efficiency. Methods: The present study was designed to assess the performance of GeneXpert in 761 extra-pulmonary and 384 pulmonary specimens from patients clinically suspected of TB and compare with Phenotypic, Genotypic and Composite reference standards [CRS]. Results: Comparison of GeneXpert results to CRS, demonstrated sensitivity of 100% and 90.68%, specificity of 100% and 99.62% for pulmonary and extra-pulmonary samples. On comparison with culture, sensitivity for Rifampicin [Rif] resistance detection was 87.5% and 81.82% respectively, while specificity was 100% for both pulmonary and extra-pulmonary TB. On comparison to sequencing of rpoB gene [Rif resistance determining region, RRDR], sensitivity was respectively 93.33% and 90% while specificity was 100% in both pulmonary and extra-pulmonary TB. GeneXpert assay missed 533CCG mutation in one sputum and dual mutation [517 & 519] in one pus sample, detected by sequencing. Sequencing picked dual mutation [529, 530] in a sputum sample sensitive to Rif, demonstrating, not all RRDR mutations lead to resistance. Conclusions: Current study reports observations in a patient care setting in a high burden region, from a large collection of pulmonary and extra-pulmonary samples and puts to rest questions regarding sensitivity, specificity, detection of infrequent mutations and mutations responsible for low-level Rif resistance by GeneXpert. Improvements in the assay could offer further improvement in sensitivity of detection in different patient samples; nevertheless it may be difficult to improve sensitivity of Rif resistance detection if only one gene is targeted. Assay specificity was high both for TB detection and Rif resistance detection. Despite a few misses, the assay offers major boost to early diagnosis of TB and MDR-TB, in difficult to diagnose pauci-bacillary TB. [ABSTRACT FROM AUTHOR]

Background: Stigmatising and discriminating attitudes may discourage tuberculosis (TB) patients from actively seeking medical care, hide their disease status, and discontinue treatment. It is expected that appropriate knowledge regarding TB should remove stigmatising and discriminating attitudes. In this study we assessed the prevalence of stigmatising and discriminating attitudes towards TB patients among general population and their association with knowledge regarding TB. Method: A cross-sectional knowledge, attitude and practice survey was conducted in 30 districts of India in January-March 2011. A total of 4562 respondents from general population were interviewed using semi-structured questionnaires which contained items to measure stigma, discrimination and knowledge on TB. Result: Of the 4562 interviewed, 3823 were eligible for the current analysis. Of these, 73% (95% CI 71.4–74.2) had stigmatising and 98% (95% CI 97.4–98.3) had discriminating attitude towards TB patients. Only 17% (95% CI 15.6–18.0) of the respondents had appropriate knowledge regarding TB with even lower levels observed amongst females, rural areas and respondents from low income groups. Surprisingly stigmatising (adjusted OR 1.31 (0.78–2.18) and discriminating (adjusted OR 0.79 (0.43–1.44) attitudes were independent of knowledge regarding TB. Conclusion: Stigmatising and discriminating attitudes towards TB patients remain high among the general population in India. Since these attitudes were independent of the knowledge regarding TB, it is possible that the current disseminated knowledge regarding TB which is mainly from a medical perspective may not be adequately addressing the factors that lead to stigma and discrimination towards TB patients. Therefore, there is an urgent need to review the messages and strategies currently used for disseminating knowledge regarding TB among general population and revise them appropriately. The disseminated knowledge should include medical, psycho-social and economic aspects of TB that not only informs people about medical aspects of TB disease, but also removes stigma and discrimination. [ABSTRACT FROM AUTHOR]

Background: Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods: A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results: Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion: The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with ‘presumptive TB’ rather than ‘presumptive DR-TB’ and tailor the treatment regimen based on the resistance patterns. [ABSTRACT FROM AUTHOR]

Background: QuantiFERON-TB Gold In-Tube (QFT) is an IFNγ-release assay used in the diagnosis of Mycobacterium tuberculosis (MTB) infection. The risk of TB progression increases with the magnitude of the MTB-specific IFNγ-response. QFT reversion, also associated with low Tuberculin Skin Test responses, may therefore represent a transient immune response with control of M. tuberculosis infection. However, studies at the single cell level have suggested that the quality (polyfunctionality) of the T-cell response is more important than the quantity of cytokines produced. Objective: To explore the quality and/or magnitude of mycobacteria-specific T-cell responses associated with QFT reversion and persistent QFT-positivity. Methods: Multi-color flowcytometry on prospectively collected peripheral blood mononuclear cells was applied to assess mycobacteria-specific T-cell responses in 42 QFT positive Indian adolescents of whom 21 became QFT negative (reverters) within one year. Ten QFT consistent negatives were also included as controls. Results: There was no difference in the qualitative PPD-specific CD4+ T-cell response between QFT consistent positives and reverters. However, compared with QFT consistent positives, reverters displayed lower absolute frequencies of polyfunctional (IFNγ+IL2+TNFα+) CD4+ T-cells at baseline, which were further reduced to the point where they were not different to QFT negative controls one year later. Moreover, absolute frequencies of these cells correlated well with the magnitude of the QFT-response. Conclusion: Whereas specific polyfunctional CD4+ T-cells have been suggested to protect against TB progression, our data do not support that higher relative or absolute frequencies of PPD-specific polyfunctional CD4+ T-cells in peripheral blood can explain the reduced risk of TB progression observed in QFT reverters. On the contrary, absolute frequencies of these cells correlated with the QFT-response, suggesting that this readout reflects antigenic load. [ABSTRACT FROM AUTHOR]

Background: Private Practitioners (PP) are the primary source of health care for patients in India. Limited representative information is available on TB management practices of Indian PP or on the efficacy of India’s Revised National Tuberculosis Control Programme (RNTCP) to improve the quality of TB management through training of PP. Methods: We conducted a cross-sectional survey of a systematic random sample of PP in one urban area in Western India (Pune, Maharashtra). We presented sample clinical vignettes and determined the proportions of PPs who reported practices consistent with International Standards of TB Care (ISTC). We examined the association between RNTCP training and adherence to ISTC by calculating odds ratios and 95% confidence intervals. Results: Of 3,391 PP practicing allopathic medicine, 249 were interviewed. Of these, 55% had been exposed to RNTCP. For new pulmonary TB patients, 63% (158/249) of provider responses were consistent with ISTC diagnostic practices, and 34% (84/249) of responses were consistent with ISTC treatment practices. However, 48% (120/249) PP also reported use of serological tests for TB diagnosis. In the new TB case vignette, 38% (94/249) PP reported use of at least one second line anti-TB drug in the treatment regimen. RNTCP training was not associated with diagnostic or treatment practices. Conclusion: In Pune, India, despite a decade of training activities by the RNTCP, high proportions of providers resorted to TB serology for diagnosis and second-line anti-TB drug use in new TB patients. Efforts to achieve universal access to quality TB management must account for the low quality of care by PP and the lack of demonstrated effect of current training efforts. [ABSTRACT FROM AUTHOR]

Scrub typhus is a commonly encountered rickettsial disease of the Indian subcontinent. In India, scrub typhus is being now reported from several areas where it was previously unknown. We report clinical profile and complications of an outbreak of scrub typhus in children from the north Indian state of Uttarakhand. a region not previously known to have endemic disease. We describe the results of a prospective observational study of children with scrub typhus, at a tertiary hospital during the year 2013. The diagnosis was confirmed serologically by an IgM ELISA test. Sixty-two children were diagnosed with scrub typhus. All presented with fever. Other common symptoms were vomiting (59%), facial swelling (53%), cough (24%), abdominal pain (35%), breathlessness (26%) and decreased urine output (21 %). High grade fever (> 101 °F) was recorded in 95% of the children. Other common signs observed in cases of scrub typhus were hepatomegaly (77%), splenomegaly (63%), edema (37%). tender lymphadenopathy (42%) and hypotension (35%). An eschar was observed in 23% of patients. Meningoencephalitis (30.6%), severe thrombocytopenia (27.4%), shock (17.7%), hepatitis (16.1%) and acute kidney injury (11.3%) were the most commonly encountered complications. Eighty-seven percent of children became afebrile within 48 hours of initiating an appropriate antibiotic. Median time to defervescence was 24 hours. The overall mortality rate was 6.4%. Pediatricians should keep a high index of suspicion for scrub typhus in any febrile child having a maculopapular rash, hepatosplenomegaly, lymphadenopathy, thrombocytopenia and features suggestive of capillary leak. Pending serological confirmation, early empirical therapy with doxycycline or azithromycin should be started, as delay in treatment would result in life threatening complications. [ABSTRACT FROM AUTHOR]

Background: Limited data are available about tuberculosis treatment models of care for internally displaced populations in chronic, low-intensity conflict zones. This study aimed to detail experiences of a Médecins Sans Frontières tuberculosis programme in Andhra Pradesh-Chhattisgarh border area, India, from January to December 2012. Methods: The study was a description of two retrospective, observational cohorts receiving category I tuberculosis treatment, either intermittent directly observed treatment (DOT) or daily self-administered therapy (SAT) depending on the security of the area and access to health care services. Results: A total of 55 and 17 new tuberculosis patients under DOT and SAT respectively, with complete outcomes were included in the study. Most patients registered were new cases suffering from pulmonary, smear-positive tuberculosis. More than half of the patients in both cohorts were cured or completed treatment: 38/55 (69%) patients were successfully treated under DOT compared to 9/17 (53%) under SAT. Of the patients with adverse outcomes, the ratios of loss to follow up: failure: died were 10∶4:3 under DOT and 7∶0:1 under SAT. A much smaller proportion of patients under DOT (18%) were lost to follow up than under SAT (41%). Discussion: Maximum efforts are required to implement successful tuberculosis control programmes for internally displaced populations in conflict zones. Our study suggests that complete tuberculosis treatment can be given to patients using either intermittent DOT or daily SAT, depending on security and access to health services. National TB programmes should include SAT strategies for tuberculosis treatment as these may be an alternative feasible option in conflict settings. [ABSTRACT FROM AUTHOR]

Background: Multi-drug resistant tuberculosis (MDR TB) is a major health challenge in India that is gaining increasing public attention, but the implications of India's evolving MDR TB epidemic are poorly understood. As India's MDR TB epidemic is transitioning from a treatment-generated to transmission-generated epidemic, we sought to evaluate the potential effectiveness of the following two disease control strategies on reducing the prevalence of MDR TB: a) improving treatment of non-MDR TB; b) shortening the infectious period between the activation of MDR TB and initiation of effective MDR treatment. Methods and Findings: We developed a dynamic transmission microsimulation model of TB in India. The model followed individuals by age, sex, TB status, drug resistance status, and treatment status and was calibrated to Indian demographic and epidemiologic TB time trends. The main effectiveness measure was reduction in the average prevalence reduction of MDR TB over the ten years after control strategy implementation. We find that improving non-MDR cure rates to avoid generating new MDR cases will provide substantial non-MDR TB benefits but will become less effective in reducing MDR TB prevalence over time because more cases will occur from direct transmission – by 2015, the model estimates 42% of new MDR cases are transmission-generated and this proportion continues to rise over time, assuming equal transmissibility of MDR and drug-susceptible TB. Strategies that disrupt MDR transmission by shortening the time between MDR activation and treatment are projected to provide greater reductions in MDR prevalence compared with improving non-MDR treatment quality: implementing MDR diagnostic improvements in 2017 is expected to reduce MDR prevalence by 39%, compared with 11% reduction from improving non-MDR treatment quality. Conclusions: As transmission-generated MDR TB becomes a larger driver of the MDR TB epidemic in India, rapid and accurate MDR TB diagnosis and treatment will become increasingly effective in reducing MDR TB cases compared to non-MDR TB treatment improvements. [ABSTRACT FROM AUTHOR]

Background: Infection-related acute kidney injury (AKI) is an important preventable cause of morbidity and mortality in the tropical region. The prevalence and outcome of kidney involvement, especially AKI, in scrub typhus is not known. We investigated all patients with undiagnosed fever and multisystem involvement for scrub typhus and present the pattern of renal involvement seen. Methods: From September 2011 to November 2012, blood samples of all the patients with unexplained acute febrile illness and/or varying organ involvement were evaluated for evidence of scrub typhus. A confirmed case of scrub typhus was defined as one with detectable Orientia tsutsugamushi deoxyribonucleic acid (DNA) in patient's blood sample by nested polymerase chain reaction (PCR) targeting the gene encoding 56-kDa antigen and without any alternative etiological diagnosis. Renal involvement was defined by demonstration of abnormal urinalysis and/or reduced glomerular filtration rate. AKI was defined as per Kidney Disease: Improving Global Outcomes (KDIGO) definition. Results: Out of 201 patients tested during this period, 49 were positive by nested PCR for scrub typhus. Mean age of study population was 34.1±14.4 (range 11–65) years. Majority were males and a seasonal trend was evident with most cases following the rainy season. Overall, renal abnormalities were seen in 82% patients, 53% of patients had AKI (stage 1, 2 and 3 in 10%, 8% and 35%, respectively). The urinalysis was abnormal in 61%, with dipstick positive albuminuria (55%) and microscopic hematuria (16%) being most common. Acute respiratory distress syndrome (ARDS) and shock were seen in 57% and 16% of patients, respectively. Hyperbilirubinemia was associated with AKI (p = 0.013). A total of 8 patients (including three with dialysis dependent AKI) expired whereas rest all made uneventful recovery. Jaundice, oliguria, ARDS and AKI were associated with mortality. However, after multivariate analysis, only oliguric AKI remained a significant predictor of mortality (p = 0.002). Conclusions: Scrub typhus was diagnosed in 24% of patients presenting with unexplained febrile illness according to a strict case definition not previously used in this region. Renal abnormalities were seen in almost 82% of all patients with evidence of AKI in 53%. Our finding is contrary to current perception that scrub typhus rarely causes renal dysfunction. We suggest that all patients with unexplained febrile illness be investigated for scrub typhus and AKI looked for in scrub typhus patients. [ABSTRACT FROM AUTHOR]