Diagnosing adult and pediatric extrapulmonary tuberculosis by MPT64 antigen detection with immunohistochemistry and immunocytochemistry using reproduced polyclonal antibodies.

Diagnosing extrapulmonary tuberculosis (EPTB) is challenging. Immunohistochemistry or immunocytochemistry has been used to diagnose tuberculosis (TB) by detection of MPT64 antigen from various extrapulmonary specimens and has shown good diagnostic performance in our previous studies. The test can distinguish between disease caused by Mycobacterium tuberculosis (Mtb) complex and nontuberculous mycobacteria and can be applied on formalin-fixed paraffin-embedded tissue. As the antibodies previously used were in limited supply, a new batch of polyclonal antibodies was developed for scale-up and evaluated for the first time in this study. Our aim was to assess the diagnostic accuracy of the MPT64 test with reproduced antibodies in the high burden settings of Pakistan and India. Patients were enrolled prospectively. Samples from suspected sites of infection were collected and subjected to histopathologic and/or cytologic evaluation, routine TB diagnostics, GeneXpert MTB/RIF (Xpert), and the MPT64 antigen detection test. Patients were followed until the end of treatment. Based on a composite reference standard (CRS), 556 patients were categorized as TB cases and 175 as non-TB cases. The MPT64 test performed well on biopsies with a sensitivity and specificity of 94% and 75%, respectively, against a CRS. For cytology samples, the sensitivity was low (36%), whereas the specificity was 81%. Overall, the MPT64 test showed higher sensitivity (73%) than Xpert (38%) and Mtb culture (33%). The test performed equally well in adults and children. We found an additive diagnostic value of the MPT64 test in conjunction with histology and molecular tests, increasing the yield for EPTB. In conclusion, immunochemical staining with MPT64 antibodies improves the diagnosis of EPTB in high burden settings and could be a valuable addition to routine diagnostics.

Interventions to promote household waste segregation: A systematic review.

Waste segregation at source, particularly at the household level, is an integral component of sustainable solid waste management, which is a critical public health issue. Although multiple interventions have been published, often with contradictory findings, few authors have conducted a comprehensive systematic synthesis of the published literature. Therefore, we undertook a systematic review to synthesize all published interventions conducted in any country in the world which targeted household-level waste segregation with or without additional focus on recycling or composting. Following PRISMA guidelines, Web of Science, Medline, Global Health, and Google Scholar were searched using a search strategy created by combining the keywords 'Waste', 'Segregation', and 'Household'. Two-stage blinded screening and consensus-based conflict resolution were done, followed by quality assessment, data extraction, and narrative synthesis. 8555 articles were identified through the database searches and an additional 196 through grey literature and citation searching. After excluding 2229 duplicates and screening title abstracts of 6522 articles, 283 full texts were reviewed, and 78 publications reporting 82 intervention studies were included in the data synthesis. High methodological heterogeneity was seen, excluding the possibility of a meta-analysis. Most (n = 60) of the interventions were conducted in high-income countries. Interventions mainly focused on information provision. However, differences in the content of information communicated and mode of delivery have not been extensively studied. Finally, our review showed that the comparison of informational interventions with provision of incentives and infrastructural modifications needs to be explored in-depth. Future studies should address these gaps and, after conducting sufficient formative research, should aim to design their interventions following the principles of behaviour change.

Programmed Death Ligand -1 and Gene Mutation Characterization of Lung Malignancies in Patients at a Rural Hospital in Central India.

INTRODUCTION: Lung malignancy is one of the most common neoplasms worldwide. Accurate histology sub-typing and identification of gene mutations in lung tumours are considered important to administer targeted therapy for improved clinical outcome. Our aim is to determine the frequency of EGFR mutation and Programmed death ligand-1 (PD -L1) status of lung malignancies in patients attending a rural hospital in Central India. MATERIALS AND METHODS: Formalin-fixed histology diagnosed lung malignancy (n=99) bronchoscopic/trucut lung biopsies were identified and the tissue blocks and slides were retrieved. Histology typing and staging of the lesions was assessed. PD-L1 expression on biopsy was detected by immunohistochemistry using commercially available primary antibody. PD-L1 expression was assessed and semi-quantified based on the intensity and proportion of tumour cells stained for the marker. EGFR gene mutation at exon19 and 21 was detected by polymerase chain reaction of tissue from paraffin blocks. Final analysis was performed on 87 biopsies for status of EGFR mutation and PD-L1 expression. RESULTS: The average age of lung malignancies patients was 63 years, with a preponderance of males. Advance disease in stage III and stage IV was more common in squamous cell carcinoma as compared to adenocarcinoma (p < 0.01). Mutations at exon 19-21 of the EGFR gene were detected in 7/87 (8%) cases of adenocarcinoma and all of these patients were non-smokers. A total of 52.9% of biopsies showed PD-L1 expression, which was higher in adenocarcinoma patients (p=0.04), smokers (p=0.00), and stage II and III patients (p= 0.00). CONCLUSION: EGFR gene mutations at exon 19 or 21 are seen in lung adenocarcinoma cases. PD-L1 expression was observed in EGFR mutated tissues. Our results should be further validated with large sample size and multicenter clinical data before extrapolation to design immunotherapy strategies.

Significance of non-granulomatous cytomorphology on fine needle aspirate in lymphadenitis cases classified as tuberculous by using a composite reference standard.

BACKGROUND: Fine needle aspiration cytology (FNAC) is established as a first line investigation for tuberculous lymphadenitis (TBLA). We aimed to describe the various cytomorphologic features of tuberculosis (TB) on FNAC and their contribution in the diagnostic decision-making in suspected TBLA cases. METHODS: Patients with presumptive TBLA were prospectively enrolled (n = 266) and subjected to routine diagnostic work-up for TB, including FNAC samples, and followed until the end of treatment. Patients were categorized as TB or non-TB cases based on a composite reference standard of which the various cytomorphologic patterns were compared. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy was calculated using cross-tabulation. RESULTS: Fifty-six patients were categorized as bacteriologically confirmed TB, 102 as clinically confirmed TB and 108 as non-TB. The most common cytomorphologic pattern among TB cases (59%) was granulomatous inflammation with necrosis, however, about one-third of tuberculous lymphadenitis patients presented with non-granulomatous inflammation, with 21% showing only necrosis and 13% presenting with a reactive pattern. The overall sensitivity and specificity of FNAC was 85% and 66%, respectively. CONCLUSIONS: We found that about one-third of TBLA patients presented without granulomas on FNA, highlighting the importance of considering TB in a wide spectrum of cytomorphology in a high TB burden setting. Our study supports the use of FNAC as a first-line investigation tool for diagnosing TBLA in a low-resource setting due to its relative simplicity and good sensitivity. However, the low specificity of FNAC, emphasizes the need for a second-tier confirmatory test with improved specificity.

Syndromic surveillance system during mass gathering of Panchkroshi Yatra festival, Ujjain, Madhya Pradesh, India.

Background: The health implications surrounding a mass gathering pose significant challenges to public health officials. The use of syndromic surveillance provides an ideal method for achieving the public health goals and objectives at such events. In the absence of published reports of systematic documentation of public health preparedness in mass gatherings in the local context, we describe the public health preparedness and demonstrate the operational feasibility of a tablet-based participatory syndromic surveillance among pilgrims during the annual ritual circumambulation- Panchkroshi Yatra. Methods: A real-time surveillance system was established from 2017-2019 to capture all the health consultations done at the designated points (medical camps) in the Panchkroshi yatra area of the city Ujjain in Madhya Pradesh. We also surveyed a subset of pilgrims in 2017 to gauge satisfaction with the public health measures such as sanitation, water, safety, food, and cleanliness. Results: In 2019, injuries were reported in the highest proportion (16.7%; 794/4744); most numbers of fever cases (10.6%; 598/5600) were reported in 2018, while 2017 saw the highest number of patient presentations of abdominal pain (7.73%; 498/6435). Conclusion: Public health and safety measures were satisfactory except for the need for setting up urinals along the fixed route of the circumambulation. A systematic data collection of selected symptoms among yatris and their surveillance through tablet could be established during the panchkroshi yatra, which can complement the existing surveillance for detecting early warning signals. We recommend the implementation of such tablet-based surveillance during such mass gathering events.

Effectiveness of electrical vestibular nerve stimulation as adjunctive therapy to improve the cognitive functions in patients with Parkinson's disease.

OBJECTIVES: The present study was undertaken to observe the effectiveness of electrical vestibular stimulation in improving cognitive functions in patients with Parkinson's disease. METHODS: Randomized controlled trial (ClinicalTrials.gov Identifier: NCT04450550). 30 cases of PD, including both males and females were recruited in the study by convenient sampling after obtaining written informed consent. After recruiting, the participants were randomly assigned into two groups. The control group (n=15) received placebo stimulation whereas the intervention group (n=15) received electrical vestibular stimulation administered for 12 weeks. Auditory, visual reaction time and spatial and verbal memory were recorded before and after 6 weeks and after 12 weeks of intervention and compared. RESULTS: There was a significant improvement in both auditory and visual reaction time of right and left-hand responses. Also, significant improvement was observed in both the spatial and verbal memory of the patients. CONCLUSIONS: There was a significant improvement in the auditory and visual reaction time and spatial and verbal memory in the participants after the electrical vestibular nerve stimulation administration. No side effects were reported by the study participants and they have expressed willingness to continue the intervention after the study period also. The study recommends further detailed studies with a higher sample size to adopt electrical vestibular nerve stimulation as adjunctive therapy in the management of Parkinson's disease.

Effectiveness of electrical vestibular nerve stimulation on the range of motion in patients with Parkinson's disease.

OBJECTIVES: The present study was undertaken to observe the effectiveness of electrical vestibular stimulation on the range of motion (ROM) in patients with Parkinson's disease (PD). METHODS: The present study was a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04450550). The study participants were assessed at three points of time. After recording baseline cognitive functions, electrical vestibular nerve stimulation was administered to the intervention group and placebo stimulation was administered to the control group for 12 weeks. Post-intervention parameters were recorded after 6 weeks and after 12 weeks after the intervention in both control and intervention groups. A total of 30 cases of PD, including both males and females were recruited in the study by convenient sampling after obtaining written informed consent. All ROM and flexibility measurements were recorded using a universal goniometer and standard protocol with help of an experienced physiotherapist at our hospital. RESULTS: There was a significant improvement in the hip internal and external rotation right and left sides. There was a significant improvement in the hip extension right and left. There was a significant improvement in the ankle plantarflexion left and ankle dorsiflexion right and left followed by the intervention. There was a significant decline in the hip internal rotation on right and left sides. There was a significant decline in the hip extension and ankle dorsiflexion on the left side. CONCLUSIONS: The study results confirm the improvement of motor activities of patients with PD followed by vestibular stimulation. Further detailed studies are recommended to support the application of vestibular stimulation as an alternative therapy in the management of motor functions in patients with PD.

Correlation Between Individual Child-Level Antibiotic Consumption and Antibiotic-Resistant Among Commensal Escherichia coli: Results from a Cohort of Children Aged 1-3 Years in Rural Ujjain India.

Background: The global expansion of antibiotic-resistant bacteria is a serious concern and is increasing worldwide in both pathogenic and commensal bacteria. The study determined the correlation between individual child-level antibiotic consumption and antibiotic resistance among the commensal Escherichia coli (E.coli) in a cohort of 125 children in rural Ujjain, India. Methods: During a two-year period between August 2014 and September 2016, stool samples were collected at seven-time points from a cohort of 125 children; aged 1-3. A total of six colonies of E.coli per stool sample were collected for antibiotic susceptibility testing. Antibiotic consumption data was collected during the healthcare-seeking follow-up done during the same period. At each of the seven-time points correlation between antibiotic consumption (Defined Daily Dose-DDD/100 patient-days) and antibiotic resistance (number of resistant isolates) was analyzed independently using the Spearman correlation coefficient. Further, mixed-effects logistic regression models were built to study correlation between child-level consumption of penicillin with the number of E.coli isolates resistant to ampicillin, consumption of cephalosporin with resistance to cefotaxime and ceftazidime, consumption of fluoroquinolones with resistance to nalidixic acid and consumption of cotrimoxazole with resistance to cotrimoxazole. Results: Out of 756 illness episodes reported in 125 children 42% were with antibiotic prescriptions and reported a total antibiotic consumption of 55DDD/100 patient-days. The most common antibiotics used were cefixime (J01DD08;72 DDD/100patient/days) followed by ofloxacin (J01MA01;51DDD/100patient-days), cefpodoxime (J01DD13;38DDD/100patient-days) and amoxicillin (J01CA04;28DDD/100patient-days). The highest percentage of resistance was found to the ampicillin (67%) followed by nalidixic acid (52%) and cefotaxime (44%) and when summarized, more than 90% were resistant to cefotaxime, ceftazidime, and co-trimoxazole in commensal E.coli isolates. The consumption of cephalosporins showed weak positive correlation with the resistance to cefotaxime (Coefficient±SE=0.13 ± 0.09,p<0.001). Conclusion: Our findings showed no correlation between individual-level antibiotic consumption and resistance development in commensal E.coli in a rural community environment.

Utility of constructed wetlands for treatment of hospital effluent and antibiotic resistant bacteria in resource limited settings: A case study in Ujjain, India.

Increasing generation of wastewater and its indiscriminate disposal is detrimental to human and animal health. Resource-limited settings often struggle for efficient wastewater treatment systems owing to lack of funds and operational difficulties. Therefore, alternative treatment systems involving low expenditure and simplistic operations are need of the hour. Constructed wetlands are one such alternative that can efficiently remove variety of pollutants from wastewater. In this study, we have assessed the utility of constructed wetlands for treatment of hospital wastewater in Ujjain. An in-house wetland system was designed and constructed using Typha latifolia and Phragmites karka. Results showed that wetland was efficient for removal of various physico-chemical and biological contaminants, namely, biochemical-oxygen-demand (77.1%), chemical-oxygen-demand (64.9%), turbidity (68.3%), suspended-solids (63%), total-phosphorus (58.7%), nitrate-nitrogen (33%), fecal coliforms (96.8%), and total coliforms (95.6%). Paired t test revealed that removal efficiencies for various parameters were significantly different among Phragmites, Typha, and control cells (p ≤ 0.05). Study also depicted that most of the bacterial isolates in inlet wastewater were selectively resistant to antibiotics (ciprofloxacin and sulphamethaxazole) as well and these isolates were also removed. Precisely, Typha was fairly suitable for antibiotic resistant bacteria removal. Thus, constructed wetlands were found to be one of the suitable options for wastewater treatment in resource-limited settings. PRACTITIONER POINTS: Constructed wetlands are one of the suitable options for wastewater treatment in resource limited settings. These systems involve wetland vegetation, soil, and associated microbial assemblages to improve the water quality. Typha and Phragmites were found to be efficient for treating the hospital wastewater. Experiments showed that antibiotic resistant bacteria may also be removed through constructed wetland systems. Easy operation, cost effectiveness, and efficiency are important attributes.

Dynamics of Household Waste Segregation Behaviour in Urban Community in Ujjain, India: A Framework Analysis.

Waste segregation practices must be socially acceptable, affordable, context-specific, and participatory, which is essential for promoting waste segregation. Therefore, this study explored the urban community members' motivation, opportunity, and household waste segregation ability. We performed a qualitative study in Ujjain city, India. Ten focus group discussions and eight in-depth interviews were conducted with female and male household members in residential and slum areas. All interviews were digitally recorded, transcribed, and translated. We used the thematic framework technique using the Motivation-Opportunity-Ability-Behaviour theory for analysis. Three themes were constructed: motivation, where household members are motivated to sort waste yet fear the consequences of improper sorting; ability, where household waste segregation is rapidly gaining acceptance as a social norm; and opportunities, involving convenient facilities and a social support system for household members towards waste segregation. This study contributes to developing a knowledge base on waste segregation behaviour and a repertoire to facilitate evidence-based management and policymaking. There is a need for educational intervention and women's self-help groups' involvement to develop community orientation and waste segregation literacy. Finally, this study emphasizes the importance of all three behavioural change components, i.e., motivation, opportunity, and ability, in managing sustainable waste segregation practices.

Antibiotic Use before, during, and after Seeking Care for Acute Febrile Illness at a Hospital Outpatient Department: A Cross-Sectional Study from Rural India.

Antibiotic resistance is a naturally occurring phenomenon, but the misuse and overuse of antibiotics is accelerating the process. This study aimed to quantify and compare antibiotic use before, during, and after seeking outpatient care for acute febrile illness in Ujjain, India. Data were collected through interviews with patients/patient attendants. The prevalence and choice of antibiotics is described by the WHO AWaRe categories and Anatomical Therapeutic Chemical classes, comparing between age groups. Units of measurement include courses, encounters, and Defined Daily Doses (DDDs). The antibiotic prescription during the outpatient visit was also described in relation to the patients' presumptive diagnosis. Of 1000 included patients, 31.1% (n = 311) received one antibiotic course, 8.1% (n = 81) two, 1.3% (n = 13) three, 0.4% (n = 4) four, 0.1% (n = 1) five, and the remaining 59.0% (n = 590) received no antibiotics. The leading contributors to the total antibiotic volume in the DDDs were macrolides (30.3%), combinations of penicillins, including ß-lactamase inhibitors (18.8%), tetracyclines (14.8%), fluoroquinolones (14.6%), and third-generation cephalosporins (13.7%). 'Watch' antibiotics accounted for 72.3%, 52.7%, and 64.0% of encounters before, during, and after the outpatient visit, respectively. Acute viral illness accounted for almost half of the total DDDs at the outpatient visit (642.1/1425.3, 45.1%), for which the macrolide antibiotic azithromycin was the most frequently prescribed antibiotic (261.3/642.1, 40.7%).

Clinical and histology features as predictor of severity of mucormycosis in post-COVID-19 patients: An experience from a rural tertiary setting in Central India.

BACKGROUND: An upsurge in cases of rhinosinusitis with or without associated orbital and/or cerebral involvement by mucormycosis has been observed in post-COVID-19 patients. Our objective is to evaluate the clinical and histopathology features of these patients to determine the severity and develop a scoring on the extent on tissue invasion. METHOD: We prospectively enrolled and analyzed 95 post-COVID-19 patients who presented with the invasive mucormycosis of the head and neck region. Clinical and histology details were noted in predesigned forms. Various histology variables were graded from I to III to propose a scoring system for the severity of the disease. RESULTS: Mucormycosis was common in males with a mean age of 46.8 ± 11 years. Facial pain was the most common presenting complaint and 77% of the patients were diabetic. Most cases (n = 59) showed a moderate degree of neutrophilic infiltrate with ⩾50% tissue necrosis and angioinvasion in three or more vessels with a fungal load of 2+/3+. Histology severity grade III was observed in patients who died from cerebral mucormycosis (n = 3) and septicemia (n = 2) and in patients who had undergone orbital exenteration (n = 6). CONCLUSION: The histopathology and severity score classification was directly correlated with the outcome of the patients. Further evaluation and a larger study will help to validate the proposed scoring for its clinical use in all forms and causes of mucormycosis.

Red Cell Distribution Width as a Predictor of Mortality in Patients With Clinical Sepsis: Experience From a Single Rural Center in Central India.

INTRODUCTION: Early diagnosis of sepsis and its severity is essential for appropriate treatment to improve patient survival, especially in resource-limited settings. The aim of the present study was to study the role of red blood cell distribution (RDW) as a biomarker for the early detection of severe sepsis defined clinically and also in the prediction of mortality from sepsis. METHODS: The cross-sectional study included a total of 175 subjects who met the inclusion criteria for the diagnosis of severe sepsis. After a thorough clinical examination, blood samples were taken from all patients within 3 hours of presenting the disease. The RDW values and other investigations were studied on the day of admission compared to other severity markers with the mortality index of 30 days. RESULT: The RDW value was significantly higher in patients with severe sepsis and in non-survivor patients than in survivors (P < .0001). There was a strong correlation between the SOFA score and RDW in predicting the disease outcome with the Pearson correlation coefficient of r = .46. The area under the receiver operating characteristic curve was found to be 0.852 at a CI of 95% (0.796-0.909) with RDW 17.15, sensitivity was 88.6% and specificity was 63.5%. There was a positive correlation with Pearson's correlation coefficient of r = .46 between RDW and the SOFA score. CONCLUSIONS: RDW can be used as a potential marker for the early detection of severe sepsis and in the prediction of the outcome. Large multicenter prospective studies can confirm the utility of this routinely available marker for patients with sepsis.

Determinants and pathways of healthcare-seeking behaviours in under-5 children for common childhood illnesses and antibiotic prescribing: a cohort study in rural India.

OBJECTIVES: To explore the healthcare-seeking pathways, antibiotic prescribing and determine the sociodemographic factors associated with healthcare-seeking behaviour (HSB) of caregivers for common illnesses in under-5 (U-5) children in rural Ujjain, India. STUDY DESIGN: Prospective cohort study. STUDY SETTING AND STUDY SAMPLE: The cohort included 270 U-5 children from selected six villages in rural demographic surveillance site, of the R.D. Gardi Medical College, Ujjain, Madhya Pradesh, India. A community-based cohort was visited two times weekly for over 113 weeks (August 2014 to October 2016) to record the HSB of caregivers using HSB diaries. Sociodemographic information was also solicited. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: first point of care, healthcare-seeking pathway and quantify antibiotic prescribing for the common acute illnesses. SECONDARY OUTCOME: HSB risk factors were determined using mixed-effects multinomial logistic regression. RESULTS: A total of 60 228 HSB follow-up time points for 270 children were recorded with a total of 2161 acute illness episodes. The most common illnesses found were respiratory tract infections (RTI) (69%) and gastrointestinal tract infections (8%). No healthcare was sought in 33% of illness episodes, mostly for RTIs. The most common healthcare-seeking pathway was to informal healthcare providers (IHCPs, 49% of illness episodes). The adjusted relative risk for obtaining no treatment, home treatment and treatment by IHCPs was higher for RTIs (aRR=11.54, 1.82 and 1.29, respectively), illiterate mothers (aRR=2.86, 2.38 and 1.93, respectively), and mothers who were homemakers (aRR=2.90, 4.17 and 2.10, respectively). Socioeconomic status was associated with HSB, with the highest aRR for no treatment in the lowest two socioeconomic quintiles (aRR=6.59 and 6.39, respectively). Antibiotics were prescribed in 46% (n=670/1450) illness episodes and the majority (85%, n=572/670) were broad spectrum. CONCLUSION: In our rural cohort for many acute episodes of illnesses, no treatment or home treatment was done, which resulted in overall reduced antibiotic prescribing. The most common healthcare-seeking pathway was to visit IHCPs, which indicates that they are major healthcare providers in rural areas. Most of the antibiotics were prescribed by IHCPs and were commonly prescribed for illnesses where they were not indicated.

Trends, relationships and case attribution of antibiotic resistance between children and environmental sources in rural India.

Bacterial antibiotic resistance is an important global health threat and the interfaces of antibiotic resistance between humans, animals and the environment are complex. We aimed to determine the associations and overtime trends of antibiotic resistance between humans, animals and water sources from the same area and time and estimate attribution of the other sources to cases of human antibiotic resistance. A total of 125 children (aged 1-3 years old) had stool samples analysed for antibiotic-resistant bacteria at seven time points over two years, with simultaneous collection of samples of animal stools and water sources in a rural Indian community. Newey-West regression models were used to calculate temporal associations, the source with the most statistically significant relationships was household drinking water. This is supported by use of SourceR attribution modelling, that estimated the mean attribution of cases of antibiotic resistance in the children from animals, household drinking water and wastewater, at each time point and location, to be 12.6% (95% CI 4.4-20.9%), 12.1% (CI 3.4-20.7%) and 10.3% (CI 3.2-17.3%) respectively. This underlines the importance of the 'one health' concept and requires further research. Also, most of the significant trends over time were negative, suggesting a possible generalised improvement locally.

Effects of improved information and volunteer support on segregation of solid waste at the household level in urban settings in Madhya Pradesh, India (I-MISS): protocol of a cluster randomized controlled trial.

BACKGROUND: Segregation of household waste at the source is an effective and sustainable strategy for management of municipal waste. However, household segregation levels remain insufficient as waste management approaches are mostly top down and lack local support. The realisation and recognition of effective, improved and adequate waste management may be one of the vital drivers for attaining environmental protection and improved health and well-being. The presence of a local level motivator may promote household waste segregation and ultimately pro-environmental behaviour. The present cluster randomized control trial aims to understand if volunteer based information on waste segregation (I-MISS) can effectively promote increased waste segregation practices at the household level when compared with existing routine waste segregation information in an urban Indian setting. METHODS: This paper describes the protocol of an 18 month two-group parallel,cluster randomised controlled trialin the urban setting of Ujjain, Madhya Pradesh, India. Randomization will be conducted at ward level, which is the last administrative unit of the municipality. The study will recruit 425 households in intervention and control groups. Assessments will be performed at baseline (0 months), midline (6 months), end line (12 months) and post intervention (18 months). The primary outcome will be the comparison of change in proportion of households practicing waste segregation and change in proportion of mis-sorted waste across the study period between the intervention and control groups as assessed by pick analysis. Intention to treat analysis will be conducted. Written informed consent will be obtained from all participants. DISCUSSION: The present study is designed to study whether an external motivator, a volunteer selected from the participating community and empowered with adequate training, could disseminate waste segregation information to their community, thus promoting household waste segregation and ultimately pro-environmental behaviour. The study envisages that the volunteers could link waste management service providers and the community, give a local perspective to waste management, and help to change community habits through information, constant communication and feedback. TRIAL REGISTRATION: The study is registered prospectively with Indian Council of Medical Research- Clinical Trial Registry of India ( CTRI/2020/03/024278 ).

Monitoring of Water Quality, Antibiotic Residues, and Antibiotic-Resistant Escherichiacoli in the Kshipra River in India over a 3-Year Period.

The emergence of antibiotic resistance is a major global and environmental health issue, yet the presence of antibiotic residues and resistance in the water and sediment of a river subjected to excessive anthropogenic activities and their relationship with water quality of the river are not well studied. The objectives of the present study were a) to investigate the occurrence of antibiotic residues and antibiotic-resistant Escherichiacoli (E.coli) in the water and sediment of the Kshipra river in India at seven selected sites during different seasons of the years 2014, 2015, and 2016 and b) to investigate the association between antibiotic residues and antibiotic-resistant E.coli in water and sediment and measured water quality parameters of the river. Antibiotic residues and resistant E.coli were present in the water and sediment and were associated with the measured water quality parameters. Sulfamethoxazole was the most frequently detected antibiotic in water at the highest concentration of 4.66 µg/L and was positively correlated with the water quality parameters. Significant (p < 0.05) seasonal and spatial variations of antibiotic-resistant E.coli in water and sediment were found. The resistance of E.coli to antibiotics (e.g., sulfamethiazole, norfloxacin, ciprofloxacine, cefotaxime, co-trimoxazole, ceftazidime, meropenem, ampicillin, amikacin, metronidazole, tetracycline, and tigecycline) had varying associations with the measured water and sediment quality parameters. Based on the results of this study, it is suggested that regular monitoring and surveillance of water quality, including antibiotic residues and antibiotic resistance, of all rivers should be taken up as a key priority, in national and Global Action Plans as these can have implications for the buildup of antibiotic resistance.

Stable high frequencies of sulfadoxine-pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine-pyrimethamine in Ujjain, Madhya Pradesh, India.

BACKGROUND: Artesunate plus sulfadoxine-pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimethamine were 9% and > 80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015-2016 after 3-4 years of ASP use, are reported. METHODS: Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16-185, pfdhps 436-632 and K13 407-689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism. RESULTS: Sulfadoxine-pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R + 108 N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108 N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively. CONCLUSION: The frequency of P. falciparum with reduced susceptibility to sulfadoxine-pyrimethamine remained high, but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use.

Mass bathing events in River Kshipra, Central India- influence on the water quality and the antibiotic susceptibility pattern of commensal E.coli.

BACKGROUND: Antibiotic resistance is one of the major global health emergencies. One potential source of dissemination of resistant bacteria is mass gatherings, e.g. mass bathing events. We evaluated the physicochemical parameters of water quality and the antibiotic resistance pattern in commensal Escherichia coli from river-water and river-sediment in pre-, during- and post-mass bathing events in river Kshipra, Central India. METHOD/DESIGN: Water and sediment samples were collected from three selected points during eight mass bathing events during 2014-2016. Water quality parameters (physical, chemical and microbiological) were analyzed using standard methods. In river water and sediment samples, antibiotic susceptibility patterns of isolated E. coli to 17 antibiotics were tested. RESULTS: pH, turbidity and dissolved oxygen were significantly lower and total dissolved solid, free carbon dioxide were higher during mass bathing, whilst TSS, BOD and COD were lowest in pre-bathing and highest in post-bathing period. E.coli with multi drug resistance (MDR) or extended spectrum beta-lactamase (ESBL) production were between 9-44% and 6-24%, respectively in river-water as well as river-sediment. Total coliform count/ml and E. coli count were higher during-and post-bathing in river water than in pre-bathing period. Thus, the percentage of resistance was significantly higher during and post-bathing period (p<.05) than in pre-bathing. Colony forming unit (CFU)/ml in river-sediment was much higher than in river-water. Percentage of resistance was significantly higher in river-water (p<.05) than in river-sediment. CONCLUSIONS: Antibiotic resistance in E.coli isolated from the Kshipra River showed significant variation during mass bathing events. Guidelines and regulatory standards are needed to control environmental dissemination of resistant bacteria.

Effect of Yoga versus Light Exercise to Improve Well-Being and Promote Healthy Aging among Older Adults in Central India: A Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Aging is a natural process associated with many functional and structural changes. These changes may include impaired self-regulation, changes in tissues and organs. Aging also affects mood, physical status and social activity. There are adverse changes in cognitive behavior, perceived sensation and thinking processes. Regular physical activity can alleviate many health problems; yet, many older adults are inactive. Yoga is one of the scientific and popular lifestyle practice considered as the integration of mind, body and soul. Results of previous studies reported positive effects of yoga on multiple health outcomes in elderly. However, there is scarcity of scientific information where yoga's effect is examined on over well-being and on multiple health outcomes simultaneously in elderly. This protocol describes methods for a 12-week yoga-based intervention exploring the effects of yoga on well-being in physically inactive elderly living in community. Methods and analysis: This two group parallel single blind randomized controlled trial that will be conducted at a designated facility of R.D. Gardi Medical College, Ujjain, Madhya Pradesh, Central India. A 12-week 60-min yoga intervention three times weekly is designed. Comparison group participants will undergo a 60-min program comprising light exercise focusing on conventional stretching to improve mobility. After screening, 144 participants aged 60-80 years will be recruited. The primary outcome is subjective well-being. Secondary outcomes include mobility, fall risk, cognition, anxiety and depression, mood and stress, sleep quality, pain, physical activity/sedentary behavior and cardio-metabolic risk factors. Assessments will be conducted at baseline (0 week), after the intervention (12+1 week) and at follow-up (36+1 week). Intention-to-treat analyses with mixed linear modeling will be applied. DISCUSSION: Through this trial, we aim to determine whether elderly people in the intervention group practicing yoga show more favorable primary (well-being) and secondary outcomes than those in the light exercise focusing on conventional stretching group. We assume that yoga may be practiced to maintain health, reduce particular symptoms commonly associated with skeletal pain, assist in pain relief and enhance well-being. We anticipate that practicing yoga will improve well-being and mental health and may lead to significant improvement in depression, pain and sleep quality.Ethics and dissemination: This study is approved by the Institutional Ethics Committee of R.D. Gardi Medical College, Ujjain, IEC Ref No. 09/2018. All participants would be provided with written and verbal information about the purpose of the project and would be free to withdraw from the study at any time. Refusal to participate in the study would not have any negative consequences. Confidentiality of the information of each participant would be ensured. Knowledge obtained would be disseminated to stakeholders through workshops, meetings and relevant scientific conferences. TRIAL REGISTRATION: The trial is prospectively registered with the Indian Council of Medical Research Trial Registry CTRI/2018/07/015051.