Short-term exposure to air pollution and emergency room visits for acute respiratory symptoms among adults.

OBJECTIVE: To examine the short-term effect of ambient air pollution on daily acute respiratory emergency room visits among adults.METHODS: A time-series study (June 2017-February 2019) was carried out among adults (≥18 years) visiting a multi-specialty hospital in Delhi. We evaluated the association between the daily levels of particulate matter (PM) <2.5 µm in diameter (PM2.5) and PM <10 µm in diameter (PM10), ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and sulphur dioxide and daily count of emergency room (ER) visits for acute respiratory symptoms. Generalised additive model (GAM) was used with the Poisson link function to analyse the associations for 0-1 to 0-7 lag days.RESULTS: A total of 69,400 ER visits were recorded, of which 2,669 were by adults due to acute respiratory symptoms. At 0-7 lag days, an increment of 1 standard deviation in NO2 and PM2.5 concentration was associated with a percentage increase in acute respiratory ER visits of respectively 53.0% (95% CI 30.84-78.97) and 19.5% (95% CI 4.53-36.65). During 0-7 lag days, a positive trend was observed at higher concentrations of CO (>1.86-3.28 mg/m³), while a negative significant association was observed at low concentrations of CO (<1.171 mg/m³).CONCLUSION: Short-term exposure to ambient NO2 and PM2.5 was associated with acute respiratory emergency visits of adults at lag 0-7 days.

Scrub typhus in patients with acute febrile illness: a 5-year study from India.

BACKGROUND: Scrub typhus was once thought to be a disease of rural origin and was confined to specific pockets in South Asia. Early diagnosis and treatment is extremely important as it is associated with high mortality if left untreated. AIM: To delineate the clinical and molecular epidemiology of scrub typhus in patients presenting with acute febrile illness from various parts of India. METHODS: During the study period of 5 years (October 2013 to October 2018), a total of 1742 patients with acute febrile illness <15 days were enrolled after taking informed consent. Patients were diagnosed using IgM Enzyme-linked immunosorbent assay (ELISA) based on the pre-determined region specific cut offs. Patients with positive IgM ELISA were also subjected to IgM Immunofluorescence assay and nested polymerase chain reaction (PCR) assay. The demographic and relevant clinical details of the patients were documented and analyzed. RESULTS: A total of 210 (12.1%) patients were diagnosed with scrub typhus. Of these, nested PCR was positive in only 85 patients. Sequencing and phylogenetic analysis showed that the predominant circulating genotypes were Gilliam and Karp. On multivariate analysis, acute respiratory distress syndrome, myocarditis, encephalitis/encephalopathy, jaundice and splenomegaly were significantly more common in those patients who were diagnosed with scrub typhus. A total of 14 patients diagnosed with scrub typhus succumbed to the illness. CONCLUSION: Patients with fever, headache, pulmonary manifestations, CNS manifestations, myocarditis, transaminitis or thrombocytopenia presenting in the monsoon and post-monsoon season should be evaluated for scrub typhus irrespective of the geographical location in India.

Genetic variations in olfactory receptor gene OR2AG2 in a large multigenerational family with asthma.

It is estimated from twin studies that heritable factors account for at-least half of asthma-risk, of which genetic variants identified through population studies explain only a small fraction. Multi-generation large families with high asthma prevalence can serve as a model to identify highly penetrant genetic variants in closely related individuals that are missed by population studies. To achieve this, a four-generation Indian family with asthma was identified and recruited for examination and genetic testing. Twenty subjects representing all generations were selected for whole genome genotyping, of which eight were subjected to exome sequencing. Non-synonymous and deleterious variants, segregating with the affected individuals, were identified by exome sequencing. A prioritized deleterious missense common variant in the olfactory receptor gene OR2AG2 that segregated with a risk haplotype in asthma, was validated in an asthma cohort of different ethnicity. Phenotypic tests were conducted to verify expected deficits in terms of reduced ability to sense odors. Pathway-level relevance to asthma biology was tested in model systems and unrelated human lung samples. Our study suggests that OR2AG2 and other olfactory receptors may contribute to asthma pathophysiology. Genetic studies on large families of interest can lead to efficient discovery.

Emerging multidrug resistance isolates of hospital-acquired bacterial meningitis in a tertiary care centre in North India.

Purpose. Acute bacterial meningitis continues to be a potentially life threatening condition. Hospital-acquired meningitis is rapidly increasing and adding an immense burden to the health system due to the emergence of multidrug resistance isolates. The purpose of this study is to find the antibiotic susceptibility pattern of the bacteria detected from hospital- and community-acquired meningitis.Methodology. A total of 400 Cerebrospinal fluid (CSF) samples from the suspected meningitis cases were collected and processed for cell count, biochemical examination, Gram staining, latex agglutination and culture. Bacteria grown on blood, chocolate and Mac-conkey agar were identified by matrix-assisted laser desorption/ionization-time of flight. Antibiotic susceptibility tests were performed as per Clinical and Laboratory Standard Institute guidelines.Results. Of the isolates, most prevalent Gram negative organisms in hospital-acquired bacterial meningitis were Escherichia coli 13 (27.08 %), Acinetobacter baumannii 12 (25 %), Klebsiella pneumoniae 5 (10.42 %), Pseudomonas aeruginosa 4 (8.33 %) and Gram positive organisms were Staphylococcus aureus 4 (8.33 %), Enterococcus faecium 3 (6.25 %) and CONS 2 (4.16 %). Streptococcus pneumoniae 3 (6.25 %) was the predominant organism in community-acquired bacterial meningitis. All the Gram negative isolates were multidrug resistance. Only colistin and imipenem were effective antibiotics against them. Likewise Gram positive organisms were susceptible to most of the antibiotics tested. However, E. faecium was only susceptible to Vanco+Teicoplanin.Conclusion. In hospital-acquired bacterial meningitis, multidrug resistance Gram negative bacteria are a huge challenge for the treatment of patients. Hence, antimicrobial stewardship should be followed to counteract with the emerging multidrug resistance isolates.

Point-of-care urine lipoarabinomannan antigen detection for diagnosis of tuberculosis in children.

Diagnosis of tuberculosis (TB) in children remains challenging due to the paucibacillary nature of the disease. Detection of TB using urine lipoarabinomannan (LAM) antigen was evaluated in children with presumed TB. Children with presumed intrathoracic tuberculosis (ITTB) and lymph node TB (LNTB) were enrolled. Expectorated or induced sputum or gastric aspirates from ITTB patients and fine-needle cytological aspirates from LNTB patients were subjected to Ziehl-Neelsen staining, MGIT™960™ culture and Xpert® MTB/RIF testing. Urine samples were tested to detect LAM, and the sensitivity and specificity calculated. Of 280 children with presumed ITTB and 101 with presumed LNTB, respectively 71 (25.3%) and 25 (24.7%) were categorised as 'confirmed TB', 70 (25%) and 33 (32.7%) as 'unconfirmed TB', and 139 (49.6%) and 43 (42.5%) as 'unlikely TB'. Respectively 8 (2.8%) children with ITTB and 3 (2.9%) with LNTB were positive on smear, 56 (20.0%) and 23 (22.7%) on Xpert, and 50 (17.8%) and 9 (8.9%) on culture. LAM assay sensitivity was 73.2% in confirmed ITTB cases, and 76% in confirmed LNTB cases; LAM assay specificity in children with ITTB and those with LNTB initiated on anti-tuberculosis treatment was respectively 92% and 93%. Detection of TB using the LAM assay was significantly better than detection using Xpert (P < 0.05 vs. P < 0.002). Urinary LAM testing showed high specificity and sensitivity, was detected in more cases initiated on treatment than reference tests, and improved disease detection by 38.5% in ITTB patients and by 41.6% in LNTB patients. .

Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in HIV-infected Indian children.

SETTING: Co-infection with the human immunodeficiency virus (HIV) may lead to inadequate plasma concentrations of anti-tuberculosis drugs in children with tuberculosis (TB). OBJECTIVE: To describe the influence of HIV infection on the pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in children. DESIGN: Prospective drug estimation study in two cohorts of children: HIV-infected (n = 24) and non-HIV-infected (n = 32) with TB. Dosages used were based on earlier World Health Organization recommendations. All four drugs were estimated simultaneously using liquid chromatography mass spectrometry. RESULTS: The HIV-TB co-infected children had a mean age of 105.9 months (standard deviation 43.1); there were 10 girls (41.7%). The maximum plasma concentration (Cmax), time taken to achieve Cmax, area under curve from 0-4 h and 2 h concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) were not affected by the HIV status of the children. Ethambutol (EMB) concentrations were lower in HIV-TB co-infected children. Inadequate 2 h concentrations of INH, RMP and EMB were found in the majority of the children in both groups. PZA concentrations were adequate in almost all children. Younger age and lower dose were associated with lower 2 h concentrations of INH and RMP. CONCLUSION: Inadequate concentrations of INH, RMP and EMB in both HIV-TB-infected and non-HIV-infected children provide support for the recently revised recommended doses of INH and RMP. EMB levels were lower in HIV-infected children; however, more studies are needed to validate this observation.

Home visits by community health workers to improve identification of serious illness and care seeking in newborns and young infants from low- and middle-income countries.

The objectives of this review were to evaluate the effect of home visits by trained community health workers (CHWs) to successfully identify newborns and young infants (up to 59 days of age) with serious illness and improve care seeking from a health facility. The authors searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. Abstracts of all articles were read by two authors independently and relevant articles selected. Data were extracted in a pretested questionnaire by two authors independently. Statistical analysis was performed using Review Manager software. A meta-analysis of included randomized controlled trials (RCTs) was carried out. Pooled estimates (risk ratios (RRs) with 95% confidence intervals (CIs)) of the evaluated outcome measures were calculated by the generic inverse variance method. Seven articles were identified for inclusion in the review. None of them compared the diagnosis of serious illness in young infants by health workers to a 'gold standard' diagnosis. Three studies were available for evaluating the ability of CHWs to identify seriously ill young infants/signs of serious illness. These studies suggest that sensitivity to identify serious illness ranged from 33.3 to 90.5% and specificity from 75.61 to 98.4%. For the outcome of improved care seeking from a health facility, after pooling the data from six RCTs with 4760 subjects in the intervention and 4398 subjects in the control arm, there was a significant improvement in care seeking in the home visit arm (RR=1.35; 95% CI=1.15 to 1.58). Moderate quality evidence indicated that home visits by trained CHWs were associated with improved care-seeking for sick young infants from health facilities by appropriate health care providers in resource-limited settings. However, there is a lack of data regarding successful identification of serious illness. Evidence from validation studies supports the implementation of home visits by trained CHWs for improving outcomes in sick newborns and young infants in resource-limited areas. Further well-designed studies evaluating the effect of home visits by CHWs on successful identification of seriously ill newborns and young infants should include verification by a 'gold standard'.

Mortality and Other Outcomes in Relation to First Hour Fluid Resuscitation Rate: A Systematic Review.

OBJECTIVE: To determine the effect of different regimen of first hour fluid administration rates on mortality and severe consequences of impaired circulation in 2 to 60 months old children with impaired circulation. DESIGN: Systematic review of randomized controlled trials. DATA SOURCES: Various databases including PubMed, Cochrane Library and EMBASE were searched. RESULTS: We found only two relevant trials; one was excluded as there was no comparator arm. Only one study (The FEAST Trial) compared boluses with maintenance fluid alone in children with severe febrile illness and one or more signs of impaired perfusion. The 48 hour mortality was more in the bolus group (RR 1.45, 95% CI 1.13,1.86). The quality of evidence is rated as moderate. For the children who met the WHO criteria for shock (severely impaired circulation) (n=65 children), those receiving boluses had higher mortality (RR 2.40, 95% CI 0.84, 6.88); the quality of evidence was rated as very low. CONCLUSION: A single large randomized controlled trial conducted in low-resource settings indicates that administration of fluid bolus is associated with higher mortality in comparison to the maintenance fluids alone in children with severe febrile illness and one or more signs of impaired perfusion. The findings are not generalizable to contexts with different severity of and different causes of shock and in centers with better facilities. There is urgent need for research in different settings to determine the optimal rate of fluid resuscitation in the first hour in children presenting with impaired circulation, particularly with severely impaired circulation.

Outcomes of Category II anti-tuberculosis treatment in Indian children.

SETTING: The emerging threat of multidrug-resistant tuberculosis (MDR-TB) has cast doubt on the efficacy of Category II anti-tuberculosis treatment in retreatment cases. Data on outcomes of treatment with the Category II regimen in children are scarce. OBJECTIVE: To study outcomes of Category II anti-tuberculosis treatment in Indian children. DESIGN: Charts belonging to patients registered between 2004 and 2012 at the Paediatric Tuberculosis Clinic, All India Institute of Medical Sciences, New Delhi, India, were reviewed, and children receiving Category II anti-tuberculosis treatment were included in the study. Outcomes were recorded as treatment success and poor outcome, which included treatment failure and default. RESULTS: A total of 125 children (mean age 101.6 months, standard deviation 42.9; girls 58 [46.4%]) were initiated on Category II anti-tuberculosis treatment, mainly due to worsening clinical conditions (36.8%) and relapse (36%). Treatment success, treatment failure and default were recorded in respectively 80 (64%), 20 (16%) and 25 (20%) children. Children who were non-adherent to previous treatment tended to default from Category II treatment as well (11.8% in previous non-defaulters vs. 37.5% in previous defaulters, P = 0.004). CONCLUSION: Category II anti-tuberculosis treatment was effective in approximately 60% of children who had failed or defaulted from the previous regimen. All efforts should be made to isolate Mycobacterium tuberculosis and perform drug susceptibility testing to identify MDR-TB in children.

Prevalence and risk factors for allergic bronchopulmonary aspergillosis in Indian children with cystic fibrosis.

OBJECTIVES: Allergic bronchopulmonary aspergillosis (ABPA) is a common complication in patients with cystic fibrosis. This cross-sectional study was planned to determine the prevalence and risk factors for ABPA in Indian children with cystic fibrosis. METHODS: Clinical evaluation, spirometry, chest radiograph, sputum, total IgE, specific IgE for Aspergillus fumigatus, IgG precipitins and skin prick tests were done in 33 CF patients. RESULTS: Prevalence of allergic bronchopulmonary aspergillosis was 18.2% (95% CI 6.9% - 35.4%): allergic bronchopulmonary aspergillosis was higher in patients with low cystic fibrosis score, age >12 years, atopy, and eosinophilia. CONCLUSION: Prevalence of ABPA is higher in Indian children with cystic fibrosis.

Effect of micronutrient deficiency on QuantiFERON-TB Gold In-Tube test and tuberculin skin test in diagnosis of childhood intrathoracic tuberculosis.

BACKGROUND/OBJECTIVES: Data on performance of QuantiFERON-TB Gold In-Tube test (QFT) and tuberculin skin test (TST) in children with active tuberculosis from high burden countries in the context of micronutrient deficiency are scarce. The objective of this study was to evaluate the effect of micronutrient deficiency on the performance of TST and QFT in children with intrathoracic tuberculosis. SUBJECTS/METHODS: Children with probable intrathoracic tuberculosis underwent TST, QFT, gastric lavages and induced sputum examination for AFB (Acid-Fast Bacilli) smear and culture. Zinc, copper, ferritin and vitamin D were measured on stored serum samples. The study used cross-sectional data at initiation of anti-tubercular therapy. RESULTS: Three hundred and sixty-two children (median age 115.5 months (interquartile range: 73, 144), 200 (55.3%) girls) were enrolled in the study. Microbiological confirmation of tuberculosis could be obtained in 128 patients. TST and QFT were positive in 337 (93%) and 297 (82%) children, respectively. Performance of both the tests was unaffected by weight-for-age and height-for-age 'z-scores' or by serum copper levels. TST was not affected by serum zinc and ferritin levels. Children with negative QFT results had lower mean serum zinc level (P=0.01) and higher ferritin levels (P=0.007) as compared to those with positive test. Higher proportion of children with positive TST were vitamin D deficient/insufficient (P=0.003). CONCLUSION: Micronutrient status, especially serum levels of zinc, may influence the performance of QFT in children with intrathoracic tuberculosis. Considering the high prevalence of zinc deficiency in developing countries, QFT should be used cautiously for diagnosing tuberculosis.

Role of the QuantiFERON®-TB Gold In-Tube test in the diagnosis of intrathoracic childhood tuberculosis.

SETTING: Tertiary care hospitals in India. OBJECTIVE: To compare the performance of the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) with that of the tuberculin skin test (TST) in the diagnosis of intrathoracic childhood tuberculosis (TB). METHODS: Children with intrathoracic TB were enrolled in a randomised controlled trial studying micronutrient supplementation in intrathoracic TB. They underwent TST and QFT-GIT before starting daily anti-tuberculosis treatment. RESULTS: Of 362 children (median age 115.5 months, IQR 73-144, 55% girls) enrolled in the study, microbiological confirmation of TB was obtained in 128 (35%). The TST was positive in 337 (93%, 95%CI 90-95.5) and QFT-GIT in 297 (82%, 95%CI 77.8-85.6). Sensitivity of TST and QFT-GIT in culture-confirmed TB cases was respectively 90.5% (95%CI 84.1-94.5) and 82.6% (95%CI 74.9-88.4). QFT-GIT positivity rate correlated with TST induration (P < 0.001). TST was influenced by the disease spectrum (P = 0.004) and the age of the children (P = 0.002); QFT-GIT remained unaffected by these factors. Bacille Calmette-Guérin immunisation status, weight-for-age Z-scores and microbiological confirmation of Mycobacterium tuberculosis did not influence the performance of either test. CONCLUSION: In high-burden countries, QFT-GIT is comparable to TST and offers no added advantage in the diagnosis of childhood intrathoracic TB.

Multiple locus sequence typing of Salmonella Typhi, isolated in north India - a preliminary study.

BACKGROUND & OBJECTIVES: In India enteric fever is a major public health problem and Salmonella Typhi is the most common aetiologic agent. Any control strategy for such infections depends to a large extent on the understanding of the disease and relatedness of strains across the world. Multi locus sequence typing (MLST) is one such method of genotyping of bacteria based upon housekeeping genes of known function and chromosome position. MLST data of pathogens are important to determine the molecular evolution by a stable and reproducible method. This study was undertaken to determine the sequence types of representatives S. Typhi isolates obtained from enteric fever patients in a tertiary care centre in north India, over a period of 20 years (1990-2010). METHODS: A total of 30 representative isolates of S. Typhi identified by biochemical and serological tests were subjected to multi locus sequence typing (MLST). Seven housekeeping genes of known function and chromosome position were used for the typing by MLST. Sequencing was carried out by using an automated DNA sequencer and results were analyzed to generate phylogenetic tree. RESULTS: MLST pattern grouped S. Typhi into two sequence types- ST1 and ST2. ST1 was predominantly present followed by ST2. INTERPRETATION & CONCLUSIONS: By MLST the presence of both sequence types, ST1 and ST2, was found in S. Typhi isolates in our region. Predominately ST1 was present followed by ST2. These preliminary results corroborate the global distribution of both sequence types of S. Typhi and also emphasize for the continuous screening of S. Typhi.

Antibodies that cross-neutralize the tier-2 pseudoviruses are produced in antiretroviral-naïve HIV-1-infected children from northern India.

In this cross-sectional study, we evaluated the efficiency of the plasma of 38 antiretroviral-naïve HIV-1-infected children from northern India against a standard panel of pseudoviruses (3 clade C and 3 clade B) by TZM-bl assay. Neutralization potential was observed to a variable extent, with a potency ranging up to reciprocal ID(50) titers of 1967. Cross-neutralization was observed in 28.9 % (11/38) of the children. There was a significant positive correlation between viremia and neutralization efficiency against two of the viruses studied (Du172 r = 0.49; p = 0.007 and RHPA r = 0.47; p = 0.01), suggesting that persistent antigenic stimulation is necessary for the generation of broadly neutralizing antibody responses in these children. Further mapping of the epitope specificities of the neutralization determinants in the polyclonal plasma would provide important information for immunogen design.

Association between reproductive factors and breast cancer in an urban set up at central India: a case-control study.

BACKGROUND: Epigenetic changes, geography and environmental factors do surpass the genetic factors in the development of breast cancer. This study investigates the association of reproductive factors with the breast cancer in this context. OBJECTIVE: To detect the association of reproductive risk factors with breast cancer in an urban set up at central India. STUDY DESIGN: Matched paired community-based case-control study. MATERIALS AND METHODS: The study was conducted for a period of a year from October 2008 to August 2009 in Bhopal (MP). Demographic data and reproductive risk factor related information were collected using structured questionnaire. Data analysis was done by Epi-info and SPSS 16. RESULTS: History of using oral contraceptive pills (OR = 3.02, 95% CI: 1.28-7.11), history of not having breastfeeding (OR = 3.62, 95% CI: 1.29-10.16) and family history of breast cancer (OR = 3.98, 95%CI: 1.06-14.826) were associated significantly with the occurrence of breast cancer in multivariate analysis. CONCLUSIONS: The findings of the present study suggests that positive family history of breast cancer and history of using OCP may be the epigenetic factors promoting the occurrence of breast cancer while breastfeeding reduces the possibility of acquiring breast cancer.

Burden of healthcare-associated infections in a paediatric intensive care unit of a developing country: a single centre experience using active surveillance.

Healthcare-associated infections (HAIs) are an important cause of morbidity and mortality among critically ill patients of all age groups. This prospective surveillance study was performed to estimate the burden of HAIs in a paediatric intensive care unit (PICU) of a developing country. During the 12-month study, 187 patients were treated in the PICU for ≥48h, of whom 36 patients had 44 episodes of HAIs. The crude infection rate and incidence density (ID) of HAI were 19.3/100 patients and 21/1,000 patient-days, respectively. Of the 44 episodes of HAI, 27 (61%) were healthcare-associated pneumonia (HAP), 12 (27%) were bloodstream infections (HA-BSI) and four (9%) were urinary tract infections. Mean length of stay and mortality were significantly higher in patients who developed an HAI [25 vs 7 days (P<0.0001) and 50% vs 27.8% (P<0.005), respectively]. Acinetobacter spp. were the commonest infecting bacteria in both HAP and HA-BSI. For developing countries, active surveillance is essential to reduce the burden of HAIs in high risk groups.

Anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis.

OBJECTIVE: Prevalence and clinical significance of anti-cyclic citrullinated peptide (CCP) antibodies in Indian patients with juvenile idiopathic arthritis (JIA). METHODS: Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 78 patients with JIA which included all 3 major subtypes of the disease: pauciarticular, polyarticular afld systemic onset. Values above 5 relative units were taken as positive. Associations between anti-CCP antibodies and clinical and laboratory and radiological parameters were determined. RESULTS: Anti-CCP antibodies were positive in only 2 of 34 (5.9%) patients with pauciarticular JIA and 3 of 17 (17.6%) of systemic,.pnset JIA, whereas it was positive in 13 of 27 (48.1%) of polyarticular JIA patients (p < 0.001). Furthermore, it was seen that among patients with polyarticular JIA, RF-lgM positive patients had higher rate of anti-CCP antibody positivity with 7 of 8 (87.5%) patients having positive anti-CCP antibody (p<0.001). Similarly, patients with erosions (11/19; p<0.001) and deformities (5/-10; p<0.001) were found to have significant association with anti-CCP antibody positivity. CONCLUSION: Anti-CCP antibodies could be detected more frequently in the sera of JIA patients with severe manifestations like-erosions and deformity. It was also more significantly associated with seropositive polyarticular JIA than other types. It can be presumed from these results that anti-CCP antibodies can be used as a marker to predict severe course of JIA at the onset to guide optimal aggressive therapy.