Association of water, sanitation, hygiene and food practices with enteric fever in a paediatric cohort in North India.

BACKGROUND: Our aim was to assess the association of water, sanitation and hygiene (WASH) and food practices with culture-confirmed enteric fever in children <15 years of age. METHODS: We followed a cohort of 6000 children from an urban low socioeconomic neighbourhood in South Delhi for 2 years to estimate burden of culture-confirmed enteric fever. Risk ratios (RRs) were estimated to study the association between WASH practices and enteric fever. We assessed the microbiological quality of drinking water and conducted geospatial analysis to evaluate the distribution of enteric fever cases around households with contaminated drinking water. RESULTS: A total of 5916 children in 3123 households completed survey. Piped water (82%) was the major source of household drinking water. One-third (32%) of the households treated water before consumption. Almost all households had sanitary toilets (99.9%) and 16% used shared toilets. Consumption of food from street vendors and unnamed ice creams more than once a week was observed in children from 12.7% and 38.4% households, respectively. Eighty culture-confirmed enteric fever cases were reported. The risk of enteric fever was 71% higher in children belonging to households having food from outside once a week or more (RR 1.71, 95% CI 1.00 to 2.94). The RR for enteric fever in children living in households with availability of safe drinking water was 0.75 (95% CI 0.45 to 1.26). We found that 14.8% of the households had presence of coliforms or Escherichia coli in their household drinking water. The odds of having a case of enteric fever within a 5 and 25 m buffer zone around households with contaminated drinking water were 4.07 (95% CI 0.81 to 20.5) and 1.44 (95% CI 0.69 to 3.00), respectively. CONCLUSION: In addition to WASH practices, optimal food hygiene may have a role in urban low socioeconomic population to control enteric fever. TRIAL REGISTRATION NUMBER: CTRI/2017/09/009719.

Incidence of lab-confirmed dengue fever in a pediatric cohort in Delhi, India.

BACKGROUND: Our aim was to estimate the overall and age-specific incidence of lab-confirmed dengue fever using ELISA based assays among children 6 months to 15 years in Delhi. METHODS: We enrolled a cohort of 984 children aged 6 months to <14 years in South Delhi and followed-up weekly for fever for 24 months or till 15 completed years of child-age. Households of the enrolled children were geo-tagged. NS1, IgM and IgG assays were conducted using ELISA method to confirm dengue fever in children with ≥3 consecutive days of fever. Molecular typing was done in a subset of NS1 positive cases to identify the circulating serotypes. PRINCIPAL FINDINGS: We had a total of 1953 person-years (PY) of follow up. Overall, there were 4208 episodes of fever with peaks during June to November. The overall incidence (95%CI) of fever was 215/100 PY (209 to 222). A total of 74/1250 3-day fever episodes were positive for acute dengue fever (NS1 and/or IgM positive). The overall incidence (95%CI) of acute dengue fever was 37.9 (29.8 to 47.6) per 1000 PY; highest among children aged 5 to 10 years (50.4 per 1000 PY, 95% CI 36.5 to 67.8). Spatial autocorrelation analysis suggested a clustering pattern for the dengue fever cases (Moran's Index 0.35, z-score 1.8, p = 0.06). Dengue PCR was positive in 16 of the 24 specimens tested; DEN 3 was the predominant serotype identified in 15/24 specimens. CONCLUSIONS: We found a high incidence of dengue fever among under 15-year children with clustering of cases in the community. DEN 3 was the most commonly circulating strain encountered. The findings underscore the need for development of affordable pre-vaccination screening strategy as well as newer dengue vaccines for young children while continuing efforts in vector control.

Prevalence of reproductive tract infections including sexually transmitted infections among married women in urban and peri-urban mid to low socioeconomic neighbourhoods of Delhi, North India: an observational study protocol.

INTRODUCTION: The Global Health Sector Strategy on sexually transmitted infections (STIs), endorsed by the World Health Assembly in 2016 aims to end STIs as public health threat by 2030. WHO conducts global estimates of prevalence to monitor progress towards achieving the same. However, limited laboratory confirmed data exist of STIs and reproductive tract infections (RTIs) apart from few prevalence surveys among key populations and clinic-based reports, including in India. Syndromic approach is the cornerstone of RTI/STI management and to maximise the diagnostic accuracy, there is a need to determine the main aetiologies of vaginal discharge. This study aims to estimate the prevalence of common STIs and RTIs and their aetiological organisms in symptomatic and asymptomatic women living in the urban and peri-urban, mid to low socioeconomic neighbourhoods of Delhi, North India. METHODS AND ANALYSIS: A cross-sectional study will be conducted among 440 married women who participated in the 'Women and Infants Integrated Interventions for Growth Study (WINGS)'. Information on sociodemographic profile, sexual and reproductive health will be collected, followed by examination and collection of vaginal swabs for nucleic acid amplification tests to diagnose Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis and microscopy to identify bacterial vaginosis and Candida albicans. Treatment will be as per the syndromic approach recommendations in the Indian National Guidelines. Data will be analysed to estimate prevalence, presence of symptoms and signs associated with laboratory confirmed RTIs/STIs using STATA V.16.0 (StataCorp). ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics review committees of the WHO and Society for Applied Studies (SAS/ERC/RHR-RTI/STI/2020). Approval has been obtained by the WINGS investigators from SAS ethics research committee to share the contact details of the participants with the investigators. The findings will be published in peer-reviewed journals and disseminated through scientific conferences. TRIAL REGISTRATION NUMBER: CTRI/2020/03/023954.

Effect of Community-Initiated Kangaroo Mother Care on Fecal Biomarkers of Gut Function in Low Birth Weight Infants in North India: A Randomized Clinical Trial.

This individually randomized trial was conducted to estimate the effect of promoting community-initiated Kangaroo Mother Care (ciKMC) in low birth weight (LBW) infants on gut inflammation and permeability. Participants included 200 stable LBW infants (weighing 1,500-2,250 g) in North India enrolled between May and October 2017. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding through home visits. The mothers in the intervention arm were supported to practice ciKMC until 28 days after birth, i.e., the neonatal period, or till the baby wriggled out of KMC position, if earlier. Infant stool specimens were collected during the first week of birth, and within 1 week after end of the neonatal period. Concentrations of fecal neopterin (nmol/L), myeloperoxidase (ng/mL), and alpha-1-antitrypsin (µg/mL) were determined using ELISA, and composite enteric enteropathy (EE) score at the end of the neonatal period was calculated by principal component analysis. We did not find any substantial difference in means between the ciKMC and control arm infants in the log-transformed values of neopterin (0.03; 95% CI -0.15 to 0.21), myeloperoxidase (0.28; 95% CI -0.05 to 0.61) and alpha-1-antitrypsin (0.02; 95% CI -0.30 to 0.34). The mean (SD) composite EE score was 13.6 (7.5) in the ciKMC and 12.4 (8.3) in the control arm infants, and the adjusted difference in means was, 0.4 (95% CI -1.8 to 2.7). Our findings suggest that the promotion of ciKMC did not affect gut inflammation and permeability in our target population of LBW infants in North India.

Effect of Community-Initiated Kangaroo Mother Care on Postpartum Depressive Symptoms and Stress Among Mothers of Low-Birth-Weight Infants: A Randomized Clinical Trial.

Importance: Approximately 1 in 5 women in low- and middle-income countries experience postpartum depression, and the risk is higher among mothers of low-birth-weight (LBW) infants. Kangaroo mother care (KMC) is effective in improving survival among LBW infants, but the benefits of KMC for mothers are not well described. Objective: To estimate the effects of community-initiated KMC (ciKMC) on maternal risk of moderate-to-severe postpartum depressive symptoms and on salivary cortisol concentration, a biomarker of stress. Design, Setting, and Participants: This was an unmasked, parallel-group, individually randomized clinical trial. Participants included 1950 mothers of stable LBW infants (weighing 1500-2250 g) in rural and semiurban low-income populations in North India enrolled between April 2017 and March 2018. Data analysis was performed from January to July 2020. Interventions: Eligible participants were randomly assigned to the intervention or control group by block randomization. The mothers in the intervention group were supported to practice ciKMC until 28 days after birth or until the infant wriggled out of the KMC position (ie, was no longer staying in the KMC position). The intervention included promotion and support of skin-to-skin contact and exclusive breastfeeding through home visits. Main Outcomes and Measures: Postpartum depressive symptoms at the end of the neonatal period were measured using the Patient Health Questionnaire-9, with a score of 10 or higher used to identify moderate-to-severe depressive symptoms. Salivary cortisol concentration was measured in a subsample of 550 mothers before and after breastfeeding on day 28 after birth. Results: Of the 1950 participants (mean [SD] age, 23 [3.5] years), outcome assessment was completed for 974 of 1047 participants (93%) in the intervention group and 852 of 903 participants (94%) in the control group. Sixty-four percent of participants (1175 of 1826 participants) belonged to the lowest 3 wealth quintiles. The proportion of mothers with moderate-to-severe postpartum depressive symptoms was 10.8% (95% CI, 8.9%-12.9%; 105 of 974 mothers) in the intervention group vs 13.6% (95% CI, 11.4%-16.1%; 116 of 852 mothers) in the control group. The adjusted relative risk of moderate-to-severe maternal postpartum depressive symptoms was 0.75 (95% CI, 0.59-0.96), or an efficacy of 25%. There was no difference in day-28 salivary cortisol concentration between the ciKMC and control group mothers before or after breastfeeding. The analysis estimated that supporting 36 mothers to perform KMC at home would prevent 1 mother from experiencing moderate-to-severe postpartum depressive symptoms. Conclusions and Relevance: These findings suggest that ciKMC practice may substantially reduce the risk of moderate-to-severe maternal postpartum depressive symptoms. This evidence supports KMC as an intervention to be incorporated in essential newborn care programs in low- and middle-income settings. Trial Registration: Clinical Trials Registry-India Identifier: CTRI/2017/04/008430.

Incidence of Enteric Fever in a Pediatric Cohort in North India: Comparison with Estimates from 20 Years Earlier.

BACKGROUND: An earlier cohort in 1995-1996 showed a very high burden of typhoid in Delhi. Our aim was to estimate the current overall and age-specific incidence of culture-confirmed enteric fever among children aged 6 months to 15 years in Delhi. METHODS: We enrolled a cohort of 6000 children aged 6 months to <14 years in South Delhi and followed them up weekly for 24 months or until 15 completed years of child age, whichever was earlier. Blood culture to confirm enteric fever was done in children with ≥3 consecutive days of fever. RESULTS: We recorded a total of 14 650 episodes of fever in the 11 510 person-years (PY) of follow-up. A total of 81 fever episodes were positive for enteric fever. The incidence (95% confidence interval) of all enteric fever was 703.7 (560.5-874.7) per 100 000 PY. The incidences of typhoid and paratyphoid fevers were 608.1 (95% confidence interval, 481.1-768.7) and 111.7 (59.5-191.1) per 100 000 PY, respectively, highest among children aged 10-15 years. CONCLUSIONS: Despite a 35% reduction in incidence compared with the 1995-1996 cohort, our study suggested a substantial burden of enteric fever in the population. Continued efforts to improve water, sanitation, and hygiene parameters along with implementation of novel vaccination strategies and disease surveillance can help achieve the goal of disease elimination.

Evaluation of Antimicrobial Susceptibility Profile in Salmonella Typhi and Salmonella Paratyphi A: Presenting the Current Scenario in India and Strategy for Future Management.

BACKGROUND: Systematic studies to estimate the disease burden of typhoid and paratyphoid in India are limited. Therefore, a multicenter study on the Surveillance of Enteric Fever in India was carried out to estimate the incidence, clinical presentation, and antimicrobial resistance (AMR) trend. The data presented here represent the national burden of AMR in Salmonella Typhi and Salmonella Paratyphi A. METHODS: Antimicrobial susceptibility testing was performed for S. Typhi and S. Paratyphi A (n = 2373) isolates collected prospectively during a 2-year period from November 2017 to January 2020. RESULTS: Of 2373 Salmonella isolates, 2032 (85.6%) were identified as S. Typhi and 341 (14.4%) were S. Paratyphi A. Approximately 2% of S. Typhi were multidrug-resistant (MDR), whereas all 341 (100%) of S. Paratyphi A isolates were sensitive to the first-line antimicrobials. Among 98% of ciprofloxacin nonsusceptible isolates, resistance (minimum inhibitory concentration [MIC] >0.5 µg/mL) was higher in S. Typhi (37%) compared with S. Paratyphi A (20%). Azithromycin susceptibility was 99.9% and 100% with a mean MIC of 4.98 µg/mL for S. Typhi and 7.39 µg/mL for S. Paratyphi A respectively. Ceftriaxone was the only agent that retained 100% susceptibility. Moreover, beta-lactam/beta-lactamase inhibitors showed potent in vitro activity against the study isolates. CONCLUSIONS: Data obtained from this systematic surveillance study confirms the declining trend of MDR Salmonella isolates from India. The higher prevalence of ciprofloxacin nonsusceptibility enforces to limit its use and adhere to the judicious usage of azithromycin and ceftriaxone for enteric fever management.

Typhoid and paratyphoid fever co-infection in children from an urban slum of Delhi.

We report two cases of co-infection with Salmonella Typhi and Salmonella Paratyphi A identified by blood culture and confirmed by serotyping from an ongoing fever surveillance cohort in an urban slum in New Delhi. Co-infections such as these have important implications on diagnosis, treatment options including choice of antimicrobial(s), disease outcome and strategy for prevention.

ROTAVAC® does not interfere with the immune response to childhood vaccines in Indian infants: A randomized placebo controlled trial.

A phase III randomized double-blind placebo-controlled trial was conducted in the urban neighborhoods of Delhi to assess whether Oral Rotavirus Vaccine ROTAVAC® interferes with the immune response to childhood vaccines when coadministered. Infants aged 6 weeks were randomized to receive three doses of either ROTAVAC® or placebo along with childhood vaccines: Oral Polio Vaccine and vaccines against Diphtheria, Pertussis, Tetanus, Hepatitis B and Haemophilus influenza type b given as Pentavalent at 6, 10, 14 weeks of age. Blood specimens were collected from all infants at baseline and 4 weeks post dose 3 to assess the immune response to antigens in Oral Polio Vaccine, Pentavalent and ROTAVAC® vaccines. Non-inferiority of immune response to all vaccine components of the childhood vaccines when ROTAVAC® was administered concurrently was demonstrated. Non-inferior immune responses to childhood vaccines were evaluated based on the seroprotective levels of antibodies against polio types 1, 2, and 3, Diphtheria toxoid, Tetanus toxoid, Haemophilus influenza type b anti- polyribosyl ribitol phosphate antibodies and Hepatitis B antibodies; and the Geometric Mean Concentration for Pertussis. The proportion of infants who seroconverted (≥4 fold rise) was 38.6% in the ROTAVAC® group and 12.2% in the placebo group. The frequency and severity of immediate adverse events, adverse events and serious adverse events were similar in both groups. None of the five reported deaths were considered to be related to the ROTAVAC® and no case of intussusception meeting Brighton Diagnostic Certainty Level I criteria was reported. This study demonstrated that ROTAVAC® can be safely administered with childhood vaccines without interfering with the immune response to the antigens contained in these vaccines.