Environmental Surveillance for Salmonella Typhi and its Association With Typhoid Fever Incidence in India and Malawi.

BACKGROUND: Environmental surveillance (ES) for Salmonella Typhi potentially offers a low-cost tool to identify communities with a high burden of typhoid fever. METHODS: We developed standardized protocols for typhoid ES, including sampling site selection, validation, characterization; grab or trap sample collection, concentration; and quantitative PCR targeting Salmonella genes (ttr, staG, and tviB) and a marker of human fecal contamination (HF183). ES was implemented over 12 months in a historically high typhoid fever incidence setting (Vellore, India) and a lower incidence setting (Blantyre, Malawi) during 2021-2022. RESULTS: S. Typhi prevalence in ES samples was higher in Vellore compared with Blantyre; 39/520 (7.5%; 95% confidence interval [CI], 4.4%-12.4%) vs 11/533 (2.1%; 95% CI, 1.1%-4.0%) in grab and 79/517 (15.3%; 95% CI, 9.8%-23.0%) vs 23/594 (3.9%; 95% CI, 1.9%-7.9%) in trap samples. Detection was clustered by ES site and correlated with site catchment population in Vellore but not Blantyre. Incidence of culture-confirmed typhoid in local hospitals was low during the study and zero some months in Vellore despite S. Typhi detection in ES. CONCLUSIONS: ES describes the prevalence and distribution of S. Typhi even in the absence of typhoid cases and could inform vaccine introduction. Expanded implementation and comparison with clinical and serological surveillance will further establish its public health utility.

Comprehensive profiling of social mixing patterns in resource poor countries: a mixed methods research protocol.

Background: Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling. Methods: To address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures.We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants' interactions with household members using high resolution data from the proximity sensors and calculating infants' proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member. Discussion: Our qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies.

Influence of publicly funded conditional cash transfer programms on utilization patterns of healthcare services for acute childhood illness.

BACKGROUND: Conditional cash transfers are widespread and effective for utilization of targeted health services, but there is little evidence of their influence on the utilization of non-targeted or extended general healthcare services. Using data from a population-based health utilization survey, we evaluated the influence of conditional cash transfers for maternal and immunization services on the utilization of healthcare services for acute childhood illnesses. METHODS: Participants included mothers or primary caretakers of children <2 y of age residing in 2407 households in urban Vellore, Tamil Nadu, India. Mothers of children with illness in the preceding month were interviewed on presenting symptoms, provider choice and beneficiary status of maternal and immunization-based conditional cash transfer programs. RESULTS: Of 2407 children <2 y of age, about 48% reported being beneficiaries of maternal and immunization-based conditional cash transfers. Beneficiary status was associated with an increased use of public services (adjusted relative risk [aRR] 3.14 [95% confidence interval {CI} 1.96 - 5.02]) but not the use of private services (aRR 1.42 [95% CI 0.97 - 2.08]) relative to home or informal care. CONCLUSIONS: Our findings indicate financial incentives for use of maternal and immunization services could have an indirect, non-targeted effect on utilization of formal healthcare for acute childhood illnesses.

Intussusception hospitalizations before rotavirus vaccine introduction: Retrospective data from two referral hospitals in Tamil Nadu, India.

BACKGROUND: The indigenous oral rotavirus vaccine Rotavac® was introduced into the public immunization system in India in 2016 and will be expanded in phases. This data will describe the epidemiology of intussusception in India in absence of rotavirus vaccination and will help in setting up or designing a safety monitoring system. METHODS: Medical records of intussusception cases between 2013 and 2016 in two major referral hospitals in Tamil Nadu, India were reviewed, and data on clinical presentation and management and outcome were collated. RESULTS: A total of 284 cases of intussusception were diagnosed and managed at the two centers of which 280/284 could be classified as level 1 by the Brighton criteria. Median age at presentation was 8 months (Inter Quartile Range, IQR 6-17.2) with a male to female ratio of 2.1:1. Over half (57.7%) required surgical intervention while the rest underwent non-surgical or conservative management. CONCLUSIONS: Retrospective data from referral hospitals is sufficient to classify cases of intussusception by the Brighton criteria. These baseline data will be useful for monitoring when rotavirus vaccination is introduced.

Utilization of Preventive and Curative Services in Five Rural Blocks in Vellore, India.

This health utilization survey of 720 children (age <2 y) from 5 rural blocks in Vellore district identified that 80% used government facilities for preventive care while >80% used private facilities for curative services. Only 0.7% were home deliveries, 46% reported illness in the two-week recall, and 83% sought care for these illness.

Study design and baseline results of an open-label cluster randomized community-intervention trial to assess the effectiveness of a modified mass deworming program in reducing hookworm infection in a tribal population in southern India.

INTRODUCTION: Hookworm infection is a leading cause of iron deficiency anemia and malnutrition in resource-poor settings. Periodic mass deworming with anthelminthic drugs remains the cornerstone of hookworm control efforts worldwide. Reinfection following treatment occurs, reflecting the human host's inability to acquire immunity following exposure to an untreated reservoir of infection. This cluster randomized trial will evaluate the effectiveness of a modified, population-based, mass deworming strategy in reducing hookworm infection in an endemic southern Indian population. METHODS: Forty five tribal villages were randomized into three groups: one received annual treatment; the second received two rounds of treatment at 1-month intervals; and the third received four rounds of treatment - two rounds 1 month apart at the beginning, followed by another two after 6 months. Stool samples collected through cross-sectional parasitological surveys pre- and post-intervention, and at 3-monthly intervals for a period of 1 year were tested for presence of hookworm ova. Long-term effectiveness of treatment will be assessed through another survey conducted 2 years after the last treatment cycle. RESULTS: From a population of 11,857 individuals, 8681 (73.2%) were found to be eligible and consented to participate, out-migration being the primary reason for non-participation. Baseline stool samples were obtained from 2082 participants, with 18.5% having hookworm infection, although majority were low intensity infections (<2000 eggs per gram of feces). DISCUSSION: This study will help identify the optimal mass deworming strategy that can achieve the greatest impact in the shortest period of time, particularly in settings where long-term program sustainability is a challenge.

Racecadotril in the Management of Rotavirus and Non-rotavirus Diarrhea in Under-five Children: Two Randomized, Double-blind, Placebo-controlled Trials.

OBJECTIVE: To study the effect of racecadotril on reduction in the duration of acute rotavirus and non-rotavirus diarrhea. DESIGN: Two randomized double-blind placebo-controlled trials. SETTING: Community-based trial in an urban area in Vellore, hospital-based trial at a secondary hospital in Vellore. PARTICIPANTS: 199 and 130 3-59 month old children in the community- and hospital-based trials, respectively. METHODS: Racecadotril (1.5 mg/kg/dose, thrice a day for three days) or placebo were given to manage acute diarrhea in both trials. MAIN OUTCOME MEASURE: Median duration of diarrhea. RESULTS: Among 124 children completing the hospital trial, the median duration of diarrhea was 25 h in both arms (P=0.5); median total stool weight was 74 g/kg and 53.5 g/kg in racecadotril group and placebo group, respectively (P=0.4); and average fluid intake per day was 3.6 mL/kg/h and 3mL/kg/h in racecadotril and placebo arms, respectively (P=0.3). Among rotavirus-positive children, median duration of diarrhea was 26.9 h and 30.2 h in racecadotril and placebo arms, respectively (P=0.7). In the community, 196 completed the trial, the median duration of diarrhea was 2 days for both arms (P=0.8) and rotavirus positive children had similar outcomes with median diarrheal duration of 3 d in both arms (P=0.4). CONCLUSIONS: Treatment with racecadotril did not reduce diarrheal duration, stool volume or the requirement for fluid replacement in children with acute gastroenteritis, both with and without rotavirus infection.

Direct Medical Costs in Children with Rotavirus and Non-rotavirus Diarrhea Admitted to a Pediatric Intensive Care Unit and High Dependency Unit in Delhi.

OBJECTIVE: To estimate direct medical costs of diarrheal hospitalization of children <5 years admitted in pediatric intensive care unit (PICU) or high dependency unit (HDU). METHODS: Analysis of medical records and hospital bills of 84 children during two time frames, 2005-08 and 2012-14. RESULTS: Direct medical costs in PICU increased from INR 17,941 to INR 50,663 per child for rotavirus diarrhea and INR 11,614 to INR 27,106 for non-rotavirus diarrhea, and in HDU from approximately INR 5,800 to INR 10,500 per child for all-cause diarrhea between the two time frames. CONCLUSIONS: Costs of PICU and HDU care are high and should be included in cost-effectiveness analysis of vaccination.

Direct and Indirect Costs of Pediatric Gastroenteritis in Vellore, India.

OBJECTIVE: To determine costs of pediatric gastroenteritis in out-patient and in-patient facilities. METHODS: Cross-sectional survey of children with acute gastroenteritis attending out-patient clinic (n=30) or admitted in the ward (n=30) for management in the Christian Medical College, Vellore, India from July-September 2014 to estimate direct (drugs, tests, consultation/hospitalization) and indirect (travel, food, lost wages) costs associated with the episode. RESULTS: Median direct and indirect costs were Rs 590 and Rs 190 for out-patient management and Rs 7258 and Rs. 610 for hospitalization, constituting 1.1% and 11% of median annual household income, respectively. CONCLUSIONS: Escalating healthcare costs need tracking for evaluation of interventions.

The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants.

BACKGROUND: Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries, similarly to other oral vaccines. The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem. Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens, we aimed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity. METHODS: We did a double-blind, randomised, placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district, India. Infants were eligible to participate if they were 6-11 months old, available for the study duration, and lacked serum neutralising antibodies to serotype-3 poliovirus. Infants were randomly assigned (1:1) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days, followed by serotype-3 monovalent oral poliovirus vaccine on day 14. The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per-protocol population (ie, all those who received azithromycin or placebo, oral poliovirus vaccine, and provided a blood sample according to the study protocol). Safety outcomes were assessed in all infants enrolled in the study. The trial is registered with the Clinical Trials Registry India, number CTRI/2014/05/004588. FINDINGS: Between Aug 5, 2014, and March 21, 2015, 754 infants were randomly assigned: 376 to receive azithromycin and 378 to placebo. Of these, 348 (93%) of 376 in the azithromycin group and 357 (94%) of 378 infants in the placebo group completed the study per protocol. In the azithromycin group, 175 (50%) seroconverted to serotype-3 poliovirus compared with 192 (54%) in the placebo group (risk ratio 0·94, 95% CI 0·81-1·08; p=0·366). Azithromycin reduced faecal biomarkers of environmental enteropathy (calprotectin, myeloperoxidase, α1-antitrypsin) and the prevalence of bacterial but not viral or eukaryotic pathogens. Viral pathogens were associated with lower seroconversion. Three serious adverse events were reported (two in the azithromycin group and one in the placebo group), but none was considered related to the study interventions. INTERPRETATION: Azithromycin did not improve the immunogenicity of oral poliovirus vaccine despite reducing biomarkers of environmental enteropathy and the prevalence of pathogenic intestinal bacteria. Viral interference and innate antiviral immune mechanisms might be more important determinants of the immunogenicity of live-virus oral vaccines. FUNDING: Bill & Melinda Gates Foundation.

Purple urine bag syndrome: time for awareness.

Purple urine bag syndrome occurs commonly in long-term catheterized patients causing significant stress for patients, care takers, and health care providers. This may lead to unwarranted investigation as well as treatment when not identified early. Demographic changes in Indian population with increasing geriatric care make it a case to increase awareness of this condition among health care providers in primary and secondary care settings.

Intussusception in southern India: comparison of retrospective analysis and active surveillance.

Surveillance for intussusception is a post marketing requirement for rotavirus vaccines following observation of a small increased risk of intussusception after rotavirus vaccination in some global settings. This study presents the clinical presentation and outcomes of children who presented with intussusception at a large tertiary care facility directly (non-surveillance) as retrospective analysis of a period where rotavirus vaccine was not in routine use, or as part of active surveillance in a phase III oral rotavirus vaccine trial. Hospital records of children under 2 years of age treated for intussusception between 1 January 2010 and 31 August 2013 at the Christian Medical College Hospital, Vellore, India, were reviewed. Sixty-one cases of intussusception in children under two years of age presented at the hospital. An additional 16 cases of ultrasound diagnosed intussusception were identified through the active surveillance of a cohort of 1500 children participating in a rotavirus phase III trial in the same period. In the nonsurveillance group, median age at presentation was 214 days (IQR 153-321) with 52 events (85.3%) occurring in the first year of life. Cases were seen year-round with no definitive evidence of seasonality. Thirty-one (50.8%) intussusceptions required surgical reduction, 26 (42.6%) had pneumatic reduction and 2 (3.3%) barium enema reduction. Two intussusceptions (3.3%) resolved spontaneously. There were no deaths, all children were discharged after recovery. Active surveillance identified 16 children with a median age at event of 375 days (IQR 248-574). Nine (56%) children had small bowel or transient intussusception that resolved spontaneously. Seven intussusceptions were reduced radiologically; none required surgery. In summary, there were significant differences between presentation and outcomes in cases of intussusception identified by passive and active surveillance, likely related to enhanced and early detection of intussusception through active monitoring in the trial. The WHO recommendation of sentinel hospital based surveillance for post-marketing surveillance after rotavirus vaccine introduction is likely to a better approach than active surveillance.

A study on morbidity among automobile service and repair workers in an urban area of South India.

INTRODUCTION: Service sector in Indian industrial growth has obtained significant numbers. Automobile service industry is one of the largest in the world with a majority of the workers in unorganized sector of the industry. This study was carried out among auto service industry workers in Vellore urban area to assess possible occupation related morbidity. MATERIALS AND METHODS: A cross-sectional observation study was carried out among 106 automobile repair shop workers. RESULTS: Half (47%) suffered work related stress, 32 (30.2%) reported exposure to dust, 81 (76%) to heat, and 50 (17%) to hazardous chemicals and heavy metals. More than 90% reported over exposure to petroleum products. A third reported cough for more than 2 weeks, more than a quarter reported gastrointestinal symptoms associated with work. Half of them reported musculoskeletal complaints associated with work with a quarter reporting un-intentional work place injuries. A tenth of them were found to have reduced pulmonary function on testing and nearly half had impaired sensory functions in peripheries. Reduced pulmonary function was found to be significantly associated with heavy metal exposure (P = 0.001). Peripheral neuropathy was significantly associated with years of occupation (P = 0.001), exposure to petroleum products (P = 0.03) and exposure to heavy metals (P = 0.018). DISCUSSION: Half of the workers were unaware of health problems associated with their occupational exposures and thereby the use of personal protection is abysmally low. A very high proportion of workers had symptoms of cough, breathlessness, abdominal pain, abdominal discomfort and muscle aches. Almost a quarter of the workers had un-intentional occupational injuries in the last 6 months. Though they work in a high-risk environment with chances of fire hazard, falls and chemical exposures, none of the workshops had fire-extinguishers, first aid kits or any such safety devices.

Prevalence of diabetes and pre-diabetes and associated risk factors among tuberculosis patients in India.

BACKGROUND: Diabetes mellitus (DM) is recognised as an important risk factor to tuberculosis (TB). India has high TB burden, along with rising DM prevalence. There are inadequate data on prevalence of DM and pre-diabetes among TB cases in India. Aim was to determine diabetes prevalence among a cohort of TB cases registered under Revised National Tuberculosis Control Program in selected TB units in Tamil Nadu, India, and assess pattern of diabetes management amongst known cases. METHODS: 827 among the eligible patients (n = 904) underwent HbA1c and anthropometric measurements. OGTT was done for patients without previous history of DM and diagnosis was based on WHO criteria. Details of current treatment regimen of TB and DM and DM complications, if any, were recorded. A pretested questionnaire was used to collect information on sociodemographics, habitual risk factors, and type of TB. FINDINGS: DM prevalence was 25.3% (95% CI 22.6-28.5) and that of pre-diabetes 24.5% (95% CI 20.4-27.6). Risk factors associated with DM among TB patients were age (31-35, 36-40, 41-45, 46-50, >50 years vs <30 years) [OR (95% CI) 6.75 (2.36-19.3); 10.46 (3.95-27.7); 18.63 (6.58-52.7); 11.05 (4.31-28.4); 24.7 (9.73-62.7) (p<0.001)], positive family history of DM [3.08 (1.73-5.5) (p<0.001)], sedentary occupation [1.69 (1.10-2.59) (p = 0.016)], and BMI (18.5-22.9, 23-24.9 and ≥25 kg/m(2) vs <18.5 kg/m(2)) [2.03 (1.32-3.12) (p = 0.001); 0.87 (0.31-2.43) (p = 0.78); 1.44 (0.54-3.8) (p = 0.47)]; for pre-diabetes, risk factors were age (36-40, 41-45, 46-50, >50 years vs <30 years) [2.24 (1.1-4.55) (p = 0.026); 6.96 (3.3-14.7); 3.44 (1.83-6.48); 4.3 (2.25-8.2) (p<0.001)], waist circumference [<90 vs. ≥90 cm (men), <80 vs. ≥80 cm (women)] [3.05 (1.35-6.9) (p = 0.007)], smoking [1.92 (1.12-3.28) (p = 0.017)] and monthly income (5000-10,000 INR vs <5000 INR) [0.59 (0.37-0.94) (p = 0.026)]. DM risk was higher among pulmonary TB [3.06 (1.69-5.52) (p<0.001)], especially sputum positive, than non-pulmonary TB. INTERPRETATION: Nearly 50% of TB patients had either diabetes or pre-diabetes.