Programmatic Effectiveness of a Pediatric Typhoid Conjugate Vaccine Campaign in Navi Mumbai, India.

BACKGROUND: The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the Navi Mumbai Municipal Corporation (NMMC) implemented a typhoid conjugate vaccine (TCV) campaign. The campaign targeted all children aged 9 months through 14 years within NMMC boundaries (approximately 320 000 children) over 2 vaccination phases. The phase 1 campaign occurred from 14 July 2018 through 25 August 2018 (71% coverage, approximately 113 420 children). We evaluated the phase 1 campaign's programmatic effectiveness in reducing typhoid cases at the community level. METHODS: We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai and offered blood cultures to children who presented with fever ≥3 days. We used a cluster-randomized (by administrative boundary) test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched test-positive, culture-confirmed typhoid cases with up to 3 test-negative, culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression. RESULTS: Between 1 September 2018 and 31 March 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (programmatic effectiveness, 56%; 95% confidence interval [CI], 25% to 74%; P = .002). Cases aged ≥5 years were 0.37 times as likely (95% CI, .19 to .70; P = .002) and cases during the first year of surveillance were 0.30 times as likely (95% CI, .14 to .64; P = .002) to live in vaccine campaign communities. CONCLUSIONS: Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.

Enteroviruses Associated with Hand Foot and Mouth Disease in Navi Mumbai, Maharashtra, India in 2022.

An outbreak of Hand Foot and Mouth Disease (HFMD) which occurred in August-September, 2022 in Navi Mumbai, India was prospectively investigated, to delineate the clinical manifestations and identify the etiological agent. Molecular characterization at ICMR-National Institute of Virology (NIV), Mumbai unit reported 69 (88.5%) cases out of 78 clinically diagnosed HFMD cases positive for enteroviruses. Thirty-nine (56.5%) children were positive for CVA6, 11 (15.9%) for CVA16, and one for CVA4 (1.4%). One case of co-infection (CVA16, CVA6) was reported. Fourteen (17.9%) cases had recurrent disease in the same season. CVA6 was associated with unusual extension of the rash beyond the conventional areas of hands, feet, and mouth, with involvement of body areas including face, axillae and trunk. Whole genome sequencing classified CVA6 as group D3 and CVA16 isolates as group B1c. Co-infection and recurrence of disease with atypical symptoms observed in this study highlight the need for continued vigilance of the evolutionary clinical characteristics of the enteroviruses causing HFMD.

Multisystem Inflammatory Syndrome in Children: Experience from October 2020 to January 2021 at a Tertiary Hospital in Navi Mumbai, India.

Although presentation of multisystem inflammatory syndrome (MIS-C) in children is typically with fever and symptoms like diarrhea, vomiting, rash, conjunctival injection, or shock, the spectrum of associated multisystem involvement is wide. Here, we present an account of patients with MIS-C that presented at a tertiary hospital in Navi Mumbai, India in the latter half of the pandemic from October 2020 to January 2021. We retrospectively studied the clinical features of 12 patients satisfying World Health Organization criteria for MIS-C. Eleven (91.6%) required PICU admission. Median age was 7 years and two had comorbidity. At the time of presentation, eight (66.6%) had respiratory failure, four (33.3%) had shock, and one (8.3%) had renal failure. The most common system involved was respiratory (75%) followed by mucocutaneous manifestations (66.6%). Seven patients (58.3%) showed involvement of >4 systems. Atypical presentations included a 14-year-old male with COVID-19 like pulmonary involvement on computed tomography, and a 20-month-old male with gross hematuria, nephrotic range proteinuria, and rapidly progressive renal failure. Elevated N-terminal-pro B-type natriuretic peptide was seen in 75% patients and abnormal two-dimensional echo in 50%. All patients were treated with intravenous methylprednisolone at 30 mg/kg/day for 5 days. Death occurred in three (25%), all of whom had hypotensive shock at presentation. In the wake of an ongoing pandemic, any febrile child with nonspecific symptoms suggestive of multisystem involvement warrants suspicion of MIS-C and should be evaluated with the help of markers of systemic inflammation and organ involvement, after ruling out other obvious causes. We report good response to methylprednisolone in patients without hypotensive shock at presentation and its use as firstline drug may be considered in settings with financial constraints.

Population structure and antimicrobial resistance patterns of Salmonella Typhi and Paratyphi A amid a phased municipal vaccination campaign in Navi Mumbai, India.

We performed whole-genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patterns of emergence and spread of antimicrobial resistance. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 quinolone resistance-determining region mutations. Two H58 isolates carried an IncX3 plasmid containing blaSHV-12, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant isolates from India independently evolved on multiple occasions. Among S. Typhi, we identified two main clades circulating (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (odds ratio [OR] = 0.72 per km; 95% credible interval [CrI]: 0.66-0.79). This effect was seen for distances up to 5 km (OR = 0.65 per km; 95% CrI: 0.59-0.73) but not seen for distances beyond 5 km (OR = 1.02 per km; 95% CrI: 0.83-1.26). There was a non-significant reduction in odds of clustering for pairs of isolates in vaccination communities compared with non-vaccination communities or mixed pairs compared with non-vaccination communities. Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. IMPORTANCE Enteric fever remains a major public health concern in many low- and middle-income countries, as antimicrobial resistance (AMR) continues to emerge. Geographical patterns of typhoidal Salmonella spread, critical to monitoring AMR and planning interventions, are poorly understood. We performed whole-genome sequencing of S. Typhi and S. Paratyphi A isolates collected in Navi Mumbai, India before and after a typhoid conjugate vaccine introduction. From timed phylogenies, we found two dominant circulating lineages of S. Typhi in Navi Mumbai-lineage 2.2, which expanded following a single introduction a decade prior, and 4.3.1 (H58), which had been introduced repeatedly from other parts of India, frequently containing "triple mutations" conferring high-level ciprofloxacin resistance. Using Bayesian hierarchical statistical models, we found that spatial distance between cases was strongly associated with genetic clustering at a fine scale (<5 km). Together, these findings suggest that antimicrobial-resistant S. Typhi frequently flows between cities and then spreads highly locally, which may inform surveillance and prevention strategies.

Aortic thrombosis in a neonate with COVID-19-related fetal inflammatory response syndrome requiring amputation of the leg: a case report.

Neonatal infection with SARS-CoV-2 is considered to have no major complications. A neonate with lower limb gangrene owing to spontaneous aortic thrombosis in the setting of a fetal inflammatory response syndrome (FIRS) post-intrauterine COVID-19 infection is presented. A healthy full-term newborn discharged from hospital on Day 3 developed irritability and progressive blackish discoloration of the toes of the right lower limb on Day 6 of life. Doppler imaging revealed acute thrombosis of the abdominal aorta with a critically ischaemic right lower limb. On Day 11 of life, SARS-CoV-2 RT-PCR was negative but total antibodies (IgG and IgM) were positive in both mother and neonate. The neonate showed raised inflammatory markers including CRP, ESR, interleukin-6, procalcitonin, ferritin and LDH along with elevated N-terminal pro-brain natriuretic peptide and D-dimer. In the absence of clinical signs of sepsis, FIRS was diagnosed. The neonate was treated with corticosteroids, heparin infusion and recombinant tissue plasminogen activator, and required surgical embolectomy followed by right limb amputation. By Day 31 of life, inflammatory markers showed serial return to normal and the neonate was discharged on oral steroids and aspirin. Intrauterine SARS-CoV-2 infection may trigger a systemic inflammatory response in some fetuses which is similar to post-COVID-19 multisystem inflammatory syndrome in children (MIS-C). Development of lower limb gangrene is a unique COVID-19-related neonatal complication and is attributed to thrombo-inflammation.ABBREVIATIONSCRP: C-reactive protein; FIRS: fetal inflammatory response syndrome; MIS-C: multisystem inflammatory syndrome in children; NT-proBNP: N-terminal pro-brain natriuretic peptide; RT-PCR: real-time polymerase chain reaction.

A study of critically ill children presenting with seizures regardless of seizure duration admitted in the PICU of a tertiary hospital in India.

Our aim was to study the clinical profile, immediate outcome and risk factors associated with poor outcome in critically ill children presenting with seizures requiring PICU admission. As seizures lasting 10 min or more can potentially cause brain damage, we included all children regardless of seizure duration. The records of 157 children aged 1 month to 16 years admitted in the PICU at a tertiary hospital in India with seizures as the presenting symptom during a three-year period were studied retrospectively. Median age of patients was 4 years. 34 (21%) had pre-existing epilepsy and 33 (21%) had previous developmental delay/neuro-deficit. Seizure duration was > 30 min in 75 (47.7%) and 56 (35.6%) required the use of more than 2 antiseizure drugs. 101 (64%) had acute symptomatic seizures, 28 (17%) remote symptomatic and 27 (17.1%) had unknown cause. New onset neurological deficit was seen in 18 (15.6%) and 14 (8.9%) died. Young age, high PEWS score at presentation, prolonged/recurrent seizures, CNS infection, need for multiple antiseizure drugs and ventilation/pressor use were risk factors for poor outcome. Neurological outcome and survival of children in our study were good. Further all-inclusive studies irrespective of seizure duration are needed to obtain a complete picture of critical children presenting with seizures.

Age Specific Peak Expiratory Flow Nomogram in Children.

OBJECTIVE: To determine peak flow rate nomogram in children between 5 to 12 y of age in suburban population. METHODS: This was a cross-sectional study randomly done on 5000 healthy school children. Mini-Wright flow meter was used for measurement of peak expiratory flow rate (PEFR). The range of age, weight and height were defined and linear and multiple regression analysis were performed. RESULTS: Correlation between PEFR and height was more significant and between PEFR and weight was lower. On the basis of height, the regression equation for both sexes were drawn; Boys: PEFR = 3.29 (Height in cm) - 218.38; Girls: PEFR = 3.25 (Height in cm) - 216.49. CONCLUSIONS: Thus, region specific nomograms for PEFR for assessing the severity and monitoring of airway obstruction in relation to age, sex, weight and height of children can be determined.