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In 2013, during the 66th session of the Regional Committee of the WHO South-East Asia Region (SEAR), the 11 SEAR countries (1) adopted the goals of eliminating measles (2) and [...]

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. [ABSTRACT FROM AUTHOR]

Destruction of all poliovirus containing materials, safe and secure handling of retained polioviruses for vaccine production, and research will be obligatory to eliminate facility‐associated risks. Polioviruses and poliovirus potentially infectious materials (PIM) including fecal or respiratory samples requiring containment have been defined in World Health Organization‐Global Action Plan (GAP III) documents. Non‐polio laboratories culturing viruses from PIM are most affected as cell cultures of human and monkey origin are also poliovirus permissive. CRISPR gene‐editing technology was used to knockout the poliovirus receptor (PVR/CD155) gene in the rhabdomyosarcoma (RD) cell line. PVR knockout RD cell susceptibility was tested using known non‐polio enterovirus (NPEV) types. A selected clone (RD‐SJ40) was field evaluated for virus isolation from 626 stool samples of acute flaccid paralysis cases. Poliovirus nonpermissive cells derived from the RD cell line did not show CD155‐specific cell‐surface immunofluorescence. CD155 gene sequencing confirmed nucleotide base pair deletions within exon2 and exon3. The CD155 knockout RD‐SJ40 cells did not support the growth of poliovirus from positive stool samples. All NPEV types were isolated in RD and RD‐SJ40 cells. CRISPR correctly edited the CD155 gene of RD cells to render them poliovirus nonpermissive while susceptibility to NPEV remained unchanged. RD‐SJ40 cells are safe for NPEV isolation from poliovirus PIM without derogating GAP III containment requirements. [ABSTRACT FROM AUTHOR]

Each year in the United States, more than 400,000 residential fires claim the lives of approximately 3600 people and injure approximately an additional 18,600.[1] Although these figures reflect a gradual […]

Background In December 2017, the World Health Organization (WHO) prequalified the first typhoid conjugate vaccine (TCV; Typbar-TCV). While no safety concerns were identified in pre- and postlicensure studies, WHO's Global Advisory Committee on Vaccine Safety recommended robust safety evaluation with large-scale TCV introductions. During July–August 2018, the Navi Mumbai Municipal Corporation (NMMC) launched the world's first public sector TCV introduction. Per administrative reports, 113 420 children 9 months–14 years old received TCV. Methods We evaluated adverse events following immunization (AEFIs) using passive and active surveillance via (1) reports from the passive NMMC AEFI surveillance system, (2) telephone interviews with 5% of caregivers of vaccine recipients 48 hours and 7 days postvaccination, and (3) chart abstraction for adverse events of special interest (AESIs) among patients admitted to 5 hospitals using the Brighton Collaboration criteria followed by ascertainment of vaccination status. Results We identified 222/113 420 (0.2%) vaccine recipients with AEFIs through the NMMC AEFI surveillance system: 211 (0.19%) experienced minor AEFIs, 2 (0.002%) severe, and 9 serious (0.008%). At 48 hours postvaccination, 1852/5605 (33%) caregivers reported ≥1 AEFI, including injection site pain (n = 1452, 26%), swelling (n = 419, 7.5%), and fever (n = 416, 7.4%). Of the 4728 interviews completed at 7 days postvaccination, the most reported AEFIs included fever (n = 200, 4%), pain (n = 52, 1%), and headache (n = 42, 1%). Among 525 hospitalized children diagnosed with an AESI, 60 were vaccinated; no AESIs were causally associated with TCV. Conclusions No unexpected safety signals were identified with TCV introduction. This provides further reassurance for the large-scale use of Typbar-TCV among children 9 months–14 years old. [ABSTRACT FROM AUTHOR]

Background Typhoid fever prevention and control efforts are critical in an era of rising antimicrobial resistance among typhoid pathogens. India remains one of the highest typhoid disease burden countries, although a highly efficacious typhoid conjugate vaccine (TCV), prequalified by the World Health Organization in 2017, has been available since 2013. In 2018, the Navi Mumbai Municipal Corporation (NMMC) introduced TCV into its immunization program, targeting children aged 9 months to 14 years in 11 of 22 areas (Phase 1 campaign). We describe the decision making, implementation, and delivery costing to inform TCV use in other settings. Methods We collected information on the decision making and campaign implementation in addition to administrative coverage from NMMC and partners. We then used a microcosting approach from the local government (NMMC) perspective, using a new Microsoft Excel–based tool to estimate the financial and economic vaccination campaign costs. Results The planning and implementation of the campaign were led by NMMC with support from multiple partners. A fixed-post campaign was conducted during weekends and public holidays in July–August 2018 which achieved an administrative vaccination coverage of 71% (ranging from 46% in high-income to 92% in low-income areas). Not including vaccine and vaccination supplies, the average financial cost and economic cost per dose of TCV delivery were $0.45 and $1.42, respectively. Conclusion The first public sector TCV campaign was successfully implemented by NMMC, with high administrative coverage in slums and low-income areas. Delivery cost estimates provide important inputs to evaluate the cost-effectiveness and affordability of TCV vaccination through public sector preventive campaigns. [ABSTRACT FROM AUTHOR]

Background: The Prevention of Mother-to-Child Transmission of HIV (PMTCT) program in India is one of the largest in the world. It uses outreach workers (ORWs) to facilitate patient uptake of services, however, the challenges faced by the ORWs, and their views about the effectiveness of this program are unknown. Methods: The COMmunity-Home Based INDia (COMBIND) Prevention of Mother to Child Transmission of HIV study evaluated an integrated mobile health and behavioral intervention to enhance the capacity of ORWs in India. To understand the challenges faced by ORWs, and their perceptions of opportunities for program improvement, four group discussions were conducted among 60 ORW from four districts of Maharashtra, India, as part of the baseline assessment for COMBIND. Data were qualitatively analyzed using a thematic approach. Results: Numerous personal-, social-, and structural-level challenges existed for ORW as they engaged with their patients. Personal-level challenges for ORWs included disclosure of their own HIV status and travelling costs for home visits. Personal-level challenges for patients included financial costs of travelling to ART centers, non-adherence to ART, loss of daily wages, non-affordability of infant formula, lack of awareness of the baby’s needs, financial dependence on family, four time points (6weeks, 6 months, 12 months and 18 months) for HIV tests, and need for nevirapine (NVP) prophylaxis. Social-level challenges included lack of motivation by patients and/or health care staff, social stigma, and rude behavior of health care staff and their unwillingness to provide maternity services to women in the PMTCT programme. Structural-level challenges included cultural norms around infant feeding, shortages of HIV testing kits, shortages of antiretroviral drugs and infant NVP prophylaxis, and lack of training/knowledge related to PMTCT infant feeding guidelines by hospital staff. The consensus among ORWs was that there was a critical need for tools and training to improve their capacity to effectively engage with patients, and deliver appropriate care, and for motivation through periodic feedback. Conclusions: Given the significant challenges in PMTCT programme implementation reported by ORW, novel strategies to address these challenges are urgently needed to improve patient engagement, and access to and retention in care. [ABSTRACT FROM AUTHOR]

Cervical cancer is a leading cause of cancer-associated mortality among women in India, with 96,922 new cases and 60,078 deaths each year, almost one-fifth of the global burden. In 2018, Sikkim state in India introduced human papillomavirus (HPV) vaccine for 9–13-year-old girls, primarily through school-based vaccination, targeting approximately 25,000 girls. We documented the program's decision-making and implementation processes. We conducted a post-introduction evaluation in 2019, concurrent with the second dose campaign, by interviewing key stakeholders (state, district, and local level), reviewing planning documents, and observing cold chain sites in two purposefully-sampled community areas in each of the four districts of Sikkim. Using standard questionnaires, we interviewed health and education officials, school personnel, health workers, community leaders, and age-eligible girls on program decision-making, planning, training, vaccine delivery, logistics, and communication. We conducted 279 interviews and 29 observations in eight community areas across four districts of Sikkim. Based on reported administrative data, Sikkim achieved >95% HPV vaccination coverage among targeted girls for both doses via two campaigns; no severe adverse events were reported. HPV vaccination was well accepted by all stakeholders; minimal refusal was reported. Factors identified for successful vaccine introduction included strong political commitment, statewide mandatory school enrollment, collaboration between health and education departments at all levels, and robust social mobilization strategies. Sikkim successfully introduced the HPV vaccine to multiple-age cohorts of girls via school-based vaccination, demonstrating a model that could be replicated in other regions in India or similar low- and middle-income country settings. [ABSTRACT FROM AUTHOR]

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 bla SHV-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., Competing Interests: The authors declare no conflict of interest.

Navi Mumbai Municipal Corporation (NMMC), a local government in Mumbai, India, implemented the first public sector TCV campaign in 2018. This study estimated the delivery costs of this TCV campaign using a Microsoft Excel-based tool based on a micro-costing approach from the government (NMMC) perspective. The campaign's financial (direct expenditures) and economic costs (financial costs plus the monetized value of additional donated or existing items) incremental to the existing immunization program were collected. The data collection methods involved consultations with NMMC staff, reviews of financial and programmatic records of NMMC and the World Health Organization (WHO), and interviews with the health staff of sampled urban health posts (UHPs). Three UHPs were purposively sampled, representing the three dominant residence types in the catchment area: high-rise, slum, and mixed (high-rise and slum) areas. The high-rise area UHP had lower vaccination coverage (47%) compared with the mixed area (71%) and slum area UHPs (76%). The financial cost of vaccine and vaccination supplies (syringes, safety boxes) was $1.87 per dose, and the economic cost was $2.96 per dose in 2018 US dollars. Excluding the vaccine and vaccination supplies cost, the financial delivery cost across the 3 UHPs ranged from $0.37 to $0.53 per dose, and the economic delivery cost ranged from $1.37 to $3.98 per dose, with the highest delivery costs per dose in the high-rise areas. Across all 11 UHPs included in the campaign, the weighted average financial delivery cost was $0.38 per dose, and the economic delivery cost was $1.49 per dose. WHO has recommended the programmatic use of TCV in typhoid-endemic countries, and Gavi has included TCV in its vaccine portfolio. This first costing study of large-scale TCV introduction within a public sector immunization program provides empirical evidence for policymakers, stakeholders, and future vaccine campaign planning., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

We used publicly available data to describe epidemiology, genomic surveillance, and public health and social measures from the first 3 COVID-19 pandemic waves in southern Africa during April 6, 2020-September 19, 2021. South Africa detected regional waves on average 7.2 weeks before other countries. Average testing volume 244 tests/million/day) increased across waves and was highest in upper-middle-income countries. Across the 3 waves, average reported regional incidence increased (17.4, 51.9, 123.3 cases/1 million population/day), as did positivity of diagnostic tests (8.8%, 12.2%, 14.5%); mortality (0.3, 1.5, 2.7 deaths/1 million populaiton/day); and case-fatality ratios (1.9%, 2.1%, 2.5%). Beta variant (B.1.351) drove the second wave and Delta (B.1.617.2) the third. Stringent implementation of safety measures declined across waves. As of September 19, 2021, completed vaccination coverage remained low (8.1% of total population). Our findings highlight opportunities for strengthening surveillance, health systems, and access to realistically available therapeutics, and scaling up risk-based vaccination.

In 2013, during the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR), the 11 SEAR countries* adopted goals to eliminate measles and control rubella and congenital rubella syndrome by 2020 † (1). To accelerate progress in India (2,3), a phased § nationwide supplementary immunization activity (SIA) ¶ using measles-rubella vaccine and targeting approximately 410 million children aged 9 months-14 years commenced in 2017 and will be completed by first quarter of 2019. To ensure a high-quality SIA, planning and preparation were monitored using a readiness assessment tool adapted from the WHO global field guide** (4) by the India Ministry of Health and Family Welfare. This report describes the results and experience gained from conducting SIA readiness assessments in 24 districts of three Indian states (Andhra Pradesh, Kerala, and Telangana) during the second phase of the SIA. In each selected area, assessments were conducted 4-6 weeks and 1-2 weeks before the scheduled SIA. At the first assessment, none of the states and districts were on track with preparations for the SIA. However, at the second assessment, two (67%) states and 21 (88%) districts were on track. The SIA readiness assessment identified several preparedness gaps; early assessment results were immediately communicated to authorities and led to necessary corrective actions to ensure high-quality SIA implementation., Competing Interests: No conflicts of interest were reported.

With the rapid scale-up in use of antiretroviral therapy (ART), monitoring the quality of care and factors that may lead to emergence of HIV drug resistance (HIVDR) is an important focus point for programme managers. The National AIDS Control Organisation of India embarked on strengthening the ART programme for continuous quality improvement (CQI), using defined quality-of-care indicators (QCIs), including World Health Organization (WHO) early-warning indicators (EWIs) for HIVDR. In this feasibility study, done during July 2014, an integrated QCI and EWI tool developed by WHO India was pilot tested across 18 purposively selected ART centres. At seven ART centres, the EWI 1 target of >90% on-time pill pick-up was achieved for adult patients, while among the paediatric age group (<15 years old) it was not achieved by any centre. EWI 2 (retention of patients in ART care at 12 months after initiation) showed that two centres had retention of both adult and paediatric patients of >85% at 12 months of ART, while 11 centres had retention between 75% and 85%. EWI 3 (pharmacy stock-out) for adult and paediatric patients showed that 11 ART centres reported a minimum of one stock-out for the first-line ART drugs in the reporting period, while EWI 4 targets (pharmacy dispensing practices) were achieved by all the centres, for both adults and children. Average retention in care at 6, 12 and 24 months after ART initiation was 82%, 77% and 71%, respectively. This feasibility study showed that EWI analyses were much simpler to conduct if information was sought only for patients receiving ART, for whom the quality of record-keeping is better and more consistent. The activity has highlighted the need for improved quality of record-keeping at the facilities and implementation of specific interventions to ensure better patient follow-up. After modifications, use of the tool will be phased in across all the ART centres in India.