Discovery, development, and deployment of a user-centered point-of-care digital information system to treat and track hypertension and diabetes patients under India Hypertension Control Initiative 2019-2022, India.

Background: Hypertension affects 28.5% of Indians aged 18-69. Real-time registration and follow-up of persons with hypertension are possible with point-of-care digital information systems. We intend to describe herein the experiences of discovering, developing, and deploying a point-of-care digital information system for public health facilities under the India Hypertension Control Initiative. Methods: We have adopted an agile and user-centered approach in each phase in selected states of India since 2017. A multidisciplinary team adopted a hybrid approach with quantitative and qualitative methods, such as contextual inquiries, usability testing, and semi-structured interviews with healthcare workers, to document and monitor utility and usability. Results: During the discovery phase, we adopted a storyboard technique to understand the requirement of a digital information system. The participatory approach in discovery phase co-designed the information system with the nurses and doctors at Punjab state of India. Simple, which is the developed information system, has a front-end Android mobile application for healthcare workers and a backend dashboard for program managers. As of October 2022, over 24,31,962 patients of hypertension and 8,99,829 diabetes were registered in the information system of 10,017 health facilities. The median duration of registering a new patient was 50 seconds, and for recording a follow-up visit was 14 seconds in the app. High satisfaction was reported in 100 app users' quarterly interviews. Conclusion: Simple was implemented by administering a user-centered approach and agile techniques. It demonstrated high utility and usability among users, highlighting the benefits of a user-centered approach for effective digital health solutions.

India Hypertension Control Initiative: Blood Pressure Control Using Drug and Dose-Specific Standard Treatment Protocol at Scale in Punjab and Maharashtra, India, 2022.

Background: Hypertension treatment coverage is low in India. A stepwise simple treatment protocol is one of the strategies to improve hypertension treatment in primary care. We estimated the effectiveness of various protocol steps to achieve blood pressure (BP) control in public sector health facilities in Punjab and Maharashtra, India, where the India Hypertension Control Initiative (IHCI) was implemented. Methods: We analyzed the records of people enrolled for hypertension treatment and follow-up under IHCI between January 2018 and December 2021 in public sector primary and secondary care facilities across 23 districts from two states. Each state followed a different treatment protocol. We calculated the proportion with controlled BP at each step of the protocol. We also estimated the mean decline in BP pre- and post-treatment. Results: Of 281,209 patients initiated on amlodipine 5 mg, 159,292 continued on protocol drugs and came for a follow-up visit during the first quarter of 2022. Of 33,450 individuals who came for the follow-up in Punjab and 125,842 in Maharashtra, 70% and 76% had controlled BP, respectively, at the first step with amlodipine 5 mg. In Punjab, at the second step with amlodipine 10 mg, the cumulative BP control increased to 75%. A similar 5% (76%-81%) increase was seen in the second step after adding telmisartan 40 mg in Maharashtra. Overall, the mean (SD) systolic blood pressure (SBP) decreased by 16 mmHg from 148 (15) mmHg at the baseline in Punjab. In Maharashtra, the decline in the mean (SD) SBP was about 15 mmHg from the 144 (18) mmHg baseline. Conclusion: Simple drug- and dose-specific protocols helped achieve a high control rate among patients retained in care under program conditions. We recommend treatment protocols starting with a single low-cost drug and escalating with the same or another antihypertensive drug depending on the cost and availability.

Improving the availability of antihypertensive drugs in the India Hypertension Control Initiative, India, 2019-2020.

BACKGROUND: Antihypertensive drug supply is sometimes inadequate in public sector health facilities in India. One of the core strategies of the India Hypertension Control Initiative (IHCI) is to improve the availability of antihypertensive drugs in primary and secondary care facilities. We quantified the availability of antihypertensive drugs in 2019-20 and described the practices in supply chain management in 22 districts across four states of India. METHODS: Twenty-two districts from 4 states (Punjab, Madhya Pradesh, Telangana, and Maharashtra) were studied. We described the practices and challenges in supply chain management. We collected data on drug procurement from 2018 to 2020 and drug availability from April 2019 to March 2020. Quantity procured, the proportion of facilities with stockout at the end of each quarter, and availability of drugs in patient days were tabulated. RESULTS: All states selected drug- and dose-specific protocols with Amlodipine as the initial drug and shifted to morbidity-based forecasting. The total number of antihypertensive tablets procured for the 22 districts increased from 16 million in 2017-2018 to 160 million in 2019-2020. The proportion of facilities with Amlodipine stock-out was below 5% during the study period. Amlodipine stock was available for at least 60 patient days from the third quarter of 2019 onward in all districts. CONCLUSIONS: This study demonstrates that including best practices can gradually strengthen the procurement and supply chain for antihypertensives in a low-resource setting. As the program was rapidly growing, there were still gaps in the procurement and distribution system which needed to be addressed to ensure the adequacy of drugs. We recommend that best practices, including choosing a single protocol, basing supply on projected patient load rather than an increment from historical levels, and using simple stock management tools, be replicated in other districts in India to increase and sustain coverage of hypertension treatment.

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.

Delivery cost of the first public sector introduction of typhoid conjugate vaccine in Navi Mumbai, India.

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.

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.

The India Hypertension Control Initiative-early outcomes in 26 districts across five states of India, 2018-2020.

Hypertension is the leading single preventable risk factor for cardiovascular disease. The India Hypertension Control Initiative (IHCI) project was designed to improve hypertension control in public sector clinics. The project was launched in 2018-2019 in 26 districts across five states: Punjab (5), Madhya Pradesh (3), Kerala (4), Maharashtra (4), and Telangana (10), with five core strategies: standard treatment protocol, reliable supply of free antihypertensive drugs, team-based care, patient-centered care, and an information system to track individual patient treatment and blood pressure control. All states implemented simple treatment protocols with three drugs: a long-acting dihydropyridine calcium channel blocker (amlodipine), angiotensin receptor blocker (telmisartan), and thiazide or a thiazide-like diuretic (hydrochlorothiazide or chlorthalidone). Medication supplies were adequate to support at least one month of treatment. Overall, 570,365 hypertensives were enrolled in 2018-2019; 11% did not have follow-up visits in the most recent 12 months. Clinic-level blood pressure control averaged 43% (range 22-79%) by Jan-March, 2020. The proportion of the estimated people with hypertension who had it controlled and documented in public clinics increased three-fold, albeit from very low levels (1.4-5.0%). The IHCI demonstrated the feasibility of implementing protocol-based hypertension treatment and control supported by a reliable drug supply and accurate information systems at scale in Indian primary health care facilities. Lessons from the IHCI's initial phase will inform plans to improve screening in health care facilities, increase retention in care, and ensure a sustained supply of drugs as part of a nationwide hypertension control program.

Suspended Particulate Matter Analysis of Pre and During Covid Lockdown Using Google Earth Engine Cloud Computing: A Case Study of Ukai Reservoir.

Presence of suspended particulate matter (SPM) in a waterbody or a river can be caused by multiple parameters such as other pollutants by the discharge of poorly maintained sewage, siltation, sedimentation, flood and even bacteria. In this study, remote sensing techniques were used to understand the effects of pandemic-induced lockdown on the SPM concentration in the lower Tapi reservoir or Ukai reservoir. The estimation was done using Landsat-8 OLI (Operational Land Imager) having radiometric resolution (12-bit) and a spatial resolution of 30 m. The Google Earth Engine (GEE) cloud computing platform was used in this study to generate the products. The GEE is a semi-automated workflow system using a robust approach designed for scientific analysis and visualization of geospatial datasets. An algorithm was deployed, and a time-series (2013-2020) analysis was done for the study area. It was found that the average mean value of SPM in Tapi River during 2020 is lowest than the last seven years at the same time.

A simple six-step guide to National-Scale Hypertension Control Program implementation.

Hypertension is the leading single preventable risk factor for death worldwide, and most of the disease burden attributed to hypertension weighs on low-and middle-income countries. Effective large-scale public health hypertension control programs are needed to control hypertension globally. National programs can follow six important steps to launch a successful national-scale hypertension control program: establish an administrative structure and survey current resources, select a standard hypertension treatment protocol, ensure supply of medication and blood pressure devices, train health care workers to measure blood pressure and control hypertension, implement an information system for monitoring patients and the program overall, and enroll and monitor patients with phased program expansion. Resolve to Save Lives, an initiative of global public health organization Vital Strategies, and its partners organized these six key steps and materials into a structured, stepwise guide to establish best practices in hypertension program design, launch, maintenance, and scale-up.

Immunogenicity of Fractional Dose Inactivated Poliovirus Vaccine in India.

INTRODUCTION: Following the withdrawal of Sabin type 2 from trivalent oral poliovirus vaccine (tOPV) in 2016, the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV) in routine immunization was recommended, either as 1 full dose (0.5mL, intramuscular) or 2 fractional doses of IPV (fIPV-0.1mL, intradermal). India opted for fIPV. We conducted a comparative assessment of IPV and fIPV. METHODS: This was a 4-arm, open-label, multicenter, randomized controlled trial. Infants were enrolled and vaccines administered according to the study design, and the blood was drawn at age 6, 14, and 18 weeks for neutralization testing against all 3 poliovirus types. RESULTS: Study enrolled 799 infants. The seroconversion against type 2 poliovirus with 2 fIPV doses was 85.8% (95% confidence interval [CI]: 80.1%-90.0%) when administered at age 6 and 14 weeks, 77.0% (95% CI: 70.5-82.5) when given at age 10 and 14 weeks, compared to 67.9% (95% CI: 60.4-74.6) following 1 full-dose IPV at age 14 weeks. CONCLUSION: The study demonstrated the superiority of 2 fIPV doses over 1 full-dose IPV in India. Doses of fIPV given at 6 and 14 weeks were more immunogenic than those given at 10 and 14 weeks. Clinical Trial Registry of India (CTRI). Clinical trial registration number was CTRI/2017/02/007793.

Interventions to Ensure the Continuum of Care for Hypertension During the COVID-19 Pandemic in Five Indian States-India Hypertension Control Initiative.

Background: Hypertension is the leading risk factor for cardiovascular disease in India, but less than 10% of the estimated people with hypertension have blood pressure under control. The India Hypertension Control Initiative (IHCI) was implemented to strengthen hypertension management and control in public sector health facilities. Since late March 2020, lockdown due to the COVID-19 pandemic limited healthcare access and disrupted the provision of essential health services. IHCI quickly implemented adaptive interventions to improve access to medications. Objectives: To estimate the availability of antihypertensive drugs in peripheral public sector facilities during the lockdown and the proportion of patients who received drugs through community drug distribution, i.e., through Health and Wellness Centers (HWCs)/Sub-Centers (SCs), the most peripheral public sector health facilities for primary care, and home delivery. Methods: We collected data from 29 IHCI districts of 5 states (Kerala, Madhya Pradesh, Maharashtra, Punjab, and Telangana) during April-May 2020. The population included individuals diagnosed with hypertension and enrolled under IHCI in all public sector primary care health facilities. We contacted a convenience sample of more than one-third of the functional HWC/SC and analyzed the proportion of facilities and patients who received drugs. We also contacted a convenience sample of patients telephonically to estimate their self-reported availability of drugs. Conclusion: Of the 4245 HWC/SC, more than one-third were contacted telephonically, and 85-88% had received antihypertensive medications for community-level distribution. Among 721,675 patients registered until March 2020, 38.4% had received drug refills through HWC/SC or home delivery by frontline workers during the lockdown. We demonstrated the feasibility of community-level drug distribution for patients with hypertension during the COVID-19 lockdown in India. The adaptive strategy of community-based drug distribution through HWC/SC and home delivery appears feasible and may help improve access to hypertension care during the COVID-19 pandemic and beyond.

Cost-Effectiveness of Improved Hypertension Management in India through Increased Treatment Coverage and Adherence: A Mathematical Modeling Study.

Background: Despite the availability of effective and affordable treatments, only 14% of hypertensive Indians have controlled blood pressure. Increased hypertension treatment coverage (the proportion of individuals initiated on treatment) and adherence (proportion of patients taking medicines as recommended) promise population health gains. However, governments and other payers will not invest in a large-scale hypertension control program unless it is both affordable and effective. Objective: To investigate if a national hypertension control intervention implemented across the private and public sector facilities in India could save overall costs of CVD prevention and treatment. Methods: We developed a discrete-time microsimulation model to assess the cost-effectiveness of population-level hypertension control intervention in India for combinations of treatment coverage and adherence targets. Input clinical parameters specific to India were obtained from large-scale surveys such as the Global Burden of Disease as well as local clinical trials. Input hypertensive medication cost parameters were based on government contracts. The model projected antihypertensive treatment costs, avoided CVD care costs, changes in disability-adjusted life year (DALYs) and incremental cost per DALY averted (represented as incremental cost-effectiveness ratio or ICER) over 20 years. Results: Over 20 years, at 70% coverage and adherence, the hypertension control intervention would avert 1.68% DALYs and be cost-saving overall. Increasing adherence (while keeping coverage constant) resulted in greater improvement in cost savings compared to increasing coverage (while keeping adherence constant). Results were most sensitive to the cost of antihypertensive medication, but the intervention remained highly cost-effective under all one-way sensitivity analyses. Conclusion: A national hypertension control intervention in India would most likely be budget neutral or cost-saving if the intervention can achieve and maintain high levels of both treatment coverage and adherence.

Evaluation of Vaccine Safety After the First Public Sector Introduction of Typhoid Conjugate Vaccine-Navi Mumbai, India, 2018.

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.

Poliomyelitis seroprevalence in high risk populations of India before the trivalent-bivalent oral poliovirus vaccine switch in 2016.

INTRODUCTION: This study assessed the seroprevalence against all three polioviruses among the last cohort of infants aged 6-11 months who received tOPV before the tOPV-bOPV switch and had an opportunity to receive a full dose of inactivated poliovirus vaccine introduced in the routine immunization schedule. METHODS: Serum was tested for neutralizing antibodies against polioviruses among infants residing in three different risk- category states for poliovirus transmission in India viz., Bihar historically high-risk state for polio, Madhya Pradesh a State with low routine immunization coverage and Chhattisgarh with lower acute flaccid paralysis surveillance indicators. RESULTS: A total of 1113 serum samples were tested across the three states. The overall seroprevalence was 98.5% (97.7-99.2), 98.9% (98.3-99.5) and 94.4% (93.0-95.8) for poliovirus types 1, 2 and 3 respectively. The median antibody titers for corresponding serotypes were 575, 362 and 181. Infants who received five doses of tOPV showed respective seroprevalence rates of 98.7%, 98.7% and 93.7% against types 1, 2 and 3 polioviruses. There was no significant difference in seroprevalence across the group of IPV recipients. The median reciprocal titers across the groups of IPV recipient was significantly higher (p = 0.006) for poliovirus-3. CONCLUSION: The seroprevalence rates observed in the study are historically the highest in the series of serosurveys that India has conducted to assess the population immunity against polioviruses. Poliovirus 2 seroprevalence was very high at the time of the tOPV-bOPV switch in India effected in April 2016.

India Hypertension Control Initiative-Hypertension treatment and blood pressure control in a cohort in 24 sentinel site clinics.

The India Hypertension Control Initiative (IHCI) is a multi-partner initiative, implementing and scaling up a public health hypertension control program across India. A cohort of 21,895 adult hypertension patients in 24 IHCI sentinel site facilities in four Indian states (Punjab, Madhya Pradesh, Maharashtra, and Telangana), registered from January 2018 until June 2019 were assessed at baseline and then followed up for blood pressure (BP) control and antihypertensive medication use. Among all registrations, 11 274 (51%) of the patients returned for a follow-up visit between July 2019 and September 2019. Among patients returning for follow-up, 26.3% had BP controlled at registration, and 59.8% had BP controlled at follow-up (p < .001). The absolute improvement in BP control was more than two times greater in primary care (48.1 percentage point increase) than secondary care facilities (22.9 percentage point increase). Most IHCI patients received prescriptions according to state-specific treatment protocols. This study demonstrates that a scalable public health hypertension control program can yield substantial BP control improvements, especially in primary care settings. However, high loss to follow-up limits population health impact; future efforts should focus on improving systems to increase the likelihood that patients will return to the clinic for routine hypertension care.

Decision Making and Implementation of the First Public Sector Introduction of Typhoid Conjugate Vaccine-Navi Mumbai, India, 2018.

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.

Cross-sectional Serologic Assessment of Immunity to Poliovirus in Differential Risk Areas of India: India Seroprevalence Survey - 2014.

OBJECTIVE: To assess the seroprevalence against all three poliovirus serotypes in traditional high risk areas in Bihar, lowest routine immunization coverage areas in Madhya Pradesh and migrant population living in Mumbai urban slums. DESIGN: Cross-sectional Survey. SETTING: Subjects selected by house to house visit (community based) and transported to government health facilities for further study procedures. PARTICIPANTS: 1137 randomly selected healthy infants 6-11 months of age residing in the selected high-risk areas. METHODS: Serum samples from the study site were shipped to Enterovirus Research Centre (ERC), Mumbai to determine the neutralizing antibodies against all three poliovirus serotypes. Children with a reciprocal antibody titer ≥1:8 were considered seropositive to the specific poliovirus. RESULTS: Overall, seroprevalence in all the three study areas was 98%, 98% and 91% against poliovirus type-1, type-2 and type-3, respectively. Bihar had a seroprevalence of 99%, 99% and 92% against type-1, type-2 and type-3 respectively. Corresponding figures for Madhya Pradesh and Mumbai were 98%, 99% and 88% and 98%, 97% and 94%, respectively. CONCLUSION: The study found high seroprevalence against all three poliovirus types not only in the traditional high-risk areas for polio in India, but even in the areas known to have low routine immunization coverage and among the migratory clusters living in Mumbai urban slums. Type-2 seroprevalence was found to be high. These findings are reassuring against the threat of emergence of circulating vaccine derived polioviruses (cVDPVs) in the country subsequent to switch from trivalent oral polio vaccine to bivalent oral polio vaccine in the routine immunization schedule from April 2016.

Polio Endgame, Information Gaps Related to Vaccines and Immunity.

Evidence generated through research studies has guided programmatic actions and fine-tuned strategies for the Global Polio Eradication Initiative (GPEI). However, many gaps still persist in the understanding of a risk-free implementation of the polio endgame. Immediate concerns relate to the introduction of inactivated polio vaccine (IPV) and switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) in routine immunization schedule. A comprehensive understanding of mucosal immunity in populations and best response options against circulating vaccine derived poliovirus (cVDPV) outbreaks in post tOPV-bOPV switch is essential to mitigate the risks of wild and vaccine-derived poliovirus importations and emergence of cVDPVs in polio-free countries. A clearer picture is also needed on few operational issues, interference between polio vaccines and other EPI vaccines and products related to polio endgame. It is also extremely important to develop mechanisms to identify and manage long-term poliovirus excretors who may pose a risk of reintroduction into the population after global eradication of poliovirus.

Immunogenicity of a new routine vaccination schedule for global poliomyelitis prevention: an open-label, randomised controlled trial.

BACKGROUND: Polio eradication needs a new routine immunisation schedule--three or four doses of bivalent type 1 and type 3 oral poliovirus vaccine (bOPV) and one dose of inactivated poliovirus vaccine (IPV), but no immunogenicity data are available for this schedule. We aimed to assess immunogenicity of this vaccine schedule. METHODS: We did an open-label, randomised controlled trial in four centres in India. After informed consent was obtained from a parent or legally acceptable representative, healthy newborn babies were randomly allocated to one of five groups: trivalent OPV (tOPV); tOPV plus IPV; bOPV; bOPV plus IPV; or bOPV plus two doses of IPV (2IPV). The key eligibility criteria were: full-term birth (≥37 weeks of gestation); birthweight ≥2·5 kg; and Apgar score of 9 or more. OPV was administered at birth, 6 weeks, 10 weeks, and 14 weeks; IPV was administered intramuscularly at 14 weeks. The primary study objective was to investigate immunogenicity of the new vaccine schedule, assessed by seroconversion against poliovirus types 1, 2, and 3 between birth and 18 weeks in the per-protocol population (all participants with valid serology results on cord blood and at 18 weeks). Neutralisation assays tested cord blood and sera collected at 14 weeks, 18 weeks, 19 weeks, and 22 weeks by investigators masked to group allocation. This trial was registered with the India Clinical Trials Registry, number CTRI/2013/06/003722. FINDINGS: Of 900 newborn babies enrolled between June 13 and Aug 29, 2013, 782 (87%) completed the per-protocol requirements. Between birth and age 18 weeks, seroconversion against poliovirus type 1 in the tOPV group occurred in 162 of 163 (99·4%, 95% CI 96·6-100), in 150 (98·0%, 94·4-99·6) of 153 in the tOPV plus IPV group, in 153 (98·7%, 95·4-99·8) of 155 in the bOPV group, in 155 (99·4%, 96·5-100) of 156 in the bOPV plus IPV group, and in 154 (99·4%, 96·5-100) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 2 occurred in 157 (96·3%, 92·2-98·6) of 163 in the tOPV group, 153 (100%, 97·6-100·0) of 153 in the tOPV plus IPV group, 29 (18·7%, 12·9-25·7) of 155 in the bOPV group, 107 (68·6%, 60·7-75·8) of 156 in the bOPV plus IPV group, and in 121 (78·1%, 70·7-84·3) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 3 was achieved in 147 (90·2%, 84·5-94·3) of 163 in the tOPV group, 152 (99·3%, 96·4-100) of 153 in the tOPV plus IPV group, 151 (97·4%, 93·5-99·3) of 155 in the bOPV group, 155 (99·4%, 96·5-100) of 156 in the bOPV plus IPV group, and 153 (98·7%, 95·4-99·8) of 155 in the bOPV plus 2IPV group. Superiority was achieved for vaccine regimens including IPV against poliovirus type 3 compared with those not including IPV (tOPV plus IPV vs tOPV alone, p=0·0008; and bOPV plus IPV vs bOPV alone, p=0·0153). 12 serious adverse events occurred (six in the tOPV group, one in the tOPV plus IPV group, three in the bOPV group, zero in the bOPV plus IPV group, and two in the bOPV plus 2IPV group), none of which was attributed to the trial intervention. INTERPRETATION: The new vaccination schedule improves immunogenicity against polioviruses, especially against poliovirus type 3. FUNDING: WHO, through a grant from Rotary International (grant number 59735).

Polio eradication. Efficacy of inactivated poliovirus vaccine in India.

Inactivated poliovirus vaccine (IPV) is efficacious against paralytic disease, but its effect on mucosal immunity is debated. We assessed the efficacy of IPV in boosting mucosal immunity. Participants received IPV, bivalent 1 and 3 oral poliovirus vaccine (bOPV), or no vaccine. A bOPV challenge was administered 4 weeks later, and excretion was assessed 3, 7, and 14 days later. Nine hundred and fifty-four participants completed the study. Any fecal shedding of poliovirus type 1 was 8.8, 9.1, and 13.5% in the IPV group and 14.4, 24.1, and 52.4% in the control group by 6- to 11-month, 5-year, and 10-year groups, respectively (IPV versus control: Fisher's exact test P < 0.001). IPV reduced excretion for poliovirus types 1 and 3 between 38.9 and 74.2% and 52.8 and 75.7%, respectively. Thus, IPV in OPV-vaccinated individuals boosts intestinal mucosal immunity.