RESUMEN
Rabies presents with a high fatality rate, which imposes a significant global public health challenge, and therefore the use of post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising substitute for rabies immunoglobulins (RIGs) due to their high efficacy and standardized manufacturing process. A prospective, open-label, post-marketing surveillance study (PMS) was conducted at Byramjee Jeejeebhoy Medical College (BJMC), Pune. The study included patients aged more than 2 years who had recently sustained Category III-suspected rabid animal bite exposures. These patients were administered TwinRabTM at a dosage of 40 IU/kg in and around the wound as intralesional transfer, along with the anti-rabies vaccine (ARV). Adverse events (AEs) grading was performed with reference to the Food and Drug Administration (FDA) toxicity grading. In this study, 215 subjects received the TwinRabTM mAb with a 100% completion rate. Out of 215 patients, three (1.3%) patients in the range of 18 to 65 years of age showed solicited local AEs, which were resolved after the appropriate treatment intervention, but causality assessment was non-assessable. The overall tolerability assessment showed positive ratings from doctors (91.63%) and patients (67.91%) for the mAb cocktail. The PMS demonstrated the safety of TwinRabTM in patients who experienced Category III-suspected rabid animal bites, thereby supporting its potential as an alternative option for post-exposure prophylaxis in the management of animal bites for the prevention of rabies.
RESUMEN
AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated.
Asunto(s)
COVID-19 , ChAdOx1 nCoV-19 , Adulto , Humanos , Vacunas contra la COVID-19/efectos adversos , Estudios de Seguimiento , COVID-19/prevención & control , Inmunoglobulina G , Inmunogenicidad Vacunal , Anticuerpos AntiviralesRESUMEN
We provide an overview of the epidemiology and clinical course of mucormycosis in the coronavirus disease (COVID-19) pandemic era. We conducted a retrospective chart review of 178 patients with clinical or diagnostic, endoscopically or histopathologically confirmed rhino-sino-orbital or cerebral mucormycosis after COVID-19 treatment during the second wave of COVID-19 in Pune, India. Median time to symptom onset from COVID-19 detection was 28 days. Moderate or severe COVID-19 was seen in 73% of patients and diabetes in 74.2%. A total of 52.8% received steroids. Eschar over or inside the nose was seen in 75%, but baseline clinical and laboratory parameters were mostly unremarkable. Bone penetration was present in ≈90% of cases, 30% had soft-tissue swelling of the pterygopalatine fossa and 7% had cavernous sinus thrombosis, and 60% had multifocal mucormycosis. Of the 178 study cases, 151 (85%) underwent surgical debridement. Twenty-six (15%) died, and 16 (62%) of those had multifocal mucormycosis.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Mucormicosis , Enfermedades Orbitales , Humanos , India/epidemiología , Mucormicosis/diagnóstico , Mucormicosis/epidemiología , Enfermedades Orbitales/epidemiología , Pandemias , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: This phase 2/3 immunobridging study evaluated the safety and immunogenicity of the ChAdOx1 nCoV-19 Coronavirus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at the Serum Institute of India Pvt Ltd (SIIPL), following technology transfer from the AstraZeneca. METHODS: This participant-blind, observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). The study participants were enrolled from 14 hospitals across India between August 25 and October 31, 2020. Two doses of study products were given 4 weeks apart. The primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike IgG antibodies 28 days after the second dose (defined as lower limit of 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. The anti-spike IgG response was assessed using a multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Trial registration: CTRI/2020/08/027170. FINDINGS: 1601 participants were enrolled: 401 to the immunogenicity/reactogenicity cohort and 1200 to the safety cohort. After two doses, seroconversion rates for anti-spike IgG antibodies were more than 98·0% in both the groups. SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·78-1·23). SAEs were reported in ≤ 2·0% participants across the three groups; none were causally related. A total of 34 SARS-CoV-2 infections were reported; of which 6 occurred more than 2 weeks after the second dose; none were severe. INTERPRETATION: SII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Pharmacovigilance should be maintained to detect any safety signals. FUNDING: SIIPL funded the contract research organisation and laboratory costs, while the site costs were funded by the Indian Council of Medical Research. The study vaccines were supplied by SIIPL and AstraZeneca.
RESUMEN
OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.
Asunto(s)
COVID-19 , Adulto , COVID-19/terapia , Humanos , Inmunización Pasiva , India/epidemiología , Persona de Mediana Edad , SARS-CoV-2 , Sueroterapia para COVID-19RESUMEN
BACKGROUND: The monitoring framework for evaluating health system response to noncommunicable diseases (NCDs) include indicators to assess availability of affordable basic technologies and essential medicines to treat them in both public and private primary care facilities. The Government of India launched the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular diseases and Stroke (NPCDCS) in 2010 to strengthen health systems. We assessed availability of trained human resources, essential medicines and technologies for diabetes, cardiovascular and chronic respiratory diseases as one of the components of the National Noncommunicable Disease Monitoring Survey (NNMS - 2017-18). METHODS: NNMS was a cross-sectional survey. Health facility survey component covered three public [Primary health centre (PHC), Community health centre (CHC) and District hospital (DH)] and one private primary in each of the 600 primary sampling units (PSUs) selected by stratified multistage random sampling to be nationally representative. Survey teams interviewed medical officers, laboratory technicians, and pharmacists using an adapted World Health Organization (WHO) - Service Availability and Readiness Assessment (SARA) tool on handhelds with Open Data Kit (ODK) technology. List of essential medicines and technology was according to WHO - Package of Essential Medicines and Technologies for NCDs (PEN) and NPCDCS guidelines for primary and secondary facilities, respectively. Availability was defined as reported to be generally available within facility premises. RESULTS: Total of 537 public and 512 private primary facilities, 386 CHCs and 334 DHs across India were covered. NPCDCS was being implemented in 72.8% of CHCs and 86.8% of DHs. All essential technologies and medicines available to manage three NCDs in primary care varied between 1.1% (95% CI; 0.3-3.3) in rural public to 9.0% (95% CI; 6.2-13.0) in urban private facilities. In NPCDCS implementing districts, 0.4% of CHCs and 14.5% of the DHs were fully equipped. DHs were well staffed, CHCs had deficits in physiotherapist and specialist positions, whereas PHCs reported shortage of nurse-midwives and health assistants. Training under NPCDCS was uniformly poor across all facilities. CONCLUSION: Both private and public primary care facilities and public secondary facilities are currently not adequately prepared to comprehensively address the burden of NCDs in India.
Asunto(s)
Enfermedades no Transmisibles , Estudios Transversales , Instituciones de Salud , Accesibilidad a los Servicios de Salud , Humanos , India/epidemiología , Enfermedades no Transmisibles/epidemiología , Enfermedades no Transmisibles/prevención & controlRESUMEN
OBJECTIVE: To generate national estimates of key non-communicable disease (NCD) risk factors for adolescents (15-17 years) identified in the National NCD Monitoring Framework and, study the knowledge, attitudes and practices towards NCD risk behaviours among school-going adolescents. DESIGN AND SETTING: A community-based, national, cross-sectional survey conducted during 2017-2018. The survey was coordinated by the Indian Council of Medical Research-National Centre for Disease Informatics and Research with 10 reputed implementing research institutes/organisations across India in urban and rural areas. PARTICIPANTS: A multistage sampling design was adopted covering ages between 15 and 69 years-adolescents (15-17 years) and adults (18-69 years). The sample included 12 000 households drawn from 600 primary sampling units. All available adolescents (15-17 years) from the selected households were included in the survey. MAIN OUTCOME MEASURES: Key NCD risk factors for adolescents (15-17 years)-current tobacco and alcohol use, dietary behaviours, insufficient physical activity, overweight and obesity. RESULTS: Overall, 1402 households and 1531 adolescents completed the survey. Prevalence of current daily use of tobacco was 3.1% (95% CI: 2.0% to 4.7%), 25.2% (95% CI: 22.2% to 28.5%) adolescents showed insufficient levels of physical activity, 6.2% (95% CI: 4.9% to 7.9%) were overweight and 1.8% (95% CI: 1.0% to 2.9%) were obese. Two-thirds reported being imparted health education on NCD risk factors in their schools/colleges. CONCLUSION: The survey provides baseline data on NCD-related key risk factors among 15-17 years in India. These national-level data fill information gaps for this age group and help assess India's progress towards NCD targets set for 2025 comprehensively. Though the prevalence of select risk factors is much lower than in many developed countries, this study offers national evidence for revisiting and framing appropriate policies, strategies for prevention and control of NCDs in younger age groups.
Asunto(s)
Enfermedades no Transmisibles , Adolescente , Adulto , Anciano , Estudios Transversales , Humanos , India/epidemiología , Persona de Mediana Edad , Enfermedades no Transmisibles/epidemiología , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
Currently, most licensed vaccines against SARS-CoV-2 infection are approved for adults and not for children. We conducted a test negative case-control study to assess the effectiveness of Measles Containing Vaccines (MCVs) against SARS-CoV-2 infection in Pune, India, in children who were ≥1 year and <18 years of age and were tested for SARS-CoV-2 infection by Reverse transcription polymerase chain reaction (RT-PCR). The enrolled participants included 274 SARS-CoV-2 positive cases (216 vaccinated and 58 unvaccinated) along with 274 SARS-CoV-2 negative controls (265 vaccinated and 9 unvaccinated). Of the 274 cases, 180 (65.7%) were asymptomatic while 94 (34.3%) were symptomatic, all with mild severity. The number of participants with symptomatic SARS-CoV-2 infection was significantly lower in the vaccinated group compared to the unvaccinated group (p < .0001). The unadjusted overall Vaccine Effectiveness (VE) in the vaccinated group compared to unvaccinated group was 87.4% (OR = 0.126, 95% CI of VE: 73.9-93.9) while the adjusted overall VE after adjusting for age and sex was 87.5% (OR = 0.125, 95% CI of VE: 74.2-94.0). MCVs reduced incidence of laboratory confirmed SARS-CoV-2 infection in children. Number of symptomatic cases were also lower in the vaccinated group compared to the unvaccinated group. Results of our study have provided strong preliminary evidence that MCVs have a good effectiveness against SARS-CoV-2 infection in the pediatric population, which needs to be confirmed further through prospective randomized clinical trials.
Asunto(s)
COVID-19 , Sarampión , Adulto , Vacunas contra la COVID-19 , Estudios de Casos y Controles , Niño , Humanos , India/epidemiología , Estudios Prospectivos , SARS-CoV-2 , Resultado del TratamientoRESUMEN
BACKGROUND: The primary objective of National NCD monitoring survey (NNMS) was to generate national-level estimates of key NCD indicators identified in the national NCD monitoring framework. This paper describes survey study protocol and prevalence of risk factors among adults (18-69 years). MATERIALS AND METHODS: NNMS was a national level cross-sectional survey conducted during 2017-18. The estimated sample size was 12,000 households from 600 primary sampling units. One adult (18-69 years) per household was selected using the World Health Organization-KISH grid. The study tools were adapted from WHO-STEPwise approach to NCD risk factor surveillance, IDSP-NCD risk factor survey and WHO-Global adult tobacco survey. Total of 8/10 indicators of adult NCD risk factors according to national NCD disease monitoring framework was studied. This survey for the first time estimated dietary intake of salt intake of population at a national level from spot urine samples. RESULTS: Total of 11139 households and 10659 adults completed the survey. Prevalence of tobacco and alcohol use was 32.8% (95% CI: 30.8-35.0) and 15.9% (95% CI: 14.2-17.7) respectively. More than one-third adults were physically inactive [41.3% (95% CI: 39.4-43.3)], majority [98.4% (95% CI: 97.8-98.8)] consumed less than 5 servings of fruits and / or vegetables per day and mean salt intake was 8 g/day (95% CI: 7.8-8.2). Proportion with raised blood pressure and raised blood glucose were 28.5% (95% CI: 27.0-30.1) and 9.3% (95% CI: 8.3-10.5) respectively. 12.8% (95% CI: 11.2-14.5) of adults (40-69 years) had ten-year CVD risk of ≥30% or with existing CVD. CONCLUSION: NNMS was the first comprehensive national survey providing relevant data to assess India's progress towards targets in National NCD monitoring framework and NCD Action Plan. Established methodology and findings from survey would contribute to plan future state-based surveys and also frame policies for prevention and control of NCDs.
Asunto(s)
Enfermedades no Transmisibles/epidemiología , Encuestas y Cuestionarios , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Glucemia , Estudios Transversales , Conducta Alimentaria , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Fumar/epidemiología , Adulto JovenRESUMEN
BACKGROUND: India has reported more than 70,000 cases and 2000 deaths. Pune is the second city in the Maharashtra state after Mumbai to breach the 1000 cases. Total deaths reported from Pune were 158 with a mortality of 5.7%. To plan health services, it is important to learn lessons from early stage of the outbreak on course of the disease in a hospital setting. OBJECTIVES: To describe the epidemiological characteristics of the outbreak of COVID-19 in India from a tertiary care hospital. METHODS: This was a hospital-based cross-sectional study which included all admitted laboratory confirmed COVID19 cases from March 31, to April 24, 2020. The information was collected in a predesigned pro forma which included sociodemographic data, duration of stay, family background, outcome, etc., by trained staff after ethics approval. Epi Info7 was used for data analysis. RESULTS: Out of the total 197 cases, majority cases were between the ages of 31-60 years with slight male preponderance. Majority of these cases were from the slums. Breathlessness was the main presenting symptom followed by fever and cough. More than 1/5th of patients were asymptomatic from exposure to admission. The case fatality rate among the admitted cases was 29.4%. Comorbidity was one of the significant risk factors for the progression of disease and death (odds ratio [OR] = 16.8, 95% confidence interval [CI] = 7.0 - 40.1, P < 0.0001). CONCLUSION: Mortality was higher than the national average of 3.2%; comorbidity was associated with bad prognosis.
Asunto(s)
Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Adolescente , Adulto , Anciano , Betacoronavirus , COVID-19 , Comorbilidad , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Estudios Transversales , Femenino , Hospitalización , Humanos , India/epidemiología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Factores de Riesgo , SARS-CoV-2 , Factores Socioeconómicos , Análisis Espacial , Adulto JovenRESUMEN
BACKGROUND: Government of India is introducing new and relatively costly vaccines under immunization program. Monitoring of vaccine wastage is needed to guide the program implementation and forecasting. Under pilot introduction of rotavirus vaccine in two districts both 5- and 10-doses vials were used, which was considered as an opportunity for documenting the wastage. The wastage rates for other routine vaccines were also documented. METHODS: A survey conducted in two districts (Kangra, Himachal Pradesh and Pune, Maharashtra) covered 49 vaccine stores, 34 sub-centres and 34 outreach sessions collected vaccine receipt, distribution and usage data for two complete years 2016 and 2017. RESULTS: The overall wastage rates for almost all vaccines were higher in Kangra district (BCG 37.1%, DPT 32.1%, Measles 32.2%, OPV 50.8%, TT 34.1% and pentavalent 18.4%) than Pune district (BCG 35.1%, DPT 25.4%, Measles 21.7%, OPV 14.3%, TT 23.1% and pentavalent 13.2%). Wastage for pneumococcal conjugate and measles-rubella vaccines in Kangra district were 27 and 40.5%, respectively. With transition from 5- to 10-doses vials for rotavirus vaccine, wastage at stores levels increased in both Kangra (29 to 33.2%) and Pune (17.8 to 25.7%) districts. With transition from intramuscular to intradermal fractional inactivated polio vaccine, the wastage increased from 36.1 to 54.8% in Kangra and 18.4 to 26.9% in Pune district. CONCLUSIONS: The observed vaccine wastage rates for several vaccines were relatively higher than program assumption for forecasting. The observed variations in the vaccine wastage indicates need for state or region based documentation and monitoring in India for appropriate programmatic action.
Asunto(s)
Programas de Inmunización , Vacunación/estadística & datos numéricos , Vacunas/administración & dosificación , Estudios Transversales , Documentación , Programas de Gobierno , Encuestas de Atención de la Salud , Humanos , India , Evaluación de Programas y Proyectos de SaludRESUMEN
This study compares the implementation of community-based monitoring (CBM) in 45 primary health centers (PHCs) in the pilot phase in Maharashtra with the equal number of randomly selected PHCs not implementing CBM (non-CBM) from the same districts. Information was collected by teams from Community Medicine Departments by visiting selected PHCs. Establishment of monitoring committees and training of medical officers (MOs) had been completed as required but only 36.36% MOs were trained. Only 43.18% MOs received the facility report card. Most of the MOs (90.90%) attended Jansunwai and opined that it had increased community awareness and the barriers between the people and PHC staff were broken. There was no difference in fund utilization and meetings of Rugna Kalyan Samittees. Percentage of Institutional deliveries and women receiving Janani Suraksha Yojana benefits among home deliveries was more in the non-CBM group of PHCs.
Asunto(s)
Atención Primaria de Salud/organización & administración , Calidad de la Atención de Salud/organización & administración , Servicios de Salud Rural/organización & administración , Consejo Directivo/organización & administración , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , India , Medicamentos bajo Prescripción/provisión & distribución , Atención Primaria de Salud/normas , Calidad de la Atención de Salud/normas , Derivación y Consulta , Servicios de Salud Rural/normasRESUMEN
BACKGROUND: Epidemic diphtheria is still poorly understood and continues to challenge both developing and developed countries. In the backdrop of poor immunization coverage, non-existent adult boosters, weak case based surveillance and persistence of multiple foci, there is a heightened risk of re-emergence of the disease in epidemic forms in India. Investigating each outbreak to understand the epidemiology of the disease and its current status in the country is therefore necessary. Dhule a predominantly tribal and rural district in Northern Maharashtra has consistently recorded low vaccination coverages alongside sporaidic cases of diphtheria over the last years. METHODS: This study reports the findings of an onsite survey conducted to assess a recent outbreak of diphtheria in Dhule district and the response mounted to it. Secondary data regarding outbreak detection and response were obtained from the district surveillance office. Clinical data were extracted from hospital records of eleven lab confirmed cases including one death case. Frequency distributions were calculated for each identified clinical and non- clinical variable using Microsoft™ Excel® 2010. RESULTS: Our findings suggest a shift in the median age of disease to adolescents (10-15 years) without gender differences. Two cases (18%) reported disease despite immunization. Clinical symptoms included cough (82%), fever (73%), and throat congestion (64%). About 64% and 36% of the 11 confirmed cases presented with a well defined pseudomembrane and a tonsillar patch respectively. Drug resistance was observed in all three culture positive cases. One death occurred despite the administration of Anti-Diphtheric Serum in a partially immunized case (CFR 9%). Genotyping and toxigenicity of strain was not possible due to specimen contamination during transport as testing facilities were unavailable in the district. CONCLUSIONS: The outbreak raises several concerns regarding the epidemiology of diphtheria in Dhule. The reason for shift in the median age despite consistently poor immunization coverage (below 50%) remains unclear. Concomitant efforts should now focus on improving and monitoring primary immunization and booster coverages across all age groups. Gradually introducing adult immunization at ten year intervals may become necessary to prevent future vulnerabilities. Laboratory networks for genotyping and toxigenicity testing are urgently mandated at district level given the endemicity of the disease in the surrounding region and its recent introduction in remote Dhule. Contingency funds with pre- agreements to obtain ADS and DT/Td vaccines at short notice and developing standard case management protocols at district level are necessary. Monitoring the disease, emerging strains and mutations, alongside drug resistance through robust and effective surveillance is a pragmatic way forward.