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Summary Background Diphtheria is re-emerging as a public health problem in several Indian states. Most diphtheria cases are among children older than 5 years. In this study, we aimed to estimate age-specific immunity against diphtheria in children aged 5–17 years in India. Methods We used residual serum samples from a cross-sectional, population-based serosurvey for dengue infection done between June 19, 2017, and April 12, 2018, to estimate the age-group-specific seroprevalence of antibodies to diphtheria in children aged 5–17 years in India. 8309 serum samples collected from 240 clusters (122 urban and 118 rural) in 60 selected districts of 15 Indian states spread across all five geographical regions (north, northeast, east, west, and south) of India were tested for the presence of IgG antibodies against diphtheria toxoid using an ELISA. We considered children with antibody concentrations of 0·1 IU/mL or greater as immune, those with levels less than 0·01 IU/mL as non-immune (and hence susceptible to diphtheria), and those with levels in the range of 0·01 to less than 0·1 IU/mL as partially immune. We calculated the weighted proportion of children who were immune, partially immune, and non-immune, with 95% CIs, for each geographical region by age group, sex, and area of residence (urban vs rural). Findings 29·7% (95% CI 26·3–33·4) of 8309 children aged 5–17 years were immune to diphtheria, 10·5% (8·6–12·8) were non-immune, and 59·8% (56·3–63·1) were partially immune. The proportion of children aged 5–17 years who were non-immune to diphtheria ranged from 6·0% (4·2–8·3) in the south to 16·8% (11·2–24·4) in the northeast. Overall, 9·9% (7·7–12·5) of children residing in rural areas and 13·1% (10·2–16·6) residing in urban areas were non-immune to diphtheria. A higher proportion of girls than boys were non-immune to diphtheria in the northern (17·7% [12·6–24·2] vs 7·1% [4·1–11·9]; p=0·0007) and northeastern regions (20·0% [12·9–29·8] vs 12·9% [8·6–19·0]; p=0·0035). Interpretation The findings of our serosurvey indicate that a substantial proportion of children aged 5–17 years were non-immune or partially immune to diphtheria. Transmission of diphtheria is likely to continue in India until the immunity gap is bridged through adequate coverage of primary and booster doses of diphtheria vaccine. Funding Indian Council of Medical Research.

Background Brucellosis is an important neglected zoonosis. Effective cattle vaccines are available but are infrequently used in India, where rural households commonly own one or two cattle as sources of protein and income. We assessed the prevalence of infection and risk factors in humans. Methods We conducted a cross-sectional sero-survey in randomly selected individuals in 60 villages in Punjab. Infection prevalence was assessed by positive Rose Bengal testing or immunoglobulin G enzyme-linked immunosorbent assay. Risk factors were adjusted for potential confounding using multivariable analyses. Results Of the 1927 subjects who were approached, 93% agreed to participate. Age-standardised prevalence for Brucella infection was 2.24% (95% confidence interval [CI] 1.61 to 3.11). More than 60% of households kept cattle and 10% assisted with calving or abortions. Nearly all individuals consumed boiled cow/buffalo milk from their own or neighbours' cattle and 3.3% consumed goat’s milk. There was a 2.18 times increased odds (95% CI 0.96 to 4.95) of infection with calving/abortions and a 4.26 times increased odds (95% CI 1.33 to 13.6) with goat’s milk but not bovine milk consumption. Conclusions An association with calving/abortions and goat’s milk consumption was seen. Brucella vaccination of household livestock would reduce the risk to humans in such settings. Additional measures include biosecurity training around calving/abortions, education to boil all milk and for healthcare workers to test for brucellosis.

Background & Objectives: Understanding the distribution and prevalence of three major mosquito borne diseases in an area is critical for the development of effective vector control strategies and public health interventions. The present study is therefore aimed to explore the epidemiological trend of malaria, dengue and chikungunya from 2012 to 2018 in Punjab. Methods: Quantitatively retrospective data was collected from Department of Health and Family Welfare, the National Vector Borne Disease Control Programme (NVBDCP), Punjab from 2012 to March 2018. The collected data was statistically analysed. Results: In case of malaria highest prevalent districts in Punjab are Mansa and Bathinda, for dengue Patiala, Ludhiana and S.A.S. Nagar and Patiala for chikungunya. Malaria was reported mainly from rural areas while dengue and chikungunya were found more in urban areas. For all three mosquito borne diseases, males were infected more as compared to females. Malaria cases were reported in months of August and September while dengue cases increased from July to November whereas chikungunya cases were highest in months of August to October. Conclusions: These findings help in concluding the trend analysis which in turn helps us to increase our focus on disease endemic districts along with boosting the vector control strategies in respective districts. Further the control of these mosquito borne diseases can be solved by employing adequate human resources, by increasing awareness in the community by conducting health camps and strengthening the entomological surveillance for timely reduction in the breeding of the vectors, especially before the repeated rise in cases during the period from July to November each year.

Background & objectives: The state of Punjab, India is highly endemic for dengue fever as high number of confirmed dengue cases have been reported since 2013. A better understanding of vectors distribution and their seasonal variation is necessary to control the disease. Therefore, the present study was conducted in both rural and urban areas of 11 out of 22 districts of Punjab to highlight seasonal prevalence of Aedes vector mosquitoes. Methods: Entomological surveys were carried out in different seasons and all kinds of indoor and outdoor breeding habitats were examined and Aedes immatures were collected. The Stegomyia indices were calculated and compared from urban and rural areas in different seasons. Results: Both vectors of dengue, i.e. Aedes aegypti and Ae. albopictus were recorded to be prevalent. Ae. aegypti mosquitoes were observed in all districts surveyed while Ae. albopictus were found only in seven districts of Punjab. The Stegomyia indices were significantly high during monsoon as compared to pre- and post- monsoon periods. Occurrence of dengue cases were found to be correlated with the Stegomyia indices. Interpretation & conclusion: This is the first detailed study of prevalence of dengue mosquito vectors in Punjab showing the presence of Ae. aegypti and Ae. albopictus in both urban and rural areas of the state, thereby demonstrating wide distribution of this vector. Different breeding habitats identified in the study should be subjected to targeted intervention such as source reduction in order to achieve effective control of dengue cases.

Background The prevalence of chronic hepatitis C (CHC) in People Who Inject Drugs (PWID) is 8-10% as compared to 3·6% in the general population in Punjab, India. We assessed the real-world efficacy and safety of free-of-charge generic direct-acting antivirals (DAAs), sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir)±ribavirin in the microelimination of CHC in PWID in a public health setting. Methods An integrated care team at 25 sites provided algorithm based DAAs treatment to PWID supervised by telemedicine clinics between 18th June 2016 and 31st July 2019. The primary endpoint was sustained virological response at 12 weeks (SVR-12); the secondary endpoints were treatment completion, adherence, safety, and adverse events. ClinicalTrials.gov number: NCT01110447. Findings We enrolled 3477 PWID (87·2% men; mean age 33·6±12·5 years; 83·8% rural; 6·8% compensated cirrhosis). While 2280 (65·5%) patients completed treatment, 1978 patients completed 12 weeks of follow up for SVR-12. SVR-12 was achieved in 91·1% of patients per protocol, 49.5% as per intention to treat (ITT) and 90·1% in a modified ITT analysis. Of 546 (15·7%) patients with treatment interruptions, 99 (19·7%) could be traced to test for SVR-12 with a cure rate of 77·8%. There were no major adverse events or consequent treatment discontinuation. Interpretation Integrated care of PWID with CHC with DAAs is safe and effective. Measures for reducing treatment interruptions will further improve outcomes. Funding The Government of the state of Punjab, India under the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) project, funds the project.

ObjectiveDespite treatment availability, chronic hepatitis C virus (HCV) public health burden is rising in India due to lack of timely diagnosis. Therefore, we aim to assess incremental cost per quality-adjusted life year (QALY) for one-time universal screening followed by treatment of people infected with HCV as compared with a no screening policy in Punjab, India.Study designDecision tree integrated with Markov model was developed to simulate disease progression. A societal perspective and a 3% annual discount rate were considered to assess incremental cost per QALY gained. In addition, budgetary impact was also assessed with a payer’s perspective and time horizon of 5 years.Study settingScreening services were assumed to be delivered as a facility-based intervention where active screening for HCV cases would be performed at 22 district hospitals in the state of Punjab, which will act as integrated testing as well as treatment sites for HCV.InterventionTwo intervention scenarios were compared with no universal screening and treatment (routine care). Scenario I—screening with ELISA followed by confirmatory HCV-RNA quantification and treatment. Scenario II—screening with rapid diagnostic test (RDT) kit followed by confirmatory HCV-RNA quantification and treatment.Primary and secondary outcome measuresLifetime costs; life years and QALY gained; and incremental cost-effectiveness ratio for each of the above-mentioned intervention scenario as compared with the routine care.ResultsScreening with ELISA and RDT, respectively, results in a gain of 0.028 (0.008 to 0.06) and 0.027 (0.008 to 0.061) QALY per person with costs decreased by −1810 Indian rupees (−3376 to –867) and −1812 Indian rupees (−3468 to −850) when compared with no screening. One-time universal screening of all those ≥18 years at a base coverage of 30%, with ELISA and RDT, would cost 8.5 and 8.3 times more, respectively, when compared with screening the age group of the cohort 40–45 years old.ConclusionOne-time universal screening followed by HCV treatment is a dominant strategy as compared with no screening. However, budget impact of screening of all ≥18-year-old people seems unsustainable. Thus, in view of findings from both cost-effectiveness and budget impact, we recommend beginning with screening the age cohort with RDT around mean age of disease presentation, that is, 40–45 years, instead of all ≥18-year-old people.

Background The state of Punjab in India qualifies for malaria elimination because the number of cases reported through routine surveillance is in decline. However, surveillance system prevalence mainly provides malaria trends. Therefore, a prospective epidemiological study was designed to estimate the malaria burden in the state. Methods District-wise annual parasite incidence (API) was used for identification of three strata, representing high, moderate and low API zones. A total of 0.9 million people from nine districts was under malaria surveillance for 1 y. The weighted estimates of API for the three regions was calculated and combined to give an estimate of API for the total population of the state. Results Based upon the primary data generated, malaria cases from high, moderate and low malaria-endemic areas were estimated to be 3727, 904 and 106, respectively. Further, the total number of malaria cases in the state was estimated to be 4737 (95% CI 4006 to 5469) cases per annum. Conclusion Actual burden of malaria in the state of Punjab, India, is about seven to eight times higher than that reported by routine surveillance activities. However, the state still qualifies for malaria elimination but needs vigorous efforts to strengthen the active surveillance and reporting system along with implementation of effective control strategies to achieve malaria elimination.

Introduction: India introduced a hepatitis-B (HB) vaccine in the Universal Immunization Program in 2002–2003 on a pilot basis, expanded to ten states in 2007–2008 (phase-1), and the entire country in 2011–2012 (phase-2). We tested sera from a nationally representative serosurvey conducted duing 2017, to estimate the seroprevalence of different markers of HB infection among children aged 5–17 years in India and to assess the impact of vaccination. Methods: We tested sera from 8273 children for different markers of HB infection and estimated weighted age-group specific seroprevalence of children who were chronically infected (HBsAg and anti-HBc positive), and immune due to past infection (anti-HBc positive and HBsAg negative), and having serological evidence of HB vaccination (only anti-HBs positive). We compared the prevalence of serological markers among children born before (aged 11–17 years) and after (aged 5-10 years) introduction of HB-vaccine from phase-1 states. Results: Among children aged 5–8 years, 1.1% were chronic carriers, 5.3% immune due to past infection, and 23.2% vaccinated. The corresponding proportions among children aged 9–17 years were 1.1%, 8.0%, and 12.0%, respectively. In phase-1 states, children aged 5–10 years had a significantly lower prevalence of anti-HBc (4.9% vs. 7.6%, p

OBJECTIVES We assessed the efficacy of decentralized public health services and safety of direct-acting antiviral agents (DAAs) in the treatment of pediatric chronic hepatitis C (CHC) in the Mukh-Mantri Punjab Hepatitis C Relief Fund, a public-health initiative for prevention and control of CHC in Punjab, India. METHODS Consecutive children with CHC [age ≥12 to

Summary Background The burden of dengue virus (DENV) infection across geographical regions of India is poorly quantified. We estimated the age-specific seroprevalence, force of infection, and number of infections in India. Methods We did a community-based survey in 240 clusters (118 rural, 122 urban), selected from 60 districts of 15 Indian states from five geographical regions. We enumerated each cluster, randomly selected (with an Andriod application developed specifically for the survey) 25 individuals from age groups of 5–8 years, 9–17 years, and 18–45 years, and sampled a minimum of 11 individuals from each age group (all the 25 randomly selected individuals in each age group were visited in their houses and individuals who consented for the survey were included in the study). Age was the only inclusion criterion; for the purpose of enumeration, individuals residing in the household for more than 6 months were included. Sera were tested centrally by a laboratory team of scientific and technical staff for IgG antibodies against the DENV with the use of indirect ELISA. We calculated age group specific seroprevalence and constructed catalytic models to estimate force of infection. Findings From June 19, 2017, to April 12, 2018, we randomly selected 17 930 individuals from three age groups. Of these, blood samples were collected and tested for 12 300 individuals (5–8 years, n=4059; 9–17 years, n=4265; 18–45 years, n=3976). The overall seroprevalence of DENV infection in India was 48·7% (95% CI 43·5–54·0), increasing from 28·3% (21·5–36·2) among children aged 5–8 years to 41·0% (32·4–50·1) among children aged 9–17 years and 56·2% (49·0–63·1) among individuals aged between 18–45 years. The seroprevalence was high in the southern (76·9% [69·1–83·2]), western (62·3% [55·3–68·8]), and northern (60·3% [49·3–70·5]) regions. The estimated number of primary DENV infections with the constant force of infection model was 12 991 357 (12 825 128–13 130 258) and for the age-dependent force of infection model was 8 655 425 (7 243 630–9 545 052) among individuals aged 5–45 years from 30 Indian states in 2017. Interpretation The burden of dengue infection in India was heterogeneous, with evidence of high transmission in northern, western, and southern regions. The survey findings will be useful in making informed decisions about introduction of upcoming dengue vaccines in India. Funding Indian Council of Medical Research.

Hepatitis C virus (HCV) infection is a principal cause of morbidity, mortality, and economic burden, and the global elimination of HCV is now considered a public health objective. Globally, an estimated 71 million have chronic HCV infection with an estimated annual mortality of 3,99,000. The 69th World health Assembly has endorsed the global HCV elimination strategy by 2030, which is made possible because of all oral, cost-effective, efficacious, generic direct-acting antivirals. The public health strategy targets not only diagnosed chronic hepatitis C patients but also asymptomatic undiagnosed HCV-infected individuals, persons living with human immunodeficiency virus (HIV), post-transplant, thallasemia, persons who inject drugs, and the pediatric population. Mobilization of state-sponsored HCV elimination programs in a global coalition against HCV has taken root in Egypt, India, Georgia, Mongolia, China, Australia, and Brazil. This review summarizes current HCV elimination initiatives in terms of medical progress, barriers to HCV elimination, and current gaps in knowledge and social outreach from the public health perspective.

Background & objectives: Submicroscopic malaria infections with low parasite density serve as a silent reservoir for maintaining residual transmission in the population. These infections should be identified and targeted to be eliminated for sustained malaria control. The conventional methods of diagnosis such as light microscopy and rapid diagnostic kits often fail to detect low density infections. Therefore, the more sensitive molecular techniques should be employed to detect low density infections. The objectives of the study was to explore the prevalence of sub-microscopic infections in low transmission areas of Punjab using highly sensitive molecular tool. Methods: A total of 1114 finger prick blood samples were collected through active surveillance and tested for malaria diagnosis using light microscopy, RDT and PCR. Nested PCR amplification was performed using a pair of Plasmodium genus-specific primers from the 18S rRNA small subunit gene (18S rRNA). The amplified PCR products were analysed using a 2% agarose gel, stained with ethidium bromide and observed under transilluminator. Results: Test positive rate (TPR) by microscopy, RDT and PCR was 4.4, 3.95 and 5.75%, respectively. Microscopy and RDT failed to detect mixed infections whereas 0.26% cases were found to be mixed infection in PCR. Compared to LM and RDT, PCR has detected 1.3% additional positive cases. However, of the total positive cases detected by PCR, 23.4% infections were found to be submicroscopic, which could not be detected by conventional methods of diagnosis. Interpretation & conclusions: The molecular study revealed the existence of submicroscopic malaria cases in the study population which would have remained undetected by conventional methods of diagnosis. This is particularly important because Punjab state is in malaria elimination phase and targeted to achieve elimination in 2021. However, such undetected parasite positive cases may pose bigger problem any time due to continued transmission. Therefore, application of more sensitive diagnostic tools like PCR and LAMP with conventional methods may be much more useful in case detection particularly in low transmission settings for malaria elimination.

Background & Aims The prevalence of anti-hepatitis C virus antibody in Punjab, India is 3.6%, with 728,000 people estimated to have viremic chronic hepatitis C (CHC). The Mukh-Mantri Punjab Hepatitis C Relief Fund, launched on 18th June 2016, provides no-cost generic direct-acting antivirals (DAAs) with sofosbuvir + ledipasvir ± ribavirin or sofosbuvir + daclatasvir ± ribavirin with the goal of eliminating CHC from Punjab. We assessed the safety and efficacy of decentralized treatment of CHC in a public health care setting. Methods Primary care providers from 3 university and 22 district hospitals were trained to provide algorithm-based DAA treatment and supervised by telehealth clinics conducted fortnightly. The diagnosis of cirrhosis was based on clinical and radiological evidence, including aspartate aminotransferase-to-platelet ratio index (APRI ≥2.0) and FIB-4 score (>3.25), or on liver stiffness measurement ≥12.5 kPa on Fibroscan®. Results We enrolled 48,088 individuals with CHC (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhosis; 69.9% genotype [GT] 3) between 18th June 2016 to 31st July 2018. While 36,250 (75.4%) patients completed treatment, 5,497 (11.4%) had treatment interruptions and 6,341 (13.2%) patients are currently ongoing treatment. Sustained virological response at 12 weeks after treatment completion (SVR12) was achieved in 91.6% of patients per protocol, 67.6% in intention-to-treat (ITT) analysis, where all interruptions were treated as failures, and 91.2% in a modified ITT analysis where all patients with successful SVR12 in the interruptions arm were included as cured. SVR12 rates in patients with and without cirrhosis and GT3 versus non-GT3 were comparable. The SVR12 rate was 84.4% in patients who had treatment interruptions. Conclusion Decentralized care of patients with CHC using generic all-oral DAA regimens is safe and effective regardless of genotype or presence of cirrhosis. ClinicalTrials.gov number: NCT01110447. Lay summary We assessed the safety and efficacy of public health care using no-cost all-oral generic direct-acting antiviral drugs against hepatitis C in the state of Punjab, India. The goal is elimination of chronic hepatitis C (CHC) by 2030 and involves primary care providers at 25 sites in the state. We enrolled 48,088 individuals (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhotic; 69.9% genotype 3) between 18th June 2016 to 31st July 2018. Cure was achieved in 91.6% of patients, demonstrating that decentralized care of CHC with generic all-oral regimens is safe and effective.

India has a large share of the hepatitis C virus (HCV) burden of the world. Unsafe medical practices and blood transfusions are the leading modes of transmission of HCV in India. The commonest HCV genotype in India is genotype 3 followed by genotype 1. While directly acting antivirals (DAAs) agents have become available at reasonable rates in India, cost of therapy remains a major barrier for control of HCV in India. Generic DAAs have been proven to be cost-saving in prior studies. We examined data from various studies in India and elsewhere using generic DAAs, and evaluated whether they are equally efficacious as the branded drugs. Since the availability of generic DAAs in the Indian market, there is a lot of real life data as well as prospective studies in special patient populations such as hematological disorders (thalassemia and hemophilia), chronic kidney disease, hemodialysis patients, post liver and renal transplant patients on immunosuppression, intravenous drug users, confections and other high risk groups. Control of HCV infection in India requires multi pronged approach. There is a need to formulate a health educational curriculum targeting not only the high-risk population but also the general population regarding the transmission of HCV. Adopting the dual approach of treating the old cases (decreasing the reservoir pool of HCV) and decreasing the incidence of new ones would help curtail the disease and decrease liver related mortality. In this scenario, the role of efficacious low cost generic medications is essential.

Hepatitis C virus (HCV) is a globally prevalent pathogen and is a major cause of healthcare burden in India. HCV poses a significant problem in the state of Punjab, India owing to the higher prevalence of risk factors like unsafe medical practices (including unsafe injections and dental procedures) and intravenous drug use. The reported prevalence of HCV in this part of the country was 5.2% in 2012, while a recent study has shown the prevalence to be 3.2% in 2016. Similar to the other geographic belts in India, genotype 3 predominates in the state of Punjab. Control of HCV infection in Punjab requires focusing on several strategies. There is a need to formulate a health educational curriculum targeting not only the high-risk population but also the general population regarding the transmission of HCV. Training of family physicians who form the first link to patients in the community is imperative in the success of healthcare programmes. Adopting the dual approach of treating the old cases (decreasing the reservoir pool of HCV) and decreasing the incidence of new ones would help curtail the disease and decrease liver related mortality. A commendable initiative has been launched by the Punjab state government to eliminate HCV from Punjab. However, besides the initiative by the government, a concerted effort by all other stakeholders in managing the HCV burden in India, namely the doctors, the drug companies and the non-government organizations is required for control of HCV.

Tuberculosis (TB) persists as a global public health problem of serious magnitude requiring urgent attention. Current global efforts to control TB have three distinct but overlapping dimensions: humanitarian, public health, and economic. Alleviating illness, suffering, and death of individuals due to TB is the major humanitarian concern for a patient-centered approach to TB control. The public health dimension concerns proper diagnosis and treatment of patients with TB to decrease disease transmission. This necessitates the development of well-organized TB control programs (responsive and adaptable to the reforming health sector). TB is responsible for considerable direct and indirect costs to the individuals and the society. The economic dimension of TB control relates to a reduction of these costs, alleviation of poverty, and promotion of development.(1) The emergence of resistance to drugs used to treat TB, and particularly multi-drug-resistant TB (MDR TB), has become a significant public health problem and an obstacle to effective TB control.(2) Drug resistance is manifested when there is a selective growth of resistant mutants among the actively multiplying bacillary population in the presence of drugs. The emergence of drug resistance depends upon the frequency of drug resistant mutants in the susceptible bacillary population, the size of the actively multiplying bacillary population in the lesions, and the anti-microbial quality of the drugs used. Drug resistance of the Mycobacterium tuberculosis isolated from patients who have been treated for 1 month or more is defined as “acquired drug resistance”, while that of patients who have never been treated previously or treated for less than 1 month is called “primary drug resistance”.(3) Resistance to a single drug is defined as “mono resistance” and resistance to two or more drugs is defined as “poly resistance.” Resistance to at least Isoniazid and Rifampicin is termed as “MDR”.