Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Molecular detection of dengue and chikungunya viruses in surveillance of wild-caught Aedes mosquitoes in Punjab, North India.

BACKGROUND: Dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses are transmitted mainly by Aedes mosquitoes and are responsible for a significant global healthcare burden. The current study aimed to detect arboviruses in the Aedes mosquitoes in close proximity of patients during the transmission season. METHODS: Both immature and adult mosquitoes were collected from in and around the patients' houses. Mosquito pools were homogenized and extracted RNA was subjected to reverse transcription polymerase chain reaction for arboviral detection. Transovarian transmission (TOT) was assessed by screening F0 adults. Mosquito positivity was correlated with the aetiological agents identified in patients. RESULTS: Of 46 pools, 19 consisted of wild Aedes, with arboviral positivity in 53% (10/19) of pools. Among wild A. aegypti pools, positivity of DENV mono-infection, CHIKV mono-infection and DENV+CHIKV co-infection was noted in four, two and three pools, respectively. One wild pool of Aedes albopictus was positive for DENV-1. Similarly, A. aegypti F0 (adult Aedes developed from immatures) pools showed 59.2% (16/27) positivity for arboviruses. F0 Aedes showed positivity in three, six and seven pools for DENV-2, CHIKV and DENV+CHIKV, respectively, suggestive of TOT. DENV serotypes and CHIKV from 24 patients' serum samples were matched with strains isolated from Aedes and correlation was observed in four instances. CONCLUSIONS: The study detected DENV and CHIKV from wild-caught Aedes and found evidence of DENV and CHIKV TOT in F0 adults.

Mapping the stability of febrile illness hotspots in Punjab from 2012 to 2019- a spatial clustering and regression analysis.

INTRODUCTION: Febrile illnesses (FI) represent a typical spectrum of diseases in low-resource settings, either in isolation or with other common symptoms. They contribute substantially to morbidity and mortality in India. The primary objective was to study the burden of FI based on Integrated Disease Surveillance Programme (IDSP) data in Punjab, analyze geospatial and temporal trends and patterns, and identify the potential hotspots for effective intervention. METHODS: A retrospective ecological study used the district-level IDSP reports between 2012 and 2019. Diseases responsible for FI on a large scale, like Dengue, Chikungunya, Malaria (Plasmodium Falciparum, P. Vivax), Enteric fever, and Pyrexia of Unknown Origin (PUO), were included in the analysis. The digital map of Punjab was obtained from GitHub. Spatial autocorrelation and cluster analysis were done using Moran's I and Getis-Ord G* to determine hotspots of FI using the incidence and crude disease numbers reported under IDSP. Further, negative binomial regression was used to determine the association between Spatio-temporal and population variables per the census 2011. Stable hotspots were depicted using heat maps generated from district-wise yearly data. RESULTS: PUO was the highest reported FI. We observed a rising trend in the incidence of Dengue, Chikungunya, and Enteric fever, which depicted occasional spikes during the study period. FI expressed significant inter-district variations and clustering during the start of the study period, with more dispersion in the latter part of the study period. P.Vivax malaria depicted stable hotspots in southern districts of Punjab. In contrast, P. Falciparum malaria, Chikungunya, and PUO expressed no spatial patterns. Enteric Fever incidence was high in central and northeastern districts but depicted no stable spatial patterns. Certain districts were common incidence hotspots for multiple diseases. The number of cases in each district has shown over-dispersion for each disease and has little dependence on population, gender, or residence as per regression analysis. CONCLUSIONS: The study demonstrates that information obtained through IDSP can describe the spatial epidemiology of FI at crude spatial scales and drive concerted efforts against FI by identifying actionable points.

First detection and genetic identification of Rickettsia spp. from ticks collected from rodents in north India.

BACKGROUND: Changing climatic conditions and invasion of ticks in urban areas have led to a greater number of cases of tick-borne diseases, thus, becoming a matter of increasing concern. Tick borne rickettsioses are one of the important emerging diseases worldwide. Knowledge of epidemiology of the vector and pathogen in the community is essential in order to understand and prevent the transmission of the disease to healthy population. METHODS: In our present study, we trapped rodents in selected areas of Chandigarh and Punjab in north India. The rodents were screened for the presence of ticks which were further screened for the presence of rickettsial agents. PCRs targeting 17 â€‹kDa and gltA genes were carried out followed by Sanger sequencing of the positive amplicons followed by phylogenetic analysis of the sequences. RESULTS: A total of 17 ticks were collected out of which one (Rhipicephalus sanguineus) was found to be harboring a Rickettsia sp. PCR targeting gltA and 17 â€‹kDa genes of rickettsia were put up and Sanger sequencing was performed. Phylogenetic analysis revealed the sequences to be closely related to Rickettsia rhipicephali. CONCLUSION: The current study establishes the presence of rickettsial agents in the community. Although Rickettsia rhipicephali is a non-pathogenic agent, the study encourages more vigorous community surveillance should be carried out in order to determine the exact burden of rickettsial agents in our community. To our knowledge, this is the first study reporting Rickettsia rhipicephali in India.

Malaria vector sibling species distribution in different endemic districts of Punjab, India.

BACKGROUND & OBJECTIVES: Malaria transmission in Punjab, India is mainly seasonal with variation in its endemicity that may be due to varying vector behaviour in different areas of the state, primarily attributed to the existence of sibling species complexes among the vector species. So far there is no report regarding the existence of malaria vectors sibling species in the state of Punjab, therefore, the present study was planned to investigate the status of sibling species of two main vectors of malaria viz. Anopheles culcifacies and Anopheles fluviatilis in different districts of Punjab. METHODS: Mosquito collections were made through hand catch in the morning hours. Malaria vector species An. culicifacies and An. fluviatilis were morphologically identified and man hour density was calculated. Both the vector species were subjected to molecular assays for sibling species identification through amplification of D3 domain of 28S ribosomal DNA by allele-specific PCR. RESULTS: Four sibling species of An. culicifacies, were identified viz. A, B, C and E. Species A was identified from Bhatinda district, species B, C and E from. S.A.S. Nagar and species C from Hoshiarpur. Two sibling species S and T of An. fluviatilis were identified from districts S.A.S. Nagar and Rupnagar. INTERPRETATION & CONCLUSION: Presence of four sibling species of An. culicifacies and two sibling species of An. fluviatilis in Punjab necessitates planning of longitudinal studies to ascertain their role in disease transmission so that appropriate interventions may be applied to achieve malaria elimination.

Patient outcomes in public sector hepatitis C treatment programmes: a retrospective cohort analysis across five low- and middle-income countries.

OBJECTIVES: Given limited data on factors associated with hepatitis C virus (HCV) treatment discontinuation and failure in low- and middle-income countries, we aimed to describe patient populations treated for HCV in five countries and identify patient groups that may need additional support. DESIGN: Retrospective cohort analysis using routinely collected data. SETTING: Public sector HCV treatment programmes in India (Punjab), Indonesia, Myanmar, Nigeria (Nasarawa) and Vietnam. PARTICIPANTS: 104 957 patients who initiated treatment in 2016-2022 (89% from Punjab). PRIMARY OUTCOMES: Treatment completion and cure. RESULTS: Patient characteristics and factors associated with outcomes varied across countries and facilities. Across all patients, median age was 40 years (IQR: 29-52), 30.6% were female, 7.0% reported a history of injecting drugs, 18.2% were cirrhotic and 4.9% were coinfected with HIV. 79.8% were prescribed sofosbuvir+daclastasvir. Of patients with adequate follow-up, 90.6% (89,551) completed treatment. 77.5% (69,426) of those who completed treatment also completed sustained virological testing at 12 weeks (SVR12), and of those, 92.6% (64 305) were cured. In multivariable-adjusted models, in most countries, significantly lower treatment completion was observed among patients on 24-week regimens (vs 12-week regimens) and those initiated in later years of the programme. In several countries, males, younger patients <20 years and certain groups of cirrhotic patients were less likely to complete treatment or be cured. In Punjab, treatment completion was also lower in those with a family history of HCV and people who inject drugs (PWID); in other countries, outcomes were comparable for PWID. CONCLUSION: High proportions of patients completed treatment and were cured across patient groups and countries. SVR12 follow-up could be strengthened. Males, younger people and those with decompensated cirrhosis on longer regimens may require additional support to complete treatment and achieve cure. Adequate programme financing, minimal user fees and implementation of evidence-based policies will be critical to close gaps.

Cost of National Vector Borne Disease Control Programme in North India.

Background & objectives: Despite significant resources being spent on National Vector Borne Disease Control Programme (NVBDCP), there are meagre published data on health system cost upon its implementation. Hence, the present study estimated the annual and unit cost of different services delivered under NVBDCP in North India. Methodology: Economic cost of implementing NVBDCP was estimated based on data collected from three North Indian States, i.e. Punjab, Haryana and Himachal Pradesh. Multistage stratified random sampling was used for selecting health facilities across each level [i.e. subcentres (SCs), Primary Health Centres (PHCs), community health centres (CHCs) and district malaria office (DMO)] from the selected States. Data on annual consumption of both capital and recurrent resources were assessed from each of the selected facilities following bottom-up costing approach. Capital items (equipment, vehicles and furniture) were annualized over average life span using a discount rate of 3 per cent. The mean annual cost of implementation of NVBDCP was estimated for each level along with unit cost. Results: The mean annual cost of implementing NVBDCP at the level of SC, PHC and CHC and DMO was ₹ 230,420 (199,523-264,901), 686,962 (482,637-886,313), 1.2 million (0.9-1.5 million) and 9.1 million (4.6-13.5 million), respectively. Per capita cost for the provision of complete package of services under NVBDCP was ₹ 45 (37-54), 48 (29-73), 10 (6-14) and 47 (31-62) at the level of SC, PHC, CHC and DMO level, respectively. The per capita cost was higher in Himachal Pradesh (HP) at SC [₹ 69 (52-85)] and CHC [₹ 20.8 (20.7-20.8)] level and in Punjab at PHC level [₹ 89 (49-132)] as compared to other States. Interpretation & conclusions: The evidence on cost of NVBDCP can be used to undertake future economic evaluations which could serve as a basis for allocating resources efficiently, policy development as well as future planning for scale up of services.

Correction: Viral Hepatitis as a Public Health Concern: A Narrative Review About the Current Scenario and the Way Forward.

[This corrects the article DOI: 10.7759/cureus.21907.].

Viral Hepatitis as a Public Health Concern: A Narrative Review About the Current Scenario and the Way Forward.

Viral hepatitis is one of the emerging public health problems, which urgently needs special attention. The disease has a varied presentation at the time of diagnosis, and it can progress from an accidental finding to life-threatening conditions like liver cirrhosis. It belongs to the rare group of diseases that can cause chronic inflammation inside the body, and it can have a delayed presentation. It contributes substantially to the global burden on healthcare. In terms of mortality, the burden due to viral hepatitis is similar to that of HIV and tuberculosis. It is among the major global public health challenges along with other communicable diseases, such as HIV, malaria, and tuberculosis; the major difference is that there are very limited preventive models in place for viral hepatitis, especially in developing countries like India. With limited resources for diagnosis and treatment, varied levels of presentation, and a rapidly increasing burden, it can become the next silent pandemic. In the current review, the authors aimed to compile the available global strategies for combating hepatitis, protocols available for disease surveillance, and the salient points from the national program for hepatitis control in India [National Viral Hepatitis Control Program (NVHCP)], and propose some recommendations. Ensuring a health facility equipped with a rapid diagnostic kit for screening, proper lab for the confirmation, robust Health Management Information System (HMIS) portal for the data management, and organizing regular workshops for physicians and lab technicians are some of the recommendations that we put forward.

Vector and rodent surveillance for Orientia tsutsugamushi in north India.

BACKGROUND & OBJECTIVES: Scrub typhus or chigger borne typhus, caused by Orientia tsutsugamushi is an emerging vector-borne disease as large numbers of cases have been reported in various tropical countries. It is transmitted to humans through bites of infected chiggers (larval mites). The knowledge about the vector, its distribution, density and habitat are important so as to understand the epidemiology of scrub typhus in a given area. To control rickettsial infections, regular rodent-vector surveillance should be planned in areas where the disease transmission is occurring and it will also help to strengthen the existing entomological data related to the vector of scrub typhus in northern India. METHODS: In the present study, rodent-vector surveillance was planned for one whole year, covering both mite active and non-active seasons (October 2019-December 2020) in selected areas of Chandigarh and Punjab in north India. Rodent tissues and mites were also examined for the presence of O. tsutsugamushi by nested PCR for 56 kDa gene and real-time PCR for 47 kDa outer membrane protein gene. 18S gene PCR was performed for molecular identification of mites. RESULTS: In the surveillance, three types of ectoparasite, viz. mites, fleas and ticks were obtained in rodents. All mites found were of Laelapidae family. None of the pooled rodent tissue samples as well as mite samples were found positive for O. tsutsugamushi by nested PCR for rickettsial DNA. INTERPRETATION & CONCLUSION: In the present study, we did not get any evidence of carriage of O. tsutsugamushi in either mites or rodents collected and sampled in selected regions in Chandigarh and Punjab. We need to strengthen the entomological surveillance over a broader region and increase the frequency of trapping rodents to increase clarity on vector-reservoir dynamics in this geographical region.

COVID-19 in Punjab, India: Epidemiological patterns, laboratory surveillance and contact tracing of COVID-19 cases, March-May 2020.

BACKGROUND: In Punjab, first COVID-19 case was detected on March 5, 2020 followed by multiple clusters. Understanding the epidemiology of reported COVID-19 cases helps decision makers in planning future responses. We described the epidemiological patterns, laboratory surveillance and contact tracing of COVID-19 cases in Punjab. METHODS: We analysed state's COVID-19 data from March-May 2020 to describe time, place and person distribution. We analysed the laboratory surveillance and contact tracing reports to calculate frequency of testing, sample positivity rate (PR) and contacts traced per case. FINDINGS: A total of 2256 cases were reported from March-May 2020 (attack rate 75 cases/million and case fatality rate 2%). Attack rate was higher among males (81 cases/million males) and maximum affected age group was 60-69 years (164∙5 cases/million). Five of 22 districts reported almost half cases in May's first week. Mortality rate was highest among individuals >60 years (six deaths/million) and males (two deaths/million males). Of 45 deaths, 41 reported comorbidities [(hypertension (42%), diabetes (40%)]. COVID-19 testing increased from 46 samples/day (PR: 2%) in March's first week to 4000 samples/day (PR: 2∙5%) by May's end (2752 tests/million). Amritsar conducted 2035 tests/million (highest PR: 6∙5%) while Barnala conducted 4158 tests/million (lowest PR: 1%). For 2256 cases, 19,432 contacts were traced (nine contacts/case) with 11% positivity rate. INTERPRETATION: COVID-19 in Punjab mostly affected males, >60 years of age and individuals with comorbid conditions. Many districts with less testing and contact tracing had higher positivity rate. We recommended to implement and ensure adequate testing and contact tracing in all the districts of Punjab.

Foodborne illness outbreak linked to a rural community kitchen in a rural area of Patiala District, Punjab, India, 2018.

BACKGROUND: In December 2018, an acute gastroenteritis outbreak was reported from Faridpur-Gujjran village, Patiala district, Punjab, India. OBJECTIVE: The objective of this study was to describe the epidemiology and risk factors of the outbreak and recommend prevention measures. METHODS: We conducted a descriptive study and a retrospective cohort study in the village. We defined a case as vomiting or ≥3 loose feces in 24 h plus abdominal pain and/or fever in a resident of the village during December 23-28, 2018. To find cases, we conducted a house-to-house survey; to identify risk factors, we conducted a retrospective cohort study. Fecal specimens were tested for enteric pathogens; water samples were tested for fecal contamination. We also interviewed food handlers. We compared attack rates by level of exposure. From the cohort study, we calculated risk ratios with 95% confidence intervals. RESULTS: From the 261 residents of the village, we identified 116 cases (attack rate 44%) and no deaths. The median age of affected persons was 27.5 years (range 0.5-80 years). The illness was associated with eating in a community kitchen of a temple during December 23-24, 2018. Eating mixed vegetables was associated with illness. We found no pathogens in fecal specimens. All three water samples showed coliform contamination. Cooked food had been left at room temperature before serving. CONCLUSION: Improper storage practices might have led to microbial proliferation of the food served. Our findings will help guide the enforcement of food safety policies for community kitchens.

Cost-effectiveness and budget impact analysis of facility-based screening and treatment of hepatitis C in Punjab state of India.

OBJECTIVE: Despite 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 DESIGN: Decision 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 SETTING: Screening 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. INTERVENTION: Two 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 MEASURES: Lifetime 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. RESULTS: Screening 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. CONCLUSION: One-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.

Immunity against diphtheria among children aged 5-17 years in India, 2017-18: a cross-sectional, population-based serosurvey.

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.

Seroprevalence of chikungunya virus infection in India, 2017: a cross-sectional population-based serosurvey.

BACKGROUND: Since its re-emergence in 2005, chikungunya virus (CHIKV) transmission has been documented in most Indian states. Information is scarce regarding the seroprevalence of CHIKV in India. We aimed to estimate the age-specific seroprevalence, force of infection (FOI), and proportion of the population susceptible to CHIKV infection. METHODS: We did a nationally representative, cross-sectional serosurvey, in which we randomly selected individuals in three age groups (5-8, 9-17, and 18-45 years), covering 240 clusters from 60 selected districts of 15 Indian states spread across all five geographical regions of India (north, northeast, east, south, and west). Age was the only inclusion criterion. We tested serum samples for IgG antibodies against CHIKV. We estimated the weighted age-group-specific seroprevalence of CHIKV infection for each region using the design weight (ie, the inverse of the overall probability of selection of state, district, village or ward, census enumeration block, and individual), adjusting for non-response. We constructed catalytic models to estimate the FOI and the proportion of the population susceptible to CHIKV in each region. FINDINGS: From June 19, 2017, to April 12, 2018, we enumerated 117 675 individuals, of whom 77 640 were in the age group of 5-45 years. Of 17 930 randomly selected individuals, 12 300 individuals participated and their samples were used for estimation of CHIKV seroprevalence. The overall prevalence of IgG antibodies against CHIKV in the study population was 18·1% (95% CI 14·2-22·6). The overall seroprevalence was 9·2% (5·4-15·1) among individuals aged 5-8 years, 14·0% (8·8-21·4) among individuals aged 9-17 years, and 21·6% (15·9-28·5) among individuals aged 18-45 years. The seroprevalence was lowest in the northeast region (0·3% [95% CI 0·1-0·8]) and highest in the southern region (43·1% [34·3-52·3]). There was a significant difference in seroprevalence between rural (11·5% [8·8-15·0]) and urban (40·2% [31·7-49·3]) areas (p<0·0001). The seroprevalence did not differ by sex (male 18·8% [95% CI 15·2-23·0] vs female 17·6% [13·2-23·1]; p=0·50). Heterogeneous FOI models suggested that the FOI was higher during 2003-07 in the southern and western region and 2013-17 in the northern region. FOI was lowest in the eastern and northeastern regions. The estimated proportion of the population susceptible to CHIKV in 2017 was lowest in the southern region (56·3%) and highest in the northeastern region (98·0%). INTERPRETATION: CHIKV transmission was higher in the southern, western, and northern regions of India than in the eastern and northeastern regions. However, a higher proportion of the population susceptible to CHIKV in the eastern and northeastern regions suggests a susceptibility of these regions to outbreaks in the future. Our survey findings will be useful in identifying appropriate target age groups and sites for setting up surveillance and for future CHIKV vaccine trials. FUNDING: Indian Council of Medical Research.

Initial success from a public health approach to hepatitis C testing, treatment and cure in seven countries: the road to elimination.

With political will, modest financial investment and effective technical assistance, public sector hepatitis C virus (HCV) programmes can be established in low- and middle-income countries as a first step towards elimination. Seven countries, with support from the Clinton Health Access Initiative (CHAI) and partners, have expanded access to HCV treatment by combining programme simplification with market shaping to reduce commodity prices. CHAI has supported a multipronged approach to HCV programme launch in Cambodia, India, Indonesia, Myanmar, Nigeria, Rwanda and Vietnam including pricing negotiations with suppliers, policy development, fast-track registrations of quality-assured generics, financing advocacy and strengthened service delivery. Governments are leading programme implementation, leveraging HIV programme infrastructure/financing and focusing on higher-HCV prevalence populations like people living with HIV, people who inject drugs and prisoners. This manuscript aims to describe programme structure and strategies, highlight current commodity costs and outline testing and treatment volumes across these countries. Across countries, commodity costs have fallen from >US$100 per diagnostic test and US$750-US$900 per 12-week pan-genotypic direct-acting antiviral regimen to as low as US$80 per-cure commodity package, including WHO-prequalified generic drugs (sofosbuvir + daclatasvir). As of December 2019, 5900+ healthcare workers were trained, 2 209 209 patients were screened, and 120 522 patients initiated treatment. The cure (SVR12) rate was >90%, including at lower-tier facilities. Programmes are successfully implementing simplified, decentralised public health approaches. Combined with political will and affordable pricing, these efforts can translate into commitments to achieve global targets. However, to achieve elimination, additional investment in scale-up is required.

Hepatitis-B virus infection in India: Findings from a nationally representative serosurvey, 2017-18.

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<0.001) and higher prevalence of anti-HBs (37.7% vs. 14.7%, p<0.001) compared to children aged 11-17 years. HBsAg positivity, however, was not different in the two age groups. CONCLUSIONS: Children born after the introduction of HB vaccination had a lower prevalence of past HBV infection and a higher prevalence of anti-HBs. The findings of our study could be considered as an interim assessment of the impact of the hepatitis B vaccine introduction in India.

The prevalence and risk factors for human Brucella species infection in a cross-sectional survey of a rural population in Punjab, India.

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.

Burden of dengue infection in India, 2017: a cross-sectional population based serosurvey.

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.

Prevalence of submicroscopic malaria in low transmission state of Punjab: A potential threat to malaria elimination.

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.