Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9-14 years versus an established quadrivalent HPV vaccine in women aged 15-26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial.

BACKGROUND: To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9-14 years cohort. METHODS: This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9-14 years or 15-26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9-14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15-26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9-14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15-26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry - India (CTRI/2018/06/014601), and long-term follow-up is ongoing. FINDINGS: Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9-14 years and 1200 (819 women and 381 men) in the cohort aged 15-26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215-231) for girls and 222 days (217-230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216-232) for girls in the comparator vaccine group, and 222 days (216-230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67-2·32) for HPV type 6, 1·63 (1·38-1·91) for HPV type 11, 1·90 (1·60-2·25) for HPV type 16, and 2·16 (1·79-2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57-2·21) for HPV type 6, 1·46 (1·23-1·73) for HPV type 11, 1·62 (1·36-1·94) for HPV type 16, and 1·80 (1·48-2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3-4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. INTERPRETATION: We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9-14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. FUNDING: Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.

Awareness, attitudes and practices relating to Article 5.3 of the WHO Framework Convention on Tobacco Control among members of tobacco control committees in a southern Indian state.

BACKGROUND AND OBJECTIVES: The tobacco industry (TI) has undermined tobacco control policy for decades. The WHO Framework Convention on Tobacco Control Article 5.3 implementation guidelines provide guidance for preventing TI interference. Government officials responsible for policy implementation must understand these guidelines to manage TI tactics. This study assessed awareness, attitudes and practices of Article 5.3 guidelines among members of District Level Coordination Committees (DLCC) in Karnataka mandated with overseeing tobacco control activity. METHOD: A semistructured questionnaire survey of awareness, attitudes and adherence to Article 5.3 guidelines among 102 DLCC members carried out between January and July 2019. RESULT: Responses were received from 82 members, comprising 51 (62%) from health and 31 (38%) from non-health departments. Our study demonstrates a lack of understanding of Article 5.3 and its guidelines, even among those actively involved in tobacco control at the district level. Nearly 80% of respondents were aware that corporate social responsibility (CSR) by tobacco companies is an indirect form of promoting tobacco. However, 44% of members felt that CSR funding from the TI should be used to combat tobacco-related harm. A higher proportion (12%) of health respondents agreed that subsidies should be provided to tobacco agriculture compared with non-health (3%). CONCLUSION: Awareness of international guidance designed to prevent the TI influence on health policy among policymakers in this Indian state is low. Respondents from non-health departments were less aware of TI CSR. Those in health departments were more receptive towards taking a TI role in the future .

Technology-based Comprehensive Cardiac Rehabilitation Therapy (TaCT) for women with cardiovascular disease in a middle-income setting: A randomized controlled trial protocol.

Women are underrepresented in cardiac rehabilitation (CR) despite the benefits, and this is exacerbated in lower-resource settings where CR is insufficiently available. In this randomized controlled trial, the effectiveness of the Technology-based Comprehensive Cardiac Rehabilitation Therapy (TaCT) electronic cardiac rehabilitation (eCR) intervention on functional capacity, risk factors, quality of life, heart-health behaviors, symptoms, and morbidity will be tested among women with CVD in a middle-income country. Following a pilot study, a single-center, single-blinded, 2 parallel-arm (1:1 SNOSE) superiority trial comparing an eCR intervention (TaCT) to usual care, with assessments pre-intervention and at 3 and 6 months will be undertaken. One hundred adult women will be recruited. Permuted block (size 10) randomization will be applied. The 6-month intervention comprises an app, website, SMS texts with generic heart-health management advice, and bi-weekly 1:1 telephone calls with a nurse trainee. Individualized exercise prescriptions will be developed based on an Incremental Shuttle Walk Test (primary outcome) and dietary plans based on 24 h dietary recall. A yoga/relaxation video will be provided via WhatsApp, along with tobacco cessation support and a moderated group chat. At 3 months, intervention engagement and acceptability will be assessed. Analyses will be conducted based on intent-to-treat. If results of this novel trial of women-focused eCR in a middle-income country demonstrate clinically-significant increases in functional capacity, this could represent an important development for the field considering this would be an important outcome for women and would translate to lower mortality.

Potential Risk Factors of Smokeless Tobacco Consumption Among Adolescents in South India.

INTRODUCTION: Although most of the disease burden internationally is due to tobacco smoking, smokeless tobacco (SLT) use contributed to an estimated 76 000 deaths in 2017. We have studied the potential risk factors for SLT use among adolescents in South India. METHODS: A cross-sectional questionnaire survey of all students in grades 6-8 in schools in the Udupi district of Karnataka State ascertained SLT use status and potential determinants of SLT uptake. Ever SLT use was defined as any reported consumption of any SLT products, currently or at any time in the past. Independent effects on ever SLT use status were estimated using multiple logistic regression. RESULTS: Of 46 706 students from 914 participating schools, 39 282 (84.1%) provided questionnaire responses sufficiently complete for analysis. Ever SLT use was reported by 775 (2.0%) participants and in a mutually adjusted model was significantly related to age, male sex, family use, or friend's use of SLT, low socioeconomic status, high rebelliousness, and low self-esteem. After controlling for these effects, the odds of ever-SLT use were significantly higher among students who had least awareness of the harmful effects of tobacco use (odds ratio 3.7, 95% confidence interval [2.9, 4.7]) and significantly lower among those not exposed to tobacco advertising (odds ratio 0.7, 95% confidence interval [0.5, 0.8]). CONCLUSIONS: The prevalence of SLT use among children in Karnataka is relatively low when compared with other studies in India. The significant potential risk factors of SLT use include low awareness of the harmful effects of tobacco and tobacco control policies and exposure to tobacco advertising. IMPLICATIONS: The prevalence of SLT use among school going adolescents in South India is relatively low. The potential risk factors for SLT use among adolescents in southern India are similar to those for smoked tobacco. It includes age, male gender, family or friend's use of SLT, low socioeconomic status, high rebelliousness, low self-esteem, exposure to tobacco advertisement and least awareness about the harmful effects of tobacco and of tobacco control policies. The present study lays emphasis regarding creating awareness about tobacco harms and control policies for further reducing tobacco use among adolescents.

Institutional tensions, corporate social responsibility and district-level governance of tobacco industry interference: analysing challenges in local implementation of Article 5.3 measures in Karnataka, India.

INTRODUCTION: Accelerating progress on tobacco control will require Article 5.3 of the WHO Framework Convention on Tobacco Control to be systematically integrated into policies and practices of sectors beyond health at diverse government levels. However, no study has explored implementation challenges of Article 5.3 within multilevel systems such as India, where political decisions on tobacco control occur at diverse government levels, which may constrain action at local level. METHODS: Based on 33 semi-structured interviews with diverse government and civil society stakeholders across four districts in Karnataka, India (Mysore, Mangalore, Bengaluru (rural) and Udupi), this study examines challenges to implement Article 5.3 arising from competing agendas and policies of different actors at multiple levels. RESULTS: Our analysis reveals generally low levels of awareness of Article 5.3 and its guideline recommendations, even among those directly involved in tobacco control at district level. Efforts to implement Article 5.3 were also challenged by competing views on the appropriate terms of engagement with industry actors. Scope to reconcile tensions across competing health, agriculture and commercial agendas was further constrained by the policies and practices of the national Tobacco Board, thereby undermining local implementation of Article 5.3. The most challenging aspect of Article 5.3 implementation was the difficulties in restricting engagement by government officials and departments with tobacco industry corporate social responsibility initiatives given national requirements for such activities among major corporations. CONCLUSIONS: Promoting effective implementation of Article 5.3 in Karnataka will require policymakers to work across policy silos and reconcile tensions across India's national health and economic priorities.

Regulatory Compliance of Health Warnings on Tobacco Packs in Karnataka, India.

INTRODUCTION: In September 2014, the Government of India introduced legislation requiring all tobacco packaging to display a health warning covering 85% (60% pictorial, 25% text) of the principal display area of the pack, of at least 4 cm in height and 3.5 cm width, with legible text in a white font on a black background and in English and/or the same Indian language as the language used on the pack. We evaluated compliance with this legislation in the Udupi district of Karnataka, India. METHODS: We procured one example of every tobacco pack of cigarettes, beedis, chewing tobacco, and snuff sold by a convenience sample of retailers in one urban and two rural areas in each of the five administrative blocks of the Udupi district between June and August 2018. For each pack we measured the size of the health warning, calculated the proportion of the pack covered, and assessed the legibility. RESULTS: A total of 365 packs were collected from retailers, with 357 of these branded and eight, all packs of snuff, unbranded. Warnings on 320 (87.3%) packs did not reach the legally required proportional magnitude, warnings on 140 (38.4%) packs were not legible, and warnings on 117 packs (32.1%) did not meet the language requirement. Only 45 packs (12.3%) were fully compliant. CONCLUSIONS: Compliance with warning legislation in this district of India is low, highlighting the need for more effective enforcement. IMPLICATIONS: Warnings on tobacco packaging are an important and inexpensive means of communicating the harms associated with tobacco use. However, relatively few studies have explored regulatory compliance with warnings. We collected all unique tobacco packs from 66 retailers in a district in Karnataka in India and assessed whether each met the legislative requirements in terms of warning size and proportion of the pack covered, legibility, and the language used. Of the 365 packs collected, only one in eight was compliant with the legislative requirements. This study highlights the importance of assessing warning compliance and the need for enforcement in India.

Exposure to tobacco imagery in popular films and the risk of ever smoking among children in southern India.

BACKGROUND: Exposure to smoking in films is a recognised cause of smoking uptake among children. In India, in an attempt to protect children, films containing smoking are required to include tobacco control messaging including audiovisual disclaimers, on-screen health warnings when tobacco imagery is displayed and antitobacco 'health spots' before and during the film. We report a study of the association between ever smoking and exposure to tobacco imagery in locally popular films among children in Udupi district of Karnataka state in southern India. METHODS: A cross-sectional questionnaire survey of all students in grades 6-8 in schools in the Udupi district ascertained smoking status and potential confounders of smoking uptake, and whether children had seen any of 27 locally popular films we had coded and found to contain imagery of actual or implied tobacco use. Ever-smoking status was defined as any reported smoking of cigarettes, beedis or other tobacco products currently or at any time in the past. Independent effects on ever-smoking status were estimated using multiple logistic regression. RESULTS: Of 46 706 students enrolled in grades 6-8 in 914 participating schools, 39 282 (84.1%) provided questionnaire responses sufficiently complete for analysis. Ever smoking was reported by 914 (2.3%) participants and in a mutually adjusted model was significantly related to age, male sex, living in a home where smoking is allowed, having parents or siblings who smoke, low paternal education, low levels of family wealth, low self-esteem, rebelliousness and poor school performance. After allowing for these effects, the odds of ever smoking were not increased among students who had seen any of the listed films containing tobacco imagery when included in the analysis as a binary exposure (OR 0.9, 95% CI 0.4 to 2.0), and decreased in relation to level of exposure graded into tertiles of tobacco intervals seen. CONCLUSIONS: In this cross-sectional study, children in southern India who had seen films containing tobacco imagery are no more likely to smoke than those who had not, indicating that the tobacco control messaging mandated by Indian law may be attenuating the effect of tobacco imagery in films on smoking uptake.

Assessment of tobacco imagery and compliance with tobacco-free rules in popular Indian films.

BACKGROUND: Exposure to smoking in films causes smoking uptake among adolescents. Investigation of the extent to which tobacco imagery appears, or tobacco control laws are complied with in Indian films is limited, and especially so for films in regional languages. This study presents an analysis of tobacco content and compliance with tobacco control laws in popular films in several languages from the Karnataka state of India. METHODS: We used 5 min interval coding to measure actual tobacco use, implied tobacco use, tobacco paraphernalia and tobacco branding in the top 10 films identified from national box office ratings and regional distributor reports in Karnataka in 2015 and 2016. We also assessed compliance with tobacco-free film rules in India. FINDINGS: A total of 47 films, in English, Hindi, Malayalam, Tamil, Telugu and Tulu languages were coded. Any tobacco imagery was observed in 72% of films, and actual tobacco use in 50%. Tobacco imagery was equally prevalent in films classified as suitable for universal viewing (U category) or at age 12 or more (U/A category) films; and significantly more common in films made in regional than national language (Hindi). None of the films were fully compliant with legal requirements on health spots, audiovisual disclaimers and health warnings. CONCLUSIONS: Tobacco content was common in films classified as suitable for viewing by children, more among regional than national languages. Compliance with tobacco control laws was low. Stricter enforcement of tobacco-free film rules will protect children and adolescents from exposure to tobacco use on screen.

Prevalence of goiter and its association with iodine status among the women of reproductive age group in coastal villages of Udupi Taluk, Karnataka, India.

BACKGROUND: Iodine deficiency is one of the most prevalent micronutrient deficiencies globally. Women in reproductive age group are vulnerable to develop iodine deficiency as there is an increase in demand for iodine, especially during pregnancy. OBJECTIVES: The objective is to assess the prevalence of goiter and its association with iodine status and salt usage practices among the women of reproductive age group. METHODS: A community-based cross-sectional study was conducted from August 2015 to July 2017 among 1500 women of reproductive age group in five villages of Udupi Taluk. Stratified sampling design and proportion to population size of the reproductive age women in the study area was used to select the study participants. A pretested semi-structured questionnaire was used for data collection. Goiter was assessed clinically and graded as per the recommended criteria of the WHO. Salt samples from every household were collected for iodine estimation. Blood and urine samples were collected from subsample to estimate thyroid-stimulating hormone levels and urinary iodine excretion levels, respectively. RESULTS: The overall prevalence of goiter was 13% with 11.5% being Grade 1 and 1.5% being Grade 2. No significant association of goiter with urinary iodine, salt iodine levels, and salt usage practices was found. CONCLUSIONS: Median urinary iodine among the women with goiter indicates iodine sufficiency and no significant difference observed in urinary iodine levels between women with and without goiter.

Global human papilloma virus vaccine implementation: An update.

Human papillomavirus (HPV) infections continue to be one of the most common sexually transmitted infections worldwide. The oncogenic potential of this virus was well established in anogenital malignancies and oropharyngeal cancers. Even though a fall in cervical cancer rates has been reported worldwide, the subsequent rise in HPV-associated head and neck cancers among men and women have been reported from developed countries, necessitating the vaccination of adolescent boys as well. The objective of this narrative review is to provide an update on the current status of HPV vaccination worldwide. This will be helpful for clinicians in counseling parents and guardians as this vaccine mainly targets sexually naïve preadolescents. An electronic search of the databases was carried out to retrieve information concerning HPV vaccine implementation between July 2006 and 2017, with special emphasis on the current viewpoints, controversies and ethical issues. Globally, 74 countries have implemented the HPV vaccine in the national immunization schedule, and this vaccine is listed as an essential medicine by WHO. About 60% of the low- and lower-middle-income countries have implemented the vaccine with financial assistance from Gavi and WHO. The HPV vaccine is a safe vaccine with no serious adverse effects as per the data available from developed nations as well as low/lower middle/upper middle-income countries. However, long-term follow-up is essential to substantiate the impact of the vaccination programs in cancer prevention.

Possible non-sexual modes of transmission of human papilloma virus.

AIM: There is strong evidence to suggest vertical and horizontal modes of transmission of human papilloma virus (HPV), an established etiologic agent of cervical cancer. Infants, children, and adults can acquire both high-risk and low-risk infections by birth or by close contact even though HPV is mainly transmitted sexually. A thorough review of the literature was performed to assess the possible non-sexual modes of transmission of HPV. METHODS: An electronic search of databases for review articles, cross-sectional studies, cohort studies, and case reports on non-sexual modes of transmission among sexually unexposed women and children was carried out using search terms such as "human papilloma virus, HPV, transmission, horizontal transmission, vertical transmission, and fomites". Articles published between 1983 and 2015 were retrieved. RESULTS: Epidemiological and clinical data support various non-sexual modes of transmission especially at the time of birth and by close contact. Even though the role of fomites in the transmission of HPV is not well established, HPV-DNA positivity has been reported in transvaginal ultrasound probes and colposcopes after routine disinfection. CONCLUSION: Awareness needs to be spread among the public about alternate modes of transmission. For a proper understanding of the exact natural history of HPV infection acquired via the non-sexual route, long-term prospective studies need to be undertaken.

Estimating the effect of childhood socioeconomic disadvantage on oral cancer in India using marginal structural models.

BACKGROUND: Early life socioeconomic disadvantage could affect adult health directly or indirectly. To the best of our knowledge, there are no studies of the direct effect of early life socioeconomic conditions on oral cancer occurrence in adult life. METHODS: We conducted a multicenter, hospital-based, case-control study in India between 2011 and 2012 on 180 histopathologically confirmed incident oral and/or oropharyngeal cancer cases, aged 18 years or more, and 272 controls that included hospital visitors, who were not diagnosed with any cancer in the same hospitals. Life-course data were collected on socioeconomic conditions, risk factors, and parental behavior through interview employing a life grid. The early life socioeconomic conditions measure was determined by occupation of the head of household in childhood. Adult socioeconomic measures included participant's education and current occupation of the head of household. Marginal structural models with stabilized inverse probability weights were used to estimate the controlled direct effects of early life socioeconomic conditions on oral cancer. RESULTS: The total effect model showed that those in the low socioeconomic conditions in the early years of childhood had 60% (risk ratio [RR] = 1.6 [95% confidence interval {CI} = 1.4, 1.9]) increased risk of oral cancer. From the marginal structural models, the estimated risk for developing oral cancer among those in low early life socioeconomic conditions was 50% (RR = 1.5 [95% CI = 1.4, 1.5]), 20% (RR = 1.2 [95% CI = 0.9, 1.7]), and 90% (RR = 1.9 [95% CI = 1.7, 2.2]) greater than those in the high socioeconomic conditions when controlled for smoking, chewing, and alcohol, respectively. When all the three mediators were controlled in a marginal structural model, the RR was 1.3 (95% CI = 1.0, 1.6). CONCLUSION: Early life low socioeconomic condition had a controlled direct effect on oral cancer when smoking, chewing tobacco, and alcohol were separately adjusted in marginal structural models.

Voluntary medical male circumcision for HIV prevention and early resumption of sexual activity: a literature review.

A number of programs have focused on scale-up and implementation research regarding voluntary medical male circumcision; however, there is limited research with regard to factors and strategies related to abstinence compliance and the effects of resuming sex during the wound healing period (42-day post-circumcision). We searched the literature for peer-reviewed articles examining early resumption of sex during this period. This review identifies factors that may predispose a client to engage in sex during the 42-day postoperative period, examines how early resumption of sex can inhibit wound healing and increase seroconversion, and reviews strategies that may increase adherence to abstinence during the wound healing period. We found that the most common factor that may predispose a client to engage in sex before the end of the postoperative period is marriage or cohabitation with a sexual partner. With regard to the effect of sex during the postoperative period on wound healing and seroconversion, we found that adverse events incurred were mild, and there was an increased risk of seroconversion. The only strategy studied to increase compliance to abstinence during the postoperative period utilized text messaging, and the trial results indicate that text messaging did not increase abstinence compliance.

Prevalence, regional patterns and socio-demographic factors associated with poly-tobacco use in India: A secondary data analysis.

BACKGROUND: Tobacco use is associated with early, intermediate and long-term complications throughout the life course. With an influx of newer products containing nicotine, poly-tobacco use is slowly emerging as a public health concern, that is defined as existing tobacco users currently using two or more tobacco or nicotine products. While many studies have investigated single use tobacco, there is a paucity of research on regional patterns and socio-demographic factors associated with poly-tobacco use in India. OBJECTIVES: To assess prevalence of poly-tobacco use and determine the socio-demographic factors associated with poly-tobacco use in India. METHODS: Data from the Global Adult Tobacco Survey 2 (GATS, 2016-17) was analysed, which included information on tobacco use among people aged >15 years. The pattern of current tobacco status was described using descriptive statistics. Multiple logistic regression models were estimated to determine factors associated with poly-tobacco use. RESULTS: The prevalence of poly-tobacco use in India was found to be 9.8%. Among the current tobacco users, the prevalence was 33%. Significant socio-demographic factors associated with poly-tobacco use included younger age, male gender, religion and backward caste. North-eastern region reported highest prevalence of poly-tobacco use in the country, followed by the central region. CONCLUSION: The number of poly-tobacco users in India is considerably high and a matter of concern, more so in north east and central regions of the country. There is a need to create awareness about dangerous effects of all types of tobacco products and strengthen implementation of tobacco control policies with special focus on regions with high burden.

A randomized, active-controlled, multi-centric, phase-II clinical study to assess safety and immunogenicity of a fully liquid DTwP-HepB-IPV-Hib hexavalent vaccine (HEXASIIL®) in Indian toddlers.

BACKGROUND: Combination vaccines are effective in simplifying complex vaccination schedules involving multiple vaccines. A fully liquid hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)- hepatitis B (HepB)-inactivated poliovirus (IPV)-Haemophilus influenzae b (Hib) vaccine (HEXASIIL®), manufactured by Serum Institute of India Pvt. Ltd. was tested for safety and immunogenicity following booster vaccination. METHODS: This was a phase-II/III, open label, multicentric, controlled trial in toddlers (phase II) and infants (phase III) in India. This manuscript presents results of phase II. Healthy toddlers aged 12-24 months were randomized (1:1) to receive a 0.5 ml booster dose of HEXASIIL® or comparator Pentavac SD + Poliovac, intramuscularly and followed for 28 days for safety assessment. Blood samples were collected pre-vaccination and 28 days post-vaccination to assess immunogenicity. Descriptive summary statistics were provided for safety and immunogenecity analyses. RESULTS: A total of 223 subjects were randomized. One subject droped out prior to dosing, due to consent withdrawal. Thus, 222 subjects received study vaccine (110 HEXASIIL® and 112 comparator). Frequency of solicited adverse events was comparable between HEXASIIL® and comparator (85.5 % vs 90.2 %). Most local and systemic solicited AEs were mild to moderate in severity. All events resolved completely without any sequelae and none led to subject discontinuation. No vaccine related serious AE was reported. Post vaccination, seroprotection rates against tetanus, Hib and polio type 1 and 3 were 100 % in both the groups. Seroprotection rates for diphtheria (99.1 % vs 100 %) and polio type 2 (98.2 % vs 100 %) were observed in HEXASIIL® and comparator group, respectively. For Hepatitis B, seroprotection was >99 % in both groups. Seroconversion observed for Bordetella Pertussis (94.5 % vs 95.4 %) and Pertussis Toxin (77.1 % vs 87.2 %) in HEXASIIL® and comparator group, respectively. CONCLUSION: HEXASIIL® vaccine was found to be safe and immunogenic in toddlers and supported its further clinical development in infants. Clinical Trial Registration - CTRI/2019/11/022052.

Prospective study of exposure to smoking imagery in films and changes in susceptibility to smoking in a cohort of school students in Southern India.

INTRODUCTION: India has unique tobacco-free film and TV rules designed to prevent tobacco uptake. In this study, we examined the potential influence of exposure to smoking imagery in regionally famous films, on susceptibility to smoke in teenagers enrolled in schools in a district in Southern India. METHODS: A longitudinal survey of students, in grades 6 to 8 at baseline in 2017 and grades 7 to 9 one year later in 2018, ascertained prospective incident susceptibility to smoking during the study period in relation to baseline exposure to 27 locally popular films with actual or implied smoking imagery. RESULTS: We analyzed linked data from 33676 participants, and 3973 (11.8%) of the adolescents reported incident susceptibility. There was a significant increase in susceptibility to smoking with increasing exposure at baseline to smoking imagery in films on univariable analysis, highest tertile of exposure relative to no exposure (OR=1.4; 95% CI: 1.0 -2.1, ptrend<0.001), and this trend remained significant (p=0.022) after mutual adjustment for recognized confounders, highest vs no exposure (AOR=1.3; 95% CI: 0.9-1.8). We found no statistically significant association between exposure to tobacco-free film rules and change in susceptibility. CONCLUSIONS: Prospectively, watching films featuring smoking imagery increases adolescents' vulnerability to smoking. Further research revealed no difference in susceptibility change between youth who saw partially compliant films and those who watched non-compliant films. Our findings, thus, underscore the need to incorporate comprehensive approaches to prevent the inclusion of smoking imagery in films.

A phase III randomized-controlled study of safety and immunogenicity of DTwP-HepB-IPV-Hib vaccine (HEXASIIL®) in infants.

A fully liquid hexavalent containing Diphtheria (D), Tetanus (T) toxoids, whole cell Pertussis (wP), Hepatitis B (Hep B), type 1, 2, 3 of inactivated poliovirus (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (DTwP-HepB-IPV-Hib vaccine, HEXASIIL®) was tested for lot-to-lot consistency and non-inferiority against licensed DTwP-HepB-Hib + IPV in an open label, randomized Phase II/III study. In Phase III part, healthy infants received DTwP-HepB-IPV-Hib or DTwP-HepB-Hib + IPV vaccines at 6, 10 and 14 weeks of age. Blood samples were collected prior to the first dose and 28 days, post dose 3. Non inferiority versus DTwP-HepB-Hib + IPV was demonstrated with 95% CIs for the treatment difference for seroprotection/seroconversion rates. For DTwP-HepB-IPV-Hib lots, limits of 95% CI for post-vaccination geometric mean concentration ratios were within equivalence limits (0.5 and 2). Vaccine was well-tolerated and no safety concerns observed.Clinical Trial Registration - CTRI/2019/11/022052.

Acute kidney injury in scrub typhus.

BACKGROUND: We studied the urinary abnormalities and acute kidney injury (AKI) as per RIFLE criteria in scrub typhus. METHODS: A prospective case record-based study of scrub typhus was carried out from January 2009 to December 2010 in a tertiary hospital in South India. Patients were followed up until renal recovery or for at least 3 months after discharge. Univariate, chi-squared tests and multivariate logistic regression analyses were performed to identify the predictors of AKI. RESULTS: Scrub typhus was diagnosed in 259 patients. Urinary abnormalities were seen in 147 patients (56.7%) with 60 patients (23.2%) having AKI. All AKI patients had urinary abnormalities and 17 (28.3%) were oliguric. Applying RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria, R, I, F were present in 23 (38.33%), 13 (21.67%), and 24 patients (40%), respectively. Creatine phosphokinase (CPK) was raised in 33 patients (55%) and hemodialysis was required in 6 patients (10%). The case fatality rate in this study was 2 out of 259 (0.77%), both having AKI and others recovering clinically. Significant predictors of AKI were tachycardia [odds ratio (OR) 2.28], breathlessness (OR 2.281), intensive care requirement (OR 2.43), mechanical ventilation (OR 3.33), thrombocytopenia (OR 2.90) and CPK>80 U/L (OR 1.76) by univariate analysis and intensive care requirement (adjusted OR 2.89) and thrombocytopenia (AOR 2.28) by multivariable logistic regression. CONCLUSION: Scrub typhus should be part of the differential diagnosis of acute febrile illness with AKI. AKI in scrub typhus is usually mild, non-oliguric, and renal recovery occurs in most patients. Rhabdomyolysis may be contributory to AKI. Thrombocytopenia and intensive care requirement are significant predictors of AKI in scrub typhus.

Perceptions of novel warnings compared with current warning on tobacco packs, and warnings on cigarette sticks: A cross-sectional survey of college students in Southern India.

INTRODUCTION: In India there is insufficient knowledge of the risks associated with tobacco use. Increasing awareness of these risks is critical, with pictorial warnings on tobacco packs a cost-effective way to communicate this information. We explored perceptions of the current warning, 'Tobacco causes cancer', displayed on packs in India and four novel warnings about other potential impacts of tobacco use including social, financial, and environmental, but also complications with diabetes. As loose cigarette sales are common in India, we also explored perceptions of warnings on cigarette sticks. METHODS: A cross-sectional survey of college students aged ≥18 years in Karnataka, India, was conducted between January 2019 and February 2020. Participants were asked about salience, believability, and cognitive processing of warnings currently on packs. They were then shown an image of one current and four novel warnings and asked about their perceived effectiveness in preventing uptake and reducing and stopping tobacco use. They were then asked about warnings on cigarette sticks. RESULTS: Most participants (70.2%) recalled warnings on packs and considered them believable (55.7%), but only 12.0% read and 12.4% thought about them often. Warnings about the health impacts of tobacco use were viewed as most effective in preventing uptake, and reducing and stopping tobacco use. Nevertheless, at least a third of participants rated warnings pertaining to financial, social, and environmental impacts effective in preventing uptake, and reducing and stopping tobacco use. Approximately one-fifth (22.0%) thought that warnings on cigarette sticks would deter initiation. CONCLUSIONS: Our results suggest that health warnings are perceived as most effective in discouraging tobacco use among college students in Karnataka. While viewed as less effective than health warnings, novel non-health related messages were viewed as effective in preventing uptake, and reducing and stopping tobacco use by at least one in three participants. Warnings on cigarette sticks may help complement warnings on cigarette packs.

Programme and policy perspectives towards a tobacco-free generation in India: findings from a qualitative study.

OBJECTIVE: This study explored multistakeholder perspectives on existing adolescent-specific tobacco control policies and programmes, to advance India's transition towards a tobacco-free generation. DESIGN: Qualitative semi-structured interviews. SETTING: Interviews were conducted with officials involved in tobacco control at the national (India), state (Karnataka), district (Udupi) and village level. Interviews were audio recorded, transcribed verbatim and analysed thematically. PARTICIPANTS: Thirty-eight individuals representing national (n=9), state (n=9), district (n=14) and village (n=6) levels, participated. RESULTS: The study findings highlighted the need to strengthen and amend the existing Tobacco Control Law (2003) provisions, particularly in the vicinity of schools (Sections 6a and 6b). Increasing the minimum legal age to buy tobacco from 18 to 21 years, developing an 'application' for 'compliance and monitoring indicators' in Tobacco-Free Educational Institution guidelines were proposed. Policies to address smokeless tobacco use, stricter enforcement including regular monitoring of existing programmes, and robust evaluation of policies was underscored. Engaging adolescents to co-create interventions was advocated, along with integrating national tobacco control programmes into existing school and adolescent health programmes, using both an intersectoral and whole-societal approach to prevent tobacco use, were recommended. Finally, stakeholders mentioned that when drafting and implementing a comprehensive national tobacco control policy, there is a need to adopt a vision striving toward a tobacco-free generation. CONCLUSION: Strengthening and developing tobacco control programmes and policies are warranted which are monitored and evaluated rigorously, and where adolescents should be involved, accordingly.