Vi polysaccharide typhoid vaccines cannot be used in children <2 years owing to poor immunogenic and T cell independent properties. Conjugate vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children <2 years. We evaluated efficacy and safety following vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

Worldwide, viral hepatitis continues to be a cause of considerable morbidity and mortality. Mass immunization with a single dose of live attenuated HAV has been shown to significantly reduce disease burden in the community. This was a phase IV, 5-year follow up study carried out at 4 centers (Kolkata, Delhi, Mumbai and Chennai) across India. The subjects with antibody titer 20 mIU/mL). The seroconversion rates considering seroprotection levels of anti-HAV antibody titer >20 mIU/mL, following vaccination starting from 6 weeks, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months were 95.1%, 97.9%, 98.3%, 96.2%, 97.8%, 92.6% and 97.3%, respectively. The geometric mean concentration (GMC) over the years increased from 64.9 mIU/mL at 6 weeks to 38.1 mIU/mL and 135.2 mIU/mL at 6 months and 12 months, respectively and was maintained at 127.1 mIU/mL at 60 months. In conclusion, the result of this 5-year follow up study showed that the single dose of live attenuated vaccine is well tolerated and provides long-term immunogenicity in healthy Indian children.

Background: Infantile colic is characterized by prolonged periods of inconsolable, incessant crying and persistent fussing in an otherwise healthy infant. It is a self-limiting condition, but causes significant stress to mothers. AIM: To observe the role of Lactobacillus reuteriDSM 17938 in reducing crying time in colicky infants in routine clinical practice. Methods: This was a prospective observational multicentric clinic-based study. Each practitioner included approximately 30 infants < 5 months of age with infantile colic who were prescribed L. reuteri DSM 17938 for a period of 21 days. There were four physical consultations and two telephonic consultations. The parents were given a daily diary to record the duration of crying and fussing episodes and a questionnaire was administered during the consultations. Results: A total of 120 infants with a mean age of 56.9 ± 34.2 days were included in this 28-day study. The mean crying time as reported by the parents in the subject diary reduced from 248.2 ± 101.2 min, 95% CI: 229.45, 266.94 at baseline to 45.6 ± 79.1 min 95% CI: 31.02, 60.31 at study end (P < 0.01). The clinical response (defined as reduction of 50% in crying time) was observed in 85% of subjects at study end. The fussiness and parental perception of colic recorded during the consultations were reduced by 66% and 72%, respectively, at study end. The maternal depression scores were reduced to 63% at study end. Conclusion: L. reuteri DSM 17938 was associated with a significant reduction in crying time in colicky infants, and showed improvement in maternal depression.

Introduction Hepatitis A virus infection is more severe in adults than children. Although vaccination can protect adults, current childhood programs cover a large population more successfully. Childhood vaccination is, therefore, a solution to protecting adults if it induces lasting immunity. Fifteen-year protection has been demonstrated in children, but longer-term data are only available for adults. We aimed to predict long term persistence of antibody in children beyond 15 years and assess if immunological mechanisms triggered by vaccination support longer-term protection. Methods Long-term clinical studies using hepatitis A (HAV) or A/B vaccines (HAB) containing 720 or 1440 Enzyme-linked immunosorbent assay Units (EU) of hepatitis A virus antigen were identified. Duration of persistence of antibodies and possible protection was determined by descriptively comparing antibody geometric mean concentration (GMC) kinetics, as well as GMC (95% confidence interval) at 15 years post-vaccination across studies. Immunological mechanism studies describing hepatitis A vaccination were identified. Results One study in children 12–15 years (2-dose HAB 720) and four in adults (2-dose HAV 1440 and 3-dose HAB 720) showed comparable GMC kinetics and per year rates of change up to 15 years. At 15 years, the GMC in children [414.7 mEU/ml (336.9; 510.5)] was in the same range as in adults [range 282.6 (217.6; 367.0) to 550.1 (416.0; 727.4)]. Based on these data, mathematical model predictions from adult studies (showing > 85% protected at 50 years) were deemed likely to also apply to children. Studies identified, both humoral and cell-mediated responses are induced following vaccination. Conclusion Based on comparable antibody data in adults and children up to 15 years, similar longer-term antibody persistence is expected in children with 2-dose inactivated hepatitis A 720 containing vaccine at least up to 50 years. Accordingly, improving routine childhood hepatitis A vaccination coverage could protect against more severe disease in adulthood. Plain language summary Trial Registration ClinicalTrials.gov identifiers, NCT00875485, NCT01000324, NCT01037114, NCT00289757, NCT00291876.

Graphical Threatened miscarriage is a common complication of early pregnancy characterized by symptoms of vaginal bleeding with/without abdominal cramps/pain in the first trimester. Progestogens are often administered for the management of this condition. Presented herein is the protocol of an ongoing, multicentric clinical trial to investigate the efficacy and safety of micronized progesterone (natural progestogen) compared to dydrogesterone (synthetic isomer of progesterone). A total of 304 eligible pregnant women aged 20–39 years, diagnosed with threatened miscarriage, will be enrolled during 5–12 weeks of gestation and randomized equally to receive either oral dydrogesterone (40 mg stat, followed by 10 mg three times a day) or oral micronized progesterone (200 mg two times a day) up to one week after stoppage of bleeding or if bleeding does not stop, then treatment will be continued till a maximum of 14 weeks of gestation (unless miscarriage is confirmed earlier or the investigator decides to prolong treatment for better outcome or if bleeding relapses). Scheduled visits after enrollment will be conducted during 6–13, 8–14, 18–20 and 24–26 weeks of gestation, in addition to a visit at the end of treatment at 14 weeks and another after parturition. The primary endpoint of the study is the miscarriage rate before 20 weeks of gestation. Secondary endpoints include the ongoing pregnancy rate at 24 weeks, treatment-induced changes in serum levels of cytokines and time to symptom resolution. Apart from the incidence of treatment-emergent adverse events, safety endpoints include changes in complete blood count and the results of liver and kidney function tests from baseline to 14 and 24–26 weeks of gestation. Delivery outcomes are exploratory endpoints of the study. Lay summary: Almost one out of four women face miscarriage during the first trimester of pregnancy; initial symptoms include vaginal bleeding with/without abdominal cramps/pain. This paper presents the plan of how an ongoing, multicentric study will be conducted to compare the efficacy and safety of oral medications known to reduce chances of miscarriage: micronized progesterone (which is a natural female sex hormone) versus synthetic progesterone. Women aged 20–39 years who are at risk of miscarriage during the first trimester of pregnancy will be randomly treated with either medication till one week after stoppage of bleeding during early pregnancy. If bleeding does not stop, treatment will be continued till a maximum of 14 weeks of pregnancy (unless miscarriage is confirmed earlier). The participants will be monitored until delivery. The study will evaluate the proportion of participants who experience miscarriage before 20 weeks of pregnancy and those who have an ongoing pregnancy at 24 weeks. It will also look at the time taken for relief from symptoms such as vaginal bleeding and abdominal pain, outcomes of delivery and incidence of any untoward event. In addition to routine tests and scans, additional tests will check for levels of biochemical parameters in the body, which are regulated by the natural or synthetic progesterone. Clinical trial registration number: CTRI/2024/02/063174 [Registered on: 26/02/2024].