Safety and Protective Effects of Influenza Vaccination in Pregnant Women on Pregnancy and Birth Outcomes in Pune, India: A Cross-Sectional Study.

BACKGROUND: Maternal influenza vaccination provides effective protection against influenza infections in pregnant women and their newborns. In India, the influenza vaccine has not yet been offered through immunization programs, owing to the lack of sufficient safety data for pregnant Indian women. METHODS: This cross-sectional observational study enrolled 558 women admitted to the obstetrics ward of a civic hospital in Pune. Study-related information was obtained from the participants through hospital records and interviews using structured questionnaires. Univariate and multivariable analysis was used, and the chi-square test with adjusted odds ratio was estimated to account for vaccine exposure and the temporal nature of each outcome, respectively. RESULTS: Women not vaccinated against influenza during pregnancy had a higher risk of delivering very LBW infants, and possible protective effects were suggested (AOR 2.29, 95% CI 1.03 to 5.58, p = 0.03). No association was observed between maternal influenza vaccination for Caesarean section (LSCS) (AOR 0.97, 95% CI, 0.78, 1.85), stillbirth (AOR 1.8, 95% CI 0.18, 24.64) and NICU admission (AOR, 0.87, 0.29 to 2.85), and congenital anomaly (AOR, 0.81, 0.10 to 3.87). INTERPRETATION: These results show that the influenza vaccine administered during pregnancy is safe and might lower the risk of negative birth outcomes.

A Current Perspective on the Potential of Nanomedicine for Anti-Tuberculosis Therapy.

Tuberculosis (TB) is one of the ten infectious diseases that cause the highest amount of human mortality and morbidity. This infection, which is caused by a single pathogen, Mycobacterium tuberculosis, kills over a million people every year. There is an emerging problem of antimicrobial resistance in TB that needs urgent treatment and management. Tuberculosis treatment is complicated by its complex drug regimen, its lengthy duration and the serious side-effects caused by the drugs required. There are a number of critical issues around drug delivery and subsequent intracellular bacterial clearance. Drugs have a short lifespan in systemic circulation, which limits their activity. Nanomedicine in TB is an emerging research area which offers the potential of effective drug delivery using nanoparticles and a reduction in drug doses and side-effects to improve patient compliance with the treatment and enhance their recovery. Here, we provide a minireview of anti-TB treatment, research progress on nanomedicine and the prospects for future applications in developing innovative therapies.

Review on the Recent Advances on Typhoid Vaccine Development and Challenges Ahead.

Control of Salmonella enterica serovar typhi (S. typhi), the agent of typhoid fever, continues to be a challenge in many low- and middle-income countries. The major transmission route of S. typhi is fecal-oral, through contaminated food and water; thus, the ultimate measures for typhoid fever prevention and control include the provision of safe water, improved sanitation, and hygiene. Considering the increasing evidence of the global burden of typhoid, particularly among young children, and the long-term horizon for sustained, effective water and sanitation improvements in low-income settings, a growing consensus is to emphasize preventive vaccination. This review provides an overview of the licensed typhoid vaccines and vaccine candidates under development, and the challenges ahead for introduction.

Current and future cholera vaccines.

Cholera remains a major global public health problem that is primarily linked to insufficient access to safe water and proper sanitation. Oral Cholera Vaccine (OCV) has been recommended as an additional public health tool along with WASH in cholera endemic countries and in areas at risk for outbreaks. The new generation OCV is safe and offers good protection in older children and adults while limited protection in younger children less than five years of age has been observed. The combination of direct vaccine protection and vaccine herd immunity effects makes OCV highly cost-effective and, therefore, attractive for use in developing countries. Additionally, in recent studies OCV was safe in pregnant women, supporting its use in pregnant women in cholera endemic countries. However, knowledge need to be developed for current vaccines for their prolonged duration of protection and vaccines need improvements for better immune response in younger children. A single dose vaccination regimen would be more cost-effective and easier to deliver. Recent approaches have focused on designing genetically attenuated cholera strains for use in single-dose cholera vaccines. The global demand for OCV has been boosted by the WHO recommendation to use OCV and is driven largely by epidemics and outbreaks and has been increasing due to the availability of cheaper easy-to-use vaccines, feasibility of mass OCV vaccination campaigns, demonstration of protection to underserved population in precarious situations, and vaccine costs being borne by Gavi (Vaccine Alliance). For rapid access in emergency and equitable distribution of OCV in cholera-endemic low-income countries, a global OCV stockpile was established in 2013 with support from the Global Alliance for Vaccines and Immunization. The three WHO-prequalified vaccines are Dukoral®, Shanchol™, Euvichol® (and Euvichol® Plus presentation), the latter two being included in the stockpile.

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life.

UNLABELLED: Rotavirus gastroenteritis is one of the leading causes of diarrhea in Indian children less than 2 years of age. The 116E rotavirus strain was developed as part of the Indo-US Vaccine Action Program and has undergone efficacy trials. This paper reports the efficacy and additional safety data in children up to 2 years of age. In a double-blind placebo controlled multicenter trial, 6799 infants aged 6-7 weeks were randomized to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. The primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. We randomly assigned 4532 and 2267 subjects to receive vaccine and placebo, respectively, with over 96% subjects receiving all three doses of the vaccine or placebo. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. The overall incidence of severe RVGE per 100 person years was 1.3 in the vaccine group and 2.9 in the placebo recipients. Vaccine efficacy against severe rotavirus gastroenteritis in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; p<0.0001); vaccine efficacy in the second year of life of 48.9% (95% CI 17.4 to 68.4; p=0.0056) was only marginally less than in the first year of life [56.3% (95% CI 36.7 to 69.9; p<0.0001)]. The number of infants needed to be immunized to prevent one episode of severe RVGE in the first 2 years of life was 40 (95% CI 28.0 to 63.0) and for RVGE of any severity, it was 21 (95% CI 16.0 to 32.0). Serious adverse events were observed at the same rates in the two groups. None of the eight intussusception events occurred within 30 days of a vaccine dose and all were reported only after the third dose. The sustained efficacy of the 116E in the second year of life is reassuring. CLINICAL TRIAL REGISTRY: The trial is registered with Clinical Trial Registry-India (# CTRI/2010/091/000102) and Clinicaltrials.gov (# NCT01305109).

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. METHODS: We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). FINDINGS: 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product. INTERPRETATION: Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants. FUNDING: Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.