The evidence base for rotavirus vaccination in India: Current status, future needs.

Rotavirus is a leading cause of severe diarrheal disease in infants and young children worldwide. Vaccination offers the best protection against this disease, and two rotavirus vaccines were developed in India and included in its routine immunization program. The Government of India's decision to adopt this intervention was supported by a solid base of evidence from clinical trials, as well as substantial research regarding rotavirus disease burden and the potential health and economic value of immunization.

Effect of Non-Rotavirus Enteric Infections on Vaccine Efficacy in a ROTASIIL Clinical Trial.

This study examined the relative proportion of enteric pathogens associated with severe gastroenteritis (GE) among children younger than 2 years in a phase III efficacy trial of the ROTASIIL® vaccine in India, evaluated the impact of co-infections on vaccine efficacy (VE), and characterized the association between specific pathogens and the clinical profile of severe GE. Stored stool samples collected from cases of severe GE in the phase III trial were tested by quantitative polymerase chain reaction using TaqMan™ Array Cards. Etiology was attributed by calculating the adjusted attributable fraction (AF) for each pathogen.

Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines.

Introduction: Recombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PT) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates.

Methods: This is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PT and 1 µg FHA (ap1), or Td combined with ap1 (Tdap1), or with 2 µg PT and 5 µg FHA (Tdap2), or with 5 µg PT and 5 µg FHA (TdaP5 Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8 Boostrix™, GSK, Belgium), either in the second or third trimester of gestation.

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in pregnant women.

Introduction: Despite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns. Highly immunogenic vaccines containing genetically inactivated pertussis toxin (PT) and filamentous hemagglutinin (FHA) may generate comparable anti-PT antibody concentrations, even at lower doses, to chemically inactivated acellular pertussis vaccines (Tdap) shown effective for maternal immunization.

Methods: This phase 2 randomized, observer-blind, active-controlled non-inferiority trial was conducted in healthy Thai pregnant women randomly assigned to receive one dose of low-dose recombinant pertussis-only vaccine containing 1 µg PT and 1 µg FHA (ap1), or tetanus, reduced-dose diphtheria combined with ap1 (Tdap1), or combined with 2 µg PT and 5 µg FHA (Tdap2), or with 5 µg PT and 5 µg FHA (TdaP5, Boostagen®) or comparator containing 8 µg of chemically inactivated pertussis toxoid, 8 µg FHA, and 2.

Pregnancy exposure registries for drugs and vaccines in low-income and middle-income countries: scoping review protocol.

Introduction: Data regarding the safety of drugs and vaccines in pregnant women are typically unavailable before licensure. Pregnancy exposure registries (PERs) are an important source of postmarketing safety information. PERs in low-income and middle-income countries (LMICs) are uncommon but can provide valuable safety data regarding their distinct contexts and will become more relevant as the introduction and use of new drugs and vaccines in pregnancy increase worldwide.

Introducing ROTAVAC® to the occupied Palestinian Territories: Impact on diarrhea incidence, rotavirus prevalence and genotype composition.

Background: Rotavirus infection remains an important cause of morbidity and mortality in children. The introduction of vaccination programs in more than 100 countries has contributed to a decrease in hospitalizations and mortality. This study investigates the epidemiological impact of the rotavirus vaccine ROTAVAC® in the Palestinian Territories, the first country to switch from ROTARIX® to this new vaccine.

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in women of childbearing age.

Background: A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PT) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women.

Methods: A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PT and 1 μg FHA (ap1), tetanus, reduced-dose diphtheria (Td) combined to ap1 (Tdap1) or combined to recombinant pertussis containing 2 μg PT and 5 μg FHA (Tdap2), or one dose of licensed recombinant TdaP vaccine containing 5 μg PT and 5 μg FHA (Boostagen®, TdaP5) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PT), 8 μg FHA, and 2.5 μg pertactin (PRN) (Boostrix, Tdap8).

Vaccines to Prevent Meningitis: Historical Perspectives and Future Directions.

Despite advances in the development and introduction of vaccines against the major bacterial causes of meningitis, the disease and its long-term after-effects remain a problem globally. The Global Roadmap to Defeat Meningitis by 2030 aims to accelerate progress through visionary and strategic goals that place a major emphasis on preventing meningitis via vaccination. Global vaccination against type B (Hib) is the most advanced, such that successful and low-cost combination vaccines incorporating Hib are broadly available.

Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis.

Background: Although a positive association has been established, it is unclear whether lower respiratory tract infections (LRTIs) with respiratory syncytial virus (RSV) cause chronic wheezing illnesses. If RSV-LRTI were causal, we would expect RSV-LRTI prevention to reduce the incidence of chronic wheezing illnesses in addition to reducing acute disease. We aimed to evaluate the strength of evidence for a causal effect of RSV-LRTI on subsequent chronic wheezing illness to inform public health expectations for RSV vaccines.

Zika Virus in West Africa: A Seroepidemiological Study between 2007 and 2012.

According to the World Health Organization, the entire African continent is at risk of a Zika outbreak. To increase data availability on the epidemiology of Zika virus circulation in Africa, we evaluated the immunity to Zika virus in a selected cohort of subjects from West Africa between 2007 and 2012. Human serum samples were collected in 2007 and in 2011/2012 from a cohort of 2-29-year-old subjects from Mali, Senegal, and The Gambia.

Long-term immunity against yellow fever in children vaccinated during infancy: a longitudinal cohort study.

Background: A single dose of vaccine against yellow fever is routinely administered to infants aged 9-12 months under the Expanded Programme on Immunization, but the long-term outcome of vaccination in this age group is unknown. We aimed to evaluate the long-term persistence of neutralising antibodies to yellow fever virus following routine vaccination in infancy.

Methods: We did a longitudinal cohort study, using a microneutralisation assay to measure protective antibodies against yellow fever in Malian and Ghanaian children vaccinated around age 9 months and followed up for 4·5 years (Mali), or 2·3 and 6·0 years (Ghana).

Maternal immunization in Malawi: A mixed methods study of community perceptions, programmatic considerations, and recommendations for future planning.

Background: Safe, effective vaccines are given to pregnant women to protect their infants and/or themselves against certain infectious agents; however, apart from tetanus vaccination, maternal immunization in low- and middle-income countries (LMICs) remains low. Tetanus toxoid vaccine is integrated into antenatal care services in Malawi with high coverage and provides an opportunity to identify factors that facilitate successful immunization delivery to pregnant women in LMICs.

Methods: PATH and the University of Malawi's Centre for Social Research conducted a mixed-methods study in 2015 to document community perceptions of maternal immunization, using tetanus vaccine as an example, and to identify factors perceived to be important to successfully introducing other maternal vaccines, such as influenza vaccine, in Malawi.

Informing randomized clinical trials of respiratory syncytial virus vaccination during pregnancy to prevent recurrent childhood wheezing: A sample size analysis.

Background: Early RSV illness is associated with wheeze-associated disorders in childhood. Candidate respiratory syncytial virus (RSV) vaccines may prevent acute RSV illness in infants. We investigated the feasibility of maternal RSV vaccine trials to demonstrate reductions in recurrent childhood wheezing in general paediatric populations.

Forecasting demand for maternal influenza immunization in low- and lower-middle-income countries.

Immunization of pregnant women against seasonal influenza remains limited in low- and lower-middle-income countries despite being recommended by the World Health Organization (WHO). The WHO/PATH Maternal Influenza Immunization Project was created to identify and address obstacles to delivering influenza vaccines to pregnant women in low resource setting. To gain a better understanding of potential demand from this target group, we developed a model simulating pregnant women populations eligible for vaccination during antenatal care (ANC) services in all low- and lower-middle-income countries.

Implementation of maternal influenza immunization in El Salvador: Experiences and lessons learned from a mixed-methods study.

Introduction: The World Health Organization (WHO) recommends that countries prioritize pregnant women for influenza vaccination, yet few low- or middle-income countries (LMICs) have implemented maternal influenza immunization programs. To inform vaccine decision-making and operational planning in LMICs, there is a need to document and share experiences from countries that provide seasonal influenza vaccine to pregnant women, particularly those with high coverage, like El Salvador.

Methods: In 2015 and 2016, PATH and country researchers conducted a mixed-methods study to document the experience and lessons learned from maternal influenza immunization delivery and acceptance in El Salvador as part of a collaborative effort between WHO and PATH.

Global influenza seasonality to inform country-level vaccine programs: An analysis of WHO FluNet influenza surveillance data between 2011 and 2016.

By analyzing publicly available surveillance data from 2011-2016, we produced country-specific estimates of seasonal influenza activity for 118 countries in the six World Health Organization regions. Overall, the average country influenza activity period was 4.7 months.

Maternal influenza immunization in Malawi: Piloting a maternal influenza immunization program costing tool by examining a prospective program.

Background: This costing study in Malawi is a first evaluation of a Maternal Influenza Immunization Program Costing Tool (Costing Tool) for maternal immunization. The tool was designed to help low- and middle-income countries plan for maternal influenza immunization programs that differ from infant vaccination programs because of differences in the target population and potential differences in delivery strategy or venue.

Methods: This analysis examines the incremental costs of a prospective seasonal maternal influenza immunization program that is added to a successful routine childhood immunization and antenatal care program.

Incidence of laboratory-confirmed influenza disease among infants under 6 months of age: a systematic review.

Objectives: The aim of this systematic review was to assess incidence rates of laboratory-confirmed influenza (LCI) outcomes among infants under 6 months of age.

Design: Systematic literature search and review of indexed studies in PubMed, EMBASE, the Cochrane Library and CINAHL Plus from inception to 19 April 2017.

Setting: Population-based estimates from community or hospital settings.

Influenza epidemiology and immunization during pregnancy: Final report of a World Health Organization working group.

From 2014 to 2017, the World Health Organization convened a working group to evaluate influenza disease burden and vaccine efficacy to inform estimates of maternal influenza immunization program impact. The group evaluated existing systematic reviews and relevant primary studies, and conducted four new systematic reviews. There was strong evidence that maternal influenza immunization prevented influenza illness in pregnant women and their infants, although data on severe illness prevention were lacking.

Standardization of Laboratory Methods for the PERCH Study.

The Pneumonia Etiology Research for Child Health study was conducted across 7 diverse research sites and relied on standardized clinical and laboratory methods for the accurate and meaningful interpretation of pneumonia etiology data. Blood, respiratory specimens, and urine were collected from children aged 1-59 months hospitalized with severe or very severe pneumonia and community controls of the same age without severe pneumonia and were tested with an extensive array of laboratory diagnostic tests. A standardized testing algorithm and standard operating procedures were applied across all study sites.

Incidence of influenza virus infection among pregnant women: a systematic review.

Background: The World Health Organization (WHO) considers pregnant women to be a risk group for severe influenza disease. We conducted a systematic review to evaluate influenza disease incidence in pregnant women in order to inform estimates of influenza vaccine impact for low-resource countries.

Methods: We performed electronic literature searches, targeting studies on the following outcomes in pregnant women: attack rate, hospitalization rate, intensive care unit admission rate, mortality rate, and disability-adjusted life years lost.