Consequences of Shigella infection in young children: a systematic review.

Objectives: We conducted a systematic review of the longitudinal consequences of Shigella infection in children to inform the value proposition for an effective vaccine.

Methods: We searched PubMed and Embase for studies published from January 01, 1980 to December 12, 2022 and conducted in low- and middle-income countries that included longitudinal follow-up after Shigella detection among children aged <5 years, irrespective of language. We collected data on all outcomes subsequent to Shigella detection, except mortality.

Pivotal Vaccine Efficacy Trials-Study Design Considerations from a Vaccine Trial Design Working Group.

Vaccine candidates for are approaching phase 3 clinical trials in the target population of young children living in low- and middle-income countries. Key study design decisions will need to be made to maximize the success of such trials and minimize the time to licensure and implementation. We convened an ad hoc working group to identify the key aspects of trial design that would meet the regulatory requirements to achieve the desired indication of prevention of moderate or severe shigellosis due to strains included in the vaccine.

The Burden of Typhoid Fever in Sub-Saharan Africa: A Perspective.

While typhoid fever has largely been eliminated in high-income regions which have developed modern water, sanitation, and hygiene facilities, it remains a significant public health burden resulting in morbidity and mortality among millions of individuals in resource-constrained settings. Prevention and control efforts are needed that integrate several high-impact interventions targeting facilities and infrastructure, including those addressing improvements in sanitation, access to safe water, and planned urbanization, together with parallel efforts directed at effective strategies for use of typhoid conjugate vaccines (TCV). The use of TCVs is a critical tool with the potential of having a rapid impact on typhoid fever disease burden; their introduction will also serve as an important strategy to combat evolving antimicrobial resistance to currently available typhoid fever treatments.

The future of Japanese encephalitis vaccination: expert recommendations for achieving and maintaining optimal JE control.

Vaccines against Japanese encephalitis (JE) have been available for decades. Currently, most JE-endemic countries have vaccination programs for their at-risk populations. Even so, JE remains the leading recognized cause of viral encephalitis in Asia.

Streptococcus pyogenes pbp2x Mutation Confers Reduced Susceptibility to β-Lactam Antibiotics.

Two near-identical clinical Streptococcus pyogenes isolates of emm subtype emm43.4 with a pbp2x missense mutation (T553K) were detected. Minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin were 8-fold higher, and the MIC for cefotaxime was 3-fold higher than for near-isogenic control isolates, consistent with a first step in developing β-lactam resistance.

Demonstrating vaccine effectiveness during a waning epidemic: A WHO/NIH meeting report on approaches to development and licensure of Zika vaccine candidates.

Since its peak in early 2016, the incidence of Zika virus (ZIKV) cases has declined to such low levels that Phase 3 field efficacy trials may be infeasible. While great progress was made to rapidly advance several vaccine candidates into Phase 1 and 2 clinical trials, in the absence of sustained viral transmission it may be difficult to evaluate the effectiveness of ZIKV vaccine candidates by conducting traditional clinical disease endpoint efficacy studies. However, ZIKV is still circulating at low levels in some areas and is likely to re-emerge in naïve populations or in sites of prior epidemics once population immunity wanes.

Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines.

Japanese Encephalitis Surveillance and Immunization - Asia and Western Pacific Regions, 2016.

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2).

Status of vaccine research and development of vaccines for dengue.

This review on the dengue vaccine pipeline was a solicited article and drafted based on the pre-defined template for PD-VAC.

Active Surveillance for Adverse Events After a Mass Vaccination Campaign With a Group A Meningococcal Conjugate Vaccine (PsA-TT) in Mali.

Background: The monovalent meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed for use in the "meningitis belt" of sub-Saharan Africa. Mali was 1 of 3 countries selected for early introduction. As this is a new vaccine, postlicensure surveillance is particularly important to identify and characterize possible safety issues.

Lessons Learned From Enhancing Vaccine Pharmacovigilance Activities During PsA-TT Introduction in African Countries, 2010-2013.

Background: The rollout of the group A meningococcal vaccine, PsA-TT, in Africa's meningitis belt countries represented the first introduction of a vaccine specifically designed for this part of the world. During the first year alone, the number of people who received the vaccine through mass vaccination campaigns was several hundredfold higher than that of subjects who participated in the closely monitored clinical trials. Implementation of a system to identify rare but potentially serious vaccine reactions was therefore a high priority in the design and implementation of those campaigns.

Next generation dengue vaccines: A review of the preclinical development pipeline.

Dengue represents a significant and growing public health problem across the globe, with approximately half of the world's population at risk. The increasing and expanding burden of dengue has highlighted the need for new tools to prevent dengue, including development of dengue vaccines. Recently, the first dengue vaccine candidate was evaluated in Phase 3 clinical trials, and other vaccine candidates are under clinical evaluation.

Rationale for WHO's new position calling for prompt reporting and public disclosure of interventional clinical trial results.

Vasee Moorthy and colleagues explain why the WHO is calling for public disclosure of clinical trial results.

MALVAC 2012 scientific forum: accelerating development of second-generation malaria vaccines.

The World Health Organization (WHO) convened a malaria vaccines committee (MALVAC) scientific forum from 20 to 21 February 2012 in Geneva, Switzerland, to review the global malaria vaccine portfolio, to gain consensus on approaches to accelerate second-generation malaria vaccine development, and to discuss the need to update the vision and strategic goal of the Malaria Vaccine Technology Roadmap. This article summarizes the forum, which included reviews of leading Plasmodium falciparum vaccine candidates for pre-erythrocytic vaccines, blood-stage vaccines, and transmission-blocking vaccines. Other major topics included vaccine candidates against Plasmodium vivax, clinical trial site capacity development in Africa, trial design considerations for a second-generation malaria vaccine, adjuvant selection, and regulatory oversight functions including vaccine licensure.

Immunization-safety monitoring systems for the 2009 H1N1 monovalent influenza vaccination program.

The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.

Attitudes and beliefs of parents concerned about vaccines: impact of timing of immunization information.

Objectives: To determine if giving vaccine-information materials before the 2-month vaccination visit to mothers with concerns about vaccine safety positively changed their attitudes and beliefs about vaccine safety.

Methods: Mothers who indicated concerns about infant vaccinations were recruited from 2 separate sites in Tennessee and California and were given vaccine information at 1 of 3 times: during a prenatal visit; a 1-week postpartum well-child visit; or a 2-month vaccination visit. A separate group of concerned mothers was assigned to be followed longitudinally at all 3 time points and was analyzed separately.

The association between intentional delay of vaccine administration and timely childhood vaccination coverage.

Objectives: We evaluated the association between intentional delay of vaccine administration and timely vaccination coverage.

Methods: We used data from 2,921 parents of 19- to 35-month-old children that included parents' reports of intentional delay of vaccine administration. Timely vaccination was defined as administration with > or = 4 doses of diphtheria, tetanus, and pertussis; > or = 3 doses of polio vaccine; > or = 1 dose of measles, mumps, and rubella vaccine; > or = 3 doses of Haemophilus influenzae type b vaccine; > or = 3 doses of hepatitis B vaccine; and > or = 1 dose of varicella vaccine by 19 months of age, as reported by vaccination providers.

Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila.

Ionotropic glutamate receptors (iGluRs) mediate neuronal communication at synapses throughout vertebrate and invertebrate nervous systems. We have characterized a family of iGluR-related genes in Drosophila, which we name ionotropic receptors (IRs). These receptors do not belong to the well-described kainate, AMPA, or NMDA classes of iGluRs, and they have divergent ligand-binding domains that lack their characteristic glutamate-interacting residues.

An essential role for a CD36-related receptor in pheromone detection in Drosophila.

The CD36 family of transmembrane receptors is present across metazoans and has been implicated biochemically in lipid binding and transport. Several CD36 proteins function in the immune system as scavenger receptors for bacterial pathogens and seem to act as cofactors for Toll-like receptors by facilitating recognition of bacterially derived lipids. Here we show that a Drosophila melanogaster CD36 homologue, Sensory neuron membrane protein (SNMP), is expressed in a population of olfactory sensory neurons (OSNs) implicated in pheromone detection.