Continued emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin oral poliovirus vaccines (OPVs) has stimulated development of two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence. We aimed to assess safety and immunogenicity of the two novel OPV candidates compared with a monovalent Sabin OPV in children and infants. We did two single-centre, multi-site, partly-masked, randomised trials in healthy cohorts of children (aged 1-4 years) and infants (aged 18-22 weeks) in Panama: a control phase 4 study with monovalent Sabin OPV2 before global cessation of monovalent OPV2 use, and a phase 2 study with low and high doses of two novel OPV2 candidates. All participants received one OPV2 vaccination and subsets received two doses 28 days apart. Parents reported solicited and unsolicited adverse events. Type 2 poliovirus neutralising antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days post-vaccination. Primary objectives were to assess safety in all participants and non-inferiority of novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants (non-inferiority margin 10%). These studies were registered with ClinicalTrials.gov, NCT02521974 and NCT03554798. The control study took place between Oct 23, 2015, and April 29, 2016, and the subsequent phase 2 study between Sept 19, 2018, and Sept 30, 2019. 150 children (50 in the control study and 100 of 129 assessed for eligibility in the novel OPV2 study) and 684 infants (110 of 114 assessed for eligibility in the control study and 574 of 684 assessed for eligibility in the novel OPV2 study) were enrolled and received at least one study vaccination. Vaccinations were safe and well tolerated with no causally associated serious adverse events or important medical events in any group. Solicited and unsolicited adverse events were overwhelmingly mild or moderate irrespective of vaccine or dose. Nearly all children were seroprotected at baseline, indicating high baseline immunity. In children, the seroprotection rate 28 days after one dose was 100% for monovalent OPV2 and both novel OPV2 candidates. In infants at day 28, 91 (94% [95% CI 87-98]) of 97 were seroprotected after receiving monovalent OPV2, 134 (94% [88-97]) of 143 after high-dose novel OPV2-c1, 122 (93% [87-97]) of 131 after low-dose novel OPV2-c1, 138 (95% [90-98]) of 146 after high-dose novel OPV2-c2, and 115 (91% [84-95]) of 127 after low-dose novel OPV2-c2. Non-inferiority was shown for low-dose and high-dose novel OPV2-c1 and high-dose novel OPV2-c2 despite monovalent OPV2 recipients having higher baseline immunity. Both novel OPV2 candidates were safe, well tolerated, and immunogenic in children and infants. Novel OPV2 could be an important addition to our resources against poliovirus given the current epidemiological situation. Fighting Infectious Diseases in Emerging Countries and Bill & Melinda Gates Foundation.

Invasive meningococcal disease is a serious infection that occurs worldwide. Neisseria meningitidis remains one of the leading causes of bacterial meningitis in all ages. Despite the availability of safe and effective vaccines against invasive meningococcal disease, few countries in Latin America implemented routine immunization programs with these vaccines. The Americas Health Foundation along with Fighting Infectious Disease in Emerging Countries recently sponsored a consensus conference. Six experts in infectious diseases from across the region addressed questions related to this topic and formulated the following recommendations: (1) standardized passive and active surveillance systems should be developed and carriage studies are mandatory; (2) a better understanding of the incidence, case fatality rates and prevalent serogroups in Latin America is needed; (3) countries should make greater use of the polymerase chain reaction assays to improve the sensitivity of diagnosis and surveillance of invasive meningococcal disease; (4) vaccines with broader coverage and more immunogenicity are desirable in young infants; (5) prevention strategies should include immunization of young infants and catch-up children and adolescents and (6) because of the crowded infant immunization schedule, the development of combined meningococcal vaccines and the coadministration with other infant vaccines should be explored.

Environmental surveillance was recommended for risk mitigation in a novel oral polio vaccine-2 (nOPV2) clinical trial (M5-ABMG) to monitor excretion, potential circulation, and loss of attenuation of the two nOPV2 candidates. The nOPV2 candidates were developed to address the risk of poliovirus (PV) type 2 circulating vaccine-derived poliovirus (cVDPV) as part of the global eradication strategy. Between November 2018 and January 2020, an environmental surveillance study for the clinical trial was conducted in parallel to the M5-ABMG clinical trial at five locations in Panama. The collection sites were located upstream from local treatment plant inlets, to capture the excreta from trial participants and their community. Laboratory analyses of 49 environmental samples were conducted using the two-phase separation method. Novel OPV2 strains were not detected in sewage samples collected during the study period. However, six samples were positive for Sabin-like type 3 PV, two samples were positive for Sabin-like type 1 PV, and non-polio enteroviruses NPEVs were detected in 27 samples. One of the nOPV2 candidates has been granted Emergency Use Listing by the World Health Organization and initial use started in March 2021. This environmental surveillance study provided valuable risk mitigation information to support the Emergency Use Listing application.

In Latin America, adult influenza is a serious disease that exacts a heavy burden in terms of morbidity, mortality, and cost. Although much has been written about the disease itself, relatively little information has been compiled on what could be done to reduce its impact across the region, particularly from the perspective of clinicians with first-hand experience in confronting its effects. To fill this data gap, in 2011, the Pan American Health and Education Foundation (PAHEF) and the U.S.-based nonprofit Fighting Infectious Diseases in Emerging Countries (FIDEC) organized a conference and convened a panel of Latin American scientist-clinicians with experience and expertise in adult influenza in the region tol) discuss the major issues related to the disease and 2) develop and produce a consensus statement summarizing its impact as well as current efforts to diagnose, prevent, and treat it. The consensus panel concluded a more concerted and better-coordinated effort was needed to reduce the adverse impact of seasonal influenza and future pandemics, including more surveillance, more active involvement by both governmental and nongovernmental organizations, and a much greater effort to vaccinate more adults, especially those at high risk of contracting the disease. In addition, a new approach for diagnosing influenza was recommended.

In the context of polio eradication, novel oral polio vaccines for type 2 (nOPV2) were developed, and types 1 and 3 polioviruses are being developed. We aimed to generate trivalent oral poliovirus vaccine (tOPV) safety and immunogenicity data as a reference for comparing with novel OPV formulations. This was a single-center, open-label, phase 4 study in March 2016 in the Dominican Republic with healthy children previously vaccinated with ≥3 doses of tOPV receiving one dose of tOPV and vaccine-naïve infants receiving 3 doses of tOPV. Safety and immunogenicity were assessed. No serious adverse reactions or important medical reactions were reported. Seroconversion (SC) rates at Day 28 in children were 32.7%, 36.7%, and 46.9% for types 1, 2, and 3, respectively, and seroprotection (SP) rates 28 days after one dose increased from 89.8% at baseline to 93.9%, 98.0% to 100%, and 83.7% to 98.0% for types 1, 2, and 3, respectively. In infants, SC rates were 88.5%, 98.1%, and 96.2% for types 1, 2, and 3, respectively. SP rates at Day 84 were 93.3%, 100%, and 96.2% for types 1, 2, and 3, respectively. This information can be used as a reference to compare with novel monovalent or trivalent OPVs under development.