High SARS-CoV-2 attack rates in areas with low detection after community transmission established in Port Vila, Vanuatu, April 2022.

Objective: On 4 March 2022, the first community-acquired case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Vanuatu, with community transmission occurring subsequently. It was expected that the number of notified SARS-CoV-2 cases would be an underestimate of the true infection rate of this outbreak; however, the magnitude of underreporting was unknown. The purpose of this study was to provide a population-based estimate of SARS-CoV-2 infection shortly after the first reports of community transmission, to understand the level of underdetection and undernotification in Vanuatu and thus to inform ongoing prevention and response activities. Methods: We conducted a cross-sectional SARS-CoV-2 prevalence study in two geographical administrative areas in Port Vila, Vanuatu in April 2022. All residents in selected areas were eligible. Trained teams conducted demographic and behavioural interviews and collected nasal specimens. Specimens were tested by polymerase chain reaction. The primary outcomes were the rates of SARS-CoV-2 attack (point prevalence) and cumulative attack, underdetection, notification and household secondary attack. Results: A total of 252 people from 84 households participated. Among 175 people who had a sample collected, 91 were SARS-CoV-2-positive (attack rate 52.0%). Most cases had not been detected before the study (underdetection rate 91.5%). More than half of previously detected cases were notified (notification rate 65.2%). Discussion: Within the first few weeks of community transmission, more than half of participants in the selected areas had evidence of SARS-CoV-2 infection; however, most infections had been undetected. This study provides important information about the rapid spread of novel infectious diseases in Vanuatu.

Comparison of strategies for daily surveillance of international travellers quarantined in Vanuatu, October-December 2020.

Objective: To prevent importation of coronavirus disease 2019 (COVID-19) to Vanuatu, since March 2020, all travellers to the country have been required to complete a 14-day quarantine in a government-designated facility. A short message service (SMS, or "text message") system was developed to collect information on symptoms of COVID-19 among travellers in quarantine. A trial within a cohort study was conducted among travellers arriving to Vanuatu by air from 27 October to 7 December 2020 to assess SMS acceptability, efficiency and utility and whether SMS-based health monitoring was as effective as in-person monitoring in identifying people with COVID-19 symptoms. Methods: Control group participants received standard monitoring (daily in-person visits) and participants in the intervention group received a daily SMS text requesting a response coded for symptom development. Differences between the two groups were determined using χ2 tests. Results: Of the 495 eligible travellers, 423 participated; 170 were allocated to the control group and 253 to the intervention group. At least one return SMS text was received from 50% (107/212) of participants who were confirmed to have received an SMS text. Less than 2% (4/253) of the intervention group and 0% of the control group reported symptoms. Discussion: The SMS intervention had a high level of acceptability. SMS is a useful tool to monitor symptom development among people in quarantine and for broader public health programmes that require follow up.

Mathematical Modeling for Removing Border Entry and Quarantine Requirements for COVID-19, Vanuatu.

The Pacific Island country of Vanuatu is considering strategies to remove border restrictions implemented during 2020 to prevent imported coronavirus disease. We performed mathematical modeling to estimate the number of infectious travelers who had different entry scenarios and testing strategies. Travel bubbles and testing on entry have the greatest importation risk reduction.

Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study.

BACKGROUND: The MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks-15 months of age). METHODS: Five schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone. Routine pediatric vaccines (DTaP-IPV/Hib, PCV7/PCV13, MMR, and varicella) were administered per approved schedules. Proportions of participants with serum bactericidal antibodyassay with human complement (hSBA) titers ≥1:4 and ≥1:8, SBA with baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128, and immune responses against concomitant vaccines were determined. RESULTS: Tenderness and irritability were the most frequent solicited injection site and systemic reactions. Similar proportions of participants achieved an hSBA titer ≥1:8 for all four serogroups regardless of whether 2 or 3 doses were administered in the first year of life. Following a second-year dose, 91-100% of participants achieved the threshold for all 4 serogroups in all schedules regardless of the number of doses in the first year of life. Similar responses were seen with rSBA. Immunogenicity and safety profile of concomitant vaccines was similar whether the MenACYW-TT conjugate vaccine was administered or not. CONCLUSION: MenACYW-TT conjugate vaccine administered with pediatric vaccines is safe and immunogenic regardless of the schedule and does not affect the immunogenicity or safety of the concomitant vaccines. CLINICAL TRIAL REGISTRY: NCT01049035.

Challenges to implementation and strengthening of initial COVID-19 surveillance in Vanuatu: January-April 2020.

The Pacific island nation of Vanuatu is vulnerable to emerging infectious diseases, including epidemics and pandemics; chronic food and water insecurity; and natural hazards, including cyclones, earthquakes, tsunamis, landslides and flooding. In March 2020, the World Health Organization characterized the outbreak of novel coronavirus disease 2019 (COVID-19) as a global pandemic. By the end of April 2020, Vanuatu had reported no confirmed cases of COVID-19. Data from several sources are collected in Vanuatu's COVID-19 surveillance system to provide an overview of the situation, including data from case investigations and management, syndromic surveillance for influenza-like illness, hospital surveillance and laboratory surveillance. Review of data collected from January to the end of April 2020 suggests that there was no sustained increase in influenza-like illness in the community and no confirmed cases were identified. Lessons learnt from the early implementation of surveillance activities, the changing landscape of laboratory testing and pharmaceutical interventions, as well as the global experience, particularly in other Pacific island countries, will inform the refinement of COVID-19 surveillance activities in Vanuatu.

Lessons from COVID-19-free Vanuatu: intensive health operations for Phase 1 of repatriation and quarantine, May-July 2020.

International borders to Vanuatu closed on 23 March 2020 due to the global COVID-19 pandemic. In May-July 2020, the Government of Vanuatu focused on the safe and timely return of citizens and residents while ensuring Vanuatu remained COVID-19 free. Under Phase 1 of repatriation, between 27 May and 23 June 2020, 1522 people arrived in the capital, Port Vila, and were placed in compulsory government-mandated 14-day quarantine in 15 hotels. Pre-arrival health operations included collection of repatriate information, quarantine facility assessments, training for personnel supporting the process, and tabletop and functional exercises with live scenario simulations. During quarantine, health monitoring, mental health assessments and psychosocial support were provided. All repatriates completed 14 days of quarantine. One person developed symptoms consistent with COVID-19 during quarantine but tested negative. Overall health operations were considered a success despite logistical and resource challenges. Lessons learnt were documented during a health sector after-action review held on 22 July 2020. Key recommendations for improvement were to obtain timely receipt of repatriate information before travel, limit the number of repatriates received and avoid the mixing of "travel cohorts," ensure sufficient human resources are available to support operations while maintaining other essential services, establish a command and control structure for health operations, develop training packages and deliver them to all personnel supporting operations, and coordinate better with other sectors to ensure health aspects are considered. These recommendations were applied to further improve health operations for subsequent repatriation and quarantine, with Phase 2 commencing on 1 August 2020.

Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized, multicenter study in infants.

BACKGROUND: Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. METHODS: This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6months (primary vaccination) and 15-18months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. RESULTS: Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines' antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5-96.7% and 99.6-100% of participants achieved anti-PRP levels ≥0.15µg/mL, while 78.3-89.8% and 97.9-99.1% had anti-PRP levels ≥1µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related. CONCLUSION: Hib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3+1 schedule.

Influenza A (H1N1) 2009 two-dose immunization of US children: an observer-blinded, randomized, placebo-controlled trial.

The goal of this pediatric clinical trial was to assess the safety and immunogenicity of two different doses of a monovalent inactivated pandemic (H1N1) 2009 vaccine in US children aged 6 months to 9 years of age. Randomized, observer-blinded, US multicenter phase 2 study assessing 2 doses of vaccine given 21 days apart in 474 children aged 6-35 months or 3-9 years. Children in each age group were randomly assigned to receive either a pandemic (H1N1) 2009 vaccine containing 7.5 or 15 µg of hemagglutinin (HA) or placebo in a 4:4:1 ratio. Primary outcome was hemagglutination inhibition (HI) antibody responses 21 days following each vaccination. Safety was monitored throughout the study. The first dose of either A H1N1 vaccine formulation was more immunogenic in children older than 3 years than in younger children. 45-50% of children aged 6-35 months and 69-75% of children aged 3-9 year-old attained HI titers of ≥ 1:40. A second dose of A H1N1 vaccine further increased HI antibody responses with seroprotection and seroconversion rates reaching 90-99% in both age groups. Interestingly, the pandemic (H1N1) 2009 vaccine formulations elicited similar rates of solicited and unsolicited injection site and systemic reactions as the placebo. The data therefore demonstrate the high level immunogenicity in infants and children of an (H1N1) 2009 influenza vaccine displaying a safety and reactogenicity profile similar to placebo.

Toward greater equity and efficiency in rate setting: the adult residential rehabilitation programs in Massachusetts.

In FY 2001, the Massachusetts Bureau of Substance Abuse Services contracted with 64 adult-only residential rehabilitation facilities. All were paid on an undifferentiated class rate basis at $55 per resident-day. This study uses cost and other information from program-submitted Uniform Financial Reports to measure the facility-specific costs of providing residential rehabilitation services, distinguish the program and site-specific factors responsible for the facility cost differences, and then use this information to suggest alternative, more equitable, and more efficient approaches to rate setting. This analysis finds that a uniform rate structure is substantially inefficient and inequitable.