The impact of alternative delivery strategies for novel tuberculosis vaccines in low-income and middle-income countries: a modelling study.

BACKGROUND: Tuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks resulting from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low-income and middle-income countries (LMICs) in several delivery scenarios. METHODS: We calibrated a tuberculosis model to 105 LMICs (accounting for 93% of global incidence). Vaccine scenarios were implemented as the base-case (routine vaccination of those aged 9 years and one-off vaccination for those aged 10 years and older, with country-specific introduction between 2028 and 2047, and 5-year scale-up to target coverage); accelerated scale-up similar to the base-case, but with all countries introducing vaccines in 2025, with instant scale-up; and routine-only (similar to the base-case, but including routine vaccination only). Vaccines were assumed to protect against disease for 10 years, with 50% efficacy. FINDINGS: The base-case scenario would prevent 44·0 million (95% uncertainty range 37·2-51·6) tuberculosis cases and 5·0 million (4·6-5·4) tuberculosis deaths before 2050, compared with equivalent estimates of cases and deaths that would be predicted to occur before 2050 with no new vaccine introduction (the baseline scenario). The accelerated scale-up scenario would prevent 65·5 million (55·6-76·0) cases and 7·9 million (7·3-8·5) deaths before 2050, relative to baseline. The routine-only scenario would prevent 8·8 million (95% uncertainty range 7·6-10·1) cases and 1·1 million (0·9-1·2) deaths before 2050, relative to baseline. INTERPRETATION: Our results suggest novel tuberculosis vaccines could have substantial impact, which will vary depending on delivery strategy. Including a one-off vaccination campaign will be crucial for rapid impact. Accelerated introduction-at a pace similar to that seen for COVID-19 vaccines-would increase the number of lives saved before 2050 by around 60%. Investment is required to support vaccine development, manufacturing, prompt introduction, and scale-up. FUNDING: WHO (2020/985800-0). TRANSLATIONS: For the French, Spanish, Italian and Dutch translations of the abstract see Supplementary Materials section.

Durability of Vaccine-Induced and Natural Immunity Against COVID-19: A Narrative Review.

Vaccines developed against SARS-CoV-2 have proven to be highly effective in preventing symptomatic infection. Similarly, prior infection with SARS-CoV-2 has been shown to provide substantial protection against reinfection. However, it has become apparent that the protection provided to an individual after either vaccination or infection wanes over time. Waning protection is driven by both waning immunity over time since vaccination or initial infection, and the evolution of new variants of SARS-CoV-2. Both antibody and T/B-cells levels have been investigated as potential correlates of protection post-vaccination or post-infection. The activity of antibodies and T/B-cells provide some potential insight into the underlying causes of waning protection. This review seeks to summarise what is currently known about the waning of protection provided by both vaccination and/or prior infection, as well as the current information on the respective antibody and T/B-cell responses.

End-point definition and trial design to advance tuberculosis vaccine development.

Tuberculosis (TB) remains a leading infectious cause of death worldwide and the coronavirus disease 2019 pandemic has negatively impacted the global TB burden of disease indicators. If the targets of TB mortality and incidence reduction set by the international community are to be met, new more effective adult and adolescent TB vaccines are urgently needed. There are several new vaccine candidates at different stages of clinical development. Given the limited funding for vaccine development, it is crucial that trial designs are as efficient as possible. Prevention of infection (POI) approaches offer an attractive opportunity to accelerate new candidate vaccines to advance into large and expensive prevention of disease (POD) efficacy trials. However, POI approaches are limited by imperfect current tools to measure Mycobacterium tuberculosis infection end-points. POD trials need to carefully consider the type and number of microbiological tests that define TB disease and, if efficacy against subclinical (asymptomatic) TB disease is to be tested, POD trials need to explore how best to define and measure this form of TB. Prevention of recurrence trials are an alternative approach to generate proof of concept for efficacy, but optimal timing of vaccination relative to treatment must still be explored. Novel and efficient approaches to efficacy trial design, in addition to an increasing number of candidates entering phase 2-3 trials, would accelerate the long-standing quest for a new TB vaccine.

Impact of COVID-19 Disruptions on Global BCG Coverage and Paediatric TB Mortality: A Modelling Study.

The impact of COVID-19 disruptions on global Bacillus Calmette-Guérin (BCG) coverage and paediatric tuberculosis (TB) mortality is still unknown. To fill this evidence-gap and guide mitigation measures, we estimated the impact of COVID-19 disruptions on global BCG coverage and paediatric TB mortality. First, we used data from multiple sources to estimate COVID-19-disrupted BCG vaccination coverage. Second, using a static mathematical model, we estimated the number of additional paediatric TB deaths in the first 15 years of life due to delayed/missed vaccinations in 14 scenarios-varying in duration of disruption, and magnitude and timing of catch-up. We estimated a 25% reduction in global BCG coverage within the disruption period. The best-case scenario (3-month disruption, 100% catch-up within 3 months) resulted in an additional 886 (0.5%) paediatric TB deaths, and the worst-case scenario (6-month disruption with no catch-up) resulted in an additional 33,074 (17%) deaths. The magnitude of catch-up was found to be the most influential variable in minimising excess paediatric TB mortality. Our results show that ensuring catch-up vaccination of missed children is a critical priority, and delivery of BCG alongside other routine vaccines may be a feasible way to achieve catch-up. Urgent action is required to support countries with recovering vaccination coverages to minimise paediatric deaths.

Experience from five Asia-Pacific countries during the first wave of the COVID-19 pandemic: Mitigation strategies and epidemiology outcomes.

BACKGROUND: With no vaccines or specific treatments, non-pharmaceutical interventions are the only tools for controlling the human-to-human transmission of the COVID-19 disease, which appeared in Wuhan, China last December and has spread globally since. Here we describe and compare the first-wave mitigation strategies and epidemiology of five Asia-Pacific countries that responded rapidly to the epidemic. METHODS: From January to April 2020, mitigation measures and epidemiological data for Singapore, South Korea, Japan, Taiwan, Hong Kong were screened from official local government websites and a review of investigational studies was conducted. Daily case reports and mitigation measures information were extracted. Epidemiological estimates were calculated and compared between countries. RESULTS: All five countries combined measures, focusing on contact tracing, testing, isolation efforts and healthcare management. Epidemiological data varied temporally and geographically: incubation period ranged 3.9-7.1 days, effective reproduction number at time t (Rt) ranged 0.48-1.5, with intensive care admissions 1-3% of hospitalised patients, and case fatality rates were 0.1-3%. Extrinsic estimates to the virus were lower than global estimates. CONCLUSION: Implemented mitigation strategies in these countries allowed a rapid and successful control or delay of the first COVID-19 pandemic wave. These are valuable examples to inform subsequent waves.

Impact of COVID-19 on routine immunisation in South-East Asia and Western Pacific: Disruptions and solutions.

BACKGROUND: Data on COVID-19-induced disruption to routine vaccinations in the South-East Asia and Western Pacific regions (SEAR/WPR) have been sparse. This study aimed to quantify the impact of COVID-19 on routine vaccinations by country, antigen, and sector (public or private), up to 1 June 2020, and to identify the reasons for disruption and possible solutions. METHODS: Sanofi Pasteur teams from 19 countries in SEAR/WPR completed a structured questionnaire reporting on COVID-19 disruptions for 13-19 routinely delivered antigens per country, based on sales data, government reports, and regular physician interactions. Data were analysed descriptively, disruption causes ranked, and solutions evaluated using a modified public health best practices framework. FINDINGS: 95% (18/19) of countries reported vaccination disruption. When stratified by country, a median of 91% (interquartile range 77-94) of antigens were impacted. Infancy and school-entry age vaccinations were most impacted. Both public and private sector healthcare providers experienced disruptions. Vaccination rates had not recovered for 39% of impacted antigens by 1 June 2020. Fear of infection, movement/travel restrictions, and limited healthcare access were the highest-ranked reasons for disruption. Highest-scoring solutions were separating vaccination groups from unwell patients, non-traditional vaccination venues, virtual engagement, and social media campaigns. Many of these solutions were under-utilised. INTERPRETATION: COVID-19-induced disruption of routine vaccination was more widespread than previously reported. Adaptable solutions were identified which could be implemented in SEAR/WPR and elsewhere. Governments and private providers need to act urgently to improve coverage rates and plan for future waves of the pandemic, to avoid a resurgence of vaccine-preventable diseases. FUNDING: Sanofi Pasteur.

Review of the role of big data and digital technologies in controlling COVID-19 in Asia: Public health interest vs. privacy.

BACKGROUND: Asia has been at the forefront of leveraging big data and digital technologies to strengthen measures against SARS-CoV-2 spread. Understanding strengths and challenges of these new approaches is important to inform improvements and implementation. In this review, we aimed to explore how these tools were utilized in four countries in Asia to facilitate COVID-19 preventative control measures. METHODS: We conducted a pragmatic review of English-language literature and web-based information in Pubmed, MedRxiv, national and international public health institution websites and media sources between 1st January-3rd August 2020 to identify examples of big data and digital technologies to facilitate COVID-19 preventative control measures in Taiwan, South Korea, Hong Kong, and Singapore. Results were summarized narratively by common technological themes, and examples of integration highlighted. RESULTS: Digital tools implemented included real-time epidemiological dashboards, interactive maps of case location, mobile apps for tracing patients' contacts and geofencing to monitor quarantine compliance. Examples of integration of tools included linkage of national health and immigration databases to identify high-risk individuals in Taiwan, and the use of multiple digital surveillance sources to map patients' movements in South Korea. Challenges in balancing privacy and public good were identified. CONCLUSIONS: Digital technologies have facilitated and strengthened traditional public health measures for prevention of SARS-CoV-2 spread in Asia. Resolving issues around privacy concerns would improve future preparedness, implementation speed and uptake of digital measures. The significant technological advances and lessons learned can be adopted or adapted by other countries to ensure public health preparedness for future waves of COVID-19 and other pandemics.