Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression.

BACKGROUND: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. METHODS: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1-6 months after full vaccination. FINDINGS: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer-BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9-29·8) among people of all ages and 20·7 percentage points (10·2-36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4-41·6) in people of all ages and 32·0 percentage points (11·0-69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1-15·4) in people of all ages and 9·5 percentage points (5·7-14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. INTERPRETATION: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20-30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. FUNDING: Coalition for Epidemic Preparedness Innovations.

Duration of Protection After Vaccination Against Yellow Fever: A Systematic Review and Meta-Analysis.

The duration of protection after a single dose of yellow fever vaccine is a matter of debate. To summarize the current knowledge, we performed a systematic literature review and meta-analysis. Studies on the duration of protection after 1 and ≥2 vaccine doses were reviewed. Data were stratified by time since vaccination. In our meta-analysis, we used random-effects models. We identified 36 studies from 20 countries, comprising more than 17 000 participants aged 6 months to 85 years. Among healthy adults and children, pooled seroprotection rates after single vaccination dose were close to 100% by 3 months and remained high in adults for 5 to 10 years. In children vaccinated before age 2 years, the seroprotection rate was 52% within 5 years after primary vaccination. For immunodeficient persons, data indicate relevant waning. The extent of waning of seroprotection after yellow fever vaccination depends on age and immune status at primary vaccination.

Dengue vaccine development: challenges and prospects.

PURPOSE OF REVIEW: Dengue vaccine development is a high public health priority. To date, no dengue vaccine is in widespread use. Here we review the challenges in dengue development and the latest results for the second-generation dengue vaccines. RECENT FINDINGS: The biggest hurdle is the immunological interaction between the four antigenically distinct dengue serotypes. The advantages of second-generation dengue vaccines are the inclusion of nonstructural proteins of the dengue backbone and a more convenient dosing with reduced numbers of doses needed. SUMMARY: Although dengue-primed individuals can already benefit from vaccination with the first licensed dengue vaccine CYD-TDV, the public health need for the dengue-naive population has not yet been met. The urgent need remains to identify correlates of both protection and enhancement; until such correlates have been identified, all second-generation dengue vaccines still need to go through full phase 3 trials. The 5-year efficacy and safety data for both second-generation dengue vaccines are imminent.

Achieving global equity for COVID-19 vaccines: Stronger international partnerships and greater advocacy and solidarity are needed.

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.

COVID-19 transmission and the safety of air travel during the pandemic: a scoping review.

PURPOSE OF REVIEW: To examine the literature assessing safety of air travel relating to coronavirus disease 2019 (COVID-19) transmission from January 2020 to May 2021. The COVID-19 pandemic has had an unprecedented impact on air travel and global mobility, and various efforts are being implemented to determine a safe way forward. As the pandemic evolves, so do the challenges that force various stakeholders, including the aviation industry, health authorities, and governments, to reassess and adapt their practices to ensure the safety of travellers. RECENT FINDINGS: The literature was reviewed for multiple aspects of air travel safety during the COVID-19 pandemic. Recurring themes that surfaced included the pivotal role of commercial air travel in the geographic spread of COVID-19, the efficacy of travel restrictions and quarantines, inflight transmission risk and the role of preventive measures, the utility of pre and post flight testing, the development of effective vaccines and subsequent challenges of vaccine passports, and the ongoing threat of novel highly transmissible variants. SUMMARY: Much uncertainty lies ahead within the domains of these findings, and ongoing research, discourse and review will be necessary to navigate and determine the future direction and safety of air travel. Recovery will be slow, necessitating innovative, multipronged and collaborative solutions.

Dengue.

Mortality from severe dengue is low, but the economic and resource burden on health services remains substantial in endemic settings. Unfortunately, progress towards development of effective therapeutics has been slow, despite notable advances in the understanding of disease pathogenesis and considerable investment in antiviral drug discovery. For decades antibody-dependent enhancement has been the prevalent model to explain dengue pathogenesis, but it was only recently demonstrated in vivo and in clinical studies. At present, the current mainstay of management for most symptomatic dengue patients remains careful observation and prompt but judicious use of intravenous hydration therapy for those with substantial vascular leakage. Various new promising technologies for diagnosis of dengue are currently in the pipeline. New sample-in, answer-out nucleic acid amplification technologies for point-of-care use are being developed to improve performance over current technologies, with the potential to test for multiple pathogens using a single specimen. The search for biomarkers that reliably predict development of severe dengue among symptomatic individuals is also a major focus of current research efforts. The first dengue vaccine was licensed in 2015 but its performance depends on serostatus. There is an urgent need to identify correlates of both vaccine protection and disease enhancement. A crucial assessment of vector control tools should guide a research agenda for determining the most effective interventions, and how to best combine state-of-the-art vector control with vaccination.

Modelling the effect of a dengue vaccine on reducing the evolution of resistance against antibiotic due to misuse in dengue cases.

BACKGROUND: This paper intends to check whether and how a hypothetical dengue vaccine could contribute to issue of evolution of bacteria resistance against antibiotics by reducing the number of patients that would inappropriately being treated with antibiotics. METHODS: We use a new mathematical model that combines, in a novel way, two previously published papers, one on the evolution of resistance against antibiotics and one classical Ross-Macdonald model for dengue transmission. RESULTS: The model is simulated numerically and reproduces a real case of evolution of resistance against antibiotics. In addition the model shows that the use of a hypothetical dengue vaccine could help to curb the evolution of resistance against an antibiotic inappropriately used in dengue patients. Both the increase in the proportion of resistant bacteria due to the misuse of antibiotics in dengue cases as a function of the fraction of treated patients and the reduction of that proportion as a function of vaccination coverage occur in a highly non-linear fashion. CONCLUSION: The use of a dengue vaccine is helpful in reducing the rate of evolution of antibiotic resistance in a scenario of misuse of the antibiotics in dengue patients.

Two complementary model-based methods for calculating the risk of international spreading of a novel virus from the outbreak epicentre. The case of COVID-19.

We present two complementary model-based methods for calculating the risk of international spread of the novel coronavirus SARS-CoV-2 from the outbreak epicentre. One model aims to calculate the number of cases that would be exported from an endemic country to disease-free regions by travellers. The second model calculates the probability that an infected traveller will generate at least one secondary autochthonous case in the visited country. Although this paper focuses on the data from China, our methods can be adapted to calculate the risk of importation and subsequent outbreaks. We found an average R0 = 5.31 (ranging from 4.08 to 7.91) and a risk of spreading of 0.75 latent individuals per 1000 travellers. In addition, one infective traveller would be able to generate at least one secondary autochthonous case in the visited country with a probability of 23%.

A reverse transcription loop-mediated isothermal amplification for broad coverage detection of Asian and African Zika virus lineages.

BACKGROUND: Early detection of Zika virus (ZIKV) infection during the viremia and viruria facilitates proper patient management and mosquito control measurement to prevent disease spread. Therefore, a cost-effective nucleic acid detection method for the diagnosis of ZIKV infection, especially in resource-deficient settings, is highly required. METHODS: In the present study, a single-tube reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of both the Asian and African-lineage ZIKV. The detection limit, strain coverage and cross-reactivity of the ZIKV RT-LAMP assay was evaluated. The sensitivity and specificity of the RT-LAMP were also evaluated using a total of 24 simulated clinical samples. The ZIKV quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was used as the reference assay. RESULTS: The detection limit of the RT-LAMP assay was 3.73 ZIKV RNA copies (probit analysis, P ≤ 0.05). The RT-LAMP assay detected the ZIKV genomes of both the Asian and African lineages without cross-reacting with other arthropod-borne viruses. The sensitivity and specificity of the RT-LAMP assay were 90% (95% CI = 59.6-98.2) and 100% (95% CI = 78.5-100.0), respectively. The RT-LAMP assay detected ZIKV genome in 9 of 24 (37.5%) of the simulated clinical samples compared to 10 of 24 (41.7%) by qRT-PCR assay with a high level of concordance (κ = 0.913, P < 0.001). CONCLUSION: The RT-LAMP assay is applicable for the broad coverage detection of both the Asian and African ZIKV strains in resource-deficient settings.

Only strict quarantine measures can curb the coronavirus disease (COVID-19) outbreak in Italy, 2020.

Several Italian towns are under lockdown to contain the COVID-19 outbreak. The level of transmission reduction required for physical distancing interventions to mitigate the epidemic is a crucial question. We show that very high adherence to community quarantine (total stay-home policy) and a small household size is necessary for curbing the outbreak in a locked-down town. The larger the household size and amount of time in the public, the longer the lockdown period needed.

Dengue vaccine development: status and future.

Dengue, the most common arbovirus, represents an increasingly significant cause of morbidity worldwide, including in travelers. After decades of research, the first dengue vaccine was licensed in 2015: CYD-TDV, a tetravalent live attenuated vaccine with a yellow fever vaccine backbone. Recent analyses have shown that vaccine performance is dependent on serostatus. In those who have had a previous dengue infection, i.e., who are seropositive, the efficacy is high and the vaccine is safe. However, in seronegative vaccinees, approximately 3 years after vaccination the vaccine increases the risk of developing severe dengue when the individual experiences a natural dengue infection.The World Health Organization recommends that this vaccine be administered only to seropositive individuals. Current efforts are underway to develop rapid diagnostic tests to facilitate prevaccination screening. Two second-generation dengue vaccine candidates, both also live attenuated recombinant vaccines in late-stage development, may not present the same limitations because of differences in the backbone used, but results of phase 3 trials need to be available before firm conclusions can be drawn.Dengue is increasingly frequent in travelers, but the only licensed dengue vaccine to date can be used only in seropositive individuals. However, the vast majority of travelers are seronegative. Furthermore, the primary series of three doses given 6 months apart renders this vaccine difficult in the travel medicine context.

Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator-controlled, Randomized Superiority Trial.

BACKGROUND: Antibody titres and vaccine effectiveness decline within 6 months after influenza vaccination in older adults. Biannual vaccination may be necessary to provide year-round protection in the tropics, where influenza circulates throughout the year. METHODS: Tropical Influenza Control Strategies (TROPICS1) was a single-center, 1:1 randomized, observer-blinded, active-comparator-controlled, superiority study in 200 community-resident adults aged ≥65 years. Participants received a standard-dose trivalent inactivated influenza vaccination (IIV3) at enrollment, and either tetanus-diphtheria-pertussis vaccination or IIV3 6 months later. The primary outcome was the proportion of participants with haemagglutination-inhibition (HI) geometric mean titre (GMT) ≥1:40 1 month after the second vaccination (month 7). Secondary outcomes included GMTs to month 12, the incidence of influenza-like illness (ILI), and adverse reactions after vaccination. RESULTS: At month 7, the proportion of participants with an HI tire ≥1:40 against A/H1N1 increased by 21.4% (95% confidence interval [CI] 8.6-33.4) in the semiannual vaccination group. This proportion was not significantly higher for A/H3N2 (4.3, 95% CI -1.1-10.8) or B (2.1, 95% CI -2.0-7.3). Semiannual vaccination significantly increased GMTs against A/H1N1 and A/H3N2, but not B, at month 7. Participants receiving a repeat vaccination of IIV3 reported a significantly lower incidence of ILI in the 6 months after the second vaccination (relative vaccine effectiveness 57.1%, 95% CI 0.6-81.5). The frequency of adverse events was similar after the first and second influenza vaccinations. CONCLUSIONS: Semiannual influenza vaccination in older residents of tropical countries has the potential to improve serological measures of protection against infection. Alternative vaccination strategies should also be studied. CLINICAL TRIALS REGISTRATION: NCT02655874.

The first licensed dengue vaccine: can it be used in travelers?

PURPOSE OF REVIEW: The first dengue vaccine (Dengvaxia) was endorsed by the European Medicine Agency and the US Food and Drug Administration. Given the excess risk of severe dengue in seronegative vaccinees, use is restricted to seropositive individuals. Dengvaxia confers high protection against severe dengue in seropositive vaccinees. RECENT FINDINGS: With increasing global travel, the probability of travelers being seropositive increases. Such seropositive travelers may be at increased risk of severe dengue as a result of a second dengue infection during repeat travel. Nevertheless, the use of Dengvaxia in travelers requires a careful analysis of all the factors. Seropositive travelers only present a minority of all travelers. A validated rapid diagnostic test to screen for dengue serostatus is not yet available. Such a test should be highly specific to avoid inadvertent vaccination of seronegative individuals. The three-dose regimen precludes the use in most travelers who tend to present at travel clinics less than 6 weeks prior to departure. Furthermore, questions about potential sub-optimal immunogenicity in seropositives in nonendemic settings, and the need and timing of boosters remain unanswered. SUMMARY: Although there could potentially be substantial protection against severe dengue in seropositive travelers, Dengvaxia is far from an ideal travel vaccine.

Modelling an optimum vaccination strategy against ZIKA virus for outbreak use.

We present a model to optimise a vaccination campaign aiming to prevent or to curb a Zika virus outbreak. We show that the optimum vaccination strategy to reduce the number of cases by a mass vaccination campaign should start when the Aedes mosquitoes' density reaches the threshold of 1.5 mosquitoes per humans, the moment the reproduction number crosses one. The maximum time it is advisable to wait for the introduction of a vaccination campaign is when the first ZIKV case is identified, although this would not be as effective to minimise the number of infections as when the mosquitoes' density crosses the critical threshold. This suboptimum strategy, however, would still curb the outbreak. In both cases, the catch up strategy should aim to vaccinate at least 25% of the target population during a concentrated effort of 1 month immediately after identifying the threshold. This is the time taken to accumulate the herd immunity threshold of 56.5%. These calculations were done based on theoretical assumptions that vaccine implementation would be feasible within a very short time frame.

Duration of Influenza Vaccine Effectiveness: A Systematic Review, Meta-analysis, and Meta-regression of Test-Negative Design Case-Control Studies.

Background: Whether influenza vaccination offers protection for the duration of an influenza season was called into question recently after analysis of data from test-negative design (TND) case-control studies. Method: The published literature was systematically reviewed to identify TND studies that estimated the change in vaccine effectiveness (VE) with respect to time since vaccination. Results: Fourteen studies were identified through the literature search as meeting eligibility criteria. Meta-analyses were performed to compare VE 15-90 days after vaccination to VE 91-180 days after vaccination. A significant decline in VE was observed for influenza virus subtype A/H3 (change in VE, -33; 95% confidence interval [CI], -57 to -12) and type B (change in VE, -19; 95% CI, -33 to -6). VE declined for influenza virus subtype A/H1, but this difference was not statistically significant (change in VE -8; 95% CI, -27 to 21). A multivariable mixed-effects meta-regression model indicated that the change VE was associated with the proportion of study participants who were cases and the proportion who were vaccinated controls (P < .05). This could reflect biological effects such as (1) mismatch between the vaccine received and the circulating strains (among cases), (2) herd immunity (among controls), or (3) the reduced power of individual TND studies in the later parts of an influenza outbreak. Conclusions: Exploration of new influenza vaccination strategies must be a priority for influenza control, particularly in tropical countries with year-round influenza virus activity.

Innovative and New Approaches to Laboratory Diagnosis of Zika and Dengue: A Meeting Report.

Epidemics of dengue, Zika, and other arboviral diseases are increasing in frequency and severity. Current efforts to rapidly identify and manage these epidemics are limited by the short diagnostic window in acute infection, the extensive serologic cross-reactivity among flaviviruses, and the lack of point-of-care diagnostic tools to detect these viral species in primary care settings. The Partnership for Dengue Control organized a workshop to review the current landscape of Flavivirus diagnostic tools, identified current gaps, and developed strategies to accelerate the adoption of promising novel technologies into national programs. The rate-limiting step to bringing new diagnostic tools to the market is access to reference materials and well-characterized clinical samples to facilitate performance evaluation. We suggest the creation of an international laboratory-response consortium for flaviviruses with a decentralized biobank of well-characterized samples to facilitate assay validation. Access to proficiency panels are needed to ensure quality control, in additional to in-country capacity building.