The COVID-19 pandemic has shown a markedly low proportion of cases among children
. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower ...propensity to show clinical symptoms or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from China, Italy, Japan, Singapore, Canada and South Korea. We estimate that susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years, and that clinical symptoms manifest in 21% (95% credible interval: 12-31%) of infections in 10- to 19-year-olds, rising to 69% (57-82%) of infections in people aged over 70 years. Accordingly, we find that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low. Our age-specific clinical fraction and susceptibility estimates have implications for the expected global burden of COVID-19, as a result of demographic differences across settings. In countries with younger population structures-such as many low-income countries-the expected per capita incidence of clinical cases would be lower than in countries with older population structures, although it is likely that comorbidities in low-income countries will also influence disease severity. Without effective control measures, regions with relatively older populations could see disproportionally more cases of COVID-19, particularly in the later stages of an unmitigated epidemic.
Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence ...interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.
Herd protection through interruption of transmission has contributed greatly to the impact of pneumococcal conjugate vaccines (PCVs) and may enable the use of cost-saving reduced dose schedules. To ...aid PCV age targeting to achieve herd protection, we estimated which population age groups contribute most to vaccine serotype (VT) pneumococcal transmission.
We used transmission dynamic models to mirror pre-PCV epidemiology in England and Wales, Finland, Kilifi in Kenya and Nha Trang in Vietnam where data on carriage prevalence in infants, pre-school and school-aged children and adults as well as social contact patterns was available. We used Markov Chain Monte Carlo methods to fit the models and then extracted the per capita and population-based contribution of different age groups to VT transmission.
We estimated that in all settings, < 1-year-old infants cause very frequent secondary vaccine type pneumococcal infections per capita. However, 1-5-year-old children have the much higher contribution to the force of infection at 51% (28, 73), 40% (27, 59), 37% (28, 48) and 67% (41, 86) of the total infection pressure in E&W, Finland, Kilifi and Nha Trang, respectively. Unlike the other settings, school-aged children in Kilifi were the dominant source for VT infections with 42% (29, 54) of all infections caused. Similarly, we estimated that the main source of VT infections in infants are pre-school children and that in Kilifi 39% (28, 51) of VT infant infections stem from school-aged children whereas this was below 15% in the other settings.
Vaccine protection of pre-school children is key for PCV herd immunity. However, in high transmission settings, school-aged children may substantially contribute to transmission and likely have waned much of their PCV protection under currently recommended schedules.
Influenza vaccine policies that maximise health benefit through efficient use of limited resources are needed. Generally, influenza vaccination programmes have targeted individuals 65 y and over and ...those at risk, according to World Health Organization recommendations. We developed methods to synthesise the multiplicity of surveillance datasets in order to evaluate how changing target populations in the seasonal vaccination programme would affect infection rate and mortality.
Using a contemporary evidence-synthesis approach, we use virological, clinical, epidemiological, and behavioural data to develop an age- and risk-stratified transmission model that reproduces the strain-specific behaviour of influenza over 14 seasons in England and Wales, having accounted for the vaccination uptake over this period. We estimate the reduction in infections and deaths achieved by the historical programme compared with no vaccination, and the reduction had different policies been in place over the period. We find that the current programme has averted 0.39 (95% credible interval 0.34-0.45) infections per dose of vaccine and 1.74 (1.16-3.02) deaths per 1,000 doses. Targeting transmitters by extending the current programme to 5-16-y-old children would increase the efficiency of the total programme, resulting in an overall reduction of 0.70 (0.52-0.81) infections per dose and 1.95 (1.28-3.39) deaths per 1,000 doses. In comparison, choosing the next group most at risk (50-64-y-olds) would prevent only 0.43 (0.35-0.52) infections per dose and 1.77 (1.15-3.14) deaths per 1,000 doses.
This study proposes a framework to integrate influenza surveillance data into transmission models. Application to data from England and Wales confirms the role of children as key infection spreaders. The most efficient use of vaccine to reduce overall influenza morbidity and mortality is thus to target children in addition to older adults. Please see later in the article for the Editors' Summary.
Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is ...currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam.
In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant's carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly.
In this study, we observed that cross-sectional contact and infection studies could help identify pneumococcal transmission routes and that preschool-age children may be the largest reservoir for pneumococcal transmission to infants in Nha Trang, Vietnam.
We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7) programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype ...replacement and predict the impact of higher valency vaccines.
Nasopharyngeal swabs were taken from children <5 y old and family members (n=400) 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs) were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT) carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49). The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence.
Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.
Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for impacts on heterologous viruses following vaccination. We aimed to estimate the population level ...impact of their interaction. We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit its parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam. The data supported either a 41% (95%CrI: 36–54) reduction in susceptibility following infection and for 10.0 days (95%CrI 7.1–12.8) thereafter, or no change in susceptibility following infection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0–11.4); or 16.6 fold (95%CrI 14.5–18.4) in the moderate or low interaction scenarios. Absence of either pathogen was not to the detriment of the other. We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.
The spread of antibiotic resistance, a major threat to human health, is poorly understood. Simple population-level models of bacterial transmission predict that above a certain rate of antibiotic ...consumption in a population, resistant bacteria should completely eliminate non-resistant strains, while below this threshold they should be unable to persist at all. This prediction stands at odds with empirical evidence showing that resistant and non-resistant strains coexist stably over a wide range of antibiotic consumption rates. Not knowing what drives this long-term coexistence is a barrier to developing evidence-based strategies for managing the spread of resistance. Here, we argue that competition between resistant and sensitive pathogens within individual hosts gives resistant pathogens a relative fitness benefit when they are rare, promoting coexistence between strains at the population level. To test this hypothesis, we embed mechanistically explicit within-host dynamics in a structurally neutral pathogen transmission model. Doing so allows us to reproduce patterns of resistance observed in the opportunistic pathogens Escherichia coli and Streptococcus pneumoniae across European countries and to identify factors that may shape resistance evolution in bacteria by modulating the intensity and outcomes of within-host competition.
Between September 2014 and February 2015, the number of Ebola virus disease (EVD) cases reported in Sierra Leone declined in many districts. During this period, a major international response was put ...in place, with thousands of treatment beds introduced alongside other infection control measures. However, assessing the impact of the response is challenging, as several factors could have influenced the decline in infections, including behavior changes and other community interventions. We developed a mathematical model of EVD transmission, and measured how transmission changed over time in the 12 districts of Sierra Leone with sustained transmission between June 2014 and February 2015. We used the model to estimate how many cases were averted as a result of the introduction of additional treatment beds in each area. Examining epidemic dynamics at the district level, we estimated that 56,600 (95% credible interval: 48,300–84,500) Ebola cases (both reported and unreported) were averted in Sierra Leone up to February 2, 2015 as a direct result of additional treatment beds being introduced. We also found that if beds had been introduced 1 month earlier, a further 12,500 cases could have been averted. Our results suggest the unprecedented local and international response led to a substantial decline in EVD transmission during 2014–2015. In particular, the introduction of beds had a direct impact on reducing EVD cases in Sierra Leone, although the effect varied considerably between districts.
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