Age-Dependent Risk of Respiratory Syncytial Virus Infection: A Systematic Review and Hazard Modeling From Serological Data.

BACKGROUND: There is no immunization campaign that currently exist for respiratory syncytial virus (RSV). Seroprevalence studies are critical for assessing epidemiological dynamics before and during an immunization program. A systematic literature review was conducted to summarize the evidence from seroprevalence studies on RSV. METHODS: A systematic search of age-dependent RSV seroprevalence was conducted using the PubMed database and EMBASE. Age-dependent force of infections (FoI) and the decay rate of immunity were estimated. A mixture finite model was used, estimating the age-dependent disease state and the antibody concentrations in susceptible and infected or recovered populations. RESULTS: Twenty-one studies were identified from 15 countries, with studies using enzyme-linked immunosorbent assay being the most represented. Using a catalytic model, the age-dependent force of infection was estimated to be the lowest in infants aged 6 months to 1 year and increased in older age groups. The proportion ever-infected/recovered was estimated to be above 90% by 3 years of age. CONCLUSIONS: The number of seroprevalence studies covering a broad range of ages are limited. The age-dependent FoI indicated that the risk of infection was greatest among those aged >5 years. Additional data using valid assays are required to describe the transmission dynamics of RSV infection.

Trend change of the transmission route of COVID-19-related symptoms in Japan.

OBJECTIVES: The Japanese prime minister declared a state of emergency on April 7 2020 to combat the outbreak of coronavirus disease 2019 (COVID-19). This declaration was unique in the sense that it was essentially driven by the voluntary restraint of the residents. We examined the change of the infection route by investigating contact experiences with COVID-19-positive cases. STUDY DESIGN: This study is a population-level questionnaire-based study using a social networking service (SNS). METHODS: To assess the impact of the declaration, this study used population-level questionnaire data collected from an SNS with 121,375 respondents (between March 27 and May 5) to assess the change in transmission routes over the study period, which was measured by investigating the association between COVID-19-related symptoms and (self-reported) contact with COVID-19-infected individuals. RESULTS: The results of this study show that the declaration prevented infections in the workplace, but increased domestic infections as people stayed at home. However, after April 24, workplace infections started to increase again, driven by the increase in community-acquired infections. CONCLUSIONS: While careful interpretation is necessary because our data are self-reported from voluntary SNS users, these findings indicate the impact of the declaration on the change in transmission routes of COVID-19 over time in Japan.

Age and geographic dependence of Zika virus infection during the outbreak on Yap island, 2007.

Intensive surveillance of Zika virus infection conducted on Yap Island has provided crucial information on the epidemiological characteristics of the virus, but the rate of infection and medical attendance stratified by age and geographical location of the epidemic have yet to be fully clarified. In the present study, we reanalyzed surveillance data reported in a previous study. Likelihood-based Bayesian inference was used to gauge the age and geographically dependent force of infection and age-dependent reporting rate, with unobservable variables imputed by the data augmentation method. The inferred age-dependent component of the force of infection was suggested to be up to 3-4 times higher among older adults than among children. The age-dependent reporting rate ranged from 0.7% (5-9 years old) to 3.3% (50-54 years old). The proportion of serologically confirmed cases among total probable or confirmed cases was estimated to be 44.9%. The cumulative incidence of infection varied by municipality: Median values were over 80% in multiple locations (Gagil, Tomil, and Weloy), but relatively low values (below 50%) were derived in other locations. However, the possibility of a comparably high incidence of infection was not excluded even in municipalities with the lowest estimates. The results suggested a high degree of heterogeneity in the Yap epidemic. The force of infection and reporting rate were higher among older age groups, and this discrepancy implied that the demographic patterns were remarkably different between all infected and medically attended individuals. A higher reporting rate may have reflected more severe clinical presentation among adults. The symptomatic ratio in dengue cases is known to correlate with age, and our findings presumably indicate a similar tendency in Zika virus disease.

Accurate forecasts of the effectiveness of interventions against Ebola may require models that account for variations in symptoms during infection.

Epidemiological models are routinely used to predict the effects of interventions aimed at reducing the impacts of Ebola epidemics. Most models of interventions targeting symptomatic hosts, such as isolation or treatment, assume that all symptomatic hosts are equally likely to be detected. In other words, following an incubation period, the level of symptoms displayed by an individual host is assumed to remain constant throughout an infection. In reality, however, symptoms vary between different stages of infection. During an Ebola infection, individuals progress from initial non-specific symptoms through to more severe phases of infection. Here we compare predictions of a model in which a constant symptoms level is assumed to those generated by a more epidemiologically realistic model that accounts for varying symptoms during infection. Both models can reproduce observed epidemic data, as we show by fitting the models to data from the ongoing epidemic in the Democratic Republic of the Congo and the 2014-16 epidemic in Liberia. However, for both of these epidemics, when interventions are altered identically in the models with and without levels of symptoms that depend on the time since first infection, predictions from the models differ. Our work highlights the need to consider whether or not varying symptoms should be accounted for in models used by decision makers to assess the likely efficacy of Ebola interventions.

Time dependent risk of cytomegalovirus infection in Japan.

Cytomegalovirus (CMV), a major cause of congenital infections, has high morbidity and mortality rates associated with it. However, a decline in the proportion of anti-CMV antibody-positive individuals has been observed. The present study aimed to quantify the time-dependent transmission dynamics of CMV infection in Japan by analysing the seroepidemiological datasets for pregnant women collected from five cord blood banks from 1996 to 2009. By employing a mathematical model and using the maternal age distribution of child births from the census data, we computed the seroprevalence among the pregnant Japanese women as a function of time. A decreasing trend was observed for the force of infection, i.e. the rate at which susceptible individuals are infected, which decreased from 0.04 to 0.03 (/year) over the period from 1996 to 2009. While the total number of births has steadily declined in Japan over time, the estimated number of live births at risk of CMV infection has increased over time. Our data reveal that in 2009 in Japan, at least 0.3 million women may have been at risk of contracting a CMV infection during the perinatal period. Moreover, about 2,726 congenital CMV infections were expected to have occurred in 2009. The average age at infection has already reached the child bearing age, and it must be noted that the age at infection can be elevated even more, reaching close to 30 years old which is the ongoing mean age at child delivery. It must be remembered that, if vaccine can become one of the options for the control of CMV in the future, the vaccination can lead to further elevation of age at infection, which may coincide with further elevation of mothers' age of delivery in Japan.

Protective efficacy of an IL-12-expressing baculoviral malaria vaccine.

Interleukin-12 (IL-12) plays an important role in antigen-specific adaptive immunity against Plasmodium sporozoites, and this requirement allows for a new approach to developing an effective malaria vaccine. In this study, we examined whether IL-12 could enhance protective efficacy of a baculovirus-based malaria vaccine. For this aim, a baculoviral vector expressing murine IL-12 (mIL-12) under the control of CMV promoter (BES-mIL-12-Spider) and a baculoviral vector expressing Plasmodium falciparum circumsporozoite protein (PfCSP) with post-transcriptional regulatory element of woodchuck hepatitis virus (BDES-sPfCSP2-WPRE-Spider) were generated. BES-mIL-12-Spider produced bioactive IL-12 which activates splenocytes, resulting in induction of IFN-γ. When co-immunized with BES-mIL-12-Spider and BDES-sPfCSP2-WPRE-Spider, the mouse number for high IgG2a/IgG1 ratios and the geometric mean in this group were both increased as compared with those of the other groups, indicating a shift towards a Th1-type response following immunization with BES-mIL-12-Spider. Finally, immunization with BDES-sPfCSP2-WPRE-Spider plus BES-mIL-12-Spider had a higher protective efficacy (73%) than immunization with BDES-sPfCSP2-WPRE-Spider alone (30%) against challenge with transgenic Plasmodium berghei sporozoites expressing PfCSP. These results suggest that co-administration of IL-12 expressing baculoviral vector, instead of IL-12 cDNA, with viral-vectored vaccines provides a new feasible vaccine platform to enhance Th1-type cellular immune responses against Plasmodium parasites.

Assessing the risk of observing multiple generations of Middle East respiratory syndrome (MERS) cases given an imported case.

To guide risk assessment, expected numbers of cases and generations were estimated, assuming a case importation of Middle East respiratory syndrome (MERS). Our analysis of 36 importation events yielded the risk of observing secondary transmission events at 22.7% (95% confidence interval: 19.3­25.1). The risks of observing generations 2, 3 and 4 were estimated at 10.5%, 6.1% and 3.9%, respectively. Countries at risk should be ready for highly variable outcomes following an importation of MERS.

The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro.

Anti-malarial transmission-blocking vaccines (TBVs) aim to inhibit the transmission of Plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. Successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. There are currently only five lead TBV candidates under examination. There is a consequent need to identify novel antigens to allow the formulation of new potent TBVs. Here we describe the design and evaluation of a potential TBV (BDES-PbPSOP12) targeting Plasmodium berghei PSOP12 based on the baculovirus dual expression system (BDES), enabling expression of antigens on the surface of viral particles and within infected mammalian cells. In silico studies have previously suggested that PSOP12 (Putative Secreted Ookinete Protein 12) is expressed within the sexual stages of the parasite (gametocytes, gametes and ookinetes), and is a member of the previously characterized 6-Cys family of plasmodial proteins. We demonstrate that PSOP12 is expressed within the sexual/ookinete forms of the parasite, and that sera obtained from mice immunized with BDES-PbPSOP12 can recognize the surface of the male and female gametes, and the ookinete stages of the parasite. Immunization of mice with BDES-PbPSOP12 confers modest but significant transmission-blocking activity in vivo by active immunization (53.1% reduction in oocyst intensity, 10.9% reduction in oocyst prevalence). Further assessment of transmission-blocking potency ex vivo shows a dose-dependent response, with up to a 76.4% reduction in intensity and a 47.2% reduction in prevalence observed. Our data indicates that PSOP12 in Plasmodium spp. could be a potential new TBV target candidate, and that further experimentation to examine the protein within human malaria parasites would be logical.

Optimal design of studies of influenza transmission in households. II: comparison between cohort and case-ascertained studies.

Both case-ascertained household studies, in which households are recruited after an 'index case' is identified, and household cohort studies, where a household is enrolled before the start of the epidemic, may be used to test and estimate the protective effect of interventions used to prevent influenza transmission. A simulation approach parameterized with empirical data from household studies was used to evaluate and compare the statistical power of four study designs: a cohort study with routine virological testing of household contacts of infected index case, a cohort study where only household contacts with acute respiratory illness (ARI) are sampled for virological testing, a case-ascertained study with routine virological testing of household contacts, and a case-ascertained study where only household contacts with ARI are sampled for virological testing. We found that a case-ascertained study with ARI-triggered testing would be the most powerful design while a cohort design only testing household contacts with ARI was the least powerful. Sensitivity analysis demonstrated that these conclusions varied by model parameters including the serial interval and the risk of influenza virus infection from outside the household.

Incubation period as part of the case definition of severe respiratory illness caused by a novel coronavirus.

Non-specific symptoms of acute respiratory viral infections make it difficult for many countries without ongoing transmission of a novel coronavirus to rule out other possibilities including influenza before isolating imported febrile individuals with a possible exposure history. The incubation period helps differential diagnosis, and up to two days is suggestive of influenza. It is worth including the incubation period in the case definition of novel coronavirus infection.

Household transmission of influenza (H1N1-2009) in Japan: age-specificity and reduction of household transmission risk by zanamivir treatment.

This study investigated household transmission data for influenza (H1N1-2009) in Japan in order to quantify the age-specific risk of infection and estimate the impact of antiviral treatment on the risk of household transmission. Among a total of 1547 households, involving 4609 household contacts, the secondary attack ratio (SAR) was estimated to be 11.4%. School children aged 5 - 18 years dominated the index cases. Age-specific infectiousness and susceptibility were highest among 0 - 4-year olds, with SAR estimated at 19.4% and 29.6%, respectively. Zanamivir treatment within 24 and 24 - 48 h of illness onset in index cases, respectively, reduced the risk of household transmission to 0.57 (95% CI 0.44, 0.73) and 0.58 (95% CI 0.38, 0.86) times that among those receiving the same treatment at > 48 h and those not receiving treatment. The preventive performance of antiviral treatment and prophylaxis should be further examined in randomized controlled trials.

Estimating reproduction numbers for adults and children from case data.

We present a method for estimating reproduction numbers for adults and children from daily onset data, using pandemic influenza A(H1N1) data as a case study. We investigate the impact of different underlying transmission assumptions on our estimates, and identify that asymmetric reproduction matrices are often appropriate. Under-reporting of cases can bias estimates of the reproduction numbers if reporting rates are not equal across the two age groups. However, we demonstrate that the estimate of the higher reproduction number is robust to disproportionate data-thinning. Applying the method to 2009 pandemic influenza H1N1 data from Japan, we demonstrate that the reproduction number for children was considerably higher than that of adults, and that our estimates are insensitive to our choice of reproduction matrix.

An epidemiological analysis of the foot-and-mouth disease epidemic in Miyazaki, Japan, 2010.

An epidemic of foot-and-mouth disease occurred in Miyazaki, Japan, beginning in late March 2010. Here, we document the descriptive epidemiological features and investigate the between-farm transmission dynamics. As of 10 July 2010, a total of 292 infected premises have been confirmed with a cumulative incidence for cattle and pig herds of 8.5% and 36.4%, respectively, for the whole of Miyazaki prefecture. Pig herds were more likely to be infected than cattle herds (odds ratio = 4.3 [95% confidence interval (CI): 3.2, 5.7]). Modelling analysis suggested that the relative susceptibility of a cattle herd is 4.2 times greater than a typical pig herd (95% CI: 3.9, 4.5), while the relative infectiousness of a pig herd is estimated to be 8.0 times higher than a cattle herd (95% CI: 5.0, 13.6). The epidemic peak occurred around mid-May, after which the incidence started to decline and the effective reproduction numbers from late May were mostly less than unity, although a vaccination programme in late May could have masked symptoms in infected animals. The infected premises were geographically confined to limited areas in Miyazaki, but sporadic long-distance transmissions were seen within the prefecture. Given that multiple outbreaks in Far East Asian countries have occurred since early 2010, continued monitoring and surveillance is deemed essential.

Potential effectiveness of public health interventions during the equine influenza outbreak in racehorse facilities in Japan, 2007.

An outbreak of equine influenza (H3N8) occurred among fully vaccinated racehorses in Japan from August to September, 2007. To assess the potential effectiveness of public health interventions other than vaccination (i.e. movement restriction, isolation and quarantine), which started immediately on the date of detection of the first febrile case, a simple epidemiological model was developed and applied to the observed data. The epidemic curves in five racehorse facilities revealed consistent temporal patterns: (i) a sharp increase in symptom onset of cases during the first 3 days, which is thought to reflect the incubation period before interventions and (ii) thereafter, a continuous decline in incidence reflecting successful control. Whereas the reproduction number before interventions was 2.4-24.7, the estimate declined to 0.1-0.3 following interventions. The effectiveness of all the countermeasures was assessed by the relative reduction in the reproduction number and ranged from 88.0% to 99.5%. The combined effect of vaccination prior to the outbreak and other public health interventions is thought to have helped control the outbreak in 2007.

A simple mathematical approach to deciding the dosage of vaccine against pandemic H1N1 influenza.

Results from early clinical trials have shown that a single dose of pandemic H1N1 influenza vaccine may generate sufficient antibody response, but the relevance of this fact to public health decision making has yet to be clarified. The present study compares the risk of clinical attack (i.e. clinical attack rate) between one- and two-dose vaccination schemes. If the efficacies do not greatly vary between one- and two-dose schemes, one-dose vaccination may well be supported. Nevertheless, two-dose vaccination is shown to result in less morbidity if the vaccine efficacies are greatly diminished by reducing the dose. As long as the detailed efficacy estimates rest on theoretical assumptions, single-dose vaccination may only be sufficiently justified in a specific setting where the number of vaccines is extremely limited.

Epidemiological and transmissibility analysis of influenza A(H1N1)v in a southern hemisphere setting: Peru.

We present a preliminary analysis of 1,771 confirmed cases of influenza A(H1N1)v reported in Peru by 17 July including the frequency of the clinical characteristics, the spatial and age distribution of the cases and the estimate of the transmission potential. Age-specific frequency of cases was highest among school age children and young adults, with the lowest frequency of cases among seniors, a pattern that is consistent with reports from other countries. Estimates of the reproduction number lie in the range of 1.2 to 1.7, which is broadly consistent with previous estimates for this pandemic in other regions. Validation of these estimates will be possible as additional data become available.