Estimating the transmission parameters of pneumococcal carriage in households

This paper analyses Streptococcus pneumoniae transmission dynamics in households using longitudinal data on pneumococcal (Pnc) carriage in the United Kingdom. Ten consecutive swabs were taken at 4-week intervals from all members of 121 households. The family status is derived from the observed Pnc carriage status of each family member. Transition matrices are built for each family size and composition containing the observed frequency of transitions between family statuses over a 28-day interval. A density-dependent transmission model is fitted to derive maximum-likelihood estimates of the duration of carriage and acquisition rates from the community and from infected individuals within the household. Parameter values are estimated for children (<5 years) and adults (5+years). The duration of carriage is longer in children <5 years of age than in older family members (51 vs. 19 days). Children are 3–4 times more likely than adults to acquire Pnc infection from the community. Transmission rates within the household suggest that adults are more infectious but less susceptible than children. Transmission within the household is most important in large families. The proportion of household-acquired infection ranges from 29 to 46% in households of three persons to 38–50% in larger households. Evidence of density-dependent within-household transmission is found, although the strength of this relationship is not clear from the model estimates

Austerity, measles and mandatory vaccination: cross-regional analysis of vaccination in Italy 2000-14.

Background: Italy has experienced a resurgence in measles since 2015. Although much emphasis has been placed on the role of individuals opting out of vaccination, here we test the hypothesis that large budget reductions in public health spending were also a contributing factor. Methods: Multi-variate statistical models were used to assess the relationship between measles, mumps and rubella (MMR) coverage and real public health expenditure per-capita across Italy's 20 regions covering the period 2000-14. Results: Between 2010 and 2014 Italy's public health expenditure fell by over 2%, although varying among regions. Fixed effects models estimate that each 1% reduction in per-capita public health expenditure was associated with a decrease of 0.5 percentage points (95% CI: 0.36-0.65 percentage points) in MMR coverage, after adjusting for time and regional-specific time trends. The consequences can be illustrated by comparing two regions, Lazio, where public health spending fell by 5% and MMR coverage by over 3 percentage points, and Sardinia, a historically deprived region, where public health spending partly rose and MMR rates remained approximately steady. Conclusion: Adoption of austerity policies in the Italian health system was found to be significantly associated with declining vaccination rates for MMR. However, the recent introduction of mandatory vaccination for Italian children may help counteract this trend

Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: A longitudinal household study

Background. Natural immunity to Streptococcus pneumoniae is thought to be induced by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies of carriage of and immune responses to S. pneumoniae have been conducted using sophisticated immunological laboratory techniques.Methods. We enrolled 121 families with young children into this study. Nasopharyngeal (NP) swabs were collected monthly for 10 months from all family members and were cultured in a standard fashion. Cultured S. pneumoniae isolates were serotyped. At the beginning (month 0) and end (month 10) of the study, venous blood was collected from family members 118 years old. Serotype-specific antipolysaccharide immunoglobulin G (IgG) and functional antibody and antibodies to pneumolysin, pneumococcal surface protein A (PspA), and pneumococcal surface antigen A (PsaA) were measured in paired serum samples.Results. Levels of anticapsular IgG increased significantly after carriage of serotypes 9V, 14, 18C, 19F, and 23F by an individual or family member. For serotype 14, a higher level of anticapsular IgG at the beginning of the study was associated with reduced odds of carriage (P = .0006). There was a small (similar to 20%) but significant increase in titers of antibodies to PsaA and pneumolysin but no change in titers of antibody to PspA.Conclusions. Adults respond to NP carriage by mounting anticapsular and weak antiprotein antibody responses, and naturally induced anticapsular IgG can prevent carriage

Social contact structures and time use patterns in the Manicaland Province of Zimbabwe.

BACKGROUND: Patterns of person-to-person contacts relevant for infectious diseases transmission are still poorly quantified in Sub-Saharan Africa (SSA), where socio-demographic structures and behavioral attitudes are expected to be different from those of more developed countries. METHODS AND FINDINGS: We conducted a diary-based survey on daily contacts and time-use of individuals of different ages in one rural and one peri-urban site of Manicaland, Zimbabwe. A total of 2,490 diaries were collected and used to derive age-structured contact matrices, to analyze time spent by individuals in different settings, and to identify the key determinants of individuals' mixing patterns. Overall 10.8 contacts per person/day were reported, with a significant difference between the peri-urban and the rural site (11.6 versus 10.2). A strong age-assortativeness characterized contacts of school-aged children, whereas the high proportion of extended families and the young population age-structure led to a significant intergenerational mixing at older ages. Individuals spent on average 67% of daytime at home, 2% at work, and 9% at school. Active participation in school and work resulted the key drivers of the number of contacts and, similarly, household size, class size, and time spent at work influenced the number of home, school, and work contacts, respectively. We found that the heterogeneous nature of home contacts is critical for an epidemic transmission chain. In particular, our results suggest that, during the initial phase of an epidemic, about 50% of infections are expected to occur among individuals younger than 12 years and less than 20% among individuals older than 35 years. CONCLUSIONS: With the current work, we have gathered data and information on the ways through which individuals in SSA interact, and on the factors that mostly facilitate this interaction. Monitoring these processes is critical to realistically predict the effects of interventions on infectious diseases dynamics

Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors

Background: Social contact patterns shape the transmission of respiratory infections spread via close interactions. There is a paucity of observational data from schools and households, particularly in developing countries. Portable wireless sensors can record unbiased proximity events between individuals facing each other, shedding light on pathways of infection transmission. Design and methods: The aim is to characterize face-to-face contact patterns that may shape the transmission of respiratory infections in schools and households in Kilifi, Kenya. Two schools, one each from a rural and urban area, will be purposively selected. From each school, 350 students will be randomly selected proportional to class size and gender to participate. Nine index students from each school will be randomly selected and followed-up to their households. All index household residents will be recruited into the study. A further 3-5 neighbouring households will also be recruited to give a maximum of 350 participants per household setting. The sample size per site is limited by the number of sensors available for data collection. Each participant will wear a wireless proximity sensor lying on their chest area for 7 consecutive days. Data on proximal dyadic interactions will be collected automatically by the sensors only for participants who are face-to-face. Key characteristics of interest include the distribution of degree and the frequency and duration of contacts and their variation in rural and urban areas. These will be stratified by age, gender, role, and day of the week. Expected results: Resultant data will inform on social contact patterns in rural and urban areas of a previously unstudied population. Ensuing data will be used to parameterize mathematical simulation models of transmission of a range of respiratory viruses, including respiratory syncytial virus, and used to explore the impact of intervention measures such as vaccination and social distancing

Modelling the impact of local reactive school closures on critical care provision during an influenza pandemic

Despite the fact that the 2009 H1N1 pandemic influenza strain was less severe than had been feared, both seasonal epidemics of influenza-like-illness and future influenza pandemics have the potential to place a serious burden on health services. The closure of schools has been postulated as a means of reducing transmission between children and hence reducing the number of cases at the peak of an epidemic; this is supported by the marked reduction in cases during school holidays observed across the world during the 2009 pandemic. However, a national policy of long-duration school closures could have severe economic costs. Reactive short-duration closure of schools in regions where health services are close to capacity offers a potential compromise, but it is unclear over what spatial scale and time frame closures would need to be made to be effective. Here, using detailed geographical information for England, we assess how localized school closures could alleviate the burden on hospital intensive care units (ICUs) that are reaching capacity. We show that, for a range of epidemiologically plausible assumptions, considerable local coordination of school closures is needed to achieve a substantial reduction in the number of hospitals where capacity is exceeded at the peak of the epidemic. The heterogeneity in demand per hospital ICU bed means that even widespread school closures are unlikely to have an impact on whether demand will exceed capacity for many hospitals. These results support the UK decision not to use localized school closures as a control mechanism, but have far wider international public-health implications. The spatial heterogeneities in both population density and hospital capacity that give rise to our results exist in many developed countries, while our model assumptions are sufficiently general to cover a wide range of pathogens. This leads us to believe that when a pandemic has severe implications for ICU capacity, only widespread school closures (with their associated costs and organizational challenges) are sufficient to mitigate the burden on the worst-affected hospitals

Estimating infectious disease parameters from data on social contacts and serological status

In dynamic models of infectious disease transmission, typically various mixing patterns are imposed on the so-called Who-Acquires-Infection-From-Whom matrix (WAIFW). These imposed mixing patterns are based on prior knowledge of age-related social mixing behavior rather than observations. Alternatively, one can assume that transmission rates for infections transmitted predominantly through non-sexual social contacts, are proportional to rates of conversational contact which can be estimated from a contact survey. In general, however, contacts reported in social contact surveys are proxies of those events by which transmission may occur and there may exist age-specific characteristics related to susceptibility and infectiousness which are not captured by the contact rates. Therefore, in this paper, transmission is modeled as the product of two age-specific variables: the age-specific contact rate and an age-specific proportionality factor, which entails an improvement of fit for the seroprevalence of the varicella-zoster virus (VZV) in Belgium. Furthermore, we address the impact on the estimation of the basic reproduction number, using non-parametric bootstrapping to account for different sources of variability and using multi-model inference to deal with model selection uncertainty. The proposed method makes it possible to obtain important information on transmission dynamics that cannot be inferred from approaches traditionally applied hitherto.Comment: 25 pages, 6 figure

measles vaccination no time to rest

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Mathematical modelling long-term effects of replacing Prevnar7 with Prevnar13 on invasive pneumococcal diseases in England and Wales

England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7) with its 13-valent equivalent (PCV13), partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether. A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i) different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii) a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13. Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000–62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether. Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch

RSV modelling meeting

A group of investigators gathered to review the landscape of predictive mathematical modelling of RSV intervention programmes, and to identify gaps in knowledge and strategy options being explored. The objective was to set an agenda for future modelling and related research, to explore possible areas for collaborations, and provide an informed status update for various stakeholders