Vaccine induced herd immunity for control of respiratory syncytial virus disease in a low-income country setting

Background: Respiratory syncytial virus (RSV) is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children. Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6m). Would vaccinating older children have a significant public health impact? We developed a mathematical model to explore the benefits of a vaccine against RSV. Methods and Findings: We have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting. To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data. Vaccination is assumed to elicit an immune response equivalent to primary infection. Our results show that immunisation of young children (5–10m) is likely to be a highly effective method of protection of infants (<6m) against hospitalisation. The majority benefit is derived from indirect protection (herd immunity). A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters. Conclusions: This result suggests that vaccinating older infants and children against RSV can have a major public health benefit

Sustained reduction in vaccine-type invasive pneumococcal disease despite waning effects of a catch-up campaign in Kilifi, Kenya: A mathematical model based on pre-vaccination data.

BACKGROUND: In 2011, Kenya introduced the 10-valent pneumococcal conjugate vaccine together with a catch-up campaign for children aged <5years in Kilifi County. In a post-vaccination surveillance study based in Kilifi, there was a substantial decline in invasive pneumococcal disease (IPD). However, given the continued circulation of the vaccine serotypes it is possible that vaccine-serotype disease may re-emerge once the effects of the catch-up campaign wear off. METHODS: We developed a compartmental, age-structured dynamic model of pneumococcal carriage and invasive disease for three serotype groups: the 10-valent vaccine serotypes and two groups of non-vaccine serotypes based on their susceptibility to mutual competition. The model was calibrated to age- and serotype-specific data on carriage and IPD in the pre-vaccination era and used to predict carriage prevalence and IPD up to ten years post-vaccination in Kilifi. The model was validated against the observed carriage prevalence after vaccine introduction. RESULTS: The model predicts a sustained reduction in vaccine-type pneumococcal carriage prevalence from 33% to 8% in infants and from 30% to 8% in 1-5year olds over the 10-year period following vaccine introduction. The incidence of IPD is predicted to decline across all age groups resulting in an overall reduction of 56% in the population, corresponding to 10.4 cases per 100,000 per year. The vaccine-type IPD incidence is estimated to decline by 83% while non-vaccine-type IPD incidence is predicted to increase by 52%. The model's predictions of carriage prevalence agrees well with the observed data in the first five years post-vaccination. CONCLUSION: We predict a sustained and substantial decline in IPD through PCV vaccination and that the current regimen is insufficient to fully eliminate vaccine-serotype circulation in the model. We show that the observed impact is likely to be sustained despite waning effects of the catch-up campaign

Quantifying social contacts in a household setting of rural Kenya using wearable proximity sensors

International audienc

Determinants of high residual post-PCV13 pneumococcal vaccine-type carriage in Blantyre, Malawi:a modelling study

Background In November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to 7 years after introduction (2015–2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in high-income countries, and impact was asymmetric across age groups. Methods A dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage. Results Accumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49–82.26%), similar to previous estimates. Ten-year projected vaccine impact (VT carriage reduction) among 0–9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02–81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection. Conclusions There are both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by an age-specific, local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact on carriage (and therefore herd protection) has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.</p

Individual’s daily behaviour and intergenerational mixing in different social contexts of Kenya

We investigated contact patterns in diverse social contexts in Kenya and the daily behaviours that may play a pivotal role in infection transmission to the most vulnerable leveraging novel data from a 2-day survey on social contacts and time use (TU) from a sample of 1407 individuals (for a total of 2705 person days) from rural, urban formal, and informal settings. We used TU data to build six profiles of daily behaviour based on the main reported activities, i.e., Homestayers (71.1% of person days), Workers (9.3%), Schoolers (7.8%), or locations at increasing distance from home, i.e., Walkers (6.6%), Commuters (4.6%), Travelers (0.6%). In the rural setting, we observed higher daily contact numbers (11.56, SD 0.23) and percentages of intergenerational mixing with older adults (7.5% of contacts reported by those younger than 60 years vs. less than 4% in the urban settings). Overall, intergenerational mixing with older adults was higher for Walkers (7.3% of their reported contacts), Commuters (8.7%), and Homestayers (5.1%) than for Workers (1.5%) or Schoolers (3.6%). These results could be instrumental in defining effective interventions that acknowledge the heterogeneity in social contexts and daily routines, either in Kenya or other demographically and culturally similar sub-Saharan African settings

Individual's daily behaviour and intergenerational mixing in different social contexts of Kenya

none8: We investigated contact patterns in diverse social contexts in Kenya and the daily behaviours that may play a pivotal role in infection transmission to the most vulnerable leveraging novel data from a 2-day survey on social contacts and time use (TU) from a sample of 1407 individuals (for a total of 2705 person days) from rural, urban formal, and informal settings. We used TU data to build six profiles of daily behaviour based on the main reported activities, i.e., Homestayers (71.1% of person days), Workers (9.3%), Schoolers (7.8%), or locations at increasing distance from home, i.e., Walkers (6.6%), Commuters (4.6%), Travelers (0.6%). In the rural setting, we observed higher daily contact numbers (11.56, SD 0.23) and percentages of intergenerational mixing with older adults (7.5% of contacts reported by those younger than 60&nbsp;years vs. less than 4% in the urban settings). Overall, intergenerational mixing with older adults was higher for Walkers (7.3% of their reported contacts), Commuters (8.7%), and Homestayers (5.1%) than for Workers (1.5%) or Schoolers (3.6%). These results could be instrumental in defining effective interventions that acknowledge the heterogeneity in social contexts and daily routines, either in Kenya or other demographically and culturally similar sub-Saharan African settings.noneDel Fava, Emanuele; Adema, Irene; Kiti, Moses C; Poletti, Piero; Merler, Stefano; Nokes, D James; Manfredi, Piero; Melegaro, AlessiaDel Fava, Emanuele; Adema, Irene; Kiti, Moses C; Poletti, Piero; Merler, Stefano; Nokes, D James; Manfredi, Piero; Melegaro, Alessi

Sensitivity analyses.

<p><b>A</b>: the median impact of vaccination in terms of proportion of RSV hospital admissions averted at 70% coverage at different ages with the bars showing the 95% range of results. The red dot indicates the highest median predicted impact (63% at 6m). <b>B</b>) the optimal age to vaccinate if the objective is to maximize the proportion of >80% reduction (black line) or minimize the proportion of <40% reduction (blue). The red dot shows the month at which the highest proportion of 80% reduction or the lowest proportion of 40% reduction is achieved on the black and blue lines respectively.</p

Rapid review of social contact patterns during the COVID-19 pandemic

We identified 12 studies reporting social contact patterns during the COVID-19 pandemic. Eight studies were conducted in European countries and eleven collected data during the initial mitigation period in the spring of 2020 marked by government-declared lockdowns. Some studies collected additional data after relaxation of initial mitigation. Most study settings reported a mean of between 2-5 contacts per person per day, a substantial reduction compared to pre-COVID rates, which ranged from 7-26 contacts per day. This reduction was pronounced for contacts outside of the home. Consequently, levels of assortative mixing by age substantially declined. After relaxation of initial mitigation, mean contact rates increased but did not return to pre-COVID levels. Increases in contacts post-relaxation were driven by working-age adults

The effect of different ages at immunisation for different coverage with the base parameter set (Table 1) for the diary (A) and synthetic (B) contact matrices.

<p>The contour plots show the proportions of hospitalisations prevented by immunisation at different coverage (x-axis) by age at immunisation (y-axis) calculated over a 10 year time after transients have died away. <b>A</b>) diary WAIFW, estimated duration in M class, 2.3m. <b>B</b>) synthetic mixing WAIFW, estimated duration in M class 4.0m. In A, the most hospitalisations are prevented by vaccination at ~11m, and in B at ~6m.</p

Model parameters that have been included in the sensitivity analysis, their upper and lower bounds and their probability density functions.

<p>Model parameters that have been included in the sensitivity analysis, their upper and lower bounds and their probability density functions.</p