Biology subjects

Flasche, S.

Publications and source records attributed to Flasche, S..

7 recordsLinked to original sources

bioRxiv2018

The merits of sustaining pneumococcal vaccination after transitioning from Gavi support - a modelling and cost-effectiveness study for Kenya

IntroductionMany low income countries soon will need to consider whether to continue pneumococcal conjugate vaccine (PCV) use at full costs as they transition from Gavi support. Using Kenya as a case study we assessed the incremental cost-effectiveness of continuing PCV use.\n\nMethodsWe fitted a dynamic compartmental model of pneumococcal carriage to annual carriage prevalence surveys and invasive pneumococcal disease (IPD) incidence in Kilifi, Kenya, and predicted disease incidence and related mortality for either continuing PCV use beyond 2022, the start of Kenyas transition from Gavi support, or its discontinuation. We calculated the costs per disability-adjusted-life-year (DALY) averted and associated prediction intervals (PI).\n\nResultsWe predicted that overall IPD incidence will increase by 93% (PI: 72% - 114%) from 8.5 in 2022 to 16.2 per 100,000 per year in 2032, if PCV use is discontinued. Continuing vaccination would prevent 15,355 (PI: 10,196-21,125) deaths and 112,050 (PI: 79,620- 130,981) disease cases during that time. Continuing PCV after 2022 will require an estimated additional US$15.6 million annually compared to discontinuing vaccination. The incremental cost per DALY averted of continuing PCV was predicted at $142 (PI: 85 - 252) in 2032.\n\nConclusionContinuing PCV use is essential to sustain its health gains. Based on the Kenyan GDP per capita of $1445, and in comparison to other vaccines, continued PCV use at full costs is cost-effective. These arguments support an expansion of the vaccine budget, however, affordability may be a concern.\n\nFundingFunded by the Wellcome Trust.

epidemiology↗

bioRxiv2017

Within-host dynamics explain the coexistence of antibiotic-sensitive and resistant bacteria

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Empirically, resistant strains gradually increase in prevalence as antibiotic consumption increases, but current mathematical models predict a sharp transition between full sensitivity and full resistance. In other words, we do not understand what drives persistent coexistence between resistant and sensitive strains of disease-causing bacteria in host populations. Without knowing what drives patterns of resistance, we cannot accurately predict the impact of potential strategies for managing resistance. Here, we show that within-host dynamics--bacterial growth, strain competition, and host immune responses--promote frequency-dependent selection for resistant strains, explaining patterns of resistance at the population level. By capturing these processes in a parsimonious mathematical framework, we resolve a long-standing conflict between theory and observation. Our models capture widespread coexistence for multiple bacteria-drug combinations across 30 European countries and explain associations between carriage prevalence and resistance prevalence among bacterial subtypes. A mechanistic understanding of resistance evolution is needed to accurately forecast the impact and effectiveness of resistance-management strategies.

epidemiology↗

bioRxiv2017

Identifying Human Encounters That Shape The Transmission Of Streptococcus Pneumoniae And Other Respiratory Infections

Although patterns of social contacts are believed to be an important determinant of infectious disease transmission, there is little empirical evidence to back this up. Indeed, no previous study has linked individuals risk of respiratory infection with their current pattern of social contacts. We explored whether the frequency of different types of social encounters were associated with current pneumococcal carriage and self-reported acute respiratory symptoms (ARS), though a survey in Uganda in 2014. In total 566 participants were asked about their daily social encounters and about symptoms of ARS in the last two weeks. A nasopharyngeal specimen was also taken from each participant. We found that the frequency of physical (i.e. skin-to-skin), long ([≥]1h) and household contacts - which capture some measure of close (i.e. relatively intimate) contact -, was higher among pneumococcal carriers than non-carriers, and among people with ARS compared to those without, irrespective of their age. With each additional physical encounter the age-adjusted risk of carriage and ARS increased by 6% (95%CI 2-9%) and 9% (1-18%) respectively. In contrast, the number of casual contacts (<5 minutes long) was not associated with either pneumococcal carriage or ARS. A detailed analysis by age of contacts showed that the number of close contacts with young children (<5 years) was particularly higher among older children and adult carriers than non-carriers, while the higher number of contacts among people with ARS was more homogeneous across contacts of all ages. Our findings provide key evidence that the frequency of close interpersonal contact is important for transmission of respiratory infections, but not that of casual contacts. Such results strengthen the evidence for public health measures based upon assumptions of what contacts are important for transmission, and are important to improve disease prevention and control efforts, as well as inform research on infectious disease dynamics.\n\nAuthor summaryAlthough social contacts are an important determinant for the transmission of many infectious diseases it is not clear how the nature and frequency of contacts shape individual infection risk. We explored whether frequency, duration and type of social encounters were associated with someones risk of respiratory infection, using nasopharyngeal carriage (NP) of Streptococcus pneumoniae and acute respiratory symptoms as endpoints. To do so, we conducted a survey in South-West Uganda collecting information on peoples social encounters, respiratory symptoms, and pneumococcal carriage status. Our results show that both pneumococcal carriage and respiratory symptoms are independently associated with a higher number of social encounters, irrespective of a persons age. More specifically, our findings strongly suggest that the frequency of close contacts is important for transmission of respiratory infections, particularly pneumococcal carriage. In contrast, our study showed no association with the frequency of short casual contacts. Those results are essential for both improving disease prevention and control efforts as well as informing research on infectious disease dynamics and transmission models.

epidemiology↗

bioRxiv2017

Predicting The Impact Of Pneumococcal Conjugate Vaccine Programme Options In Vietnam: A Dynamic Transmission Model

BackgroundCatch-up campaigns (CCs) at the introduction of the pneumococcal conjugate vaccines (PCVs) may accelerate the impact of PCVs. However, limited vaccine supplies may delay vaccine introduction if additional doses are needed for such campaigns. We studied the relative impact of introducing PCV13 with and without catch-up campaign, and the implications of potential introduction delays.\n\nMethodsWe used a dynamic transmission model applied to the population of Nha Trang in Sout central Vietnam. Four strategies were considered: routine vaccination (RV) only, and RV alongside catch-up campaigns among <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was parameterised with local data on human social contact rates, and was fitted to local carriage data. Post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics, including serotype competition, vaccine efficacy and duration of protection.\n\nResultsOur model predicts elimination of vaccine-type (VT) carriage across all age groups within 10 years of introduction in all scenarios with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years after introduction, with the highest impact in the first year, when IPD incidence is predicted to be 11% (95%CrI 9 - 14%) lower than RV with CC1, 25% (21 - 30 %) lower with CC2 and 38% (32 - 46%) lower with CC5.\n\nHowever, CCs would only prevent more cases of IPD insofar such campaigns do not delay introduction by more than 31 (95%CrI 30 - 32) weeks with CC1, 58 (53 - 63) weeks with CC2 and 89 (78 - 101) weeks for CC5.\n\nConclusionCCs are predicted to offer a substantial additional reduction in pneumococcal disease burden over RV alone, if their implementation does not result in much introduction delay. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.

epidemiology↗

bioRxiv2017

Characteristics Of Human Encounters And Social Mixing Patterns Relevant To Infectious Diseases Spread By Close Contact: A Survey In Southwest Uganda

Quantification of human interactions relevant to infectious disease transmission through social contact is central to predict disease dynamics, yet data from low-resource settings remain scarce. We undertook a social contact survey in rural Uganda, whereby participants were asked to recall details about the frequency, type, and socio-demographic characteristics of any conversational encounter that lasted for [≥]5 minutes (henceforth defined as contacts) during the previous day. An estimate of the number of casual contacts (i.e. <5 minutes) was also obtained. A total of 568 individuals were included. On average participants reported having routine contact with 7.2 individuals (range 1-25). Children aged 5-14 years had the highest frequency of contacts and the elderly ([≥]65 years) the fewest (P<0.001). A strong age-assortative pattern was seen, particularly outside the household and increasingly so for contacts occurring further away from home. Adults aged 25-64 years tended to travel more and further than others, and males travelled more frequently than females. Our study provides detailed information on contact patterns and their spatial characteristics in an African setting. It therefore fills an important knowledge gap that will help more accurately predict transmission dynamics and the impact of control strategies in such areas.

epidemiology↗

bioRxiv2017

Assessing The Efficiency Of Catch-Up Campaigns For Introduction Of Pneumococcal Conjugate Vaccine; A Modelling Study Based On Data From Kilifi, Kenya

BackgroundThe World Health Organisation recommends the use of catch-up campaigns as part of the introduction of pneumococcal conjugate vaccines (PCVs) to accelerate herd protection and hence PCV impact. The value of a catch-up campaign is a trade-off between the costs of vaccinating additional age groups and the benefit of additional direct and indirect protection. There is a paucity of observational data, particularly from low-middle income countries to quantify the optimal breadth of such catch-up campaigns.\n\nMethodsIn Kilifi, Kenya PCV10 was introduced in 2011 using the 3-dose EPI infant schedule and a catch-up campaign in children <5 years old. We fitted a transmission dynamic model to detailed local data including nasopharyngeal carriage and invasive pneumococcal disease (IPD) to infer the marginal impact of the PCV catch-up campaign over hypothetical routine cohort vaccination in that setting, and to estimate the likely impact of alternative campaigns and their dose-efficiency.\n\nResultsWe estimated that, within 10 years of introduction, the catch-up campaign among <5y olds prevents an additional 65 (48 to 84) IPD cases, compared to PCV cohort introduction alone. Vaccination without any catch-up campaign prevented 155 (121 to 193) IPD cases and used 1321 (1058 to 1698) PCV doses per IPD case prevented. In the years after implementation, the PCV programme gradually accrues herd protection and hence its dose-efficiency increases: 10 years after the start of cohort vaccination alone the programme used 910 (732 to 1184) doses per IPD case averted. We estimated that a two-dose catch-up among <1y olds uses an additional 910 (732 to 1184) doses per additional IPD case averted. Furthermore, by extending a single dose catch-up campaign to children 1 to <2y old and subsequently to 2 to <5y olds the campaign uses an additional 412 (296 to 606) and 543 (403 to 763) doses per additional IPD case averted. These results were not sensitive to vaccine coverage, serotype competition, the duration of vaccine protection or the relative protection of infants.\n\nConclusionsWe find that catch-up campaigns are a highly dose-efficient way to accelerate population protection against pneumococcal disease.

epidemiology↗

bioRxiv2017

Exploring The Role Of Competition Induced By Non-Vaccine Serotypes For Herd Protection

The competitive pressure from non-vaccine serotypes may have helped pneumococcal conjugate vaccines (PCVs) to limit vaccine serotype (VT) prevalence. We aim to investigate if, consequently, the indirect protection of higher valency vaccines could fall short of the profound effects of current formulations.\n\nWe compare three previously described pneumococcal models harmonized to simulate 20 serotypes with a combined pre-vaccination prevalence in <5y old children of 40%. We simulate vaccines of increasing valency by adding serotypes in order of their competitiveness and explore their ability to reduce VT carriage by 95% within 10 years after introduction.\n\nAll models predict that additional valency will reduce indirect vaccine effects and hence the overall vaccine impact on carriage both in children and adults. Consequently, the minimal effective coverage (efficacy against carriage * vaccine coverage) needed to eliminate vaccine type carriage increases with increasing valency. One model predicts this effect to be modest while the other two predict that high-valency vaccines may struggle to eliminate VT pneumococci unless vaccine efficacy against carriage can be substantially improved. Similar results were obtained when settings of higher transmission intensity and different PCV formulations were explored.\n\nFailure to eliminate carriage as a result of increased valency could lead to overall decreased impact of vaccination if the disease burden caused by the added serotypes is low. Hence a comparison of vaccine formulations of varying valency, and pan-valent formulations in particular, should consider the invasiveness of targeted serotypes, as well as efficacy against carriage.

ecology↗