Samik Datta

Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis

BACKGROUND The full extent to which childhood pneumococcal conjugate vaccines (PCV) can indirectly reduce illness in unvaccinated populations is not known. We aimed to estimate the magnitude and timing of indirect effects of PCVs on invasive pneumococcal disease. METHODS In this systematic review and meta-analysis, we searched bibliographic databases for non-randomised quasi-experimental or observational studies reporting invasive pneumococcal disease changes following PCV introduction in unvaccinated populations (studies published Sept 1, 2010, to Jan 6, 2016), updating the previous systematic review of the same topic (studies published Jan 1, 1994, to Sept 30, 2010). Two reviewers extracted summary data by consensus. We used a Bayesian mixed-effects model to account for between-study heterogeneity to estimate temporal indirect effects by pooling of invasive pneumococcal disease changes by serotype and serogroup. FINDINGS Data were extracted from 70 studies included in the previous review and 172 additional studies, covering 27 high-income and seven middle-income countries. The predicted mean times to attaining a 90% reduction in invasive pneumococcal disease were 8·9 years (95% credible interval [CrI] 7·8-10·3) for grouped serotypes contained in the seven-valent PCV (PCV7), and 9·5 years (6·1-16·6) for the grouped six additional serotypes contained in the 13-valent PCV (PCV13) but not in PCV7. Disease due to grouped serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV23) decreased at similar rates per year in adults aged 19-64 years (relative risk [RR] 0·85, 95% CrI 0·75-0·95) and 65 years and older (0·87, 0·84-0·90). However, we noted no changes in either group in invasive pneumococcal disease caused by the additional 11 serotypes covered by PPV23 but not PCV13. INTERPRETATION Population childhood PCV programmes will lead, on average, to substantial protection across the whole population within a decade. This large indirect protection should be considered when assessing vaccination of older age groups. FUNDING Policy Research Programme of the Department of Health, England.

A stability analysis of the power-law steady state of marine size spectra.

This paper investigates the stability of the power-law steady state often observed in marine ecosystems. Three dynamical systems are considered, describing the abundance of organisms as a function of body mass and time: a “jump-growth” equation, a first order approximation which is the widely used McKendrick–von Foerster equation, and a second order approximation which is the McKendrick–von Foerster equation with a diffusion term. All of these yield a power-law steady state. We derive, for the first time, the eigenvalue spectrum for the linearised evolution operator, under certain constraints on the parameters. This provides new knowledge of the stability properties of the power-law steady state. It is shown analytically that the steady state of the McKendrick–von Foerster equation without the diffusion term is always unstable. Furthermore, numerical plots show that eigenvalue spectra of the McKendrick–von Foerster equation with diffusion give a good approximation to those of the jump-growth equation. The steady state is more likely to be stable with a low preferred predator:prey mass ratio, a large diet breadth and a high feeding efficiency. The effects of demographic stochasticity are also investigated and it is concluded that these are likely to be small in real systems.

Modelling the spread of American foulbrood in honeybees

We investigate the spread of American foulbrood (AFB), a disease caused by the bacterium Paenibacillus larvae, that affects bees and can be extremely damaging to beehives. Our dataset comes from an inspection period carried out during an AFB epidemic of honeybee colonies on the island of Jersey during the summer of 2010. The data include the number of hives of honeybees, location and owner of honeybee apiaries across the island. We use a spatial SIR model with an underlying owner network to simulate the epidemic and characterize the epidemic using a Markov chain Monte Carlo (MCMC) scheme to determine model parameters and infection times (including undetected ‘occult’ infections). Likely methods of infection spread can be inferred from the analysis, with both distance- and owner-based transmissions being found to contribute to the spread of AFB. The results of the MCMC are corroborated by simulating the epidemic using a stochastic SIR model, resulting in aggregate levels of infection that are comparable to the data. We use this stochastic SIR model to simulate the impact of different control strategies on controlling the epidemic. It is found that earlier inspections result in smaller epidemics and a higher likelihood of AFB extinction.

Predicting the spread of the Asian hornet ( Vespa velutina ) following its incursion into Great Britain

The yellow-legged or Asian hornet (Vespa velutina) is native to South-East Asia, and is a voracious predator of pollinating insects including honey bees. Since its accidental introduction into South-Western France in 2004, V. velutina has spread to much of western Europe. The presence of V. velutina in Great Britain was first confirmed in September 2016. The likely dynamics following an initial incursion are uncertain, especially the risk of continued spread, and the likely success of control measures. Here we extrapolate from the situation in France to quantify the potential invasion of V. velutina in Great Britain. We find that, without control, V. velutina could colonise the British mainland rapidly, depending upon how the Asian hornet responds to the colder climate in Britain compared to France. The announcement that a second hornet had been discovered in Somerset, increases the chance that the invasion first occurred before 2016. We therefore consider the likely site of first invasion and the probabilistic position of additional founding nests in late 2016 and early 2017. Given the potential dispersion of V. velutina, we conclude that vigilance is required over a large area to prevent the establishment of this threat to the pollinator population.

Efficient use of sentinel sites: detection of invasive honeybee pests and diseases in the UK

Sentinel sites, where problems can be identified early or investigated in detail, form an important part of planning for exotic disease outbreaks in humans, livestock and plants. Key questions are: how many sentinels are required, where should they be positioned and how effective are they at rapidly identifying new invasions? The sentinel apiary system for invasive honeybee pests and diseases illustrates the costs and benefits of such approaches. Here, we address these issues with two mathematical modelling approaches. The first approach is generic and uses probabilistic arguments to calculate the average number of affected sites when an outbreak is first detected, providing rapid and general insights that we have applied to a range of infectious diseases. The second approach uses a computationally intensive, stochastic, spatial model to simulate multiple outbreaks and to determine appropriate sentinel locations for UK apiaries. Both models quantify the anticipated increase in success of sentinel sites as their number increases and as non-sentinel sites become worse at detection; however, unexpectedly sentinels perform relatively better for faster growing outbreaks. Additionally, the spatial model allows us to quantify the substantial role that carefully positioned sentinels can play in the rapid detection of exotic invasions.

The impact of current infection levels on the cost-benefit of vaccination

When considering a new vaccine programme or modifying an existing one, economic cost-benefit analysis, underpinned by predictive epidemiological modelling, is a key component. This analysis is intimately linked to the willingness to pay for additional QALYs (quality-adjusted life-years) gained; currently in England and Wales a health programme is economically viable if the cost per QALY gained is less than £ 20,000, and models are often used to assess if a vaccine programme is likely to fall below this threshold cost. Before a programme begins, infection levels are generally high and therefore vaccination may be expected to have substantial effects and therefore will often be economically viable. However, once a programme is established, and infection rates are lower, it might be expected that a re-evaluation of the programme (using current incidence information) will show it to be less cost-effective. This is the scenario we examine here with analytical tools and simple ODE models. Surprisingly we show that in most cases the benefits from maintaining an existing vaccination programme are at least equal to those of starting the programme initially, and in the majority of scenarios the differences between the two are minimal. In practical terms, this is an extremely helpful finding, allowing us to assert that the action of immunising individuals does not de-value the vaccination programme.

The role of case proximity in transmission of visceral leishmaniasis in a highly endemic village in Bangladesh

Background Visceral leishmaniasis (VL) is characterised by a high degree of spatial clustering at all scales, and this feature remains even with successful control measures. VL is targeted for elimination as a public health problem in the Indian subcontinent by 2020, and incidence has been falling rapidly since 2011. Current control is based on early diagnosis and treatment of clinical cases, and blanket indoor residual spraying of insecticide (IRS) in endemic villages to kill the sandfly vectors. Spatially targeting active case detection and/or IRS to higher risk areas would greatly reduce costs of control, but its effectiveness as a control strategy is unknown. The effectiveness depends on two key unknowns: how quickly transmission risk decreases with distance from a VL case and how much asymptomatically infected individuals contribute to transmission. Methodology/Principal findings To estimate these key parameters, a spatiotemporal transmission model for VL was developed and fitted to geo-located epidemiological data on 2494 individuals from a highly endemic village in Mymensingh, Bangladesh. A Bayesian inference framework that could account for the unknown infection times of the VL cases, and missing symptom onset and recovery times, was developed to perform the parameter estimation. The parameter estimates obtained suggest that, in a highly endemic setting, VL risk decreases relatively quickly with distance from a case—halving within 90m—and that VL cases contribute significantly more to transmission than asymptomatic individuals. Conclusions/Significance These results suggest that spatially-targeted interventions may be effective for limiting transmission. However, the extent to which spatial transmission patterns and the asymptomatic contribution vary with VL endemicity and over time is uncertain. In any event, interventions would need to be performed promptly and in a large radius (≥300m) around a new case to reduce transmission risk.