Publications
28 results found
Pons-Salort M, Lambert B, Kamau E, et al., 2023, Changes in transmission of Enterovirus D68 (EV-D68) in England inferred from seroprevalence data., eLife, Vol: 12, ISSN: 2050-084X
The factors leading to the global emergence of Enterovirus D68 (EV-D68) in 2014 as a cause of acute flaccid myelitis (AFM) in children are unknown. To investigate potential changes in virus transmissibility or population susceptibility, we measured the seroprevalence of EV-D68-specific neutralising antibodies in serum samples collected in England in 2006, 2011, and 2017. Using catalytic mathematical models, we estimate an approximately 50% increase in the annual probability of infection over the 10-year study period, coinciding with the emergence of clade B around 2009. Despite such increase in transmission, seroprevalence data suggest that the virus was already widely circulating before the AFM outbreaks and the increase of infections by age cannot explain the observed number of AFM cases. Therefore, the acquisition of or an increase in neuropathogenicity would be additionally required to explain the emergence of outbreaks of AFM. Our results provide evidence that changes in enterovirus phenotypes cause major changes in disease epidemiology.
Pons-Salort M, John J, Watson OJ, et al., 2022, Reassessing reported deaths and estimated infection attack rate during the first 6 months of the COVID-19 epidemic, Delhi, India., Emerging Infectious Diseases, Vol: 28, ISSN: 1080-6040
India reported >10 million coronavirus disease (COVID-19) cases and 149,000 deaths in 2020. To reassess reported deaths and estimate incidence rates during the first 6 months of the epidemic, we used a severe acute respiratory syndrome coronavirus 2 transmission model fit to data from 3 serosurveys in Delhi and time-series documentation of reported deaths. We estimated 48.7% (95% credible interval 22.1%-76.8%) cumulative infection in the population through the end of September 2020. Using an age-adjusted overall infection fatality ratio based on age-specific estimates from mostly high-income countries, we estimated that just 15.0% (95% credible interval 9.3%-34.0%) of COVID-19 deaths had been reported, indicating either substantial underreporting or lower age-specific infection-fatality ratios in India than in high-income countries. Despite the estimated high attack rate, additional epidemic waves occurred in late 2020 and April-May 2021. Future dynamics will depend on the duration of natural and vaccine-induced immunity and their effectiveness against new variants.
Pons-Salort M, Lambert B, Kamau E, et al., 2021, Changes in transmission of Enterovirus D68 (EV-D68) in England inferred from seroprevalence data
<jats:title>Abstract</jats:title><jats:p>The factors leading to the global emergence of enterovirus D68 (EV-D68) in 2014 as a cause of acute flaccid myelitis (AFM) in children are unknown. To investigate potential changes in virus transmissibility or population susceptibility, we measured the seroprevalence of EV-D68-specific neutralising antibodies in serum samples collected in England in 2006, 2011 and 2017. Using catalytic mathematical models, we estimate an approximately two-fold increase in the basic reproduction number over the 10-year study period, coinciding with the emergence of clade B around 2009. Despite such increase in transmission, the virus was already widely circulating before the AFM outbreaks and the increase of infections by age cannot explain the observed number of AFM cases. Therefore, the acquisition of or an increase in neuropathogenicity would be additionally required to explain the emergence of outbreaks of AFM. Our results provide evidence that changes in enterovirus phenotypes cause major changes in disease epidemiology.</jats:p>
Pons-Salort M, John J, Watson OJ, et al., 2021, Reconstructing the COVID-19 epidemic in Delhi, India: infection attack rate and reporting of deaths
<jats:title>Abstract</jats:title><jats:p>India reported over 10 million COVID-19 cases and 149,000 deaths in 2020. To estimate exposure and the potential for further spread, we used a SARS-CoV-2 transmission model fit to seroprevalence data from three serosurveys in Delhi and the time-series of reported deaths to reconstruct the epidemic. The cumulative proportion of the population estimated infected was 48.7% (95% CrI 22.1% – 76.8%) by end-September 2020. Using an age-adjusted overall infection fatality ratio (IFR) based on age-specific estimates from mostly high-income countries (HICs), we estimate that 15.0% (95% CrI 9.3% – 34.0%) of COVID-19 deaths were reported. This indicates either under-reporting of COVID-19 deaths and/or a lower age-specific IFR in India compared with HICs. Despite the high attack rate of SARS-CoV-2, a third wave occurred in late 2020, suggesting that herd immunity was not yet reached. Future dynamics will strongly depend on the duration of immunity and protection against new variants.</jats:p>
Park SW, Pons-Salort M, Messacar K, et al., 2021, Epidemiological dynamics of enterovirus D68 in the United States and implications for acute flaccid myelitis, SCIENCE TRANSLATIONAL MEDICINE, Vol: 13, ISSN: 1946-6234
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Nouvellet P, Bhatia S, Cori A, et al., 2021, Reduction in mobility and COVID-19 transmission, Nature Communications, Vol: 12, ISSN: 2041-1723
In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts.Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world.Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation.In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.
Park SW, Farrar J, Messacar K, et al., 2021, Epidemiological dynamics of enterovirus D68 in the US: implications for acute flaccid myelitis., medRxiv
The lack of active surveillance for enterovirus D68 (EV-D68) in the US has hampered the ability to assess the relationship with predominantly biennial epidemics of acute flaccid myelitis (AFM), a rare but serious neurological condition. Using novel surveillance data from the BioFire® Syndromic Trends (Trend) epidemiology network, we characterize the epidemiological dynamics of EV-D68 and demonstrate strong spatiotemporal association with AFM. Although the recent dominant biennial cycles of EV-D68 dynamics may not be stable, we show that a major EV-D68 epidemic, and hence an AFM outbreak, would still be possible in 2020 under normal epidemiological conditions. Significant social distancing due to the ongoing COVID-19 pandemic could reduce the size of an EV-D68 epidemic in 2020, illustrating the potential broader epidemiological impact of the pandemic.
Grassly NC, Pons-Salort M, Parker EPK, et al., 2020, Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study, Lancet Infectious Diseases, Vol: 20, Pages: 1381-1389, ISSN: 1473-3099
BACKGROUND: WHO has called for increased testing in response to the COVID-19 pandemic, but countries have taken different approaches and the effectiveness of alternative strategies is unknown. We aimed to investigate the potential impact of different testing and isolation strategies on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and PCR test sensitivity over time since infection. We estimated the reduction in the effective reproduction number (R) achieved by testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols. The expected effectiveness of different testing strategies was defined as the percentage reduction in R. We reviewed data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics and examined their implications for the use of so-called immunity passports. FINDINGS: If all individuals with symptoms compatible with COVID-19 self-isolated and self-isolation was 100% effective in reducing onwards transmission, self-isolation of symptomatic individuals would result in a reduction in R of 47% (95% uncertainty interval [UI] 32-55). PCR testing to identify SARS-CoV-2 infection soon after symptom onset could reduce the number of individuals needing to self-isolate, but would also reduce the effectiveness of self-isolation (around 10% would be false negatives). Weekly screening of health-care workers and other high-risk groups irrespective of symptoms by use of PCR testing is estimated to reduce their contribution to SARS-CoV-2 transmission by 23% (95% UI 16-40), on top of reductions achieved by self-isolation following symptoms, assuming results are available at 24 h. The effectiveness of test and trace depends strongly on coverage and the timelines
Dighe A, Cattarino L, Cuomo-Dannenburg G, et al., 2020, Response to COVID-19 in South Korea and implications for lifting stringent interventions, BMC Medicine, Vol: 18, Pages: 1-12, ISSN: 1741-7015
Background After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the US. This has led to substantial interest in their “test, trace, isolate” strategy. However, it is important to understand the epidemiological peculiarities of South Korea’s outbreak and characterise their response before attempting to emulate these measures elsewhere.MethodsWe systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, Rt, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. Results We estimated that after the initial rapid growth in cases, Rt dropped below one in early April before increasing to a maximum of 1.94 (95%CrI; 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June Rt was back below one where it remained until the end of our study (July 13th). Despite less stringent “lockdown” measures, strong social distancing measures were implemented in high incidence areas and studies measured a considerable national decrease in movement in late-February. Testing capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly however we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact-tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. ConclusionsWhilst early adoption of testing and contact-tracing are likely to be important for South Korea’s successf
van Elsland S, Watson O, Alhaffar M, et al., 2020, Report 31: Estimating the burden of COVID-19 in Damascus, Syria: an analysis of novel data sources to infer mortality under-ascertainment
The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported substantially lower mortality rates than in Europe and the Americas. One hypothesis is that these countries have been ‘spared’, but another is that deaths have been under-ascertained (deaths that have been unreported due to any number of reasons, for instance due to limited testing capacity). However, the scale of under-ascertainment is difficult to assess with currently available data. In this analysis, we estimate the potential under-ascertainment of COVID-19 mortality in Damascus, Syria, where all-cause mortality data has been reported between 25th July and 1st August. We fit a mathematical model of COVID-19 transmission to reported COVID-19 deaths in Damascus since the beginning of the pandemic and compare the model-predicted deaths to reported excess deaths. Exploring a range of different assumptions about under-ascertainment, we estimate that only 1.25% of deaths (sensitivity range 1% - 3%) due to COVID-19 are reported in Damascus. Accounting for under-ascertainment also corroborates local reports of exceeded hospital bed capacity. To validate the epidemic dynamics inferred, we leverage community-uploaded obituary certificates as an alternative data source, which confirms extensive mortality under-ascertainment in Damascus between July and August. This level of under-ascertainment suggests that Damascus is at a much later stage in its epidemic than suggested by surveillance reports, which have repo. We estimate that 4,340 (95% CI: 3,250 - 5,540) deaths due to COVID-19 in Damascus may have been missed as of 2nd September 2020. Given that Damascus is likely to have the most robust surveillance in Syria, these findings suggest that other regions of the country could have experienced similar or worse mortality rates due to COVID-19.
Jorgensen D, Pons Salort M, Shaw A, et al., 2020, The role of genetic sequencing and analysis in the polio eradication program, Virus Evolution, Vol: 6, ISSN: 2057-1577
Genetic sequencing of polioviruses detected through clinical and environmental surveillance is used to confirm detection, identify their likely origin, track geographic patterns of spread and determine the appropriate vaccination response. The critical importance of genetic sequencing and analysis to the Global Polio Eradication Initiative has grown with the increasing incidence of vaccine-derived poliovirus infections in Africa specifically (470 reported cases in 2019), and globally, alongside persistent transmission of serotype 1 wild-type poliovirus in Pakistan and Afghanistan (197 reported cases in 2019). Adapting what has been learned about the virus genetics and evolution to address these threats has been a major focus of recent work. Here we review how phylogenetic and phylogeographic methods have been used to trace the spread of wild-type polioviruses and identify the likely origins of vaccine-derived polioviruses. We highlight the analysis methods and sequencing technology currently used and the potential for new technologies to speed up poliovirus detection and the interpretation of genetic data. At a pivotal point in the eradication campaign with the threat of anti-vaccine sentiment and donor and public fatigue, innovation is critical to maintain drive and overcome the last remaining circulating virus.
Nouvellet P, Bhatia S, Cori A, et al., 2020, Report 26: Reduction in mobility and COVID-19 transmission
In response to the COVID-19 pandemic, countries have sought to control transmission of SARS-CoV-2by restricting population movement through social distancing interventions, reducing the number ofcontacts.Mobility data represent an important proxy measure of social distancing. Here, we develop aframework to infer the relationship between mobility and the key measure of population-level diseasetransmission, the reproduction number (R). The framework is applied to 53 countries with sustainedSARS-CoV-2 transmission based on two distinct country-specific automated measures of humanmobility, Apple and Google mobility data.For both datasets, the relationship between mobility and transmission was consistent within andacross countries and explained more than 85% of the variance in the observed variation intransmissibility. We quantified country-specific mobility thresholds defined as the reduction inmobility necessary to expect a decline in new infections (R<1).While social contacts were sufficiently reduced in France, Spain and the United Kingdom to controlCOVID-19 as of the 10th of May, we find that enhanced control measures are still warranted for themajority of countries. We found encouraging early evidence of some decoupling of transmission andmobility in 10 countries, a key indicator of successful easing of social-distancing restrictions.Easing social-distancing restrictions should be considered very carefully, as small increases in contactrates are likely to risk resurgence even where COVID-19 is apparently under control. Overall, strongpopulation-wide social-distancing measures are effective to control COVID-19; however gradualeasing of restrictions must be accompanied by alternative interventions, such as efficient contacttracing, to ensure control.
Dighe A, Cattarino L, Cuomo-Dannenburg G, et al., 2020, Report 25: Response to COVID-19 in South Korea and implications for lifting stringent interventions, 25
While South Korea experienced a sharp growth in COVID-19 cases early in the global pandemic, it has since rapidly reduced rates of infection and now maintains low numbers of daily new cases. Despite using less stringent “lockdown” measures than other affected countries, strong social distancing measures have been advised in high incidence areas and a 38% national decrease in movement occurred voluntarily between February 24th - March 1st. Suspected and confirmed cases were isolated quickly even during the rapid expansion of the epidemic and identification of the Shincheonji cluster. South Korea swiftly scaled up testing capacity and was able to maintain case-based interventions throughout. However, individual case-based contact tracing, not associated with a specific cluster, was a relatively minor aspect of their control program, with cluster investigations accounting for a far higher proportion of cases: the underlying epidemic was driven by a series of linked clusters, with 48% of all cases in the Shincheonji cluster and 20% in other clusters. Case-based contacts currently account for only 11% of total cases. The high volume of testing and low number of deaths suggests that South Korea experienced a small epidemic of infections relative to other countries. Therefore, caution is needed in attempting to duplicate the South Korean response in settings with larger more generalized epidemics. Finding, testing and isolating cases that are linked to clusters may be more difficult in such settings.
Grassly N, Pons Salort M, Parker E, et al., 2020, Report 16: Role of testing in COVID-19 control
The World Health Organization has called for increased molecular testing in response to the COVID-19 pandemic, but different countries have taken very different approaches. We used a simple mathematical model to investigate the potential effectiveness of alternative testing strategies for COVID-19 control. Weekly screening of healthcare workers (HCWs) and other at-risk groups using PCR or point-of-care tests for infection irrespective of symptoms is estimated to reduce their contribution to transmission by 25-33%, on top of reductions achieved by self-isolation following symptoms. Widespread PCR testing in the general population is unlikely to limit transmission more than contact-tracing and quarantine based on symptoms alone, but could allow earlier release of contacts from quarantine. Immunity passports based on tests for antibody or infection could support return to work but face significant technical, legal and ethical challenges. Testing is essential for pandemic surveillance but its direct contribution to the prevention of transmission is likely to be limited to patients, HCWs and other high-risk groups.
Blake IM, Pons Salort M, Molodecky N, et al., 2018, Type 2 Poliovirus Detection After Global Withdrawal of Trivalent Oral Vaccine, New England Journal of Medicine, Vol: 379, Pages: 834-845, ISSN: 0028-4793
BackgroundMass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses.MethodsWe analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine–derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2.ResultsThe prevalence of Sabin-2 poliovirus in stool samples declined from 3.9% (95% confidence interval [CI], 3.5 to 4.3) at the time of OPV2 withdrawal to 0.2% (95% CI, 0.1 to 2.7) at 2 months after withdrawal, and the detection rate in sewage samples declined from 71.0% (95% CI, 61.0 to 80.0) to 13.0% (95% CI, 8.0 to 20.0) during the same period. However, 12 months after OPV2 withdrawal, Sabin-2 poliovirus continued to be detected in stool samples (<0.1%; 95% CI, <0.1 to 0.1) and sewage samples (8.0%; 95% CI, 5.0 to 13.0) because of the use of OPV2 in response to VDPV2 outbreaks. Nine outbreaks were reported after OPV2 withdrawal and were associated with low coverage of routine immunization (odds ratio, 1.64 [95% CI, 1.14 to 2.54] per 10% absolute decrease) and low levels of population immunity (odds ratio, 2.60 [95% CI, 1.35 to 5.59] per 10% absolute decrease) within affected cou
Pons Salort M, Grassly NC, 2018, Serotype-specific immunity explains the incidence of diseases caused by human enteroviruses, Science, Vol: 361, Pages: 800-803, ISSN: 0036-8075
Human enteroviruses are a major cause of neurological and other diseases. More than 100 serotypes are known that exhibit unexplained complex patterns of incidence, from regular cycles to more irregular patterns, and new emergences. Using 15 years of surveillance data from Japan (2000–2014) and a stochastic transmission model with accurate demography, we show that acquired serotype-specific immunity can explain the diverse patterns of 18 of the 20 most common serotypes (including Coxsackieviruses, Echoviruses, and Enterovirus-A71). The remaining two serotypes required a change in viral characteristics, including an increase in pathogenicity for Coxsackievirus-A6, which is consistent with its recent global rise in incidence. On the basis of our findings, we are able to predict outbreaks 2 years ahead of time (2015–2016). These results have implications for the impact of vaccines under development.
Harvala H, Broberg E, Benschop K, et al., 2018, Recommendations for enterovirus diagnostics and characterisation within and beyond Europe, JOURNAL OF CLINICAL VIROLOGY, Vol: 101, Pages: 11-17, ISSN: 1386-6532
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Pons-Salort M, Oberste MS, Pallansch MA, et al., 2018, The seasonality of nonpolio enteroviruses in the United States: Patterns and drivers, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 115, Pages: 3078-3083, ISSN: 0027-8424
Nonpolio enteroviruses are diverse and common viruses that can circulate year-round but tend to peak in summer. Although most infections are asymptomatic, they can result in a wide range of neurological and other diseases. Many serotypes circulate every year, and different serotypes predominate in different years, but the drivers of their geographical and temporal dynamics are not understood. We use national enterovirus surveillance data collected by the US Centers for Disease Control and Prevention during 1983−2013, as well as demographic and climatic data for the same period, to study the patterns and drivers of the seasonality of these infections. We find that the seasonal pattern of enterovirus cases is spatially structured in the United States and similar to that observed for historical prevaccination poliomyelitis (1931−1954). We identify latitudinal gradients for the amplitude and the timing of the peak of cases, meaning that those are more regularly distributed all year-round in the south and have a more pronounced peak that arrives later toward the north. The peak is estimated to occur between July and September across the United States, and 1 month earlier than that for historical poliomyelitis. Using mixed-effects models, we find that climate, but not demography, is likely to drive the seasonal pattern of enterovirus cases and that the dew point temperature alone explains ∼30% of the variation in the intensity of transmission. Our study contributes to a better understanding of the epidemiology of enteroviruses, demonstrates important similarities in their circulation dynamics with polioviruses, and identifies potential drivers of their seasonality.
Pons-Salort M, Molodecky NA, O'Reilly KM, et al., 2016, Population immunity against serotype-2 poliomyelitis Leading up to the global withdrawal of the oral poliovirus vaccine: spatio-temporal modelling of surveillance data, Plos Medicine, Vol: 13, ISSN: 1549-1676
BackgroundGlobal withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s).Methods and FindingsIn August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004–30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children <36 mo old identified with non-polio acute flaccid paralysis (AFP) reported through polio surveillance, information on immunisation activities with different oral poliovirus vaccine (OPV) formulations, and serotype-specific estimates of the efficacy of these OPVs against poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity within and among districts. Forward projections of immunity, based on these estimates and planned immunisation activities, were produced through to April 2016 using a cohort model.Estimated population immunity was negatively correlated with the probability of VDPV2 poliomyelitis being reported in a district. In Nigeria and Pakistan, declines in immunity during 2008–2009 and 2012–2013, respectively, were associated with outbreaks of VDPV2. Immunity has since improved in both countries as a result of increased use of trivalent OPV, and projections generally indicated sustained or improved immunity in April 2016, such that the majority of districts (99% [95% uncertainty interval 97%–100%] in Nigeria and 84% [95% uncertainty interval 77%–91%] in Pakistan) had >70
Pons-Salort M, Burns CC, Lyons H, et al., 2016, Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame, PLOS Pathogens, Vol: 12, ISSN: 1553-7366
Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immuni
Parker EP, Molodecky NA, Pons-Salort M, et al., 2015, Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame., Expert Review of Vaccines, Vol: 14, Pages: 1113-1123, ISSN: 1744-8395
The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio.
Pons Salort M, Parker E, Grassly N, 2015, The epidemiology of non-polio enteroviruses: recent advances and outstanding questions, Current Opinion in Infectious Diseases, Vol: 28, Pages: 479-487, ISSN: 1473-6527
Purpose of reviewThere are over 100 serotypes of human enteroviruses, which cause a spectrum ofillnesses, including meningitis, encephalitis, paralysis, myocarditis and rash.Increasing incidence of hand-foot-and-mouth disease in the Asia-Pacific and recentoutbreaks of enterovirus-associated disease, such as severe respiratory illness in theUnited States in 2014, highlight the threat of these viruses to human health.Recent findingsWe describe recent outbreaks of human enteroviruses and summarise knowledgegaps regarding their burden, spectrum of diseases and epidemiology.SummaryReported outbreaks of respiratory, neurological, skin and eye diseases associatedwith human enteroviruses have increased in frequency and size in recent years.Improved molecular diagnostics and genetic sequence analysis are beginning toreveal the complex dynamics of individual serotypes and genotypes, and theircontribution to these outbreaks. However, the biological mechanisms underlying theiremergence and transmission dynamics remain elusive. They are likely to involvechanges in the virus, such as fitness, antigenicity, virulence or tropism, and in thehuman population, such as levels of sanitation and of homo- and heterotypicimmunity. Improvements in surveillance, serological surveys and detailed geneticand antigenic characterisation of viral populations would help to elucidate thesemechanisms. This will be important for the design of outbreak control and vaccinedevelopment strategies.
de Celles MD, Pons-Salort M, Varon E, et al., 2015, Interaction of vaccination and reduction of antibiotic use drives unexpected increase of pneumococcal meningitis, Scientific Reports, Vol: 5, Pages: 1-11, ISSN: 2045-2322
Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.
Pons-Salort M, Serra-Cobo J, Jay F, et al., 2014, Insights into Persistence Mechanisms of a Zoonotic Virus in Bat Colonies Using a Multispecies Metapopulation Model, PLOS ONE, Vol: 9, ISSN: 1932-6203
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- Citations: 13
Pons-Salort M, Thiebaut ACM, Guillemot D, et al., 2013, HPV genotype replacement: too early to tell, LANCET INFECTIOUS DISEASES, Vol: 13, Pages: 1012-1012, ISSN: 1473-3099
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- Citations: 8
Bernard E, Pons-Salort M, Favre M, et al., 2013, Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: a meta-analysis of observational studies, BMC INFECTIOUS DISEASES, Vol: 13
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- Citations: 35
Pons-Salort M, Letort V, Favre M, et al., 2013, Exploring individual HPV coinfections is essential to predict HPV-vaccination impact on genotype distribution: A model-based approach, VACCINE, Vol: 31, Pages: 1238-1245, ISSN: 0264-410X
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- Citations: 13
Pons-Salort M, van der Sanden B, Juhem A, et al., 2012, A Computational Framework to Assess the Efficacy of Cytotoxic Molecules and Vascular Disrupting Agents against Solid Tumours, MATHEMATICAL MODELLING OF NATURAL PHENOMENA, Vol: 7, Pages: 49-77, ISSN: 0973-5348
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- Citations: 7
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