Imperial College London

ProfessorNicholasGrassly

Faculty of MedicineSchool of Public Health

Prof of Infectious Disease & Vaccine Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3264n.grassly Website

 
 
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Location

 

G36Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

116 results found

Parker EPK, Grassly NC, 2016, Polio vaccination: preparing for a change of routine (vol 388, pg 107, 2016), LANCET, Vol: 388, Pages: E2-E2, ISSN: 0140-6736

Journal article

Pons-Salort M, Burns CC, Lyons H, Blake IM, Jafari H, Oberste MS, Kew OM, Grassly NCet 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

Journal article

Parker EPK, Grassly NC, 2016, Polio vaccination: preparing for a change of routine, Lancet, Vol: 388, Pages: 9-15, ISSN: 1474-547X

Journal article

Grassly NC, Praharaj I, Babji S, Kaliappan SP, Giri S, Venugopal S, Parker EP, Abraham A, Muliyil J, Doss S, Raman U, Liu J, Peter JV, Paranjape M, Jeyapaul S, Balakumar S, Ravikumar J, Srinivasan R, Bahl S, Iturriza-Gómara M, Uhlig HH, Houpt ER, John J, Kang Get al., 2016, The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants, Lancet Infectious Diseases, Vol: 16, Pages: 905-914, ISSN: 1473-3099

BACKGROUND: Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries, similarly to other oral vaccines. The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem. Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens, we aimed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity. METHODS: We did a double-blind, randomised, placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district, India. Infants were eligible to participate if they were 6-11 months old, available for the study duration, and lacked serum neutralising antibodies to serotype-3 poliovirus. Infants were randomly assigned (1:1) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days, followed by serotype-3 monovalent oral poliovirus vaccine on day 14. The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per-protocol population (ie, all those who received azithromycin or placebo, oral poliovirus vaccine, and provided a blood sample according to the study protocol). Safety outcomes were assessed in all infants enrolled in the study. The trial is registered with the Clinical Trials Registry India, number CTRI/2014/05/004588. FINDINGS: Between Aug 5, 2014, and March 21, 2015, 754 infants were randomly assigned: 376 to receive azithromycin and 378 to placebo. Of these, 348 (93%) of 376 in the azithromycin group and 357 (94%) of 378 infants in the placebo group completed the study per protocol. In the azithromycin group, 175 (50%) seroconverted to serotype-3 poliovirus compared with 192 (54%) in the placebo group (risk rati

Journal article

John J, Van Aart CJC, Grassly NC, 2016, The burden of typhoid and paratyphoid in India: systematic review and meta-analysis, PLOS Neglected Tropical Diseases, Vol: 10, ISSN: 1935-2735

BackgroundTyphoid is an important public health challenge for India, especially with the spread of antimicrobial resistance. The decision about whether to introduce a public vaccination programme needs to be based on an understanding of disease burden and the age-groups and geographic areas at risk.MethodsWe searched Medline and Web of Science databases for studies reporting the incidence or prevalence of typhoid and paratyphoid fever confirmed by culture and/or serology, conducted in India and published between 1950 and 2015. We used binomial and Poisson mixed-effects meta-regression models to estimate prevalence and incidence from hospital and community studies, and to identify risk-factors.ResultsWe identified 791 titles and abstracts, and included 37 studies of typhoid and 18 studies of paratyphoid in the systematic review and meta-analysis. The estimated prevalence of laboratory-confirmed typhoid and paratyphoid among individuals with fever across all hospital studies was 9.7% (95% CI: 5.7–16.0%) and 0.9% (0.5–1.7%) respectively. There was significant heterogeneity among studies (p-values<0.001). Typhoid was more likely to be detected among clinically suspected cases or during outbreaks and showed a significant decline in prevalence over time (odds ratio for each yearly increase in study date was 0.96 (0.92–0.99) in the multivariate meta-regression model). Paratyphoid did not show any trend over time and there was no clear association with risk-factors. Incidence of typhoid and paratyphoid was reported in 3 and 2 community cohort studies respectively (in Kolkata and Delhi, or Kolkata alone). Pooled estimates of incidence were 377 (178–801) and 105 (74–148) per 100,000 person years respectively, with significant heterogeneity between locations for typhoid (p<0.001). Children 2–4 years old had the highest incidence.ConclusionsTyphoid remains a significant burden in India, particularly among young children, despite apparen

Journal article

Lopman BA, Grassly NC, 2016, Editorial Commentary: Pediatric Norovirus in Developing Countries: A Picture Slowly Comes Into Focus, Clinical Infectious Diseases, Vol: 62, Pages: 1218-1220, ISSN: 1537-6591

Journal article

Blake IM, Chenoweth P, Okayasu H, Donnelly C, Aylward RB, Grassly NCet al., 2016, Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication, Emerging Infectious Diseases, Vol: 22, Pages: 449-456, ISSN: 1080-6040

As the global eradication of poliomyelitis approaches the final stages, prompt detection of new outbreaks is critical to enable a fast and effective outbreak response. Surveillance relies on reporting of acute flaccid paralysis (AFP) cases and laboratory confirmation through isolation of poliovirus from stool. However, delayed sample collection and testing can delay outbreak detection. We investigated whether weekly testing for clusters of AFP by location and time, using the Kulldorff scan statistic, could provide an early warning for outbreaks in 20 countries. A mixed-effects regression model was used to predict background rates of nonpolio AFP at the district level. In Tajikistan and Congo, testing for AFP clusters would have resulted in an outbreak warning 39 and 11 days, respectively, before official confirmation of large outbreaks. This method has relatively high specificity and could be integrated into the current polio information system to support rapid outbreak response activities.

Journal article

Gambhir M, Grassly NC, Burton MJ, Solomon AW, Taylor HR, Mabey DC, Blake IM, Basanez M-Get al., 2015, Estimating the Future Impact of a Multi-Pronged Intervention Strategy on Ocular Disease Sequelae Caused by Trachoma: A Modeling Study, Ophthalmic Epidemiology, Vol: 22, Pages: 394-402, ISSN: 1744-5086

Purpose: Trachoma control programs are underway in endemic regions worldwide. They are based on the SAFE strategy (Surgery for trichiasis, Antibiotic distribution, Facial cleanliness, and Environmental improvement). Although much is known about the effect of community-wide treatment with antibiotics on the prevalence of Chlamydia trachomatis, the impact of the SAFE strategy on severe ocular disease sequelae (the main focus of the Global Elimination of blinding Trachoma by 2020 program) remains largely unknown.Methods: We use a mathematical model to explore the impact of each of the components of the SAFE strategy, individually and together, on disease sequelae, arising from repeat infection and subsequent conjunctival scarring. We ask whether two elimination goals, to reduce the prevalence of trachomatous trichiasis to 1 per 1000 persons, and the incidence of corneal opacity to 1 per 10,000 persons per annum, are achievable, and which combinations of interventions have the greatest impact on these indicators.Results: In high prevalence communities (here, >20% infection of children aged 1–9 years), a combination of efforts is needed to bring down sustainably the prevalence and incidence of ocular disease sequelae.Conclusion: The mass delivery of antibiotics is highly beneficial for the clearance of infection, inflammation and prevention of subsequent scarring, but needs to be supplemented with sustained reductions in transmission and surgery to consider realistically the elimination of blindness by the year 2020.

Journal article

O'Reilly KM, cori A, Durry E, Wadood MZ, Bosan A, Aylward RB, Grassly NCet al., 2015, A new method to estimate the coverage of mass vaccination campaigns against poliomyelitis from surveillance data., American Journal of Epidemiology, Vol: 182, Pages: 961-970, ISSN: 1476-6256

Mass vaccination campaigns with the oral poliovirus vaccine targeting children aged <5 years are a critical component of the global poliomyelitis eradication effort. Monitoring the coverage of these campaigns is essential to allow corrective action, but current approaches are limited by their cross-sectional nature, nonrandom sampling, reporting biases, and accessibility issues. We describe a new Bayesian framework using data augmentation and Markov chain Monte Carlo methods to estimate variation in vaccination coverage from children's vaccination histories investigated during surveillance for acute flaccid paralysis. We tested the method using simulated data with at least 200 cases and were able to detect undervaccinated groups if they exceeded 10% of all children and temporal changes in coverage of ±10% with greater than 90% sensitivity. Application of the method to data from Pakistan for 2010–2011 identified undervaccinated groups within the Balochistan/Federally Administered Tribal Areas and Khyber Pakhtunkhwa regions, as well as temporal changes in coverage. The sizes of these groups are consistent with the multiple challenges faced by the program in these regions as a result of conflict and insecurity. Application of this new method to routinely collected data can be a useful tool for identifying poorly performing areas and assisting in eradication efforts.

Journal article

Ho DK, Sawicki C, Grassly N, 2015, Antibiotic Resistance in Streptococcus pneumoniae after Azithromycin Distribution for Trachoma., Journal of Tropical Medicine, Vol: 2015, ISSN: 1687-9694

Trachoma is caused by Chlamydia trachomatis and is a leading cause of blindness worldwide. Mass distribution of azithromycin (AZM) is part of the strategy for the global elimination of blinding trachoma by 2020. Although resistance to AZM in C. trachomatis has not been reported, there have been concerns about resistance in other organisms when AZM is administered in community settings. We identified studies that measured pneumococcal prevalence and resistance to AZM following mass AZM provision reported up to 2013 in Medline and Web of Science databases. Potential sources of bias were assessed using the Cochrane Risk of Bias Tool. A total of 45 records were screened, of which 8 met the inclusion criteria. We identified two distinct trends of resistance prevalence, which are dependent on frequency of AZM provision and baseline prevalence of resistance. We also demonstrated strong correlation between the prevalence of resistance at baseline and at 2-3 months (r = 0.759). Although resistance to AZM in C. trachomatis has not been reported, resistance to this commonly used macrolide antibiotic in other diseases could compromise treatment. This should be considered when planning long-term trachoma control strategies.

Journal article

Grassly NC, 2015, New vaccine strategies to finish polio eradication, LANCET INFECTIOUS DISEASES, Vol: 15, Pages: 864-865, ISSN: 1473-3099

Journal article

Parker EP, Molodecky NA, Pons-Salort M, O'Reilly KM, Grassly NCet 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.

Journal article

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.

Journal article

Grassly NC, Kang G, Kannpmann B, 2015, Biological challenges to effective vaccines in the developing world, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436

Journal article

Grassly NC, 2014, Immunogenicity and Effectiveness of Routine Immunization With 1 or 2 Doses of Inactivated Poliovirus Vaccine: Systematic Review and Meta-analysis, JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: S439-S446, ISSN: 0022-1899

Journal article

John J, Giri S, Karthikeyan AS, Iturriza-Gomara M, Muliyil J, Abraham A, Grassly NC, Kang Get al., 2014, Effect of a single inactivated poliovirus vaccine dose on intestinal immunity against poliovirus in children previously given oral vaccine: an open-label, randomised controlled trial, LANCET, Vol: 384, Pages: 1505-1512, ISSN: 0140-6736

Journal article

Parker EPK, Kampmann B, Kang G, Grassly NCet al., 2014, Influence of Enteric Infections on Response to Oral Poliovirus Vaccine: A Systematic Review and Meta-analysis, JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: 853-864, ISSN: 0022-1899

Journal article

Jafari H, Deshpande JM, Sutter RW, Bahl S, Verma H, Ahmad M, Kunwar A, Vishwakarma R, Agarwal A, Jain S, Estivariz C, Sethi R, Molodecky NA, Grassly NC, Pallansch MA, Chatterjee A, Aylward RBet al., 2014, Efficacy of inactivated poliovirus vaccine in India, SCIENCE, Vol: 345, Pages: 922-925, ISSN: 0036-8075

Journal article

Blake IM, Martin R, Goel A, Khetsuriani N, Everts J, Wolff C, Wassilak S, Aylward RB, Grassly NCet al., 2014, The role of older children and adults in wild poliovirus transmission, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 111, Pages: 10604-10609, ISSN: 0027-8424

Journal article

Mangal TD, Aylward RB, Grassly NC, 2014, Integration, community engagement, and polio eradication in Nigeria Reply, LANCET GLOBAL HEALTH, Vol: 2, Pages: E316-E316, ISSN: 2214-109X

Journal article

Mangal TD, Aylward RB, Mwanza M, Gasasira A, Abanida E, Pate MA, Grassly NCet al., 2014, Key issues in the persistence of poliomyelitis in Nigeria: a case-control study, LANCET GLOBAL HEALTH, Vol: 2, Pages: E90-E97, ISSN: 2214-109X

Journal article

Li LM, Grassly NC, Fraser C, 2014, Genomic analysis of emerging pathogens: methods, application and future trends, GENOME BIOLOGY, Vol: 15, ISSN: 1474-760X

Journal article

Mangal TD, Aylward RB, Grassly NC, 2013, The Potential Impact of Routine Immunization with Inactivated Poliovirus Vaccine on Wild-type or Vaccine-derived Poliovirus Outbreaks in a Posteradication Setting, AMERICAN JOURNAL OF EPIDEMIOLOGY, Vol: 178, Pages: 1579-1587, ISSN: 0002-9262

Journal article

Grassly NC, 2013, The final stages of the global eradication of poliomyelitis, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 368, ISSN: 0962-8436

Journal article

Doddington BJ, Bosch J, Oliver JA, Grassly NC, Garcia G, Schmidt BR, Garner TWJ, Fisher MCet al., 2013, Context-dependent amphibian host population response to an invading pathogen, ECOLOGY, Vol: 94, Pages: 1795-1804, ISSN: 0012-9658

Journal article

Koukounari A, Moustaki I, Grassly NC, Blake IM, Basanez M-G, Gambhir M, Mabey DCW, Bailey RL, Burton MJ, Solomon AW, Donnelly CAet al., 2013, Using a Nonparametric Multilevel Latent Markov Model to Evaluate Diagnostics for Trachoma, American Journal of Epidemiology, Vol: 177, Pages: 913-922, ISSN: 0002-9262

In disease control or elimination programs, diagnostics are essential for assessing the impact of interventions, refining treatment strategies, and minimizing the waste of scarce resources. Although high-performance tests are desirable, increased accuracy is frequently accompanied by a requirement for more elaborate infrastructure, which is often not feasible in the developing world. These challenges are pertinent to mapping, impact monitoring, and surveillance in trachoma elimination programs. To help inform rational design of diagnostics for trachoma elimination, we outline a nonparametric multilevel latent Markov modeling approach and apply it to 2 longitudinal cohort studies of trachoma-endemic communities in Tanzania (2000–2002) and The Gambia (2001–2002) to provide simultaneous inferences about the true population prevalence of Chlamydia trachomatis infection and disease and the sensitivity, specificity, and predictive values of 3 diagnostic tests for C. trachomatis infection. Estimates were obtained by using data collected before and after mass azithromycin administration. Such estimates are particularly important for trachoma because of the absence of a true “gold standard” diagnostic test for C. trachomatis. Estimated transition probabilities provide useful insights into key epidemiologic questions about the persistence of disease and the clearance of infection as well as the required frequency of surveillance in the postelimination setting.

Journal article

O'Reilly KM, Durry E, ul Islam O, Quddus A, Abid N, Mir TP, Tangermann RH, Aylward RB, Grassly NCet al., 2012, The effect of mass immunisation campaigns and new oral poliovirus vaccines on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001-11: a retrospective analysis, LANCET, Vol: 380, Pages: 491-498, ISSN: 0140-6736

Journal article

Grassly NC, Jafari H, Bahl S, Sethi R, Deshpande JM, Wolff C, Sutter RW, Aylward RBet al., 2012, Waning Intestinal Immunity After Vaccination With Oral Poliovirus Vaccines in India, JOURNAL OF INFECTIOUS DISEASES, Vol: 205, Pages: 1554-1561, ISSN: 0022-1899

Journal article

Solomon AW, Engels D, Bailey RL, Blake IM, Brooker S, Chen JX, Chen JH, Churcher TS, Drakely CJ, Edwards T, Fenwick A, French MD, Gabrielli AF, Grassly NC, Harding-Esch E, Holland MJ, Koukounari A, Lammie PJ, Leslie J, Mabey DCW, Rhajaoui M, Secor WE, Stothard JR, Wei H, Willingham AL, Zhou XN, Peeling RWet al., 2012, A Diagnostics Platform for the Integrated Mapping, Monitoring and Surveillance of Neglected Tropical Diseases: Rationale and Target Product Profiles, PLoS Neglected Tropical Diseases

Journal article

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