Mark Jit
Mark Jit
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Chair and Professor of the Department of Global and Environmental Health
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Professional overview
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Mark Jit is the inaugural chair and a professor in the Department of Global and Environmental Health. He was formerly head of the Department of Infectious Disease Epidemiology & Dynamics and co-director of the Global Health Economics Centre (GHECO) at the London School of Hygiene & Tropical Medicine (LSHTM). He holds honorary appointments at LSHTM as well as the University of Hong Kong (HKU) and the National University of Singapore (NUS).
Dr. Jit’s research focuses on epidemiological and economic modeling of vaccines to support evidence-based public health decision making. He has published papers covering a range of vaccine-preventable or potentially vaccine-preventable diseases including COVID-19, measles, HPV, pneumococcus, rotavirus, influenza, Group B Streptococcus, dengue, EV71 and RSV as well as methodological papers advancing the ways vaccines are evaluated. This work has influenced many of the major changes to immunization policy in countries around the world. Dr. Jit has served on a number of expert advisory committees in the UK as well as for international organizations such as the World Health Organization. He also organises or contributes to academic and professional courses on vaccine modeling, economics and decision science around the world.
Dr. Jit received his BSc and PhD in Mathematics from University College London, specializing in mathematical biology, and a Master of Public Health degree from King’s College London.
Visit Dr. Jit's Google Scholar's page to learn more about his research portfolio.
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Education
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BSc, Mathematics, University College LondonPhD, Mathematics, University College LondonMPH, Public Health, King's College London
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Honors and awards
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Clarivate Highly Cited Researcher (20222023)Fellow of the Academy of Medical Sciences (2023)Training Fund Award, Health Protection Agency (2007)Andrew Rosen Prize, University College London (1999)Institute of Mathematics and its Applications Award (1998)Departmental Research Studentship, University College London (1998)Student Union Commendation, University College London (1997)Fillon Prize, University College London (1996)Pathfinder Award, University College London (1995)
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Publications
Publications
Exploring surveillance data biases when estimating the reproduction number : With insights into subpopulation transmission of COVID-19 in England
AbstractSherratt, K., Abbott, S., Meakin, S. R., Hellewell, J., Munday, J. D., Bosse, N., Jit, M., & Funk, S. (n.d.).Publication year
2021Journal title
Philosophical Transactions of the Royal Society B: Biological SciencesVolume
376Issue
1829AbstractThe time-varying reproduction number (R t: the average number of secondary infections caused by each infected person) may be used to assess changes in transmission potential during an epidemic. While new infections are not usually observed directly, they can be estimated from data. However, data may be delayed and potentially biased. We investigated the sensitivity of R t estimates to different data sources representing COVID-19 in England, and we explored how this sensitivity could track epidemic dynamics in population sub-groups. We sourced public data on test-positive cases, hospital admissions and deaths with confirmed COVID-19 in seven regions of England over March through August 2020. We estimated R t using a model that mapped unobserved infections to each data source. We then compared differences in R t with the demographic and social context of surveillance data over time. Our estimates of transmission potential varied for each data source, with the relative inconsistency of estimates varying across regions and over time. R t estimates based on hospital admissions and deaths were more spatio-temporally synchronous than when compared to estimates from all test positives. We found these differences may be linked to biased representations of subpopulations in each data source. These included spatially clustered testing, and where outbreaks in hospitals, care homes, and young age groups reflected the link between age and severity of the disease. We highlight that policy makers could better target interventions by considering the source populations of R t estimates. Further work should clarify the best way to combine and interpret R t estimates from different data sources based on the desired use. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.From cervical cancer elimination to eradication of vaccine-type human papillomavirus : Feasibility, public health strategies and cost-effectiveness
AbstractJit, M., Prem, K., Benard, E., & Brisson, M. (n.d.).Publication year
2021Journal title
Preventive MedicineVolume
144AbstractThe Director-General of the World Health Organization has called for global action towards elimination of cervical cancer as a public health problem. Cervical cancer is caused by human papillomavirus (HPV), an infectious agent with no non-human reservoir. One way to achieve this is through very high levels of vaccine coverage that could enable global eradication of vaccine-type HPV. Using the case study of India, we show that HPV eradication can meet all the Dahlem and Strüngmann criteria for feasibility of eradication. It can be achieved with 90% gender-neutral HPV vaccine coverage together with 95% coverage in high-risk groups such as female sex workers. Such a strategy would likely be cost-effective compared to no vaccination. Although it would be more costly in the short-term than achieving cervical cancer elimination alone, it would save costs in the long-term by removing or at least sharply reducing the need for preventive measures.Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection
AbstractJit, M., CMMID COVID-19 Working Group, A., McCarthy, C. V., Sandmann, F. G., Eggo, R. M., Knight, G. M., Flasche, S., Foss, A. M., Klepac, P., Jafari, Y., Waterlow, N. R., Meakin, S. R., Lei, J., Villabona-Arenas, C. J., Procter, S. R., Abbott, S., Funk, S., Bosse, N. I., O'Reilly, K., … Jit, M. (n.d.).Publication year
2021Journal title
Journal of Hospital InfectionVolume
111Page(s)
205-207Abstract~Global diarrhoea-associated mortality estimates and models in children : Recommendations for dataset and study selection
AbstractButkeviciute, E., Prudden, H. J., Jit, M., Smith, P. G., Kang, G., Riddle, M. S., Lopman, B. A., Pitzer, V. E., Lanata, C. F., Platts-Mills, J. A., Breiman, R. F., Giersing, B. K., & Hasso-Agopsowicz, M. (n.d.).Publication year
2021Journal title
VaccineVolume
39Issue
32Page(s)
4391-4398AbstractBackground: Multiple factors contribute to variation in disease burden, including the type and quality of data, and inherent properties of the models used. Understanding how these factors affect mortality estimates is crucial, especially in the context of public health decision making. We examine how the quality of the studies selected to provide mortality data, influence estimates of burden and provide recommendations about the inclusion of studies and datasets to calculate mortality estimates. Methods: To determine how mortality estimates are affected by the data used to generate model outputs, we compared the studies used by The Institute of Health Metrics and Evaluation (IHME) and Maternal and Child Epidemiology Estimation (MCEE) modelling groups to generate enterotoxigenic Escherichia coli (ETEC) and Shigella-associated mortality estimates for 2016. Guided by an expert WHO Working Group, we applied a modified Newcastle-Ottawa Scale (NOS) to evaluate the quality of studies used by both modelling groups. Results: IHME and MCEE used different sets of ETEC and Shigella studies in their models and the majority of studies were high quality. The distribution of the NOS scores was similar between the two modelling groups. We observed an overrepresentation of studies from some countries in SEAR, AFR and WPR compared to other WHO regions. Conclusion: We identified key differences in study inclusion and exclusion criteria used by IHME and MCEE and discuss their impact on datasets used to generate diarrhoea-associated mortality estimates. Based on these observations, we provide a set of recommendations for future estimates of mortality associated with enteric diseases.How can the public health impact of vaccination be estimated?
AbstractEcheverria-Londono, S., Li, X., Toor, J., de Villiers, M. J., Nayagam, S., Hallett, T. B., Abbas, K., Jit, M., Klepac, P., Jean, K., Garske, T., Ferguson, N. M., & Gaythorpe, K. A. (n.d.).Publication year
2021Journal title
BMC public healthVolume
21Issue
1AbstractBackground: Deaths due to vaccine preventable diseases cause a notable proportion of mortality worldwide. To quantify the importance of vaccination, it is necessary to estimate the burden averted through vaccination. The Vaccine Impact Modelling Consortium (VIMC) was established to estimate the health impact of vaccination. Methods: We describe the methods implemented by the VIMC to estimate impact by calendar year, birth year and year of vaccination (YoV). The calendar and birth year methods estimate impact in a particular year and over the lifetime of a particular birth cohort, respectively. The YoV method estimates the impact of a particular year’s vaccination activities through the use of impact ratios which have no stratification and stratification by activity type and/or birth cohort. Furthermore, we detail an impact extrapolation (IE) method for use between coverage scenarios. We compare the methods, focusing on YoV for hepatitis B, measles and yellow fever. Results: We find that the YoV methods estimate similar impact with routine vaccinations but have greater yearly variation when campaigns occur with the birth cohort stratification. The IE performs well for the YoV methods, providing a time-efficient mechanism for updates to impact estimates. Conclusions: These methods provide a robust set of approaches to quantify vaccination impact; however it is vital that the area of impact estimation continues to develop in order to capture the full effect of immunisation.How to Prevent Vaccines Falling Victim to Their Own Success : Intertemporal Dependency of Incidence Levels on Indirect Effects in Economic Reevaluations
AbstractSandmann, F., Ramsay, M., Edmunds, W. J., Choi, Y. H., & Jit, M. (n.d.).Publication year
2021Journal title
Value in HealthVolume
24Issue
10Page(s)
1391-1399AbstractObjectives: Incremental cost-effectiveness analyses may inform the optimal choice of healthcare interventions. Nevertheless, for many vaccines, benefits fluctuate with incidence levels over time. Reevaluating a vaccine after it has successfully decreased incidences may eventually cause a disease resurgence if switching to a vaccine with lower indirect benefits. Decisions may successively alternate between vaccines alongside repeated rises and falls in incidence and when indirect effects from historic use are ignored. Our suggested proposal aims to prevent suboptimal decision making. Methods: We used a conceptual model of demand to illustrate alternating decisions between vaccines because of time-varying levels of indirect effects. Similar to the concept of subsidies, we propose internalizing the indirect effects achievable with vaccines. In a case study over 60 years, we simulated a hypothetical 10-year reevaluation of 2 oncogenic human papillomavirus vaccines, of which only 1 protects additionally against anogenital warts. Results: Our case study showed that the vaccine with additional warts protection is initially valued higher than the vaccine without additional warts protection. After 10 years, this differential decreases because of declines in warts incidence, which supports switching to the nonwarts vaccine that causes a warts resurgence eventually. Instead, pricing the indirect effects separately supports continuing with the warts vaccine. Conclusions: Ignoring how the observed incidences depend on the indirect effects achieved with a particular vaccine may lead to repeated changes in vaccines at successive reevaluations, with unintended resurgences, economic inefficiencies, and eroding vaccine confidence. We propose internalizing indirect effects to prevent vaccines falling victim to their own success.HPV16 and HPV18 seropositivity and DNA detection among men who have sex with men : A cross-sectional study conducted in a sexual health clinic in London
AbstractKing, E. M., Mesher, D., Sonnenberg, P., Linley, E., Panwar, K., Beddows, S., Soldan, K., Borrow, R., Jit, M., & Gilson, R. (n.d.).Publication year
2021Journal title
Sexually transmitted infectionsVolume
97Issue
5Page(s)
382-386AbstractObjectives Men who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection and related diseases compared with men who have sex exclusively with women. From April 2018, there has been a phased roll-out of HPV vaccination offered to MSM aged up to 45 years old who are attending sexual health clinics and HIV clinics in England. The vaccine is most effective if delivered prior to HPV infection. We estimated the proportion of MSM with no current vaccine-type infection and no serological evidence of prior infection, in a study undertaken prior to vaccine introduction. Methods We conducted a cross-sectional study among 484 MSM aged 18-40 years old who attended a sexual health clinic in London between 2010 and 2012. We estimated the prevalence of current and past infection by testing for HPV DNA in anogenital samples and for serum antibodies to HPV16 and HPV18. Results The median age was 30 years (IQR 25-35). The prevalence of HPV16 and HPV18 DNA was 13.2% and 6.2%, respectively. Seropositivity for HPV16 and HPV18 was 28.5% and 17.1%, respectively, with 11.4% seropositive for both types. Seropositivity for the same HPV type was strongly associated with anogenital DNA detection. 279 MSM (57.6%) tested negative for both HPV16 and HPV18 serology and were DNA negative for these two types; only 5 MSM (1.0%) were seropositive and DNA positive for both HPV types. Conclusions This is the first study to determine both the prevalence of HPV DNA in anogenital samples and HPV seroprevalence among MSM attending a sexual health clinic in the UK. Over half of MSM in this study had no evidence of a previous or current infection with either of the high-risk HPV types included in the quadrivalent vaccine, which supports the rationale for opportunistic HPV vaccination of MSM attending sexual health clinics.Impact of covid-19-related disruptions to measles, meningococcal a, and yellow fever vaccination in 10 countries
AbstractVIMC Working Group on COVID-19 Impact on Vaccine Preventable Disease, A., Gaythorpe, K., Abbas, K., Huber, J., Karachaliou, A., Thakkar, N., Woodruff, K., Li, X., Echeverria-Londono, S., Ferrari, M., Jackson, M. L., McCarthy, K., Perkins, A., Trotter, C., & Jit, M. (n.d.).Publication year
2021Journal title
eLifeVolume
10AbstractBackground: Childhood immunisation services have been disrupted by COVID-19. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic. Methods: We used 2-3 models per infection to estimate the health impact of 50% reduced routine vaccination coverage and delaying campaign vaccination for measles, meningococcal A and yellow fever vaccination in 3-6 high burden countries per infection. Results: Reduced routine coverage in 2020 without catch-up vaccination may increase measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns may lead to measles outbreaks and increases in yellow fever burden in some countries. For meningococcal A vaccination, short term disruptions in 2020 are unlikely to have a significant impact. Conclusion: The impact of COVID-19-related disruption to vaccination programs varies between infections and countries.Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England
AbstractCMMID COVID-19 Working Group, A., Munday, J. D., Sherratt, K., Meakin, S., Endo, A., Pearson, C. A., Hellewell, J., Abbott, S., Bosse, N. I., Eggo, R. M., Simons, D., O’Reilly, K., Russell, T. W., Lowe, R., Leclerc, Q. J., Emery, J. C., Klepac, P., Nightingale, E. S., Quaife, M., … Funk, S. (n.d.).Publication year
2021Journal title
Nature communicationsVolume
12Issue
1AbstractIn early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.Importance of patient bed pathways and length of stay differences in predicting COVID-19 hospital bed occupancy in England
AbstractISARIC4C investigators, A., CMMID COVID-19 Working Group, A., Leclerc, Q. J., Fuller, N. M., Keogh, R. H., Diaz-Ordaz, K., Sekula, R., Semple, M. G., Baillie, J. K., Openshaw, P. J., Carson, G., Alex, B., Bach, B., Barclay, W. S., Bogaert, D., Chand, M., Cooke, G. S., Docherty, A. B., Dunning, J., … Jit, M. (n.d.).Publication year
2021Journal title
BMC health services researchVolume
21Issue
1AbstractBackground: Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and their impact on predicted hospital bed occupancy. Methods: We obtained data from University College Hospital (UCH) and the ISARIC4C COVID-19 Clinical Information Network (CO-CIN) on hospitalised patients with COVID-19 who required care in general ward or critical care (CC) beds to determine possible bed pathways and LoS. We developed a discrete-time model to examine the implications of using either bed pathways or only average LoS by bed type to forecast bed occupancy. We compared model-predicted bed occupancy to publicly available bed occupancy data on COVID-19 in England between March and August 2020. Results: In both the UCH and CO-CIN datasets, 82% of hospitalised patients with COVID-19 only received care in general ward beds. We identified four other bed pathways, present in both datasets: “Ward, CC, Ward”, “Ward, CC”, “CC” and “CC, Ward”. Mean LoS varied by bed type, pathway, and dataset, between 1.78 and 13.53 days. For UCH, we found that using bed pathways improved the accuracy of bed occupancy predictions, while only using an average LoS for each bed type underestimated true bed occupancy. However, using the CO-CIN LoS dataset we were not able to replicate past data on bed occupancy in England, suggesting regional LoS heterogeneities. Conclusions: We identified five bed pathways, with substantial variation in LoS by bed type, pathway, and geography. This might be caused by local differences in patient characteristics, clinical care strategies, or resource availability, and suggests that national LoS averages may not be appropriate for local forecasts of bed occupancy for COVID-19. Trial registration: The ISARIC WHO CCP-UK study ISRCTN66726260 was retrospectively registered on 21/04/2020 and designated an Urgent Public Health Research Study by NIHR.Incidence and disease burden of herpes zoster in the population aged ≥50 years in China : Data from an integrated health care network
AbstractSun, X., Wei, Z., Lin, H., Jit, M., Li, Z., & Fu, C. (n.d.).Publication year
2021Journal title
Journal of InfectionVolume
82Issue
2Page(s)
253-260AbstractBackground: Herpes zoster (HZ) mainly affects elderly and immunocompromised individuals and is characterized by a painful vesicular rash. Data on the epidemiology of HZ, particularly in unvaccinated individuals aged ≥50 years, are still limited in China. Thus, this study aimed to evaluate the epidemiological features, disease burden, and associated risk factors of HZ in the population aged ≥50 years in China. Methods: We evaluated HZ patients who were aged ≥50 years between January 1, 2015 and December 31, 2017 in the electronic health record database of Yinzhou district. HZ and its complications were identified using ICD-10 codes. In addition, post-herpetic neuralgia (PHN) as a complication of HZ was defined as pain occurring or persisting 90 days after rash onset. The disease burden was estimated according to the duration of hospitalization, frequency of visits, pharmacological treatment cost, and examination cost. Cox proportional hazards regression was used to investigate the associated risk factors for HZ. Results: The overall incidence of HZ was 6.64 per 1000 person-years. Of the 4,313 initial episodes from 2015 to 2017, there were 99 recurrent cases. In total, 7.26% and 3.94% of the HZ patients had PHN and other complications, respectively. The average frequency of outpatient visits was significantly lower in patients with initial disease than that in patients with recurrence (3.6 vs. 6.7 per patient). The mean duration of hospital stay was longer in the recurrent episode than that in the initial episode (24.0 vs. 21.6 days). The inpatient and outpatient cost per new-onset HZ was approximately ¥8116.9 and ¥560.2 per patient, respectively. Age; female sex; suburban residency; and presence of immunocompromised disease, hypertension, or diabetes were significantly associated with the development of HZ. Conclusion: The incidence and recurrence rates of HZ showed different trends with increasing age. The presence of HZ-related complications increased the direct medical costs. Our findings help provide a basis for developing appropriate strategies for HZ prevention and control.Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7
AbstractCMMID COVID-19 Working Group, A., Davies, N. G., Jarvis, C. I., van Zandvoort, K., Clifford, S., Sun, F. Y., Funk, S., Medley, G., Jafari, Y., Meakin, S. R., Lowe, R., Quaife, M., Waterlow, N. R., Eggo, R. M., Lei, J., Koltai, M., Krauer, F., Tully, D. C., Munday, J. D., … Brady, O. (n.d.).Publication year
2021Journal title
NatureVolume
593Issue
7858Page(s)
270-274AbstractSARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)1). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39–72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness.Informing Global Cost-Effectiveness Thresholds Using Country Investment Decisions : Human Papillomavirus Vaccine Introductions in 2006-2018
AbstractJit, M. (n.d.).Publication year
2021Journal title
Value in HealthVolume
24Issue
1Page(s)
61-66AbstractObjectives: Cost-effectiveness analysis can guide decision making about health interventions, but the appropriate cost-effectiveness threshold to use is unclear in most countries. The World Health Organization (WHO) recommends vaccinating girls 9 to 14 years against human papillomavirus (HPV), but over half the world's countries have not introduced it. This study aimed to investigate whether country-level decisions about HPV vaccine introduction are consistent with a particular cost-effectiveness threshold, and to estimate what that threshold may be. Methods: The cost-effectiveness of vaccinating 12-year-old girls was estimated in 179 countries using the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model, together with vaccine price data from World Health Organization's Market Information for Access to Vaccines database. In each year from 2006 to 2018, countries were categorized based on (1) whether they had introduced HPV vaccination, and (2) whether the incremental cost-effectiveness ratio for HPV vaccine introduction fell below a certain cost-effectiveness threshold. Results: A cost-effectiveness threshold of 60% to 65% of GDP per capita has the best ability to discriminate countries that introduced vaccination, with a diagnostic odds ratio of about 7. For low-income countries the optimal threshold was lower, at 30% to 40% of GDP per capita. Conclusions: A cost-effectiveness threshold has some ability to discriminate between HPV vaccine introducer and non-introducer countries, although the average threshold is below the widely used threshold of 1 GDP per capita. These results help explain the current pattern of HPV vaccine use globally. They also inform the extent to which cost-effectiveness thresholds proposed in the literature reflect countries’ actual investment decisions.Lives saved with vaccination for 10 pathogens across 112 countries in a pre-covid-19 world
AbstractToor, J., Echeverria-Londono, S., Li, X., Abbas, K., Carter, E. D., Clapham, H. E., Clark, A., de Villiers, M. J., Eilertson, K., Ferrari, M., Gamkrelidze, I., Hallett, T. B., Hinsley, W. R., Hogan, D., Huber, J. H., Jackson, M. L., Jean, K., Jit, M., Karachaliou, A., … Gaythorpe, K. A. (n.d.).Publication year
2021Journal title
eLifeVolume
10AbstractBackground: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000–2030 across 112 countries. Methods: Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios. Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000–2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases. Conclusions: This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.Modeling the effect of vaccination on selection for antibiotic resistance in Streptococcus pneumoniae
AbstractDavies, N. G., Flasche, S., Jit, M., & Atkins, K. E. (n.d.).Publication year
2021Journal title
Science Translational MedicineVolume
13Issue
606AbstractVaccines against bacterial pathogens can protect recipients from becoming infected with potentially antibiotic-resistant pathogens. However, by altering the selective balance between antibiotic-sensitive and antibiotic-resistant bacterial strains, vaccines may also suppress-or spread-antibiotic resistance among unvaccinated individuals. Predicting the outcome of vaccination requires knowing what drives selection for drug-resistant bacterial pathogens and what maintains the circulation of both antibiotic-sensitive and antibiotic-resistant strains of bacteria. To address this question, we used mathematical modeling and data from 2007 on penicillin consumption and penicillin nonsusceptibility in Streptococcus pneumoniae (pneumococcus) invasive isolates from 27 European countries. We show that the frequency of penicillin resistance in S. pneumoniae can be explained by between-host diversity in antibiotic use, heritable diversity in pneumococcal carriage duration, or frequency-dependent selection brought about by within-host competition between antibiotic-resistant and antibiotic-sensitive S. pneumoniae strains. We used our calibrated models to predict the impact of non-serotype-specific pneumococcal vaccination upon the prevalence of S. pneumoniae carriage, incidence of disease, and frequency of S. pneumoniae antibiotic resistance. We found that the relative strength and directionality of competition between drug-resistant and drug-sensitive pneumococcal strains was the most important determinant of whether vaccination would promote, inhibit, or have little effect upon the evolution of antibiotic resistance. Last, we show that country-specific differences in pathogen transmission substantially altered the predicted impact of vaccination, highlighting that policies for managing antibiotic resistance with vaccines must be tailored to a specific pathogen and setting.Models of COVID-19 vaccine prioritisation : a systematic literature search and narrative review
AbstractSaadi, N., Chi, Y. L., Ghosh, S., Eggo, R. M., McCarthy, C. V., Quaife, M., Dawa, J., Jit, M., & Vassall, A. (n.d.).Publication year
2021Journal title
BMC MedicineVolume
19Issue
1AbstractBackground: How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes. Methods: We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed. Results: The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage. Conclusion: The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands : a national matched cohort study
AbstractHorváth-Puhó, E., van Kassel, M. N., Gonçalves, B. P., de Gier, B., Procter, S. R., Paul, P., van der Ende, A., Søgaard, K. K., Hahné, S. J., Chandna, J., Schrag, S. J., van de Beek, D., Jit, M., Sørensen, H. T., Bijlsma, M. W., & Lawn, J. E. (n.d.).Publication year
2021Journal title
The Lancet Child and Adolescent HealthVolume
5Issue
6Page(s)
398-407AbstractBackground: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands. Methods: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts. Findings: 2258 children—1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)—were identified to have iGBS disease and followed up for a median of 14 years (IQR 7–18) in Denmark and 9 years (6–11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78–9·35] for Denmark and 6·73 [3·76–12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44–2·18]) and the Netherlands (2·28 [1·64–3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79–2·09], pMulti-country collaboration in responding to global infectious disease threats : lessons for Europe from the COVID-19 pandemic
AbstractJit, M., Ananthakrishnan, A., McKee, M., Wouters, O. J., Beutels, P., & Teerawattananon, Y. (n.d.).Publication year
2021Journal title
The Lancet Regional Health - EuropeVolume
9AbstractSince 2005, the world has faced several public health emergencies of international concern arising from infectious disease outbreaks. Of these, the COVID-19 pandemic has had by far the greatest health and economic consequences. During these emergencies, responses taken by one country often have an impact on other countries. The implication is that coordination between countries is likely to achieve better outcomes, individually and collectively, than each country independently pursuing its own self-interest. During the COVID-19 pandemic, gaps in multilateral cooperation on research and information sharing, vaccine development and deployment, and travel policies have hampered the speed and equity of global recovery. In this Health Policy article, we explore how multilateral collaboration between countries is crucial to successful responses to public health emergencies linked to infectious disease outbreaks. Responding to future global infectious disease threats and other health emergencies will require the creation of stronger mechanisms for multilateral collaboration before they arise. A change to the governance of multilateral institutions is a logical next step, with a focus on providing equal ownership and leadership opportunities to all member countries. Europe can be an example and advocate for stronger and better governed multilateral institutions.Optimal human papillomavirus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources : a mathematical modelling analysis
AbstractDrolet, M., Laprise, J. F., Martin, D., Jit, M., Bénard, É., Gingras, G., Boily, M. C., Alary, M., Baussano, I., Hutubessy, R., & Brisson, M. (n.d.).Publication year
2021Journal title
The Lancet Infectious DiseasesVolume
21Issue
11Page(s)
1598-1610AbstractBackground: Introduction of human papillomavirus (HPV) vaccination has been slow in low-income and middle-income countries (LMICs) because of resource constraints and worldwide shortage of vaccine supplies. To help inform WHO recommendations, we modelled various HPV vaccination strategies to examine the optimal use of limited vaccine supplies and best allocation of scarce resources in LMICs in the context of the WHO global call to eliminate cervical cancer as a public health problem. Methods: In this mathematical modelling analysis, we developed HPV-ADVISE LMIC, a transmission-dynamic model of HPV infection and diseases calibrated to four LMICs: India, Vietnam, Uganda, and Nigeria. For different vaccination strategies that encompassed use of a nine-valent vaccine (or a two-valent or four-valent vaccine assuming high cross-protection), we estimated three outcomes: reduction in the age-standardised rate of cervical cancer, number of doses needed to prevent one case of cervical cancer (NNV; as a measure of efficiency), and the incremental cost-effectiveness ratio (ICER; in 2017 international $ per disability-adjusted life-year [DALY] averted). We examined different vaccination strategies by varying the ages of routine HPV vaccination and number of age cohorts vaccinated, the population targeted, and the number of doses used. In our base case, we assumed 100% lifetime protection against HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58; vaccination coverage of 80%; and a time horizon of 100 years. For the cost-effectiveness analysis, we used a 3% discount rate. Elimination of cervical cancer was defined as an age-standardised incidence of less than four cases per 100 000 woman-years. Findings: We predicted that HPV vaccination could lead to cervical cancer elimination in Vietnam, India, and Nigeria, but not in Uganda. Compared with no vaccination, strategies that involved vaccinating girls aged 9–14 years with two doses were predicted to be the most efficient and cost-effective in all four LMICs. NNV ranged from 78 to 381 and ICER ranged from $28 per DALY averted to $1406 per DALY averted depending on the country. The most efficient and cost-effective strategies were routine vaccination of girls aged 14 years, with or without a later switch to routine vaccination of girls aged 9 years, and routine vaccination of girls aged 9 years with a 5-year extended interval between doses and a catch-up programme at age 14 years. Vaccinating boys (aged 9–14 years) or women aged 18 years or older resulted in substantially higher NNVs and ICERs. Interpretation: We identified two strategies that could maximise efforts to prevent cervical cancer in LMICs given constraints on vaccine supplies and costs and that would allow a maximum of LMICs to introduce HPV vaccination. Funding: World Health Organization, Canadian Institute of Health Research, Fonds de recherche du Québec–Santé, Compute Canada, PATH, and The Bill & Melinda Gates Foundation. Translations: For the French and Spanish translations of the abstract see Supplementary Materials section.Projecting contact matrices in 177 geographical regions : An update and comparison with empirical data for the COVID-19 era
AbstractPrem, K., van Zandvoort, K., Klepac, P., Eggo, R. M., Davies, N. G., Cook, A. R., & Jit, M. (n.d.).Publication year
2021Journal title
PLoS computational biologyVolume
17Issue
7Page(s)
1DUMMUYAbstractMathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.Projections of human papillomavirus (HPV) vaccination impact in Ethiopia, India, Nigeria and Pakistan : A comparative modelling study
AbstractPortnoy, A., Abbas, K., Sweet, S., Kim, J. J., & Jit, M. (n.d.).Publication year
2021Journal title
BMJ Global HealthVolume
6Issue
11AbstractIntroduction Cervical cancer is the second most common cancer among women in Ethiopia, India, Nigeria and Pakistan. Our study objective was to assess similarities and differences in vaccine-impact projections through comparative modelling analysis by independently estimating the potential health impact of human papillomavirus (HPV) vaccination. Methods Using two widely published models (Harvard and Papillomavirus Rapid Interface for Modelling and Economics (PRIME)) to estimate HPV vaccination impact, we simulated a vaccination scenario of 90% annual coverage among 10 cohorts of 9-year-old girls from 2021 to 2030 in Ethiopia, India, Nigeria and Pakistan. We estimated potential health impact in terms of cervical cancer cases, deaths and disability-adjusted life years averted among vaccinated cohorts from the time of vaccination until 2100. We harmonised the two models by standardising input data to comparatively estimate HPV vaccination impact. Results Prior to harmonising model assumptions, the range between PRIME and Harvard models for number of cervical cancer cases averted by HPV vaccination was: 262 000 to 2 70 000 in Ethiopia; 1 640 000 to 1 970 000 in India; 330 000 to 3 36 000 in Nigeria and 111 000 to 1 33 000 in Pakistan. When harmonising model assumptions, alignment on HPV type distribution significantly narrowed differences in vaccine-impact estimates. Conclusion Despite model differences, the Harvard and PRIME models yielded similar vaccine-impact estimates. The main differences in estimates are due to variation in interpretation around data on cervical cancer attribution to HPV-16/18. As countries make progress towards WHO targets for cervical cancer elimination, continued explorations of underlying differences in model inputs, assumptions and results when examining cervical cancer prevention policy will be critical.Quantifying long-term health and economic outcomes for survivors of group B Streptococcus invasive disease in infancy : Protocol of a multi-country study in Argentina, India, Kenya, Mozambique and South Africa
AbstractProcter, S. R., Paul, P., Dangor, Z., Bassat, Q., Abubakar, A., Santhanam, S., Libster, R., Gonçalves, B. P., Madhi, S. A., Bardají, A., Mwangome, E., Mabrouk, A., John, H. B., Sánchez Yanotti, C., Chandna, J., Sithole, P., Mucasse, H., Katana, P. V., Koukounari, A., … Lawn, J. E. (n.d.).Publication year
2021Journal title
Gates Open ResearchVolume
4AbstractSepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa. The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization.Quarantine and testing strategies in contact tracing for SARS-CoV-2 : a modelling study
AbstractCentre for the Mathematical Modelling of Infectious Diseases COVID-19 working group, A., Quilty, B. J., Clifford, S., Hellewell, J., Russell, T. W., Kucharski, A. J., Flasche, S., Edmunds, W. J., Atkins, K. E., Foss, A. M., Waterlow, N. R., Abbas, K., Lowe, R., Pearson, C. A., Funk, S., Rosello, A., Knight, G. M., Bosse, N. I., Procter, S. R., … Davies, N. G. (n.d.).Publication year
2021Journal title
The Lancet Public HealthVolume
6Issue
3Page(s)
e175-e183AbstractBackground: In most countries, contacts of confirmed COVID-19 cases are asked to quarantine for 14 days after exposure to limit asymptomatic onward transmission. While theoretically effective, this policy places a substantial social and economic burden on both the individual and wider society, which might result in low adherence and reduced policy effectiveness. We aimed to assess the merit of testing contacts to avert onward transmission and to replace or reduce the length of quarantine for uninfected contacts. Methods: We used an agent-based model to simulate the viral load dynamics of exposed contacts, and their potential for onward transmission in different quarantine and testing strategies. We compared the performance of quarantines of differing durations, testing with either PCR or lateral flow antigen (LFA) tests at the end of quarantine, and daily LFA testing without quarantine, against the current 14-day quarantine strategy. We also investigated the effect of contact tracing delays and adherence to both quarantine and self-isolation on the effectiveness of each strategy. Findings: Assuming moderate levels of adherence to quarantine and self-isolation, self-isolation on symptom onset alone can prevent 37% (95% uncertainty interval [UI] 12–56) of onward transmission potential from secondary cases. 14 days of post-exposure quarantine reduces transmission by 59% (95% UI 28–79). Quarantine with release after a negative PCR test 7 days after exposure might avert a similar proportion (54%, 95% UI 31–81; risk ratio [RR] 0·94, 95% UI 0·62–1·24) to that of the 14-day quarantine period, as would quarantine with a negative LFA test 7 days after exposure (50%, 95% UI 28–77; RR 0·88, 0·66–1·11) or daily testing without quarantine for 5 days after tracing (50%, 95% UI 23–81; RR 0·88, 0·60–1·43) if all tests are returned negative. A stronger effect might be possible if individuals isolate more strictly after a positive test and if contacts can be notified faster. Interpretation: Testing might allow for a substantial reduction in the length of, or replacement of, quarantine with a small excess in transmission risk. Decreasing test and trace delays and increasing adherence will further increase the effectiveness of these strategies. Further research is required to empirically evaluate the potential costs (increased transmission risk, false reassurance) and benefits (reduction in the burden of quarantine, increased adherence) of such strategies before adoption as policy. Funding: National Institute for Health Research, UK Research and Innovation, Wellcome Trust, EU Horizon 2021, and the Bill & Melinda Gates Foundation.Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection
AbstractJombart, T., Ghozzi, S., Schumacher, D., Taylor, T. J., Leclerc, Q. J., Jit, M., Flasche, S., Greaves, F., Ward, T., Eggo, R. M., Nightingale, E., Meakin, S., Brady, O. J., Medley, G. F., Höhle, M., & Edmunds, W. J. (n.d.).Publication year
2021Journal title
Philosophical Transactions of the Royal Society B: Biological SciencesVolume
376Issue
1829AbstractAs several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.SARS-CoV-2 infection risk during delivery of childhood vaccination campaigns : a modelling study
AbstractCMMID COVID-19 Working Group, A., Procter, S. R., Abbas, K., Flasche, S., Griffiths, U., Hagedorn, B., O’Reilly, K. M., Waterlow, N. R., Villabona-Arenas, C. J., Munday, J. D., Medley, G. F., Lowe, R., Mee, P., Liu, Y., Gimma, A., van Zandvoort, K., Hellewell, J., Tully, D. C., Brady, O., … Jit, M. (n.d.).Publication year
2021Journal title
BMC MedicineVolume
19Issue
1AbstractBackground: The COVID-19 pandemic has disrupted the delivery of immunisation services globally. Many countries have postponed vaccination campaigns out of concern about infection risks to the staff delivering vaccination, the children being vaccinated, and their families. The World Health Organization recommends considering both the benefit of preventive campaigns and the risk of SARS-CoV-2 transmission when making decisions about campaigns during COVID-19 outbreaks, but there has been little quantification of the risks. Methods: We modelled excess SARS-CoV-2 infection risk to vaccinators, vaccinees, and their caregivers resulting from vaccination campaigns delivered during a COVID-19 epidemic. Our model used population age structure and contact patterns from three exemplar countries (Burkina Faso, Ethiopia, and Brazil). It combined an existing compartmental transmission model of an underlying COVID-19 epidemic with a Reed-Frost model of SARS-CoV-2 infection risk to vaccinators and vaccinees. We explored how excess risk depends on key parameters governing SARS-CoV-2 transmissibility, and aspects of campaign delivery such as campaign duration, number of vaccinations, and effectiveness of personal protective equipment (PPE) and symptomatic screening. Results: Infection risks differ considerably depending on the circumstances in which vaccination campaigns are conducted. A campaign conducted at the peak of a SARS-CoV-2 epidemic with high prevalence and without special infection mitigation measures could increase absolute infection risk by 32 to 45% for vaccinators and 0.3 to 0.5% for vaccinees and caregivers. However, these risks could be reduced to 3.6 to 5.3% and 0.1 to 0.2% respectively by use of PPE that reduces transmission by 90% (as might be achieved with N95 respirators or high-quality surgical masks) and symptomatic screening. Conclusions: SARS-CoV-2 infection risks to vaccinators, vaccinees, and caregivers during vaccination campaigns can be greatly reduced by adequate PPE, symptomatic screening, and appropriate campaign timing. Our results support the use of adequate risk mitigation measures for vaccination campaigns held during SARS-CoV-2 epidemics, rather than cancelling them entirely.