Mark Jit

Mark Jit
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
The contribution of pre-symptomatic infection to the transmission dynamics of COVID-2019
Failed generating bibliography.AbstractPublication year
2020Journal title
Wellcome Open ResearchVolume
5AbstractBackground: Pre-symptomatic transmission can be a key determinant of the effectiveness of containment and mitigation strategies for infectious diseases, particularly if interventions rely on syndromic case finding. For COVID-19, infections in the absence of apparent symptoms have been reported frequently alongside circumstantial evidence for asymptomatic or pre-symptomatic transmission. We estimated the potential contribution of pre-symptomatic cases to COVID-19 transmission. Methods: Using the probability for symptom onset on a given day inferred from the incubation period, we attributed the serial interval reported from Shenzen, China, into likely pre-symptomatic and symptomatic transmission. We used the serial interval derived for cases isolated more than 6 days after symptom onset as the no active case finding scenario and the unrestricted serial interval as the active case finding scenario. We reported the estimate assuming no correlation between the incubation period and the serial interval alongside a range indicating alternative assumptions of positive and negative correlation. Results: We estimated that 23% (range accounting for correlation: 12 - 28%) of transmissions in Shenzen may have originated from pre-symptomatic infections. Through accelerated case isolation following symptom onset, this percentage increased to 46% (21 - 46%), implying that about 35% of secondary infections among symptomatic cases have been prevented. These results were robust to using reported incubation periods and serial intervals from other settings. Conclusions: Pre-symptomatic transmission may be essential to consider for containment and mitigation strategies for COVID-19.The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study
Failed generating bibliography.AbstractPublication year
2020Journal title
The Lancet Public HealthVolume
5Issue
5Page(s)
e261-e270AbstractBackground: In December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures in response to the outbreak, including extended school and workplace closures. We aimed to estimate the effects of physical distancing measures on the progression of the COVID-19 epidemic, hoping to provide some insights for the rest of the world. Methods: To examine how changes in population mixing have affected outbreak progression in Wuhan, we used synthetic location-specific contact patterns in Wuhan and adapted these in the presence of school closures, extended workplace closures, and a reduction in mixing in the general community. Using these matrices and the latest estimates of the epidemiological parameters of the Wuhan outbreak, we simulated the ongoing trajectory of an outbreak in Wuhan using an age-structured susceptible-exposed-infected-removed (SEIR) model for several physical distancing measures. We fitted the latest estimates of epidemic parameters from a transmission model to data on local and internationally exported cases from Wuhan in an age-structured epidemic framework and investigated the age distribution of cases. We also simulated lifting of the control measures by allowing people to return to work in a phased-in way and looked at the effects of returning to work at different stages of the underlying outbreak (at the beginning of March or April). Findings: Our projections show that physical distancing measures were most effective if the staggered return to work was at the beginning of April; this reduced the median number of infections by more than 92% (IQR 66–97) and 24% (13–90) in mid-2020 and end-2020, respectively. There are benefits to sustaining these measures until April in terms of delaying and reducing the height of the peak, median epidemic size at end-2020, and affording health-care systems more time to expand and respond. However, the modelled effects of physical distancing measures vary by the duration of infectiousness and the role school children have in the epidemic. Interpretation: Restrictions on activities in Wuhan, if maintained until April, would probably help to delay the epidemic peak. Our projections suggest that premature and sudden lifting of interventions could lead to an earlier secondary peak, which could be flattened by relaxing the interventions gradually. However, there are limitations to our analysis, including large uncertainties around estimates of R0 and the duration of infectiousness. Funding: Bill & Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.The effect of time since measles vaccination and age at first dose on measles vaccine effectiveness – A systematic review
Hughes, S. L., Bolotin, S., Khan, S., Li, Y., Johnson, C., Friedman, L., Tricco, A. C., Hahné, S. J., Heffernan, J. M., Dabbagh, A., Durrheim, D. N., Orenstein, W. A., Moss, W. J., Jit, M., & Crowcroft, N. S. (n.d.).Publication year
2020Journal title
VaccineVolume
38Issue
3Page(s)
460-469AbstractBackground: In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We aimed to assess whether measles vaccine effectiveness (VE) waned over time, and if so, whether differentially in measles-eliminated and measles-endemic settings. Methods: We performed a systematic literature review of studies that reported VE and time since vaccination with measles-containing vaccine (MCV). We extracted information on case definition (clinical symptoms and/or laboratory diagnosis), method of vaccination status ascertainment (medical record or vaccine registry), as well as any biases which may have arisen from cold chain issues and a lack of an age at first dose of MCV. We then used linear regression to evaluate VE as a function of age at first dose of MCV and time since MCV. Results: After screening 14,782 citations, we identified three full-text articles from measles-eliminated settings and 33 articles from measles-endemic settings. In elimination settings, two-dose VE estimates increased as age at first dose of MCV increased and decreased as time since MCV increased; however, the small number of studies available limited interpretation. In measles-endemic settings, one-dose VE increased by 1.5% (95% CI 0.5, 2.5) for every month increase in age at first dose of MCV. We found no evidence of waning VE in endemic settings. Conclusions: The paucity of data from measles-eliminated settings indicates that additional studies and approaches (such as studies using proxies including laboratory correlates of protection) are needed to answer the question of whether VE in measles-eliminated settings wanes. Age at first dose of MCV was the most important factor in determining VE. More VE studies need to be conducted in elimination settings, and standards should be developed for information collected and reported in such studies.The effect of travel restrictions on the geographical spread of COVID-19 between large cities in China: A modelling study
Quilty, B. J., Diamond, C., Liu, Y., Gibbs, H., Russell, T. W., Jarvis, C. I., Prem, K., Pearson, C. A., Clifford, S., Flasche, S., Emery, J. C., Auzenbergs, M., Davies, N., Nightingale, E. S., Van Zandvoort, K., Jombart, T., Deol, A. K., Edmunds, W. J., Hellewell, J., … Jit, M. (n.d.).Publication year
2020Journal title
BMC MedicineVolume
18Issue
1AbstractBackground: To contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China. Methods: We estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to February 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios to simulate the effect of local non-pharmaceutical interventions. Results: We find that in the four cities, given the potentially high prevalence of COVID-19 in Wuhan between December 2019 and early January 2020, local transmission may have been seeded as early as 1-8 January 2020. By the time the cordon sanitaire was imposed, infections were likely in the thousands. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities. Reduced transmissibility resulted in a notable decrease in the incidence of infection in the four studied cities. Conclusions: Our results indicate that sustained transmission was likely occurring several weeks prior to the implementation of the cordon sanitaire in four major cities of mainland China and that the observed decrease in incidence was likely attributable to other non-pharmaceutical, transmission-reducing interventions.The impact of maternal RSV vaccine to protect infants in Gavi-supported countries: Estimates from two models
Baral, R., Li, X., Willem, L., Antillon, M., Vilajeliu, A., Jit, M., Beutels, P., & Pecenka, C. (n.d.).Publication year
2020Journal title
VaccineVolume
38Issue
33Page(s)
5139-5147AbstractBackground: Interventions to protect young infants against respiratory syncytial virus (RSV) are in advanced phases of development and are expected to be available in the foreseeable future. Gavi, the Vaccine Alliance, included maternal vaccines and infant monoclonal antibodies for RSV as part of the 2018 vaccine investment strategy (VIS) and decided to support these products subject to licensure, World Health Organization prequalification, Strategic Advisory Group of Experts recommendation, and meeting the financial assumptions used as the basis of the investment case. Impact estimates reported in this manuscript were used to inform the Gavi VIS. Methods: We compared two independent vaccine impact models to evaluate a potential maternal RSV vaccine's impact on infant health in 73 Gavi-supported countries. Key inputs were harmonized across both models. We analyzed various scenarios to evaluate the effect of uncertain model parameters such as vaccine efficacy, duration of infant protection, and infant disease burden. Estimates of averted cases, severe cases, hospitalizations, deaths, and disability-adjusted life years (DALYs) were calculated over the 2023–2035 horizon. Findings: A maternal RSV vaccine with 60% efficacy offering 5 months of infant protection implemented across 73 low- and middle-income countries could avert 10.1–12.5 million cases, 2.8–4.0 million hospitalizations, 123.7–177.7 thousand deaths, and 8.5–11.9 million DALYs among infants under 6 months of age for the duration of analysis (2023–2035). Maternal RSV vaccination was projected to avert up to 42% of estimated RSV deaths among infants under 6 months in year 2035. Alternative scenario analyses with higher disease burden assumptions showed that a maternal vaccine could avert as many as 325–355 thousand deaths among infants under 6 months. Interpretation: RSV maternal immunization is projected to substantially reduce mortality and morbidity among young infants if introduced across Gavi-supported countries. Funding: This work was supported by Bill & Melinda Gates Foundation, Seattle, WA, and Respiratory Syncytial Virus Consortium in Europe. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation or of the Respiratory Syncytial Virus Consortium. LW is supported by Research Foundation–Flanders (1234620 N).The impact of vaccination on gender equity: Conceptual framework and human papillomavirus (HPV) vaccine case study
Portnoy, A., Clark, S., Ozawa, S., & Jit, M. (n.d.).Publication year
2020Journal title
International Journal for Equity in HealthVolume
19Issue
1AbstractBackground: Although the beneficial effects of vaccines on equity by socioeconomic status and geography are increasingly well-documented, little has been done to extend these analyses to examine the linkage between vaccination and gender equity. In this paper, evidence from the published literature is used to develop a conceptual framework demonstrating the potential impact of vaccination on measures of gender equity. This framework is then applied to human papillomavirus (HPV) vaccination in three countries with different economic and disease burden profiles to establish a proof of concept in a variety of contexts. Methods: We conducted a literature review examining evidence on the linkage between health outcomes and dimensions of gender equity. We utilized the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to estimate cervical cancer incidence and deaths due to HPV types 16/18 by age in each country. We estimated labor force participation and fertility effects from improvements in health, and converted these into inputs consistent with those used to calculate the United Nations Gender Inequality Index to assess gender equity. Results: In our case study, we found that HPV vaccination among girls could help narrow socioeconomic gender disparities by quantifying the main pathways by which HPV vaccination improves health, which enables improvement in gender equity indicators such as labor force participation and maternal mortality ratios. While these improvements are small when averaged over the entire population, the components measured - labor force participation and maternal mortality ratio - account for 50% of the index scores. Conclusions: This proof of concept model is a starting point to inform future health and economic analyses that might incorporate the impact of gender equity as an additional impact of vaccination in improving the health and well-being of the population.The role of vaccines in combating antimicrobial resistance
Jit, M., & Cooper, B. (n.d.). In Challenges to Tackling Antimicrobial Resistance (1–).Publication year
2020Page(s)
181-206Using a real-world network to model localized COVID-19 control strategies
Failed generating bibliography.AbstractPublication year
2020Journal title
Nature MedicineVolume
26Issue
10Page(s)
1616-1622AbstractCase isolation and contact tracing can contribute to the control of COVID-19 outbreaks1,2. However, it remains unclear how real-world social networks could influence the effectiveness and efficiency of such approaches. To address this issue, we simulated control strategies for SARS-CoV-2 transmission in a real-world social network generated from high-resolution GPS data that were gathered in the course of a citizen-science experiment3,4. We found that tracing the contacts of contacts reduced the size of simulated outbreaks more than tracing of only contacts, but this strategy also resulted in almost half of the local population being quarantined at a single point in time. Testing and releasing non-infectious individuals from quarantine led to increases in outbreak size, suggesting that contact tracing and quarantine might be most effective as a ‘local lockdown’ strategy when contact rates are high. Finally, we estimated that combining physical distancing with contact tracing could enable epidemic control while reducing the number of quarantined individuals. Our findings suggest that targeted tracing and quarantine strategies would be most efficient when combined with other control measures such as physical distancing.A Scoping Review of Investment Cases for Vaccines and Immunization Programs
Sim, S. Y., Jit, M., Constenla, D., Peters, D. H., & Hutubessy, R. C. (n.d.).Publication year
2019Journal title
Value in HealthVolume
22Issue
8Page(s)
942-952AbstractBackground: Many investment cases have recently been published intending to show the value of new health investments, but without consistent methodological approaches. Objectives: To conduct a scoping review of existing investment cases (using vaccines and immunization programs as an example), identify common characteristics that define these investment cases, and examine their role within the broader context of the vaccine development and introduction. Methods: A systematic search was conducted from January 1980 to November 2017 to identify investment cases in the area of vaccines and immunization programs from gray literature and electronic bibliographic databases. Investment case outcomes, objectives, key variables, target audiences, and funding sources were extracted and analyzed according to their reporting frequency. Results: We found 24 investment cases, and most of them aim to provide information for decisions (12 cases) or advocate for a specific agenda (9 cases). Outcomes presented fell into 4 broad categories—burden of disease, cost of investment, impact of investment, and other considerations for implementation. Number of deaths averted (70%), incremental cost-effectiveness ratios (67%), and reduction in health and socioeconomic inequalities (54%) were the most frequently reported outcome measures for impact of investment. Health system capacity (79%) and vaccine financing landscape (75%) were the most common considerations for implementation. A sizable proportion (41.4%) of investment cases did not reveal their funding sources. Conclusions: This review describes information that is critical to decision making about resource mobilization and allocation concerning vaccines. Global efforts to harmonize investment cases more broadly will increase transparency and comparability.Adjusting for Inflation and Currency Changes Within Health Economic Studies
Turner, H. C., Lauer, J. A., Tran, B. X., Teerawattananon, Y., & Jit, M. (n.d.).Publication year
2019Journal title
Value in HealthVolume
22Issue
9Page(s)
1026-1032AbstractObjectives: Within health economic studies, it is often necessary to adjust costs obtained from different time periods for inflation. Nevertheless, many studies do not report the methods used for this in sufficient detail. In this article, we outline the principal methods used to adjust for inflation, with a focus on studies relating to healthcare interventions in low- and middle-income countries. We also discuss issues relating to converting local currencies to international dollars and US$ and adjusting cost data collected from other countries or previous studies. Methods: We outlined the 3 main methods used to adjust for inflation for studies in these settings: exchanging the local currency to US$ or international dollars and then inflating using US inflation rates (method 1); inflating the local currency using local inflation rates and then exchanging to US$ or international dollars (method 2); splitting the costs into tradable and nontradable resources and using method 1 on the tradable resources and method 2 on the nontradable resources (method 3). Results: In a hypothetical example of adjusting a cost of US$100 incurred in Vietnam from 2006 to 2016 prices, the adjusted cost from the 3 methods were US$116.84, US$172.09, and US$161.04, respectively. Conclusions: The different methods for adjusting for inflation can yield substantially different results. We make recommendations regarding the most appropriate method for various scenarios. Moving forward, it is vital that studies report the methodology they use to adjust for inflation more transparently.Antimicrobial Resistance in the Asia Pacific region: A meeting report
Yam, E. L. Y., Hsu, L. Y., Yap, E. P. H., Yeo, T. W., Lee, V., Schlundt, J., Lwin, M. O., Limmathurotsakul, D., Jit, M., Dedon, P., Turner, P., & Wilder-Smith, A. (n.d.).Publication year
2019Journal title
Antimicrobial Resistance and Infection ControlVolume
8Issue
1AbstractThe Asia Pacific region, home to two-thirds of the world's population and ten of the least developed countries, is considered a regional hot-spot for the emergence and spread of antimicrobial resistance (AMR). Despite this, there is a dearth of high-quality regional data on the extent of AMR. Recognising the urgency to close this gap, Singapore organised a meeting to discuss the problems in the region and frame a call for action. Representatives from across the region and beyond attended the meeting on the "Antimicrobial Resistance in the Asia Pacific & its impact on Singapore" held in November 2018. This meeting report is a summary of the discussions on the challenges and progress in surveillance, drivers and levers of AMR emergence, and the promising innovations and technologies that could be used to combat the increasing threat of AMR in the region. Enhanced surveillance and research to provide improved evidence-based strategies and policies are needed. The major themes that emerged for an action plan are working towards a tailored solution for the region by harnessing the One Health approach, enhancing inter-country collaborations, and collaboratively leverage upon new emerging technologies. A regionally coordinated effort that is target-driven, sustainable and builds on a framework facilitating communication and governance will strengthen the fight against AMR in the Asia Pacific region.Clinical impact and cost-effectiveness of primary cytology versus human papillomavirus testing for cervical cancer screening in England
Bains, I., Choi, Y. H., Soldan, K., & Jit, M. (n.d.).Publication year
2019Journal title
International Journal of Gynecological CancerVolume
29Issue
4Page(s)
669-675AbstractObjectives In England, human papillomavirus (HPV) testing is to replace cytological screening by 2019-2020. We conducted a model-based economic evaluation to project the long-term clinical impact and cost-effectiveness of routine cytology versus HPV testing. Methods An individual-based model of HPV acquisition, natural history, and cervical cancer screening was used to compare cytological screening and HPV testing with cytology triage for women aged 25-64 years (with either 3- or 5-year screening intervals for women aged under 50 years). The model was fitted to data from England's National Health Service Cervical Screening Programme. Both clinical and economic outcomes were projected to inform cost-effectiveness analyses. Results HPV testing is likely to decrease annual cytology testing (by 2.76 million), cervical cancer incidence (by 290 cases), and health system costs (by £13 million). It may increase the number of colposcopies, although this could be reduced without leading to more cancers compared with primary cytology by increasing the interval between screens to 5 years. The impact in terms of quality-adjusted life-years (QALYs) depends on the quality of life weight given to colposcopies versus cancer. Conclusions England's move from cytology to HPV screening may potentially be life-saving and cost-effective. Cost-effectiveness can be improved further by extending the interval between screens or using alternative triage methods such as partial or full genotyping.Combining serological and contact data to derive target immunity levels for achieving and maintaining measles elimination
Funk, S., Knapp, J. K., Lebo, E., Reef, S. E., Dabbagh, A. J., Kretsinger, K., Jit, M., Edmunds, W. J., & Strebel, P. M. (n.d.).Publication year
2019Journal title
BMC MedicineVolume
17Issue
1AbstractBackground: Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90-95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns. Methods: We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination. Results: We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5-9-year-olds than established previously. Conclusions: The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5-9-year-olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.Determinants of methicillin-resistant Staphylococcus aureus (MRSA) prevalence in the Asia-Pacific region: A systematic review and meta-analysis
Lim, W. W., Wu, P., Bond, H. S., Wong, J. Y., Ni, K., Seto, W. H., Jit, M., & Cowling, B. J. (n.d.).Publication year
2019Journal title
Journal of Global Antimicrobial ResistanceVolume
16Page(s)
17-27AbstractObjectives: Published literature on methicillin-resistant Staphylococcus aureus (MRSA) in the Asia–Pacific region was reviewed to document the prevalence of MRSA in the region and to examine the impact of variability in study design on the reported MRSA prevalence data. Methods: This review included studies reporting MRSA prevalence between 2000 and 2016. Studies were excluded if they did not contain complete information on antimicrobial susceptibility testing (AST) methods. Primary outcomes were the proportion of MRSA among S. aureus isolates (resistance proportion) or among individual samples (prevalence). Results: A total of 229 studies in 19 countries/territories were included in the study. There was substantial heterogeneity in both outcomes (resistance proportion, I 2 = 99.59%; prevalence, I 2 = 99.83%), precluding pooled averages, and meta-regression analyses revealed that these variations were explained by country income status and participant characteristics but not by methodological differences in AST. Also, no significant secular changes in MRSA prevalence or resistance proportions in Asia-Pacific were found. Conclusion: The resistance proportions and prevalence of MRSA infections in Asia-Pacific are comparable with those reported in other regions with no significant secular changes in the past decade. Country income status and characteristics of the sample population explained more variation in the reported resistance proportions and prevalence of MRSA than methodological differences in AST across locations in the region.Effect and cost-effectiveness of pneumococcal conjugate vaccination: a global modelling analysis
Chen, C., Cervero Liceras, F., Flasche, S., Sidharta, S., Yoong, J., Sundaram, N., & Jit, M. (n.d.).Publication year
2019Journal title
The Lancet Global HealthVolume
7Issue
1Page(s)
e58-e67AbstractBackground: Introduction of pneumococcal conjugate vaccines (PCVs) has substantially reduced disease burden due to Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. However, PCVs are among the most expensive vaccines, hindering their introduction in some settings and threatening sustainability in others. We aimed to assess the effect and cost-effectiveness of introduction of 13-valent PCV (PCV13) vaccination globally. Methods: We assessed the incremental cost-effectiveness ratio of PCV13 introduction by integrating two models: an ecological model (a parsimonious, mechanistic model validated with data from post-seven-valent PCV introduction in 13 high-income settings) to predict the effect of PCV on childhood invasive pneumococcal disease, and a decision-tree model to predict a range of clinical presentations and economic outcomes under vaccination and no-vaccination strategies. The models followed 30 birth cohorts up to age 5 years in 180 countries from 2015 to 2045. One-way scenario and probabilistic sensitivity analyses were done to explore model uncertainties. Findings: We estimate that global PCV13 use could prevent 0·399 million child deaths (95% credible interval 0·208 million to 0·711 million) and 54·6 million disease episodes (51·8 million to 58·1 million) annually. Global vaccine costs (in 2015 international dollars) of $15·5 billion could be partially offset by health-care savings of $3·19 billion (2·62 billion to 3·92 billion) and societal cost savings of $2·64 billion (2·13 billion to 3·28 billion). PCV13 use is probably cost-effective in all six UN regions. The 71 countries eligible for support from Gavi, the Vaccine Alliance, account for 83% of PCV13-preventable deaths but only 18% of global vaccination costs. The expected cost of PCV vaccination globally is around $16 billion per year. Interpretation: Our findings highlight the value of Gavi's support for PCV introduction in low-income countries and of efforts to improve the affordability of PCVs in countries not eligible for, or transitioning from, Gavi support. Funding: World Health Organization; Gavi, the Vaccine Alliance; and the Bill & Melinda Gates Foundation.Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trials
Clark, A., Van Zandvoort, K., Flasche, S., Sanderson, C., Bines, J., Tate, J., Parashar, U., & Jit, M. (n.d.).Publication year
2019Journal title
The Lancet Infectious DiseasesVolume
19Issue
7Page(s)
717-727AbstractBackground: The duration of protection offered by rotavirus vaccines varies across the world, and this variation is important to understanding and predicting the effects of the vaccines. There is now a large body of evidence on the efficacy of live oral rotavirus vaccines in different settings, but these data have never been synthesised to obtain robust estimates of efficacy by duration of follow-up. Our aim is to estimate the efficacy of live oral rotavirus vaccines at each point during follow-up and by mortality stratum. Methods: In our meta-regression study, we identified all randomised controlled trials of rotavirus vaccines published until April 4, 2018, using the results of a Cochrane systematic review, and cross checked these studies against those identified by another systematic review. We excluded trials that were based on special populations, trials without an infant schedule, and trials without clear reporting of numbers of enrolled infants and events in different periods of follow-up. For all reported periods of follow-up, we extracted the mean duration of follow-up (time since administration of the final dose of rotavirus vaccination), the number of enrolled infants, and case counts for rotavirus-positive severe gastroenteritis in both non-vaccinated and vaccinated groups. We used a Bayesian hierarchical Poisson meta-regression model to estimate the pooled cumulative vaccine efficacy (VE) and its waning with time for three mortality strata. We then converted these VE estimates into instantaneous VE (iVE). Findings: In settings with low mortality (15 observations), iVE pooled for infant schedules of Rotarix and RotaTeq was 98% (95% credibility interval 93–100) 2 weeks following the final dose of vaccination and 94% (87–98) after 12 months. In medium-mortality settings (11 observations), equivalent estimates were 82% (74–92) after 2 weeks and 77% (67–84) after 12 months. In settings with high mortality (24 observations), there were five different vaccines with observation points for infant schedules. The pooled iVE was 66% (48–81) after 2 weeks of follow-up and 44% (27–59) after 12 months. Interpretation: Rotavirus vaccine efficacy is lower and wanes more rapidly in high-mortality settings than in low-mortality settings, but the earlier peak age of disease in high-mortality settings means that live oral rotavirus vaccines are still likely to provide substantial benefit. Funding: Bill & Melinda Gates Foundation.Estimates of case-fatality ratios of measles in low-income and middle-income countries: a systematic review and modelling analysis
Portnoy, A., Jit, M., Ferrari, M., Hanson, M., Brenzel, L., & Verguet, S. (n.d.).Publication year
2019Journal title
The Lancet Global HealthVolume
7Issue
4Page(s)
e472-e481AbstractBackground: In the 21st century, increases in immunisation coverage and decreases in under-5 mortality have substantially reduced the global burden of measles mortality. However, the assessment of measles mortality burden is highly dependent on estimates of case-fatality ratios for measles, which can vary according to geography, health systems infrastructure, prevalence of underlying risk factors, and measles endemicity. With imprecise case-fatality ratios, there is continued uncertainty about the burden of measles mortality and the effect of measles vaccination. In this study, we aimed to update the estimations of case-fatality ratios for measles, to develop a prediction model to estimate case-fatality ratios across heterogeneous groupings, and to project future case-fatality ratios for measles up to 2030. Methods: We did a review of the literature to identify studies examining measles cases and deaths in low-income and middle-income countries in all age groups from 1980 to 2016. We extracted data on case-fatality ratios for measles overall and by age, where possible. We developed and examined several types of generalised linear models and determined the best-fit model according to the Akaike information criterion. We then selected a best-fit model to estimate measles case-fatality ratios from 1990 to 2015 and projected future case-fatality ratios for measles up to 2030. Findings: We selected 124 peer-reviewed journal articles published between Jan 1, 1980, and Dec 31, 2016, for inclusion in the final review—85 community-based studies and 39 hospital-based studies. We selected a log-linear prediction model, resulting in a mean case-fatality ratio of 2·2% (95% CI 0·7–4·5) in 1990–2015. In community-based settings, the mean case-fatality ratio was 1·5% (0·5–3·1) compared with 2·9% (0·9–6·0) in hospital-based settings. The mean projected case-fatality ratio in 2016–2030 was 1·3% (0·4–3·7). Interpretation: Case-fatality ratios for measles have seen substantial declines since the 1990s. Our study provides an updated estimation of case-fatality ratios that could help to refine assessment of the effect on mortality of measles control and elimination programmes. Funding: Bill & Melinda Gates Foundation.Global Case-Fatality Rates in Pediatric Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis
Tan, B., Wong, J. J. M., Sultana, R., Koh, J. C. J. W., Jit, M., Mok, Y. H., & Lee, J. H. (n.d.).Publication year
2019Journal title
JAMA PediatricsVolume
173Issue
4Page(s)
352-361AbstractImportance: The global patterns and distribution of case-fatality rates (CFRs) in pediatric severe sepsis and septic shock remain poorly described. Objective: We performed a systematic review and meta-analysis of studies of children with severe sepsis and septic shock to elucidate the patterns of CFRs in developing and developed countries over time. We also described factors associated with CFRs. Data Sources: We searched PubMed, Web of Science, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central systematically for randomized clinical trials and prospective observational studies from earliest publication until January 2017, using the keywords "pediatric," "sepsis," "septic shock," and "mortality." Study Selection: Studies involving children with severe sepsis and septic shock that reported CFRs were included. Retrospective studies and studies including only neonates were excluded. Data Extraction and Synthesis: We conducted our systematic review and meta-analysis in close accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled case-fatality estimates were obtained using random-effects meta-analysis. The associations of study period, study design, sepsis severity, age, and continents in which studies occurred were assessed with meta-regression. Main Outcomes and Measures: Meta-analyses to provide pooled estimates of CFR of pediatric severe sepsis and septic shock over time. Results: Ninety-four studies that included 7561 patients were included. Pooled CFRs were higher in developing countries (31.7% [95% CI, 27.3%-36.4%]) than in developed countries (19.3% [95% CI, 16.4%-22.7%]; P <.001). Meta-analysis of CFRs also showed significant heterogeneity across studies. Continents that include mainly developing countries reported higher CFRs (adjusted odds ratios: Africa, 7.89 [95% CI, 6.02-10.32]; P <.001; Asia, 3.81 [95% CI, 3.60-4.03]; P <.001; South America, 2.91 [95% CI, 2.71-3.12]; P <.001) than North America. Septic shock was associated with higher CFRs than severe sepsis (adjusted odds ratios, 1.47 [95% CI, 1.41-1.54]). Younger age was also a risk factor (adjusted odds ratio, 0.95 [95% CI, 0.94-0.96] per year of increase in age). Earlier study eras were associated with higher CFRs (adjusted odds ratios for 1991-2000, 1.24 [95% CI, 1.13-1.37]; P <.001) compared with 2011 to 2016. Time-trend analysis showed higher CFRs over time in developing countries than developed countries. Conclusions and Relevance: Despite the declining trend of pediatric severe sepsis and septic shock CFRs, the disparity between developing and developed countries persists. Further characterizations of vulnerable populations and collaborations between developed and developing countries are warranted to reduce the burden of pediatric sepsis globally..Guidelines for multi-model comparisons of the impact of infectious disease interventions
Den Boon, S., Jit, M., Brisson, M., Medley, G., Beutels, P., White, R., Flasche, S., Hollingsworth, T. D., Garske, T., Pitzer, V. E., Hoogendoorn, M., Geffen, O., Clark, A., Kim, J., & Hutubessy, R. (n.d.).Publication year
2019Journal title
BMC MedicineVolume
17Issue
1AbstractBackground: Despite the increasing popularity of multi-model comparison studies and their ability to inform policy recommendations, clear guidance on how to conduct multi-model comparisons is not available. Herein, we present guidelines to provide a structured approach to comparisons of multiple models of interventions against infectious diseases. The primary target audience for these guidelines are researchers carrying out model comparison studies and policy-makers using model comparison studies to inform policy decisions. Methods: The consensus process used for the development of the guidelines included a systematic review of existing model comparison studies on effectiveness and cost-effectiveness of vaccination, a 2-day meeting and guideline development workshop during which mathematical modellers from different disease areas critically discussed and debated the guideline content and wording, and several rounds of comments on sequential versions of the guidelines by all authors. Results: The guidelines provide principles for multi-model comparisons, with specific practice statements on what modellers should do for six domains. The guidelines provide explanation and elaboration of the principles and practice statements as well as some examples to illustrate these. The principles are (1) the policy and research question - the model comparison should address a relevant, clearly defined policy question; (2) model identification and selection - the identification and selection of models for inclusion in the model comparison should be transparent and minimise selection bias; (3) harmonisation - standardisation of input data and outputs should be determined by the research question and value of the effort needed for this step; (4) exploring variability - between- and within-model variability and uncertainty should be explored; (5) presenting and pooling results - results should be presented in an appropriate way to support decision-making; and (6) interpretation - results should be interpreted to inform the policy question. Conclusion: These guidelines should help researchers plan, conduct and report model comparisons of infectious diseases and related interventions in a systematic and structured manner for the purpose of supporting health policy decisions. Adherence to these guidelines will contribute to greater consistency and objectivity in the approach and methods used in multi-model comparisons, and as such improve the quality of modelled evidence for policy.HPV-FRAME: A consensus statement and quality framework for modelled evaluations of HPV-related cancer control
Canfell, K., Kim, J. J., Kulasingam, S., Berkhof, J., Barnabas, R., Bogaards, J. A., Campos, N., Jennett, C., Sharma, M., Simms, K. T., Smith, M. A., Velentzis, L. S., Brisson, M., & Jit, M. (n.d.).Publication year
2019Journal title
Papillomavirus ResearchVolume
8AbstractIntense research activity in HPV modelling over this decade has prompted the development of additional guidelines to those for general modelling. A specific framework is required to address different policy questions and unique complexities of HPV modelling. HPV-FRAME is an initiative to develop a consensus statement and quality-based framework for epidemiologic and economic HPV models. Its development involved an established process. Reporting standards have been structured according to seven domains reflecting distinct policy questions in HPV and cancer prevention and categorised by relevance to a population or evaluation. Population-relevant domains are: 1) HPV vaccination in pre-adolescent and young adolescent individuals; 2) HPV vaccination in older individuals; 3) targeted vaccination in men who have sex with men; 4) considerations for individuals living with HIV and 5) considerations for low- and middle-income countries. Additional considerations applicable to specific evaluations are: 6) cervical screening or integrated cervical screening and HPV vaccination approaches and 7) alternative vaccine types and alternative dosing schedules. HPV-FRAME aims to promote the development of models in accordance with an explicit framework, to better enable target audiences to understand a model's strength and weaknesses in relation to a specific policy question and ultimately improve the model's contribution to informed decision-making.Interferon gamma release assays for diagnostic evaluation of active tuberculosis (IDEA): Test accuracy study and economic evaluation
Takwoingi, Y., Whitworth, H., Rees-Roberts, M., Badhan, A., Partlett, C., Green, N., Boakye, A., Lambie, H., Marongiu, L., Jit, M., White, P., Deeks, J. J., Kon, O. M., & Lalvani, A. (n.d.).Publication year
2019Journal title
Health Technology AssessmentVolume
23Issue
23Page(s)
1-152AbstractBackground: Interferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice. Objectives: To compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB® (Oxford Immunotec, Abingdon, UK) and QuantiFERON® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs. Design: Prospective within-patient comparative diagnostic accuracy study. Setting: Secondary care. Participants: Adults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. Interventions: The index tests [T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results. Main outcome measures: Sensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test. Results: A total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT.TB was more sensitive than QFT-GIT (relative sensitivity 1.22, 95% CI 1.14 to 1.31; p < 0.001), but the specificities were similar (relative specificity 1.02, 95% CI 0.97 to 1.08; p = 0.3). For both IGRAs the sensitivity was lower and the specificity was higher for human immunodeficiency virus (HIV)-positive than for HIV-negative patients. The most promising novel antigen was Rv3615c. The added value of Rv3615c to T-SPOT.TB was a 9% (95% CI 5% to 12%) relative increase in sensitivity at the expense of specificity, which had a relative decrease of 7% (95% CI 4% to 10%). The use of current IGRA tests for ruling out active TB is unlikely to be considered cost-effective if a QALY was valued at £20,000 or £30,000. For T-SPOT.TB, the probability of being cost-effective for a willingness to pay of £20,000/QALY was 26% and 21%, when patients with indeterminate test results were excluded or included, respectively. In comparison, the QFT-GIT probabilities were 8% and 6%. Although the use of IGRAs is cost saving, the health detriment is large owing to delay in diagnosing active TB, leading to prolonged illness. There was substantial between-patient variation in the tests used in the diagnostic pathway. Limitations: The recruitment target for the HIV co-infected population was not achieved. Conclusions: Although T-SPOT.TB was more sensitive than QFT-GIT for the diagnosis of active TB, the tests are insufficiently sensitive for ruling out active TB in routine clinical practice in the UK. Novel assays offer some promise. Future work: The novel assays require evaluation in distinct clinical settings and in immunosuppressed patient groups.Mathematical modelling for antibiotic resistance control policy: Do we know enough?
Knight, G. M., Davies, N. G., Colijn, C., Coll, F., Donker, T., Gifford, D. R., Glover, R. E., Jit, M., Klemm, E., Lehtinen, S., Lindsay, J. A., Lipsitch, M., Llewelyn, M. J., Mateus, A. L., Robotham, J. V., Sharland, M., Stekel, D., Yakob, L., & Atkins, K. E. (n.d.).Publication year
2019Journal title
BMC Infectious DiseasesVolume
19Issue
1AbstractBackground: Antibiotics remain the cornerstone of modern medicine. Yet there exists an inherent dilemma in their use: we are able to prevent harm by administering antibiotic treatment as necessary to both humans and animals, but we must be mindful of limiting the spread of resistance and safeguarding the efficacy of antibiotics for current and future generations. Policies that strike the right balance must be informed by a transparent rationale that relies on a robust evidence base. Main text: One way to generate the evidence base needed to inform policies for managing antibiotic resistance is by using mathematical models. These models can distil the key drivers of the dynamics of resistance transmission from complex infection and evolutionary processes, as well as predict likely responses to policy change in silico. Here, we ask whether we know enough about antibiotic resistance for mathematical modelling to robustly and effectively inform policy. We consider in turn the challenges associated with capturing antibiotic resistance evolution using mathematical models, and with translating mathematical modelling evidence into policy. Conclusions: We suggest that in spite of promising advances, we lack a complete understanding of key principles. From this we advocate for priority areas of future empirical and theoretical research.Mortality in Pediatric Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis
Wong, J. J. M., Jit, M., Sultana, R., Mok, Y. H., Yeo, J. G., Koh, J. W. J. C., Loh, T. F., & Lee, J. H. (n.d.).Publication year
2019Journal title
Journal of Intensive Care MedicineVolume
34Issue
7Page(s)
563-571AbstractObjective: Sparse and conflicting evidence exists regarding mortality risk from pediatric acute respiratory distress syndrome (ARDS). We aimed to determine the pooled mortality in pediatric ARDS and to describe its trend over time. Data Sources and Study Selection: MEDLINE, EMBASE, and Web of Science were searched from 1960 to August 2015. Keywords or medical subject headings (MESH) terms used included “respiratory distress syndrome, adult,” “acute lung injury,” “acute respiratory insufficiency,” “acute hypoxemic respiratory failure,” “pediatrics,” and “child.” Study inclusion criteria were (1) pediatric patients aged 0 days to 18 years, (2) sufficient baseline data described in the pediatric ARDS group, and (3) mortality data. Randomized controlled trials (RCTs) and prospective observational studies were eligible. Data Extraction and Synthesis: Data on study characteristics, patient demographics, measures of oxygenation, and mortality were extracted using a standard data extraction form. Independent authors conducted the search, applied the selection criteria, and extracted the data. Methodological quality of studies was assessed. Meta-analysis using a random-effects model was performed to obtain pooled estimates of mortality. Meta-regression was performed to analyze variables contributing to change in mortality over time. Eight RCTs and 21 observational studies (n = 2274 patients) were included. Pooled mortality rate was 24% (95% confidence interval [CI]: 19-31). There was a decrease in mortality rates over 3 epochs (≤2000, 2001-2009, and ≥2010: 40% [95% CI: 24-59], 35% [95% CI: 21-51], and 18% [95% CI: 12-26], respectively, P <.001). Observational studies reported a higher mortality rate than RCTs (27% [95% CI: 24-29] versus 16% [95% CI: 12-20], P <.001). Earlier year of publication was an independent factor associated with mortality. Conclusion: Overall mortality rate in pediatric ARDS is approximately 24%. Studies conducted and published later were associated with better survival.Mortality reduction benefits and intussusception risks of rotavirus vaccination in 135 low-income and middle-income countries: a modelling analysis of current and alternative schedules
Clark, A., Tate, J., Parashar, U., Jit, M., Hasso-Agopsowicz, M., Henschke, N., Lopman, B., Van Zandvoort, K., Pecenka, C., Fine, P., & Sanderson, C. (n.d.).Publication year
2019Journal title
The Lancet Global HealthVolume
7Issue
11Page(s)
e1541-e1552AbstractBackground: Infant rotavirus vaccines have led to substantial reductions in hospital admissions and deaths due to gastroenteritis, but some studies have reported an elevated risk of intussusception, a rare bowel disorder. This analysis aimed to provide evidence on the potential mortality reduction benefits and intussusception risks of current rotavirus vaccination schedules, and to explore whether alternative schedules could have advantages. Methods: All 135 low-income and middle-income countries, defined by gross national income per capita of less than US$12 236 in the 2018 fiscal year, were included in the model. Mortality reduction benefits and intussusception risks of rotavirus vaccination were modelled by use of an Excel-based static cohort model with a finely disaggregated age structure. Numbers of rotavirus gastroenteritis deaths and intussusception deaths in each week of age were calculated for all infants born in the year 2015 between birth and age 5·0 years, with and without restrictions on age at administration. Benefit–risk ratios (rotavirus gastroenteritis deaths prevented per excess intussusception death) and other indicators were calculated for two vaccination schedules currently recommended by WHO and 16 alternative schedules. Of these schedules, it was assumed that between one and three doses would be given; the first dose of the rotavirus vaccine would be co-administered with either BCG or diphtheria–tetanus–pertussis (DTP)1; and the second or third dose would be co-administered with either DTP1, DTP2, DTP3, or measles (Meas)1. Findings: A three-dose schedule co-administered with DTP (without age restrictions) could prevent about 74 000 (95% uncertainty interval 59 000–100 000) rotavirus gastroenteritis deaths (38% reduction) and could lead to 201 (77–550) excess intussusception deaths (1·4% increase) compared with no vaccination, resulting in a benefit–risk ratio of 369:1 (160:1–895:1). The benefit–risk ratio was most favourable when the relative risk of intussusception was assumed to decline with the national under-5 mortality rate (2386:1) and least favourable with pessimistic assumptions about access to hospital for intussusception treatment (168:1). Schedules that involve giving the first dose with BCG and the second with DTP1 had the fewest excess intussusception deaths and most favourable benefit–risk ratios. Interpretation: Rotavirus vaccines have a favourable benefit–risk profile in LMICs. Neonatal schedules have the potential to prevent more rotavirus gastroenteritis deaths and cause fewer excess intussusception deaths than the schedules currently recommended by WHO, but more efficacious rotavirus vaccines would be needed to achieve more substantial mortality reduction benefits. Funding: Bill & Melinda Gates Foundation.Patterns of human social contact and contact with animals in Shanghai, China
Zhang, J., Klepac, P., Read, J. M., Rosello, A., Wang, X., Lai, S., Li, M., Song, Y., Wei, Q., Jiang, H., Yang, J., Lynn, H., Flasche, S., Jit, M., & Yu, H. (n.d.).Publication year
2019Journal title
Scientific reportsVolume
9Issue
1AbstractEast Asia is as a principal hotspot for emerging zoonotic infections. Understanding the likely pathways for their emergence and spread requires knowledge on human-human and human-animal contacts, but such studies are rare. We used self-completed and interviewer-completed contact diaries to quantify patterns of these contacts for 965 individuals in 2017/2018 in a high-income densely-populated area of China, Shanghai City. Interviewer-completed diaries recorded more social contacts (19.3 vs. 18.0) and longer social contact duration (35.0 vs. 29.1 hours) than self-reporting. Strong age-assortativity was observed in all age groups especially among young participants (aged 7–20) and middle aged participants (25–55 years). 17.7% of participants reported touching animals (15.3% (pets), 0.0% (poultry) and 0.1% (livestock)). Human-human contact was very frequent but contact with animals (especially poultry) was rare although associated with frequent human-human contact. Hence, this densely populated area is more likely to act as an accelerator for human-human spread but less likely to be at the source of a zoonosis outbreak. We also propose that telephone interview at the end of reporting day is a potential improvement of the design of future contact surveys.