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
Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis
AbstractDrobniewski, F., Cooke, M., Jordan, J., Casali, N., Mugwagwa, T., Broda, A., Townsend, C., Sivaramakrishnan, A., Green, N., Jit, M., Lipman, M., Lord, J., White, P. J., & Abubakar, I. (n.d.).Publication year
2015Journal title
Health Technology AssessmentVolume
19Issue
34Page(s)
1-188AbstractBackground: Drug-resistant tuberculosis (TB), especially multidrug-resistant (MDR, resistance to rifampicin and isoniazid) disease, is associated with a worse patient outcome. Drug resistance diagnosed using microbiological culture takes days to weeks, as TB bacteria grow slowly. Rapid molecular tests for drug resistance detection (1 day) are commercially available and may promote faster initiation of appropriate treatment. Objectives: To (1) conduct a systematic review of evidence regarding diagnostic accuracy of molecular genetic tests for drug resistance, (2) conduct a health-economic evaluation of screening and diagnostic strategies, including comparison of alternative models of service provision and assessment of the value of targeting rapid testing at high-risk subgroups, and (3) construct a transmission-dynamic mathematical model that translates the estimates of diagnostic accuracy into estimates of clinical impact. Review methods and data sources: A standardised search strategy identified relevant studies from EMBASE, PubMed, MEDLINE, Bioscience Information Service (BIOSIS), System for Information on Grey Literature in Europe Social Policy & Practice (SIGLE) and Web of Science, published between 1 January 2000 and 15 August 2013. Additional ‘grey’ sources were included. Quality was assessed using quality assessment of diagnostic accuracy studies version 2 (QUADAS-2). For each diagnostic strategy and population subgroup, a care pathway was constructed to specify which medical treatments and health services that individuals would receive from presentation to the point where they either did or did not complete TB treatment successfully. A total cost was estimated from a health service perspective for each care pathway, and the health impact was estimated in terms of the mean discounted quality-adjusted life-years (QALYs) lost as a result of disease and treatment. Costs and QALYs were both discounted at 3.5% per year. An integrated transmission-dynamic and economic model was used to evaluate the cost-effectiveness of introducing rapid molecular testing (in addition to culture and drug sensitivity testing). Probabilistic sensitivity analysis was performed to evaluate the impact on cost-effectiveness of diagnostic and treatment time delays, diagnosis and treatment costs, and associated QALYs. Results: A total of 8922 titles and abstracts were identified, with 557 papers being potentially eligible. Of these, 56 studies contained sufficient test information for analysis. All three commercial tests performed well when detecting drug resistance in clinical samples, although with evidence of heterogeneity between studies. Pooled sensitivity for GenoType® MTBDRplus (Hain Lifescience, Nehren, Germany) (isoniazid and rifampicin resistance), INNO-LiPA Rif.TB® (Fujirebio Europe, Ghent, Belgium) (rifampicin resistance) and Xpert®MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) (rifampicin resistance) was 83.4%, 94.6%, 95.4% and 96.8%, respectively; equivalent pooled specificity was 99.6%, 98.2%, 99.7% and 98.4%, respectively. Results of the transmission model suggest that all of the rapid assays considered here, if added to the current diagnostic pathway, would be cost-saving and achieve a reduction in expected QALY loss compared with current practice. GenoType MTBDRplus appeared to be the most cost-effective of the rapid tests in the South Asian population, although results were similar for GeneXpert. In all other scenarios GeneXpert appeared to be the most cost-effective strategy. Conclusions: Rapid molecular tests for rifampicin and isoniazid resistance were sensitive and specific. They may also be cost-effective when added to culture drug susceptibility testing in the UK. There is global interest in point-of-care testing and further work is needed to review the performance of emerging tests and the wider health-economic impact of decentralised testing in clinics and primary care, as well as non-health-care settings, such as shelters and prisons.Targeted vaccination in healthy school children - Can primary school vaccination alone control influenza?
AbstractThorrington, D., Jit, M., & Eames, K. (n.d.).Publication year
2015Journal title
VaccineVolume
33Issue
41Page(s)
5415-5424AbstractBackground: The UK commenced an extension to the seasonal influenza vaccination policy in autumn 2014 that will eventually see all healthy children between the ages of 2-16 years offered annual influenza vaccination. Models suggest that the new policy will be both highly effective at reducing the burden of influenza as well as cost-effective. We explore whether targeting vaccination at either primary or secondary schools would be more effective and/or cost-effective than the current strategy. Methods: An age-structured deterministic transmission dynamic SEIR-type mathematical model was used to simulate a national influenza outbreak in England. Costs including GP consultations, hospitalisations due to influenza and vaccinations were compared to potential gains in quality-adjusted life years achieved through vaccinating healthy children. Costs and benefits of the new JCVI vaccination policy were estimated over a single season, and compared to the hypothesised new policies of targeted and heterogeneous vaccination. Findings and conclusion: All potential vaccination policies were highly cost-effective. Influenza transmission can be eliminated for a particular season by vaccinating both primary and secondary school children, but not by vaccinating only one group. The most cost-effective policy overall is heterogeneous vaccination coverage with 48% uptake in primary schools and 34% in secondary schools. The Joint Committee on Vaccination and Immunisation can consider a modification to their policy of offering seasonal influenza vaccinations to all healthy children of ages 2-16 years.The broader economic impact of vaccination: Reviewing and appraising the strength of evidence
AbstractJit, M., Hutubessy, R., Png, M. E., Sundaram, N., Audimulam, J., Salim, S., & Yoong, J. (n.d.).Publication year
2015Journal title
BMC MedicineVolume
13Issue
1AbstractBackground: Microeconomic evaluations of public health programmes such as immunisation typically only consider direct health benefits and medical cost savings. Broader economic benefits around childhood development, household behaviour, and macro-economic indicators are increasingly important, but the evidence linking immunization to such benefits is unclear. Methods: A conceptual framework of pathways between immunisation and its proposed broader economic benefits was developed through expert consultation. Relevant articles were obtained from previous reviews, snowballing, and expert consultation. Articles were associated with one of the pathways and quality assessed using modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results: We found 20 studies directly relevant to one or more pathways. Evidence of moderate quality from experimental and observational studies was found for benefits due to immunisation in improved childhood physical development, educational outcomes, and equity in distribution of health gains. Only modelling evidence or evidence outside the immunization field supports extrapolating these benefits to household economic behaviour and macro-economic indicators. Conclusion: Innovative use of experimental and observational study designs is needed to fill evidence gaps around key pathways between immunisation and many of its proposed economic benefits.The economic burden of influenza-associated outpatient visits and hospitalizations in China: A retrospective survey
AbstractYang, J., Jit, M., Leung, K. S., Zheng, Y. M., Feng, L. Z., Wang, L. P., Lau, E. H., Wu, J. T., & Yu, H. J. (n.d.).Publication year
2015Journal title
Infectious Diseases of PovertyVolume
4Issue
1AbstractBackground: The seasonal influenza vaccine coverage rate in China is only 1.9 %. There is no information available on the economic burden of influenza-associated outpatient visits and hospitalizations at the national level, even though this kind of information is important for informing national-level immunization policy decision-making. Methods: A retrospective telephone survey was conducted in 2013/14 to estimate the direct and indirect costs of seasonal influenza-associated outpatient visits and hospitalizations from a societal perspective. Study participants were laboratory-confirmed cases registered in the National Influenza-like Illness Surveillance Network and Severe Acute Respiratory Infections Sentinel Surveillance Network in China in 2013. Patient-reported costs from the survey were validated by a review of hospital accounts for a small sample of the inpatients. Results: The study enrolled 529 outpatients (median age: eight years; interquartile range [IQR]: five to 20 years) and 254 inpatients (median age: four years; IQR: two to seven years). Among the outpatients, 22.1 % (117/529) had underlying diseases and among the inpatients, 52.8 % (134/254) had underlying diseases. The average total costs related to influenza-associated outpatient visits and inpatient visits were US$ 155 (standard deviation, SD US$ 122) and US$ 1,511 (SD US$ 1,465), respectively. Direct medical costs accounted for 45 and 69 % of the total costs related to influenza-associated outpatient and inpatient visits, respectively. For influenza outpatients, the mean cost per episode in children aged below five years (US$ 196) was higher than that in other age groups (US$ 129-153). For influenza inpatients, the mean cost per episode in adults aged over 60 years (US$ 2,735) was much higher than that in those aged below 60 years (US$ 1,417-1,621). Patients with underlying medical conditions had higher costs per episode than patients without underlying medical conditions (outpatients: US$ 186 vs. US$ 146; inpatients: US$ 1,800 vs. US$ 1,189). In the baseline analysis, inpatients reported costs were 18 % higher than those found in the accounts review (n = 38). Conclusion: The economic burden of influenza-associated outpatient and inpatient visits in China is substantial, particularly for young children, the elderly, and patients with underlying medical conditions. More widespread influenza vaccination would likely alleviate the economic burden of patients. The actual impact and cost-effectiveness analysis of the influenza immunization program in China merits further investigation.Thirty years of vaccination in vietnam: Impact and cost-effectiveness of the national expanded programme on immunization
AbstractJit, M., Huyen, D. T. T., Friberg, I., Van Minh, H., Kiet, P. H. T., Walker, N., Van Cuong, N., Duong, T. N., Toda, K., Hutubessy, R., Fox, K., & Hien, N. T. (n.d.).Publication year
2015Journal title
VaccineVolume
33Page(s)
A233-A239AbstractIntroduction: Countries like Vietnam transitioning to middle-income status increasingly bear the cost of both existing and new vaccines. However, the impact and cost-effectiveness of the Expanded Programme on Immunization (EPI) as a whole has never been assessed on a country level. Methods: Data on vaccine-preventable disease incidence and mortality from Vietnam's national surveillance was analysed to estimate the likely impact that vaccination in 1980-2010 may have had. Adjustment for under-reporting was made by examining trends in reported mumps incidence and in case-fatality risks for each disease. The same data were separately analysed using the Lives Saved Tool (LiST) to give an alternative estimate of impact. The financial cost of EPI in 1996-2010 was also estimated from the perspective of service provider. Results: National surveillance data suggests that up to 5.7 million diseases cases and 26,000 deaths may have been prevented by EPI. Analysis using LiST suggests that even more deaths (370,000) may have been prevented by measles and pertussis vaccination alone. The cost-effectiveness of EPI is estimated to be around $1000-$27,000 per death prevented. Conclusion: Two separate approaches to assessing EPI impact in Vietnam give different quantitative results but a common conclusion: that EPI has made a substantial impact on mortality and represents good value for money.What makes an eLife paper in epidemiology and global health?
Jit, M., Franco, E., & Jha, P. (n.d.).Publication year
2015Journal title
eLifeVolume
4Authors’ Reply to Gandjour: “Are Current Cost-Effectiveness Thresholds for Low- and Middle-Income Countries Useful? Examples from the World of Vaccines”
Newall, A. T., Jit, M., & Hutubessy, R. (n.d.). In PharmacoEconomics (1–).Publication year
2014Volume
32Issue
12Page(s)
1247Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: A transmission-dynamic modelling study
AbstractLaprise, J. F., Drolet, M., Boily, M. C., Jit, M., Sauvageau, C., Franco, E. L., Lemieux-Mellouki, P., Malagón, T., & Brisson, M. (n.d.).Publication year
2014Journal title
VaccineVolume
32Issue
44Page(s)
5845-5853AbstractBackground: Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada. Methods: We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost. Findings: Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between $7900-24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated. Interpretation: Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls.Cost-effectiveness of female human papillomavirus vaccination in 179 countries: A PRIME modelling study
AbstractJit, M., Brisson, M., Portnoy, A., & Hutubessy, R. (n.d.).Publication year
2014Journal title
The Lancet Global HealthVolume
2Issue
7Page(s)
e406-e414AbstractBackground: Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specific effects on health and economic costs. We aimed to develop and validate a simple generic model of such effects that could be used and understood in a range of settings with little external support. Methods: We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-effectiveness and health effects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine efficacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-effectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed differences between countries in terms of cost-effectiveness and health effects. Findings: In validation, PRIME reproduced cost-effectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690 000 cases of cervical cancer and 420 000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost effective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200 000 cases of cervical cancer and 100 000 deaths in some of the highest-burden countries. Interpretation: Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions. Funding: WHO.Evaluating the potential risks and benefits of infant rotavirus vaccination in England
AbstractClark, A., Jit, M., Andrews, N., Atchison, C., Edmunds, W. J., & Sanderson, C. (n.d.).Publication year
2014Journal title
VaccineVolume
32Issue
29Page(s)
3604-3610AbstractRotarix®, a vaccine for the prevention of gastroenteritis in young children, was introduced in England in July 2013. At around this time, an elevated risk of intussusception (a cause of bowel obstruction) was reported among infants vaccinated in Australia and the USA. A risk-benefit analysis compared potential vaccine-related risks (additional intussusception admissions and deaths) with estimated vaccine benefits (prevented rotavirus general practitioner visits, emergency visits, admissions and deaths) in the 2012 birth cohort. Detailed data from England included the incidence of intussusception events aged <2 years by week of age, the coverage of vaccination aged <2 years by week of age, and the incidence of rotavirus gastroenteritis (RVGE) events aged <5 years by week of age. Recent estimates of vaccine-related risk from Australia were applied during the 1-21 day period after the first and second dose of vaccination. Rotarix® is estimated to cause one additional intussusception admission in every 18,551 vaccinated English infants (5th and 95th percentiles, 6728-93,952), equivalent to 35 (7-98) additional intussusception admissions each year. The vaccine is estimated to prevent three rotavirus deaths, 13,000 rotavirus admissions, 27,000 rotavirus emergency visits and 74,000 rotavirus GP consultations in children aged <5 years, and lead to annual savings of over £11 million, each year. We estimate 375 (136-1900) fewer RVGE admissions for every additional intussusception admission, and 88 (18-852) fewer RVGE deaths for every additional intussusception death. The estimated benefits of Rotarix® vaccination would greatly exceed the potential risk in England.Excess length of stay and mortality due to Clostridium difficile infection: A multi-state modelling approach
AbstractVan Kleef, E., Green, N., Goldenberg, S. D., Robotham, J. V., Cookson, B., Jit, M., Edmunds, W. J., & Deeny, S. R. (n.d.).Publication year
2014Journal title
Journal of Hospital InfectionVolume
88Issue
4Page(s)
213-217AbstractThe burden of healthcare-associated infections, such as healthcare-acquired Clostridium difficile (HA-CDI), can be expressed in terms of additional length of stay (LOS) and mortality. However, previous estimates have varied widely. Although some have considered time of infection onset (time-dependent bias), none considered the impact of severity of HA-CDI; this was the primary aim of this study. Methods: The daily risk of in-hospital death or discharge was modelled using a Cox proportional hazards model, fitted to data on patients discharged in 2012 from a large English teaching hospital. We treated HA-CDI status as a time-dependent variable and adjusted for confounders. In addition, a multi-state model was developed to provide a clinically intuitive metric of delayed discharge associated with non-severe and severe HA-CDI respectively. Findings: Data comprised 157 (including 48 severe) HA-CDI cases among 42,618 patients. HA-CDI reduced the daily discharge rate by nearly one-quarter [hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.61-0.84] and increased the in-hospital death rate by 75% compared with non-HA-CDI patients (HR: 1.75; 95% CI: 1.16-2.62). Whereas overall HA-CDI resulted in a mean excess LOS of about seven days (95% CI: 3.5-10.9), severe cases had an average excess LOS which was twice (~11.6 days; 95% CI: 3.6-19.6) that of the non-severe cases (about five days; 95% CI: 1.1-9.5). Conclusion: HA-CDI contributes to patients' expected LOS and risk of mortality. However, when quantifying the health and economic burden of hospital-onset of HA-CDI, the heterogeneity in the impact of HA-CDI should be accounted for.Key issues and challenges in estimating the impact and cost-effectiveness of quadrivalent influenza vaccination
AbstractQuinn, E., Jit, M., & Newall, A. T. (n.d.).Publication year
2014Journal title
Expert Review of Pharmacoeconomics and Outcomes ResearchVolume
14Issue
3Page(s)
425-435AbstractEvidence has shown that quadrivalent influenza vaccines containing all four subtypes are safe and immunogenic. However, to date there have been few published studies exploring the population-level clinical and economic impact of quadrivalent compared to trivalent influenza vaccines. Economic evaluation studies need to be conducted in order to inform country-level decision making about whether (and how to) introduce and replace the current trivalent influenza vaccines with quadrivalent influenza vaccination programs. Several key issues associated with estimating the clinical and economic impact of the trivalent versus quadrivalent vaccines are discussed in this article, particularly the complexities involved in estimating the incremental preventable disease and economic burden. Other factors, such as the indirect (herd) protection from quadrivalent influenza vaccination and the timing of the replacement of trivalent influenza vaccination programs are also discussed.Nosocomial transmission of c. difficile in English hospitals from patients with symptomatic infection
AbstractVan Kleef, E., Gasparrini, A., Guy, R., Cookson, B., Hope, R., Jit, M., Robotham, J. V., Deeny, S. R., & Edmunds, W. J. (n.d.).Publication year
2014Journal title
PloS oneVolume
9Issue
6AbstractBackground: Recent evidence suggests that less than one-quarter of patients with symptomatic nosocomial Clostridium difficile infections (CDI) are linked to other in-patients. However, this evidence was limited to one geographic area. We aimed to investigate the level of symptomatic CDI transmission in hospitals located across England from 2008 to 2012. Methods: A generalized additive mixed-effects Poisson model was fitted to English hospital-surveillance data. After adjusting for seasonal fluctuations and between-hospital variation in reported CDI over time, possible clustering (transmission between symptomatic in-patients) of CDI cases was identified. We hypothesised that a temporal proximity would be reflected in the degree of correlation between in-hospital CDI cases per week. This correlation was modelled through a latent autoregressive structure of order 1 (AR(1)). Findings: Forty-six hospitals (33 general, seven specialist, and six teaching hospitals) located in all English regions met our criteria. In total, 12,717 CDI cases were identified; seventy-five per cent of these occurred >48 hours after admission. There were slight increases in reports during winter months. We found a low, but statistically significant, correlation between successive weekly CDI case incidences (phi = 0.029, 95%CI: 0.009-0.049). This correlation was five times stronger in a subgroup analysis restricted to teaching hospitals (phi = 0.104, 95%CI: 0.048-0.159). Conclusions: The results suggest that symptomatic patient-to-patient transmission has been a source of CDI-acquisition in English hospitals in recent years, and that this might be a more important transmission route in teaching hospitals. Nonetheless, the weak correlation indicates that, in line with recent evidence, symptomatic cases might not be the primary source of nosocomial CDI in England.The burden of influenza in England by age and clinical risk group: A statistical analysis to inform vaccine policy
AbstractCromer, D., Van Hoek, A. J., Jit, M., Edmunds, W. J., Fleming, D., & Miller, E. (n.d.).Publication year
2014Journal title
Journal of InfectionVolume
68Issue
4Page(s)
363-371AbstractObjectives: To assess the burden of influenza by age and clinical status and use this to inform evaluations of the age and risk-based influenza vaccination policy in the United Kingdom. Methods: Weekly laboratory reports for influenza and 7 other respiratory pathogens were extracted from the national database and used in a regression model to estimate the proportion of acute respiratory illness outcomes attributable to each pathogen. Results: Influenza accounted for ~10% of the attributed respiratory admissions and deaths in hospital. Healthy children under five had the highest influenza admission rate (1.9/1000). The presence of co-morbidities increased the admission rate by 5.7 fold for 5-14 year olds (from 0.1 to 0.56/1000), the relative risk declining to 1.8 fold in 65+ year olds (from 0.46 to 0.84/1000). The majority (72%) of influenza-attributable deaths in hospital occurred in 65+ year olds with co-morbidities. Mortality in children under 15 years was low with around 12 influenza-attributable deaths in hospital per year in England the case fatality rate was substantially higher in risk than non-risk children. Infants under 6 months had the highest consultation and admission rates, around 70/1000 and 3/1000 respectively. Conclusions: Additional strategies are needed to reduce the remaining morbidity and mortality in the high-risk and elderly populations, and to protect healthy children currently not offered the benefits of vaccination.Two-dose strategies for human papillomavirus vaccination: How well do they need to protect?
AbstractJit, M., Choi, Y. H., Laprise, J. F., Boily, M. C., Drolet, M., & Brisson, M. (n.d.).Publication year
2014Journal title
VaccineVolume
32Issue
26Page(s)
3237-3242AbstractBackground: Two-dose human papillomavirus (HPV) vaccine schedules may provide short-term protection but their long-term population impact is unknown. Methods: Two models of HPV transmission and associated cervical disease (squamous and glandular, neoplasia and cancer) were fitted to data from England and Canada on HPV epidemiology, sexual behaviour, cervical screening outcomes and cervical cancer incidence. Results: Models suggest that at 40-80% coverage, if two-dose schedules protect vaccinees for 20 years, then the benefits of the third dose are small. If two doses protect for 10 years, then the third dose may prevent as many cancers as the first two. At 80% coverage, numbers needed to receive a third dose to prevent an additional cancer are 5900-110,000 (England), 3000-5100 (Canada) with 20 years two-dose protection, and 2000-5300 (England), 760-950 (Canada) with 10 years two-dose protection. Conclusion: Results enable decision makers to quantify risks associated with two-dose schedules despite remaining uncertainties in vaccine duration and cross-protection.A Randomized, Observer-Blinded Immunogenicity Trial of Cervarix® and Gardasil® Human Papillomavirus Vaccines in 12-15 Year Old Girls
AbstractDraper, E., Bissett, S. L., Howell-Jones, R., Waight, P., Soldan, K., Jit, M., Andrews, N., Miller, E., & Beddows, S. (n.d.).Publication year
2013Journal title
PloS oneVolume
8Issue
5AbstractBackground:The current generation of Human Papillomavirus (HPV) vaccines, Cervarix® and Gardasil®, exhibit a high degree of efficacy in clinical trials against the two high-risk (HR) genotypes represented in the vaccines (HPV16 and HPV18). High levels of neutralizing antibodies are elicited against the vaccine types, consistent with preclinical data showing that neutralizing antibodies can mediate type-specific protection in the absence of other immune effectors. The vaccines also confer protection against some closely related non-vaccine HR HPV types, although the vaccines appear to differ in their degree of cross-protection. The mechanism of vaccine-induced cross-protection is unknown. This study sought to compare the breadth and magnitudes of neutralizing antibodies against non-vaccine types elicited by both vaccines and establish whether such antibodies could be detected in the genital secretions of vaccinated individuals.Methods and Findings:Serum and genital samples were collected from 12-15 year old girls following vaccination with either Cervarix® (n = 96) or Gardasil® (n = 102) HPV vaccine. Serum-neutralizing antibody responses against non-vaccine HPV types were broader and of higher magnitude in the Cervarix®, compared to the Gardasil®, vaccinated individuals. Levels of neutralizing and binding antibodies in genital secretions were closely associated with those found in the serum (r = 0.869), with Cervarix® having a median 2.5 (inter-quartile range, 1.7-3.5) fold higher geometric mean HPV-specific IgG ratio in serum and genital samples than Gardasil® (p = 0.0047). There was a strong positive association between cross-neutralizing antibody seropositivity and available HPV vaccine trial efficacy data against non-vaccine types.Conclusions:These data demonstrate for the first time that cross-neutralizing antibodies can be detected at the genital site of infection and support the possibility that cross-neutralizing antibodies play a role in the cross-protection against HPV infection and disease that has been reported for the current HPV vaccines.Trial Registration:ClinicalTrials.gov NCT00956553.Acceptability and uptake of female adolescent HPV vaccination in Hong Kong: A survey of mothers and adolescents
AbstractChoi, H. C., Leung, G. M., Woo, P. P., Jit, M., & Wu, J. T. (n.d.).Publication year
2013Journal title
VaccineVolume
32Issue
1Page(s)
78-84AbstractBackground: Organized population-based HPV vaccination programs can be effective in reducing the burden of cervical cancer, especially in the absence of a comprehensive cervical screening program (e.g. Hong Kong). Assessment of vaccine acceptability is important when evaluating the feasibility and cost-effectiveness of such vaccination programs. Methods: To provide a more representative and updated assessment on the acceptability of female adolescent HPV vaccination in Hong Kong, we conducted surveys in 2008 among 1022 mothers with daughters aged ≤18 years through random digit-dialing telephone interviewing and 2167 schoolgirls aged 11-18 years using two-stage stratified cluster sampling. We conducted the maternal survey again in 2012 with an independent group of 1005 mothers. Results: In 2008, 2.4% (95% confidence interval [CI] = 1.8-3.2%) of the recruited schoolgirls reported having received HPV vaccination. In 2012, the mothers reported that 9.1% (7.0-11.6%) of their daughters who were in the same age range (11-18 years) as the schoolgirls had been vaccinated (p < 0.01). Regarding acceptability, 27.5% (24.8-30.4%) and 37.6% (34.5-40.8%) of the mothers were willing to have their daughters vaccinated at market price in 2008 and 2012 (p < 0.01), respectively. 27.1% (25.2-29.1%) of the schoolgirls were willing to receive HPV vaccination at market price in 2008. The willingness to pay for full-course vaccination among mothers had a median of US$128/HK$1000 (50% central range = US$64-192/HK$500-1500), i.e. substantially lower than the current market price. Conclusions: The gap between acceptability and actual uptake of HPV vaccination among adolescent girls suggested that coverage is likely to be low without an organized HPV vaccination program, although the difference might be partially attributed to the possibility that at the time of the interview female adolescents who were willing to be vaccinated had not yet taken action. Policymakers should devise tailored, targeted and efficient vaccination strategies to achieve universal coverage for an effectively organized HPV vaccination program.An integrated approach to evaluating alternative risk prediction strategies: A case study comparing alternative approaches for preventing invasive fungal disease
AbstractSadique, Z., Grieve, R., Harrison, D. A., Jit, M., Allen, E., & Rowan, K. M. (n.d.).Publication year
2013Journal title
Value in HealthVolume
16Issue
8Page(s)
1111-1122AbstractObjectives This article proposes an integrated approach to the development, validation, and evaluation of new risk prediction models illustrated with the Fungal Infection Risk Evaluation study, which developed risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive fungal disease (IFD). Methods Our decision-analytical model compared alternative strategies for preventing IFD at up to three clinical decision time points (critical care admission, after 24 hours, and end of day 3), followed with antifungal prophylaxis for those judged "high" risk versus "no formal risk assessment." We developed prognostic models to predict the risk of IFD before critical care unit discharge, with data from 35,455 admissions to 70 UK adult, critical care units, and validated the models externally. The decision model was populated with positive predictive values and negative predictive values from the best-fitting risk models. We projected lifetime cost-effectiveness and expected value of partial perfect information for groups of parameters. Results The risk prediction models performed well in internal and external validation. Risk assessment and prophylaxis at the end of day 3 was the most cost-effective strategy at the 2% and 1% risk threshold. Risk assessment at each time point was the most cost-effective strategy at a 0.5% risk threshold. Expected values of partial perfect information were high for positive predictive values or negative predictive values (£11 million-£13 million) and quality-adjusted life-years (£11 million). Conclusions It is cost-effective to formally assess the risk of IFD for non-neutropenic, critically ill adult patients. This integrated approach to developing and evaluating risk models is useful for informing clinical practice and future research investment.Cost-effectiveness of human papillomavirus vaccination in low and middle income countries: A systematic review
AbstractFesenfeld, M., Hutubessy, R., & Jit, M. (n.d.).Publication year
2013Journal title
VaccineVolume
31Issue
37Page(s)
3786-3804AbstractThe World Health Organization recommends establishing that human papillomavirus vaccination is cost-effective before vaccine introduction. We searched Pubmed, Embase and the Cochrane Library to 1 April 2012 for economic evaluations of human papillomavirus vaccination in low and middle income countries. We found 25 articles, but almost all low income countries and many middle income countries lacked country-specific studies. Methods, assumptions and consequently results varied widely, even for studies conducted for the same country. Despite the heterogeneity, most studies conclude that vaccination is likely to be cost-effective and possibly even cost saving, particularly in settings without organized cervical screening programmes. However, study uncertainty could be reduced by clarity about vaccine prices and vaccine delivery costs. The review supports extending vaccination to low income settings where vaccine prices are competitive, donor funding is available, cervical cancer burden is high and screening options are limited.Cost-effectiveness of point-of-care C-reactive protein testing to inform antibiotic prescribing decisions
AbstractOppong, R., Jit, M., Smith, R. D., Butler, C. C., Melbye, H., Mölstad, S., & Coast, J. (n.d.).Publication year
2013Journal title
British Journal of General PracticeVolume
63Issue
612Page(s)
e465-e471AbstractBackground Point-of-care C-reactive protein (POCCRP) is a biomarker of inflammation that offers clinicians a rapid POC test to guide antibiotic prescribing decisions for acute cough and lower respiratory tract infections (LRTI). However, evidence that POCCRP is cost-effective is limited, particularly outside experimental settings. Aim To assess the cost-effectiveness of POCCRP as a diagnostic tool for acute cough and LRTI from the perspective of the health service. Design and setting Observational study of the presentation, management, and outcomes of patients with acute cough and LRTI in primary care settings in Norway and Sweden. Method Using hierarchical regression, data were analysed in terms of the effect on antibiotic use, cost, and patient outcomes (symptom severity after 7 and 14 days, time to recovery, and EQ-5D), while controlling for patient characteristics (self-reported symptom severity, comorbidities, and health-related quality of life) at first attendance. Results POCCRP testing is associated with non-significant positive reductions in antibiotic prescribing (P = 0.078) and increased cost (P = 0.092). Despite the uncertainty, POCCRP testing is also associated with a cost per quality-adjusted life year (QALY) gain of €9391. At a willingness-to-pay threshold of €30 000 per QALY gained, there is a 70% probability of CRP being cost-effective. Conclusion POCCRP testing is likely to provide a cost-effective diagnostic intervention both in terms of reducing antibiotic prescribing and in terms of QALYs gained.Development and validation of a risk model for identification of non-neutropenic, critically-ill, adult patients at high risk of invasive Candida infection
AbstractHarrison, D., Muskett, H., Harvey, S., Grieve, R., Shahin, J., Patel, K., Sadique, Z., Allen, E., Dybowski, R., Jit, M., Edgeworth, J., Kibbler, C., Barnes, R., Soni, N., & Rowan, K. (n.d.).Publication year
2013Journal title
Health Technology AssessmentVolume
17Issue
3Page(s)
1-30AbstractBackground There is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy. Objectives To develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive Candida infection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models. Design Systematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis. Setting Ninety-six UK adult general critical care units. Participants Consecutive admissions to participating critical care units. Interventions None. Main outcome measures Invasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasive Candida infection, defined as IFD-positive for Candida species. Results Systematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection. Data collection: Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive for Candida species. The most common site of infection was blood (55%). The incidence of IFD identified in unit was 4.7 cases per 1000 admissions, and for unit-acquired IFD was 3.2 cases per 1000 admissions. Statistical modelling: Risk models were developed at admission to the critical care unit, 24 hours and the end of calendar day 3. The risk model at admission had fair discrimination (c-index 0.705). Discrimination improved at 24 hours (c-index 0.823) and this was maintained at the end of calendar day 3 (c-index 0.835). There was a drop in model performance in the validation sample. Economic decision model: Irrespective of risk threshold, incremental quality-adjusted life-years of prophylaxis strategies compared with current practice were positive but small compared with the incremental costs. Incremental net benefits of each prophylaxis strategy compared with current practice were all negative. Cost-effectiveness acceptability curves showed that current practice was the strategy most likely to be cost-effective. Across all parameters in the decision model, results indicated that the value of further research for the whole population of interest might be high relative to the research costs. Conclusions The results of the Fungal Infection Risk Evaluation (FIRE) Study, derived from a highly representative sample of adult general critical care units across the UK, indicated a low incidence of IFD among non-neutropenic, critically ill adult patients. IFD was associated with substantially higher mortality, more intensive organ support and longer length of stay. Risk modelling produced simple risk models that provided acceptable discrimination for identifying patients at 'high risk' of invasive Candida infection. Results of the economic model suggested that the current most cost-effective treatment strategy for prophylactic use of systemic antifungal agents among non-neutropenic, critically ill adult patients admitted to NHS adult general critical care units is a strategy of no risk assessment and no antifungal prophylaxis. Funding Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.Economic analyses to support decisions about HPV vaccination in low- and middle-income countries: A consensus report and guide for analysts
AbstractJit, M., Levin, C., Brisson, M., Levin, A., Resch, S., Berkhof, J., Kim, J., & Hutubessy, R. (n.d.). In BMC Medicine (1–).Publication year
2013Volume
11Issue
1AbstractLow- and middle-income countries need to consider economic issues such as cost-effectiveness, affordability and sustainability before introducing a program for human papillomavirus (HPV) vaccination. However, many such countries lack the technical capacity and data to conduct their own analyses. Analysts informing policy decisions should address the following questions: 1) Is an economic analysis needed? 2) Should analyses address costs, epidemiological outcomes, or both? 3) If costs are considered, what sort of analysis is needed? 4) If outcomes are considered, what sort of model should be used? 5) How complex should the analysis be? 6) How should uncertainty be captured? 7) How should model results be communicated? Selecting the appropriate analysis is essential to ensure that all the important features of the decision problem are correctly represented, but that the analyses are not more complex than necessary. This report describes the consensus of an expert group convened by the World Health Organization, prioritizing key issues to be addressed when considering economic analyses to support HPV vaccine introduction in these countries.Efficacy and effectiveness of seasonal and pandemic A (H1N1) 2009 influenza vaccines in low and middle income countries: A systematic review and meta-analysis
AbstractBreteler, J. K., Tam, J. S., Jit, M., Ket, J. C., & De Boer, M. R. (n.d.).Publication year
2013Journal title
VaccineVolume
31Issue
45Page(s)
5168-5177AbstractPurpose: Influenza vaccines have been recommended for populations at risk for severe infection in low and middle income countries (LMICs) although knowledge of the evidence-base for their effectiveness and efficacy is limited in these countries. The aim of this systematic review is to provide an overview of the evidence-base for the effectiveness and efficacy of influenza vaccines in LMICs and to explore critical knowledge gaps. Methods: PubMed, EMBASE, and Cochrane were searched for seasonal and pandemic A (H1N1) 2009 influenza vaccine effectiveness and efficacy studies performed in LMICs. Eligible studies included RCTs and observational studies, published in English, French, Spanish or Portuguese between 1960 and 2011, which assessed laboratory-confirmed influenza and/or influenza-related outcomes in any population. Risk of bias was assessed by two reviewers independently. Random effects pooled estimates were obtained when sufficient data were available. Results: A total of 6465 articles were screened. Forty-one studies were included on seasonal influenza vaccine effectiveness and efficacy and one study on pandemic vaccine effectiveness. In middle income countries (MICs), efficacy of seasonal influenza vaccines was shown against laboratory-confirmed influenza in children (pooled efficacy 72% (95%CI: 65-77) and 81% (95%CI: 69-89), for one and two years follow-up respectively) and in the elderly (pooled efficacy 43% (95%CI: 25-56) and 58% (95%CI: 23-78), for live attenuated and inactivated vaccine respectively). Inactivated influenza vaccines were also found to be effective against cardiovascular outcomes in patients with coronary syndromes. Conclusions: Seasonal influenza vaccines can provide protection in children, the elderly and patients with coronary syndromes in MICs, and seem to be equally effective as compared to high income countries. Data for other high risk groups and from low income countries were limited or prone to bias, and are needed to further facilitate evidence-based decision making regarding influenza vaccination in LMICs.Influenza vaccines in low and middle income countries: A systematic review of economic evaluations
AbstractOtt, J. J., Breteler, J. K., Tam, J. S., Hutubessy, R. C., Jit, M., & De Boer, M. R. (n.d.).Publication year
2013Journal title
Human Vaccines and ImmunotherapeuticsVolume
9Issue
7Page(s)
1500-1511AbstractObjectives: Economic evaluations on influenza vaccination from low resource settings are scarce and have not been evaluated using a systematic approach. Our objective was to conduct a systematic review on the value for money of influenza vaccination in low- and middle-income countries. Methods: PubMed and EMBASE were searched for economic evaluations published in any language between 1960 and 2011. Main outcome measures were costs per influenza outcome averted, costs per quality-adjusted life years gained or disability-adjusted life years averted, costs per benefit in monetary units or cost-benefit ratios. Results: Nine economic evaluations on seasonal influenza vaccine met the inclusion criteria. These were model- or randomized-controlled-trial (RCT)-based economic evaluations from middle-income countries. Influenza vaccination provided value for money for elderly, infants, adults and children with high-risk conditions. Vaccination was cost-effective and costsaving for chronic obstructive pulmonary disease patients and in elderly above 65 y from model-based evaluations, but conclusions from RCTs on elderly varied. Conclusion: Economic evaluations from middle income regions differed in population studied, outcomes and definitions used. Most findings are in line with evidence from high-income countries highlighting that influenza vaccine is likely to provide value for money. However, serious methodological limitations do not allow drawing conclusions on cost-effectiveness of influenza vaccination in middle income countries. Evidence on cost-effectiveness from low-income countries is lacking altogether, and more information is needed from full economic evaluations that are conducted in a standardized manner.Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies
AbstractJit, M., Newall, A. T., & Beutels, P. (n.d.).Publication year
2013Journal title
Human Vaccines and ImmunotherapeuticsVolume
9Issue
4Page(s)
834-840AbstractMany countries have considered or are considering modifying their seasonal influenza immunization policies. Estimating the impact of such changes requires understanding the existing clinical and economic burden of influenza, as well as the potential impact of different vaccination options. Previous studies suggest that vaccinating clinical risk groups, health care workers, children and the elderly may be cost-effective. However, challenges in such estimation include: (1) potential cases are not usually virologically tested; (2) cases have nonspecific symptoms and are rarely reported to surveillance systems; (3) endpoints for influenza proxies (such as influenzalike illness) need to be matched to case definitions for treatment costs, (4) disease burden estimates vary from year to year with strain transmissibility, virulence and prior immunity, (5) methods to estimate productivity losses due to influenza vary, (6) vaccine efficacy estimates from trials differ due to variation in subtype prevalence, vaccine match and case ascertainment, and (7) indirect (herd) protection from vaccination depends on settingspecific variables that are difficult to directly measure. Given the importance of knowing the impact of changes to influenza policy, such complexities need careful treatment using tools such as population-based trial designs, meta-analyses, timeseries analyses and transmission dynamic models.