Mark Jit

Chair and Professor of the Department of Global and Environmental Health

Professional overview

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.

Education

BSc, Mathematics, University College London

PhD, Mathematics, University College London

MPH, Public Health, King's College London

Honors and awards

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)

Publications

Publications

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., & Jit, M. (n.d.).

Publication year

2014

Journal title

PharmacoEconomics

Volume

32

Issue

6

Page(s)

525-531

10.1007/s40273-014-0162-x

Abstract

Abstract

The World Health Organization's CHOosing Interventions that are Cost Effective (WHO-CHOICE) thresholds for averting a disability-adjusted life-year of one to three times per capita income have been widely cited and used as a measure of cost effectiveness in evaluations of vaccination for low- and middle-income countries (LMICs). These thresholds were based upon criteria set out by the WHO Commission on Macroeconomics and Health, which reflected the potential economic returns of interventions. The CHOICE project sought to evaluate a variety of health interventions at a subregional level and classify them into broad categories to help assist decision makers, but the utility of the thresholds for within-country decision making for individual interventions (given budgetary constraints) has not been adequately explored. To examine whether the 'WHO-CHOICE thresholds' reflect funding decisions, we examined the results of two recent reviews of cost-effectiveness analyses of human papillomavirus and rotavirus vaccination in LMICs, and we assessed whether the results of these studies were reflected in funding decisions for these vaccination programmes. We found that in many cases, programmes that were deemed cost effective were not subsequently implemented in the country. We consider the implications of this finding, the advantages and disadvantages of alternative methods to estimate thresholds, and how cost perspectives and the funders of healthcare may impact on these choices.

Authors’ 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., & Jit, M. (n.d.).

Publication year

2014

Journal title

PharmacoEconomics

Volume

32

Issue

12

Page(s)

1247

10.1007/s40273-014-0232-0

Abstract

Abstract

~

Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination : A transmission-dynamic modelling study

Laprise, 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

2014

Journal title

Vaccine

Volume

32

Issue

44

Page(s)

5845-5853

10.1016/j.vaccine.2014.07.099

Abstract

Abstract

Background: 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

Jit, M., Brisson, M., Portnoy, A., & Hutubessy, R. (n.d.).

Publication year

2014

Journal title

The Lancet Global Health

Volume

2

Issue

7

Page(s)

e406-e414

10.1016/S2214-109X(14)70237-2

Abstract

Abstract

Background: 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

Clark, A., Jit, M., Andrews, N., Atchison, C., Edmunds, W. J., & Sanderson, C. (n.d.).

Publication year

2014

Journal title

Vaccine

Volume

32

Issue

29

Page(s)

3604-3610

10.1016/j.vaccine.2014.04.082

Abstract

Abstract

Rotarix®, 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

Excess length of stay and mortality due to Clostridium difficile infection : A multi-state modelling approach

van Kleef, E., Green, N., Goldenberg, S. D., Robotham, J. V., Cookson, B., Jit, M., Edmunds, W. J., Deeny, S. R., & Jit, M. (n.d.).

Publication year

2014

Journal title

Journal of Hospital Infection

Volume

88

Issue

4

Page(s)

213-217

10.1016/j.jhin.2014.08.008

Abstract

Abstract

The 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

Quinn, E., Jit, M., & Newall, A. T. (n.d.).

Publication year

2014

Journal title

Expert Review of Pharmacoeconomics and Outcomes Research

Volume

14

Issue

3

Page(s)

425-435

10.1586/14737167.2014.908713

Abstract

Abstract

Evidence 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

Van 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

2014

Journal title

PloS one

Volume

9

Issue

6

10.1371/journal.pone.0099860

Abstract

Abstract

Background: 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.

Reassessing the value of vaccines

Bärnighausen, T., Berkley, S., Bhutta, Z. A., Bishai, D. M., Black, M. M., Bloom, D. E., Constenla, D., Driessen, J., Edmunds, J., Evans, D., Griffiths, U., Hansen, P., Hashmani, F. N., Hutubessy, R., Jamison, D. T., Jha, P., Jit, M., Johnson, H., Laxminarayan, R., … Walker, D. (n.d.).

Publication year

2014

Journal title

The Lancet Global Health

Volume

2

Issue

5

Page(s)

e251-e252

10.1016/S2214-109X(13)70170-0

Abstract

Abstract

~

The burden of influenza in England by age and clinical risk group : A statistical analysis to inform vaccine policy

Cromer, D., Van Hoek, A. J., Jit, M., Edmunds, W. J., Fleming, D., & Miller, E. A. (n.d.).

Publication year

2014

Journal title

Journal of Infection

Volume

68

Issue

4

Page(s)

363-371

10.1016/j.jinf.2013.11.013

Abstract

Abstract

Objectives: 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?

Jit, M., Choi, Y. H., Laprise, J. F., Boily, M. C., Drolet, M., & Brisson, M. (n.d.).

Publication year

2014

Journal title

Vaccine

Volume

32

Issue

26

Page(s)

3237-3242

10.1016/j.vaccine.2014.03.098

Abstract

Abstract

Background: 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

Draper, E., Bissett, S. L., Howell-Jones, R., Waight, P., Soldan, K., Jit, M., Andrews, N., Miller, E. A., & Beddows, S. (n.d.).

Publication year

2013

Journal title

PloS one

Volume

8

Issue

5

10.1371/journal.pone.0061825

Abstract

Abstract

Background: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

Choi, H. C., Leung, G. M., Woo, P. P., Jit, M., & Wu, J. T. (n.d.).

Publication year

2013

Journal title

Vaccine

Volume

32

Issue

1

Page(s)

78-84

10.1016/j.vaccine.2013.10.068

Abstract

Abstract

Background: 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

Sadique, Z., Grieve, R., Harrison, D. A., Jit, M., Allen, E., Rowan, K. M., & Jit, M. (n.d.).

Publication year

2013

Journal title

Value in Health

Volume

16

Issue

8

Page(s)

1111-1122

10.1016/j.jval.2013.09.006

Abstract

Abstract

Objectives 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

Fesenfeld, M., Hutubessy, R., & Jit, M. (n.d.).

Publication year

2013

Journal title

Vaccine

Volume

31

Issue

37

Page(s)

3786-3804

10.1016/j.vaccine.2013.06.060

Abstract

Abstract

The 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

Oppong, R., Jit, M., Smith, R. D., Butler, C. C., Melbye, H., Mölstad, S., & Coast, J. (n.d.).

Publication year

2013

Journal title

British Journal of General Practice

Volume

63

Issue

612

Page(s)

e465-e471

10.3399/bjgp13X669185

Abstract

Abstract

Background 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

Harrison, 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., & Jit, M. (n.d.).

Publication year

2013

Journal title

Health Technology Assessment

Volume

17

Issue

3

Page(s)

1-30

10.3310/hta17030

Abstract

Abstract

Background 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

Jit, M., Levin, C., Brisson, M., Levin, A., Resch, S., Berkhof, J., Kim, J., & Hutubessy, R. (n.d.).

Publication year

2013

Journal title

BMC Medicine

Volume

11

Issue

1

10.1186/1741-7015-11-23

Abstract

Abstract

Low- 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

Breteler, J. K., Tam, J. S., Jit, M., Ket, J. C., & De Boer, M. R. (n.d.).

Publication year

2013

Journal title

Vaccine

Volume

31

Issue

45

Page(s)

5168-5177

10.1016/j.vaccine.2013.08.056

Abstract

Abstract

Purpose: 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

Ott, J. J., Breteler, J. K., Tam, J. S., Hutubessy, R. C., Jit, M., & De Boer, M. R. (n.d.).

Publication year

2013

Journal title

Human Vaccines and Immunotherapeutics

Volume

9

Issue

7

Page(s)

1500-1511

10.4161/hv.24704

Abstract

Abstract

Objectives: 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

Jit, M., Newall, A. T., & Beutels, P. (n.d.).

Publication year

2013

Journal title

Human Vaccines and Immunotherapeutics

Volume

9

Issue

4

Page(s)

834-840

10.4161/hv.23637

Abstract

Abstract

Many 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.

Modelling the transmission of healthcare associated infections : A systematic review

van Kleef, E., Robotham, J. V., Jit, M., Deeny, S. R., & Edmunds, W. J. (n.d.).

Publication year

2013

Journal title

BMC Infectious Diseases

Volume

13

Issue

1

10.1186/1471-2334-13-294

Abstract

Abstract

Background: Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time.Methods: MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings.Results: In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries.The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data.Conclusions: Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses. Insights gained from these models could be broadened to a wider range of pathogens and settings. Improvements in the availability of data and statistical methods could enhance the predictive ability of models.

Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England

Mesher, D., Soldan, K., Howell-Jones, R., Panwar, K., Manyenga, P., Jit, M., Beddows, S., Gill, O. N., & Jit, M. (n.d.).

Publication year

2013

Journal title

Vaccine

Volume

32

Issue

1

Page(s)

26-32

10.1016/j.vaccine.2013.10.085

Abstract

Abstract

Background: Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. Methods: Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. Results: A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. Conclusions: These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types.

Trends in parameterization, economics and host behaviour in influenza pandemic modelling : A review and reporting protocol

Carrasco, L. R., Jit, M., Chen, M. I., Lee, V. J., Milne, G. J., & Cook, A. R. (n.d.).

Publication year

2013

Journal title

Emerging Themes in Epidemiology

Volume

10

Issue

1

10.1186/1742-7622-10-3

Abstract

Abstract

Background: The volume of influenza pandemic modelling studies has increased dramatically in the last decade. Many models incorporate now sophisticated parameterization and validation techniques, economic analyses and the behaviour of individuals. Methods. We reviewed trends in these aspects in models for influenza pandemic preparedness that aimed to generate policy insights for epidemic management and were published from 2000 to September 2011, i.e. before and after the 2009 pandemic. Results: We find that many influenza pandemics models rely on parameters from previous modelling studies, models are rarely validated using observed data and are seldom applied to low-income countries. Mechanisms for international data sharing would be necessary to facilitate a wider adoption of model validation. The variety of modelling decisions makes it difficult to compare and evaluate models systematically. Conclusions: We propose a model Characteristics, Construction, Parameterization and Validation aspects protocol (CCPV protocol) to contribute to the systematisation of the reporting of models with an emphasis on the incorporation of economic aspects and host behaviour. Model reporting, as already exists in many other fields of modelling, would increase confidence in model results, and transparency in their assessment and comparison.

Use of measles supplemental immunization activities (SIAs) as a delivery platform for other maternal and child health interventions : Opportunities and challenges

Johri, M., Sharma, J. K., Jit, M., & Verguet, S. (n.d.).

Publication year

2013

Journal title

Vaccine

Volume

31

Issue

9

Page(s)

1259-1263

10.1016/j.vaccine.2012.09.044

Abstract

Abstract

Measles supplementary immunization activities (SIAs) offer children in countries with weaker immunization delivery systems like India a second opportunity for measles vaccination. They could also provide a platform to deliver additional interventions, but the feasibility and acceptability of including add-ons is uncertain. We surveyed Indian programme officers involved in the current (2010-2012) measles SIAs concerning opportunities and challenges of using SIAs as a delivery platform for other maternal and child health interventions. Respondents felt that an expanded SIA strategy including add-ons could be of great value in improving access and efficiency. They viewed management challenges, logistics, and safety as the most important potential barriers. They proposed that additional interventions be selected using several criteria, of which importance of the health problem, safety, and contribution to health equity figured most prominently. For children, they recommended inclusion of basic interventions to address nutritional deficiencies, diarrhoea and parasites over vaccines. For mothers, micronutrient interventions were highest ranked.