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. 2022 Jun 17:19:100426.
doi: 10.1016/j.lanepe.2022.100426. eCollection 2022 Aug.

Transmission dynamics of the 2016-18 outbreak of hepatitis A among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks

Xu-Sheng Zhang  1 , Jason J Ong  2   3 , Louis Macgregor  2 , Tatiana G Vilaplana  4 , Simone T Heathcock  5 , Miranda Mindlin  6 , Peter Weatherburn  7 , Ford Hickson  7 , Michael Edelstein  4 , Sema Mandal  2   4 , Peter Vickerman  2
Affiliations

Transmission dynamics of the 2016-18 outbreak of hepatitis A among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks

Xu-Sheng Zhang et al. Lancet Reg Health Eur. .

Abstract

Background: Despite being vaccine-preventable, hepatitis A virus (HAV) outbreaks occur among men who have sex with men (MSM). We modelled the cost-effectiveness of vaccination strategies to prevent future outbreaks.

Methods: A HAV transmission model was calibrated to HAV outbreak data for MSM in England over 2016-2018, producing estimates for the basic reproduction number (R0) and immunity levels (seroprevalence) post-outbreak. For a hypothetical outbreak in 2023 (same R0 and evolving immunity), the cost-effectiveness of pre-emptive (vaccination between outbreaks among MSM attending sexual health services (SHS)) and reactive (vaccination during outbreak among MSM attending SHS and primary care) vaccination strategies were modelled. Effectiveness in quality-adjusted life-years (QALYs) and costs were estimated (2017 UK pounds) from a societal perspective (10-year time horizon; 3% discount rate). The incremental cost-effectiveness ratio (ICER) was estimated.

Findings: R0 for the 2016-2018 outbreak was 3·19 (95% credibility interval (95%CrI) 2·87-3·46); seroprevalence among MSM increased to 70·4% (95%CrI 67·3-72·8%) post-outbreak. For our hypothetical HAV outbreak in 2023, pre-emptively vaccinating MSM over the preceding five-years was cost-saving (compared to no vaccination) if the yearly vaccine coverage rate among MSM attending SHS was <9·1%. Reactive vaccination was also cost-saving compared to no vaccination, but was dominated by pre-emptive vaccination if the yearly vaccination rate was >8%. If the pre-emptive yearly vaccination rate fell below this threshold, it became cost-saving to add reactive vaccination to pre-emptive vaccination.

Interpretation: Although highly transmissible, existing immunity limited the recent HAV outbreak among MSM in England. Pre-emptive vaccination between outbreaks, with reactive vaccination if indicated, is the best strategy for limiting future HAV outbreaks.

Funding: NIHR.

Keywords: Cost-effectiveness; Hepatitis A virus; Immunisation; Men who have sex with men.

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Conflict of interest statement

PV has received unrestricted research grants from Gilead not related to the submitted work. This research was funded in whole, or in part, by the National Institute for Health Research Health Protection Research Unit for Behavioural Science and Evaluation and the Wellcome Trust [WT 220866/Z/20/Z].

Figures

Fig 1
Figure 1
Schematic of the model of hepatitis A virus transmission among men who have sex with men for model fitting to the 2016/18 outbreak (A) and for assessing the impact and cost-effectiveness of different vaccination strategies for the hypothetical outbreak in 2023 (B). The thick blue line denotes the effect of vaccination. Within the transmission model for the 2016/18 outbreak (panel A), individuals start as susceptible to infection; under the force of infection λ, they are exposed to HAV. When exposed they become latently infected but not yet infectious, after a latent period of L, they then become occultly infectious, with a proportion (ps) of individuals after an infectious period d1 then becoming symptomatic and the rest remaining asymptomatic but infectious. They then recover after dD days for symptomatic and d2 days for asymptomatic individuals and become immune to HAV. For the model assessing vaccination strategies (panel B), among occultly infectious individuals, there is a proportion pF developing fulminant hepatitis and a proportion pL requiring liver transplant in addition to those becoming symptomatic and asymptomatic individuals.
Fig 2
Figure 2
Model fitting to the 2016/18 hepatitis A outbreak data of 725-39=686 male cases (red dots for cases per week) with vaccination from July 2017 to July 2018. The black triangles represent the 39 imported cases. Thick blue dots represent the median and thin blue dots 95% credibility interval of the model projections. The yellow vertical line is the median of the estimated time when the model estimates the contact rate decreases, and the two green vertical lines represent the lower and upper of the 95% credibility interval.
Fig 3
Figure 3
Modelled outbreaks from 2023 with either (a) no vaccination, or (b, c and d) just pre-emptive vaccination (PV=4%, 7% and 9% per year), or (e) just reactive vaccination (RV), or (f, g and h) PV with RV (PV(4%)+RV, PV(7%)+RV, PV(9%)+RV). The percentage in PV(%) represents the yearly rate of pre-emptive vaccination of MSM who attend SHS clinics. The outbreaks are generated by 39 imported cases (as occurred in the 2016/18 outbreak - black triangles). A 30-year time period is presented to show the periodic epidemics.
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References

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