A mathematical model of Marburg virus disease outbreaks and the potential role of vaccination in control.

George Y Qian, W John Edmunds, Daniel G Bausch, Thibaut Jombart
Author Information
  1. George Y Qian: Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK. george.qian@bristol.ac.uk. ORCID
  2. W John Edmunds: Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK.
  3. Daniel G Bausch: FIND, Geneva, Switzerland.
  4. Thibaut Jombart: Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK.

Abstract

BACKGROUND: Marburg virus disease is an acute haemorrhagic fever caused by Marburg virus. Marburg virus is zoonotic, maintained in nature in Egyptian fruit bats, with occasional spillover infections into humans and nonhuman primates. Although rare, sporadic cases and outbreaks occur in Africa, usually associated with exposure to bats in mines or caves, and sometimes with secondary human-to-human transmission. Outbreaks outside of Africa have also occurred due to importation of infected monkeys. Although all previous Marburg virus disease outbreaks have been brought under control without vaccination, there is nevertheless the potential for large outbreaks when implementation of public health measures is not possible or breaks down. Vaccines could thus be an important additional tool, and development of several candidate vaccines is under way.
METHODS: We developed a branching process model of Marburg virus transmission and investigated the potential effects of several prophylactic and reactive vaccination strategies in settings driven primarily by multiple spillover events as well as human-to-human transmission. Linelist data from the 15 outbreaks up until 2022, as well as an Approximate Bayesian Computational framework, were used to inform the model parameters.
RESULTS: Our results show a low basic reproduction number which varied across outbreaks, from 0.5 [95% CI 0.05-1.8] to 1.2 [95% CI 1.0-1.9] but a high case fatality ratio. Of six vaccination strategies explored, the two prophylactic strategies (mass and targeted vaccination of high-risk groups), as well as a combination of ring and targeted vaccination, were generally most effective, with a probability of potential outbreaks being terminated within 1 year of 0.90 (95% CI 0.90-0.91), 0.89 (95% CI 0.88-0.90), and 0.88 (95% CI 0.87-0.89) compared with 0.68 (0.67-0.69) for no vaccination, especially if the outbreak is driven by zoonotic spillovers and the vaccination campaign initiated as soon as possible after onset of the first case.
CONCLUSIONS: Our study shows that various vaccination strategies can be effective in helping to control outbreaks of MVD, with the best approach varying with the particular epidemiologic circumstances of each outbreak.

Keywords

References

  1. Vaccine. 2021 Jan 8;39(2):202-208 [PMID: 33309082]
  2. BMC Infect Dis. 2016 Nov 25;16(1):708 [PMID: 27887599]
  3. N Engl J Med. 2005 May 26;352(21):2155-7 [PMID: 15917379]
  4. N Engl J Med. 2020 Apr 2;382(14):1366-1369 [PMID: 32242365]
  5. PLoS Pathog. 2009 Jul;5(7):e1000536 [PMID: 19649327]
  6. Clin Trials. 2022 Dec;19(6):647-654 [PMID: 35866633]
  7. Viruses. 2012 Oct 01;4(10):1878-927 [PMID: 23202446]
  8. Lancet Infect Dis. 2015 May;15(5):507-8 [PMID: 25932579]
  9. PLoS Negl Trop Dis. 2019 Mar 18;13(3):e0007257 [PMID: 30883555]
  10. MMWR Morb Mortal Wkly Rep. 2009 Dec 18;58(49):1377-81 [PMID: 20019654]
  11. Int J Infect Dis. 2020 Oct;99:233-242 [PMID: 32758690]
  12. Microbiol Mol Biol Rev. 2020 May 13;84(2): [PMID: 32404328]
  13. Nat Med. 2021 Apr;27(4):580-581 [PMID: 33820993]
  14. Lancet. 1982 Apr 10;1(8276):816-20 [PMID: 6122054]
  15. Emerg Infect Dis. 2009 Aug;15(8):1171-5 [PMID: 19751577]
  16. Am J Epidemiol. 2004 Sep 15;160(6):509-16 [PMID: 15353409]
  17. Lancet. 2017 Feb 4;389(10068):505-518 [PMID: 28017403]
  18. Arch Virol Suppl. 1996;11:101-14 [PMID: 8800792]
  19. Emerg Infect Dis. 2006 Mar;12(3):433-9 [PMID: 16704781]
  20. J Virol. 2006 Jul;80(13):6497-516 [PMID: 16775337]
  21. PLoS Comput Biol. 2020 Dec 10;16(12):e1008409 [PMID: 33301457]
  22. Semin Pediatr Infect Dis. 2005 Jul;16(3):219-24 [PMID: 16044395]
  23. J Infect Dis. 2015 Oct 1;212 Suppl 2:S119-28 [PMID: 26209681]
  24. N Engl J Med. 2006 Aug 31;355(9):909-19 [PMID: 16943403]
  25. Trans R Soc Trop Med Hyg. 2015 Jun;109(6):366-78 [PMID: 25820266]
  26. Emerg Infect Dis. 2017 Jun;23(6):1001-1004 [PMID: 28518032]
  27. N Engl J Med. 2014 Oct 16;371(16):1481-95 [PMID: 25244186]
  28. PLoS One. 2012;7(12):e50948 [PMID: 23251407]
  29. J Infect Dis. 2011 Nov;204 Suppl 3:S796-9 [PMID: 21987753]
  30. PLoS Pathog. 2019 Feb 28;15(2):e1007564 [PMID: 30817809]
  31. Front Immunol. 2021 Oct 27;12:774026 [PMID: 34777392]
  32. Br Med J. 1975 Nov 29;4(5995):489-93 [PMID: 811315]
  33. J Infect Dis. 2007 Nov 15;196 Suppl 2:S131-5 [PMID: 17940940]
  34. Am J Epidemiol. 2013 Nov 1;178(9):1505-12 [PMID: 24043437]
  35. BMC Infect Dis. 2020 Jul 1;20(1):461 [PMID: 32611400]

Grants

  1. MR/R015600/1/Medical Research Council
  2. MR/X020258/1/Medical Research Council
  3. VEEPED: PR-OD-1017-20002/Department of Health and Social Care

MeSH Term

Animals
Humans
Marburg Virus Disease
Chiroptera
Bayes Theorem
Disease Outbreaks
Vaccination
Marburgvirus
Models, Theoretical
Vaccines

Chemicals

Vaccines

Word Cloud

Created with Highcharts 10.0.00vaccinationoutbreaksMarburgvirusCIpotentialstrategiesdiseasetransmissioncontrolmodelwell195%zoonoticbatsspilloverAlthoughAfricahuman-to-humanpossibleseveralprophylacticdriven[95%casetargetedeffective9089outbreakBACKGROUND:acutehaemorrhagicfevercausedmaintainednatureEgyptianfruitoccasionalinfectionshumansnonhumanprimatesraresporadiccasesoccurusuallyassociatedexposureminescavessometimessecondaryOutbreaksoutsidealsooccurreddueimportationinfectedmonkeyspreviousbroughtwithoutneverthelesslargeimplementationpublichealthmeasuresbreaksVaccinesthusimportantadditionaltooldevelopmentcandidatevaccineswayMETHODS:developedbranchingprocessinvestigatedeffectsreactivesettingsprimarilymultipleeventsLinelistdata152022ApproximateBayesianComputationalframeworkusedinformparametersRESULTS:resultsshowlowbasicreproductionnumbervariedacross505-18]20-19]highfatalityratiosixexploredtwomasshigh-riskgroupscombinationringgenerallyprobabilityterminatedwithinyear90-09188-08887-0compared6867-069especiallyspilloverscampaigninitiatedsoononsetfirstCONCLUSIONS:studyshowsvariouscanhelpingMVDbestapproachvaryingparticularepidemiologiccircumstancesmathematicalroleFilovirusMarburgvirusModellingTransmissionVaccinationZoonotic

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