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Editorial: Mitigating the Risk of Disease From Tick-borne Encephalitis in U.S. Military Populations

Female Ixodes ricinus Tick ©ECDC/Photo by Francis Schaffner Female Ixodes ricinus Tick ©ECDC/Photo by Francis Schaffner

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Tick-borne encephalitis (TBE) has been a recognized threat to public health and force health protection (FHP) among U.S. military service members and other beneficiaries since at least the 1970s. TBE is caused by TBE virus, which is transmitted to humans within minutes of attachment by infected Ixodes ricinus ticks.1 Chiefly endemic in wooded areas in central and eastern Europe and the Baltic and Nordic countries, transmission occurs mainly in the spring through early autumn.2 There is no treatment beyond supportive care, and the vast majority of those infected fully recover. However, despite intensive care intervention, the case fatality rate ranges from 0.5 to 20% depending on the subtype of TBE virus.3–5 In addition, incomplete recovery with long-term neurologic sequelae can occur in 26–46% of those symptomatic cases in Europe.4 Primary prevention for tick bites includes the use of protective clothing, such as long pants/sleeves, and the use of insect repellent,6 such as DEET (chemical name: N,N-diethyl-meta-toluamide; 20 to 50% concentration) and picaridin (at least 20% concentration), on the skin. Added protection is provided by treating clothing, tents, and other gear (but not skin) with the repellent permethrin. Several TBE vaccines are available for use in Europe but have not been widely used by U.S. military personnel residing in or deployed to endemic areas because of lack of licensure by the U.S. Food and Drug Administration (FDA).

The U.S. military has been involved in studying the impact of TBE among service members since the 1980s.7,8 In 1983, Immuno AG submitted an investigational new drug (IND) application to the FDA for the TBE vaccine FSME-Immun Inject® following 25 years of use in Europe.9,10 In February 1996, TBE guidance for the U.S. Commander in Chief, Europe, regarding personnel supporting Operation Joint Endeavor stressed adherence to personal protective measures and, if at high risk, consideration for voluntary receipt of an accelerated, 3-dose TBE vaccine series under an IND protocol.11 Findings from that protocol revealed a 20%, 60%, and 80% seroconversion in the 954 individuals who had received 1, 2, or 3 doses of TBE vaccine, respectively.12 Of the 959 unvaccinated individuals, 4 (0.42%) demonstrated seroconversion and all were asymptomatic.

In subsequent years, additional publications from Europe demonstrated the scope of TBE and the efficacy of TBE vaccine.13–17 In 2011, the World Health Organization published its first position paper on TBE vaccines, and in 2012, TBE became a reportable disease entity among countries in the European Union.13,18,19 Collectively, these reports, along with a few recent high-profile cases among U.S. military service members and beneficiaries stationed in Europe, piqued Department of Defense (DoD) interest for an updated review of both the magnitude of TBE disease and an approach toward management within the U.S. military population. However, it was quickly recognized that there are challenges in assessing TBE epidemiology in U.S. military populations, including lack of recognition of the disease among U.S. and host nation providers, incomplete reporting of recognized disease, and misclassification of vaccine administration as true disease in administrative medical records (Armed Forces Health Surveillance Branch, email communications, 23–24 September 2019). These issues resulted in a large amount of concern and uncertainty regarding the threat of TBE to U.S. personnel among not only medical and public health assets within the U.S. European Command (USEUCOM) but also among the supported operational forces.

The 2 articles on TBE in this issue of the MSMR constitute an effort to provide a more accurate and precise risk assessment for U.S. military personnel stationed or deployed in USEUCOM through high-quality data that are actionable and inform FHP posture. The first article presents surveillance data including trends in TBE disease from 2006 to 2018 in U.S. military populations in Europe and reports on the efforts to identify and validate cases through multiple data sources and records review. The second article describes an in-depth review of a series of TBE cases that occurred in 2017 and 2018 in the area supported by the U.S. Army Medical Department Activity-Bavaria. These articles highlight the value and power of the centralized Defense Medical Surveillance System (DMSS) in combination with in-depth review of medical records by medical and public health personnel. Together, the 2 articles provide objective evidence that the risk to U.S. service members and beneficiaries of contracting TBE disease in Europe is small but non-zero as well as some limited evidence of increasing risk in recent years.

The risk assessment presented in the first article is relevant to discussions of pursuing additional vaccine options to enhance FHP posture against TBE. DoD Instruction 6205.0220 establishes policy, assigns responsibilities, and provides procedures to establish a uniform DoD immunization program in accordance with the authority in DoD Directive 6200.0421 and DoD Instruction 1010.10.22 For infectious diseases identified within the U.S. or in areas with frequent U.S. travelers, the military (similar to the civilian population) relies on primary prevention tools, including FDA-approved immunizations, which are administered in accordance with recommendations from the Centers for Disease Control and Prevention (CDC) and its Advisory Committee on Immunization Practices (ACIP). However, given the worldwide assignments of DoD beneficiaries, there may be diseases, such as TBE, for which a host nation approved medical product may exist but for which the manufacturer has not submitted an application for U.S. FDA approval.

When there is no available FDA-approved medical product, under DoD Instruction 6200.02,23 a DoD component may request that the Assistant Secretary of Defense for Health Affairs (ASD-HA) authorize the voluntary use of an investigational medical product for FHP use. Such requests, approval, and implementation must comply with applicable laws and FDA regulations and would involve the provision of the non-FDA approved vaccine for FHP purposes on a voluntary basis under an Emergency Use Authorization or IND protocol. TBE vaccine is currently not an FHP requirement, but the host nation approved product is authorized for voluntary receipt through TRICARE for at-risk DoD beneficiaries in endemic areas of Europe and Asia when vaccine is received from TRICARE authorized providers.24

Both USEUCOM and the Defense Health Agency, through the Immunization Healthcare Branch, the Office of the ASDHA, and other key DoD stakeholders, are working together to reduce the barriers to vaccination and increase the availability of vaccines to U.S. military beneficiaries stationed in Europe. The challenges surrounding pursuing additional vaccination options and the considerations regarding associated resources to invest will continue to be guided by accurate, precise estimates of the disease burden like the ones provided in this issue of the MSMR. Additional seroepidemiologic studies are needed in areas where DoD beneficiaries reside to better define the distribution of TBE and to guide future TBE vaccination policies in areas with high TBE incidence.25 Furthermore, it cannot be overstated that protective measures against tick-borne diseases, such as TBE, remain grounded in primary prevention.


Author affiliations: Immunization Healthcare Branch, Public Health Division, Defense Health Agency, Falls Church, VA.

REFERENCES

1. Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet. 2008;371(9627):1861–1871. 

2. Beauté J, Spiteri G, Warns-Petit E, Zeller H. Tick-borne encephalitis in Europe, 2012 to 2016. Euro Surveill. 2018;23(45).

3. Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994–98: a prospective study of 656 patients. Brain. 1999;122:2067–2078.

4. Taba P, Schmutzhard E, Forsberg P, et al. EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis. Eur J Neurol. 2017;24(10):1214–e1261.

5. LaSala PR, Holbrook M. Tick-borne flaviviruses. Clin Lab Med. 2010;30(1):221–235.

6. Rendi-Wagner P. Risk and prevention of tick-borne encephalitis in travelers. J Travel Med. 2004;11(5):307–312.

7. McNeil JG, Lednar WM, Stansfield SK, Prier RE, Miller RN. Central European tick-borne encephalitis: assessment of risk for persons in the armed services and vacationers. J Infect Dis. 1985;152(3):650–651.

8. Clement J, Leirs H, Armour V, et al. Serologic evidence for tick-borne encephalitis (TBE) in North-American military stationed in Germany. Acta Leiden. 1992;60(2):15–17.

9. Kunz C, Heinz FX, Hofmann H. Immunogenicity and reactogenicity of a highly purified vaccine against tick-borne encephalitis. J Med Virol. 1980;6(2):103–109.

10. Barrett PN, Dorner F, 1994. Tick-borne encephalitis vaccine. In: Plotkin SA, Mortimer EA, eds. Vaccines. 2nd ed. Philadelphia, PA: W. B. Saunders Company, 715–727.

11. Office of the Assistant Secretary of Defense. Health Affairs Policy Memorandum—Policy for Tick-Borne Encephalitis Preventive Measures for U.S. Forces Deployed During Operation Joint Endeavor. HA Policy 96-031. 20 February 1996.

12. Craig SC, Pittman PR, Lewis TE, et al. An accelerated schedule for tick-borne encephalitis vaccine: the American military experience in Bosnia. Am J Trop Med Hyg. 1999;61(6):874–878.

13. Kunze U, ISW-TBE. Tick-borne encephalitis—a notifiable disease: report of the 15th Annual Meeting of the International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE). Ticks Tick Borne Dis. 2013;4(5):363–365.

14. Sumilo D, Bormane A, Vasilenko V, et al. Upsurge of tick-borne encephalitis in the Baltic States at the time of political transition, independent of changes in public health practices. Clin Microbiol Infect. 2009;15(1):75–80.

15. Heinz FX, Stiasny K, Holzmann H, Grgic-Vitek M, Kriz B, Essl A, Kundi M. Vaccination and tick-borne encephalitis, central Europe. Emerg Infect Dis. 2013;19(1):69–76.

16. Kunz C. TBE vaccination and the Austrian experience. Vaccine. 2003;21(suppl 1):s50–s55.

17. Heinz FX, Stiasny K, Holzmann H, et al. Emergence of tick-borne encephalitis in new endemic areas in Austria: 42 years of surveillance. Euro Surveill. 2015;20(13):9–16.

18. World Health Organization. Vaccines against tick-borne encephalitis: WHO position paper. Wkly Epidemiol Rec. 2011;86(24):241–256.

19. European Centre for Disease Prevention and Control. Epidemiological situation of tick-borne encephalitis in the European Union and European Free Trade Association countries. https://ecdc.europa.eu/publications-data/epidemiological-situation-tick-borne-encephalitis-european-union-andeuropean. Accessed 17 October 2019.

20. Office of the Under Secretary of Defense for Personnel and Readiness. Department of Defense Instruction 6205.02. DoD Immunization Program. 23 July 2019.

21. Headquarters, U.S. Department of Defense. Directive 6200.04, Force Health Protection (FHP). 23 April 2007.

22. Office of the Under Secretary of Defense for Personnel and Readiness. Department of Defense Instruction 1010.10. Health Promotion and Disease Prevention. 12 January 2018.

23. Office of the Under Secretary of Defense for Personnel and Readiness. Department of Defense Instruction 6200.02. Application of Food and Drug Administration (FDA) Rules to Department of Defense Force Health Protection Programs. 27 February 2008.

24. Office of the Assistant Secretary of Defense Health Affairs. Chapter 12, Section 1.2. TRICARE Overseas Program (TOP) Medical Benefit Variations. In: TRICARE Policy Manual 6010.57-M. 1 February 2008.

25. Botelho-Nevers E, Gagneux-Brunon A, Velay A, et al. Tick-borne encephalitis in Auvergne-Rhône-Alpes region, France, 2017–2018. Emerg Infect Dis. 2019;25(10):1944–1948.

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