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Historical Perspective: Leptospirosis Outbreaks Affecting Military Forces

Acute Flaccid Myelitis Leptospirosis has been the cause of significant morbidity in military forces throughout history. It is transmitted to humans primarily through
contact of abraded skin or mucous membranes with water or wet soil that has been contaminated with infected animal urine. Photo by U.S. Marine Corps.

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Leptospirosis is a widespread and highly prevalent bacterial zoonotic disease that is caused by pathogenic spirochetes of the genus Leptospira. It is transmitted to humans primarily through contact of abraded skin or mucous membranes with water or wet soil that has been contaminated with infected animal urine. Many wild and domestic animals are susceptible to infection by pathogenic Leptospira bacteria including rats, dogs, cattle, goats, sheep, and swine. Once chronically infected, a carrier animal can shed Leptospira bacteria in urine for long periods of time and Leptospira bacteria can survive in water or soil for weeks to months.1 

Leptospirosis has a global distribution with an estimated 1.03 million cases and 58,900 deaths attributed to the disease annually.2 Leptospirosis incidence is highest in tropical regions. Leptospirosis also demonstrates seasonal variation in incidence. Cases in temperate regions occur predominantly in the summer and fall and cases in tropical regions increase during the rainy season.1 In the U.S., between 100–150 cases are reported each year; Puerto Rico and Hawaii consistently account for the majority of U.S. leptospirosis cases.3 Both global and national incidence are likely significantly underestimated due to underreporting, misdiagnosis, and lack of laboratory confirmation.2 

Occupational exposures are a significant source of infection and occupations involving contact with animals or infected water or soil confer increased risk (e.g., veterinarians, farmers, sewer workers).1 Increasingly, recreational activities involving fresh water, foreign travel, or a combination of the two have been implicated in leptospirosis outbreaks. Notable examples include triathlons4-6 and adventure travel activities like white water rafting and caving.7 Transmission can also occur during periods of extensive flooding and high seasonal rainfall, both of which increase the risk of exposure to water contaminated with pathogenic leptospires.8

The spectrum of disease caused by leptospirosis can be highly variable ranging from  mild and self-limiting to potentially fatal. A significant proportion of cases are asymptomatic or subclinical. When symptoms occur, the average incubation period is between 7 and 12 days, although onset can range between 3 and 30 days after exposure. Initial symptoms often include fever, chills, myalgias (i.e., muscle pain), and headache and overlap considerably with the symptoms of many other acute febrile illnesses (e.g., dengue fever, influenza, malaria). Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) occur in about half of cases. Other, less common signs and symptoms include non-productive cough, hepatosplenomegaly (enlargement of the liver and spleen), lymphadenopathy (lymph node enlargement), pharyngitis, and rash. The presence of conjunctival suffusion (redness of the conjunctiva of the eye without discharge) can help distinguish leptospirosis from other infectious diseases. In approximately 90% of cases, the disease follows a biphasic course in which an initial acute symptomatic phase lasting 5-7 days is followed by “immune” phase during which antibodies develop and symptom improvement can occur. A more severe illness, known as icteric leptospirosis or Weil’s disease, occurs in about 10% of cases. Weil’s disease is severe and rapidly progressive and the classic presentation of this form of leptospirosis includes fever, jaundice, renal failure, and hemorrhage. Frequently, other organ systems (i.e., lungs, heart, central nervous system) are also involved.1,9

There are several diagnostic tests available to screen for and confirm a diagnosis of leptospirosis although the value and accuracy of each test depends on the stage of disease. Tests that detect the presence of bacteria include polymerase chain reac tion (PCR) and culture and will yield positive results only in the acute phase. Tests that detect antibodies specific for the Leptospira bacteria include the immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) and microscopic agglutination test (MAT) which will produce positive results later in the disease process. IgM ELISA detects early production of antibodies and therefore can become positive earlier than the MAT but may produce false positive or false negative results. Direct culture of leptospires from urine or serum takes time and is very difficult with a low success rate. Although it is a complex test to control and perform, MAT is the “gold standard” test for a confirmatory leptospirosis diagnosis. A single titer of 1:100 or a 4-fold rise in titer between acute and convalescent sera is considered confirmatory.1,9,10

The Centers for Disease Control and Prevention (CDC) recommends initiation of antibiotic therapy early (before confirmation via laboratory testing) as it may prevent patients from progressing to more severe disease or may reduce the duration of disease.10 Doxycycline (100 mg orally, twice daily) is the recommended regimen for adults with mild leptospirosis who are not pregnant. Ampicillin and amoxicillin are also potential treatment options for mild cases. Severe disease requires supportive therapy (e.g., intravenous (IV) hydration, electrolyte supplementation) and both IV penicillin and ceftriaxone have been demonstrated to be equally effective for treatment.9,10

Pre-exposure prophylaxis with doxycycline (200 mg orally once per week) was effective in a double-blind trial conducted in deployed military personnel undergoing jungle training in Panama.11 This regimen is also the current standard for leptospirosis prophylaxis for U.S. military personnel experiencing short term high-risk exposure.12 In contrast, a 2009 systematic review of antibiotic prophylaxis for leptospirosis concluded that there was an unclear benefit with this regimen and it increased the odds of nausea and vomiting in those receiving prophylaxis.13

Leptospirosis in military forces

Leptospirosis has been the cause of significant morbidity in military forces throughout history. During World War I, outbreaks confirmed in French, German, and British troops were likely due, in part, to the favorable conditions conferred by trench warfare including standing water and rat infestation. Leptospirosis outbreaks during World War II were linked to troops bathing in rivers and streams.14

The term “Fort Bragg Fever” came into existence due to a leptospirosis outbreak which hospitalized 40 soldiers at Ft. Bragg in North Carolina in the summer of 1942. Similar outbreaks occurred during the summers of 1943 and 1944. Despite an extensive epidemiologic investigation, leptospirosis (specifically Leptospira autumnalis) was not determined to be the causative agent in these outbreaks until 1951.15

In 1961, a leptospirosis outbreak among U.S. Army troops occurred in the Panama Canal Zone and subsequent serological testing identified multiple serotypes of Leptospira as potential etiologic agents.16 Throughout the remainder of that decade, leptospirosis also caused significant disease in U.S. military personnel during the Vietnam War. One study estimated that leptospirosis accounted for 20% of acute febrile illnesses among service members in South Vietnam.17

Leptospirosis continued to have a significant impact on U.S. military members in Panama, especially on troops training at the Jungle Operations Training Center (JOTC). Between 1977-1982, surveillance on U.S. Army units undergoing the 3 week training course at the JOTC identified 91 confirmed and probable cases of leptospirosis. This translates to an annualized incidence of 41% (41,000 cases per 100,000 p-yrs).18

In 1987, a waterborne outbreak of leptospirosis in Okinawa, Japan in U.S. military personnel included two distinct case clusters which differed by time and place of exposure. Attack rates were higher in the case cluster designated as recreational swimmers (47%) than among those in the cluster undergoing training at the Jungle Warfare Training Center (JWTC) (18%).19 This outbreak prompted the initiation of doxycycline prophylaxis at the JWTC.12

Leptospirosis outbreaks affecting both U.S. and foreign military personnel since 1990 are summarized in Table 1.

EDITORIAL COMMENT

This summary of leptospirosis outbreaks in U.S. and foreign military members demonstrates that leptospirosis poses a significant risk to military members through both occupational and recreational exposures.

Several of the reported outbreaks occurred during military training exercises conducted in endemic regions or in environments likely to pose a high risk of exposure. While the best way to avoid infection is to avoid contact with potentially contaminated bodies of water, operational and military needs may not allow for exposure avoidance. In these cases, preventive efforts should focus on chemoprophylaxis, the use of protective clothing and footwear, and covering cuts and abrasions with occlusive dressings.

The highest reported attack rates in military personnel (41% in Panama18 and 42% in Okinawa12) have occurred in troops undergoing jungle warfare training. Attack rates of this magnitude underscore that intense and concentrated exposure to contaminated environments can have a significant impact on unit capabilities.18

Although the standard doxycycline prophylaxis protocol was employed for personnel undergoing training in the 2014 Okinawa outbreak, Dierks et al. noted the apparent failure of doxycycline prophylaxis in this case and recommended further study into an ideal prophylaxis regimen with special emphasis on the evaluation of dosing frequency.12 In addition, measures to increase adherence with any prophylaxis regimen are warranted.

Participation in recreational and water sport-related activities also pose a risk for military personnel as demonstrated by outbreaks in Guam in 2014 and Oahu in 1992. Military personnel should be educated to increase awareness of how the disease is contracted and to avoid contact with high risk bodies of water. High risk behaviors such as swallowing water and swimming with cuts or abrasions should be minimized. Any exposure to contaminated bodies of water should be avoided, especially in cases where posted warnings are located.

Although no outbreak in military personnel has yet been documented as a result of participation in a humanitarian or relief mission, these activities can also be a source of risk. U.S. military personnel are frequently deployed in support of disaster relief and after extreme weather events, especially in regions where leptospirosis is endemic and where conditions (e.g., flooding) increase risk for leptospirosis transmission. Threat briefings to military members engaged in these missions can emphasize measures to reduce exposure. Preventing future leptospirosis outbreaks requires vigilance on the part of line officers and preventive medicine staff to ensure that military personnel have been informed of both exposure risks and any and all available means of risk reduction.

REFERENCES

1. Haake DA, Levett PN. Leptospirosis in humans. Curr Top Microbiol Immunol. 2015;387:65–97.
2. Costa F, Hagan JE,  Calcagno J, et al. Global Morbidity and Mortality of  Leptospirosis: A Systematic Review. PLoS Negl Trop Dis. 2015;9(9):e0003898.
3. Centers for Disease Control and Prevention. Leptospirosis: Fact Sheet for Clinicians. https:// www.cdc.gov/leptospirosis/pdf/fs-leptospirosis-clinicians-eng-508.pdf. Accessed 1 December 2018.
4. Pagès F, Larrieu S, Simoes J, et al. Investigation of a leptospirosis outbreak in triathlon participants, Réunion Island, 2013. Epidemiol Infect. 2016;144(3):661–9.
5. Brockmann S, Piechotowski I, Bock-Hensley O, et al. Outbreak of leptospirosis among triathlon participants in Germany, 2006. BMC Infect Dis. 2010;10:91.
6. Morgan J, Bornstein SL, Karpati AM, et al. Outbreak of leptospirosis among triathlon participants and community residents in Springfield, Illinois, 1998. Clin Infect Dis. 2002;34(12):1593–1599.
7. Gundacker ND, Rolfe RJ, Rodriguez JM. Infections associated with adventure travel: A systematic review. Travel Med Infect Dis. 2017;16:3–10.
8. Saulnier  DD,  Brolin  Ribacke  K, von Schreeb J. No calm after the storm: A systematic review of human health following flood and storm disasters. Prehosp Disaster Med. 2017;32(5):568–579.
9. Jiménez JIS, Marroquin JLH, Richards GA, Amin P. Leptospirosis: Report from the task force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine. J Crit Care. 2018;43:361–365.
10. Centers for Disease Control and Prevention. CDC Yellow Book 2018: Health Information for International Travel. New York: Oxford University Press; 2017.
11. Takafuji ET, Kirkpatrick JW, Miller RN, et al. An efficacy trial of doxycycline chemoprophylaxis against leptospirosis. N Engl J Med. 1984;310(8):497–500.
12. Dierks J, Servies T, Do T. A study on the leptospirosis outbreak among US Marine trainees in Okinawa, Japan. Mil Med. 2018;183(3-4):e208– e212.
13. Brett-Major DM, Lipnick RJ. Antibiotic prophylaxis for leptospirosis. Cochrane Database Syst Rev. 2009;(3):CD007342.
14. Christopher GW, Agan MB, Cieslak TJ, Olson PE. History of U.S. military contributions to the study of bacterial zoonoses. Mil Med. 2005 Apr; 170 (4 Suppl): 39–48.
15. Gochenour WS Jr, Smadel JE, Jackson EB, Evans LB, Yager RH. Leptospiral etiology of Fort Bragg Fever. Public Health Rep. 1952;67(8):811–813.
16. Gale NB, Alexander AD, Evans LB, Yager RH. An outbreak of leptospirosis among U.S. army troops in the Canal Zone. Am J Trop Med Hyg. 1966 Jan; 15 (1): 64–70.
17. Berman SJ, Irving GS, Kundin WD, Gunning JJ, Watten RH. Epidemiology of the acute fevers of unknown origin in South Vietnam: effect of laboratory support upon clinical diagnosis. Am J Trop Med Hyg. 1973;22(6):796–801.
18. Kelley PW et al. Diseases Transmitted Primarily from Animals to Humans. In: Military Preventive Medicine: Mobilization and Deployment. Vol.2. Washington, D.C.:Borden Institute; 2005: 939-943.
19. Corwin A, Ryan A, Bloys W, Thomas R, Deniega B, Watts D. A waterborne outbreak of leptospirosis among United States military personnel in Okinawa, Japan. Int J Epidemiol. 1990;19(3):743–748.
20. Brinker AJ, Blazes DL. An outbreak of Leptospirosis among United States military personnel in Guam. Trop Dis Travel Med Vaccines. 2017;3:16.
21. ProMED-mail. Leptospirosis—Malaysia: (Selangor) military. 2011; 4 Dec: 20111204.3531. http:// www.promedmail.org. Accessed 10 Nov 2018.
22. Hochedez P, Escher M, Decoussy H, et al. Outbreak of leptospirosis among canyoning participants, Martinique, 2011. Euro Surveill. 2013;18(18):20472.
23. Lupi O, Netto MA, Avelar K, Romero C, Bruniera R, Brasil P. Cluster of leptospirosis cases among military personnel in Rio de Janeiro, Brazil. Int J Infect Dis. 2013;17(2):e129–31.
24. Hadad E, Pirogovsky A, Bartal C, et al. An outbreak of leptospirosis among Israeli troops near the Jordan River. Am J Trop Med Hyg. 2006;74(1):127–131.
25. Russell KL, Montiel Gonzalez MA, Watts DM, et al. An outbreak of leptospirosis among Peruvian military recruits. Am J Trop Med Hyg. 2003;69(1):53–57.
26. Katz AR, Sasaki DM, Mumm AH, Escamilla J, Middleton CR, Romero SE. Leptospirosis on Oahu: an outbreak among military personnel associated with recreational exposure. Mil Med.

Summary of leptospirosis outbreaks af fecting U.S. and foreign military personnel, 1990 to present 1997;162(2):101–104.


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