CBRNE - Plague Clinical Presentation
- Author: Susan E Dufel, MD, FACEP; Chief Editor: Robert G Darling, MD, FACEP more...
History
In general, after an incubation period of 1-6 days, the history suggests a severe and rapidly progressive sepsis.
Recent travel in the Southwestern and Pacific Coast regions of the United States, particularly in New Mexico, Arizona, California, and Utah, should raise suspicion of a fleabite. Although imported plague is rare, similar suspicion should exist for any recent travel to endemic areas outside the United States. Fewer than 10% of patients recall a prior fleabite.
Close contact with any potentially infected host or rural environment should raise suspicion for the plague. Historically, the rat has been believed to be the main plague host; however, currently in the United States, the ground and rock squirrels are the most common hosts. In recent years, the domestic cat has emerged as a prominent host that transmits the plague to veterinarians.[13]
A sudden increase in the incidence of severe pneumonia in previously healthy individuals should raise concern for pneumonic plague possibly deployed as a bioterrorism weapon.
Symptoms include the following:[14, 2]
- Fever
- Chills
- Myalgias
- Sore throat
- Headache
- Weakness
- Malaise
- Enlarged, painful, swollen lymph node
- Abdominal pain - Only presenting symptom more common in a patient presenting with septicemic plague (primary blood-borne plague) versus one presenting with bubonic plague
- Nausea, vomiting (bloody at times)
- Constipation, diarrhea, and black or tarry stools
- Gastrointestinal complaints (may precede a bubo)
- Cough, which may be productive of bloody sputum
- Shortness of breath
- Stiff neck (if meningitic infiltration by plague bacillus has occurred)
Physical
In general, after an incubation period of 1-6 days, the plague presents with the physical findings of severe and rapidly progressive sepsis with or without features of pneumonia. Multiple organ involvement occurs. Pneumonic plague may present only as a severe pneumonia.
- Temperature of 37-40.9°C, tachycardia, tachypnea, and hypotension, if in late septic shock
- Inguinal bubo (60%), axillary (30%), cervical (10%), or epitrochlear (10%) (Bubo is usually no greater than 5 cm, extremely tender, erythematous, and surrounded by a boggy hemorrhagic area; patient often flexes, abducts, and externally rotates the hip near an involved inguinal node to reduce pain at the site.) Children are more likely to have a cervical or submandibular bubo.[2] Images below show a bubo and a necrotic ulcer.
A suppurative, bubo of the femoral lymph node (shown here), the most common site of the erythematous, tender, swollen, nodes in a plague victim. The next most common lymph node regions involved are the inguinal, axillary, and cervical areas. The child in the image below has an erythematous, eroded, crusting, necrotic ulcer at the presumed primary inoculation site on the left upper quadrant. This type of lesion is uncommonly found in patients with plague. Bubo location is primarily a function of the region of the body in which an infected flea inoculates plague bacilli. Courtesy of Jack Poland, PhD, CDC, Fort Collins, CO.
A suppurative, bubo of the femoral lymph node, shown in the image above, is the most common site of the erythematous, tender, swollen, nodes in a plague victim. The next most common lymph node regions involved are the inguinal, axillary (shown here), and cervical areas. The child in this photo has an erythematous, eroded, crusting, necrotic ulcer at the presumed primary inoculation site on the left upper quadrant. This type of lesion is uncommonly found in patients with plague. Bubo location is primarily a function of the region of the body in which an infected flea inoculates plague bacilli. Courtesy of Jack Poland, PhD, CDC, Fort Collins, CO.
Dermatologic findings
A maculopapular lesion may be found at the site of the fleabite; however, such lesions commonly are found at autopsy implying that, in the United States, the diagnosis often is not determined until it is too late.
Acral cyanosis, ecchymosis (shown in the image below), petechiae, and digital gangrene are seen with Y pestis septicemia (from disseminated intravascular coagulation [DIC]).
Ecchymoses at the neck base of a girl with plague. Bandage is over the site of a prior bubo aspirate. These lesions probably gave rise to the title line of the children's nursery rhyme "Ring around the rosy." Courtesy of Jack Poland, PhD, CDC, Fort Collins, CO. The medieval epithet "Black Death" is thought to have originated from the deeply cyanotic skin, ecchymoses, and/or acral necrosis associated with terminal septicemic and pneumonic plague.
The initially rose-colored purpuric lesions most likely gave rise to the child's nursery rhyme "Ring Around the Rosy."
- "Ring around the rosy" - Rose-colored purpuric macules (may be caused by the Y pestis enzyme that acts alternately as a plasminogen activator or coagulase at various temperatures or may be due to DIC)
- "Pocket full of posies" - Sweet-smelling flowers that those tending the sick would carry to ward off the stench of disease
- "Ashes, ashes" - Impending mortality or "A-choo, a-choo" - The sneezing and coughing of pneumonic plague
- "All fall down" - Death
Rare cases of ecthyma gangrenosum–like lesions and carbuncles due to blood-borne Y pestis have been described.
Other findings
- Diffuse crackles, diffuse areas of dullness to percussion (secondary to patchy consolidation of pneumonic plague), and hemoptysis
- Diffuse abdominal tenderness, with or without guarding, splenomegaly, hematochezia, or heme-positive stools
- Nuchal rigidity and diffuse muscle and joint tenderness
- Various degrees of mental status changes, ranging from mild confusion or agitation to delirium and coma
- Seizures
- Bleeding from any body site or cavity (eg, hematemesis, hematochezia, hemoptysis)
- Gangrene and necrosis (shown in the images below) of areas such as the digits, penis, and nares (ascribed to peripheral thrombosis secondary to DIC)
Acral necrosis of nose, lips, fingers (shown here) and toes (image below) and residual ecchymoses over both forearms in a patient recovering from bubonic plague that disseminated to blood and lungs. At one time, the patient's entire body was ecchymotic. Reprinted from McGovern TW, Friedlander AM. Plague. In: Sidell FR, Takafuji ET, Franz DR, eds. Medical Aspects of Chemical and Biological Warfare. Chapter 23 in: Zajtchuk R, Bellamy RF, eds. Textbook of Military Medicine. Washington, DC: US Department of the Army, Office of the Surgeon General, and Borden Institute; 1997: 493. Government publication, no copyright on photos.
Acral necrosis of nose, lips, fingers (image above) and toes (shown here) and residual ecchymoses over both forearms in a patient recovering from bubonic plague that disseminated to blood and lungs. At one time, the patient's entire body was ecchymotic. Reprinted from McGovern TW, Friedlander AM. Plague. In: Sidell FR, Takafuji ET, Franz DR, eds. Medical Aspects of Chemical and Biological Warfare. Chapter 23 in: Zajtchuk R, Bellamy RF, eds. Textbook of Military Medicine. Washington, DC: US Department of the Army, Office of the Surgeon General, and Borden Institute; 1997: 493. Government publication, no copyright on photos. - Pharyngitis culture positive for Y pestis has been seen in endemic areas in household contacts of those with bubonic plague. These patients also have associated cervical lymphadenopathy.
Causes
The etiologic agent is Y pestis, a facultative anaerobic, intracellular, gram-negative bacillus. The following are some epidemiologic factors that suggest an increased likelihood of infection with the plague:[3]
- Rural or nonurban residency, especially in geographic areas with known plague foci
- Contact with sick animals, small rodents, or other possible hosts
- Wilderness activities (eg, camping, hiking, sleeping on ground, hunting)
- Fleabite
- Recent plague in the community
- Occupation as a veterinarian
- Summer months
- Sudden influx of previously healthy patients with severe pneumonia, especially if geographically clustered
Kman NE, Nelson RN. Infectious agents of bioterrorism: a review for emergency physicians. Emerg Med Clin North Am. May 2008;26(2):517-47, x-xi. [Medline].
Prentice MB, Rahalison L. Plague. Lancet. Apr 7 2007;369(9568):1196-207. [Medline].
Casman EA, Fischhoff B. Risk communication planning for the aftermath of a plague bioattack. Risk Anal. Oct 2008;28(5):1327-42. [Medline].
Joshi K, Thakur JS, Kumar R, Singh AJ, Ray P, Jain S, et al. Epidemiological features of pneumonic plague outbreak in Himachal Pradesh, India. Trans R Soc Trop Med Hyg. May 2009;103(5):455-60. [Medline].
Bertherat E, Bekhoucha S, Chougrani S, Razik F, Duchemin JB, Houti L, et al. Plague reappearance in Algeria after 50 years, 2003. Emerg Infect Dis. Oct 2007;13(10):1459-62. [Medline].
Stenseth NC, Samia NI, Viljugrein H, Kausrud KL, Begon M, Davis S, et al. Plague dynamics are driven by climate variation. Proc Natl Acad Sci U S A. Aug 29 2006;103(35):13110-5. [Medline].
Smiley ST. Immune defense against pneumonic plague. Immunol Rev. Oct 2008;225:256-71. [Medline].
Kummer LW, Szaba FM, Parent MA, Adamovicz JJ, Hill J, Johnson LL. Antibodies and cytokines independently protect against pneumonic plague. Vaccine. Dec 9 2008;26(52):6901-7. [Medline].
Blisnick T, Ave P, Huerre M, Carniel E, Demeure CE. Oral vaccination against bubonic plague using a live avirulent Yersinia pseudotuberculosis strain. Infect Immun. Aug 2008;76(8):3808-16. [Medline].
Ayyadurai S, Houhamdi L, Lepidi H, Nappez C, Raoult D, Drancourt M. Long-term persistence of virulent Yersinia pestis in soil. Microbiology. Sep 2008;154:2865-71. [Medline].
Ben Ari T, Gershunov A, Gage KL, Snall T, Ettestad P, Kausrud KL, et al. Human plague in the USA: the importance of regional and local climate. Biol Lett. Dec 23 2008;4(6):737-40. [Medline].
Bertherat E, Bekhoucha S, Chougrani S, Razik F, Duchemin JB, Houti L. Plague reappearance in Algeria after 50 years, 2003. Emerg Infect Dis. Oct 2007;13(10):1459-62. [Medline].
Margolis DA, Burns J, Reed SL, Ginsberg MM, O'Grady TC, Vinetz JM. Septicemic plague in a community hospital in California. Am J Trop Med Hyg. Jun 2008;78(6):868-71. [Medline].
Waterer GW, Robertson H. Bioterrorism for the respiratory physician. Respirology. Jan 2009;14(1):5-11. [Medline].
Barnes AM, Quam TJ. Plague. In: Gorbach SL, Bartlett JG, Balacklow NR, eds. Infectious Diseases. 1992:1285-91.
Branda JA, Ruoff K. Bioterrorism. Clinical recognition and primary management. Am J Clin Pathol. Jun 2002;117 Suppl:S116-23. [Medline].
Burmeister RW, Tigertt WD, Overholt EL. Laboratory-acquired pneumonic plague. Report of a case and review of previous cases. Ann Intern Med. May 1962;56:789-800. [Medline].
Butler T. Yersinia species (including plagues). In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and Practice of Infectious Diseases. 3rd ed. 1990.
Butler T, Bell WR, Nguyen-Ngoc-Linh, Nguyen-Dinh-Tiep, Arnold K. Yersinia pestis infection in Vietnam. I. Clinical and hematologic aspects. J Infect Dis. May 1974;129:Suppl:S78-84. [Medline].
CDC. Human plague--United States, 1993-1994. MMWR Morb Mortal Wkly Rep. Apr 8 1994;43(13):242-6. [Medline].
Chanteau S, Rahalison L, Ralafiarisoa L, Foulon J, Ratsitorahina M, Ratsifasoamanana L. Development and testing of a rapid diagnostic test for bubonic and pneumonic plague. Lancet. Jan 18 2003;361(9353):211-6. [Medline].
Christie AB, Corbel MS. Topley and Wilson, eds. Principles of Bacteriology, Virology and Immunity. 3rd-8th ed. 1990:400-9.
Conner C. Plague. In: Pathology of Infectious Diseases. 1997:729-38.
Connor JD, Williams RA, Thompson MA, et al. Plague in San Diego [clinical conference]. West J Med. Nov 1978;129(5):394-406. [Medline].
Craven RB, Maupin GO, Beard ML, et al. Reported cases of human plague infections in the United States, 1970- 1991. J Med Entomol. Jul 1993;30(4):758-61. [Medline].
Crook LD, Tempest B. Plague. A clinical review of 27 cases. Arch Intern Med. Jun 1992;152(6):1253-6. [Medline].
Hoffman SL. Plague in the United States: the "black death" is still alive. Ann Emerg Med. Jun 1980;9(6):319-22. [Medline].
Hull HF, Montes JM, Mann JM. Septicemic plague in New Mexico. J Infect Dis. Jan 1987;155(1):113-8. [Medline].
Human plague--four states, 2006. MMWR Morb Mortal Wkly Rep. Sep 1 2006;55(34):940-3. [Medline].
Humphrey M, McGivney R, Perkins C, Harris R, Rowe J. Yersinia pestis: a case of mistaken identity. Pediatr Infect Dis J. May 1988;7(5):365-6. [Medline].
Koirala J. Plague: disease, management, and recognition of act of terrorism. Infect Dis Clin North Am. Jun 2006;20(2):273-87, viii. [Medline].
Kool JL. Risk of person-to-person transmission of pneumonic plague. Clin Infect Dis. Apr 15 2005;40(8):1166-72. [Medline].
Lazarus AA, Decker CF. Plague. Respir Care Clin N Am. Mar 2004;10(1):83-98. [Medline].
Leopold JC. Septicemic plague in a 14-month-old child. Pediatr Infect Dis. Jan-Feb 1986;5(1):108-10. [Medline].
Mann JM, Hull HF, Schmid GP, Droke WE. Plague and the peripheral smear. JAMA. Feb 17 1984;251(7):953. [Medline].
Marcus LC. Wilderness acquired zoonoses. In: Auerbach PS, Geehr EC, eds. Management of Wilderness and Environmental Emergencies. 1989.
McGovern TW, Christopher GW, Eitzen EM. Cutaneous manifestations of biological warfare and related threat agents. Arch Dermatol. Mar 1999;135(3):311-22. [Medline].
McGovern TW, Friedlander AM. Plague. Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. In: Sidell FR, Takafuji ET, Franz DR, Zajtchuk R, Bellamy RF, eds. eds. Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. Textbook of Military Medicine. Office of the Surgeon General of the Army; 1997:479-502.
Mwengee W, Butler T, Mgema S, Mhina G, Almasi Y, Bradley C. Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania. Clin Infect Dis. Mar 1 2006;42(5):614-21. [Medline].
Navas E. Problems associated with potential massive use of antimicrobial agents as prophylaxis or therapy of a bioterrorist attack. Clin Microbiol Infect. Aug 2002;8(8):534-9. [Medline].
Outbreak news. Plague, Democratic Republic of the Congo. Wkly Epidemiol Rec. Oct 20 2006;81(42):397-8. [Medline].
Perry RD, Fetherston JD. Yersinia pestis--etiologic agent of plague. Clin Microbiol Rev. Jan 1997;10(1):35-66. [Medline].
Rollins SE, Rollins SM, Ryan ET. Yersinia pestis and the plague. Am J Clin Pathol. Jun 2003;119 Suppl:S78-85. [Medline].
Rotz LD, Khan AS, Lillibridge SR, Ostroff SM, Hughes JM. Public health assessment of potential biological terrorism agents. Emerg Infect Dis. Feb 2002;8(2):225-30. [Medline].
Stenseth NC, Samia NI, Viljugrein H, Kausrud KL, Begon M, Davis S. Plague dynamics are driven by climate variation. Proc Natl Acad Sci U S A. Aug 29 2006;103(35):13110-5. [Medline].
Weir E. Plague: a continuing threat. CMAJ. Jun 7 2005;172(12):1555. [Medline].
Welty TK, Grabman J, Kompare E, et al. Nineteen cases of plague in Arizona. A spectrum including ecthyma gangrenosum due to plague and plague in pregnancy. West J Med. May 1985;142(5):641-6. [Medline].
Werner SB, Weidmer CE, Nelson BC, Nygaard GS, Goethals RM, Poland JD. Primary plague pneumonia contracted from a domestic cat at South Lake Tahoe, Calif. JAMA. Feb 17 1984;251(7):929-31. [Medline].

