YERSINIA PESTIS AND THE PLAGUE

BY

ADELOYE ADERINSOLA DORA

Yersinia pestis , the cause of bubonic and pneumonic plague in humans, persists in populations of wild rodents in many parts of the world and is transmitted primarily by the bites of infected fleas (Poland et al., 1994).

Plague caused by Yersinia pestis is categorized as a rare disease. The disease rarely occurs but when it strikes, the consequences can be devastating (Hang’ombe et al, 2012).

The infectious source of the disease was not understood until Alexandre Yersin investigated the Hong Kong epidemic in the mid-1890s (Gross, 1995).

INTRODUCTION

Although Y. pestis is usually transmitted by the bite of an infected flea or inhalation of aerosolized droplets from a person with pneumonic plague, the enteropathogenic Yersiniae are ubiquitous in the environment and are transmitted by ingestion of contaminated food or water (Eppinger et al., 2007).

Infection by the bacterium Yersinia pestis is most often associated with the infamous Black Death of the middle Ages, a pandemic that cost Europe a third of its population in the 14th and 15th

centuries. (Slack, 1989).

INTRODUCTION

Three major league pandemics have been recorded in human history: in the 6th century, in the 14th century known as the black death which killed up to an estimated 17 to 28 million people (Drancourt and Raoult, 2008), and at the end of 19th century following the spread of infection from china (Prentice and Rahalison, 2007).

Plague is a seasonal disease, with most reported human cases occurring between March and October (Orloski and Lathrop, 2003)

EPIDEMIOLOGY

EPIDEMIOLOGY

Figure 1.World distribution of plague,1998

•1000- 3000 cases reported annually across the world•Africa , Asia Northeastern Brazil•Andes Mountain Regions•US (19-40 cases a year mostly in Western areas such as New Mexico and Arizona)•About 15% of reported humans with plague die (Campbell and Dennis, 2001).

Figure 2. LIFE CYCLE AND PATHOGENESISSource : the McGram Hill Companies,Inc,Permission required for reproduction or display

 After being ingested by a flea from a rodent host, Y. pestis multiplies in the flea gut and expresses a coagulase that clots ingested blood, occluding the proventriculus (an organ between the stomach and esophagus of the flea), rendering the flea “blocked,” that is, unable to move food (blood) from its esophagus to its midgut (Hinnebusch, 1997).

Thus, the flea repeatedly attempts to feed, and because it is unable to ingest the blood, it regurgitates the newly infected blood back into the bloodstream of the mammal on which it is feeding, therefore transferring the microorganism from the flea to the mammal. (Hinnebusch, 1997).

LIFE CYCLE AND PATHOGENESIS

Approximately 25,000 to 100,000 Y. pestis organisms are inoculated into the skin of the mammal host during this process. (Reed et al., 1970).

The bacteria migrate through cutaneous lymphatics to regional lymph nodes where they are phagocytosed but resist destruction (Butler, 1995).

They rapidly multiply, causing destruction and necrosis of lymph node architecture with subsequent bacteremia, septicemia, and endotoxemia that can lead quickly to shock, disseminated intravascular coagulation, and coma(Butler, 1995).

LIFE CYCLE AND PATHOGENESIS

Patients typically develop symptoms of bubonic plague 2 to 8 days after being bitten by an infected flea (Campbell and Dennis, 1998).

Bubonic plague (Campbell and Dennis, 1998).◦ Incubation period of 2–6 days, when the bacteria is

actively replicating.◦ General malaise◦ Fever◦ Headache and chills occur suddenly at the end of

the incubation period◦ Swelling of lymph nodes resulting in buboes, the classic

sign of bubonic plague◦ Death can occur in less than 2 weeks

SYMPTOMS AND DISEASE PROGRESSION

Septicemic plague (Campbell and Dennis, 1998).◦ Hypotension◦ Hepatosplenomegaly◦ Delirium◦ Seizures in children◦ Shock◦ General malaise◦ Fever

Note: Patient may die before any symptoms appear

SYMPTOMS AND DISEASE PROGRESSION

Pneumonic plague (Spread person to person) (Campbell and Dennis, 1998)◦ Fever◦ Chills◦ Coughing◦ Chest pain◦ Dyspnea◦ Hemoptysis◦ Lethargy◦ Hypotension◦ Shock◦ 100% mortality if not treated

SYMPTOMS AND DISEASE PROGRESSION

Yersinia pestis can be identified in the laboratory by both bacteriologic and serologic methods (Guarner et al., 2002).

Diagnosis can be made from a variety of samples, including blood, aspirates from involved lymph nodes, skin scrapings, cerebrospinal fluid, urine, and sputum (Guarner et al., 2002).

Yersinia pestis appears as a pleomorphic gram negative rod and may appear as a single cell (1.0-2.0 × 0.5μm) or in short chains in smears (Guarner et al., 2002).

LABORATORY DIAGNOSIS

The organism gives a bipolar “closed-safety pin” appearance on Giemsa, Wright, or Wayson stains (but not on Gram stain) (Guarner et al., 2002).

The organism also may be identified via immunohistochemical staining using a monoclonal anti-F1 Y. pestis antibody on formalin-fixed tissue samples

Plate 1 (Guarner et al., 2002).

LABORATORY DIAGNOSIS

Yersinia pestis colonies grown on CIN agar

• Colonies are smooth, opaque, and round but may have irregular edges. Under magnification, colonies can be smooth or finely granular and might have a raised center with a flat periphery (“fried egg” appearance) or a “hammered copper” appearance (Brubaker, 1991).

• Colonies are visible on plates after 48 hours, and it is recommended that plates be incubated for a total of 7 days before being discarded(Smego et al., 1999).

A B

C D

Yersinia pestis growth on BA at

(A)48 h,

(B) 72 h, (C) 96 h,

(D) 96 h “Fried egg”Plate 2. wadsworth center , 2007.

BIOCHEMICAL TESTS

POSITIVE

WEAKLY POSITIVE NEGATIVE

CATALASE TEST

NON MOTILE MOTILE

MOTILITY TEST

POSITIVE WEAKLY POSITIVENEGATIVE

OXIDASE TEST

POSITIVENEGATIVE

UREASE TEST

• Catalase positive• Urease, indole and oxidase

negative• Non-motile at 35 -370C

(Wadsworth Centre, 2007)

There are no widely available rapid diagnostic tests for plague (American Public Health Association, 1995).

Tests that would be used to confirm a suspected diagnosis—antigen detection, IgM enzyme immunoassay, immunostaining, and polymerase chain reaction— are available only at some state health departments, the CDC, and military laboratories (American Public Health Association, 1995).

The routinely used passive hemagglutination antibody detection assay is typically only of retrospective value since several days to weeks usually pass after disease onset before antibodies develop (American Public Health Association, 1995).

LABORATORY DIAGNOSIS

Prompt initiation of appropriate antimicrobial treatment is essential. Human deaths from plague usually occur because of delays in treatment with appropriate antimicrobials either because of a delay in seeking medical care or misdiagnosis by health care providers (Infectious Diseases Society of America, 2003).

The treatment of choice for humans with plague is streptomycin (Inglesby et al., 2000).

Gentamicin has been used successfully to treat humans with plague and for animal control in veterinary medicine (Inglesby et al., 2000).

TREATMENT

Doxycycline is an appropriate choice for less complicated cases. Other treatment options include tetracycline and chloramphenicol. Sulfonamides can be used but only if other antimicrobials are not available (Inglesby et al., 2000).

Antibiotics preferably should be administered intravenously, unless a mass casualty or outbreak situation results in the overwhelming of health care facilities, in which case orally administered tetracycline, doxycycline, or ciprofloxacin is considered an acceptable alternative (Infectious Diseases Society of America,2003).

TREATMENT

1. Far from being a historic medical curiosity, this zoonotic disease continues to be a threat to the health of humans and animals throughout the world, including Eurasia, Africa, and North and South America.

2. Prompt diagnosis and immediate onset of treatment is key to reducing the mortality rates that usually follow this disease condition.

CONCLUSION

American Public Health Association (1995). Plague. In: Benenson AS, ed. Control of Communicable Diseases Manual. 353-358.

Brubaker, R.R. (1991). Factors promoting acute and chronic diseases caused by Yersinia. Clin Microbiol Rev.;4:309-324.

Butler, T. (1995). Yersinia species (including plague). In:Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases.NewYork, NY: Churchill Livingstone :2070-2078

Campbell, G.L. and Dennis, D.T. (1998). Plague and other Yersinia infections. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds.Harrison’s Principles of Internal Medicine. New York, NY: McGraw-Hill: 975-983

Eppinger, M.,. Rosovitz, M. J., Fricke, W. F., Rasko, D. A., Kokorina, G., Fayolle, C., Lindler, L. E., Carniel, E. and Ravel, J. (2007).The complete genome sequence of Yersinia pseudotuberculosis IP31758, the causative agent of Far East scarlet-like fever. Genet. 3: e142

 Gross, L. (1995). How the plague bacillus and its transmission through fleas were discovered: reminiscences from my years at the Pasteur Institute in Paris. Proc Natl Acad Sci U S A.;92:7609-7611

Hang’ombe, B. M., Samui, K. L., Nakamura, I., Kaile, D., Mweene, A. S., Kilonzo, B. S., Sawa, H., Sugimoto, C. and Wren, B. W. (2012). Evidence of Yersinia pestis DNA from fleas in an endemic plague area of Zambia. BMC Res. Notes 5:72

REFERENCES

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Poland, J.D., Quan, T.J. and Barnes, A.M. (1994). Plague. In: Beran GW, ed. Handbook of zoonoses. Boca Raton, FL: CRC Press :93–112

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