Ericka V. Hayes
The genus Yersinia is a member of the family Enterobacteriaceae and comprises more than 14 named species, 3 of which are established as human pathogens. Yersinia enterocolitica is by far the most common Yersinia species causing human disease and produces fever, abdominal pain that can mimic appendicitis, and diarrhea. Yersinia pseudotuberculosis is most often associated with mesenteric lymphadenitis. Yersinia pestis is the agent of plague and typically causes an acute febrile lymphadenitis (bubonic plague) and less often occurs as septicemic, pneumonic, pharyngeal, or meningeal plague. Other Yersinia species are uncommon causes of infections of humans, and their identification is often an indicator of immunodeficiency.
Yersinia is enzootic and can colonize pets. Infections in humans are incidental and most often result from contact with infected animals or their tissues; ingestion of contaminated water, milk, or meat; or for Y. pestis, the bite of infected fleas or inhalation of respiratory droplets (human, dog, cat). Association with human disease is less clear for Yersinia frederiksenii, Yersinia intermedia, Yersinia kristensenii , Yersinia aldovae, Yersinia bercovieri, Yersinia mollaretii, Yersinia rohdei, and Yersinia ruckeri. Some Yersinia isolates replicate at low temperatures (1-4°C [33.8-39.2°F]) or survive at high temperatures (50-60°C [122-140°F]). Thus, common food preparation and storage and common pasteurization methods might not limit the number of bacteria. Most are sensitive to oxidizing agents.
Ericka V. Hayes
Yersinia enterocolitica is a large, gram-negative coccobacillus that exhibits little or no bipolarity when stained with methylene blue and carbolfuchsin. It ferments glucose and sucrose but not lactose, is oxidase negative, and reduces nitrate to nitrite. These facultative anaerobes grow well on common culture media and are motile at 22°C (71.6°F) but not 37°C (98.6°F). Optimal growth temperature is 25-28°C (77-82.4°F); however, the organism can grow at refrigerator temperature. Y. enterocolitica includes pathogenic and nonpathogenic members. It has 6 different biotypes (1A, 1B, and 2-5). Y. enterocolitica relies on other bacteria for iron uptake, and conditions associated with iron overload increase risk of infection.
Y. enterocolitica is transmitted to humans through food, water, animal contact, and contaminated blood products. Transmission can occur from mother to newborn. Y. enterocolitica appears to have a global distribution but is seldom a cause of tropical diarrhea. In 2014, incidence of culture-confirmed Y. enterocolitica infection in the United States was 0.28 per 100,000 population (52% decrease from incidence in 1996–1998). Infection may be more common in Northern Europe. Most infections occur among children <5 yr old (incidence: 1.6-1.9 per 100,000 population), with the majority among children <1 yr old. It is estimated that Y. enterocolitica accounts for 5% of illnesses secondary to major bacterial enteric pathogens in children <5 yr old in the United States. Cases are more common in colder months and among males.
Natural reservoirs of Y. enterocolitica include pigs, rodents, rabbits, sheep, cattle, horses, dogs, and cats, with pigs being the major animal reservoir. Direct or indirect contact with animals, including pets, other domesticated animals, and wild animals, may be responsible for <1% of cases of enteric illnesses caused by Y. enterocolitica . Culture and molecular techniques have found the organism in a variety of foods and beverages, including vegetable juice, pasteurized milk, carrots, and water. Consumption of contaminated water or food, particularly undercooked pork, is the most common form of transmission to humans. A source of sporadic Y. enterocolitica infections is chitterlings (pig intestines, “chitlins”), a traditional dish in the southeastern United States as well as Latin America, often in celebration of winter holidays. The infection is often seen in young infants in the household due to contamination of bottle and food preparation when chitterlings are prepared. In one study, 71% of human isolates were indistinguishable from the strains isolated from pigs. Y. enterocolitica is an occupational threat to butchers.
In part because of its capacity to multiply at refrigerator temperatures, Y. enterocolitica can be transmitted by intravenous injection of contaminated fluids, including blood products.
Patients with conditions leading to iron overload are at higher risk of developing Yersinia infections.
The Yersinia organisms most often enter by the alimentary tract and cause mucosal ulcerations in the ileum. Necrotic lesions of Peyer patches and mesenteric lymphadenitis occur. If septicemia develops, suppurative lesions can be found in infected organs. Infection can trigger reactive arthritis and erythema nodosum , particularly in HLA-B27–positive individuals.
Virulence traits of pathogenic biotypes(1B and 2-5) are encoded by chromosomal genes and a highly conserved 70 kb virulence plasmid (pYV/pCD). The chromosomal genes control the production of heat-stable enterotoxins, and the plasmid allows penetration through the intestinal wall. Adherence, invasion, and toxin production are the essential mechanisms of pathogenesis. The bacteria mainly invade the intestinal epithelium in the Peyer patches of the ileum. After invasion, plasmid-encoded type III secretion of 3 antiphagocytic proteins protects Yersinia against the immunologic response of local macrophages. From Peyer patches, bacteria can disseminate to cause local or systemic disease. Motility appears to be required for Y. enterocolitica pathogenesis. Serogroups that predominate in human illness are O:3, O:8, O:9, and O:5,27. Yersinia does not produce siderophores and uses analogous siderophores from other bacteria or host-chelated iron stores to thrive, placing patients with iron overload, as in hemochromatosis, thalassemia, and sickle cell disease, at higher risk for infection.
Disease occurs most often as enterocolitis with diarrhea, fever, and abdominal pain. Acute enteritis is more common among younger children, and mesenteric lymphadenitis that can mimic appendicitis may be found in older children and adolescents. Incubation period is usually 4-6 days after exposure (range 1-14 days). Stools may be watery or contain leukocytes and, less often, frank blood and mucus. Duration of diarrhea is often longer for Y. enterocolitica than for other causes of acute gastroenteritis, ranging from 12-22 days in several studies. Fever is common. Notably, prominent pharyngitis may be seen in 20% of patients at presentation, which may help distinguish it from other causes of gastroenteritis. Y. enterocolitica is excreted in stool for 1-4 wk. Family contacts of a patient are often found to be asymptomatically colonized with Y. enterocolitica. Y. enterocolitica septicemia is less common and is most often found in very young children (<3 mo old) and immunocompromised persons. Systemic infection can be associated with splenic and hepatic abscesses, osteomyelitis, septic arthritis, meningitis, endocarditis, and mycotic aneurysms. Exudative pharyngitis, pneumonia, empyema, lung abscess, and acute respiratory distress syndrome occur infrequently.
Reactive complications include erythema nodosum, reactive arthritis, and rarely uveitis. These manifestations may be more common in select populations (northern Europeans), in association with HLA-B27, and in females.
Diagnosis is made typically through isolation of the organism, usually from the stool. Y. enterocolitica is easily cultured from normally sterile sites but requires special procedures for isolation from stool, where other bacteria can outgrow it. Yersinia should be cultured on selective agar (CIN, cefsulodin-irgasan-novobiocin) at 25-28°C to increase yield. If O:3 serogroup is suspected, MacConkey agar should be used at 25-28°C. Multiplex polymerase chain reaction (PCR) testing is also available. Many laboratories do not routinely perform the tests required to detect Y. enterocolitica ; procedures targeted to this organism must be specifically requested. A history indicating contact with environmental sources of Yersinia and detection of fecal leukocytes are helpful indicators of a need to test for Y. enterocolitica. The isolation of a Yersinia from stool should be followed by tests to confirm that the isolate is a pathogen. Serodiagnosis is not readily available, and utility is limited by cross-reactivity.
The clinical presentation is similar to other forms of bacterial enterocolitis. The most common considerations include Shigella, Salmonella, Campylobacter, Clostridium difficile, enteroinvasive Escherichia coli, Y. pseudotuberculosis , and occasionally Vibrio -related diarrheal disease. Amebiasis, appendicitis, Crohn disease, ulcerative colitis, diverticulitis, and pseudomembranous colitis should also be considered.
Enterocolitis in an immunocompetent patient is a self-limiting disease, and no benefit from antibiotic therapy is established. Patients with systemic infection and very young children (in whom septicemia is common) should be treated. Yersinia organisms are typically susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), aminoglycosides, third-generation cephalosporins, and quinolones, although strains resistant to quinolones have been reported. Y. enterocolitica produces β-lactamases, which are responsible for resistance to penicillins and first-generation cephalosporins. TMP-SMX is the recommended empirical treatment in children for enterocolitis (generally a 5-day course), because it has activity against most strains and is well tolerated. In severe infections such as bacteremia, third-generation cephalosporins, with or without aminoglycosides, are effective, and usually a 3 wk course of therapy is administered, with possible transition to oral therapy. Patients on deferoxamine should discontinue iron chelation therapy during treatment for Y. enterocolitica, especially if they have complicated gastrointestinal (GI) infection or extraintestinal infection.
Reactive arthritis, erythema nodosum, erythema multiforme, hemolytic anemia, thrombocytopenia, and systemic dissemination of bacteria have been reported in association with Y. enterocolitica infection. Septicemia is more common in younger children, and reactive arthritis is more common in older patients. Arthritis appears to be mediated by immune complexes, which form as a result of antigenic mimicry, and viable organisms are not present in involved joints.
Prevention centers on reducing contact with environmental sources of Yersinia. Families should be warned of the high risk of chitterling preparation, especially with young infants and children in the household. Breaking or sterilization of the chain from animal reservoirs to humans holds the greatest potential to reduce infections, and the techniques applied must be tailored to the reservoirs in each geographic area. There is no licensed vaccine.
Centers for Disease Control and Prevention. Yersinia and chitlins prevention fact sheet . [Available from:] https://www.cdc.gov/yersinia/chitlins.html [(Accessed January 21, 2019)].
Chakraborty A, Komatsu K, Roberts M, et al. The descriptive epidemiology of yersiniosis: a multistate study, 2005–2011. Public Health Rep . 2015;130:269–277.
Hale CR, Scallan E, Cronquist AB, et al. Estimates of enteric illness attributable to contact with animals and their environments in the United States. Clin Infect Dis . 2012;54(Suppl 5):S472–S479.
Huang JY, Henao OL, Griffin PM, et al. Infection with pathogens transmitted commonly through food and the effect of increasing use of culture-independent diagnostic tests on surveillance—Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2012–2015. MMWR Morb Mortal Wkly Rep . 2016;65:368–371.
Scallan E, Mahon BE, Hoekstra RM, et al. Estimates of illnesses, hospitalizations and deaths caused by major bacterial enteric pathogens in young children in the United States. Pediatr Infect Dis J . 2013;32:217–221.
Ericka V. Hayes
Yersinia pseudotuberculosis has a worldwide distribution; Y. pseudotuberculosis disease is less common than Y. enterocolitica disease. The most common form of disease is a mesenteric lymphadenitis that produces an appendicitis-like syndrome. Y. pseudotuberculosis is associated with a Kawasaki syndrome–like illness in approximately 8% of cases.
Y. pseudotuberculosis is a small, gram-negative, aerobic and facultative anaerobic coccobacillus. As with Y. enterocolitica, it ferments glucose and does not ferment lactose, is oxidase negative, catalase producing, urea splitting, and shares a number of morphologic and culture characteristics. It is differentiated biochemically from Y. enterocolitica on the basis of ornithine decarboxylase activity, fermentation of sucrose, sorbitol, and cellobiose, and other tests, although some overlap between species occurs. Antisera to somatic O antigens and sensitivity to Yersinia phages can also be used to differentiate the 2 species. Subspecies-specific DNA sequences that allow direct probe- and primer-specific differentiation of Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica have been described. Y. pseudotuberculosis is more closely related phylogenetically to Y. pestis than to Y. enterocolitica.
Y. pseudotuberculosis is zoonotic, with reservoirs in wild rodents, rabbits, deer, farm animals, various birds, and domestic animals, including cats and canaries. Transmission to humans is by consumption of or contact with contaminated animals or contact with an environmental source contaminated by animals (often water). Direct evidence of transmission of Y. pseudotuberculosis to humans by consumption of lettuce and raw carrots has been reported. The organism has a worldwide distribution; however, infections are more commonly reported in Europe, in boys, and in the winter. During 1996–2014, FoodNet reported 224 cases of infections secondary to Y. pseudotuberculosis in the United States, with an annual average incidence of 0.03 per 100,000 persons. Compared with Y. enterocolitica infections, those caused by Y. pseudotuberculosis are more likely to be invasive and occur in adolescents and adults. Iron-overloading conditions, AIDS, other immunodeficiencies, and other debilitating diseases (including liver cirrhosis) may predispose to invasive Y. pseudotuberculosis infection.
Ileal and colonic mucosal ulceration and mesenteric lymphadenitis are hallmarks of the infection. Necrotizing epithelioid granulomas may be seen in the mesenteric lymph nodes, but the appendix is often grossly and microscopically normal. The mesenteric nodes are often the only source of isolation of the organism. Y. pseudotuberculosis antigens bind directly to human leukocyte antigen (HLA) class II molecules and can function as superantigens , which might account for the clinical illness resembling Kawasaki syndrome .
Pseudoappendicitis and mesenteric lymphadenitis with abdominal pain, right lower quadrant tenderness, fever, and leukocytosis constitute the most common clinical presentation. Enterocolitis and extraintestinal spread are uncommon. Iron overload, diabetes mellitus, and chronic liver disease are often found concomitantly with extraintestinal Y. pseudotuberculosis infection. Renal involvement with tubulointerstitial nephritis, azotemia, pyuria, and glucosuria can occur. Y. pseudotuberculosis can present as a Kawasaki syndrome–like illness with fever of 1-6 days’ duration, strawberry tongue, pharyngeal erythema, scarlatiniform rash, cracked red swollen lips, conjunctivitis, sterile pyuria, periungual desquamation, and thrombocytosis. Some of these children have had coronary changes. Other uncommon manifestations include septic arthritis, massive lower GI bleeding, postaneurysmal prosthetic vascular infection, and acute encephalopathy.
PCR of involved tissue can be used to identify Y. pseudotuberculosis ; isolation by culture can require an extended interval. Involved mesenteric lymph nodes removed at appendectomy can yield the organism by culture. Abdominal CT scan or ultrasound examination of children with unexplained fever and abdominal pain can reveal a characteristic picture of enlarged mesenteric lymph nodes and thickening of the terminal ileum with or without peritoneal findings including appendiceal inflammation and periappendiceal fluid. Y. pseudotuberculosis is rarely recovered from stool. Serologic testing is available in specialized labs.
Appendicitis (most common), inflammatory bowel disease, and other intraabdominal infections should be considered. Kawasaki syndrome, staphylococcal or streptococcal disease, leptospirosis, Stevens-Johnson syndrome, and collagen vascular diseases, including acute-onset juvenile idiopathic arthritis, can mimic the syndrome with prolonged fever and rash. C. difficile colitis, meningitis, encephalitis, enteropathic arthropathies, acute pancreatitis, sarcoidosis, toxic shock syndrome, typhoid fever, and ulcerative colitis may also be considered.
Uncomplicated mesenteric lymphadenitis caused by Y. pseudotuberculosis is a self-limited disease, and antimicrobial therapy is not required. Few data exist on optimal treatment and duration of therapy. Infections with Y. pseudotuberculosis can generally be managed the same as those caused by Y. enterocolitica . Culture-confirmed bacteremia should be treated with a third-generation cephalosporin with or without an aminoglycoside, TMP-SMX, fluoroquinolones, or chloramphenicol.
Erythema nodosum and reactive arthritis can follow infection. Coronary aneurysm formation has been described with disease presenting as Kawasaki syndrome–like illness. Rare local complications of GI disease include perforation, obstruction, and intussusception.
Avoiding exposure to potentially infected animals and good food-handling practices can prevent infection. The sporadic nature of the disease makes application of targeted prevention measures difficult.
Horinouchi T, Nozu K, Hamahira K, et al. Yersinia pseudotuberculosis infection in Kawasaki disease and its clinical characteristics. BMC Pediatr . 2015;15:177.
Long C, Jones TF, Vugia DJ, et al. Yersinia pseudotuberculosis and Y. enterocolitica infections, FoodNet, 1996–2007. Emerg Infect Dis . 2010;16:566–567.
Mischnik A, Dahme T, Bekeredjian R, et al. Haemophilia-associated Yersinia pseudotuberculosis serotype O:1 septicaemia: the role of iron. J Med Microbiol . 2012;61(Pt1):157–159.
Vasala M, Hallanvuo S, Ruuska P, et al. High frequency of reactive arthritis in adults after Yersinia pseudotuberculosis O:1 outbreak caused by contaminated grated carrots. Ann Rheum Dis . 2014;73:1793–1796.
Ericka V. Hayes
Yersinia pestis is a gram-negative, facultative anaerobe that is a pleomorphic nonmotile, non–spore-forming coccobacillus and a potential agent of bioterrorism. It evolved from Y. pseudotuberculosis through acquisition of chromosomal changes and plasmid-associated factors that are essential to its virulence and survival in mammalian hosts and fleas. Y. pestis shares bipolar staining appearance with Y. pseudotuberculosis and can be differentiated by biochemical reactions, serology, phage sensitivity, and molecular techniques. Y. pestis exists in 3 biovars: Antigua (Africa), Medievalis (central Asia), and Orientalis (widespread).
Plague is endemic in at least 24 countries. Approximately 3,000 cases are reported worldwide per year, with 100-200 deaths. Plague is uncommon in the United States (0-40 reported cases/yr); most of these cases occur west of a line from east Texas to east Montana, with 80% of cases in California, New Mexico, Arizona, and Colorado. In 2015, there was a cluster of 11 cases (with 3 deaths) in 4 mo related to exposure at Yosemite National Park in California's Sierra Nevada Mountains. The epidemic form of disease killed approximately 25% of the population of Europe in the Middle Ages in one of several epidemics and pandemics. The epidemiology of epidemic plague involves extension of infection from the zoonotic reservoirs to urban rats, Rattus rattus and Rattus norvegicus, and from fleas of urban rats to humans. Epidemics are no longer seen. Selective pressure exerted by plague pandemics in medieval Europe is hypothesized for enrichment of a deletion mutation in the gene encoding CCR5 (CCR5-Δ32). The enhanced frequency of this mutation in European populations endows approximately 10% of European descendants with relative resistance to acquiring HIV-1.
The most common mode of transmission of Y. pestis to humans is through flea bites . Historically, most human infections are thought to have resulted from bites of fleas that acquired infection from feeding on infected urban rats. Less frequently, infection is caused by contact with infectious body fluids or tissues or inhalation of respiratory secretions of infected animals. Currently, most cases of plague secondary to direct animal contact or inhalation of animal secretions are related to domestic cats or dogs . Direct transmission from human to human through droplet inhalation is possible but extremely rare. Laboratory transmission of Y. pestis has been described as well. Sylvatic plague can exist as a stable enzootic infection or as an epizootic disease with high host mortality. Ground squirrels, rock squirrels, prairie dogs, rats, mice, bobcats, cats, rabbits, and chipmunks may be infected. Transmission among animals is usually by flea bite or by ingestion of contaminated tissue. Xenopsylla cheopis is the flea usually associated with transmission to humans, but >30 species of fleas have been demonstrated as vector competent, and Pulex irritans, the human flea, can transmit plague and might have been an important vector in some historical epidemics. Both sexes are similarly affected by plague, and transmission is more common in colder regions and seasons, possibly because of temperature effects on Y. pestis infections in vector fleas.
In the most common form of plague, infected fleas regurgitate organisms into a patient's skin during feeding. The bacteria translocate via lymphatics to regional lymph nodes, where Y. pestis replicates, resulting in bubonic plague. In the absence of rapidly implemented specific therapy, bacteremia can occur, resulting in purulent, necrotic, and hemorrhagic lesions in many organs. Both plasmid and chromosomal genes are required for full virulence. Pneumonic plague can be secondary to bacteremia or primary when infected material is inhaled. The organism is highly transmissible from persons with pneumonic plague and from domestic cats with pneumonic infection. This high transmissibility and high morbidity and mortality have provided an impetus for attempts to use Y. pestis as a biologic weapon.
Y. pestis infection can manifest as several clinical syndromes; infection can also be subclinical. The 3 principal clinical presentations of plague are bubonic, septicemic, and pneumonic. Bubonic plague is the most common form and accounts for 80–90% of cases in the United States. From 2-8 days after a flea bite, lymphadenitis develops in lymph nodes closest to the inoculation site, including the inguinal (most common), axillary, or cervical region. These buboes are remarkable for tenderness. Fever, chills, weakness, prostration, headache, and the development of septicemia are common. The skin might show insect bites or scratch marks. Purpura and gangrene of the extremities can develop as a result of disseminated intravascular coagulation (DIC). These lesions may be the origin of the name Black Death. Untreated plague results in death in >50% of symptomatic patients. Death can occur within 2-4 days after onset of symptoms.
Occasionally, Y. pestis establishes systemic infection and induces the systemic symptoms seen with bubonic plague without causing a bubo (primary septicemic plague ). Because of the delay in diagnosis linked to the lack of the bubo, septicemic plague carries an even higher case fatality rate than bubonic plague. In some regions, bubo-free septicemic plague accounts for 25% of cases.
Pneumonic plague is the least common but most dangerous and lethal form of the disease. Pneumonic plague can result from hematogenous dissemination, or, rarely, as primary pneumonic plague after inhalation of the organism from a human or animal with plague pneumonia or potentially from a biologic attack. Signs of pneumonic plague include severe pneumonia with high fever, dyspnea, and hemoptysis.
Meningitis, tonsillitis, or gastroenteritis can occur. Meningitis tends to be a late complication following inadequate treatment. Tonsillitis and gastroenteritis can occur with or without apparent bubo formation or lymphadenopathy.
Plague should be suspected in patients with fever and history of exposure to small animals in endemic areas. Thus, bubonic plague is suspected in a patient with a painful swollen lymph node, fever, and prostration who has been potentially exposed to fleas or rodents in the western United States. A history of camping or the presence of flea bites increases the index of suspicion.
Y. pestis is readily transmitted to humans by some routine laboratory manipulations. Thus, it is imperative to clearly notify a laboratory when submitting a sample suspected of containing Y. pestis. Laboratory diagnosis is based on bacteriologic culture or direct visualization using Gram, Giemsa, or Wayson stain of lymph node aspirates, blood, sputum, or exudates. Fluorescent antibody staining can also be done on specimens. Y. pestis grows slowly under routine culture conditions and best at temperatures that differ from those used for routine cultures in many clinical laboratories. Note some automated blood culture identification systems may misidentify Y. pestis . A rapid antigen test detecting Y. pestis F1 antigen in sputum and serum samples exists. Suspected isolates of Y. pestis should be forwarded to a reference laboratory for confirmation. Special containment shipping precautions are required. Cases of plague should be reported to local and state health departments and the Centers for Disease Control and Prevention (CDC). Serologic testing is also available.
The Gram stain of Y. pestis may be confused with Enterobacter agglomerans. Mild and subacute forms of bubonic plague may be confused with other disorders causing localized lymphadenitis and lymphadenopathy, including tularemia and cat-scratch adenitis. Septicemic plague may be indistinguishable from other forms of overwhelming bacterial sepsis.
Pulmonary manifestations of plague are similar to those of anthrax, Q fever, and tularemia, all agents with bioterrorism and biologic warfare potential. Thus, the presentation of a suspected case, and especially any cluster of cases, requires immediate reporting. Additional information on this aspect of plague and procedures can be found at http://www.bt.cdc.gov/agent/plague/ .
Patients with suspected plague should be placed on droplet isolation until pneumonia is ruled out, sputum cultures are negative, and antibiotic treatment has been administered for 48 hr. The treatment of choice for bubonic plague historically has been streptomycin (30 mg/kg/day, maximum 2 g/day, divided every 12 hr intramuscularly [IM] for 10 days). Intramuscular streptomycin is inappropriate for septicemia because absorption may be erratic when perfusion is poor. The poor central nervous system penetration of streptomycin also makes this an inappropriate drug for meningitis. Furthermore, streptomycin might not be widely and immediately available. Gentamicin (children, 7.5 mg/kg IM or intravenously [IV] divided every 8 hr; adults, 5 mg/kg IM or IV once daily) has been shown to be as efficacious as streptomycin; in patients with abscesses, an additional agent may be needed in addition to an aminoglycoside because of poor abscess penetration. Alternative treatments include doxycycline (in children who weigh <45 kg: 4.4 mg/kg/day divided every 12 hr IV, maximum 200 mg/day; not recommended for children <8 yr of age; in children who weigh ≥45 kg, 100 mg every 12 hr orally [PO]), ciprofloxacin (30 mg/kg/day divided every 12 hr, maximum 400 mg every 12 hr IV), and chloramphenicol (100 mg/kg/day IV divided every 6 hr, for children >2 yr; maximum dose 4 g/day; not widely available in the United States). Meningitis is usually treated with chloramphenicol or a fluoroquinolone. Resistance to these agents and relapses are rare. Y. pestis is susceptible in vitro to fluoroquinolones , which are effective in treating experimental plague in animals. Y. pestis is susceptible in vitro to penicillin, but penicillin is ineffective in treatment of human disease. Mild disease may be treated with oral chloramphenicol or tetracycline in children >8 yr old. Clinical improvement is noted within 48 hr of initiating treatment. Typical duration of therapy is 10-14 days, with a switch to oral therapy 2 days after defervescence and clinical improvement. Drainage of suppurative buboes may be needed; material is infectious, and appropriate precautions should be taken intraoperatively.
Postexposure prophylaxis should be given to close contacts of patients with pneumonic plague. Antimicrobial prophylaxis is recommended within 7 days of exposure for persons with direct, close contact with patient with pneumonic plague or those exposed to an accidental or terrorist-induced aerosol. Recommended regimens for children >8 yr old include doxycycline or ciprofloxacin; for children <8 yr old, doxycycline, chloramphenicol and ciprofloxacin are options for a 7-day course at the treatment doses above. Contacts of cases of uncomplicated bubonic plague do not require prophylaxis. Y. pestis is a potential agent of bioterrorism that can require mass casualty prophylaxis.
Avoidance of exposure to infected animals and fleas is the best method of prevention of infection. In the United States, special care is required in environments inhabited by rodent reservoirs of Y. pestis and their ectoparasites. Patients with plague should be isolated if they have pulmonary symptoms, and infected materials should be handled with extreme care. There is currently no available licensed vaccine for Y. pestis in the United States. Several vaccine development trials are underway, and recombinant subunit vaccines based on rF1 and rV antigens seem to be the most promising. Using baits containing live vaccines for oral immunization of wild animals may be a helpful alternative for control of epidemics.
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