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Transcript
Enterobacteriaceae Microbiology Department KUMS Dr. Mohajeri 1 a large, heterogeneous group of G-ve rods natural habitat is the intestinal tract of humans and animals facultative anaerobes or aerobes ferment a wide range of carbohydrates (Glc+) possess a complex antigenic structure produce a variety of toxins and other virulence factors catalase-positive, oxidase-negative reduce nitrate to nitrite The family includes many genera: - Escherichia - Shigella - Salmonella - Enterobacter - Klebsiella - Serratia - Proteus and others 2 Some enteric organisms, eg, E.coli, are part of the normal flora and incidentally cause disease, while others, the salmonellae and shigellae, are regularly pathogenic for humans. coliforms: - Escherichia - Enterobacter - Klebsiella - Citrobacter 3 Classification along with staphylococci and streptococci are among the most common bacteria that cause disease More than 25 genera and 110 species 4 5 Tribe I: Escherichia → Escherichia Shigella Tribe II: Edwardsielleae → Edwardsielleae Tribe III: Salmonelleae → Salmonella Tribe IV: Citrobacter → Citrobacter Tribe V: Klebsielleae → Klebsiella Enterobacter Hafnia Pantoea Serratia Tribe VI: Proteae → Proteus Morganella Providencia Tribe VII: Yersinieae → Yersinia Antigenic Structure have a complex antigenic structure: - >150 different heat-stable somatic O (LPS antigens - >100 heat-labile K (capsular) antigens - > 50 H (flagellar) antigens In S. typhi, the capsular antigens are called Vi antigens. 8 9 O antigens cell wall LPS and consist of repeating units of polysaccharide are resistant to heat and alcohol usually are detected by bacterial agglutination Antibodies to O antigens are predominantly IgM While each genus of Enterobacteriaceae is associated with specific O groups, a single organism may carry several O antigens. Thus, most shigellae share one or more O antigens with E. coli. E. coli may cross-react with some Providencia, Klebsiella and Salmonella species. 10 K antigens are external antigen but not all Enterobacteriaceae Some are polysaccharides, including the K antigens of E. coli; others are proteins K antigens may interfere with agglutination by O antisera, and they may be associated with virulence (eg, E. coli strains producing K1 antigen are prominent in neonatal meningitis, and K antigens of E. coli cause attachment of the bacteria to epithelial cells prior to gastrointestinal or urinary tract invasion). 11 Klebsiellae form large capsules consisting of polysaccharides (K antigens) covering the somatic (O or H) antigens and can be identified by capsular swelling tests with specific antisera. - capsular types 1 and 2 → human respiratory tract infections - types 8, 9, 10 and 24 → UTI 12 H antigens are located on flagella and are denatured or removed by heat or alcohol They are preserved by treating motile bacterial variants with formalin Such H antigens agglutinate with anti-H antibodies, mainly IgG Subunite name: flagellin Within a single serotype, flagellar antigens may be present in either or both of two forms, called phase 1 (conventionally designated by lower-case letters) and phase 2 (conventionally designated by Arabic numerals) 13 14 The organism tends to change from one phase to the other; this is called phase variation H antigens on the bacterial surface may interfere with agglutination by anti-O antibody. There are many examples of overlapping antigenic structures between Enterobacteriaceae and other bacteria: - Most Enterobacteriaceae share the O14 antigen of E. coli - The type 2 capsular polysaccharide of klebsiellae is very similar to the polysaccharide of type 2 pneumococci - Some K antigens cross-react with capsular polysaccharides of H.influenzae or N. meningitidis - Thus, E. coli O75:K100:H5 can induce antibodies that react with H. influenzae type b. 15 antigenic formula: - E. coli O55:K5:H21 - Salmonella schottmülleri O1,4,5,12:Hb:1,2 Colicins (Bacteriocins) Many G-ve organisms produce bacteriocins These virus-like bactericidal substances are produced by certain strains of bacteria active against some other strains of the same or closely related species Their production is controlled by plasmids. 16 e.g: - Colicins by E. coli - Marcescens by serratia - Pyocins by pseudomonas Bacteriocin-producing strains are resistant to their own bacteriocin; thus, bacteriocins can be used for "typing" of organisms. Toxins & Enzymes LPS (endotoxins), have a variety of pathophysiologic effects Many G-ve enteric bacteria also produce exotoxins of clinical importance. 17 18 Diseases Caused by Enterobacteriaceae Other Than Salmonella & Shigella Causative Organisms E. coli is a member of the normal intestinal flora. Proteus, Enterobacter, Klebsiella, Morganella, Providencia, Citrobacter and Serratia are also found as members of the normal intestinal flora but are considerably less common than E. coli The enteric bacteria generally do not cause disease. hospital-acquired infections and occasionally cause community-acquired infections The bacteria become pathogenic only when they reach tissues outside of their normal intestinal or other less common normal flora sites. 19 The most frequent sites of clinically important infection are: - the urinary tract - biliary tract - other sites in the abdominal cavity but any anatomic site (eg, bacteremia, prostate gland, lung, bone, meninges) can be the site of disease. Some of the enteric bacteria (eg, Serratia marcescens, Enterobacter aerogenes) are opportunistic pathogens. Pathogenesis & Clinical Findings depend on the site of the infection 20 E. coli Urinary Tract Infection (UTI) E. coli is the most common cause of UTI (90% of first UTIs in young women) The symptoms and signs include urinary frequency, dysuria, hematuria and pyuria. Flank pain is associated with upper tract infection. UTI can result in bacteremia with clinical signs of sepsis. Nephro (Uro) pathogenic E. coli typically produce a hemolysin. Most of the infections are caused by E. coli of a small number of O antigen types. 21 K antigen appears to be important in the pathogenesis of UTI. Pyelonephritis is associated with a specific type of pilus, P pilus, which binds to the P blood group substance. E. coli - Associated Diarrheal Diseases are classified by the characteristics of their virulence properties each group causes disease by a different mechanism The small or large bowel epithelial cell adherence properties are encoded by genes on plasmids The toxins often are plasmid- or phage-mediated. 22 E. coli virutypes Enteropathogenic E. coli (EPEC) is an important cause of diarrhea in infants, especially in developing countries adhere to the mucosal cells of the small bowel Chromosomally mediated factors promote tight adherence There is loss of microvilli (effacement), formation of filamentous actin pedestals or cup-like structures and, occasionally, entry of the EPEC into the mucosal cells. The result of EPEC infection is watery diarrhea, which is usually self-limited but can be chronic EPEC diarrhea has been associated with multiple specific serotypes of E. coli 23 Enterotoxigenic E. coli (ETEC) is a common cause of "traveler's diarrhea“ cause of a very important cause of diarrhea in infants ETEC adhere to epithelial cells of the small bowel Some strains of ETEC produce a heat-labile exotoxin (LT) that is under the genetic control of a plasmid: → its subunit B attaches to the GM1 ganglioside at the brush border of epithelial cells of the small intestine → facilitates the entry of subunit A into the cell 24 → activates adenylyl cyclase → increases the local concentration of cAMP → intense and prolonged hypersecretion of water and chlorides → inhibits the reabsorption of Na+ → diarrhea for several days LT is antigenic and cross-reacts with the enterotoxin of V. cholerae 25 Assays for LT detection: 1) fluid accumulation in the intestine of laboratory animals 2) typical cytologic changes in cultured Chinese hamster ovary cells or other cell lines 3) stimulation of steroid production in cultured adrenal tumor cells 4) binding and immunologic assays with standardized antisera to LT 26 Some strains of ETEC produce the heat-stable enterotoxin Sta, which is under the genetic control of a heterogeneous group of plasmids. STa activates guanylyl cyclase in enteric epithelial cells → stimulates fluid secretion Many STa - positive strains also produce LT The strains with both toxins produce a more severe diarrhea The plasmids carrying the genes for enterotoxins (LT, ST) also may carry genes for the colonization factors that facilitate the attachment to intestinal epithelium 27 Enterohemorrhagic E. coli (EHEC) produces verotoxin: named for its cytotoxic effect on Vero cells (a line of African green monkey kidney cells) There are at least two antigenic forms of the toxin EHEC has been associated with: - hemorrhagic colitis (HC), a severe form of diarrhea - hemolytic uremic syndrome (HUS), a disease resulting in acute renal failure Verotoxin are similar to the Shiga toxin produced by Shigella dysenteriae type 1 cooking ground beef 28 E. coli O157:H7 is the most common - does not use sorbitol, unlike most other E. coli - is negative on sorbitol MacConkey agar (sMAC) - are negative on MUG tests - Specific antisera are used to identify Enteroinvasive E. coli (EIEC) produces a disease very similar to shigellosis occurs most commonly in children in developing countries and in travelers to these countries Like shigella, EIEC strains are nonlactose or late lactose fermenters and are nonmotile produce disease by invading intestinal mucosal epithelial cells 29 Enteroaggregative E. coli (EAEC) causes acute and chronic diarrhea (> 14 days in duration) cause of food-borne disease (FBD) in industrialized countries Characterization: pattern of adherence to human cells produce ST-like toxin and a hemolysin 30 Sepsis When normal host defenses are inadequate, E. coli may reach the bloodstream and cause sepsis Newborns may be highly susceptible to E. coli sepsis because they lack IgM antibodies Sepsis may occur secondary to UTI Meningitis E. coli and group B streptococci are the leading causes of meningitis in infants Approximately 75% of E. coli from meningitis cases have the K1 antigen This antigen cross-reacts with the group B capsular polysaccharide of N. meningitidis 31 Klebsiella K. pneumoniae is present in the respiratory tract and feces of about 5% of normal individuals causes 1% of bacterial pneumonias can produce extensive hemorrhagic necrotizing consolidation of the lung occasionally produces UTI and bacteremia with focal lesions in debilitated patients K. pneumoniae, K.oxytoca → cause hospital-acquired infections K. ozaenae → causes ozena K. rhinoscleromatis → causes rhinoscleroma 32 Enterobacter aerogenes has small capsules free-living as well as in the intestinal tract causes UTI and sepsis Serratia o S. marcescens is a common opportunistic pathogen in hospitalized patients o Serratia (usually nonpigmented) causes pneumonia, bacteremia and endocarditis-especially in narcotics addicts and hospitalized patients o Only about 10% of isolates form the red pigment (prodigiosin) that has long characterized Serratia marcescens 33 Proteus produce infections in humans only when the bacteria leave the intestinal tract Produce UTI, bacteremia, pneumonia and focal lesions in debilitated patients or those receiving intravenous infusions P. mirabilis causes UTI and occasionally other infections. P. vulgaris and Morganella morganii are important nosocomial pathogens. 34 Proteus species produce urease, resulting in rapid hydrolysis of urea with liberation of ammonia Thus, in UTI with proteus, the urine becomes alkaline, promoting stone formation The rapid motility of proteus may contribute to its invasion of the urinary tract Strains of proteus vary greatly in antibiotic sensitivity 35 Providencia Providencia species (P. rettgeri, P. alcalifaciens, and P. Stuartii ) are members of the normal intestinal flora All cause UTI and occasionally other infections and are often resistant to antimicrobial therapy. Citrobacter cause UTI and sepsis 36 Diagnostic Laboratory Tests Specimens Specimens included urine, blood, pus, spinal fluid, sputum Culture Specimens are plated on both blood agar and differential media. With differential media, rapid preliminary identification of G-ve bacteria is often possible. 37 Treatment sulfonamides, ampicillin, cephalosporins, fluoroquinolones and aminoglycosides Multiple drug resistance is common and is under the control of transmissible plasmids. Epidemiology, Prevention & Control The enteric bacteria establish themselves in the normal intestinal tract within a few days after birth. Enterics found in water or milk are accepted as proof of fecal contamination from sewage or other sources. 38 E. coli serotypes should be controlled like salmonellae. many enteric bacteria are "opportunists" that cause illness in debilitated patients 39 The Shigellae The natural habitat of shigellae is limited to the intestinal tracts of humans and other primates, where they produce bacillary dysentery. With the exception of Shigella sonnei, they do not ferment lactose 40 Antigenic Structure The somatic O antigens are more than 40 serotypes. Pathogenesis & Pathology Shigella infections are almost always limited to the gastrointestinal tract. bloodstream invasion is quite rare. Shigellae are highly communicable; the infective dose (ID) is on the order of 103 organisms (whereas it usually is 105–108 for salmonellae and vibrios) 41 The essential pathologic process: - invasion of the mucosal epithelial cells (eg, M cells) by induced phagocytosis - escape from the phagocytic vacuole - multiplication and spread within the epithelial cell cytoplasm - passage to adjacent cells - Microabscesses in large intestine and terminal ileum → necrosis of the mucous membrane, superficial ulceration, bleeding, and formation of a "pseudomembrane" on the ulcerated area. 42 Toxins - Endotoxin all shigellae release their toxic LPS (endotoxin) - Shigella dysenteriae Exotoxin S. dysenteriae type 1 (Shiga bacillus) produces a heat-labile exotoxin that affects both the gut and the central nervous system (CNS). Acting as an enterotoxin, it produces diarrhea as does the E. coli verotoxin, perhaps by the same mechanism. In humans, the exotoxin also inhibits sugar and amino acid absorption in the small intestine. Acting as a "neurotoxin" 43 Patients with S. flexneri or S. sonnei infections develop antitoxin that neutralizes S. dysenteriae exotoxin in vitro. Clinical Findings The illness due to S. dysenteriae may be particularly severe. Diagnostic Laboratory Tests Specimens include fresh stool, mucus flecks and rectal swabs for culture. salmonella-shigella (SS) agar → suppress other Enterobacteriaceae and G+ve organisms are nonmotile 44 Immunity IgA antibodies in the gut may be important in limiting reinfection; these may be stimulated by live attenuated strains given orally as experimental vaccines. Serum antibodies to somatic shigella antigens are IgM. Treatment Ciprofloxacin, ampicillin, doxycycline and trimethoprim-sulfamethoxazole (SXT) Multiple drug resistance can be transmitted by plasmids Many cases are self-limited 45 Epidemiology, Prevention & Control 4F: Shigellae are transmitted by "food, fingers, feces and flies" from person to person. Most cases of shigella infection occur in children under 10 years of age. control efforts: 1) sanitary control of water, food, and milk; sewage disposal; and fly control 2) isolation of patients and disinfection of excreta 3) detection of subclinical cases and carriers, particularly food handlers 4) antibiotic treatment of infected individuals 46 The Salmonella-Arizona Group Salmonellae are often pathogenic for humans or animals when acquired by the oral route cause enteritis, systemic infection and enteric fever Most isolates are motile with peritrichous flagella They usually produce H2S They survive freezing in water for long periods Salmonellae are resistant to certain chemicals (eg, brilliant green, sodium tetrathionate, sodium deoxycholate) that inhibit other enteric bacteria The classification of salmonellae is complex. 47 The members of the genus Salmonella were originally classified on the basis of epidemiology, host range, biochemical reactions and structures of the O, H and Vi (when present) antigens. DNA-DNA hybridization studies: - seven groups ** Nearly all of the salmonella serotypes that infect humans are in DNA hybridization group I there are rare human infections with groups IIIa and IIIb. 48 e.g: S. enterica subspecies enterica serotype Typhimurium = can be shortened to S. typhimurium There are >2500 serotypes of salmonellae, including >1400 in DNA hybridization group I that can infect humans. 49 Four serotypes of salmonellae that cause enteric fever can be identified in the clinical laboratory by biochemical and serologic tests. These serotypes should be routinely identified because of their clinical significance. They are as follows: - Salmonella Paratyphi A - Salmonella Paratyphi B - Salmonella Choleraesuis - Salmonella typhi (serogroup A) (serogroup B) (serogroup C1) (serogroup D) 50 The more than 1400 other salmonellae that are isolated in clinical laboratories are serogrouped by their O antigens as A, B, C1, C2, D and E Variation: - Organisms may lose H antigens and become nonmotile. - Loss of O antigen is associated with a change from smooth to rough colony form. - Vi antigen may be lost partially or completely. 51 Pathogenesis & Clinical Findings Salmonella typhi, Salmonella Choleraesuis and perhaps Salmonella Paratyphi A and Salmonella Paratyphi B are primarily infective for humans (human source) The vast majority of salmonellae, however, are chiefly pathogenic in animals that constitute the reservoir for human infection: poultry, pigs, rodents, cattle, pets (from turtles to parrots) and many others. The organisms almost always enter via the oral route, usually with contaminated food or drink. 52 The mean infective dose to produce clinical or subclinical infection in humans is 105–108 salmonellae (but perhaps as few as 103 Salmonella typhi organisms) Among the host factors that contribute to resistance to salmonella infection are gastric acidity, normal intestinal microbial flora and local intestinal immunity. 53 Salmonellae produce three main types of disease in humans, but mixed forms are frequent: 54 The "Enteric Fevers" (Typhoid Fever) This syndrome is produced by only a few of the salmonellae, of which Salmonella typhi (typhoid fever) is the most important. The ingested salmonellae: → reach the small intestine → enter the lymphatics → enter the bloodstream → carried by the blood to many organs, including the intestine → multiply in intestinal lymphoid tissue → are excreted in stools 55 mortality rate was 10–15% Treatment with antibiotics has reduced the mortality rate to less than 1%. The principal lesions are hyperplasia and necrosis of lymphoid tissue (eg, Peyer's patches), hepatitis, focal necrosis of the liver and inflammation of the gallbladder, periosteum, lungs and other organs. 56 Bacteremia with Focal Lesions This is associated commonly with S. choleraesuis but may be caused by any salmonella serotype. Following oral infection, there is early invasion of the bloodstream (with possible focal lesions in lungs, bones, meninges, etc) but intestinal manifestations are often absent. Blood cultures are positive. 57 Enterocolitis This is the most common manifestation of salmonella infection. In the United States, Salmonella typhimurium and Salmonella enteritidis are prominent, but enterocolitis can be caused by any of the more than 1400 group I serotypes of salmonellae. Bacteremia is rare (2–4%) except in immunodeficient persons. Blood cultures are usually negative, but stool cultures are positive for salmonellae and may remain positive for several weeks after clinical recovery. 58 Diagnostic Laboratory Tests Blood for culture must be taken repeatedly. In enteric fevers and septicemias, blood cultures are often positive in the first week of the disease. Bone marrow cultures may be useful. Urine cultures may be positive after the second week. Stool specimens also must be taken repeatedly. A positive culture of duodenal drainage establishes the presence of salmonellae in the biliary tract in carriers. 59 Bacteriologic Methods for Isolation of Salmonellae Many salmonellae produce H2S Selective Medium Cultures: - salmonella-shigella (SS) agar The specimen (usually stool) also is put into selenite F or tetrathionate broth, both of which inhibit replication of normal intestinal bacteria and permit multiplication of salmonellae. After incubation for 1–2 days, this is plated on differential and selective media. biochemical reaction patterns There are commercial kits available to agglutinate and serogroup salmonellae by their O antigens: A, B, C1, C2, D and E. 60 Serologic Methods Tube Dilution Agglutination Test (Widal Test) Serum agglutinins rise sharply during the second and third weeks of Salmonella typhi infection. The Widal test to detect these antibodies against the O and H antigens has been in use for decades. The interpretive criteria when single serum specimens are tested vary, but a titer against the O antigen of >1:320 and against the H antigen of >1:640 is considered positive. High titer of antibody to the Vi antigen occurs in some carriers. The test is not useful in diagnosis of enteric fevers caused by salmonella other than S. typhi. 61 Treatment Antimicrobial therapy of invasive salmonella infections is with ampicillin, SXT or a thirdgeneration cephalosporin. Multiple drug resistance transmitted genetically by plasmids among enteric bacteria is a problem in salmonella infections. In most carriers, the organisms persist in the gallbladder (particularly if gallstones are present) and in the biliary tract. 62 Epidemiology carriers working as food handlers are "shedding" organisms Many animals, including cattle, rodents, and fowl, are naturally infected with a variety of salmonellae and have the bacteria in their tissues (meat), excreta or eggs The high incidence of salmonellae in commercially prepared chickens has been widely publicized. 63 Carriers 3% of survivors of typhoid become permanent carriers. harboring the organisms in the gallbladder, biliary tract, or, rarely, the intestine or urinary tract. Sources of Infection Water Milk and Other Dairy Products (Ice Cream, Cheese, Custard) Shellfish Eggs Meats and Meat Products From infected animals (poultry) or contamination with feces by rodents or humans. 64 Marijuana and other drugs Animal Dyes: eg, carmine, used in drugs, foods, and cosmetics. Household Pets Turtles, dogs, cats, etc. Prevention & Control Infected poultry, meats, and eggs must be thoroughly cooked. Carriers must not be allowed to work as food handlers and should observe strict hygienic precautions. 65 66 Yersinieae pleomorphic G-ve rods, bipolar staining, catalase-positive, oxidase-negative and microaerophilic or facultatively anaerobic Most have animals as their natural hosts, but they can produce serious disease in humans. The genus Yersinia includes: - Y. pestis → plague - Y. pseudotuberculosis and Yersinia enterocolitica → important causes of human diarrheal diseases 67 Yersinia pestis & Plague Plague is an infection of wild rodents, transmitted from one rodent to another and occasionally from rodents to humans by the bites of fleas. Serious infection often results, which in previous centuries produced pandemics of "black death" with millions of fatalities. Morphology & Identification G-ve rod with bipolar staining ends, nonmotile Growth is more rapid in media containing blood or tissue fluids and fastest at 30 °C In cultures on blood agar at 37 °C, colonies may be very small at 24 hours 68 A virulent inoculum, derived from infected tissue, produces gray and viscous colonies, but after passage in the laboratory the colonies become irregular and rough. The organism has little biochemical activity and this is somewhat variable. 69 Yersinia pestis (arrows) in blood 70 Antigenic Structure All yersiniae possess LPS that have endotoxic activity when released. The three pathogenic species produce antigens and toxins that act as virulence factors. They have type III secretion systems that consist of a membrane-spanning complex that allows the bacteria to inject proteins directly into cytoplasm of the host cells. 71 The virulent yersiniae produce V and W antigens, which are encoded by genes on a plasmid of approximately 70 kb. This is essential for virulence the V and W antigens yield the requirement for calcium for growth at 37 °C. In Y. pestis there is a capsular protein (fraction I) that is produced mainly at 37 °C and confers antiphagocytic properties the gene for this protein is on a plasmid of approximately 110 kb. 72 Y. pestis has a 9.6-kb plasmid that yields a: - plasminogen-activating protease - temperature-dependent coagulase activity (20-28 °C, the temperature of the flea) - fibrinolytic activity (35-37 °C, the temperature of the host). The three pathogenic yersiniae have a pathogenecity island (PAI) that encodes for an ironscavenging siderophore. 73 Among several exotoxins produced, one is lethal for mice in amounts of 1 µg. This homogeneous protein produces beta-adrenergic blockade and is cardiotoxic in animals. Its role in human infection is unknown. 74 Pathogenesis & Pathology When a flea feeds on a rodent infected with Y. pestis → the ingested organisms multiply in the gut of the flea (helped by the coagulase) → block its proventriculus so that no food can pass through → Subsequently, the "blocked" and hungry flea bites ferociously and the aspirated blood, contaminated with Y. pestis from the flea → The inoculated organisms may be phagocytosed by PMNs and monocytes. 75 → The Y. pestis organisms are killed by the PMNs but multiply in the monocytes; because the bacteria are multiplying at 37 °C → They produce the antiphagocytic protein and subsequently are able to resist phagocytosis → The pathogens rapidly reach the lymphatics and an intense hemorrhagic inflammation develops in the enlarged lymph nodes → Hemorrhagic and necrotic lesions may develop in all organs; meningitis, pneumonia. 76 Primary pneumonic plague results from inhalation of infective droplets (usually from a coughing patient), with hemorrhagic consolidation, sepsis, and death. 77 Clinical Findings 2–7 days incubation period → high fever → painful lymphadenopathy → greatly enlarged, tender nodes ("buboes") in the groin or axillae → Vomiting and diarrhea may develop with early sepsis → disseminated intravascular coagulation (DIC) → hypotension, altered mental status, and renal and cardiac failure → pneumonia and meningitis → Y. pestis multiplies intravascularly and can be seen in blood smears. 78 Diagnostic Laboratory Tests Blood is taken for culture and aspirates of enlarged lymph nodes for smear and culture. In pneumonia, sputum is cultured in possible meningitis, CSF is taken for smear and culture. Smears Spinal fluid and sputum smears should also be stained. (Wayson's stain) 79 Culture All materials are cultured on blood agar and MacConkey's agar plates and in infusion broth. All cultures are highly infectious and must be handled with extreme caution. Treatment Unless promptly treated, plague may have a mortality rate of nearly 50%; pneumonic plague, nearly 100%. The drug of choice is streptomycin. Tetracycline is an alternative drug. Drug resistance has been noted in Y. pestis. 80 Epidemiology & Control Plague is an infection of wild rodents (field mice, gerbils, moles, skunks and other animals) that occurs in many parts of the world. enzootic areas: India, Southeast Asia (especially Vietnam), Africa, North and South America The commonest vector of plague is the rat flea (Xenopsylla cheopis), but other fleas may also transmit the infection. The control of plague requires surveys of infected animals, vectors and human contacts All patients with suspected plague should be isolated 81 Contacts of patients with suspected plague pneumonia should receive tetracycline, as chemoprophylaxis. A formalin-killed vaccine is available for travelers to hyperendemic areas and for persons at special high risk 82 Y. enterocolitica & Y. pseudotuberculosis Lac-, G-ve rods, urease+, and oxidasegrow best at 25 °C and are motile at 25 °C but nonmotile at 37 °C They are found in the intestinal tract of a variety of animals, in which they may cause disease and are transmissible to humans > 50 serotypes most isolates from human disease: O3, O8, O9 There are striking geographic differences in the distribution of serotypes. Y. enterocolitica can produce a heat-stable enterotoxin. 83 Y. enterocolitica has been isolated from rodents and domestic animals (eg, sheep, cattle, swine, dogs and cats) and waters contaminated by them. Transmission to humans probably occurs by contamination of food, drink or fomites. 84 Y. pseudotuberculosis exists in at least six serotypes, but serotype O1 accounts for most human infections. Y. pseudotuberculosis occurs in domestic and farm animals and birds, which excrete the organisms in feces. Human infection probably results from ingestion of materials contaminated with animal feces. Person-to-person transmission with either of these organisms is probably rare. 85 Pathogenesis & Clinical Findings An inoculum of 108–109 yersiniae must enter the alimentary tract to produce infection. During the incubation period of 5–10 days, yersiniae multiply in the gut mucosa, particularly the ileum. The process may extend to mesenteric lymph nodes and, rarely, to bacteremia. Early symptoms include fever, abdominal pain, and diarrhea (from watery to bloody) develop arthralgia, arthritis and erythema nodosum, suggesting an immunologic reaction to the infection. 86 Very rarely, yersinia infection produces pneumonia, meningitis or sepsis; in most cases, it is self-limited. Diagnostic Laboratory Tests Specimens may be stool, blood or material obtained at surgical exploration. The number of yersiniae in stool may be small and can be increased by "cold enrichment": - a small amount of feces or a rectal swab is placed in buffered saline, pH 7.6, and kept at 4 °C for 2–4 weeks; many fecal organisms do not survive, but Y enterocolitica will multiply. Subcultures made at intervals on MacConkey agar may yield yersiniae. 87 Treatment Most yersinia infections with diarrhea are selflimited Y. enterocolitica is generally susceptible to aminoglycosides, chloramphenicol, tetracycline, SXT, piperacillin, third-generation cephalosporins, and fluoroquinolones. Prevention & Control Contact with farm and domestic animals, their feces or materials contaminated by them probably accounts for most human infections. Meat and dairy products have occasionally been indicated as sources of infection 88 89 90