2 Zoonotic Infections Zoonosis = disease of animals transmitted to man transmission may occur in several ways:direct contact with diseased flesh - eg., tularemiadrinking raw or unpasteurized cow’s or goat’s milk - eg., tuberculosisinhalation of dust particles contaminated with animal excreta orproducts - eg., psittacosiseating insufficiently cooked infected flesh - eg., trichinosisbite of insect vectors carrying infectious agents - eg., plaguebite of diseased animal - eg., rabiesbecause of their proximity to humans, domestic animals are the morecommon source of zoonoses (domestic animals may become infected bycontact with wild animals or their insect vectors)occupational risk for some professions - farmers, veterinarians, etc
3 Zoonotic InfectionsMethods of control for diseases in domestic animals that aretransmissible to humans:sacrifice or isolation of diseased and/or infected animalspasteurization of milkadequate cooking of meat before eatingvector controlvaccination of susceptible animalsDiagnosis requires either isolation of organisms or appropriate serology;pt history and clinical signs may be helpful but not sufficient tomake diagnosis
5 Yersiniabelongs to Enterobacteriaceae - gram negative rods, which fermentglucose and are oxidase negative3 species are pathogenic to manYersinia pestis = cause of plagueY. enterocolitica and Y. pseudotuberculosis = cause entercolitis (alsoknown as yersiniosis)Yersinia are small gram-negative coccobacilli which often demonstratebi-polar staining (safety-pin) using Giemsa or Wayson stainsY. pestis = non-motileY. enterocolitica and Y. pseudotuberculosis = motile at 25oC but not 37oC
6 Yersinia pestis = the plague bacillus 1. Epidemiology- infectious bacteria maintained in nature insylvatic cycle- involves rodents & rat flea (Xenopsylla cheopis)- involves ground squirrels in West, prairie dogsin the Southwest,and wood rats in South- urban plague begins when infected fleas of thesylvatic cycle infect animals living closerto humans, such as the rat- starts an urban cycle which increases riskto man
7 Genetic location and expression of virulence factors in Yersinia pestis.
8 Yersinia pestis = the plague bacillus 2. Antigenic structure- some of the major antigens are expressed on plasmids, while some onchromosome- F-1 antigen = capsule, antiphagocytic, expressed best at 37oC- V-W antigens and several Yersinia proteins (Yops) are plasmidgene products coordinately expressed at 37oC in the presence oflow Ca2+ concentrations; imp in resisting phagocytosis (V-W) as wellas intracellular survival and growth within macrophages; Yopsproteins form a type III secretion system for injecting severalYops proteins into eukaryotic cells which kills them- coagulase = clots blood in insect gut- LPS = may cause hemorrhage, vascular collapse and focal necrosis- Pla gene = plasminogen activator which degrades fibrin clots andC3b and C5a
9 Yersinia pestis = the plague bacillus 3. Clinical manifestations- Y. pestis causes human plague when bacteria are introduced into bodyby bite of infected flea. Rat fleas acquire organism during a bloodmeal on an infected rodent (usually the rat)- Y. pestis produces a coagulase which, at <27oC and with help of anenzyme in flea’s gut, clots the blood; this prevents flea fromgetting nourishment during the next feeding - regurgitates thebacteria into bite siteBubonic plague = spread of bacteria to regional lymph nodes (groin oraxillae) forming buboes (swollen, tender lymph nodes) which maysuppurate and drain; bacteria are found within macrophages innodes; septic shock with fatality rate is 75% if untreatedPneumonic plague = spread to lung can result in respiratory diseaseand aerosol dissemination; death due to respiratory failure(“Black Death”); ~100% fatal if not treated
10 Pathogenesis of Yersinia pestis in plague patients.
11 Plague: enlarged, tender inguinal lymph nodes in a Vietnamese child with bubonic plague.
12 Plague: advanced stage of inguinal lymphadenitis in bubonic plague. The nodes have undergone suppuration and the lesion has drained spontaneously.
13 Smear of lymph node aspirate from a case of bubonic plague showing many bi-polar staining Y. pestis (left, Wayson’s stain). Smear of peripheral bloodof patient with septicemic plague, showing bi-polar staining Y. pestis (right,van Gieson stain).
14 Yersinia pestis = the plague bacillus 4. Host defenses- production of specific anti-Fraction 1 antibodies will stimulatephagocytosis and promote killing by neutrophils- cell-mediated immunity will activate macrophages and assist inkilling facultative intracellular bacteria5. Diagnosis- need to isolate the causative agent - biopsy the bubo and culture6. Treatment- streptomycin, tetracycline or chloramphenicol7. Prevention and control- formalin-inactivated vaccine available for those travelling to endemicareas and those in high risk groups (only effective against bubonicplague)
15 Yersinia enterocolitica common cause of enterocolitisrodents, dogs, cats and domestic farm animals are natural hostsingestion of contaminated food or water, bacteria have affinity for Mcells in Peyer’s patches, traverse the mucosal membranes of gitract thru M cells, then grow in mesenteric lymph nodesfacultative intracellular bacteriahave many of the same genes of Y. pestis as well as invasin gene (inv)and ail (adherence invasion locus)enterocolitis = abdominal pain, diarrhea and fever; regional lymph-adenopathy; watery diarrhea due to heat-stable enterotoxinwhich stimulates cGMPoften self-limited; fluid and electrolytes if needed; TMP-SMZ andaminoglycosides if liver and spleen abscesses occur
16 Yersinia pseudotuberculosis causes an appendicitis-like syndromeingestion of contaminated food or water, bacteria have affinity for Mcells in Peyer’s patches, traverse the mucosal membranes of gitract thru M cells, then grow in mesenteric lymph nodesfacultative intracellular bacteriahave many of the same genes of Y. pestis as well as invasin gene (inv)and ail (adherence invasion locus)abdominal pain, regional lymphadenopathy; usually no diarrhea; symptomsof appendicitisTMP-SMZ, aminoglycosides, cephalosporins, and other drugs have beenused
17 Francisella non-motile gram-negative coccobacilli encapsulated F. tularensis causes tularemia or rabbit fever - spread to man directlyby ticks and deerflies; most strains which infects rabbits arehighly infectious to humans (could result from skinning rabbit, oreating infected rabbit meat, or bite of infected tick or deerfly)facultative intracellular pathogens in macrophages and monocytes
18 Francisella Clinical manifestations: - after 2-5 d incubation, organisms are multiplying in cells of RES,forming focal necrosis and small granulomas; signs and symptoms dependon how disease contracted:1. Ulceroglandular = most common; bacteria penetrates skin abrasion,produces local lesion which necrotizes and spreads to local lymphnodes with regional lymphadenopathy; could also be from tick bite2. Typhoidal = after ingestion of contaminated meat, severe typhoid-likedisease occurs, with local abscesses in Peyer’s patches andmesenteric lymph nodes; high fever and severe toxemia noted3. Oculogladular = infection via conjunctival membrane leads to swellingof eyelid, ulceration of conjunctiva and regional lymphadenopathy
19 Tularaemia: irregular ulcer at the site of the initiallesion.
20 Protection against Francisella tularensis or Yersinia pestis is cell-mediated.
21 FrancisellaDiagnosis = direct immunofluorescent antibody staining of bacteria ininfected tissues or blood; isolation and culture is dangerous forlab; serologic demonstration of rising antibody also used andis most common test usedTreatment = streptomycin or gentamicinControl = live attenuated vaccine used for lab workers; protectivegloves and goggles for hunters and trappers
22 Pasteurella 1. Characteristics - small gram-negative coccobacillus - bi-polar staining- encapsulated (A, B, D and E types; A most common)- most common strain is Pasteurella multocida2. Epidemiology- rabbits, cats and dogs carry these bacteria as normal flora of naso-pharynx and gingival crevices- cattle which carry these strains may develop fulminating hemorrhagicpneumonia when stressed or dehydrated (shipping fever); alsobeen seen in flocks of chickens and turkeys- rabbits gets snuffles (chronic nasopharyngeal infection)
23 Pasteurella 3. Pathogenesis - extracellular pathogens which resist phagocytosis due to capsule- LPS may contribute to tissue damage- pilus serves as adhesin- after entry thru skin due to animal bite, local colonization ismediated thru pilus at wound site, with spread to regionallymph nodes; acute inflammatory response follows butbacteria resist ingestion due to capsule4. Clinical manifestations- P. multocida typically is seen in infected cat and dog bites, withlocalized inflammation at the site with abscess formation andregional lymphadenopathy; osteomyelitis is a seriouscomplication of this disease
24 Protection against Pasteurella multocida is mediated by opsonic antibodies.
25 PasteurellaDiagnosis: should suspect this organism in any infected cat or dog bite;isolate organism from abscess and cultureTreatment: penicillin, tetracycline or chloramphenicol used to treatabscesses; prolonged treatment needed; abscess should bedrainedControl: no effective vaccine available; ampicillin can be usedprophylactically
26 BrucellaImp cause of disease of cattle, goats, pigs, etc. usually affecting theirreproductive organs leading to abortion, sterility and decreased milkproduction. Humans infected thru contact with diseased animals, causean acute febrile disease (undulant fever) or a more chronic processwhich may have wide array of symptomsCharacteristics:- gram-negative coccobacillus, no capsule- slow growers, aerobic, catalase and oxidase positiveB. melitensis = goats and sheepB. abortus = cattleB. suis = pigsB. canis = dogs (infrequent cause of human infections)Important source of disease for humans
27 BrucellaPredilection of brucellae for reproductive organs of ruminants due topresence of erythritol in amniotic and allantoic fluid - leads to abortionshedding huge numbers of bacteria; bacteria also establish themselvesin mammary glands, infecting milk (animals usually show no symptoms).Humans become infected by handling these animals or drinking contaminatedmilk.Brucellosis is relatively uncommon in US ( cases/yr due to animalvaccination) but endemic in many parts of world
29 Brucella Pathogenesis: - brucellae gain entrance thru broken skin, by ingestion or thru conjunctiva;carried to liver, spleen and bone marrow by lymphatics; are facultativeintracellular pathogens multiplying in RES- intracellular multiplication induces chronic inflammatory response char.by tissue lesions with minute granulomas composed of epitheliod cells,PMNs, lymphocytes and some giant cells, usu. in spleen and bone marrowClinical manifestations:- 2-4 wk incubation- onset is influenza-like, with fever, severe arm and muscle pain, sweatingand fatigue; disease may continue for weeks with fever and symptomsrising and falling in 10 d intervals (undulant fever) - most pts recoverin 3-12 months- some pts develop chronic infections with arthritis, meningitis, etc.- abortion is not seen in humans
30 Brucella Host defenses: CMI is most important Diagnosis: isolation from blood, lymph nodes and bone marrow aspirates;requires special media; serological results are often only test whichmakes diagnosisPrevention/control: live attenuated vaccines for animals; pasteurize milk;animals which are infected should be sacrificed to protect herdTreatment: combination of doxycycline and rifampin, doxycyline andgentamicin, or TMP-SMZ for pregnant women and children
31 “LEPTOSPIRA” Tightly coiled aerobic spirochete Leptospirosis (or Weil’s disease) is a zoonosis caused by pathogenic species of leptospira, Leptospira interrogans. Saprophytic strains are called L. biflexa.Characteristics:Tightly coiled aerobic spirochete-oxidation of fatty acidscan be grown in medium with rabbit serum (Fletcher’s medium)
32 Leptospira interrogans serotype icterohaemorrhagiae. Silver staining of organisms grown in culture. Notice the tightly coiled body with hooked ends.
34 Leptospira Pathogenesis: - zoonosis of rats, dogs, cats, horses, cattle and pigs- animals which develop carrier state shed leptospira in urine (evenimmunized dogs might shed organisms)- leptospires colonize kidney tubules of animals to produce a chroniccarrier state- man becomes infected with contact with urine-contaminated soiland water (often swimming or ingestion of contaminated foodor water)- leptospires enter thru mucous membranes or skin abrasions, thenspreads thru blood to all tissues- tissue damage is to endothelium of small vessels - mech unknownno LPS or toxins- greatest risk of infection is to those whose occupation brings themin most contact with animals
36 Leptospira Clinical manifestations: - biphasic disease with involvement of the CNS, kdiney and liver- 5-13% of aseptic meningitis due to leptsopires- Weil’s syndrome = severe form of leptospirosis characterized byjaundice, renal damage and interstitial nephritis
37 LeptospiraImmunity: humoral antibody response is needed for host defenseDiagnosis: serology more common than isolation and culture; a microscopicagglutination test is done using pool of leptospiral antigens and ptserum and agglutination determined by microscopy- can isolate or detect leptospira in blood or CSF early indisease, while later, most leptospires are present in urineTreatment: penicillin or doxycycline is effective if given during 1stphase of disease; animal vaccine is used for most animals atrisk of infection