Animal- and arthropod-transmitted diseases Dec 6, 2006 Ch. 27 Galán and Wolf-Watz review Plague • Infectious disease of animals and humans • Caused by a bacterium named Yersinia pestis • People usually get plague from being bitten by a rodent flea that is carrying the plague bacterium • Antibiotics are effective against plague, but if an infected person is not treated promptly, the disease is likely to cause illness or death Epidemiology • Wild rodents in certain areas are infected with plague • Outbreaks usually associated with infected rats and rat fleas (Xenopsylla cheopis) • Globally, the WHO reports 1,000 to 3,000 cases of plague each year http://www.cdc.gov/ncidod/dvbid/plague History of plague • First pandemic spread from Egypt to Europe, Africa, and Asia 542-600 • Second pandemic known as the Black Death spread from Asia to Europe in the 1300s http://bubonicplague.quickseek.com/ Natural history • Epidemics usually involve rats • Last rat-borne epidemic in the US occurred in Los Angeles in 1924-25 • Since then, all human cases in the U.S. have been sporadic cases acquired from wild rodents • Rock squirrels and their fleas are the most frequent sources of human infection in the southwestern states Courtesy of Diliff. www.mammalogy.org Geographic distribution • Averages about 18 cases per year in US • Mostly in people < 20 years of age • About 1 in 7 persons will die • Epidemic plague occurs Africa, Asia, & South America associated with domestic rats Forms of disease • Bubonic plague – enlarged, tender lymph nodes, fever, chills and prostration • Septicemic plague – fever, chills, prostration, abdominal pain, shock and bleeding into skin and other organs • Pneumonic plague – fever, chills, cough and difficulty breathing; rapid shock and death if not treated early www.cdc.gov/ncidod/dvbid/plague Diagnosis of plague • Painful, swollen lymph node, called a bubo • Onset usually 2-6 days after exposure • Disease progresses rapidly and bacteria invade the bloodstream, producing severe illness, called plague septicemia • Progression leads to lung infection or plague pneumonia • Incubation period of primary pneumonic plague is 1-3 days – Characterized by overwhelming pneumonia with high fever, cough, bloody sputum, and chills – Mortality rate > 50% Treatment • As soon as a diagnosis of suspected plague is made, the patient should be isolated, and local and state health departments should be notified • The drugs of choice are streptomycin or gentamicin, but a number of other antibiotics are also effective • Those individuals closely associated with the patient, particularly in cases with pneumonia, should be traced, identified, and evaluated Prevention • Epidemic plague is best prevented by controlling rat populations in both urban and rural areas • In regions where plague is widespread in wild rodents, the greatest threat is to people living, working, or playing in areas where the infection is active – Eliminate food and shelter for rodents – Surveillance in wild rodent populations – Use of appropriate insecticides to kill fleas The bacterium • Gram negative facultative anaerobe • Formerly classified in the family Pasteurellaceae, but based on DNADNA hybridization member of the Enterobacteriaceae family • 11 named species, but only 3 are human pathogens – Y. pestis, the etiologic agent of plague – Y. pseudotuberculosis and Y. enterocolitica http://www.cdc.gov/ncidod/dvbid/plague Diagram removed due to copyright restrictions. Zhou et al. Microbes Infect 6:1226-34, 2004. Invasion • Enteropathogenic Yersinia species invade cultured mammalian cells • Mediated by inv gene product invasin • Outer membrane protein binds β1 integrins Bacterium Bacterium Bacterium D2 Invasin Integrin No Signaling Signaling Signaling A. Low substrate density B. High substrate density C. Substrate dimerization Figure by MIT OCW. Isberg and Barnes, J Cell Sci 114:21-28, 2001. Image removed due to copyright restrictions. Neutra et al. Nature Immunol 2:1004-9, 2001. O ORRF4 OR F5 8 F4 7 1 ORF3 6 O RF 38 ORF 39 exo A OR F42 ex oB O O RF IS RF4 44 20 5 0 ORF33A repA ORF33 ORF32 ORF31 ORF29 HflC-like lI po recA 5 ORF2 3 2 ORF -like pprB 21 ORF F18 OR 17 F OR A DN II co bS co 3 F5 OR 4 e F5 55 lik OR RF ssorO re 7 p 5 re RF 58 O RF 9 O RF5 O ike ke p-l Re J-like orter-li o p S ansp r t ABC F64 OR F65 OR 66 ORF 8 ORF6 ke T4 gene 17-li 100000 bT OR OR F14 F1 3 inte gra se 10 rep region 00 0 90 00 0 caf1 caf1A caf1R ORF4 00 3000 IS100 IS100 e lik abd lam e aM -li 40 00 ke -li ike a L K-l bd m da la mb la bd ke aI -li ke 0 00 0 60 50000 e -lik 314 IS285 ORF100 ke -li F OR 6000 aJ 0 F9 p O OR arA re RF1 F11 so 1 2 l 2 OR vas A F e OR 110 F1 09 OR mu F10 rin 8 e OR F10 toxin 6A OR OR F10 F10 5 6 ORF ORF1 103A 04 ORF1 0 ORF 3 102 lik bd OR 5000 bda 4000 H- bd lam 3000 lam m 1A ORF9 a G-like lambd IS100 IS100 ORF95ORF96 ORF97 ORF98 2000 bda la ORF99 1000 lam lam 1 F13 OR n o i t c ri 7 rest anti RF12 6 O F12 5 ORRF12 lase y O A th 2 23 me F12 9 F1 1 R R O RF1 16 O O F1 OR 15A F1 5 rB ORF11 pa R O 0 700 135 0 ORF71 ORF72 ORF73 ORF74A L12-like ORF76 ORF7 OR 7 ORFF78 lamb 80 OR da V-like ORFF81 82 pMT1 T3 ligase ORF ORF70 0 8000 0 2000 caf1M 7000 8000 9000 10000 Transposase IS100 ColE1 replicon Pesticin Pesticin immunity protein Plasminogen activator Hu et al. J Bacteriol 180:5192-5202, 1998 Figure by MIT OCW. Images removed due to copyright restrictions. Jarrett et al. J Infect Dis 190:783-92, 2004. Image removed due to copyright restrictions. Hu et al. J Bacteriol 180:5192-5202, 1998 Images removed due to copyright restrictions. Figures 1 and 2 in "THE YERSINIA YSC–YOP 'TYPE III' WEAPONRY," Nature Reviews Molecular Cell Biology 3, 742-754 (2002). Cornelis Nature Rev Mol Cell Biol 3:742-754, 2002