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Monkeypox: Outbreak in the US. Rashid A. Chotani , MD, MPH Assistant Professor, School of Medicine & Public Health Center for International Emergency, Disaster & Refugee Studies Director, Global Infectious Disease Surveillance & Alert System

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Monkeypox outbreak in the us l.jpg

Monkeypox: Outbreak in the US

Rashid A. Chotani, MD, MPH

Assistant Professor, School of Medicine & Public Health

Center for International Emergency, Disaster & Refugee Studies

Director, Global Infectious Disease Surveillance & Alert System

Johns Hopkins School of Medicine & Public Health

410-614-8330


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Monkeypox

Dr. Stephen Ostroff, deputy director of the National Center for Infectious Diseases, Centers for Disease Control and Prevention answers a question during a teleconference at the CDC headquarters in Atlanta Monday, June 9, 2003

Monkeypox is a virus that health officials say has infected at least four people in the Midwest and possibly dozens more.

Officials suspect they caught the illness from exposure to pet prairie dogs.

The disease has never before been reported in the Western Hemisphere. It is usually found in remote villages in central and west Africa.


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Monkeypox: Background

  • The human monkeypox is caused by a virus belonging to the genus Orthopoxvirus

  • The virus was isolated from primate tissues in 1958

  • In 1970, human monkeypox was identified the Democratic Republic of Congo (DRC)

  • Zoonotic outbreaks were subsequently observed in the US and Europe but monkeypox was not considered a threat to humans


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Monkeypox: Background

  • Mass vaccination and then targeted vaccination in conjunction with surveillance resulted in the elimination of smallpox in 1977

  • In 1980, after certification activates, the World Health Organization (WHO), declared smallpox eradicated.

  • By 1985, except military personnel and laboratory workers exposed to orthopox virus’s smallpox vaccine was not administered to anyone


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Monkeypox: Background

  • Monkeypox clinically causes a smallpox-like disease (pustular rash, fever, respiratory symptoms) except for marked lymphadenopathy in humans but varies biologically and epidemiologically


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Monkeypox: Background

  • Incubation period is between 7 to 17 days and the disease is characterized by the onset of a

    • prodrome of fever,

    • headache,

    • backache, and

    • fatigue.

  • The rash follows the four stage progression of

    • vesiculation,

    • pustulation,

    • umbilication, and

    • encrustation evolving in the same stage over 14-21 days.


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Monkeypox: Background

  • The pocks concentrate mainly on the face, arms and legs.

  • The main source of disease transmission are animal reservoirs but person-to-person transmission has been recorded.


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Monkeypox: Background

  • The overall case-fatality in Africa has been reported to be between 1%-10%, with as high as 17% in the Democratic Republic of Congo.

  • A majority of the cases appear in children under the age of 15 years and the mortality in this age group is much higher


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Monkeypox: Epidemiology


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Monkeypox – the evolving outbreak

June 15, 2003:

  • 53 Total Suspected Cases

  • 3 States Involved

  • 12 cases confirmed

  • Monkeypox, a virus similar to smallpox, apparently jumped from possibly an imported giant Gambian rat, which is indigenous to Africa, at a Chicago-area pet distributor to pet prairie dogs.


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Monkeypox – the evolving outbreak

June 15, 2003:

  • The total number of suspected victims has risen to 53

  • Three states involved in the outbreak

    • Wisconsin (17 possible cases)

    • Indiana (25 possible cases)

    • Illinois (11 possible cases)


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Monkeypox – the evolving outbreak

June 15

  • Confirmed Cases = 12

    • Indiana 4

    • Wisconsin 4

    • Illinois 4


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Monkeypox – the evolving outbreak

  • Of the 53 cases,

    • 29 (49%) cases were among males;

    • the median age was 26 years (range: 4 to 53 years).

    • Data were unavailable for sex and age for 2 and 14 patients, respectively.

    • A total of 14 (26%) patients have been hospitalized, including a child aged <10 years with encephalitis.


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Monkeypox – the evolving outbreak

  • Clinical information from 30 cases reported in Illinois and Wisconsin

    • The earliest reported onset of illness was on 15 May 2003.

    • 73% (22) of the patients had a febrile illness which either preceded or accompanied the onset of a papular rash;

    • 64% (16) had respiratory symptoms,

    • 47% (14) had lymphadenopathy and

    • 33% (10) had sore throat.


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Monkeypox: Clinical Features in the US

Source: MMWR, CDC


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Monkeypox – the evolving outbreak

  • The rash typically progressed through stages of

    • vesiculation,

    • pustulation,

    • umbilication, and

    • encrustation.


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Monkeypox – the evolving outbreak

  • Early lesions became ulcerated in some patients.

  • Rash distribution and lesions have occurred on the

    • head,

    • trunk, and

    • extremities;

  • many patients had initial and satellite lesions on

    • palms,

    • soles, and

    • extremities.

  • Rashes were generalized in some patients.


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Negative strain electron micrograph of Monkeypox virus identified in vesicle fluid from an infected patient within the Wisconsin 2003 outbreak. Morphologic features of viruses in clinical specimen are often less distinct than cell culture isolate. Bar – 100nm.

Source: CDC


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US Outbreak: Epicurve

Source: MMWR, CDC


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Child: Secondary lesions 5/27/03, adjacent to primary inoculation site on left hand

Source: Reed at el. Marshfield Clinic


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Child, Marshfield Index Case: Primary inoculation site right index finger, 5/27/03. 14 days after prairie dog bites, 11 days post febrile illness, hospital day 5

Source: Reed at el. Marshfield Clinic


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Child: Disseminated acral lesions 5/27/03

Source: Reed at el. Marshfield Clinic


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Mother, 5/27/03, I day after vesicles & erythema at site of cat scratch. Sweats, fever, and malaise the night of 5/26/03. Had sore throat.

Source: Reed at el. Marshfield Clinic


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Mother: 05/29/03, expansion of vesicles beyond biopsy site of 05/27/03. Note satellite vesicles.

Source: Reed at el. Marshfield Clinic


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Father, 06/05/03, after fevers, sweats, malaise on 05/31-06/01/03. Feels well.

Source: Reed at el. Marshfield Clinic


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Father, 06/05/03

Source: Reed at el. Marshfield Clinic


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Monkeypox

  • Everyone who has caught it has been in close contact with the animals.

  • The rest of the victims were in families that purchased the animals.

  • One caught it from a rabbit that had been in contact with a sick prairie dog.


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A giant Gambian rat curls up in it's cage at Chicago's Lincoln Park Zoo Monday, June 9, 2003. Federal health officials are investigating four confirmed cases of monkeypox which they say are likely linked to a Gambian rat from Chicago-area pet distributor. (AP Photo/Aynsley Floyd)


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Monkeypox

  • Fear - that the virus will obtain a permanent foothold in the United States, much as West Nile virus did after a case was identified in New York City in 1999.

  • West Nile virus spread

    from coast to coast,

    infecting nearly 4200.


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Monkeypox

  • The Centers for Disease Control and Prevention (CDC) has issued interim Guidance for Use of Smallpox Vaccine, Cidofovir, and Vaccinia Immune Globulin (VIG) for prevention and treatment in the setting of outbreak of monkeypox.

  • They can be found at the following link:

    http://www.cdc.gov/ncidod/monkeypox/treatmentguidelines.htm


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Monkeypox

  • The CDC and Food and Drug Administration (FDA) has imposed embargo on export of all rodents from Africa as well as prohibitions in terms of transporting, sale, distribution or release in the environment of prairie dogs as well as African rodents including

    • tree squirrels (Heliosciurus sp.),

    • rope squirrels (Funisciurus sp.),

    • dormice (Graphiurus sp.),

    • Gambian giant pouched rats (Cricetomys sp.),

    • brush-tailed porcupines (Atherurus sp.), and

    • striped mice (Hybomys sp.).

  • Detailed guidelines are available at the following links:

    http://www.dhfs.state.wi.us/dph_bcd/monkeypox/Response.htm

    http://www.idph.state.il.us/pdf/ExecutiveOrder14.pdf


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Monkeypox

With the emergence of novel pathogens like Nipahvirus, Hantavirus, Ebola, Marburg, H5N1 (avian flu), SARS and now monkeypox, at times in unlikely geographic areas, serves a reminder that scary pathogens continue to emerge.


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Monkeypox

Resources need to be allocated for enhancing the global and national infectious disease surveillance capacity as well as active research on emerging and re-emerging infectious disease.


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Selected reading on Monkeypox

  • Marennikova SS, Seluhina EM, Mal'ceva NN, Cimiskjan KL, Macevic GR. Isolation and properties of the causal agent of a new variola-like disease (monkeypox) in man. Bull World Health Organ 1972;46:599-611.

  • Arita I, Jezek Z, Khodakevich L, Ruti K. Human monkeypox: a newly emerged orthopoxvirus zoonosis in the tropical rain forests of Africa. Am J Trop Med Hyg 1985;34:781-9.

  • Jezek Z, Fenner F. Human monkeypox. In: JL Melnick, editor. Monographs in virology. Volume 17. Basel: Karger; 1988.

  • von Magnus P, Andersen EK, Petersen KB, Birch-Andersen A. A pox-like disease in cynomolgus monkeys. Acta Pathol Microbiol Scand 1959;46:156-76.

  • Khodakevich L, Jezek Z, Messinger D. Monkeypox virus: ecology and public health significance. Bull World Health Organ 1988;66:747-52.

  • Khodakevich L, Szczeniowski M, Manbu-ma-Disu, Jezek Z, Marennikova S, Nakano J, et al. The role of squirrels in sustaining monkeypox virus transmission. Trop Geogr Med 1987;39:115-22.


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Selected reading on Monkeypox

  • Fine PE, Jezek Z, Grab B, Dixon H. The transmission potential of monkeypox virus in human populations. Int J Epidemiol 1988;17:643-50.

  • Jezek Z, Grab B, Szczeniowski MV, Paluku KM, Mutombo M. Human monkeypox: secondary attack rates. Bull World Health Organ 1988;66:465-70.

  • Jezek Z, Arita I, Mutombo M, Dunn C, Nakano JH, Szezeniowski M. Four generations of probable person-to-person transmission of human monkeypox. Am J Epidemiol 1986;123:1004-12.

  • Mukinda VB, Mwema G, Kilundu M, Heymann DL, Khan AS, Esposito JJ. Re-emergence of human monkeypox in Zaire in 1996. Lancet 1997;349:1449-50.

  • Centers for Disease Control and Prevention. Human monkeypox- Zaire, 1996-1997. MMWR Morb Mortal Wkly Rep 1997;46:304-7.


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Selected reading on Monkeypox

  • Mills JN, Childs JE, Ksiazek TG, Peters CJ, Velleca WM. Methods for trapping and sampling small mammals for virologic testing. Atlanta: Centers for Disease Control and Prevention; 1995.

  • Esposito JJ, Massung RF. Poxvirus infections in humans. In: Murray PR, Tenover F, Baron EJ, Pfaller MA, Yolken RH, editors. Manual of clinical microbiology. 6th ed. Washington: ASM Press;1995. p. 1131-8.

  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 1979;76:4350-4.

  • Loparev VN, Parsons JM, Knight JC, Panus JF, Ray CA, Buller RM, et al. A third distinct tumor necrosis factor receptor of orthopoxviruses. Proc Natl Acad Sci U S A 1998;95:3786-91.


Selected reading on monkeypox38 l.jpg

Selected reading on Monkeypox

  • Ropp SL, Esposito JJ, Loparev VN, Palumbo G. Poxviruses infecting humans. In: Murray PR, Barron CJ, Pfaller MA, Tenover FC, Yolken RH, editors. Manual of clinical microbiology. 7th ed. Washington: ASM Press; 1999. p. 1137-44.

  • Ropp SL, Jin Q, Knight JC, Massung RF, Esposito JJ. PCR strategy for identification and differentiation of smallpox and other orthopoxviruses. J Clin Microbiol 1995;33:2069-76.

  • Esposito JJ, Knight JC. Orthopoxvirus DNA: a comparison of restriction profiles and maps. Virology 1985;143:230-51.

  • Jezek Z, Szczeniowski M, Paluku KM, Mutombo M, Grab B. Human monkeypox: confusion with chickenpox. Acta Trop 1988;45:297-307.

  • Centers for Disease Control and Prevention. Human monkeypox--Kasai Oriental, Democratic Republic of Congo, February 1996-October 1997. MMWR Morb Mortal Wkly Rep 1997;46:1168-71.


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Selected reading on Monkeypox

  • Dean AG, Dean JA, Coulombier D, Burton AH, Brendel KA, Smith DC. Epi Info, version 6: A word-processing, database, and statistics program for public health on IBM-compatible microcomputers. Atlanta: Centers for Disease Control and Prevention; 1994.

  • Fenner F, Wittek R, Dumbell KR. The Orthopoxviruses. San Diego: Academic Press; 1989. p. 162-5, 312-15.

  • Ziegler DW, Hutchinson HD, Koplan JP, Nakano JH. Detection by radioimmunoassay of antibodies in human smallpox patients and vaccinees. J Clin Microbiol 1975;1:311-7.

  • Cherry JD, McIntosh K, Connor JD, Benenson AS, Alling DW, Rolfe UT, et al. Primary percutaneous vaccination. J Infect Dis 1977;135:145-54.

  • McIntosh K, Cherry JD, Benenson AS, Connor JD, Alling DW, Rolfe UT, et al. Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary percutaneous vaccination. J Infect Dis 1977;135:155-66.


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