GIDSAS Chotani, 2003 Monkeypox: Outbreak in the US Monkeypox: Outbreak in the US Rashid A. Chotani Rashid A. Chotani, MD, MPH Rashid A. Chotani Assistant.

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Chotani, 2003Chotani, 2003

Monkeypox: Monkeypox: Outbreak in the USOutbreak in the US

Rashid A. Chotani, MD, MPH, MD, MPHAssistant Professor, School of Medicine & Public HealthAssistant Professor, School of Medicine & Public Health

Center for International Emergency, Disaster & Refugee StudiesCenter for International Emergency, Disaster & Refugee StudiesDirector, Global Infectious Disease Surveillance & Alert SystemDirector, Global Infectious Disease Surveillance & Alert System

Johns Hopkins School of Medicine & Public HealthJohns Hopkins School of Medicine & Public Health410-614-8330410-614-8330

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MonkeypoxMonkeypox

Dr. Stephen Ostroff, deputy director of the Dr. Stephen Ostroff, deputy director of the National Center for Infectious Diseases, Centers National Center for Infectious Diseases, Centers for Disease Control and Prevention answers a for Disease Control and Prevention answers a question during a teleconference at the CDC question during a teleconference at the CDC headquarters in Atlanta Monday, June 9, 2003 headquarters in Atlanta Monday, June 9, 2003 Monkeypox is a virus that health officials say has Monkeypox is a virus that health officials say has infected at least four people in the Midwest and infected at least four people in the Midwest and possibly dozens more. possibly dozens more. Officials suspect they caught the illness from Officials suspect they caught the illness from exposure to pet prairie dogs. exposure to pet prairie dogs. The disease has never before been reported The disease has never before been reported in the Western Hemisphere. It is usually in the Western Hemisphere. It is usually found in remote villages in central and west found in remote villages in central and west Africa. Africa.

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Monkeypox: Monkeypox: BackgroundBackground

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

The virus was isolated from primate The virus was isolated from primate tissues in 1958 tissues in 1958

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

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

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Mass vaccination and then targeted Mass vaccination and then targeted vaccination in conjunction with vaccination in conjunction with surveillance resulted in the surveillance resulted in the elimination of smallpox in 1977 elimination of smallpox in 1977 In 1980, after certification activates, In 1980, after certification activates, the World Health Organization (WHO), the World Health Organization (WHO), declared smallpox eradicated. declared smallpox eradicated. By 1985, except military personnel By 1985, except military personnel and laboratory workers exposed to and laboratory workers exposed to orthopox virus’s smallpox vaccine orthopox virus’s smallpox vaccine was not administered to anyone was not administered to anyone

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

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

prodrome of fever, prodrome of fever, headache, headache, backache, and backache, and fatigue. fatigue.

The rash follows the four stage The rash follows the four stage progression of progression of

vesiculation, vesiculation, pustulation, pustulation, umbilication, and umbilication, and encrustation evolving in the same stage over encrustation evolving in the same stage over 14-21 days. 14-21 days.

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

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

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

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

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Monkeypox: Monkeypox: EpidemiologyEpidemiology

1970-801970-80 1981-861981-86 1996-971996-97 20012001 TotalTotal

No. of casesNo. of cases 4747 338338 344344 23*23* 752752

No. of deaths No. of deaths 88 3333 55 55 5151

Case-fatality-rate (%) Case-fatality-rate (%) 1717 9.89.8 1.51.5 1717 6.86.8

Secondary cases No. and (%)Secondary cases No. and (%) 4 (9)4 (9) 93 (28)93 (28) 268 (78)268 (78)

Secondary attack-rate among Secondary attack-rate among close susceptible contacts close susceptible contacts (%)(%)

3/40 3/40 (7.5)(7.5)

99 2323

Secondary attack-rate among Secondary attack-rate among family members not family members not vaccinated (%)vaccinated (%)

4/123 4/123 (3.3)(3.3)

9.39.3 2626

Cases in <15 years (%)Cases in <15 years (%) 40 (85)40 (85) 189 189 (93)**(93)**

8383

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Monkeypox – the evolving Monkeypox – the evolving outbreakoutbreak

June 15, 2003: June 15, 2003: 53 Total Suspected Cases53 Total Suspected Cases3 States Involved3 States Involved12 cases confirmed12 cases confirmedMonkeypox, a virus similar to Monkeypox, a virus similar to smallpox, apparently jumped smallpox, apparently jumped from possibly an imported from possibly an imported giant Gambian rat, which is giant Gambian rat, which is indigenous to Africa, at a indigenous to Africa, at a Chicago-area pet distributor Chicago-area pet distributor to pet prairie dogs.to pet prairie dogs.

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June 15, 2003: June 15, 2003:

The total number of The total number of suspected victims has risen suspected victims has risen to 53to 53

Three states involved in the outbreak

Wisconsin (17 possible cases)

Indiana (25 possible cases)

Illinois (11 possible cases)

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June 15 June 15

Confirmed Cases = 12Confirmed Cases = 12Indiana 4Indiana 4

Wisconsin 4Wisconsin 4

Illinois 4Illinois 4

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Of the 53 cases, Of the 53 cases, 29 (49%) cases were among males; 29 (49%) cases were among males;

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

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

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


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Clinical information from 30 cases Clinical information from 30 cases reported in Illinois and Wisconsinreported in Illinois and Wisconsin

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

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

64% (16) had respiratory symptoms, 64% (16) had respiratory symptoms,

47% (14) had lymphadenopathy and 47% (14) had lymphadenopathy and

33% (10) had sore throat. 33% (10) had sore throat.


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Monkeypox: Clinical Features Monkeypox: Clinical Features in the USin the US

Source: MMWR, CDCSource: MMWR, CDC

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The rash typically progressed through The rash typically progressed through stages of stages of

vesiculation, vesiculation,

pustulation, pustulation,

umbilication, and umbilication, and

encrustation. encrustation.


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Early lesions became ulcerated in some Early lesions became ulcerated in some patients. patients. Rash distribution and lesions have occurred Rash distribution and lesions have occurred on the on the

head, head, trunk, and trunk, and extremities; extremities;

many patients had initial and satellite lesions many patients had initial and satellite lesions on on

palms, palms, soles, and soles, and extremities.extremities.

Rashes were generalized in some patients.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: US Outbreak: EpicurveEpicurve

Source: MMWR, CDCSource: 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


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Child: Disseminated acral lesions 5/27/03


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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.


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

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


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Father, 06/05/03

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MonkeypoxMonkeypox

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

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

One caught it from a rabbit that had One caught it from a rabbit that had been in contact with a sick prairie dog. 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 A giant Gambian rat curls up in it's cage at Chicago's Lincoln Park Zoo Monday, June 9, 2003. Federal health Lincoln Park Zoo Monday, June 9, 2003. Federal health

officials are investigating four confirmed cases of officials are investigating four confirmed cases of monkeypox which they say are likely linked to a monkeypox which they say are likely linked to a

Gambian rat from Chicago-area pet distributor. Gambian rat from Chicago-area pet distributor. (AP Photo/Aynsley Floyd) (AP Photo/Aynsley Floyd)

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MonkeypoxMonkeypox

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

from coast to coast, from coast to coast, infecting nearly 4200.infecting nearly 4200.

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MonkeypoxMonkeypox

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

tree squirrels (tree squirrels (HeliosciurusHeliosciurus sp.), sp.), rope squirrels (rope squirrels (FunisciurusFunisciurus sp.), sp.), dormice (dormice (GraphiurusGraphiurus sp.), sp.), Gambian giant pouched rats (Gambian giant pouched rats (CricetomysCricetomys sp.), sp.), brush-tailed porcupines (brush-tailed porcupines (AtherurusAtherurus sp.), and sp.), and striped mice (striped mice (HybomysHybomys sp.). sp.).

Detailed guidelines are available at the following links:Detailed guidelines are available at the following links:http://www.dhfs.state.wi.us/dph_bcd/monkeypox/Response.htmhttp://www.dhfs.state.wi.us/dph_bcd/monkeypox/Response.htm

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

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MonkeypoxMonkeypox

With the emergence of novel With the emergence of novel pathogens like Nipahvirus, pathogens like Nipahvirus,

Hantavirus, Ebola, Marburg, H5N1 Hantavirus, Ebola, Marburg, H5N1 (avian flu), SARS and now (avian flu), SARS and now

monkeypox, at times in unlikely monkeypox, at times in unlikely geographic areas, serves a reminder geographic areas, serves a reminder

that scary pathogens continue to that scary pathogens continue to emerge. emerge.

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MonkeypoxMonkeypox

Resources need to be allocated Resources need to be allocated for enhancing the global and for enhancing the global and national infectious disease national infectious disease

surveillance capacity as well as surveillance capacity as well as active research on emerging and active research on emerging and re-emerging infectious disease.re-emerging infectious disease.

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Selected reading on MonkeypoxSelected reading on MonkeypoxMarennikova SS, Seluhina EM, Mal'ceva NN, Cimiskjan KL, Macevic GR. 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. Bull World Health Organ 1972;46:599-611. Arita I, Jezek Z, Khodakevich L, Ruti K. 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. Am J Trop Med Hyg 1985;34:781-9. Jezek Z, Fenner F. Human monkeypox. In: JL Melnick, editor. Monographs in Jezek Z, Fenner F. Human monkeypox. In: JL Melnick, editor. Monographs in virology. Volume 17. Basel: Karger; 1988. virology. Volume 17. Basel: Karger; 1988. von Magnus P, Andersen EK, Petersen KB, Birch-Andersen A. A pox-like von Magnus P, Andersen EK, Petersen KB, Birch-Andersen A. A pox-like disease in cynomolgus monkeys. Acta Pathol Microbiol Scand 1959;46:156-disease in cynomolgus monkeys. Acta Pathol Microbiol Scand 1959;46:156-76. 76. Khodakevich L, Jezek Z, Messinger D. Khodakevich L, Jezek Z, Messinger D. Monkeypox virus: ecology and public health significance. Bull World Health Bull World Health Organ 1988;66:747-52. Organ 1988;66:747-52. Khodakevich L, Szczeniowski M, Manbu-ma-Disu, Jezek Z, Marennikova S, Khodakevich L, Szczeniowski M, Manbu-ma-Disu, Jezek Z, Marennikova S, Nakano J, et al. Nakano J, et al. The role of squirrels in sustaining monkeypox virus transmission. Trop Geogr Med 1987;39:115-22. Trop Geogr Med 1987;39:115-22.

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Selected reading on MonkeypoxSelected reading on MonkeypoxFine PE, Jezek Z, Grab B, Dixon H. Fine PE, Jezek Z, Grab B, Dixon H. The transmission potential of monkeypox virus in human populations. Int J Epidemiol 1988;17:643- Int J Epidemiol 1988;17:643-50. 50. Jezek Z, Grab B, Szczeniowski MV, Paluku KM, Mutombo M. Jezek Z, Grab B, Szczeniowski MV, Paluku KM, Mutombo M. Human monkeypox: secondary attack rates. Bull World Health Organ Bull World Health Organ 1988;66:465-70. 1988;66:465-70. Jezek Z, Arita I, Mutombo M, Dunn C, Nakano JH, Szezeniowski M. 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. Am J Epidemiol 1986;123:1004-12. Mukinda VB, Mwema G, Kilundu M, Heymann DL, Khan AS, Mukinda VB, Mwema G, Kilundu M, Heymann DL, Khan AS, Esposito JJ. Esposito JJ. Re-emergence of human monkeypox in Zaire in 1996. Lancet 1997;349:1449-50. Lancet 1997;349:1449-50. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. Human monkeypox- Zaire, 1996-1997. MMWR Morb Mortal Wkly Rep 1997;46:304-7. MMWR Morb Mortal Wkly Rep 1997;46:304-7.

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Selected reading on MonkeypoxSelected reading on MonkeypoxMills JN, Childs JE, Ksiazek TG, Peters CJ, Velleca WM. Mills JN, Childs JE, Ksiazek TG, Peters CJ, Velleca WM. Methods for trapping and sampling small mammals for Methods for trapping and sampling small mammals for virologic testing. Atlanta: Centers for Disease Control and virologic testing. Atlanta: Centers for Disease Control and Prevention; 1995. Prevention; 1995. Esposito JJ, Massung RF. Poxvirus infections in humans. In: Esposito JJ, Massung RF. Poxvirus infections in humans. In: Murray PR, Tenover F, Baron EJ, Pfaller MA, Yolken RH, Murray PR, Tenover F, Baron EJ, Pfaller MA, Yolken RH, editors. Manual of clinical microbiology. 6th ed. Washington: editors. Manual of clinical microbiology. 6th ed. Washington: ASM Press;1995. p. 1131-8. ASM Press;1995. p. 1131-8. Towbin H, Staehelin T, Gordon J. 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. Proc Natl Acad Sci U S A 1979;76:4350-4. Loparev VN, Parsons JM, Knight JC, Panus JF, Ray CA, Loparev VN, Parsons JM, Knight JC, Panus JF, Ray CA, Buller RM, et al. Buller RM, et al. A third distinct tumor necrosis factor receptor of orthopoxviruses. Proc Natl Acad Sci U S A 1998;95:3786-91. Proc Natl Acad Sci U S A 1998;95:3786-91.

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Selected reading on MonkeypoxSelected reading on MonkeypoxRopp SL, Esposito JJ, Loparev VN, Palumbo G. Poxviruses Ropp SL, Esposito JJ, Loparev VN, Palumbo G. Poxviruses infecting humans. In: Murray PR, Barron CJ, Pfaller MA, Tenover infecting humans. In: Murray PR, Barron CJ, Pfaller MA, Tenover FC, Yolken RH, editors. Manual of clinical microbiology. 7th ed. FC, Yolken RH, editors. Manual of clinical microbiology. 7th ed. Washington: ASM Press; 1999. p. 1137-44. Washington: ASM Press; 1999. p. 1137-44. Ropp SL, Jin Q, Knight JC, Massung RF, Esposito JJ. 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. J Clin Microbiol 1995;33:2069-76. Esposito JJ, Knight JC. Esposito JJ, Knight JC. Orthopoxvirus DNA: a comparison of restriction profiles and maps. Virology Virology 1985;143:230-51.1985;143:230-51.Jezek Z, Szczeniowski M, Paluku KM, Mutombo M, Grab B. Jezek Z, Szczeniowski M, Paluku KM, Mutombo M, Grab B. Human monkeypox: confusion with chickenpox. Acta Trop Acta Trop 1988;45:297-307. 1988;45:297-307. Centers for Disease Control and Prevention.Centers for Disease Control and Prevention. Human monkeypox----Kasai Oriental, Democratic Republic of Congo, February 1996-Kasai Oriental, Democratic Republic of Congo, February 1996-October 1997. MMWR Morb Mortal Wkly Rep 1997;46:1168-71. October 1997. MMWR Morb Mortal Wkly Rep 1997;46:1168-71.

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Selected reading on MonkeypoxSelected reading on MonkeypoxDean AG, Dean JA, Coulombier D, Burton AH, Brendel KA, Smith DC. Epi Dean AG, Dean JA, Coulombier D, Burton AH, Brendel KA, Smith DC. Epi Info, version 6: A word-processing, database, and statistics program for Info, version 6: A word-processing, database, and statistics program for public health on IBM-compatible microcomputers. Atlanta: Centers for public health on IBM-compatible microcomputers. Atlanta: Centers for Disease Control and Prevention; 1994. Disease Control and Prevention; 1994. Fenner F, Wittek R, Dumbell KR. The Orthopoxviruses. San Diego: Fenner F, Wittek R, Dumbell KR. The Orthopoxviruses. San Diego: Academic Press; 1989. p. 162-5, 312-15. Academic Press; 1989. p. 162-5, 312-15. Ziegler DW, Hutchinson HD, Koplan JP, Nakano JH.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. J Clin Microbiol 1975;1:311-7. Cherry JD, McIntosh K, Connor JD, Benenson AS, Alling DW, Rolfe UT, Cherry JD, McIntosh K, Connor JD, Benenson AS, Alling DW, Rolfe UT, et al. et al. Primary percutaneous vaccination. J Infect Dis 1977;135:145-54. J Infect Dis 1977;135:145-54. McIntosh K, Cherry JD, Benenson AS, Connor JD, Alling DW, Rolfe UT, McIntosh K, Cherry JD, Benenson AS, Connor JD, Alling DW, Rolfe UT, et al. 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. J Infect Dis 1977;135:155-66.

GIDSAS Chotani, 2003 Monkeypox: Outbreak in the US Monkeypox: Outbreak in the US Rashid A. Chotani Rashid A. Chotani, MD, MPH Rashid A. Chotani Assistant.

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