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Monkeypox
Historical Perspective and O
verview
2006
One Medicine Symposium
December 6-7, 2006
Research Triangle Park
C. Gregory Smith, MD, MPH
General Communicable Disease Control Branch
Epidem
iology Section
North Carolina Division of Public Health
Poxviruses by G
enus
•Orthopoxvirus
–Cowpox, Monkeypox, Vaccinia, Variola (Smallpox), Camelpox
•Yatapoxvirus
–Tanapox, Yatapox (non-human primates, humans incidentally)
•Parapoxvirus
–Orf, Pseudocowpox, Bovine Papular Stomatitis, Sealpox
•Molluscipoxvirus
–Molluscipox (Molluscum contagiosum) human &
nh primates
•Avipoxvirus
(Fowlpox-birds)
•Capripoxvirus(Sheep pox-sheep, goats, cows)
•Leporipoxvirus(M
yxoma-squirrels, rodents, rabbits)
•Suipoxvirus(Swinep
ox)
Orthopoxviruses
Yes
Direct contact,
Respiratory
droplets
US, Russia
(laboratories)
Eradicated
1980 W
HO
Humans
No known
anim
al
reservoirs
Humans
Variola
Smallpox
(SPXV)
Direct contact
Direct contact,
Respiratory
droplets
Direct contact
Direct contact
Mode of
Transm
ission
Probably
Africa, Asia
Camels
Camels,
? H
umans
Camelpox
(CMPV)
Yes
Central and
West Africa
Rodents
Humans,
monkeys,
rodents
Monkeypox
(MPXV)
Yes
Europe,
Africa, Asia
Rodents
Humans,
cats, cattle
rodents
Cowpox
(CPV)
?? Indian
Subcontinent
Buffulopoxvirus
Unknown
Humans
Vaccinia
(? Extinct
horsepoxvirus)
Protection
by Vaccinia
Vaccination
Geographic
Region
Primary
Reservoir
Host
Species
Monkeypox Virus (M
PXV)
FamilyPoxviridae
Subfamily Chrodopoxvirinae
Genus Orthopoxvirus
MPX
Pat
ient-Ele
ctro
nm
icro
gra
ph o
f Skin
Bio
psy
-Mar
shfiel
d C
linic
, M
arsh
fiel
d,W
I
MPX
His
torica
l N
ote
s
•1958-Initial discovery
-Den
mark-O
utbreak in laboratory primates
•1970-First human case identified in Zaire
9 m
o child who had not been vaccinated against SPX
•1970-1994: Following eradication of SPX in sub-
Saharan Africa, about 400 cases of MPX were
reported from the tropical-forested countries of
West and Central Africa
–95% of these were recorded in Zaire following intense
surveillance from 1982-1986
–Epidem
iologic and laboratory studies during this period
provided the foundation of our knowledge about MPX in the
natural setting.
Epid
emio
logy o
f M
PX
in A
fric
a•
Sporadic viral zoonosis confined to equatorial rain forests of West
and Central Africa
•Natural history is not clear
•Monkeys, other primates, including humans, are susceptible but
are unlikely reservoir hosts
•Antibody evidence indicates that wild rodents (African tree
squirrels, Gambian giant rats, elephant shrews, etc) serve as
primary viral reservoirs
•Routes of exposure and transm
ission have not been clearly
delineated but butchering m
onkeys and contact with sick
primates and rodents are thought to be the primary sources of
exposure
•Increased trade in bush m
eat is one possible risk factor for
outbreaks of human M
PX in enzootic areas
•Cases of MPX ten
d to occur singly or in small clusters.
Human-to-human transm
ission occurs infrequently
•2005
Updat
ed fro
m F
rien
d. M
PX
-A
Les
son N
ot Y
et L
earn
ed…
; U
SG
S C
ircu
lar1
285; 2006 p
170.
MPX
-susp
ecte
d w
ildlife
res
ervoirs
Source: Friend M
. Monkeypox-A
Lesson Not Yet Learned. In: Disease Emergence and
Resurgence: The W
ildlife H
uman Connection. USGS Circular 1285; 2006.
MPX
Clinic
al Illnes
s
•Incubation period: like SPX--12 days (R
ange 7-17 days)
•Signs and symptoms also sim
ilar to smallpox:
•Fever, HA, myalgias, backache, swollen lymph nodes,
general feeling of discomfort and exhaustion,
generalized pustular rash
•Rash resembles the ordinary or modified form
s of SPX
macules papules vesicles pustules
umbilication scabbing desquamation
Differen
ces Compared to SPX
•Lymphadenopathy tends to be more prominent than in
SPX and occurs early in the disease.
•Routes/mechanisms of p-t-p transm
ission are sim
ilar to
those for SPX but secondary transm
ission in M
PX is
lower, about 8%.
Sim
ilarities Compared to SPX
MPX
Clinic
al Illnes
s
Sim
ilarities Compared to SPX
•Illn
ess la
sts 2 to 4
wee
ks
Differences Compared to SPX
•Cas
e fa
tality
rat
io for M
PX
is le
ss c
om
par
ed to S
PX
–Among unvaccinated populations in W
est Africa, the
CFR varies between 1%-10%.
–It m
ay be higher in children
–For comparison CFR for SPX is 20-50%
Lym
phad
enopat
hy is th
e princi
pal
clinic
al fin
din
g
that
hel
ps to
distinguish m
onkey
pox fro
m sm
allp
ox.
Photos from Nalca et al. ClinInfectious Dis, 2005:41 (15 Dec) 1767.
Differential Diagnosis R
are
Common
Common
Lesions on
palm
s/soles
6-14 days
14-21 days
14-21 days
Tim
e to
desquamation
Heterogeneous rash
Homogenous
Homogenous
Lesion Stage
Centripetal
Centrifugal
Centrifugal (m
ainly)
Lesion
Distribution
Superficial (2-4 m
m)
Unilocular
Deep (4-6 m
m)
Multilocu
lar
Superficial to Deep
(4-6 m
m) M
ultilocular
Lesion Depth
None
None
Moderate to severe
Lymphadenopathy
Mild
Severe
Moderate
Headache, severity
Mild
Moderate
Moderate
Malaise, severity
Mild or None
Severe
Moderate
Fever, severity
0-2 days
2-4 days
1-4 days
Prodrome Pd
12-14 days
7-17 days
7-17 days
Incubation Pd
Chickenpox
Smallpox
Monkeypox
Is M
PX likely to become endemic
in the human population?
•MPX virus genome lacks some of the
immunomodulatory genes possessed by the
SPX virus genome.
•This suggests that MPX is unlikely to
become endem
ic in the human population.
Prevention
•Due to genetic sim
ilarities between smallpox and
monkeypox, vaccination with Vaccinia
virus
protects against both diseases.
Fam
ous W
ord
s
“Ther
e is
no e
vid
ence
that
monkey
pox
will bec
om
e a
public
hea
lth thre
at
outsid
e of en
zootic
area
s.”
Control of Com
munic
able
Disea
ses M
anual
APH
A, c.
2000
Illu
stra
tion b
y John E
van
s
MPX H
uman Cases
WI 39
IN 16
IL 12
MO 2
KS 1
OH 1
50 G
ambia
n G
iant Rat
s
510 D
orm
ice
53 R
ope
Squirre
ls
47 T
ree
Squirre
ls
100 S
trip
ed M
ice
2 B
rush
tailed
porc
upin
es
Imported from
Accra, Ghana to US
April 9, 2003
West African Rodents
Illustration Source:
Friend M
. USGS 2006
2003 M
PX
Outb
reak
in U
S•
First h
um
an c
ases
dia
gnose
d in m
id a
nd lat
e M
ay in
Wisco
nsin a
nd Illin
ois
•By July
71 c
ases
in six
Mid
wes
tern
had
bee
n
reported
to C
DC
–W
isco
nsin 39 India
na
16 Illinois 1
2
–M
isso
uri 2
Kan
sas 1
Ohio
1
•Cla
ssific
atio
n
–35 L
abora
tory
confirm
ed
–36 S
usp
ect or pro
bab
le
Sourc
e: N
alca
et al
. Clinic
al Infe
ctio
us D
isea
ses V
ol 41 D
ec 1
5,2005
Sym
pto
m h
ighlights to the
right ad
ded
.
Rash
Fever
Chills
Adenopathy
Monkeypox: Signs and Symptoms 2003 US O
utbreak-34 Patients
Headache
Sore throat
Myalgias
Sweats
Cough
Sourc
e: N
alca
et al
. Clinic
al Infe
ctio
us D
isea
ses 2005:4
1 (15 D
ec),1767.
Monkeypox Rash in M
idwestern US O
utbreak Cases
Sourc
e: N
alca
et al
. Clinic
al Infe
ctio
us D
isea
ses 2005:4
1 (15 D
ec),1749.
Hosp
ital
ized
10 Y
ear O
ld G
irl w
ith M
PX
Ret
rophar
yngea
l A
bsc
ess, T
rach
eal Im
pin
gem
ent, a
nd C
ervic
al L
ym
phad
enopat
hy
Hum
an M
onkey
pox C
ase
Def
initio
n
Updat
ed inte
rim
def
initio
n Jan
uar
y 2
004
•Clinical Criteria
–Rash (macu
lar, papular, vesicular, or pustular; generalized or
localized; discrete or confluent)
–Fever (subjective or measured tem
p of >99.3 F (37.4C)
–Other signs and symptoms
•Chills and/or sw
eats
•Headache
•Back
ache
•Lymphadenopathy
•Sore Throat
•Cough
•Shortness of Breath
Hum
an M
onkey
pox C
ase
Def
initio
n
Updat
ed inte
rim
def
initio
n Jan
uar
y 2
004
•Epidem
iologic Criteria
–Exposure to an exotic or wild m
ammalian pet
obtained on or after April 15, 2003, with clinical signs
of illness (e.g., conjunctivitis, respiratory symptoms,
and/or rash)
–Exposure to an exotic or wild m
ammalian pet with or
without clinical signs of illness that has been in
contact with either a m
ammalian pet or a human with
monkeypox
–Exposure to a suspect, probable, or confirm
ed case of
monkeypox
Hum
an M
onkey
pox C
ase
Def
initio
n
Updat
ed inte
rim
def
initio
n Jan
uar
y 2
004
•Laboratory Criteria
–Isolation of monkeypox virus in culture
–Demonstration of monkeypox virus DNA by
polymerase chain reaction testing of a clinical
specim
en
–Demonstration of virus morp
hologically consistent
with an orthopoxvirus by electron m
icroscopy in the
absence of exposure to another orthopoxvirus
–Demonstration of presence of orthopoxvirus in tissue
using immunohistochem
ical testing m
ethods in the
absence of exposure to another orthopoxvirus
Hum
an M
onkey
pox C
ase
Cla
ssific
atio
n
•Suspect Case
–Meets one of the epidem
iologic criteria AND
–Fever or unexplained rash ANDtw
o or more other signs or symptoms with
onset of first sign or symptom <21 days after last exposure m
eeting
epidem
iologic criteria
•Probable Case
–Meets one of the epidem
iologic criteria AND
–Fever AND
–Vesicular-pustular rash with onset of first sign or symptom <21 days after
last exposure m
eeting epidem
iologic criteria
OR If rash is present but the type is not described, dem
onstrates elevated
levels of IgM antibodies reactive with
orthopox virus between at least days 7 to 56 after rash onset
•Confirm
ed Case
–Meets one of the laboratory criteria
Hum
an M
onkey
pox C
ase
Excl
usion C
rite
ria
•A case m
ay be excluded as a suspect or probable
monkeypox case if:
–An alternative diagnosis can fully explain the illness, O
R
–The case was reported on the basis of primary or secondary
exposure to an exotic or wild m
ammalian pet or a human (see
epidem
iologic criteria) subsequently determined not to have
monkeypox, provided other possible epidem
iologic criteria are
not present, O
R
–A case without a rash does not develop a rash within 10 days of
onset of clinical symptoms consistent with m
onkeypox
–The case is determined to be negative for non-variola generic
orthopoxvirus by polymerase chain reaction testing of a well
sampled rash lesion by the approved Laboratory Response
Network
(LRN) protocol.
–The case is determined to have undetectable levels of IgM
antibody during the period of 7-56 days after rash onset.
NC
Res
ponse
•A
ctiv
e su
rvei
llan
ce-feb
rile
ras
h illnes
s
•V
eter
inar
y P
ublic
Hea
lth
–Loca
l H
ealth D
epar
tmen
ts
–N
C D
epar
tmen
t of A
gricu
lture
-reg
ula
tes Pet
Sto
res
–Lic
ense
d V
eter
inar
ians
–Loca
l Pet
Sto
res-
public
hea
lth iss
ues
–In
div
idual
s w
ith P
ets
Prairie Dog with Owner
Take to
veterinarian
Animal is
sick Veterinarian examines
animal, history, physical &
maintains full records
Animal is healthy
or doesn’t appear
to have MPX
Return
animal to
owner
Animal is sick &
appears to have MPX
DVM notifies LH Dept
and NCDA&CS
immediately: Does DVM
allow owner to keep?
Euthanize animal:
Incinerate or freeze according
to instructions by LHD or
NCDA
Animal is
healthy
Animal
remains at
hom
e of
owner
Owner seeks
permission from
NCDA/LHDept
to give to
refuge
Order given to
euthanize
animal
Give to refuge, refuge keeps animal on
premises, maintains full records,
notifies LHD or NCDA if animal sickens,
dies, escapes
•Refuge space
available
Refuge space
available and
Perm
ission given
Refuge space not
available
Or
Perm
ission not given
Prairie Dogs: Most Social Mem
bers of the Squirrel Family
Genus Cynomys-5 Species
Bla
ck-tai
led (C ludovicianus)*
dry
pla
ins ce
ntral
TX
to C
anad
a
White-
tailed
(C leucurus)-w
este
rn U
S, CO
, U
T, W
Y, M
T
Gunnison’s
(C gunnisoni)-Four co
rner
s 5000-1
1,0
00 ft
Uta
h (C parvidens)-s
mal
lest, ESA
: th
reat
ened
Mex
ican
(C mexicanus)-ESA
: en
dan
ger
ed
In 1900, a prairie dog settlem
ent on the high
plains of TX extended 100 by 250 m
iles with
an estim
ated population of 400 m
illion.
Predators:Hawks, owls, eagles, ravens, coyotes,
badgers, ferrets, snakes, andhumans
* Sold in pets stores
in US and abroad
Public Health Risks:
•Plague from fleas
•Tularemia (Japan)
•Salm
onellosis
Photos: US Fish &
Wildlife Service
Anim
als In
fect
ed w
ith M
PX
V
13 lin
ed g
round squirre
l
Pra
irie
dog
Adapted from : Friend M
. Circu
lar Monkeypox-A
Lesson Not Yet Learned. In:
Disease Emergen
ce and Resurgen
ce: The Wildlife H
uman Connection. USGS 1285; 2006.
Black-footed Ferret -im
portant predator of prairie dogs-PDsexterm
inated
Thought extinct until sm
all colony discovered in 1981 near Meeteetse, Wyoming
Mustela nigripes
.
Photos: US Fish and W
ildlife Service
North American Black-footed Ferret
One of three ferrets in the world:
European ferret (European polecat) (Mustela putorius)
Domesticated (Mustela putorius furo)
Pets
Led to Discovery of Influenza Virus
Anim
al Model for Influen
za
North American black-footed ferret (Mustela nigripes)
Fossil evidence indicates it is descended from the Siberian
ferret which crossed into NA during the Pleistocene Period
Siberian ferret (Steppe polecat) (Mustela eversmannii)
closest relative of BFF
Black-footed Ferret Facts
•1967 Listed as federally endangered species, thought to be extinct
•1981 Small population discovered by a rancher near Meeteetse, WY
•1984 Estim
ated population of 129 crashed due to canine distemper-no
immunity
•1985 Six ferrets in the Meeteetse population were captured and m
oved to
captive breeding facilities at the WY G
ame and Fish Department’sSybille
Research Facility-all died from canine distemper
•1987 Rem
aining 18 ferrets captured -Initial breeding efforts unsuccessful
•1988 Breeding success
•1992 Reintroduction to the wild
•1998 SSP captive breeding facilities 425 born with 321 kits surviving
•2006 W
ild population now approx 700-850 in five western states
–BFF live in Prairie Dog burrows 90 %
BFF diet is PD
–Single ferret family requires 100 acres of PD colony for sustenance
Threats to wild BFF population:
–Loss of prairie dog habitat
–Predators
–Disease (canine distemper, plague**, influenza)
–MPX if captive prairie dogs infected with M
PX were released into
wild
Threats to captive BFF population (VA, KY, WY, AZ, CO, Canada):
–Disease as above and M
PX if M
PX-infected prairie dogs were fed to ferrets
What good are G
ambian giant rats, anyway?
Excellent, cheap, replaceable
detectors for land m
ines.
Wines M. For Sniffing O
ut Land M
ines, A Platoon of Twitching Noses. The New York
Times M
ay 18, 2004.
http://www.acs.appstate.edu/~kms/classes/psy3202/RatsLandMines.htm
www.taipeitimes.com
www.thaiclinic.com
Ref
eren
ces
•Control of Communicable Diseases Manual. James Chin, MD, MPH,
Editor, 17thEdition 2000, American Public Health Association,
Washington D.C. pp 458-459.
•Landyl ID
, Ziegler P, Kim
a A. A human infection caused by m
onkeypox
virus in Basankusu Territory, Dem
ocratic Republic of the Congo (DRC).
Bull W
HO 1972;46:593-7.
•Breman JG. Monkeypox: an emerging infection for humans? In: Scheld
WM, Craig W
A, Hughes JM, eds. Emerging Infections 4. Washington,
DC: ASM Press, 2000:45-76.
•Shchelkunov SN, Totm
enin AV, Babkin IV, et al. H
uman m
onkeypox and
smallpox viruses: genomic comparison. FEBS Lett 2001;509:66-70.
•Shchelkunov SN, Totm
enin AV, Safronov PF, et al. Analysis of the
monkeypox genome. Virol 2002;297:172-94.
•World H
ealth O
rganization. Technical Advisory G
roup on H
uman
Monkeypox: report of a W
HO m
eeting. Geneva, Switzerland, January
11-
-12, 1999.
•Jezek ZM, Scczeniowski KM, Paluku M
, Putombo M
, Grab B. Human
monkeypox: clinical features of 282 patients. J Infect Dis 1987;156:293--8.
Ref
eren
ces-
continued
•Hutin YJF, Williams RJ, Malfait P, et al. O
utbreak of human m
onkeypox,
Democratic Republic of Congo, 1996-1997. Emerg Infect Dis 2001;7:434-8.
•Khodakevich L, Jezek Z, Kinzana K
. 1986 Isolation of monkeypox from a wild
squirrel. Lancet 1986;1:98-9.
•State of Wisconsin, Departm
ent of Health and Family Services. Emergency order.
Available at http://www.dhfs.state.wi.us/dph_bcd/m
onkeypox/Response.htm
.
•State of Illinois. Executive order in response to orthopox outbreak. Available at
http://www.idph.state.il.us/pdf/ExecutiveOrder14.pdf.
•CDC/FDA: Joint CDC/FDA Interim
Final Rule
http://www.fda.gov/ohrms/dockets/98cfr/03-27557.htm
•Reed K
D, Melski JW, Graham M
B, Kazm
ierczak JJ, et al. The detection of
monkeypox in humans in the W
estern H
emisphere. N Engl J M
ed 2004Jan 22;
350(4):342-50. Comment/author reply 2004 (Apr 22:350(17):1790-1.
•Guarner J, Johnson BJ, Paddock CD. Monkeypox transm
ission and pathogenesis in
prairie dogs. Emerg Infect Dis. 2004 (Mar;10(3):426-31.
•Langohr IM, Stevenson G
W, Thacker H
L, et al. Extensive lesions of monkeypox in a
prairie dog. Vet Pathol. 2004 Nov; 41(6):702-7.
•Huhn G
D, Bauer AM, Yorita K
et al. Clinical characteristics of human m
onkeypox
and risk factors for severe disease. CID
2005; 41 (15 December):1742-51.
•Nalca A, Rim
oin A, Bavari S et al. Reemergence of monkeypox: prevalence,
diagnostics, and countermeasures. CID
2005; 41 (15 December): 1765-71.
•Friend M
. M
onkeypox-a lesson not yet learned. In: Disease Emergence and
Resurgence: The W
ildlife-H
uman Connection: USGS Circular 1285; 2006 168-171.
Accessed 11/13/2006http://wildlifedisease.nbii.gov/documents/pg%20168-
170%20Monkeypox.pdf
Ref
eren
ces-
continued
•CDC. Human m
onkeypox-K
asai Orien
tal, Zaire, 1996-O
ctober 1997. M
MWR Dec 12, 1997; 46
(49);1168-71.http://www.cdc.gov/m
mwr/preview/m
mwrhtm
l/00050245.htm
•CDC. Human m
onkeypox-K
asai Orien
tal, Zaire, 1996-1997. M
MWR Apr 11, 1997; 46(14);304-7.
http://w
ww.cdc.gov/m
mwr/preview/m
mwrhtm
l/00048673.htm
•CDC. Multistate outbreak of monkeypox—Illinois, Indiana, and W
isconsin, MMWR June 13,
2003; 52(23) 537-40.http://w
ww.cdc.gov/m
mwr/preview/m
mwrhtm
l/mm5223a1.htm
•CDC. Update m
ultistate outbreak of monkeypox—Illinois, Indiana, Kansas, M
issouri, Ohio, and
Wisconsin, MMWR June 20, 2003; 52(24) 562-4.
http://w
ww.cdc.gov/m
mwr/preview/m
mwrhtm
l/mm5224a1.htm
•CDC. Update m
ultistate outbreak of monkeypox—Illinois, Indiana, Kansas, M
issouri, Ohio, and
Wisconsin M
MW
R June 27, 2003; 52(25) 589-90.
http://w
ww.cdc.gov/m
mwr/preview/m
mwrhtm
l/mm5225a4.htm
•CDC. Update m
ultistate outbreak of monkeypox—Illinois, Indiana, Kansas, M
issouri, Ohio, and
Wisconsin M
MW
R July 4, 2003; 52(26) 616-8.
http://w
ww.cdc.gov/m
mwr/preview/m
mwrhtm
l/mm5226a5.htm
•CDC. Update m
ultistate outbreak of monkeypox—Illinois, Indiana, Kansas, M
issouri, Ohio, and
Wisconsin, 2003. MMWR. July 11, 2003; 52(27) 642-6.
http://w
ww.cdc.gov/m
mwr/preview/m
mwrhtm
l/mm5227a5.htm
Ref
eren
ces-
continued
•CDC: Information on m
onkeypox:
http://w
ww.cdc.gov/ncidod/m
onkeypox/index.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/clinicians.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/vet.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/factsheet.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/qa.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/anim
als.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/smallpoxvaccine_mpox.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/vaccineqa.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/casedefinition.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/treatm
entguidelines.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/anim
alguidance.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/anim
alcasedefinition.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/anim
alhandlers.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/diagspecim
ens.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/autopsy.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/labbiosafetyguide.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/specim
enguide.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/specim
entrackingform.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/infectioncontrol.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/embargoqa.htm
•http://edocket.access.gpo.gov/2003/03-27557.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/law.htm
•http://w
ww.cdc.gov/ncidod/m
onkeypox/pet.htm