Opinion
Update on the Monkeypox Outbreak
VIEWPOINT
Carlos del Rio, MD The current monkeypox outbreak was declared a Pub-
Division of Infectious lic Health Emergency of International Concern (PHEIC)
Diseases, Department by the World Health Organization (WHO) director-
of Internal Medicine,
general on July 23, 2022. As of August 9, 2022, nearly
Grady Health System,
Emory University 32 000 confirmed cases of monkeypox had been re-
School of Medicine, ported across 82 nonendemic countries.1 Given the rapid
Atlanta, Georgia. pace with which cases are being diagnosed, a coordi-
nated international response is essential.2
Preeti N. Malani, MD,
MSJ
The first US case of monkeypox was reported on
Division of Infectious May 7, 2022, and as of August 9, 2022, nearly 9500 con-
Diseases, Department firmed cases have been reported. On August 4, 2022,
of Internal Medicine, the Biden administration declared monkeypox a public
University of Michigan,
Ann Arbor; and health emergency, giving federal agencies the ability to
Associate Editor, JAMA. quickly direct funds toward vaccines, therapeutics, and
other immediate needs.
How Is Monkeypox Spread?
Multimedia Monkeypox is transmitted primarily through direct skin-
to-skin contact with infectious lesions. In the current out-
break, most cases have occurred among men who ac-
quired the infection through sexual or intimate contact
with other men. Contact with materials used by a per-
son with monkeypox including clothing, bedding, or sex
toys may lead to transmission.3
Monkeypox can be transmitted during sexual activ-
ity, but it is not considered to be a sexually transmitted
infection because the virus can be acquired without
having sex. In addition, even though the monkeypox
virus has been detected in semen, it remains unclear if
monkeypox can be transmitted through semen, vaginal
secretions, urine, or feces.4 Transmission may occur
across the placenta to the fetus in pregnant people. It is
unknown if the virus can be transmitted by individuals
without skin lesions or how often the virus is spread
through respiratory secretions. The virus is not spread
by casual contact.
Clinical Characteristics
As of July 25, 2022, the US Centers for Disease Control
and Prevention (CDC) reported that 99.1% of US cases are
among individuals assigned male sex at birth, with a me-
dian age of 35 years (range 18-76 years).5 Most of the cases
have occurred among men who have sex with men but
at least 13 cases have been reported among persons as-
signed female sex at birth, including one pregnant indi-
vidual, and at least 2 children have become infected.
The mean incubation period from time of expo-
sure to first symptom onset has been estimated at 7.6
days (95% CI, 6.2-9.7),5 with 95% of individuals devel-
Corresponding
Author: Carlos
oping symptoms within 17.1 days. The initial symptoms
del Rio, MD, are those of a flu-like illness with fever, malaise, head-
Emory University ache, and fatigue often accompanied by lymphadenop-
School of Medicine,
athy. Shortly after the prodrome, a rash appears with le-
49 Jesse Hill Jr Dr SE,
Atlanta, GA 30303 sions starting as macules that progress to papules,
(cdelrio@emory.edu). vesicles, and then pustules before scabbing.
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In the current outbreak, common symptoms also in-
clude anorectal pain, proctitis with bleeding, and penile
edema with balanitis and phimosis. Sore throat, odyno-
phagia, epiglottitis, and tonsillitis are also reported.
The largest series published to date included 528 pa-
tients across 16 countries; 98% of the cases were among
men who identified as gay or bisexual and 41% were liv-
ing with HIV. The most common locations of lesions were
the anogenital area (73%); trunk, arms, or legs (55%);
face (25%); and palms and soles (10%). Most persons
had fewer than 10 lesions and almost 10% presented
with a single genital lesion.6
For most individuals, monkeypox is not life-
threatening but it is disruptive and painful and could
generate social stigma. Known complications of
monkeypox may include pneumonia, encephalitis, and
eye infections, which occur mostly in children younger
than 8 years and individuals who are immunocompro-
mised or pregnant. Hospitalization is uncommon and
the major reason for admission has been pain control,
typically from anorectal or oral pain. People with
monkeypox should remain in isolation for the duration
of illness, which typically lasts 2 to 4 weeks. Mortality is
rare, but so far at least 4 people in nonendemic coun-
tries have died.7
Testing for Monkeypox
Any unusual skin lesion, particularly in the anogenital
area, should be investigated. The rash may be limited to
a few lesions or only a single lesion. The CDC’s nonva-
riola orthopoxvirus polymerase chain reaction test
(cleared by the US Food and Drug Administration [FDA])
can detect monkeypox and is the test currently being
performed. With testing expanded to 5 commercial labo-
ratories, access to testing has increased; however, re-
sults are still taking 2 to 3 days in many places. There are
no data supporting the use of other sample types such
as blood, saliva, or genital secretions for testing.
Treatment
For most patients, the management is symptomatic, in-
cluding treatment of pain. Monkeypox is a member of the
Orthopoxvirus genus in the family Poxviridae, another
member of that genus is the variola virus, which causes
smallpox. As a result, while there are no antivirals cur-
rently approved for monkeypox, tecovirimat, an antivi-
ral drug approved for the treatment of smallpox based on
animal data, has been made available to treat monkey-
pox via an expanded access Investigational New Drug
(IND) protocol. Tecovirimat is available as an oral capsule
and as an injectable for intravenous administration.
Treatment is currently recommended for people in-
fected with monkeypox with severe disease or who are
at high risk for severe disease (individuals who are im-
munocompromised, pregnant or lactating, or have atopic
(Reprinted) JAMA Published online August 11, 2022 E1
 Opinion Viewpoint

dermatitis; children <8 years) and those with 1 or more complica-
tions. The CDC and FDA recently simplified the protocol by stream-
lining the postadministration monitoring and data requirements.
In addition, several clinical trials (PALM-007, PLATINUM, WHO/ARNS,
and ACTG5418) are underway or planned to provide necessary data
on the safety and efficacy of tecovirimat for monkeypox. Optimal
drug absorption of the oral formulation requires concurrent intake
of a high-fat meal (ideally about 600 calories and 25 g of fat).
currently only administering a single dose of JYNNEOS vaccine.
On August 9, 2022, the FDA issued an Emergency Use Authoriza-
tion (EUA) for the JYNNEOS vaccine to allow clinicians to use the vac-
cine by intradermal injection for individuals aged 18 years or older
who are determined to be at high risk for monkeypox infection.
This is expected to increase the total number of doses available for
use by up to 5-fold. The lower dose is immunologically noninferior
to the standard dose, but it is more reactogenic.10

Vaccines Preventing Spread of Infection

Currently, 2 vaccines can be used to prevent monkeypox: the
Bavarian Nordic JYNNEOS vaccine, which is FDA approved for small-
pox and monkeypox, and ACAM2000, approved only for smallpox
but granted an expanded-access IND protocol allowing use against
monkeypox. The JYNNEOS vaccine uses a live, attenuated vaccinia
virus that is incapable of replicating, and it is administered as a 2-dose
series. Peak antibody response occurs 2 weeks after receipt of the
2-dose JYNNEOS vaccine. The ACAM2000 vaccine uses a live vac-
cinia virus capable of replicating and is administered as a single dose
but requires multiple skin punctures. Both vaccines are thought
to be at least 85% effective at preventing monkeypox. 8 The
ACAM2000 vaccine has comparable immunogenicity to that of
the Dryvax vaccine (the previously licensed smallpox vaccine) and,
like Dryvax, it has been associated with an unexpectedly high rate
of myocarditis and pericarditis.9
A helpful feature of both vaccines is that they can be adminis-
tered as postexposure prophylaxis. When administered up to 4 days
after exposure, vaccination can prevent disease onset altogether,
but even receipt of vaccination up to 2 weeks following exposure
can reduce symptom severity.
The Biden administration is working to increase availability of
the JYNNEOS vaccine, but vaccine supply is still severely limited with
around 1 million doses available in the US. In contrast, more than
100 million doses of ACAM2000 are available in the Strategic Na-
tional Stockpile. Given the urgency of the situation, some have ad-
vocated for use of the ACAM2000 but the high risk of adverse
events, risk if administered to people who are immunocompro-
mised or with certain skin conditions like eczema, and operational
issues (administration requires a bifurcated needle) make JYNNEOS
a better choice. Given limited supplies, most health departments are
With appropriate use of personal protective equipment, the risk of
transmission of monkeypox in the health care setting is low. Health
care workers should wear a gown, gloves, eye protection, and
a NIOSH-approved particulate respirator equipped with N95 filters
or higher. A patient with suspected or confirmed monkeypox infec-
tion should be masked immediately, have lesions covered with
a gown or sheet, and be placed in isolation in a single-person room.
A person with monkeypox infection should avoid close con-
tact with others until the skin lesions are completely healed, which
can take several weeks. It is unknown whether recovery from
monkeypox protects against subsequent infection but given the lim-
ited supply of vaccine, individuals already infected should not be
prioritized for vaccination.
Public Health Lessons
The current monkeypox outbreak illustrates why global health can-
not be ignored. Despite monkeypox being endemic in Africa for
decades, clinical trials on treatments and vaccines were not done.
Now more than 3 months into the global monkeypox outbreak,
there is much to learn. While test capacity has been increased,
more is needed. Contact tracing is not happening, and data sys-
tems are not informing the response in rapid fashion. Many indi-
viduals at risk for monkeypox may not be engaged with the health
care system, making diagnosis, containment, and prevention
challenging. The demand for vaccines far exceeds availability.
Although the supply of tecovirimat has increased, this drug must
still be used under an IND protocol, which limits access. In addition,
a decentralized and wholly underresourced public health infra-
structure is even more strained as officials must now respond to
both COVID-19 and monkeypox.

ARTICLE INFORMATION
Published Online: August 11, 2022.
doi:10.1001/jama.2022.14857
Conflict of Interest Disclosures: Dr del Rio
reported receipt of grants from the National
Institutes of Health/National Institute of Allergy and
Infectious Diseases to his institution. No other
disclosures were reported.
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