Version of Record: https://www.sciencedirect.

com/science/article/pii/S0896841122000634
Manuscript_15598d95500c910f1378ce775558ba0d

The 2022 Outbreak and the Pathobiology

of the Monkeypox Virus

Narendra Kumara, Arpan Acharyaa, Howard E. Gendelmana,d,e,

Siddappa N. Byrareddya,b,c,*

aDepartment of Pharmacology and Experimental Neuroscience, College of Medicine,

University of Nebraska Medical Center, Omaha, NE, USA
bDepartment of Genetics, Cell Biology and Anatomy, College of Medicine, University
of Nebraska Medical Center, Omaha, NE, USA
cDepartment of Biochemistry and Molecular Biology, College of Medicine, University
of Nebraska Medical Center, Omaha, NE, USA
dDepartment of Pathology and Microbiology, College of Medicine, University of
Nebraska Medical Center, Omaha, NE, USA
eDepartment of Pharmaceutical Sciences, College of Pharmacy, University of
Nebraska Medical Center, Omaha, NE, USA

∗Corresponding author
Dr. Siddappa N. Byrareddy, Department of Pharmacology and Experimental
Neuroscience, Durham Research Center-I, Room 8052, 985880 Nebraska Medical
Center Omaha, NE, 68198-5880, USA, phone 402 559 4044; fax 402 559 3733
email [email protected]

Keywords: Monkeypox Outbreak 2022, Viral Pathogenesis, Prevention, Antiviral

Therapies, Transmission

1
© 2022 published by Elsevier. This manuscript is made available under the Elsevier user license
https://www.elsevier.com/open-access/userlicense/1.0/
Abstract

Ever since reports of monkeypox virus infection in individuals who returned from
Nigeria to the USA, one who returned to Texas (July 2021) and the other to the
Washington, DC area (November 2021), the number of monkeypox infection have
dramatically increased, sounding an alarm of potential for spreading of the virus
throughout the USA. During 2022, there was a report of monkeypox virus infection
(May 6, 2022) in a British national following a visit to Nigeria who developed readily
recognizable signs and symptoms of monkeypox virus infection. An outbreak of
monkeypox virus infection was first reported on May 6, 2022. This occurred in a
British national following a visit to Nigeria who subsequently developed typical
monkeypox disease signs and symptoms. Soon following this report, case numbers
climbed rapidly. By June 10, 2022, more than 1,500 cases have been reported in 43
countries, including Europe and North America. While the prevalence of the
monkeypox virus is well known in central and western Africa, its presence in the
developed world has raised disturbing signs for worldwide spread. While infection
was reported during the past half-century, starting in the Democratic Republic of
Congo in 1970, in the United States, only sporadic monkeypox cases have been
reported. All cases have been linked to international travel or through African animal
imports. The monkeypox virus is transmitted through contact with infected skin, body
fluids, or respiratory droplets. The virus spreads from oral and nasopharyngeal fluid
exchanges or by intradermal injection; then rapidly replicates at the inoculation site
with spreads to adjacent lymph nodes. Monkeypox disease begins with constitutional
symptoms that include fever, chills, headache, muscle aches, backache, and fatigue.
Phylogenetically the virus has two clades. One clade emerged from West Africa and
the other in the Congo Basin of Central Africa. During the most recent outbreak, the
identity of the reservoir host or the primary carriage remains unknown. African
rodents are the suspected intermediate hosts. At the same time, the Centers for
Disease Control affirmed that there are no specific treatments for the 2022
monkeypox virus infection; existing antivirals shown to be effective against smallpox
may slow monkeypox spread. A smallpox vaccine JYNNEOS (Imvamune or
Imvanex) may also be used to prevent infection. The World Health Organization
(WHO), has warned that the world could be facing a formidable infectious disease

2
challenge in light of the current status of worldwide affairs. These affairs include the
SARS-COVID-19 pandemic and the Ukraine-Russia war. In addition, the recent rise
in case of numbers worldwide could continue to threaten humankind. With this in
mind, strategies to mitigate the spread of monkeypox are urgently warranted.

3
1. Introduction
Concerns about the occurrence of one viral pandemic after another have reached a

fever pitch. COVID-19 will soon likely enter an endemic stage. After more than two

years of substantive global economic and healthcare impact of COVID-19,

unfortunately, we will likely be facing a second new viral outbreak. The second

etiological agent is the "monkeypox virus" (MPV). MPV is not new, and it was first

discovered in 1958 in Copenhagen. It was isolated from a research facility that

housed laboratory animals where monkeys had been shipped from Singapore to

Denmark [1]. The name monkeypox was coined for the initial isolate [2]. The first

case of animal-to-human zoonotic MPV transmission was reported in 1970 in the

Democratic Republic of Congo (DRC) [3]. The MPV belongs to the Orthopoxvirus

genus of the Poxviridae family. Variola (smallpox), vaccinia (a research vector tool

deployed for the smallpox vaccine), and cowpox viruses belong to the Orthopoxvirus

genus. MPV is a double-stranded DNA virus. The poxviruses are known to have a

brick-shaped or oval structure measuring 200 to 400 nm [4].

2. Epidemiology

The first documented MPV case was in a nine-month-old child from DRC in 1970 [5].

MPV outbreaks have risen since 1970 but are primarily contained within the African

continent. Notably, there has been limited viral spread to Europe and North America

[6]. Up to 48 confirmed cases of monkeypox were reported in six African countries

between 1970 to 1979. These included DRC (n=38), Cameroon (n=1), Côte d’Ivoire

(n=1), Liberia (n=4), Nigeria (n=3), and Sierra Leone (n=1). By 1986, more than 400

human MPV cases were reported, with mortality approaching 10%.

4
Small viral outbreaks occur routinely in equatorial Central and West Africa [7],

including 500 cases in DRC alone between 1991-1999 [8]. The Congo basin remains

endemic in the DRC and includes a high case fatality rate (CFR) [9]. In the DRC,

1,000 cases/year were reported.

2.1 Viral Re-Emergence

On May 18, 2022, 14, 7, and 13 cases of MPV infection were reported in Portugal,

Spain, and Canada, respectively [10]. On May 19, 2022, Belgium, Sweden, and Italy

confirmed their first MPV cases. On May 20, Australia reported two cases. One was

from Melbourne and a second from Sydney. Both patients recently returned from

Europe. France, Germany, and the Netherlands confirmed their first cases on May

20. The Health Secretary of the United Kingdom (UK) reported another eleven cases

of MPV on May 20, with a total number of 71 [11]. Belgium became the first country

to introduce a 21-day mandatory quarantine for MPV [11]. Switzerland and Israel

confirmed their first cases on May 21. Spain reported the first case on May 18, 2022.

On June 3, Spain recently reported an increase in number of 20 cases bringing the

country's total cases to 186 [12]. On May 23, Denmark reported its first case. This

was from an individual that returned from the Canary Islands. In Canada, Quebec

announced 15 confirmed cases on May 24, 2022, where at that time, the Czech

Republic confirmed its first case. The reported person participated in an international

music festival in Belgium. The United Arab Emirates confirmed its first case in late

May, a 29-year-old female visitor from West Africa. Slovenia also confirmed its first

case. Until May 24, 19 countries have reported MPV cases. However, the source of

the ongoing outbreak of MPV remains to be confirmed. The evolving nature of MPV

5
has suggested human-to-human and or animal-to-human transmission of MPV.

Infections first took place in a person who traveled from the endemic regions of

Africa to North America and Europe and then spread [13] (Table 1).

2.2 Outbreak in the US

The first confirmed case of MPV was reported in 2003 in the US. Forty-seven known

cases of MPV disease were confirmed in six states (Illinois, Indiana, Kansas,

Missouri, Ohio, and Wisconsin). After contacting pet prairie dogs, each of these

patients was MPV infected [14]. Imported small mammals infected these pets from

Ghana. Animals imported to Texas from Ghana in April 2003 were the likely source

of viral spread. This animal transport contained 800 small mammals, including

African giant pouched rats, rope squirrels, tree squirrels, brush-tailed porcupines,

striped mice, and dormice [15]. The Centers for Disease Control (CDC) confirmed

that nine dormice, two giant African pouched rats, and three rope squirrels were

infected with MPV. Few infected animals were housed near prairie dogs, an Illinois

animal facility. These pets were sold before signs of infection. People got an MPV

infection after having contact with the prairie dogs. On November 16, 2021, the CDC

and the Maryland Department of Health confirmed that one case of MPV infection is

a US resident. This patient -had returned from Nigeria to the United States. CDC

also reported another case of Monkeypox in July 2021 of Texas, who also traveled

from Nigeria to the US. MPV does not occur naturally in the US. Still, there have

been cases associated with international travel or contact with imported animals from

areas where the disease is more common. On May 18 in Massachusetts, a case was

6
 Country Confirmed Suspected Total Date of the Last updated
cases cases first case

confirmed by the CDC of a person who had recently returned from Canada. CDC

has also informed of Monkeypox clusters that have been found in early to mid-May in

several countries that do not typically report MPV, including Europe and North

America [16]. Until June 9, 45 cases of MPV infection have been confirmed in the US

(Table 2).

7
1 United Kingdom 366 0 366 May 6, 2022 June 10, 2022

2 Spain 275 0 275 May 18, 2022 June 10, 2022

3 Portugal 209 0 209 May 18, 2022 June 9, 2022

4 Germany 165 0 165 May 20, 2022 June 10, 2022

5 Canada 112 23 135 May 19, 2022 June 10, 2022

6 France 91 0 91 May 20, 2022 June 9, 2022

7 Netherlands 60 0 60 May 20, 2022 June 9, 2022

8 USA 45 0 45 May 18, 2022 June 9, 2022

9 Italy 32 0 32 May 19, 2022 June 10, 2022

10 Belgium 24 0 24 May 19, 2022 June 8, 2022

11 Switzerland 14 0 14 May 21, 2022 June 10, 2022

12 UAE 13 0 13 May 24, 2022 June 7, 2022

13 Ireland 9 0 9 May 27, 2022 June 10, 2022

14 Australia 8 0 8 May 20, 2022 June 9, 2022

15 Czech Republic 6 0 6 May 24, 2022 June 1, 2022

16 Slovenia 6 0 6 May 24, 2022 June 6, 2022

17 Sweden 6 0 6 May 19, 2022 June 10, 2022

18 Ghana 5 0 5 June 8, 2022 June 8, 2022

19 Denmark 4 0 4 May 23, 2022 June 10, 2022

20 Israel 4 0 4 May 21, 2022 June 9, 2022

21 Finland 3 0 3 May 27, 2022 June 9, 2022

8
22 Hungary 3 0 3 May 31, 2022 June 10, 2022

23 Argentina 2 0 2 May 27, 2022 May 27, 2022

24 Mexico 2 0 2 May 28, 2022 June 8, 2022

25 Norway 2 0 2 May 31, 2022 June 1, 2022

26 Latvia 2 0 2 June 3, 2022 June 8, 2022

27 Austria 1 0 1 May 22, 2022 May 30, 2022

28 Malta 1 0 1 May 28, 2022 May 28, 2022

29 Greece 1 0 1 June 8, 2022 June 8, 2022

30 Gibraltar 1 0 1 June 1, 2022 June 1, 2022

31 Morocco 1 0 1 June 2, 2022 June 2, 2022

32 Brazil 1 9 10 June 9, 2022 June 9, 2022

33 Poland 1 0 1 June 10, 2022 June 10, 2022

34 Uganda 0 4 4 June 8, 2022

35 Bolivia 0 3 3 June 3, 2022

36 Mauritius 0 3 3 June 2, 2022

37 Iceland 0 2 2 June 9, 2022

38 Bahamas 0 1 1 June 7, 2022

39 Bangladesh 0 1 1 June 10, 2022

40 Cayman Island 0 1 1 June 2, 2022

41 Kosovo 0 1 1 June 4, 2022

42 Haiti 0 1 1 June 1, 2022

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43 Uruguay 0 1 1 June 5, 2022

Total 1475 50 1525

Table 1. 2022 MPV global outbreak (excluding Africa) [17, 18].

3. Signs and symptoms of viral infection

The signs and symptoms of MPV infection reflect a milder form of smallpox [19]. The

difference is that MPV infection but not smallpox causes lymphadenopathy. The

onset of MPV infection is fever, chills, headache, muscle aches, backache, and

fatigue with progression to exhaustion. The incubation period of monkeypox is most

commonly 7 to 14 days but may take up to 21 days. After the appearance of fever,

the infected person develops a rash on the face, followed by dissemination to other

body parts (Figure 1). Lesions start within the oropharynx and then appear

throughout the body. Serum antibodies are detected around 2 weeks post-exposure

[20]. The mortality rate ranges from 1 to 10% based on the clade of the infecting

MPV strain and the availability of modern healthcare [21].

10
Figure 1. Signs and symptoms of MPV infection (Created using BioRender program).

4. Viral cell entry and pathogenesis

MPV can enter its host through the oropharynx, nasopharynx, or intradermal routes.

The virus replicates at the inoculation site and then spreads to regional lymph nodes.

Following a period of initial viremia, the virus spreads to other body organs. MPV has

a similar morphology to other known orthopoxviruses. MPVs are oval or brick-

shaped and are enveloped by a lipoprotein-based outer membrane [22]. The MPV

genome is a linear double-stranded DNA (197 kb). Although the MPV is a DNA virus,

its life cycle occurs in the cytoplasm. Several proteins are required for viral DNA

replication, transcription, and virion assembly [23]. Poxviruses enter the host cells by

macropinocytosis endocytosed and by fusion [24] (Figure 2).

11
Figure 2. Cytosolic MPV pathways for the viral life cycle. Enveloped Virion (EV) enters the host cell
by fusion and the mature virion (MV) by micropinocytosis or fusion (Created using BioRender
program).

Phylogenetically MPV has two clades: the West African and the Congo. The Congo

clade originated from Central Africa (Congo Basin) known as the Congo clade. The

Congo clade is more pathogenic than the west African clade [25]. Recent

sequencing data suggest that the MPV genomic sequence of the present strains

detected in Europe (Portugal) matches the West African clade, indicating a milder

form of the disease but this needs to be confirmed [26]. In 2003 U.S. outbreak in the

West African clade suggests that disease severity differs across clades [25].

Generally, West African monkeypox infections show less severity in humans and

non-human primates [25, 27, 28]. However, this 2003 U.S. outbreak had several

12
hospitalized patients and severe disease but no fatalities [29]. Congo MPV induces

T-cell receptor (TCR) mediated T-cell activation. However, of interest, inflammatory

cytokine production is inhibited if the human cells are derived from individuals who

had been previously infected with the monkeypox virus. This suggests that monkey

poxvirus may produce a modulator that suppresses host T-cell responses [30]. A

gene that inhibits complement enzymes is present in Central Africa but is absent in

the West African clade. It is a critical immune-modulating factor that potentially

increases the virulence of the Central African clade compared to the West African

clade [31, 32]. Furthermore, it has been reported that the Central African monkeypox

clade selectively downregulates host responses compared to the West African clade,

as reflected by its ability to specifically modulate apoptosis in the host [33]. A

Comparison between the Central African strain (ZAI-96) and three West African

strains (SL-V70, COP-58, and WRAIR-61) revealed a 0.55-0.56% nucleotide

difference between the Central African strains and the West African strains [34]. This

genetic analysis showed that two virus strains clustered separately. The central

African strain has 173 unique functional genes, while the West African strain is

predicted to have 171 unique genes. There is a difference in virulence between the

two strains; therefore, 56 virulence genes were examined, and 53 were shared in

both strains. The most significant differences between the two strains are in the

orthologs of BR-203, BR-209, and COP-C3L [34].

5. Novel Viral Mutations

MPV is a DNA virus and generally does not show many mutations compared to RNA

viruses like HIV or SARS-CoV-2 [35]. However, as reported, the virus isolated from

the 2022 outbreak of MPV seems to have more mutations. It means the virus is

13
evolving to spread more efficiently. Surprisingly, the isolates from the 2022 outbreak

shared 40 mutations that distinguish it from its closest variant. In typical evolutionary

timelines, one would expect a virus-like MPV to pick up many mutations that may

take over 50 years. However, it looks like MPV has mutated because of its ability to

transmit among people. Some mutations do not have any harmful effects on the

virus, but some can be harmful, and some mutations can take advantage of other

strains. There is not enough evidence on how MPV interacts with the host or how the

consequences of these mutations affect the rates of virus replication. In some host's

(human) immune systems, enzymes are known to induce mutations in viruses if they

encounter [36]. If hosts trigger enough mutations, some of the mutations will be

deleterious. Based on available sequences, MPV virus evolution seems to have

taken off in 2017. Since 2017, that has been circulating in humans and suggested

that MPV has a mutation rate around 10 times higher than the virus's standard

mutation rate. Currently, information is lacking on how new mutations in MPV

interact with the host (human) or what these individual mutations could do.

Nevertheless, many mutations in gene sequences of MPV from the current outbreak

are alarming to Scientists, and more studies are needed to understand the

mechanism of action of these newly evolved mutations [37].

5.1. Multiple viral strains are responsible for the 2022 outbreak
The CDC, Atlanta, GA issued a report (Friday, June 3, 2022) that suggests the
existence of at least two distinct clades of MPV in the outbreaks that have occurred
outside of Africa. The CDC sequenced 10 different virus isolates from the recent
outbreaks within the USA and found that these isolates are different from the viruses
that have been sequenced by several countries that are involved in the large
outbreak that is spreading in and from Europe. The European outbreak appears to

14
be driven primarily by the gay, bisexual, and MSM community. Out of the 10 US
isolates, 3 appeared to be distinct from the remaining 7 isolates. The 3 divergent
isolates appear to have a common lineage but also appear to differ from one another
[38]. Of interest, these 3 divergent isolates appear to have originated in different
geographical locations. One appears to have originated in Nigeria, the second in
West Africa and the third in the Middle East or East Africa. As of June 10, 2022,
there have been 49 cases reported in the USA occurring in 17 different states (see
Table 2)
S.N. State Cases*
1 Arizona 1
2 California 10
3 Colorado 3
4 District of Columbia 2
5 Florida 5
6 Georgia 1
7 Hawaii 3
8 Illinois 4
9 Massachusetts 1
10 New York 11
11 Pennsylvania 1
12 Oklahoma 1
13 Rhode Island 1
14 Texas 1
15 Utah 2
16 Virginia 1
17 Washington 1
Total 49
* Last updated on June 10, 2022 (Source: CDC)

Table 2. Distribution of US MPV cases [18].

6. Transmission

The reservoir host of MPV remains unknown. However, African rodents are

suspected of playing a part in the transmission of infection. MPV transmission occurs

through contact with skin lesions of the infected animals, body fluids or respiratory

droplets [39] (Figure 3). The virus enters the body through the respiratory tract,

broken skin, or mucous membranes (eyes, nose, or mouth). Transmission from

15
animal to human may occur through scratch, bite, bush meat preparation, or direct or

indirect contact with body fluids or lesion material [40]. Human to-human

transmission occurs through large respiratory droplets, sneezing, coughing, etc.

Respiratory droplets do not travel more than a few feet; therefore, prolonged face-to-

face contact is necessary for transmission to occur. Other transmission methods

from human to human are direct contact with the viral lesion and body fluids and

indirect contact with infected materials through clothing or infected linens.

16
Figure 3. MPV transmission. From rodents to monkeys (1). From monkey to human (2). From rodents
to humans (3). From infected person to healthy people through cough droplets (4). From infected
person to healthy people through direct skin contact (5). (Created using BioRender program).

Mother-to-child transmission (MTCT) may also occur via the placenta (congenital

Monkeypox), via close contact during and after birth. Although close physical contact

is needed for the transmission of Monkeypox, it is not clear whether the monkeypox

virus can be transmitted through sexual routes. Further research studies with well-

controlled animal models are needed to understand better whether the virus

transmits through the sexual route. In 2020, based on mathematical modeling and

comparison with smallpox viruses, it was shown that the reproduction number (R) for

MPV is >1, which indicates that it has an epidemic potential [40]. The quarantine of

exposed and infected persons can prevent viral spread [41]. Therefore, identifying

infected individuals and quarantining the potentially infected individual for an

extended period, such as up to 3 weeks, is critical to controlling the viral spread.

7. Diagnosis
Diagnostic assays are essential to confirm MPV infection and need to be correlated

with clinical and epidemiological information. Diagnosis of MPV infection is based on

history, clinical symptoms, and laboratory tests. The latter include PCR, ELISA,

western blot, and Immunohistochemistry. Confirmatory diagnosis is critical to rule out

other possible infectious diseases like smallpox [42]. Lesion exudate or crust is

collected on a swab to isolate viral nucleic acids for diagnosis. Viral DNA is then

used for the MPV genome-specific real-time polymerase chain reaction (RT-PCR)

test. On the other hand, MPV proteins are used for western blot analysis to confirm

the monkeypox virus infection [21]. As per WHO, the RT-PCR test is the preferred

test for diagnosing monkey poxvirus during acute infection [43].

17
8. Prevention

Some preventative measures can be taken to avoid MPV infection. This includes but

is not limited to (1) avoiding direct contact with animals that are suspected of

harboring MPV, especially in geographical locations where monkeypox disease is

prevalent, and (2) isolation of infected patients in a negative pressure room to

prevent human to human spread of the virus, (3) isolate and euthanize the animals

suspected to be the reservoirs of the virus, (4) avoid contact with any material that

has been in contact with a sick animal or human, (5) Front-line workers taking care

of MPV infected patients and other high-risk individuals who are expected to come in

contact with the infected persons should wear proper personal protective equipment

(PPE) that are capable of preventing air-borne infectious agents which includes N-95

mask, entire body covered water resistance gowns, double-layered gloves among

others.

Due to their genetic similarities, the smallpox vaccine is expected to provide some

protection against MPV infection. According to the United States CDC, prevention of

MPV is expected if the vaccine is administered within four days of exposure to MPV

due to the virus's long incubation period. It is reasoned that such vaccination should

provide complete protection against the disease [13]. To limit the current outbreak of

MPV, health departments have implemented policies to administer smallpox

vaccines to front-line workers taking care of the infected patients in many countries.

On May 24, 2022, the United States CDC decided to release some of their

JYNNEOS vaccine (a live vaccinia vaccine originally approved for smallpox virus in

18
2019) from their National stockpile for persons at high risk of coming in contact with

MPV [44]. However, the use of this vaccine is not recommended for the general

public. On May 25, the German government had a press release outlining a plan to

buy 40,000 smallpox vaccine produced by Bavarian Nordic. On May 26, the United

Kingdom Health Security Agency announced that it had already produced 20,000

doses of the smallpox vaccine to combat the rise of MPV cases. Modified Vaccinia

virus Ankara (MVA) is a third-generation vaccine against smallpox [45]. USA and

Canada have licensed MVA to use against monkeypox. Bavarian Nordic is in contact

with the European Medicines Agency (EMA) for the approval of the MVA vaccine

[46].

9. Treatment

Monkeypox disease usually induces mild symptoms, and most patients recover

without therapy. Per the CDC guidelines, there is currently no specific treatment for

monkeypox virus infections. However, antiviral drugs approved to treat smallpox may

be used to treat monkeypox disease. Cidofovir (Vistide) is an antiviral medication

that inhibits the viral DNA polymerase and effectively against poxviruses in in-vitro

and preclinical studies [42]. As per the current CDC guidelines, this drug may be

used to treat severely ill monkeypox patients, but the clinical outcome remains

unknown. Tecovirimat (ST-246) is an antiviral medication used to treat human

smallpox disease in adults and pediatric patients. This antiviral drug is approved by

the FDA and can be used to treat Monkeypox during an outbreak. Tecovirimat is

given orally (200 mg capsule) as an injectable formulation. Vaccinia Immune

Globulin Intravenous (VIGIV) is used to treat complications due to vaccinia

19
vaccination, including eczema vaccinium, severe generalized vaccinia, and

infections induced by vaccinia virus. VIGIV can be used for the treatment of

Monkeypox during an outbreak. Brincidofovir (Tembexa) is an antiviral drug that the

FDA approved to treat human smallpox disease in adult and pediatric patients. CDC

is currently developing an EA-IND to use Brincidofovir as a treatment strategy for

Monkeypox.

Other antiviral therapeutic drugs have also shown some effects against

Orthopoxviruses species as antiviral therapeutics. These include CMX-001, which is

a modified cidofovir drug. It lacks the extent of nephrotoxicity seen with cidofovir and

has demonstrated antiviral activity against Orthopoxvirus species, including

Monkeypox [42, 47] ST-246 drug (Tecovirimat, also known as TPOXX) is another

promising antiviral effect against a variety of Orthopoxviruses species. It blocks the

release of the intracellular virus from the cell [42, 47]. The use of these drugs in

endemic areas to treat MPV infections can be considered, and physicians are

allowed to make these decisions depending on the status of the infected persons.

10. Conclusions and future prospectives

The WHO has issued a warning that the world may yet face another major challenge

after having met the challenges of the COVID-19 pandemic in the form of the

Monkeypox outbreak in the backdrop of the catastrophic Ukraine-Russian war. Until

June 10, 2022, 1,475 cases have been confirmed worldwide. The UK itself has

reported 366 - cases of Monkeypox. In other countries like Spain (n=275), Portugal

(n=209), Canada (n=112), and the USA (n=45), the number of cases has grown

substantially. Therefore, this MPV outbreak is becoming a concern for the whole

20
world at present. The Monkeypox outbreak has been a focus of attention to

scientists, epidemiologists, clinicians, and policy leaders. The UK health department

has issued an advisory on self-isolation for monkeypox patients. Belgium is the first

country to announce a quarantine of three weeks for monkeypox patients. One can

control this disease by vaccinations, good hygiene practices, and self-isolation or

quarantine for the patients and their contacts. It is important to note that many cases

have been detected in the Men having Sex with Men (MSM) population, and this

population is at a higher risk of other STDs like HIV/AIDS. The virus exploits this

particular group of people for transmission, which is unique to the current outbreak

and was not reported previously. Nevertheless, whether MPV is transmitted by

sexual route or not remains an enigma for clinical virologists. There are reports from

Spain of spreading the MPV among People living with HIV (PLWH) who are on

combinational antiretroviral therapy (cART) and have entirely suppressed viremia

[48]. Therefore, the pathophysiology of MPV and HIV coinfection needs to be closely

monitored. People living with HIV have a compromised immune system; accordingly,

how the immune system of PLWH will react against MPV remains to be explored.

Other comorbidities, including coinfection of MPV and other STDs like hepatitis B or

C infection, will require close monitoring in the coming days. This will also be a

formidable task and a big challenge.

The need of the hour is to plan aggressively and put into place an active contract

tracing program, quarantine the exposed and infected persons with MPV, and use

post-exposure vaccines that may prevent the further spread of the virus. The world is

currently facing economic challenges due to the COVID-19 pandemic. The current

rise in monkeypox cases in the USA and the world will immediately threaten

economic growth prospects. The economic challenges will become more challenging

21
if this monkeypox disease is not brought under control quickly. Social distancing and

social stigma are also other challenges for people. People are already facing this

situation for the last two years. The awareness of the disease dynamics remains

poorly defined, even among the wealthier and more educated parts of the

population. People have resisted being screened for the disease and flouted

quarantines with impunity. Cough hygiene is mainly absent. Hand hygiene is equally

suspect in developing countries. Therefore, better public health strategies are

urgently needed, including controlled studies in animal models and others, to prevent

the spread of the virus. Special attention needs be given to children, the elderly, and

pregnant women since they are more susceptible to transmission.

Declaration of competing interest

The authors declare no conflicts of interest.

Acknowledgments
This work was partially supported by the National Institute of Allergy and Infectious

Diseases grants R01 AI129745, R01 AI113883, and DA052845 to S.N.B.

Furthermore, S.N.B. acknowledges independent research and development (IRAD)

funding from the National Strategic Research Institute (NSRI) at the University of

Nebraska. Further, this work is partially supported by National Institutes of Health

grants R01 NS034239; T32 NS105594; R01 NS036126; R01 MH115860; R01

NS126089; R01 AI145542; R01 AI158160; R01 MH121402; and R01 AI129745 and

University of Nebraska Foundation to HEG (donations from the Carol Swarts, M.D.

Emerging Neuroscience Research Laboratory; the Margaret R. Larson

Professorship; and the Frances and Louie Blumkin, and Harriet Singer

Endowments).

22
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