Monkey Pox is a zoonotic disease transmitted from animals to humans. It is originated in Africa and then spread throughout the world. Recently epidemiology of Monkeypox has been changing which was once confined to the African continent. In this presentation, The epidemiology, geography distribution, transmission, and its changing epidemiology of Monkeypox is discussed.

1. Changing epidemiologyof MonkeyPox: A potential threat?
Bhargavi Dadimi
P-2389
Division of VPE
CREDIT SEMINAR

2. Monkeypox is an emerging/re-emerging zoonotic disease caused by monkeypox virus
(Bunge et al., 2022)
First identified in captive monkeys at the state serum institute, Copenhagen, Denmark in
1958. (Shanmugaraj et al., 2022)
First monkeypox case was reported in 9 month old child in Democratic Republic of
Congo (formerly Zaire) in 1970- 9 m after the eradication of smallpox. (CDC,2022)
Monkeypox is regarded as the most important orthopoxvirus infection in human beings
since the eradication of smallpox (Giulio and Eckburg, 2004)
Introduction

3.  Virus: Monkeypox virus (MPXV)
 Genus: Orthopoxvirus
 Family: Poxviridae
 Genome: dsDNA
Orthopoxvirus
Variola
virus
cowpox virus vaccinia virus
Monkeypox virus
Smallpox
Used in
smallpox
vaccination
Two genetic clades of MPXV: 1. West African clade (WA)
2. Central African clade/Congo Basin clade (CB)
Introduction
(Bunge et al., 2022)
(Sklenovska et al., 2022)

4. First outbreak outside Africa in USA, 2003
Historical events
1970-
1979
1980-
1989
1990-
1999
2000-
2009
2010-
2019
2020-
2022
MPXV first
discovered
First human
case in DRC
48 cases in Africa
>300 cases in Africa
>500 cases in Africa
>10000 cases in Africa
>19 thousand cases in Africa
Cases were found in non-African
countries in 2018-2019
Cases in US, Australia, Israel
and European countries
1958
1970
(Shanmugaraj et al., 2022)

5. MPXV are ovoid or brick shaped (Parker et al., 2007)
Corrugated outer lipoprotein membrane
Size of the virion ranges from 200-250 nm (Alakunle et al., 2020)
Core appears as biconcave structure with two lateral bodies
Genome: Double stranded DNA viruses (197kb) (Kungleman et al., 2014)
Life cycle occurs in the cytoplasm of infected cells. (Hughes et al., 2010)
The genes encoding for housekeeping functions are highly conserved among
OPVs and are present in the central region of the genome
while those that encode for the virus–host interactions are less conserved and
are located in the termini region (Remichkowa, 2010)
Morphology of the virion

6. 1.Data paucity on Natural Reservoir
and Maintenance host of MPXV
2.Detection of MPXV in a widerage of
rodents spp. & NHP
Epidemiology
Epidemiology
There is no definitive reservoir or natural host for MPXV (Nalca et al., 2005)
Rodents and non-human primates have been determined to be potential natural reservoir and
incidental hosts of the virus (Peterson et al., 2019)
The difficulty in understanding the
Pathogen–host associations
Epidemiology
Natural history
Ecological and climatic effects of MPXV
Host species distribution
(Nasir et al., 2019)

7. Epidemiology
Geographical distribution
 Monkeypox virus was endemic to Africa (Likos et al., 2007)
 MPXV Endemic countries:
• Cameroon
• Central African Republic (CAR)
• Nigeria
• Liberia
• Sierra Leone
• Democratic Republic of Congo (DRC)
First outbreak outside Africa occurred in the United States in 2003
MPX has been reported in 28 non-endemic countries across 4 WHO regions till date
(SSHAP,2022)

8. Endemic West African clade
Endemic Congo Basin (Central African) clade
Both clades recorded
West African clade outbreak in 2022
Suspected cases
Geographical distribution
(WHO,2022)
42 countries reported 2103 cases to WHO till June 17th, 2022

9. (WHO, 2022)
Distribution of MPX cases

10. Transmission
2 means of mokeypox transmission
Human-human transmission Animal-human transmission
• Respiratory droplets
• Contact with body fluids
• Skin lesions of infected persons
• Contaminated patients environment
• Contact with natural hosts
• Bush meat consumption
Nosocomial transmission has been reported (Nasir et al., 2018)
Sexual transmission- speculated for infected individuals with lesions in genital regions and groins
R0 for CB clade- 0.6 to 1, lower in WA clade. (Alakunle et al., 2020)
Transmission
(Kabuga et al., 2019)

11. Primarily animals, typically rodents
Bites Scratches Consumption of bush meat
Human-to-human transmission is possible, but limited
Through close contact with infected respiratory tract secretions
or skin lesions
MPXV
Transmission
(Alakunle et al., 2020)

12.  Febrile prodrome period for 1-4 days with headache and fatigue (CDC,2022)
 A rash usually appears 1-3 days after the appearance of fever (CDC,2022)
 Centrifugal development of deep well-circumscribed macular-papular, vesicular, pustular
and finally crusted scab lesions (Giulio and Eckburg,2004)
 Lesions last for 1-3 days at each stage and progress simultaneously (Sklevensko et al., 2020)
 Lymphadenopathy (distinguishing feature from smallpox)-90% of cases
(Shanmugaraj et al., 2022)
 Lesion distribution is mainly peripheral-but can cover the whole body in severe illness.
Complications involve CNS, airway compromise from lymphadenitis (Adalja et al., 2022)
Miscarriage in pregnant women (Adalja et al., 2022)
Clinical picture

13. Enlarged lymph nodes
Pox lesions
Monkeypox lesions
Adalja et al., 2022)

14. The tale of two clades
 MPX is not part of mandatory reporting in other countries than the DRC, which might introduce
a bias
West African clade
< 1%
Never documented
Less common
Central African clade/Congo Basin clade
Up to 11%
Documented (Upton 6 sequential events)
More common
CFR
H-H transmission
Occurrence
The tale of two clades
(Sklenovska et al., 2022)

15. Why is the difference??
The tale of two clades
Why is this difference??
1
2
3
4
Central African clade prevents T-cell receptor mediated T-cell activation,
inhibits inflammatory cytokine production in human cells
(Hendrickson et al., 2014)
A gene that inhibits complement enzymes is absent in West African clade.
Central African monkeypox strains selectively down regulate host responses
compared to West African strains, specifically apoptosis in the host
Central African monkeypox appears to selectively silence transcription of genes
involved in host immunity during an infection

16. First outbreak in humans outside of Africa was determined in the U.S in 2003. (CDC,2015)
The source of the outbreak was traced back to native prairie dogs (Cynomys spp)
housed with African rodents.
1. Funiscuirus spp.
2. Heliosciurus spp.
3. Cricetomys spp.
4. Atherurus spp.
5. Graphiurus spp.
6. Hybomys spp.
African rodents that infected the prairie dogs
at an Illinois pet distributor
Exportation of monkeypox virus from African
continent
CDC,2015

17. Texas
Chicago
Prairie dogs brought from
Texas to Chicago pet shop
GIANT GAMBIAN RAT PRAIRIE DOGS HUMAN
Disease carried into US by rats
imported from Africa as exotic pets
Disease spread to prairie dogs
captured in Texas for use as pets
Contact disease when scratched
or bitten by prairie dogs

18. The largest West African MPX outbreak in history began in Nigeria in September 2017.
(Yinka et al., 2019
Unlinked travelers infected with MPXV from Nigeria arrived in United Kingdom (2) and Singapore
(1) in 2018. (Erez et al., 2019)
Israeli national returning from Nigeria to Israel. (Ng et al., 2019)
These exportations represent the first time a human host was documented to transfer MPXV from the
African continent.
The source of the 2003 United States (US) MPX outbreak was determined to be a shipment of
rodents from West Africa. (Mauldin et al., 2020)
Exportation of monkeypox virus from African
continent

19. Singapore
Nigeria

20. First ever outbreak outside Africa (endemic region) occurred in 2003 in the USA (CDC,2015)
The outbreak- counted 47 patients, with 37 confirmed and 10 probable MPXV infection
No deaths (CDC,2003)
No person to person transmission (CDC,2003)
Majority of the cases in US outbreak occurred in adults
Strain- West African clade (Reed et al., 2004)
First ever outbreak outside Africa

21. Characteristic Smallpox Monkeypox Chickenpox
Incubation period 7-17days 7-17days 10-21days
Prodromal period 1-4days 1-4days 0-2days
Prodromal fever Yes Yes Uncommon
Fever Yes, often >40 Yes, 38.5 and 40.5 Yes, up to 38.8
Malaise Yes Yes Yes
Headache Yes Yes Yes
Lymphadenopathy No Yes No
Lesions on palms or soles Yes Yes Rare
Lesion distribution Centrifugal Centrifugal Centripetal
Lesion appearance Hard & deep, well
circumscribed
Hard & deep, well
circumscribed
Superficial, irregular borders,
dewdrop on a rose petal
Lesion progression Lesions are often in one
stage of development on
body
Lesions are often in one
stage of development on
body
Lesions are often in multiple
stages of development
Comparison of clinical features
(McCullum and Damon, 2014)

22. Monkepox in India
• A 5 year child from Ghaziabad, Uttar Pradesh
presented to an ENT clinic on May 23, 2022
• Child was found with excessive rashes and
itching
• Samples were sent to NIV, pune
• Child was tested negative for MPXV
(Indian Express,June 4, 2022)

23. Changing face of MPX epidemiology
1. Change in number of cases
1970s- 48 total cases were reported from 6
African countries
1980s- 357 total cases with 9x rise in DRC
1990s- 519 total cases, DRC-511
2000s- Emerged in USA, South Sudan
2010s- Re-emerged in Nigeria (after 4
decades) and Sierra Leone (after 3
decades)
Emerged in UK, Singapore, Israel
2020s- Reported in 42 countries

24. Changing face of MPX epidemiology
2. No. of cases/clade/decade
Decade Central African clade West African clade Total cases
1970-1979 38 9 47
1980-1989 355 1 356
1990-1999 520 0 520
2000-2009 92 confirmed
10,027 suspected
47 139
10,027
2010-2019 85 confirmed
18,788 suspected
195 280
18,788
2020- Counting Counting Counting
The most affected country by MPXV is DRC, followed by Nigeria

25. Changing face of MPX epidemiology
3. Demographic characteristics
a. Median age of MPX:
1970s- 4 years
1980s- 5 years
2000s- 10 years
2010s- 21 years
b. Case Fatality Rate:
1970s to 1990s- 100% of deaths were in
children
2000-2019- 37.5% of deaths are in children
c. Mode of Transmission:
• 1980s- 72.5% cases from animal source (1), 27.5% cases from human source (2)
• 1990s-22% of the cases are 1, and 78% from secondary
• Nigeria (2017-2018) outbreak: Route of transmission was unkown in 62.3% of cases
Of remaining- 78.3% linked humans
Remaining 8.2% linked to animals
(Bunge et al., 2022; McCullum and Damon, 2020))

26.  Smallpox vaccination was stopped in 1980
 Resulted in drop of immunity against orthopox viruses
Eradication of smallpox
Waning immunity
 The influence of vaccination cessation is reflected in the age pattern of incidence
 Children are more affected than adults
Created an immunological niche
Possible explanations for increase in incidence of MPX
Cessation of smallpox vaccination
1
(Garske et al., 2014)

27.  Logging of rain forests
 Recurrent war
 Civil unrest
Encroachment of forest areas
1. Shelter and
2. Food (Bush meat-monkeys and
small rodents)
Monkeypox
Possible explanations for increase in incidence of MPX
Higher or more frequent exposure to animal reservoir species
2
(Kantele et al., 2016)

28. Increased prevalence in immunocompromised hosts
Provide more opportunity for MPXV to acquire mutations that increase its fitness to humans.
Increased transmissibility, virulence and pathogenic potential
Possible explanations for increase in incidence of MPX
Increased human to human transmission rate
3
Advances in diagnostic potential and health
4
(Rimoin et al., 2010)
(Li et al., 2017)

29. Is MPX is Gay community related disease??! Are they to be blamed??
Definitely Not
There is no known biological trait of monkeypox virus that increases its
proclivity to infect MSM (Daskalakis et al, 2022)
Infectious diseases occur at different rates because of social, economic, and
environmental factors, not biological ones
MPX in Gay community
 To date, most of the cases outside endemic countries have been reported in gay,
bisexual and in men who have sex with other men (MSM) (Daskalakis et al, 2022)
 Disease presentation include atypical symptoms- lesions restricted to genital and anal
regions

30.  This may result in stigma and misguided confidence that an outbreak is contained within
that population.
 Prematurely narrow appropriate public health response.
 Narrow focus threatens the health of other communities that might also have a higher risk
for being affected.
Such associations can create stigma that outlives the outbreak and lost opportunities to
detect and address the infection in other populations.
Risk of stigmatising gay and bisexual men

31. Phenotypic methods
 Based on clinical diagnosis
 Crop like appearance of MPXV
 Lesion and centrifugal lesion
 High sensitivity: 93-98%
 Low specificity: 9-26%
Diagnosis
Phenotypic methods Genotypic methods Immunological methods
(Alakunle et al., 2020)

32. Genotypic methods
PCR or RT-PCR
Genes targeting conserved regions of :
1. Extracellular-envelope protein region (B6R)
2. DNA Polymerase gene (E9L)
3. DNA –dependent RNA-polymerase subunit 18 (rpo18 and F3L)
Method of choice for routine diagnosis
Restriction Fragment length Polymorphism (RFLP)- Time consuming
Whole genome sequencing- gold standard for characterization of MPXV
Expensive (Cohen-Gihan et al., 2020)
Diagnosis
Phenotypic methods Genotypic methods Immunological methods

33. Immunological methods
ELISA for IgG and IgM antibodies detection
Immunohistochemistry for viral antigen detection
Electron microscopy
Intracytoplasmic brick shaped with lateral bodies and central core
Measurinng 200-300 nm
Not a definitive diagnosis
Diagnosis
Phenotypic methods Genotypic methods Immunological methods
(Brown et al., 2019)
(Risi et al., 2019)

34. 1. MVA-BN (JYNNEOS, IMVAMUNE, IMVANEX)- Attenuated vaccinia virus
Newer generation smallpox vaccination
FDA indication for smallpox vaccination
2. ACAM2000- Live Vaccinia virus
Older generation smallpox vaccination
Can be used off-lable
3. LC16m8- Attenuated Vaccinia virus
Licensed for use in Japan
Vaccinia immune globulin- used in cases where vaccine is contrindicated.
Vaccines
Smallpox vaccination was approximately 85% protective against monkeypox (Fine et al., 21988)

35. 1. Tecovirimat (ST-246 or TPOXX)- A4-trifluoromethylphenol derivative
• Approved by the FDA
• TPOXX interacts with F13L genes
• Blocks the release of intracellular virus from cells.
2. Cidofovir
3. Brincidofovir
 Brincidofovir is more efficacious (25x) than cidofovir
because of increased intracellular uptake
There has not been any specific curative treatment for MPXV, it is only
managed through supportive care and symptomatic treatment
Treatment
Inhibit viral DNA polymerase

37. Wayforward
Appearance of outbreaks beyond Africa highlites the geographical spread and global
relevance of the disease.
Increased surveillance and detection of monkeypox cases are essential tools for
understanding the continously changing epidemiology
Comprehensive strategies to strengthen the health system need to be initiated in the long run.