Management of monkey pox

1. OVERVIEW OF HUMAN
MONKEY POX VIRUS DISEASE
BY
Dr. ABDULLAHI Asara Mohammed
Department of Internal Medicine,
Infectious and Tropical Diseases Unit,
ABUTH, SHIKA.

2. OUTLINE
• INTRODUCTION
• AETIOLOGY AND CHAIN OF TRANSMISSION
• CLINICAL MANIFESTATION
• CASE DEFINITION
• DIAGNOSIS
• DIFFERENTIALS
• CASE MANAGEMENT
• PROGNOSIS
• CONCLUSION

3. INTRODUCTION
• Monkeypox (MPX) is a viral zoonotic disease
• MPX occurs primarily around the rainforest of West and Central Africa……..
• Geographical spread of cases increasing…………………
• Causative virus first isolated in 1958 ( Statens Serum institute, Copenhagen,
Denmark)……………….
• First human MPX identified in 1970 in a 9/12 old boy (DRC)………………..
• First reported cases in Nigeria (1971)…………………………………

4. INTRODUCTION
• First reported human cases outside Africa 2003…………………………
• Re-emergence in Nigeria 2017…………………..
• Prior Smallpox vaccination offers some cross-protection to Monkey pox
• Children, pregnant women and immune-compromised are prone to severe
disease
• Prevention remains the key………………………………

5. AETIOLOGY/CHAIN OF TRANSMISSION/TRANSMISSION
Aetiology
• MPX virus a DS DNA virus
• Family: Poxviridae Genus: Orthopoxvirus
• Virus divided into two clades: WA and CA or Congo basin clade……
• Other important viruses in the Orthopoxvirus genus are
I. Variola virus….
II. Vaccinia virus..
III. Cowpox virus

6. ?RESERVOIRS

7. AETIOLOGY/CHAIN OF TRANSMISSION/
TRANSMISSION
GENERIC DIAGRAM ILLUSTRATING CHAIN OF TRANSMISSION
PRIMARY LINKS: Infectious Agent, Susceptible host and Route of
transmission
SECONDARY LINKS: Reservoir, portal of entry and portal of Exit.

8. AETIOLOGY/CHAIN OF
TRANSMISSION/TRANSMISSION
• Let us now create a MPX chain of transmission based on available
evidence……………………..

9. AETIOLOGY/CHAIN OF
TRANSMISSION/TRANSMISSION
Mode of Transmission of MPX
I. Animal to human transmission
II. Human to Human transmission
III. Contaminated environment to human transmission

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Human
Environment
to man
Animal
Human to
human
Exposure
Portal of
entry
Mucosa
Skin Respiratory
Transmission

11. AETIOLOGY/CHAIN OF TRANSMISSION/MODE
OF TRANSMISSION
Animal to Human transmission Human to Human transmission Env. to Human transmission
• From bites or scratches,
• From activities such as hunting,
skinning, trapping, cooking,
playing with carcasses,
• Eating animals, such as NHP,
terrestrial rodents, antelopes
and gazelles, and tree squirrels
• Direct contact with infectious
skin or mucocutaneous
lesions……..
• Respiratory droplets (and
possibly short-range aerosols
requiring prolonged close
contact)
• From contaminated
clothing or linens that have
infectious skin particles (also
described as fomite transmission)
• Contaminated surfaces and
equipment

12. MPX UPDATE
Disease Outbreak News by WHO as at 8/6/2022
• From 28 countries in four regions where MPX is not usual or had not
previously occurred.
Confirmed Cases: 1285 majority from EU(1112)
Probable case: 1 Death: 0
• From Africa
Suspected cases: 1536
Confirmed Cases: 59
Death: 72
Source: Multi-country monkeypox outbreak: situation update( WHO June
2022)

13. MPX UPDATE
COUNTRY CONFIRMED CASES SUSPECTED CASES DEATH
CAMEROON 3 28 2
CAR 8 17 2
REPUBLIC OF CONGO 2 7 3
DRC 10 1356 64
LIBERIA 0 4 0
NIGERIA 31 110 1
SIERRIA LEONE 0 2 0
GHANA 5 12 0
CUMULATIVE 59 1536 72
Source: Multi-country monkeypox outbreak: situation update( WHO June 2022)

14. Timeline of reported human monkeypox
outbreaks

15. MPX UPDATE
NUMBER OF CONFIRMED CASES PER CLADES
DECADE CA CLADE(N) WA CLADE(N) TOTAL CONFIRMED
CASES*
1970-1979 38 9 47
1980-1989 355 1 356
1990-1999 520 0 520
2000-2009 92 47 139
2010-2019 85 195 280
Adapted from:Bunge EM et al. (2022) The changing epidemiology of human monkeypox—
A potential threat? A systematic review. PLoS Negl Trop Dis 16(2): e0010141.
https://doi.org/10.1371/ journal.pntd.0010141

16. MPX UPDATE
Pooled CFR for MPX SOME MAJOR CONCERNS
• Re-emergence in WA
• Increasing global spread
• Some identified cases with no
known epidemiological link
• ? Emerging route of transmission,
reservoirs,…………………..
• Adapted: PLOS Neglected Tropical
Diseases |
https://doi.org/10.1371/journal.pn
td.0010141

17. CLINICAL MANIFESTATION
• Patients may be symptomatic or Asymptomatic
• I.P:5–21 days. Usually 6-13 days
• Infection usually mild-to-moderate in nature
• Clinical course divided into two periods: Invasion/prodromal period
and Skin eruption period

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Pathophysiology…Cond
Oral sores, genital
ulcers, cornea lesions,
pneumonia
Skin rash
Lymphadenopathy
Fever, systemic
symptoms
Human
Environment
to man
Animal
Respiratory
Skin
Human to
human
Lymphatics
Mucosa-GIT,
others
Skin Blood
Mucosa-GIT,
others
Exposure
Portal of
entry
Primary viremia
Secondary viremia
Specific symptoms and
signs

19. CLINICAL MANIFESTATION
Invasion/Prodromal Period/Pre-eruptive stage(0-5
days)
Skin Eruption Period( within 1-3 days of fever onset)
• Fever,
• Intense headache,
• Lymphadenopathy,
• Back pain,
• Myalgia (muscle ache) and an intense asthenia
• Conjunctivitis
• Photophobia
• Pruritus
• Mouth sores
• Rashes appear in various stages often beginning on
the face and then spreading elsewhere on the
body.
• The face (in 95% of cases), and palms of the hands
and soles of the feet (in 75% of cases) are most
affected.
• The rashes are evolving in nature: Maculpapular,
vesicles, pustules, crusts….

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 The rash lesions evolve from
 macules (lesions with a flat base) to
 papules (raised firm lesions) to
 vesicles (filled with clear fluid) to
 pustules (filled with yellowish fluid)
 Crusting is the last stage
 The rash affects
 The Face in 95% of cases
 The Palms and soles of the feet (75%)
 Oral mucous membranes (70%)
 Genitalia (30%)
 The Conjunctivae and Cornea (20%)
 It may take three weeks for crusts to disappear
Rash resolved, Pitted scars and/or areas of lighter or
darker skin may remain after scabs have fallen off.
 Once all scabs have fallen off, a person is no
longer contagious.

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Usually 6 to 16 days, but can range
from 5 to 21 days
Develops within 1-3 days after
appearance of fever
14 to 21 days after appearance
of rash
Incubation period
Fever and constitutional
symptoms
Skin rash/mucosal lesions
Systemic manifestations
Sequelae and
complications
Complete resolution
Exposure to monkeypox virus
Chronology of signs and symptoms

22. COMPLICATIONS
• Secondary bacteria infection of
skin lesions
• Septic dermatitis
• Sepsis
• Bronchopneumonia
• GIT: Vomiting, diarrhea,
• Malnutrition
• AKI
• Eye: Keratitis, corneal ulceration
• Encephalitis
• Seizures
• Ulcers
• Mental health
• Death

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Sequelae
 Skin colour changes
• Hyperpigmentation
• Hypopigmentation
 Scars
• Pitted scars
• Hypertrophic scars
 Contractures
 Alopecia
• Usually partial and reversible
 Deformity
• May follow poorly treated skin lesions and
ulcers , urethral strictures
 Psychological dysfunction

24. MPX PICTURE GALLERY

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MPX Acute illness: Rash
Clinic Day 1 Day 6

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Presentation of Lesions
Localized Disseminated

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Genital ulcers

28. CASE DEFINITIONS
Case Definition: NCDC guidelines
Suspected Case Probable Case Confirmed case
• An acute illness with fever >38.3oC,
intense headache,
lymphadenopathy, back pain, myalgia, and
intense asthenia followed
one to three days later by a progressively
developing rash often
beginning on the face (most dense) then
spreading elsewhere on the
body, including soles of feet and palms of
hand.
• A case that meets the clinical case
definition, is not laboratory
confirmed, but has an
epidemiological link to a
confirmed case
• A clinically compatible case
that is laboratory
confirmed………..

29. CASE DEFINITIONS
• So who is a contact?.................................................
Contact
• Any person who has been in direct or indirect contact with a
confirmed case since onset of symptoms i.e. contact with skin lesions,
oral secretions, urine, faeces, vomitus, blood, sexual contact, sharing
a common space (anyone who has been in close proximity with or
without physical contact with a confirmed case).

30. CASE DEFINITIONS
RECOMMENDED CONTACT CATEGORIZATION FOR MPX
Type 1:Direct contact with skin lesions of a confirmed MPX case
- vesicles, pustules, crusts etc. (including sexual contact) OR direct
contact with a confirmed animal case
Type 2:Direct contact with body fluids of confirmed MPX
case (blood, urine, vomitus, faeces, stool, sputum etc.)
Type 3: Sharing of common space with case…………………………….

31. DIAGNOSIS
Laboratory investigations done for various reasons
I. Definitive diagnosis of MPX- PCR with or without sequencing, Viral
Culture.
II. Suggestive but no definitive test……
III. Investigation for underlying co-morbidities……
IV. Investigation to rule out differentials
V. Investigation for Complications
VI. Investigation for Monitoring

32. DIAGNOSIS
Test Description
PCR (including real-time PCR) Tests for the presence of MPXV specific DNA signatures
Viral culture/isolation Live virus is grown and characterized from a patient specimen
Electron microscopy Clear image of a brick-shaped particle for visual classification of a poxvirus
Immunohistochemistry Tests for the presence of OPXV specific antigens
Anti-OPXV IgG Tests for the presence of OPXV antibodies
Anti-OPXV IgM Tests for the presence of OPXV antibodies
Tetracore OrthopoxBioThreat Alert test for the presence of OPXV antigens
Source: Katy Brown K and Leggat P.A. Human Monkeypox: Current State of Knowledge and Implications for the
Future. Trop. Med. Infect. Dis. 2016, 1, 8; doi:10.3390/tropicalmed1010008

33. DIFFERENTIALS
Infectious diseases Non-infectious diseases
• Chickenpox
• Meascles
• Molluscum contagiosum
• Bacterial skin infections such as impetigo
• Disseminated Cryptococcosis
• Disseminated gonococcus infection(DGI)
• Scabies……………………..
• Syphilis…………………..
• Herpes zoster
• Disseminated Herpes simplex
• Foot and mouth disease, dengue fever………
• STI with genital and/or cutaneous manifestation
• E.t.c
• Allergic skin reactions i.e medication induced or
otherwise
• Vasculitis
• Palmo plantar keratoderma
• E.t.c

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Monkeypox: Differential diagnosis
Symptoms Monkeypox Chickenpox Measles
Fever Fever >38°C
Rash after 1-3
days
Fever to 39°C
Rash after 0-2
days
High fever to
40.5°C, Rash
after 2-4 days
Rash
appearance
Maculopapular,
vesicles,
pustules
present at the
same stage on
any area
Macules,
papules,
vesicles,
present in
several
stages
Non-vesicular
rash in
different
stages
Rash
development
Slow, 3-4 weeks Rapid, appear in
crops over
several days
Rapid, 5-7 days
Rash
distribution
Starts on head;
more dense on
face and limbs;
appears on
palms and soles
Starts on head;
more dense on
body; absent on
palms and soles
Starts on
head and
spreads; may
reach hands
and feet
Classic
feature
Lymphadenopathy Itchy rash Koplik spots
Death Up to 11% Rare Varies widely

35. DIFFERENTIALS
Important STI to rule out depending on site of lesions
I. Syphillis
II. LGV
III. Chancroid
IV. Granuloma inguinale
V. Genital Herpes

36. CASE MANAGEMENT
• Human MPx is essentially a self limiting illness in majority of cases
• Complete resolution expected in 3-4 weeks in most cases
• Management is mainly symptomatic and supportive guided by
principles
• Tecovirimat an antiviral is not widely available……………….

37. CASE MANAGEMENT
Principles of management( Credit:NCDC)
• Protection of compromised skin and/or mucous membranes
• Rehydration therapy
• Alleviation of distressful symptoms
• Provision of nutritional support
• Treatment of complications
• Prevention and management of long term sequelae
• Psychosocial support
• Treatment of comorbidities

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System affected/
syndrome
Treatment
objective
Therapeutic considerations/
Clinical setting
Follow-
up/Monitoring
Fever Prevent and treat
episodes of fever
Antipyretic medications, external cooling Routine
temperature
monitoring
Pain Relieve pain Analgesics Pain monitoring
Pruritus Prevent and relieve skin
itching
Warm bath/warm clothing
Calamine Lotion
Antihistamines
Evidence of scratch
marks
Exfoliation, skin
compromise
Minimize insensible
fluid loss, promote
lesion healing
Clean with normal saline , clean ulcers with
povidone-iodine solution or other antiseptic
solution, moisturized dressings, topical antibiotics
(e.g., mupiricon, surgical debridement, skin grafts
if necessary
Lesion count / rash
burden, body
weight, fluid intake /
output
Superinfection skin Prevention/treatment of
secondary bacterial
infections, promote
lesion healing
Oral/intravenous antibiotics, incision and
drainage, advanced wound management (e.g.,
negative pressure wound therapy)
Fever,
pain/tenderness,
erythema, edema,
exudate, warmth
Inflammation/
lymphadenopathy
Minimize pain and
decrease size of
lymphadenopathy
Oral/intravenous anti-inflammatory/analgesic
medications
Size of
lymphadenopathy,
pain/ tenderness
Supportive Treatment Considerations - 1

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System affected/
syndrome
Treatment objective Therapeutic considerations/
Clinical setting
Follow-up/Monitoring
Respiratory tract Maintain patent airways,
prevent respiratory
infection, atelectasis, and
respiratory compromise
Suctioning of the nasopharynx and airways,
incentive spirometry, chest physiotherapy,
bronchodilation, oral/intravenous antibiotics for
prophylaxis/treatment, nebulizer treatments,
bronchoscopy, noninvasive ventilation (e.g., BiPAP
or CPAP), intubation/ventilation
Respiratory rate, pulse oximetry
Sepsis Hemodynamic stabilization Oral/intravenous antibiotics, hemodynamic (e.g.,
intravenous fluid hydration and vasopressors),
supplemental oxygen, corticosteroids, insulin
Hemodynamic monitoring (e.g.,
pulse rate, blood pressure)
Gastrointestinal/ mouth &
throat sores
Minimize mucosal pain and
disruption of food intake,
promote lesion healing
Oral/topical analgesic medications
I.V Antibiotics
Lesion burden, pain scale,
food/fluid intake
Gastrointestinal/ vomiting,
diarrhea
Minimize gastrointestinal
fluid losses
Oral/intramuscular antiemetic and antidiarrheal
medications, oral/intravenous rehydration
Frequency and volume of
emesis and diarrhea, body
weight, fluid intake / output
Ocular infection Prevent corneal scarring
and vision impairment
Ophthalmic antibiotics/antivirals and corticosteroids.
Refer to Ophthalmologists
Vision testing
Supportive Treatment Considerations -2

40. CASE MANAGEMENT
THERAPEUTICS AND VACCINE PIPELINE
Antivirals
• In patients with MPX, it is preferable to use antivirals under
randomized clinical trials (RCTs)…………….
Antiviral Brief description
Tecovirimat Inhibit viral env formation by inh. VP37…..
Brincidofovir Approved for treatment of smallpox, embryo fetal toxicity
Cidofovir DNA polymerase inhibitor, Approval is for CMV, Found to have activity against
poxviruses…….,nephrotoxic
NIOCH-14 Tecovirimat analogue……………………….

41. CASE MANAGEMENT
• Immune globulin: Vaccinia immune globulin(VIG)…………………………..
• Vaccines………………………………………

42. CASE MANAGEMENT
Vaccines examples Generation Approval for Smallpox Approval for monkeypox
Vaccinia, various strains*
from national production
1 Various countries Various national
production (SEP), held by various
countries
NO
ACAM20 (Emergent
BioSolutions)
2 USA - Approved USA - EIND for PEP
LC16m8 (KM Biologics) 3 Japan - Full MA (1975) USA - EIND
(2014)
NO
MVA-BN (Bavarian
Nordic)
3 EU: Imvanex has been authorised
under exceptional circumstances
(2013) Canada: Full MA (2013) USA:
Full MA (2019)
USA, full MA (2019)
Canada, full MA (2019)
LC16m8∆ 4

43. CASE MANAGEMENT
Vaccines and Immunization: Interim guidance by WHO(14/6/2022)
Few points from the document
I. Currently Mass vaccination for MPX is nor required nor
recommended
II. PEP recommended for contact of cases ideally within 4 days of
exposure to prevent onset of disease………
III. PrEP for High risk group……………..
IV. Decision for use of vaccines should based on full assessment of risk
and benefit on a case by case basis……………

44. PROGNOSIS
• Generally good if promptly recognized and managed well…………….
• Certain factors have been shown to affect prognosis with associated
unfavourable outcome
• Prompt recognition of these bad prognostic factors with prompt
management is necessary to reduce morbidity and mortality

45. PROGNOSIS
Some factors shown to affect MPX severity and prognosis
Factors Remark
Belonging to high risk group Children, Pregnant women, Immunosuppresion
Clade of MPX virus CB clade> WA clade
Presence of clinical signs and
symptoms of complications
………………………………………………
Laboratory Abnormalities Elevated
transaminases,hypoalbuminaemia,leukocytosis,low
BUN, thrombocytopenia e.t.c
Skin lesions severity…….. Mild(<25 lesions), Mod(25-99), Sev(100-250) and Very
severe(>250)

46. CONCLUSION
• MPX is a viral zoonotic disease
• Rising global cases worrisome
• Need for increase index of suspicion for prompt diagnosis and
management
• Global response through coordinated one health approach necessary
to control and/or prevent MPX…………..

47. REFERENCES
• National Monkeypox Public Health Response Guidelines NCDC 2019
• Clinical management and IPC for Monkeypox. Interim rapid response guidance.
WHO(10/6/2022)
• NCDC Regional MPX Case management training slides
• Ladnyj, I. D., Ziegler, P., & Kima, E. (1972). A human infection caused by
monkeypox virus in Basankusu Territory, Democratic Republic of the
Congo. Bulletin of the World Health Organization, 46(5), 593–597.
• Kidokoro, M., & Shida, H. (2014). Vaccinia Virus LC16m8∆ as a Vaccine Vector for
Clinical Applications. Vaccines, 2(4), 755–771.
https://doi.org/10.3390/vaccines2040755

48. THANK YOU FOR LISTENING