Monkey Pox slides; Get to learn the risk factors,presentation and management of Mpox

Mpox is a public health concern

1. MPox Disease Dr Suilanji Sivile Infectious Disease Specialist University Teaching Hospital 95 95 95

2. Other emerging and reimaging disease

3. Outline Background Epidemiology C linical Presentations Diagnosis Treatment

4. Introduction The genus Orthopoxvirus , Parapoxvirus , Molluscipoxvirus , and Yatapoxvirus are the belongs to the family of Poxviridae, . The orthopoxvirus Variola is the causative agent of smallpox, which in 1980 was declared by the World Health Organization (WHO) to be eradicated worldwide. Other orthopoxviruses known to infect humans are cowpox, vaccinia, and monkeypox. There is cross-reactive among members of the genus orthopoxvirus species Vaccinia virus is the orthopoxvirus species now characterized as the constituent of smallpox vaccine. The demonstration that orthopoxviruses can be created de novo using synthetic biology techniques makes possible targets for bio-terrorism

5. Monkey Pox Virus Monkeypox was first recognized by Von Magnus in Copenhagen in 1958 as an exanthem of primates in captivity. Monkeypox virus was so named because it was first detected in captive Asiatic monkeys; however, the virus has been found naturally only in Africa among rodents. First cases of human monkey pox noted in the 1970s during smallpox surveillance activities in Africa and was clinically indistinguishable from smallpox, Poxvirus are large and brick shaped with virions range in length from 220 to 450 nm and in width and depth from 140 to 260 nm

6. Mpox disease Usually a self-limited with symptoms lasting from 2 to 4 weeks Severe cases can occur. 2022 CFR 3–6% Transmitted to humans through close contact with an infected person or animal, or with material contaminated with the virus Monkeypox is a viral zoonotic disease that occurs primarily in tropical rainforest areas of central and west Africa and is occasionally exported to other regions Pathophysiology known from animal models with entry through the lungs and skin

7. Mpox Transmission Indirect contact with lesion material such as clothing or linens Respiratory secretions during prolonged, face-to-face contact or intimate physical contact (kissing, cuddling, sex) Placenta in infected pregnant person to fetus Direct contact with infectious rash, scabs, body fluids cdc.gov/poxvirus/mpox/if-sick/transmission.html.

8. Monkeypox History First described in monkeys used for research in 1958 1 First human case in 1970 Transmitted to humans by infected animals (mostly rodents) Countries in Central and West Africa experienced “endemic” outbreaks Outbreak in 2003 in USA 2017 outbreak in Nigeria suggested that sexual transmission may have occurred 2 Major outbreak in 2022-2023 Current outbreak in Africa 1. cdc.gov/poxvirus/monkeypox/about/index.html. 2. Ogoina. PLoS One. 2019;14:e0214229. 3. Durski. MMWR. 2018;67:306. Countries Reporting Monkeypox Cases, 1970-2023 1990-1999 Before 1990 2000-2009 2010-2017

9. Monkeypox Outbreak in 2022 66,471 infections (as of September 25, 2022) 97.4% (33595/34483) with available data are male Among those with known HIV status, 46.6% (7647/16401) are PWH 26 deaths 106 countries 2022 Monkeypox Outbreak: Global Trends. Geneva: World Health Organization, 2022. Available online: https://worldhealthorg.shinyapps.io/mpx_global/ (last cited: [Sept 28, 2022]).

10. Mpox Classic Clinical Manifestations Orthopoxvirus in Poxviridae family Same genus as variola virus (causes smallpox), vaccinia virus (used in smallpox vaccine), and cowpox virus Incubation: 5-13 days (range 3-17 days) Illness: 2-4 wk Infectious from prodrome until scabs fall off and fresh layer of skin forms Clinical presentation similar to smallpox Clad I and Clad II disease Prodrome: fever, malaise, headache, weakness, lymphadenopathy Rash: appears shortly after prodrome Typically lesions develop simultaneously and evolve together Well-circumscribed, deep seated with umbilication, painful When disseminated, often centrifugal: arms, legs, hands, feet; can involve palms and soles 4 stages (macular, papular, vesicular, pustular) before scabbing who.int/news-room/fact-sheets/detail/monkeypox. cdc.gov/poxvirus/mpox/symptoms/index.html.

11. Clinical Progression of MPox

12. Mpox Symptoms in 2022-2024 Outbreak: Men N = 34,350 cases with ≥1 symptom reported in country with ≥2 unique symptoms worldhealthorg.shinyapps.io/mpx_global. Any rash Fever Systemic rash Genital rash Any lymphadenopathy Headache Muscle ache General lymphadenopathy Fatigue Local lymphadenopathy Sore throat Rash, unknown location Oral rash Chills Cough Vomiting Lymphadenopathy, location unknown Anogenital pain and/or bleeding Other Asymptomatic Conjunctivitis Diarrhea Genital edema Symptom Proportion of cases with reported symptom, % 25 50 75 100 90.3 58.5 54.4 50.4 30.6 28.8 26.2 23.5 18.4 16.5 13.0 9.9 8.1 7.4 2.3 2.1 1.3 1.1 0.7 0.7 0.5 0.3 0.1

13. Mpox Symptoms in 2022-2024 Outbreak: Women N = 1371 cases with ≥1 symptom reported in country with ≥2 unique symptoms worldhealthorg.shinyapps.io/mpx_global. Any rash Systemic rash Fever Headache Muscle ache Genital rash Any lymphadenopathy Sore throat Fatigue General lymphadenopathy Local lymphadenopathy Chills Oral rash Cough Vomiting Rash, unknown location Asymptomatic Lymphadenopathy, location unknown Conjunctivitis Other Anogenital pain and/or bleeding Diarrhea Genital edema Symptom Proportion of cases with reported symptom, % 25 50 75 100 84.2 70.2 50.5 37.4 29.1 28.4 16.6 15.9 11.1 10.7 9.6 8.8 6.1 4.2 3.8 1.7 1.2 1.0 1.0 0.4 0.4 0.1 0.0

14. Mpox Complications: 2022-2024 Outbreak Characteristic, n (%) Overall May 2022 - March 2024 (N = 88,513) Recent October 2023 - April 2024 (N = 1692) Hospitalized (for isolation or medical treatment) 5785 (10.9) 123 (15.3) ICU 48 (0.3) 0 (0) Died 144 (0.3) 3 (0.4) worldhealthorg.shinyapps.io/mpx_global.

15. International Case Series of Monkeypox: Clinical Presentation Clinical presentation was similar between PWH and people without HIV Thornhill. NEJM . 2022;387:679. Reported Clinical Features, n (%) All Persons (N = 528) Rash or skin lesions 500 (95) Fever 330 (62) Lymphadenopathy 295 (56) Pharyngitis 113 (21) Headache 145 (27) Lethargy or exhaustion 216 (41) Myalgia 165 (31) Low mood 54 (10) Proctitis or anorectal pain 75 (14) Characteristic, n (%) All Persons (N = 528) Site of skin lesions Anogenital area Face Trunk or limbs Palms or soles 383 (73) 134 (25) 292 (55) 51 (10) No. of skin lesions <5 5-10 11-20 >20 207 (39) 131 (25) 112 (21) 56 (11) Mucosal lesions present 217 (41)

16. International Case Series of Monkeypox: Treatment and Outcomes No difference in frequency of hospital admission between PWH and people without HIV Overall, no apparent differences in clinical presentation or disease severity between PWH and people without HIV Most PWH were well controlled with high CD4 cell counts 3 new HIV infections identified Thornhill. NEJM . 2022;387:679. Treatment, n (%) All Persons (N = 528) Medical care setting Inpatient Outpatient 70 (13) 458 (87) Received monkeypox-specific treatment 25 (5) Treatment Cidofovir Tecovirimat Vaccinia immune globulin Other 12 (2) 8 (2) 1 (<1) 2 (<1)

17. Risk Progression by Rash Stage

18. C onfirmed MPox

19. Extra Cutaneous Manifestations of MPox Danger Signs loss of vision delirium, loss of consciousness, convulsions respiratory distress bleeding, inability to produce urine signs of sepsis Long-term sequelae pockmarks, scarring or loss of pigmentation corneal ulcers and blindness corneal ulcers and blindness

20. Pattern of Rash Mpox vs Chicken Pox

21. Comparison Mpox, Chickenpox & Measles

22. Differentials for Rash Illness

23. Diagnosis Medical history – includes travel history Lab tests for polymerase chain reaction (PCR) test skin lesion swabs Recommended specimen: skin lesion material lesion from any part of body acceptable if visible lesion Use two sterile synthetic swabs (such as polyester, or nylon) per lesion Swab lesion vigorously to collect adequate DNA Not necessary to de-roof the lesion before swabbing Approximately 3 lesions per patient from different locations on the body or from lesions which differ in appearance

24. Case definitions Suspect Case New characteristic rash*  OR Meets one of the epidemiologic criteria and has a high clinical suspicion for mpox Probable Case No suspicion of other recent  Orthopoxvirus  exposure (e.g.,  Vaccinia virus  in ACAM2000 vaccination)  AND  demonstration of the presence of Orthopoxvirus  DNA by polymerase chain reaction of a clinical specimen  OR Orthopoxvirus  using immunohistochemical or electron microscopy testing methods  OR Demonstration of detectable levels of anti- orthopoxvirus IgM antibody during the period of 4 to 56 days after rash onset

25. C ase defintion Confirmed Case Demonstration of the presence of monkeypox virus (MPXV) DNA by polymerase chain reaction testing or Next-Generation sequencing of a clinical specimen  OR  isolation of MPXV in culture from a clinical specimen EPIDEMIOLOGICAL LINK IS CRITICAL

26. Primary Prevention Vaccination Indications for PPV For people with confirmed exposure to monkeypox through public health investigation, contact tracing, or risk exposure assessments For people with presumed exposure to Monkeypox Know a sexual partner within the past 14 days who was diagnosed with monkeypox Have had multiple sex partners in the past 14 days in an area with Monkeypox

27. Monkeypox Treatment Recommendations Supportive care including pain management Antivirals can be considered in the following scenarios: Severe disease Hemorrhagic, large number of lesions, sepsis, encephalitis, ocular, hospitalization Involvement of anatomic areas that might result in serious sequelae Pharynx, penile foreskin, vulva, vagina, urethra, or rectum People at high risk for severe disease Immunosuppressed (including advanced or poorly controlled HIV), pediatric patients (especially aged <8 yr), pregnant or breastfeeding, conditions affecting skin integrity cdc.gov/poxvirus/monkeypox/clinicians/treatment.html

28. Monkeypox Treatment Options Tecovirimat (approved for smallpox) Authorized by EMA under “exceptional circumstances” and FDA under compassionate use for treatment of monkeypox Cidofovir Brincidofovir VIGIV Can be considered for severe cases Can be considered for prophylactic use in an exposed person with severe immunodeficiency in T-cell function for which smallpox vaccination following exposure to monkeypox virus is contraindicated cdc.gov/poxvirus/monkeypox/clinicians/treatment.html . england.nhs.uk/commissioning/wp-content/ uploads/sites/12/2022/09/B2008-Tecovirimat-treatment-for-patients-hospitalised-due-to-monkeypox.pdf.

29. Vaccination Recommendations for PWH Vaccination for PEP, ideally within 4 days of exposure, but up to 14 and expanded PEP (PEP++) for those who may have been more likely to be exposed Vaccine JYNNEOS/Imvanex (MVA-BN) ACAM2000 Vaccine virus Replication-deficient modified vaccinia Ankara Replication-competent vaccinia virus Indication Smallpox and monkeypox Smallpox Recommendations in adult PWH not previously vaccinated against smallpox with: CD4 cell count ≥200 cells/mm 3 0.5 mL SC/IM or 0.1 mL intradermal (with supply constraints) + Second dose after ≥28 days Do not administer Recommendations in PWH not previously vaccinated against smallpox with: CD4 cell count <200 cells/mm 3 0.5 mL SC/IM + Second dose after ≥28 days Do not administer cdc.gov/poxvirus/monkeypox/interim-considerations/special-populations.html. assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1100600/ recommendations-for-pre-and-post-exposure-vaccination-during-a-monkeypox-incident-26-august-2022.pdf.