mpox

Paul G. Auwaerter, M.D.

MICROBIOLOGY

DNA virus and member of the orthopoxvirus genus of the Poxviridae family, monkeypox is similar to smallpox (variola virus), smallpox vaccine (vaccinia virus), and cowpox virus.
- In November 2022, WHO renamed "monkeypox" to "MPOX," with some using lowercase "mpox," allowing for a 1-year transition when both names would be recognized.
  - The idea was to reduce the stigma and discrimination associated with the "monkeypox" name and ensure that the infection is not associated much with non-human primates.
- WHO is using Roman numerals for MPXV variants.
  - The former Congo Basin (Central African) clade is now Clade I.
    - Has high reported human-to-human transmission rates and mortality (up to 10%).
    - It tends to affect children > adults, with higher mortality than Clade II.
  - The former West African clade is Clade II.
    - Clade IIa
      - It causes a mild illness with limited human-to-human transmission and low mortality (~1-3%).
    - Clade IIb refers to variants circulating in the 2022 global outbreak.
Although initially named monkeypox, the animal reservoir is believed to be African rodents but has not been fully defined.

CLINICAL

Previously, an uncommon zoonotic disease spread between infected animals, humans, and contaminated materials.
- First isolated in 1958, with the first human case in 1970, most human cases are seen in Central and West Africa.
  - Before 2022, cases in the U.S. were predominantly imported or due to contact with animals.
  - Progressively, more cases have been described annually in Africa (DRC and West Africa) since the 1970s.
- It resembles smallpox but is milder and less transmissible.
- A large number of cases in Nigeria since 2017 can be traced as the basis of the current WHO global public health emergency.
Outbreaks in the U.S.
- 2003: 71 confirmed or suspected cases.
  - The first U.S. outbreak was traced to the importation of Gambian giant rats, squirrels, and dormice, which spread to prairie dogs sold as pets.[32]
    - Eighteen were hospitalized, and no deaths.
- 2022 outbreak: low-level transmission of Clade II continues worldwide.
  - The U.S. has the highest number of cases, and weekly reports are no longer updated. See CDC case counts for current numbers.
  - Numbers are likely to underestimate actual cases.
    - Cases have vastly decreased in the U.S.; a recent cluster of cases in Chicago heightened concerns that they could re-emerge with less vigilance and immunization among risk groups.
      - New cases continue to be found in the U.S. and other countries, suggesting this may be here to stay as an ongoing disease in humans outside Africa.
      - This is likely due to both behavioral changes and immunization.
  - Spread within social networks implicated, reported in men who have sex with men (MSM), bisexual; few reports in women or children.
  - Deaths are rare in the U.S. and other non-endemic countries during this outbreak. This clade of mpox virus appears milder than the disease acquired in Africa.
    - CDC report of deaths in October 2022[17] found the majority are Black MSM with advanced HIV, not on ART.
  - 2025: Low levels of clade II cases continue worldwide.
- The 2023 outbreak continues to current (2025) in Democratic Republic of the Congo (DRC). Due to Clade I or Ib, the country has the highest recorded cases, and most provinces report cases.
  - WHO declared a Public Health Emergency of International Concern in August 2024 based on >15,000 cases and 537 deaths in the DRC.
    - Much of the spread appears to be within Congolese households and children.
    - Subtype clade 1b, which emerged in eastern DRC and is now found in nearby countries, including Kenya, Rwanda and Uganda, is causing increased concern.
  - Travel-related cases have been seen in Europe since the summer of 2024.
  - Clade 1 in the U.S.: patients with a travel history with infection confirmed first in California (2024); Georgia (Jan 2025).
    - CDC judges risk for widespread clade 1 transmission in U.S. as currently low.
Transmission
- The virus may be acquired through contact, including intact skin and mucous membranes. Most human infections are believed to be respiratory droplet-acquired.
  - Animal-to-human transmission is seen following an infected animal bite or scratch, butchering bush meat, direct contact with body fluids or lesions, or contaminated materials.
  - Acquisition by human-to-human is believed to be predominantly large respiratory droplets among African cases, although they may also be sexually transmitted or through social networks.
    - As a large pox virus, it is not believed to be aerosolizable but can be spread by droplets.
    - The virus enters the body via broken skin, respiratory tract or mucous membranes.
    - Household and nosocomial transmission described
    - Fomite transmission occurs via contaminated clothing or bed sheets.
  - From acquisition to first symptoms, it may range from 5 to 21 days but averages 1 to 2 weeks.
Human-to-dog transmission was documented, which is not unexpected since this poxvirus can be spread among mammals, especially small mammals[22].
- The virus’s worrisome aspect of entering other animal populations makes control difficult.
Symptoms: note that some get a rash first, then symptoms; others experience only a rash.
- Initial viral prodrome
  - Fever, chills, headache, myalgia, back pain, fatigue
    - Occasionally, sore throat with lesions on the tongue and oral mucosa
- Rash phase, typically 1 to 3 days after symptom onset.
  - Viral exanthem, flat/red, becomes nodular, umbilicated, and pox-like with fluid/pus before crusting.
    - Lesions, described as painful, appear in the same stage of development on a single site of the body.
    - Lymphadenopathy often accompanies this phase.
  - For example, in Africa, the rash often begins on the face [Fig 1], and then spreads [Fig 2], including the palms [Fig 3].
    - Skin lesions do not develop in all infected people.
  - 2022 outbreak: nodular, pustular, pox-like, and may have eschar, [Fig 4] and [Fig 5]
    - Consider all oral, genital and anal (proctitis, too) lesions potentially due to mpox.
      - The rash may appear as pustules, blisters or pimples that may be pruritic or painful.
      - Rectal involvement may cause bloody stools (tenesmus), rectal bleeding, severe rectal pain, and local purulence.
      - Rash onset and evolution are not synchronous; lesions may range in several stages.
        Lesion(s) may range from a single spot to a grouping to disseminated cutaneous across the body.
        Lesions may produce pain until crusting when they are often pruritic.
        The rash is not always on the palms or soles.
    - Fever, headache, myalgia, fatigue
    - Lymphadenopathy
    - Respiratory symptoms include dry cough, sore throat and nasal congestion.
- The illness resolves within 4 weeks.
- Mortality ranges from 1 to 10% in reported series from Africa; the 2022 outbreak appears milder though capable of severe illness, especially in immunocompromised people.
  - Most deaths occur in children or people with HIV.
    - Lessons from the 2022 outbreak showed that more severe disease occurs in people immunocompromised or living with HIV, particularly advanced HIV.
  - Risk factors for severe illness appear to be fever ≥ 38.3ºC and > 100 skin lesions.
Differential diagnosis: varicella zoster (primary infection, aka chickenpox), other pox infections (cowpox, orf), smallpox.
- Consider herpes zoster (shingles), measles, and STIs, i.e., syphilis, HSV, LGV and chancroid.
- Test for STIs in mpox patients as above, including HIV if not known.
Diagnosis:
- Clinical suspicion is necessary; contact the local/state health department for assistance in diagnosis.
- Real-time PCR of skin lesion material; obtain two specimens for testing.
  - Obtain multiple samples and dry collection; do not add or store them in viral or universal transport media.
  - CDC guidance for specimen collection
    - Contact lab for specimen requirements.
    - Wear PPE
    - Skin lesion, pharyngeal and rectal swabs are appropriate.
- Serology is perhaps helpful if specimens are not present.
  - Submitting specimens to CDC instructions link.
- CDC case definitions:
  - Suspect, probable, and confirmed
  - Confirmed:
    - Confirmation of Orthopoxvirus DNA by PCR or NGS of a clinical specimen or isolation of the virus in culture is required.
  - Probable:
    - No suspicion of other recent Orthopoxvirus exposure (e.g., Vaccinia virus in ACAM2000 vaccination) and show demonstration of
      - Orthopoxvirus DNA
        PCR from a clinical specimen or
        Immunohistochemical or electron microscopy or
        Detectable anti-orthopoxvirus IgM antibody 4 to 56 days after rash onset
    - Suspect
      - New characteristic rash or
      - Meets one of the epidemiologic criteria and has a high clinical suspicion for mpox
  - Epidemiological criteria: within 21d onset
    - Contact with a person or people with a similar appearing rash or who received a diagnosis of confirmed or probable mpox or
    - Close or intimate in-person contact with individuals in a social network experiencing mpox activity, this includes men who have sex with men (MSM) who meet partners through an online website, digital application ("app"), or social event (e.g., a bar or party) or
    - Traveled outside the U.S. to a country with confirmed cases of mpox or where MPXV is endemic or
    - Had contact with a dead or live wild animal or exotic pet that is an African endemic species or used a product derived from such animals (e.g., game meat, creams, lotions, powders, etc.)
  - Exclusions:
    - Alternate diagnosis achieved
    - The rash doesn’t develop within 5d of illness onset
    - A good quality specimen doesn’t contain Orthopoxvirus DNA or orthopox antibodies.
- Interim CDC definition for clade 1 mpox (June 2024, see link above)
  - Similar to the above definitions but has uses testing to discriminate mpox clade I and II and has epidemiological links such as--
    - Within 21 days of illness onset:
      - Traveled to an area with evidence of sustained human-to-human transmission of clade I mpox or where clade I MPXV is endemic or
      - Reports having contact with a person with confirmed, probable or suspect clade I mpox or
      - Had close or intimate in-person contact with individuals in a social network currently experiencing clade I mpox activity or
      - Had contact with a dead or live wild animal or exotic pet that is a central African endemic species or used a product derived from such animals (e.g., game meat, creams, lotions, powders, etc.)
    - If travel history is elicited, contact local/state health department.
- CDC recommends that clinicians collect two specimens for each patient, each from multiple lesions, preferably from different locations on the body and from lesions with differing appearances.

SITES OF INFECTION

Oral: oral ulceration(s) or pharyngitis.
Ocular: may threaten vision and suggest rapid treatment initiation, though there is limited data on effectiveness in this situation.
Cutaneous: Before crusting, macular or papular lesions evolve into nodules, vesicles, or pustules (pox lesions). Lesions often start on the face, mouth, genitals or anus. It may remain limited in a regional area and spread over the body, including palms and soles.
LN: lymphadenopathy
Pulmonary: pneumonitis, particularly in severe cases
Proctitis: may be severe; a frequent reason for hospital admission
Cardiac: myocarditis, pericarditis, myopericarditis
CNS: encephalitis, myelitis
- Lymphocytic pleocytosis in CSF.
- MRI may have enhancing lesions.

TREATMENT

General

There are no approved treatments for mpox.
- Most patients recover with supportive care.
- Patients with severe disease or if immunocompromised may benefit from antiviral medications.
  - Severe disease includes involvement--
    - Ocular
    - Cardiac
    - CNS
    - Complicated mucosal disease (pharyngeal, genital or rectal)
    - Progressive spread, especially if with underlying severe immunosuppression, including advanced HIV
  - Patients with eczema or atopy
CDC recommends approaching it as similar to smallpox, as a consideration for those with severe disease (CNS, hemorrhagic, requiring hospitalization) or those at high risk (immunocompromised, children < 8 yrs, pregnant/breastfeeding women, or experiencing complications).
- State and territorial health authorities can direct their requests for medical countermeasures to treat mpox to the CDC Emergency Operations Center (770-488-7100).
  - CDC Interim Guidance for mpox treatment recommendations[2] (MMWR 3/3/2023), based on low levels of evidence, e.g., animal model, human case series, and expert experience (no RCT data).
  - This 2023 guidance does not include recent evidence from PALM and STOMP trials that do not suggest most patients benefit from antivirals.
    - PALM007: showed no faster resolution in patients with clade 1 disease in the Congo with skin lesions in this 600-person trial. Mortality was the same in both arms of this tecovirimat vs. placebo RCT, 1.7%.
    - STOMP: examined tecovirimat in clade II patients; NIH ceased trial early when there was no difference when 75% of enrollment (719 participants) was achieved in terms of speeding lesion resolution or pain.
  - Consider the use of antivirals if:
    - Severe disease or evidence of organ system involvement or disseminated infection
    - People at high risk and those who may develop the severe disease may be evaluated on a case-by-case basis (e.g., children < 8, based on smallpox and endemic mpox, although glade IIb outbreak disease is rare in children and appears mild).
      - Immunocompromised condition
        Advanced HIV not on ART, common high-risk group. European reports state that 30-51% of cases with known HIV.
        Specific guidance from the CDC for this group.
        CD4 < 350 may be at risk for not clearing the mpox virus.
      - Hx of atopic dermatitis, exfoliative skin conditions
      - Complicated infected (secondary bacterial infection, gastroenteritis, bronchopneumonia or concurrent disease or comorbidities)
      - Accidental inoculation into the eye, genitals or anus
        Author note: uncertain how this might differ from the customary acquisition in the 2022 outbreak; however, it could represent a lab accident issue, large inoculum, or, ocular, unknown consequence.
- Antivirals (see smallpox module for additional details): It is important to note that there are limited data on the use of these drugs in mpox. Reduce immunosuppression if feasible.
  - The efficacy of treating mpox with tecovirimat is not established for severe disease.
    - Tecovirimat (TPOXX): oral or IV drug (if absorption is uncertain), FDA-approved for smallpox treatment in adults and children ≥ 13 kg.
    - CDC has an Expanded Access Investigational New Drug (EA-IND) protocol.
    - The oral drug should be taken with a high-fat meal (~ 600ca with at least 25mg fat).
    - Note: The STOMP trial did not show significant safety concerns with the drug.
  - Other therapies are infrequently used and may be combined in severely ill or immunosuppressed patients. The change in 2023 is to consider combination therapy in the severely immunosuppressed at the outset.
    - Tecovirimat PLUS/MINUS
      - Brincidofovir: oral drug, FDA-approved on June 4, 2021, for smallpox in all ages, including neonates.
        CDC has an E-IND to facilitate the use in mpox.
        It often causes a brisk elevation in LFTs, prompting discontinuance.
        It needs to be taken on an empty stomach or low-fat meal (~400 calories, 25% max calories from fat).
      - Cidofovir: injectable, has in vitro activity but little human data. Has been used as part of combination therapy for patients with severe disease and immunocompromised.
        It needs to be administered with probenecid.
        Check for drug interactions w/ probenecid.
      - Vaccinia immune globulin (VIVIG)
      - It potentially has cross-reactivity, but it is unknown if it is effective for mpox.
        Has been used as part of combination therapy for patients with severe disease and immunocompromised.
      - Licensed for treatment of complications or aberrant infections due to vaccinia vaccination
      - CDC holds EA-IND allows using VIVIG in an orthopoxvirus outbreak, including mpox.
  - Severely ill and immunocompromised patients with disseminated or persistent infection:
    - CDC suggests combination therapy[17] for those with progression OR despite initial treatment.
    - For example, tecovirimat IV + cidofovir or brincidofovir + VIVIG.
  - Ocular lesions: tecovirimat +/- topical trifluridine.
    - Obtain ophthalmology consultation.
  - Myopericarditis
    - Antivirals suggested.
    - Cardiology consultation; rule out other causes, e.g., receipt of mRNA SARS-CoV-2 vaccine or COVID.
  - CNS disease:
    - Some clinicians employ immunosuppressive therapy with antivirals. There is little data upon which to guide a recommendation, which needs to weigh risks versus benefits.
      - Corticosteroids, IVIG, plasmapheresis or plasma exchange.
    - Tecovirimat penetrates CNS well.
  - Supportive care:
    - Analgesia, especially for oropharyngeal or rectal, may also require narcotics or PCA.
    - IV fluids

Prevention

Monitoring: People with suspected or confirmed mpox should be monitored for 21d after the last contact or potential close exposure.
- If symptoms develop, they should self-isolate and contact their PCP and local health department.
- CDC monitoring recommendations.
Prevention of exposure:
- Avoid direct or intimate contact with people with mpox who have active rashes
- WHO has suggested limiting sexual partners.
- Avoid contact with objects used by people with mpox, including bed linens, towels, and clothing.
- Avoid respiratory secretions and close contact without PPE in people with mpox.
General measures if suspected or confirmed mpox:
- Isolate infected patients from others.
- Hand hygiene after contact with infected animals or humans.
  - Use soap and water or an alcohol-based sanitizer.
- Avoid contact with animals that could harbor the virus (including animals that are sick or found dead in areas where mpox occurs).
- Avoid direct contact with any potentially contaminated materials.
  - CDC notes that the mpox virus can be killed using a standard washing machine with warm water and detergent.
- Use appropriate personal protective equipment (PPE) for patient care (gown, gloves, respirator, and eye protection).
- CDC Infection Prevention and Control of Monkeypox for healthcare settings; for those sent home, CDC isolation recommendations vary depending on the home situation and if people at high risk are present (young children, immunocompromised).
Vaccines: CDC vaccine recommendations (2022, last checked 2/8/25) for at-risk or people with mpox contacts. Vaccine supply is no longer limited.
- CDC has changed the language of pre-exposure prophylaxis (PrEP) to "vaccination before exposure" in the U.S., offered to at-risk groups, including gay, bisexual, and other MSM, transgender, and nonbinary people who, in the last six months, have had sex in a commercial sex venue currently offered PrEP strategy.
  - People with HIV or other immunosuppression with the potential for exposure to mpox should be vaccinated.
  - Known or suspected exposure to someone with mpox
  - Sex partner in the past two weeks who was diagnosed with mpox
  - Gay, bisexual, or other men who have sex with men or a transgender, nonbinary, or gender-diverse person who in the past 6 months has had any of the following:
    - A new diagnosis of one or more sexually transmitted diseases (e.g., chlamydia, gonorrhea, or syphilis)
    - More than one sex partner
  - Any of the following in the past 6 months:
    - Sex at a commercial sex venue (like a sex club or bathhouse)
    - Sex-related to a large commercial event or in a geographic area (city or county, for example) where mpox virus transmission is occurring
    - Sex in exchange for money or other items
  - Sex partner with any of the above risks
  - Anticipation of any of the above scenarios
  - Work in settings where you may be exposed to mpox:
    - Work with orthopoxviruses in a laboratory
- Post-exposure prophylaxis (PEP): Ideally, it is administered within 4 days of exposure; later (d5-14) use may decrease the severity of infection if it occurs; however, both concepts are not evidence-based yet for MPXV.
  - Offer to those with known or presumed exposure.
  - If administered on days 4-14 post-contact, it may not prevent infection but could lessen the severity if acquired.
  - Routine administration of vaccines to the general public is not recommended.
- FDA has approved JYNNEOS^TM(MVA-BN in 2019, also known as Imvamune or Imvanex in the UK, an attenuated live virus vaccine that is non-replicating for the prevention of mpox; ACIP recommends pre-exposure prophylaxis (PrEP) for occupational exposures).
  - FDA-approved for mpox prevention, though efficacy data is limited and observational.
    - Some preliminary data have found among U.S. males aged 18–49 years eligible for JYNNEOS vaccination, mpox incidence was 14x as high among unvaccinated males compared with those who had received a first vaccine dose ≥14 days earlier.
  - SC injection for ≥ 18 years with risks for mpox or exposure
    - Granted SC immunization for adolescents < 18 years determined to be at high risk for mpox.
  - Two doses four weeks apart to render sufficient efficacy for protection.
    - Limited data for vaccine efficacy (VE) exists. Real-world data from Aug ’22 - Mar ’23 suggests VE was 75% for 1 dose and 86% for 2 doses of the JYNNEOS vaccine,
  - It appears to have fewer side effects than the smallpox vaccine/vaccinia.
  - Intradermal method using 0.1ml instead of 0.5 mL SC now with FDA EUA (8/9/2022, now with a fact sheet, see link) based on 2015 data suggesting equivalent generation of neutralizing antibody titers in healthy adults compared to the SC method.
    - Only authorized for ≥ 18 years; used when supply is limited.
- Smallpox vaccine
  - ACAM2000 (live attenuated): more adverse reactions than JYNNEOS.
  - 85% vaccine efficacy when used in Africa to prevent mpox.
  - A far larger supply in the U.S. stockpile, but aging status may mean lower potency.
  - Not currently used for mpox, as a primarily non-lethal disease, ACAM2000 is judged too dangerous a vaccine to use in these circumstances compared to smallpox.

Selected Drug Comments

Drug	Recommendation
Brincidofovir	The FDA-approved oral drug is available in tablets or suspension for smallpox in neonates and above. Three patients received the drug for mpox in a UK case series, though uncertain if it helped in their good outcome[25]. None of the three in this series completed the course due to rising LFTs. CDC holds e-IND for use in mpox
Cidofovir	The U.S. maintains a Strategic National Stockpile for use in the case of smallpox. The drug has in vitro activity; however, it has not been used in a way that enables an understanding of effectiveness against mpox. Has been part of combination therapy employed for people with severe disease, especially among the immunocompromised/AIDS.
Tecovirimat	FDA-approved for smallpox. Although early observational data found that non-severely immunocompromised leads to improvement by d3. However, recent RCTs (PALM007 clade I and STOMP, clade II) failed to show improvement in lesion resolution or pain compared to placebo with the mortality the same in PALM007 in the antiviral and placebo arms, although non-statistically significant subanalysis suggested some benefit in those with severe disease. The trials did not address whether the drug might help those who are severely immunosuppressed or have serious disease or if the drug was used in combination. Evidence suggests for those with mild-moderate disease, supportive care alone is appropriate.
VIVIG	The CDC controls vaccine immune globulin (IV) primarily for the treatment of complications of vaccinia vaccination, including EZ, progressive vaccinia, and generalized vaccinia. It is unknown how effective its use would be in mpox. Has been part of combination therapy employed for people with severe disease, especially among the immunocompromised/AIDS.

FOLLOW UP

If new lesions are forming ≥ 7d of antiviral therapy, consider:
- Orthopoxvirus PCR testing of new lesions
- Assess for superinfection (bacterial)
- Serology to assess IgM response
- Tecovirimat pharmacokinetic testing
- Tecovirimat resistance testing
Upon crusting of lesions, patients are thought to be non-infectious; however, viral kinetics in mpox are not fully described.
Sterile abscesses, bacterial superinfection, and bacteremia are seen.
Isolation practices for confirmed mpox.
- Isolate at home or another location for the duration of the illness.
- Isolation ceases when all symptoms have resolved, including all skin lesions that have healed with a fresh layer of skin (not just crusted).
  - Duration ranges from 2-4 weeks.
- While with rash, cover all parts of the skin with clothing, gloves or bandages.
- Wear a tight-fitting mask, even with no fever or respiratory symptoms.
- Do not share items with others, avoid close contact, and wash hands with alcohol-based sanitizer or soap and water.

OTHER INFORMATION

Low level of cases continue; may expect clusters of cases may occur in the U.S. and elsewhere, especially among high-risk individuals who may gather for community events.
- Two-dose JYNNEOS vaccination is strongly recommended for all at-risk groups.
- Those who have only received one dose are encouraged to get a second dose for improved protection against infection.
- Two-dose efficacy studies have noted the range from 66-86%. Lower rates were seen among immunocompromised, advanced HIV or one dose (51%).
An increase in mpox cases has been ascribed to the successful eradication of smallpox and the cessation of vaccinia immunization programs.

Basis for recommendation

Dalton AF, Diallo AO, Chard AN, et al. Estimated Effectiveness of JYNNEOS Vaccine in Preventing Mpox: A Multijurisdictional Case-Control Study - United States, August 19, 2022-March 31, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(20):553-558. [PMID:37200229]
Comment: More complete data is available, and this is from real-world data for vaccine efficacy which found VE was 75% for one dose and 86% for two doses. This was irrespective of the route of administration or immune status. These data have led to the strong recommendation to recommend a two-dose schedule for risk groups.
Rao AK, Schrodt CA, Minhaj FS, et al. Interim Clinical Treatment Considerations for Severe Manifestations of Mpox - United States, February 2023. MMWR Morb Mortal Wkly Rep. 2023;72(9):232-243. [PMID:36862595]
Comment: Updated guidance based on low levels of evidence for the use of tecovirimat, brincidofovir, cidofovir, trifluridine ophthalmic solution, and vaccinia immune globulin intravenous,
Rao AK, Petersen BW, Whitehill F, et al. Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(22):734-742. [PMID:35653347]
Comment: The ACIP recommended use of this replication-deficient live Vaccinia virus vaccine for people at risk of orthopox infection from potential occupational exposures. On November 3, 2021, ACIP voted to recommend JYNNEOS preexposure prophylaxis as an alternative to ACAM2000 for certain persons at risk for orthopoxviruses.
O'Shea J, Filardo TD, Morris SB, et al. Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection - United States, August 2022. MMWR Morb Mortal Wkly Rep. 2022;71(32):1023-1028. [PMID:35951495]
Comment: The guidance is directed explicitly at people with HIV as they are a substantial portion of the current outbreak. The concern is that they may be at increased risk for severe infection, so using tecovirimat is suggested. The cut-off is not known, but some consider CD4 < 350 as a value. They also note early administration of vaccines (≤4 days after exposure) might prevent monkeypox, and later use (5–14 days after exposure) might decrease the severity of monkeypox if infection occurs---although this is unstudied re: MPVX.
CDC. Mpox Vaccination. Interim Guidance https://www.cdc.gov/poxvirus/mpox/clinicians/vaccines/vaccine-consideratio... last updated 8/2/23, accessed 2/13/2025)
Comment: Updated guidance. Compared to October 2022 recommendations:
Continued emphasis on vaccination: Mpox vaccination should continue to be offered to people with the highest potential for exposure to mpox.
Updated guidance: People with HIV infection or other causes of immunosuppression who have had recent or anticipate potential mpox exposure should be vaccinated against mpox.
JYNNEOS is the main vaccine used in the US. Two SQ administrations are recommended. Also, those who were exposed to mpox can receive PEP immunization.
Mpox: Treatment Information for Healthcare Professionals. https://www.cdc.gov/mpox/hcp/clinical-care (last updated 1/30/2025, accessed 2/13/2025)
Comment: Treatment should be considered in sensitive anatomical areas with a risk of scarring and those with severe illness. Also, those at high risk of severe mpox infections. Recent trials showing a lack of efficacy of tecovirimat in mild-moderate disease have not yet been incorporated. Combination therapy is often employed in progressive disease in those with advanced immunosuppression. Advice is also given for brincidofovir, VIVIG, and cidofovir.

References

Rohilla S, Gaidhane S, Balaraman AK, et al. Ophthalmic Manifestations of the Mpox Virus: A Systematic Review and Meta-Analysis. J Infect Dis. 2025. [PMID:39913333]
Comment: In this review of the literature and meta-analysis, conjunctivitis is the most common ophthalmic complication of Mpox, followed by notable rates for keratitis, eye lesions, and visual impairment. Visual impairment ranged considerably in studies. The treatment effect is not addressed.
Musuka G, Moyo E, Tungwarara N, et al. A critical review of mpox outbreaks, risk factors, and prevention efforts in Africa: lessons learned and evolving practices. IJID Reg. 2024;12:100402. [PMID:39157420]
Comment: While most in North America focused on Clade II, Clade I and Ib have been wreaking havoc in the DRC for years, with increasing cases in other African countries. This is an informative perspective on the insufficient efforts to stymie the outbreak.
Berry MT, Khan SR, Schlub TE, et al. Predicting vaccine effectiveness for mpox. Nat Commun. 2024;15(1):3856. [PMID:38719852]
Comment: Authors argue that delaying a second dose provides more durable immunity, and allows for more first doses to be given in an outbreak situation.
Leonard CM, Poortinga K, Nguyen E, et al. Mpox Outbreak - Los Angeles County, California, May 4-August 17, 2023. MMWR Morb Mortal Wkly Rep. 2024;73(2):44-48. [PMID:38236779]
Comment: Mpox has been identified especially in gay, bisexual and other MSM in the LA County region since spring of 2023. The majority of patients were not immunized, particularly among younger Black, African American, Hispanic, and Latino persons with HIV.
Hazra A, Zucker J, Bell E, et al. Mpox in people with past infection or a complete vaccination course: a global case series. Lancet Infect Dis. 2024;24(1):57-64. [PMID:37678309]
Comment: This report comprises the largest series of people who have reinfection or infection after two doses of JYNNEOS. People who experienced infection after natural immunity (7) had shorter and less severe illnesses. This population was mostly young, gay/bisexual, sexually active men. Typically, fewer lesions were seen, including in the mucosa, with less need for hospitalization or teciviromat.
Deputy NP, Deckert J, Chard AN, et al. Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States. N Engl J Med. 2023;388(26):2434-2443. [PMID:37199451]
Comment: Case-control data using EHRs found that those without 1 or 2 doses of JYNNEOS were more likely to acquire mpox, suggesting effectiveness.
Ogoina D, James HI. Mpox among Linked Heterosexual Casual Partners in Bayelsa, Nigeria. N Engl J Med. 2023;388(22):2101-2104. [PMID:37195934]
Comment: Without a high index of suspicion, mpox appears likely to go underdiagnosed in the heterosexual population, as this letter reflecting some experience in West Africa suggests.
Li P, Li J, Ayada I, et al. Clinical Features, Antiviral Treatment, and Patient Outcomes: A Systematic Review and Comparative Analysis of the Previous and the 2022 Mpox Outbreaks. J Infect Dis. 2023;228(4):391-401. [PMID:36735342]
Comment: This review includes 33 of 73 identified studies for this meta-analysis that compares Clade I and Clade II outbreak data. Insufficient information is available to assess the tecovirimat effect.
Payne AB, Ray LC, Kugeler KJ, et al. Incidence of Monkeypox Among Unvaccinated Persons Compared with Persons Receiving ≥1 JYNNEOS Vaccine Dose - 32 U.S. Jurisdictions, July 31-September 3, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(40):1278-1282. [PMID:36201401]
Comment: Most in the US, as of this writing (Oct 2022), had only received one dose of the vaccine due to supply and administration constraints. It appears that one dose does offer some protection based on this observational sample.
Hagan LM, Beeson A, Hughes S, et al. Monkeypox Case Investigation - Cook County Jail, Chicago, Illinois, July-August 2022. MMWR Morb Mortal Wkly Rep. 2022;71(40):1271-1277. [PMID:36201399]
Comment: Close exposure in jail setting to index patient did NOT cause new cases
Miller MJ, Cash-Goldwasser S, Marx GE, et al. Severe Monkeypox in Hospitalized Patients - United States, August 10-October 10, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(44):1412-1417. [PMID:36327164]
Comment: CDC report wherein they offered consultation to 57 severely ill patients who were predominantly Black with AIDS. Among this group, which is a biased sample, nearly one-third (30%) received ICU-level care, and 21% of patients died. Combination therapy was offered, tecovirimat/cidofovir/VIVIG and suggested for those with severe or progressive disease despite initial therapy. Twelve deaths were reported by CDC, which participated in management. The majority were Black men with advanced HIV and had severe disease ascribed to an immunocompromising state. Not all deaths yet directly attributed to a cause, and one was not thought to be related to MPXV. Combination therapy was often employed, with tecovirimat +/- cidofovir and VVIG. Only four patients were on ART.
Luong Nguyen LB, Ghosn J, Durier C, et al. A prospective national cohort evaluating ring MVA vaccination as post-exposure prophylaxis for monkeypox. Nat Med. 2022. [PMID:35831633]
Comment: The authors note in this letter that recent cases in Nigeria (3552) with only one reported fatality, far less than the 1-10% range reported in earlier years. Modified Vaccinia Ankara–Bavarian Nordic (MVA-BN) is a third-generation live vaccine that is non-replicating and reports predominantly African and European experience with PEP, which appears effective.
Orviz E, Negredo A, Ayerdi O, et al. Monkeypox outbreak in Madrid (Spain): clinical and virological aspects. J Infect. 2022. [PMID:35830908]
Comment: Spain has the most reported cases; this experience from Madrid from May to June 2022 is reported for 48 men. The mean age was 35 years, and 87.5% were MSM; lesions appeared in the area where they had sexual intercourse (genital or anal). Sequencing found the isolates consistent with the western African clade, specifically the Nigerian outbreak of 2017-18 that had low mortality.
Kwok KO, Wei WI, Tang A, et al. Estimation of local transmissibility in the early phase of monkeypox epidemic in 2022. Clin Microbiol Infect. 2022. [PMID:35817231]
Comment: No doubt an imperfect estimate based on early data suggests that in UK, Portugal and Spain, the Ro ranged between 1.3 to 2.1.
Aden TA, Blevins P, York SW, et al. Rapid Diagnostic Testing for Response to the Monkeypox Outbreak - Laboratory Response Network, United States, May 17-June 30, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(28):904-907. [PMID:35834423]
Comment: During the first month and a half of the US monkeypox outbreak, the CDC evaluated 2009 specimens from their external lab network on suspicion of monkeypox. The CDC found that 36% were positive for non-variola Orthopoxvirus. All of those sequenced to date were from the West African clade, similar to findings from patients in Spain and the UK.
Seang S, Burrel S, Todesco E, et al. Evidence of human-to-dog transmission of monkeypox virus. Lancet. 2022. [PMID:35963267]
Comment: In a brief report from Paris, two men with MPXV had subsequent skin lesions in their Italian greyhound PCR positive for MPXV. This canine isolate had 100% homology with one of the patients. The men did sleep with their dog. Worrisome, this is the first report ever in the medical history of viral transmission to a dog. It is not absolutely certain that the dog didn’t harbor the virus first, but it seems unlikely.
Philpott D, Hughes CM, Alroy KA, et al. Epidemiologic and Clinical Characteristics of Monkeypox Cases - United States, May 17-July 22, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(32):1018-1022. [PMID:35951487]
Comment: Early US experience n = 1195. Median age 35, men 98.7%, 94% with MSM in the prior 3 weeks, 41% w/ HIV. Rash in 100% with genitals the most common site (46%). Fever in 63%, lymphadenopathy in 59%.
Du Z, Shao Z, Bai Y, et al. Reproduction number of monkeypox in the early stage of the 2022 multi-country outbreak. J Travel Med. 2022. [PMID:36006837]
Comment:
Using data as of 7/22/22, this group estimates a Ro of 1.29 (95% CI, 1.26-1.33).
Adler H, Gould S, Hine P, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. 2022;22(8):1153-1162. [PMID:35623380]
Comment: The current state-of-the-art review and clinical experience regarding management. Oral antivirals (brincidofovir and tecovirimat) were used but had an uncertain effect in this small patient series. Patients had a surprisingly long period of PCR detection of viral DNA.
Russo AT, Grosenbach DW, Chinsangaram J, et al. An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. Expert Rev Anti Infect Ther. 2021;19(3):331-344. [PMID:32882158]
Comment: This oral drug has broad activity against many known orthopox viruses.
Hutson CL, Kondas AV, Mauldin MR, et al. Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model. mSphere. 2021;6(1). [PMID:33536322]
Comment: Animal model of monkeypox, however, authors state that dosing selection may have impacted results.
Petersen E, Kantele A, Koopmans M, et al. Human Monkeypox: Epidemiologic and Clinical Characteristics, Diagnosis, and Prevention. Infect Dis Clin North Am. 2019;33(4):1027-1043. [PMID:30981594]
Comment: Authors have organized clinical data and impressions from outbreaks of monkeypox in Africa and the UK. Increase in monkeypox cases has been ascribed to the successful eradication of smallpox and the cessation of vaccinia immunization programs.
Grosenbach DW, Honeychurch K, Rose EA, et al. Oral Tecovirimat for the Treatment of Smallpox. N Engl J Med. 2018;379(1):44-53. [PMID:29972742]
Comment: Animal model data lead to approval of the drug for smallpox since human data is impossible.
Huhn GD, Bauer AM, Yorita K, et al. Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis. 2005;41(12):1742-51. [PMID:16288398]
Comment: Risk factors for severe disease appeared to be two: fever ≥ 38.3°C and > 100 lesions.
Learned LA, Reynolds MG, Wassa DW, et al. Extended interhuman transmission of monkeypox in a hospital community in the Republic of the Congo, 2003. Am J Trop Med Hyg. 2005;73(2):428-34. [PMID:16103616]
Comment: Six cases among those in this pediatric outbreak had an extended chain of transmission among humans. Authors aptly noted the potential for more concerning and widespread transmission among humans in future if cases are not contained early in an outbreak.
Centers for Disease Control and Prevention (CDC). Update: multistate outbreak of monkeypox--Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. MMWR Morb Mortal Wkly Rep. 2003;52(27):642-6. [PMID:12855947]
Comment: The report describes 71 cases, 35 lab-confirmed and 36 suspected cases, with the majority exposed to prairie dogs. Use of smallpox vaccine included pre-exposure administration to 3 veterinarians, 2 lab workers, and two healthcare workers and post-exposure to 23 individuals. All 35 confirmed cases traced back to prairie dogs housed, at an Illinois animal distributor, with Gambian giant rats and dormice that originated from Ghana.
Rating: Important