Update on Mpox-what the primary care clinician should know

Background and Epidemiology

The 2022 mpox epidemic transformed a previously neglected disease endemic to Western and Central Africa into a significant international concern. Mpox is a syndrome caused by the Monkeypox Virus (MPXV), a member of the Orthopoxvirus genus within the Poxviridae family¹. MPXV was first isolated and described in 1958 by researchers in Denmark, who named the virus monkeypox due to the first known host, but this notably does not correlate with the animal reservoir for the disease, which is unknown^2–5.

Two different MPXV clades have been identified; Clade I and Clade II , which is comprised of two different subclades designated IIa and IIb ⁶. In a mouse model, clade I appears to be most virulent (and is reported to cause up to 10% mortality in humans), with clade IIb as the least virulent ⁷. Clade IIb virus has driven the majority of cases in the 2022 outbreak ^6,7.

The first known human mpox case was described in 1970 in the Democratic Republic of the Congo in a 9-month-old infant ⁸. Subsequent outbreaks have occurred primarily in West and Central Africa, with increasing frequency and case counts after the 1970s ⁹. It is suspected that as smallpox immunity waned with decreasing vaccination campaigns, the number of mpox outbreaks increased in a population more susceptible to orthopoxviruses ¹⁰. The first major outbreak of mpox in the western hemisphere took place in the United States in 2003, when 47 human cases were reported after contact with domesticated prairie dogs infected with MPXV from imported Ghanaian rodents ^11–13. There were no cases of human-to-human transmission^12,13.

The first confirmed case in the 2022 outbreak dated to May 6, 2022, in the United Kingdom, followed by several cases that were unrelated to the first case and without recent travel history, indicating local transmission of MPXV ³. Cases went on to be reported worldwide, prompting the WHO to declare mpox a global health emergency on July 23, 2022 ^14,15.

Within the United States, the first identified case was reported on May 17, 2022. Incidence rose rapidly, peaking in August 2022, with nearly 700 cases per day. From October 2022 CDC data , the median age of those diagnosed with mpox was 34 years old. In patients with available data, 95% of cases were men, of whom 75% reported sexual contact with another man in the last 21 days. In the cases with known HIV status (only 20% of total cases), 57% cases had mpox and HIV co-infection ¹⁶. As of this writing, there have been over 87,500 cases worldwide, with 147 deaths. Over 85,900 cases were in areas that have not previously had mpox cases. The United States has contributed the bulk of cases with over 30,000, followed by Brazil with nearly 11,000 and Spain with over 7,500 ¹⁷.

After August 2022, mpox incidence steadily declined, leading the US Department of Health and Human Services to allow the mpox public health emergency to expire on January 31, 2023 ¹⁸, with the WHO following suit on May 11, 2023 ¹⁹. The decrease in cases was likely driven by a combination of factors including behavioral changes ²⁰ and immunity due to both vaccination and natural infection²¹. In the spring of 2023, however, a resurgence of mpox was observed in Chicago, Illinois, with 13 cases reported between April 17 and May 5, 2023. Notably, 69% of these were previously fully vaccinated with JYNNEOS ^21,22. The European Centre for Disease Prevention and Control has also reported an increase of cases in April and early May 2023 with 17 new cases across 8 countries ¹⁴.

Transmission

Transmission of the current epidemic of MPXV Clade IIb is thought be primarily through close physical contact, such as occurs during sexual activity. In the initial international case series by Thornhill et al, skin and anogenital lesions had the highest rate of positivity (97%), with much lower rates in samples from the nasopharynx (26%), blood (7%) and urine (3%)²³. Further reports have suggested higher MPXV loads in genital, skin lesion, and rectal samples than in those from pharyngeal, urine, blood, or nasopharyngeal samples, demonstrating more inefficient respiratory transmission^24,25. Viral DNA is shed for up to 3 weeks after symptom onset, though some studies have shown low-level detectable DNA for longer periods²⁶. In one cohort study from Spain, replication-competent virus was found only in the first 21 days at any body site, with skin lesions having the highest viral loads and longest duration of replication-competent virus ²⁷. No MPXV transmissions have been observed after lesions have healed. Presymptomatic transmission has been reported up to 4 days before symptom onset ²⁶.

Household transmission: to children

Household transmission to children has been rare in the United States during this outbreak. In a case series from California, the overall rate of mpox in children was low, representing only 0.3% cases in California.The MPXV calculated secondary attack rate was 4.7%. ²⁸.

Healthcare-associated transmission

Overall HCP acquisition rates appear low—in a report published on Colorado healthcare personnel (HCP) exposed to mpox, there were 0 cases of mpox despite overall low rates (23%) of adherence to recommended personal protective equipment²⁹. This is also consistent with prior outbreaks, where the rate of transmission to HCP is extremely low, with only 1 case reported prior to the 2022 outbreak ³⁰. The greatest risk of mpox transmission to HCP appears to be with needlestick injuries from equipment used to unroof vesicles or lesions ^31–34,35.

Clinical presentation

Until the 2022 outbreak, descriptions of the mpox clinical syndrome were drawn from a relatively few endemic and epidemic case series. In this context, the initial symptom in most infected individuals was a systemic prodrome consisting of fever, headache, myalgias, malaise, and lymphadenopathy, which was then followed by the development of a characteristic rash. Skin lesions were typically described as disseminated and synchronous, progressing through stages from macule, to papule, vesicle, pustule, then scab ^36,37.

The recent outbreak has been notable for key differences in presentation. Rash has been the initial symptom in approximately half of patients and can be asynchronous. Most patients will, however, experience at least one systemic symptom at some time during the course of their infection ^38–41. Generalized lymphadenopathy may be present during prodrome, but localized lymphadenopathy is more common.

Lesions can exist in any of the stages noted above, with frequent umbilication in the papular/pustular stage (Figure 1). They are typically painful, especially entering the papular phase, and can become pruritic as they scab and heal. A majority of individuals have involvement of the oral and/or anogenital areas, with or without affected skin at other sites including the palms and soles. Most have fewer than 20 lesions at presentation and, importantly, cases have been reported of mucosal infection without visible skin lesions.

Figure 1:

Stages of mpox lesions

Mucosal involvement is common and may reflect the site(s) of exposure. In a case series from the 2022 outbreak, proctitis was noted in approximately 20-30% of mpox cases ^42–44 and was a frequent driver of hospital admission ^45–46. Proctitis typically presents with anorectal pain, tenesmus, and discharge with or without diarrhea or constipation. External lesions around the anus may or may not be visible. Sore throat may occur as part of the systemic infectious syndrome, but direct oropharyngeal mucosal involvement is also relatively common. The least frequent, but potentially most morbid, mucosal manifestation is ocular infection, which can include conjunctivitis, blepharitis, or keratitis ^47–49.

Immunocompromised individuals can develop more severe manifestations, including high-burden skin and mucosal lesions, as well as other organ involvement such as pneumonia or encephalitis. Notably, individuals with well-controlled HIV present with similar symptoms and disease severity as those without HIV ⁴⁵. In all individuals, lesions may develop bacterial superinfection with resulting ulceration and/or cellulitis.

Laboratory abnormalities occur frequently and are nonspecific, including cytopenias (especially lymphopenia), thrombocytosis, and transaminase elevation.

Differential Diagnosis

Previous literature regarding differential diagnoses for mpox relied primarily on differentiating this infection from smallpox, with mpox distinguished by the presence of lymphadenopathy and synchronous skin lesions. In the post-smallpox era, mpox differential diagnosis hinges on the clinical syndromes and risk groups noted above. Differential diagnoses based on clinical syndrome are reported in Table 1, along with differentiating characteristics for each pathogen.

Table 1:

Differential diagnoses of mpox-related syndromes and distinguishing features of other pathogens

Syndrome	Common infectious differentials	Distinguishing features
Rash (localized or general)
	HSV	- History of prior outbreaks. - Generalized rash less common - Systemic symptoms uncommon with localized rash
	VZV	- Dermatomal distribution (shingles) - Isolated anogenital involvement less common
	Molluscum contagiosum	- Lesions typically painless - Systemic symptoms, mucosal involvement, and lesions on palms/soles less common
	Secondary syphilis	- Rash lacks vesicles or umbilication, though can be ulcerated or pustular
	Acute HIV	- Umbilication of skin lesions and anogenital involvement are uncommon
Genital ulcer
	HSV	- History of prior outbreaks - Systemic symptoms are rare
	Primary syphilis	- Typically painless
	LGV	- Ulcer typically painless, often resolved at time of presentation
	Chancroid	- Currently rare in the United States
Proctitis
	Gonorrhea	- No papular/vesicular lesions - No systemic symptoms
	Chlamydia (serovars D-K)	- No papular/vesicular lesions - No systemic symptoms
	Lymphogranuloma venereum	- Genital ulcer typically not concurrent with proctitis
	Secondary Syphilis	- Can present with rectal mass, but genital ulcers are generally not concurrent
	HSV	- History of prior outbreaks
	Enteric bacteria	- No ulcers or skin/mucosal lesions

As rash is present in almost all patients with mpox, this directs the primary differential diagnosis, with each alternative agent having distinct rash characteristics. HSV and VZV can resemble the vesicular lesions of mpox, and molluscum contagiosum the more umbilicated stage, while secondary syphilis can cause a diffuse rash (which is classically macular, but can be pustular or ulcerative) accompanied by systemic symptoms. Finally, while rash is a less common presentation, HIV should be ruled out in all individuals presenting with the symptoms above and relevant epidemiologic risk.

Individuals presenting with genital ulcer disease should additionally be considered for diagnoses of HSV, syphilis, chancroid, and lymphogranuloma venereum. Genital herpes (HSV) in particular can be difficult to distinguish from mpox, with prior episodes being the primary clue on history, and NAAT testing being the only way to definitively distinguish these.

Chlamydia (including LGV), gonorrhea, HSV, and syphilis should also be part of the differential diagnosis for individuals with proctitis. Proctocolitis, in which individuals develop abdominal pain and diarrhea in addition to rectal pain, tenesmus, and discharge can be caused by LGV as well as enteric organisms such as Salmonella, Shigella, and Campylobacter, especially among MSM ⁵⁰.

All patients suspected of mpox should undergo comprehensive STI testing regardless of specific symptoms. This should include, at a minimum, HIV antibody/antigen testing, syphilis serologies, and gonorrhea/chlamydia nucleic acid amplification testing (NAAT) from the rectum, pharynx, and urine/cervix as indicated.

Testing/diagnosis

PCR analysis of specimens obtained from infected body sites is the primary means of confirming a diagnosis of mpox. The CDC has published a helpful guide for medical professionals collecting specimens to be sent for testing, which is available at (https://www.cdc.gov/poxvirus/mpox/clinicians/prep-collection-specimens.html). Serology is not routinely used.

Skin lesions are the recommended source of specimens, and can comprise swabs of intact lesions or exudate, as well as samples of crust. At least two lesions from different body sites and different stages should be sampled, with two swabs sent per lesion. Swabs should be made from a synthetic material such as nylon or Dacron – not cotton. Both dry swabs and viral transport media can be used, but bacterial transport media should be avoided as these can interfere with the PCR assay. It is important to confirm the exact swab/transport media requirement with the lab processing the specimen prior to testing. Requirements for specimens sent to the CDC can be found at the URL above.

Once mpox is suspected, and prior to swabbing lesions, the CDC recommends that providers don appropriate PPE, defined as gown, gloves, eye protection, and a respirator (e.g. N95) mask. Swabs should be held in such a way that the gloved fingers do not touch any part of the final specimen—for swabs transported in liquid media, this means holding the swab above the portion that will ultimately be submerged. Swabs should be pressed firmly against the lesion and swiped back and forth, with this process repeated on the other side of the swab. Unroofing lesions is not recommended, as this is not required for an adequate sample and incurs a risk of needlestick injury and iatrogenic infection. If accepted by the lab handling the specimen, crusts at least 4 mm x 4 mm can be removed with forceps or another sterile instrument and transported in a dry, sterile container.

If a patient has no skin lesions, but mpox is still suspected, virus has been successfully detected at other sites including oropharyngeal and rectal mucosa as well as urine, although this testing is not currently FDA-approved, nor available from commercial labs ⁵¹. At least one study has shown that testing one of these other sites in addition to skin lesions does not increase diagnostic yield ⁵².

All laboratories performing mpox testing should report positive results to the applicable local health department. In order to report suspected mpox clinicians can contact their state health department or the CDC Emergency Operations Center at (770-488-7100).

Transmission Precautions

People with mpox who do not require hospitalization should make every attempt to limit contact with others to prevent spread of the virus. Ideally this would be isolation at home in a area separated from other individuals, but this may not always be practical. The CDC recommends that individuals with mpox avoid close, skin-to-skin contact including sexual contact until all lesions have healed completely and all other symptoms have resolved. Crowds and congregate settings should be avoided when possible, and clothes, gloves, and/or bandages should cover all skin lesions when in shared spaces. Items that may have come into contact with infected lesions or mucosa, such as clothes, towels, bedding, and eating or drinking utensils, should not be shared. These items should be washed or disinfected before being used by other individuals. The CDC additionally recommends that people with mpox wear a well-fitting mask when in close contact with others, although the role of respiratory transmission in the recent outbreak remains unclear. Additional caution should be taken to avoid contact with high-risk individuals including immunocompromised people. People with mpox and those around them can be reassured that brief contact such as a short conversation, or even prolonged proximity without physical contact has not been shown to spread mpox ⁵³.

Prognosis

Fortunately, the course of mpox is self-limited in most cases; according to CDC statistics, the United States’ case fatality rate for mpox was 1.3 per 1000 cases. However, this statistic changes dramatically among immunosuppressed individuals. Nearly 94% of US deaths due to mpox occurred among people with HIV, and among the subset of those with available data, all had CD4 counts less than 200. ⁵⁴.

While most survivors experience no long-term sequelae, scarring at lesion sites has been reported, and can be of cosmetic concern in areas such as the face or genitals ⁵⁵. Concern has also been raised for risk of strictures of the anus or urethra.

The timeline of mpox recovery varies based on severity, and illness can be prolonged among those with severe disease and especially immunosuppression. For most individuals, however, the total course of illness is approximately 2-4 weeks, and nearly all patients can expect to make a full recovery.

Post-exposure Prophylaxis (PEP)

Individuals with exposure to mpox should be offered a dose of mpox vaccine as post-exposure prophylaxis. Vaccination is recommended within 4 days for optimal efficacy, but receipt of vaccine between 4 and 14 days may also confer some degree of protection. Those who do not go on to develop symptomatic infection should complete the full 2-dose vaccine series. Thus far, evidence for this practice is limited to use of smallpox vaccine in 30 exposed individuals during the much smaller 2003 US mpox outbreak, with only 1 subsequent symptomatic infection ⁵⁶. While efforts are underway to evaluate this strategy during the 2022 outbreak ⁵⁷, public data regarding efficacy is not yet available. Some clinics may have the capacity to keep mpox vaccine on hand for both primary and post-exposure prophylaxis. In cases where this is not feasible, primary care providers should contact their local health department regarding vaccine availability.

Primary Prevention

Vaccination efforts have been central to containing the recent mpox outbreak. The principal vaccine currently in use is based on Modified Vaccinia Ankara (MVA), a live but replication-deficient virus strain developed in the late stages of the global campaign to eradicate smallpox. Unlike prior smallpox vaccines such ACAM2000 or Dryvax, vaccines based on MVA are NOT capable of causing infection. Of note, vaccines based on this virus are not a recent development—one was deployed in Germany in the 1970s as a primer for other smallpox vaccines, where it was administered to over 100,000 people with an excellent safety profile⁵⁸. The currently available product in the United States is manufactured by Bavarian Nordic under the trade name JYNNEOS.

Mpox vaccine is administered as a two-dose series of either subcutaneous or intradermal injections spaced 4 weeks apart. Intradermal administration typically is performed on the volar surface of the forearm, and subcutaneous dosing over the tricep or deltoid (adults) or anterolateral thigh (children <12). Intradermal dosing has been favored during periods of limited vaccine supply due to the lower dose required, allowing for increased numbers of individuals to be vaccinated, but only the subcutaneous route is FDA licensed at this time. Evidence for intradermal administration is based on studies showing comparable levels of resulting antibody titers, but there is not yet clinical data comparing the two routes of administration ⁵⁹. At present, they are considered interchangeable.

At the time of publication, the CDC recommends mpox vaccination for primary prevention in groups at elevated risk of infection (Box 1). The full vaccination recommendations can be accessed at: https://www.cdc.gov/poxvirus/mpox/interim-considerations/overview.html

Box 1: Mpox vaccination (Modified Vaccinia Ankara).

Schedule

2 doses administered 28 days apart

Groups recommended for primary prevention

• Gay and bisexual men who have sex with men with either:

  • more than 1 sex partner in the last 6 months
  • any STI in the last 6 months

• Individuals engaging in sex at a commercial sex venue or in association with a large public event

• Sexual partners of individuals in the above groups

• Individuals with immunosuppression (including HIV) who anticipate contact with mpox

• Those with occupational risk, primarily lab workers

Post-exposure prophylaxis

• Preferably within 4 days of exposure, may offer some protection out to 14 days

Estimates of vaccine efficacy from restrospective data have ranged from 35.8-86% for one dose, and 66-88.5% for two doses of vaccine ^60–64.

Vaccination side effects are rare ⁶⁵. Local reactions such as pain, erythema, swelling, or pruritis are the most common, and can be managed with topical emollients, cold compresses, and/or oral antihistamines. Intradermal vaccination appears to confer a higher risk of local cutaneous adverse reaction, with erythema lasting only a few days ⁶⁶, but subsequent hyperpigmentation that may be more prolonged ⁶⁷.

Vaccine Equity

The mpox epidemic has disproportionately affected GBMSM community and certain racial and ethnic groups. In the United States, the incidence of mpox was highest in Black and Hispanic men, with a RR of 6.9 in Black men and a RR of 4.1 in Hispanic men, when compared to White men. Unfortunately, vaccination rates were also lower in these groups, with the lowest vaccination-to-case ratios observed in Black men (8.8) and Hispanic men (16.2) compared to White men (42.5). Early in the outbreak, vaccination rates were lower in Black and Hispanic men than in White men, perhaps reflecting structural barriers to accessing vaccination when resources were limited. The disparity in vaccination-to-case ratios reflected the greater unmet vaccination needs in the groups most vulnerable to mpox infection ⁶⁸.

Protection from prior mpox infection or smallpox vaccination

Given the prior widespread use of smallpox vaccine (discontinued in the USA in 1972), there has been considerable interest in ascertaining the degree of protection conferred by these earlier vaccine products. Cross-sectional studies from the Democratic Republic of Congo suggest that mpox incidence increased significantly after the discontinuation of routine smallpox vaccination, and that previously vaccinated individuals had a lower risk of future mpox infection ^69,70.

However, at least one study in the recent outbreak has failed to find any association between history of smallpox vaccine receipt and risk of infection ⁴³. At present, history of prior smallpox vaccination should not be a factor in the decision to vaccinate against mpox.

The degree of protection conferred by prior mpox infection is also currently unknown. At present, previously infected individuals are considered immune, but there have now been several reported cases of potential re-infection ^71,72. The degree and durability of infection conferred by prior infection, as well as the effect of immune compromise on these parameters, remains to be established.

Management Considerations

The majority of patients with mpox achieve full recovery, regardless of whether they receive treatment or not. Although the Food and Drug Administration (FDA) has not approved any therapies specifically for mpox, supportive care measures have been used for pain control while medications initially developed for smallpox treatment have been reutilized as medical countermeasures (Table 2). These countermeasures may be beneficial for patients who are at risk for severe disease such as those who are immunocompromised, those with severe disease, and those with lesions in areas that might result in serious sequelae, e.g. the eye or urethra. Nonetheless, no medications have been definitively proven effective in randomized controlled trials. The CDC maintains a clinical guidance resource page for clinicians addressing both supportive care as well as medical countermeasures at https://www.cdc.gov/poxvirus/mpox/clinicians/clinical-guidance.html. Patients requiring medical countermeasures should be managed in consultation with infectious diseases specialists and/or local health authorities. See Figure 2 for suggested workflow for initial evaluation of mpox in the primary care setting.

Table 2:

Mpox treatment

Location of Lesions	Proctitis	Oropharyngeal lesions	Skin and genital lesions
Supportive Care	Stool softeners Lidocaine gel Sitz baths Anti-inflammatories Opioids	Antiseptic mouthwash Viscous lidocaine Saltwater gargles Anti-inflammatories Opioids	Wash with gentle emollients Apply petroleum jelly to skin lesions Consider Duoderm dressing for persistent lesions Antibiotics if required for bacterial superinfection
Medical Countermeasures	Indication		Standard Dosing
Tecovirimat	First line for those with severe disease or at risk for severe disease. Available through clinical trials or EA-IND.		600mg PO or IV twice daily (3x daily for those >120 kg) for 14 days
Brincidofovir	Second-line therapy for those who cannot receive tecovirimat, side effect profiles may determine which drug to choose. One animal study suggests that combined treatment with tecovirimat might be synergistic and is an option for individuals with severe or progressive disease.		200mg PO weekly x 2 weeks
Cidofovir			5mg/Kg IV weekly x 2 weeks
VIGIV	Individuals unable or unlikely to mount a robust immune response (immunocompromised due to disease or medications)		6-9,000 units/kg IV once
Trifluridine	Individuals with ocular disease		One drop every 2 hours x 2 weeks

Figure 2:

Suggested workflow for mpox in the primary care setting

Abbreviations: CDC=Centers for Disease Control, PO=oral intake

Supportive care guidelines

Recommendations for supportive care primarily derive from expert consensus. In the case of proctitis, stool softeners can help reduce pain during defecation while topical therapies such as sitz baths and lidocaine gels may offer additional comfort. Caution is advised when using topical steroids due to the risk of local immunosuppression. Over-the-counter analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen are often adequate, though prescription pain relievers such as gabapentin or opioids have been used for some patients with severe pain. For those experiencing pharyngeal disease, viscous lidocaine and saltwater gargles can provide additional relief. Finally, considering that secondary bacterial infection is a possible complication, antibiotics should be considered when bacterial superinfection is suspected ^73,74.

Tecovirimat

Tecovirimat is an antiviral medication originally engineered to treat variola virus for the treatment of smallpox. Its mechanism of action involves inhibiting viral protein p37, a target that is highly specific and conserved across orthopoxviruses. The Food and Drug Administration (FDA) approved tecovirimat in 2018 under the Animal Efficacy Rule, a regulation permitting drug approval for severe or life-threatening conditions where human efficacy trials are neither ethical nor practical. Before the recent outbreak, only human safety studies were accessible ⁷⁵.

For those needing treatment during the 2022 outbreak, tecovirimat became first-line treatment, with more than 6,800 courses administered across the United States via a CDC expanded access investigational new drug (EA-IND) protocol ^76,77. While safety data is encouraging, there is currently no randomized controlled human efficacy data ⁷⁸. An observational study of 154 patients receiving Tecovirimat showed that HIV status didn’t affect clinical presentations or treatment results ⁴⁵. However, a report from the CDC showed that all 27 mpox-associated fatalities had been treated with tecovirimat and a study out of Rome found no evidence of large effect of tecovirimat in healing time or time to viral clearance in a small hospitalized population ^79,80. Given the limited data available, tecovirimat, through a clinical trial, should be offered to patients with advanced HIV or severe disease, with the EA-IND available to those unable to enroll in a trial. Information about how to access tecovirimat through STOMP or the EA-IND can be found at https://www.cdc.gov/poxvirus/mpox/clinicians/obtaining-tecovirimat.html.

Cidofovir/Brincidofovir

Cidofovir diphosphate is a competitive inhibitor of DNA polymerase, approved by the FDA for treatment of CMV retinitis. Cidofovir can be used topically, intralesionally, or intravenously. Animal studies point to potential effectiveness against orthopoxviruses, but no human data currently confirms efficacy in treating mpox. Case studies suggest possible improvements following intravenous cidofovir administration^81,82, however, due to the relatively low mortality rate of this disease and the substantial risk of renal injury, intravenous cidofovir has been mainly used for individuals with severe disease and significant immunosuppression.

Brincidofovir is an oral prodrug of cidofovir available through an EA-IND, which is believed to cause less renal toxicity but that may induce hepatotoxicity ⁵⁰. Animal studies suggest that the combination of tecovirimat and brincidofovir may act synergistically ⁸³. This pairing should be contemplated for patients with severe immunosuppression and progressive disease.

Vaccinia Immunoglobulin (VIGIV)

The passive transfer of antibodies against the vaccinia virus is presumed to provide cross-protection against mpox and VIGIV, and may provide additional beneficial immunocompromised individuals, particularly those with advanced HIV. Case reports indicate improvement following this therapy, suggesting that VIGIV should be evaluated in patients with advanced HIV and severe mpox ⁸⁴.

Trifluridine drops

Trifluridine drops, which are FDA-approved for treatment of herpes simplex virus eye infections, are believed to have activity against orthopoxviruses ^85–88. They should be considered for all patients with ocular disease.

Conclusion

The 2022 outbreak was the most widespread epidemic of mpox to date, significant not only for large case numbers but also the disproportionate burden of disease among men who have sex with men and people with HIV. At the time of writing, incidence is low, but there remains significant risk of resurgence within communities where immunity from vaccination or prior infection is low ⁸⁹. Differentiating mpox from other infections will depend in part on current disease dynamics—providers should stay abreast of their local epidemiology. Continued efforts to vaccinate at-risk individuals are critical to avoiding further instances of generalized transmission. Treatment remains primarily supportive given the self-limited nature of disease. Antiviral therapy, particularly with tecovirimat, shows promise, but should ideally be undertaken in the context of a clinical trial as there is not yet definitive proof of efficacy.

Synopsis:

Mpox is a viral infection which primarily caused sporadic outbreaks in West and Central Africa until causing a global epidemic in 2022. The disease has disproportionately affected people with HIV and men who have sex with men. Transmission is via close physical contact, including sexual contact. Infection presents with a characteristic rash, with frequent anogenital involvement—PCR of skin lesions is diagnostic. Death is almost exclusively limited to those with advanced immunosuppression. Vaccination is available for primary prevention and post-exposure prophylaxis. Treatment consists of supportive care, with antiviral medications available via clinical trials and/or for patients with severe disease.

Key points:

1. Mpox is a viral pathogen in the Orthopox family related to smallpox

2. The 2022 outbreak has disproportionately affected MSM and people with HIV.

3. Manifestations include a characteristic rash without or without systemic prodrome, and frequent anogenital involvement

4. Differential diagnosis is based on clinical syndrome and is comprised mainly of other sexually transmitted infections

5. Vaccination is available both as primary and post-exposure prophylaxis and is critical to preventing epidemic resurgence

Clinics care points.

• Primary prevention with vaccination is effective, and should be offered to all at-risk individuals

• Post-exposure prophylaxis using the mpox vaccine may avert infection or shorten symptom duration/severity

• Individuals with suspected or confirmed mpox should receive comprehensive STI screening

• Individuals with suspected or confirmed mpox should self-isolate at home when possible, and avoid close physical contact until all symptoms/lesions have resolved

• Local or state health departments should be notified of new cases of confirmed mpox

• Supportive care is the mainstay of treatment, consisting of topical and/or systemic analgesia as well as treatment for bacterial superinfection and co-occurring STIs if present

• For individuals with severe disease, consultation should be sought with a local infectious disease expert and/or the CDC

• Medical countermeasures are available for individuals with severe disease. Individuals with or without severe disease can be enrolled in STOMP, an efficacy study of the antiviral medication tecovirimat