Although the spotlight has been on the COVID-19 pandemic during the past few years, attention has turned toward the recent outbreak of monkeypox.

First observed among humans in 1970 during efforts to eradicate variola virus in the Democratic Republic of the Congo, monkeypox outbreaks have historically been endemic to countries in Africa.1 However, recent surveillance by the World Health Organization (WHO) has put monkeypox top of mind for many clinicians, including those in the United States. Monkeypox has been confirmed among individuals in 12 countries, with most laboratory-confirmed cases observed among those in Portugal, Spain, and the United Kingdom (range, 21-30).2 The US Centers for Disease Control and Prevention (CDC) also issued an alert about monkeypox following its occurrence among an individual in Massachusetts on May 18.

For further insight into monkeypox, we spoke with Paritosh Prasad, MD. Dr Prasad is Director of the Highly Infectious Disease Unit at the University of Rochester Medical Center, as well as Infectious Disease Editor for VisualDx. 

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As a re-emerging infectious zoonotic disease that typically recurs periodically in Africa, what information is important for clinicians in Western countries to consider regarding prior cases of the infection?

Dr Prasad: The primary mechanism of monkeypox transmission is through contact with infected bodily fluids or lesions, with prolonged close contact generally required for transmission. The invasion period ranges between 0 and 5 days and is marked by fever, [severe] headache, myalgia, fatigue, and lymphadenopathy. Skin lesions develop 1 to 3 days after onset of fever in a centrifugal pattern with most over the face and extremities rather than the trunk. Locations include the face (95%), the palms and soles of hands (75%), the oral mucous membranes (70%), genitalia (30%), and conjunctiva (20%).4 The occurrence of lesions over the genitalia seems to be increased for this current outbreak, and conjunctival lesions may threaten sight. The initial rash evolves from macules, then papules to vesicles, and pustules later form and “crust over”, and the number of lesions can vary from 1 to more than 1000. 

Credit: Images used with permission from VisualDX

A WHO surveillance program from 1981 to 1986 in the Democratic Republic of the Congo reported that monkeypox had an associated reproduction number (R0) of less than 1 and that the risk for human-to-human transmission was low enough as to not present a significant public health risk.5 It remains to be seen if the R0 of the current outbreak is different than this prior finding.

The longest chain of infection identified in these studies was 4 generations, though in more recent outbreaks among countries in Africa it has increased to between 6 and 9 generations. Again, it is unclear how applicable this is to the current outbreak.

There are 2 clades of monkeypox, the more infectious Congo Basin clade with a mortality rate of approximately 10% and the less infectious West African clade with a mortality rate of approxiatemly 3%.

The 2003 outbreak in the US involved the West African clade imported to the US through infected rodents, transmitted to native prairie dogs in storage situations, and thereafter transmitted to their human owners through a variety of routes.6 There were no associated fatalities with this outbreak. The most severe disease manifestations in prior outbreaks of monkeypox in Africa were observed among children younger than 5 years of age.

The secondary attack rate of monkeypox in unvaccinated individuals was 9.3% compared with 37% to 88% for smallpox, indicating a decreased risk for transmission. 

Can you speak to the status of current rapid diagnostics for human monkeypox infections?

Dr Prasad: Polymerase Chain Reaction (PCR) assays using skin lesions (roof or fluid from vesicles and pustules and/or dry crusts) are the optimal sample. Blood PCR is limited by short duration of viremia relative to timing of sample acquisition after symptoms and not recommended. Presently these PCRs are available through the CDC and State reference laboratories.

Presently, antigen and antibody detection methods are not recommended due to cross-reactivity with other orthopoxviruses. This was a greater issue in the era of smallpox eradication and vaccination efforts. 

Can you describe the latest research on antiviral efficacy for human monkeypox infections?

Dr Prasad: There are no proven antiviral therapeutics against monkeypox. Antiviral drugs with in vitro activity against smallpox hypothesized to have efficacy against monkeypox include cidofovir, brincidofovir, and ST-246 (tecovirimat). Jynneos is a vaccine licensed in the US to prevent monkeypox and smallpox and likely has an 85% efficacy in preventing monkeypox based on data from previous outbreaks in Africa.7 ACAM2000 is a live vaccinia virus vaccine that can be used in individuals exposed to monkeypox through an expanded access investigational new drug protocol. Vaccinia immunoglobulin data are not available for its efficacy against monkeypox, and there is no proven benefit in its treatment of smallpox complications. 

Current evidence on the use prophylactic antibiotics against secondary cutaneous infection is anecdotal. Can you provide additional input? 

Dr Prasad: The risk of secondary cutaneous infection after any ulcerative skin disease exists, but as the primary risk is impairment of the cutaneous barrier and no amount of prophylactic antibiotic can sterilize the skin microbiota. It is unlikely that prophylactic antibiotics to avoid secondary cutaneous infection will be of significant benefit.

In light of the CDC’s recent alert about monkeypox cases, are there any clinical features of monkeypox other than swollen lymph nodes that clinicians should be aware of that would help differentiate the infection from that of smallpox? And can you provide input on differential diagnosis challenges for this infection more generally?

Dr Prasad: I think the issue here is not about distinguishing monkeypox from smallpox as much as it will be distinguishing it from other more common presentations involving febrile illnesses with macules, papules, and vesicles.

As far as distinguishing smallpox from monkeypox, smallpox does not usually involve headache and begins with small red spots on the tongue and in the mouth, which then change to sores that break open; only after this does the rash develop over the face and rest of the body. Although initial involvement of monkeypox also includes the mouth, the development of oral ulcers early into infection seems less prominent than that described with smallpox. The limited differential includes disseminated or localized varicella (these lesions are often more itchy; whereas monkeypox lesions are painful); herpes simplex virus and eczema herpeticum; molluscum contagiosum; syphilis (primary with chancre, and secondary with rash [over the] hands and feet); measles; and drug-related rash.

Is there any information you can share regarding the risk for nosocomial transmission of monkeypox, particularly among patients in US hospitals? 

Dr Prasad: Use of standard washing machines with warm water and detergent for bedding and clothing is enough for disinfection and hospital protocols far exceed this, as all soiled materials are uniformly handled with gloves. The current protocols in place due to the COVID-19 pandemic may be of significant benefit for reducing nosocomial transmission rates in US hospitals. Widespread masking requirements would be expected to reduce the spread of infected droplets to health care workers.

The widespread transition to single use and disposable medical technologies and the emphasis on environmental cleaning and disinfection is likely to significantly reduce the risk for nosocomial transmission. 

Can you describe the reservoir of zoonotic viruses in the United States?

Dr Prasad: The natural reservoir of monkeypox is unknown but a variety of rodents (rats, mice, squirrels, and prairie dogs), rabbits and non-human primates (both new and old world monkeys) are susceptible to infection. The full host range is still unknown.


  1. Centers for Disease Control and Prevention. About monkeypox. Accessed online May 24, 2022.
  2. World Health Organization. Disease outbreak news; multi-country monkeypox outbreak in non-endemic countries. Published online May 21, 2022. Accessed online May 24, 2022.
  3. Centers for Disease Control and Prevention. 2022 United States monkeypox case. Accessed online May 24, 2022.
  4. World Health Organization. Monkeypox. Accessed online May 24, 2022.
  5. World Health Organization. The global eradication of smallpox: final report of the global commission for the certification of smallpox eradication. 1980. Accessed online May 24, 2022.
  6. Reed KD, Melski JW, Graham MB, et al. The detection of monkeypox in humans in the western hemisphere. N Engl J Med. 2004;350:342-350. doi.10.1056/NEJMoa032299
  7. Centers for Disease Control and Prevention. Monkeypox and smallpox vaccine guidance. Updated December 2, 2019. Accessed online May 24, 2022.

This article originally appeared on Infectious Disease Advisor