And then came Monkeypox: what to know about the recent outbreak

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

First observed in humans in 1970 during smallpox virus eradication efforts in the Democratic Republic of Congo, outbreaks of monkeypox have always been endemic in African countries.1 However, recent surveillance by the World Health Organization (WHO) has put monkeypox high on the list for many clinicians, including those in the United States. Monkeypox has been confirmed in individuals in 12 countries, with most laboratory-confirmed cases seen in Portugal, Spain and the United Kingdom (range, 21-30).2 The US Centers for Disease Control and Prevention (CDC) has also issued a monkeypox alert following its outbreak in an individual in Massachusetts on May 18.3

For more information on monkeypox, we spoke with Paritosh Prasad, MD. Dr. Prasad is Director of the Highly Infectious Diseases Unit at the University of Rochester Medical Center, as well as Infectious Diseases Editor for VisualDx.

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As a re-emerging infectious zoonotic disease that usually reappears periodically in Africa, what information should clinicians in Western countries take into account regarding previous cases of infection?

Doctor Prasad: The main mechanism of transmission of monkeypox is contact with infected body fluids or lesions, with prolonged close contact usually being required for transmission. The period of invasion varies between 0 and 5 days and is marked by fever, [severe] headaches, myalgias, fatigue and lymphadenopathy. Skin lesions develop 1-3 days after the onset of fever in a centrifugal pattern, mostly on the face and extremities rather than the trunk. Locations include face (95%), palms and soles (75%), oral mucosa (70%), genitals (30%) and conjunctiva (20%).4 The occurrence of genital lesions appears to be increased for this current outbreak, and conjunctival lesions may be sight threatening. The initial rash progresses 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) less than 1 and that the risk of human-to-human transmission was low enough not to pose a significant risk to public health.5 It remains to be seen whether the R0 of the current epidemic is different from this earlier finding.

The longest chain of infection identified in these studies was 4 generations, although in more recent epidemics among countries in Africa it has increased to between 6 and 9 generations. Again, it’s unclear to what extent this applies to the current outbreak.

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

The 2003 outbreak in the United States involved the West African clade imported into the United States by infected rodents, transmitted to native prairie dogs in storage situations, and then transmitted to their human owners through various routes.6 There were no deaths associated with this outbreak. The most severe manifestations of the disease in previous outbreaks of monkeypox in Africa have been seen in children under 5 years of age.

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

Can you talk about the state of current rapid diagnostics for human monkeypox infections?

Doctor Prasad: Polymerase chain reaction (PCR) tests using skin lesions (roof or fluid from vesicles and pustules and/or dry scabs) are the optimal specimen. Blood PCR is limited by the short duration of viremia relative to the time of sample acquisition after symptoms and is not recommended. Currently, these PCRs are available from CDC and state reference laboratories.

Currently, antigen and antibody detection methods are not recommended due to cross-reactivity with other orthopoxviruses. It was a bigger problem in the era of smallpox eradication and vaccination efforts.

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

Doctor Prasad: There is no proven antiviral treatment for monkeypox. Antiviral drugs with in vitro activity against smallpox thought to have efficacy against monkeypox include cidofovir, brincidofovir, and ST-246 (tecovirimat). Jynneos is a vaccine licensed in the United States to prevent monkeypox and smallpox and is likely 85% effective in preventing monkeypox based on data from previous outbreaks in ACAM2000 is a live vaccinia virus vaccine that can be used in people exposed to monkeypox through a new experimental protocol with expanded access. Data on vaccinia immunoglobulin are not available for its effectiveness against monkeypox, and there is no proven benefit in its treatment of smallpox complications.

Current evidence on the use of prophylactic antibiotics against secondary skin infection is anecdotal. Can you provide additional information?

Doctor Prasad: The risk of secondary skin infection after any ulcerative dermatosis exists, but since the main risk is damage to the skin barrier and no amount of prophylactic antibiotic can sterilize the skin microbiota. Prophylactic antibiotics to prevent secondary skin infection are unlikely to be of significant benefit.

In light of the recent CDC alert regarding 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 information on the challenges of differential diagnosis for this infection more generally?

Doctor Prasad: I think the issue here is not so much to distinguish monkeypox from smallpox as to distinguish it from other more common presentations involving febrile illnesses with macules, papules, and vesicles.

When it comes to distinguishing between smallpox and monkeypox, smallpox usually does not involve headaches and begins as small red spots on the tongue and in the mouth, which later develop into sores that develop open; only then does the rash develop on the face and the rest of the body. Although the initial involvement of monkeypox also includes the mouth, the development of mouth ulcers early in the infection appears to be less than that described for smallpox. The limited differential includes disseminated or localized chickenpox (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 of nosocomial transmission of monkeypox, particularly among patients in US hospitals?

Doctor Prasad: The use of standard washing machines with hot water and detergent for bedding and clothing is sufficient for disinfection and hospital protocols go well beyond this, as all soiled materials are handled evenly with gloves. Current protocols in place due to the COVID-19 pandemic may be of significant benefit in reducing nosocomial transmission rates in US hospitals. Widespread masking requirements should reduce the spread of infected droplets to healthcare workers.

The widespread shift to single-use and disposable medical technologies and the emphasis on environmental cleaning and disinfection are likely to significantly reduce the risk of nosocomial transmission.

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

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


  1. Centers for Control and Prevention of Disasters. About monkeypox. Accessed online May 24, 2022.
  2. World Health Organization. epidemic news; outbreak of monkeypox in several countries in non-endemic countries. Published online May 21, 2022. Accessed online May 24, 2022.
  3. Centers for Control and Prevention of Disasters. Cases of monkeypox in the United States in 2022. Accessed online May 24, 2022. .html
  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 English J med. 2004;350:342-350. doi.10.1056/NEJMoa032299
  7. Centers for Control and Prevention of Disasters. Advice on monkeypox and smallpox vaccines. Updated December 2, 2019. Accessed online May 24, 2022.