By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: Data on outcomes of monkeypox cases managed in Europe and North America are limited but provide some clues on epidemiology, clinical manifestations, treatment, and outcome.
SOURCE: Adler H, Gould S, Hine P, et al; NHS England High Consequence Infectious Diseases (Airborne) Network. Clinical features and management of human monkeypox: A retrospective observational study in the UK. Lancet Infect Dis 2022; May 24:S1473-3099(22)00228-6. doi: 10.1016/S1473-3099(22)00228-6. [Online ahead of print].
Adler and colleagues retrospectively reviewed the cases of seven patients with monkeypox in the United Kingdom seen between 2018 and 2021 and cared for at centers in Liverpool and Newcastle. Four of the seven acquired their infection in the United Kingdom. One of the three infected outside the United Kingdom was a healthcare worker who became ill 18 days after exposure to one of the other cases in the series. The exposure occurred in the absence of the use of personal protective equipment (PPE), and illness occurred despite the receipt of smallpox vaccine six days after exposure. All seven patients had pleomorphic skin lesions with monkeypox deoxyribonucleic acid (DNA) detected in the skin lesions of each patient as well as on swabs from their upper respiratory tracts, and DNA also was detected in the blood in six patients and the urine in four patients.
The first three patients in the series were given brincidofovir for treatment. However, the authors concluded that they observed no benefit of this therapy, which was discontinued in each patient earlier than planned, at least in part because of elevation of serum transaminases. One of the three patients developed abscesses on the left thigh and ankle, both of which required drainage; bacteria were not detected in the drainage. The thigh abscess, which was drained 21 days post-diagnosis, at which time the patient was still viremic, yielded monkeypox DNA. Another of the three patients, the first of the cohort, had persisting ulcerating inguinal and scrotal lesions that remained polymerase chain reaction (PCR)-positive for monkeypox DNA for several weeks after clearance of viremia. The third patient still was viremic at day 39, but monkeypox DNA was not detectable at day 45.
The fourth patient in the series notably had inguinal lymphadenopathy that persisted after resolution of skin lesions. The three other cases, seen in 2021, comprised a household cluster. The family of four traveled from Nigeria and developed illness, and the father became ill after arrival. The youngest child subsequently became ill, and the entire family was admitted to the high consequence infectious diseases (HCID) center. On day 14 of the child’s illness, her mother became ill. The mother was treated with tecovirimat with rapid clearance of viral DNA from blood and without the occurrence of further skin lesions.
COMMENTARY
Between May and mid-June of 2022, more than 1,600 cases of monkeypox were identified in more than 30 countries. Clinicians who may confront these cases should acquire a knowledge base dealing with the epidemiology, clinical presentation, and management.
Although monkeypox in Central Africa has a mortality rate of approximately 10%, in West Africa it is as low as approximately 1%, a difference apparently due to the presence of differing viral clades in these geographic regions. Fortunately, the available evidence indicates the virus in the cases being seen in Europe and North America is similar to one previously seen in travelers from Nigeria. Also, certain to be an important determinant of the outcome of infection is the general health status of those affected, raising the possibility that monkeypox fatality may, in general, be more benign outside of Africa. The best published data on this point arise from a prior outbreak in the United States.
In 2003, 37 individuals acquired confirmed monkeypox in the Midwestern United States as a result of contact with pet prairie dogs that had been infected by rodents imported from Ghana.1 The median duration of fever in the patients for whom the information was available was eight days (range, two to 13 days), and the median duration of skin lesions was 12 days (range, seven to 24 days). Lesions were monomorphic in two-thirds of cases and were centrifugally distributed in one-half of cases. Lesions were localized in 8/32 (25.8%), with groin and/or buttock lesions in 3/32 (9.4%). Hemorrhagic pustules were present in two patients. More than 100 lesions were present in 6/30 (6.7%), with 4/6 having > 250 lesions. One-third were thrombocytopenic. Of the 34 patients, 19 (56%) were noted to have lymphadenopathy.
Nine patients were hospitalized and five were considered severely ill, but there were no deaths. Two patients, both children, required mechanical ventilation, one with encephalitis and one with tracheal impingement by lymphadenopathy and a retropharyngeal abscess.
Monkeypox is known to be transmitted by contact with infected sites and by large respiratory droplets. Fortunately, transmission appears to be somewhat restricted. In the 2003 event, which involved 37 cases, no secondary cases were identified.
An additional point of reference is a 2021 case of monkeypox in a traveler who flew from Nigeria to Dallas through Atlanta.2,3 Several days after arrival, he developed skin lesions of monkeypox and was taken to a hospital. The astute emergency department physician suspected monkeypox and contacted the Centers for Disease Control and Prevention (CDC), who subsequently confirmed the infection. The CDC identified 223 contacts. Although 85% were deemed to have minimal risk, the remainder had an intermediate risk, but no transmissions were identified.
While these experiences provide insight into the likelihood of transmission in the United States, the unusual epidemiology of the current occurrence in which transmission appears largely related to intimate skin-to-skin contact may provide different results. It also is possible that the virus has changed, but there is, to date, no molecular evidence of this.
Some unusual aspects of monkeypox should be noted. In contrast to smallpox, in which it is uncommon, lymphadenopathy has been described previously in approximately one-half of patients. In one case, this contributed to tracheal compression and the need for intubation. In another case, lower extremity abscesses occurred and required drainage, with monkeypox DNA detected in the recovered pus. Persistent presence of viral DNA in blood and respiratory secretions was common in the U.K. experience, and low PCR cycle thresholds suggested (but did not prove) that the virus was replication-competent and, thus, capable of being transmitted.
Management of identified cases involves effective infection control with standard, contact, and aerosol isolation and consideration of antiviral therapy. The most promising such therapy, albeit based only on laboratory and animal studies to date, plus the single case in the U.K. series, is tecovirimat, which is available for use via a CDC Investigational New Drug application.
Individuals with significant exposures may be candidates for early vaccination, preferably with Jynneos, which consists of vaccinia virus that has been engineered to make it replication-incompetent.
There is much yet to be learned about the current international outbreak — stay tuned.4
REFERENCES
- Huhn GD, Bauer AM, Yorita K, et al. Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis 2005;41:1742-1751.
- Rao AK, Schulte J, Chen TH, et al. Monkeypox in a traveler returning from Nigeria — Dallas, Texas, July 2021. MMWR Morb Mortal Wkly Rep 2022;71:509-516.
- Deresinski S. A case of monkeypox in a returned traveler. Infectious Disease Alert 2022;41:92-93.
- Centers for Disease Control and Prevention. U.S. Monkeypox 2022: Situation summary. https://www.cdc.gov/poxvirus/monkeypox/response/2022/index.html
Data on outcomes of monkeypox cases managed in Europe and North America are limited but provide some clues on epidemiology, clinical manifestations, treatment, and outcome.
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