- Recent outbreaks of monkeypox have disproportionately affected men who have sex with men
- U.K. researchers reviewed cases that occurred in the several years before the present outbreak
- These cases provide insight into symptoms, outcomes and experimental treatments
Monkeypox is a virus that is related to another virus called smallpox. Infection with monkeypox virus can cause an illness called monkeypox.
An outbreak of monkeypox-related illness is occurring primarily in Europe and North America and is related to the apparent spread of monkeypox virus mostly among gay, bisexual and other men who have sex with men (MSM). For background on this and monkeypox in general, see the CATIE News article: An outbreak of monkeypox in Canada and other countries.
In the past, there have been cases of monkeypox in high-income countries, mostly in people who had visited places where monkeypox traditionally occurs. A team of researchers in the UK recently conducted a study whereby they reviewed the medical records of people who had been hospitalized for monkeypox in that country between 2018 and 2021. The report, which is in press in Lancet Infectious Diseases, is rich in detail and will likely be helpful to doctors and nurses who have patients with monkeypox in the current outbreak. Furthermore, the report has some information about the effect of antiviral drugs. This CATIE News bulletin is a summary of the report.
Study details
In the UK study there were seven participants—four males and three females. Six of them were adults between the ages of 30 and 50. The seventh individual was an infant less than two years old. None of the participants had immunological dysfunction caused by the following:
- infections such as HIV, hepatitis B virus or hepatitis C virus
- cancer
- taking medicines for conditions such as rheumatoid arthritis, Crohn’s disease, colitis, psoriasis
- taking transplant medicines
Participants had swabs and/or fluid samples tested every two to three days with PCR (polymerase chain reaction) for genetic information from monkeypox virus. The fluids collected were mostly blood and urine, and the areas that were swabbed included inside the nose and the back of the throat as well as persistent skin lesions. In some cases, fluid from monkeypox lesions was also tested for the presence of the virus.
Prior to the diagnosis of monkeypox, none of the participants had been vaccinated against smallpox. The smallpox vaccine confers about 85% protection from infection with monkeypox virus.
According to the researchers, four people were infected outside the UK and three others inside the UK.
Results – early signs and symptoms
Prior to the diagnosis of monkeypox in the study, four people had early signs that something was wrong. They reported fever combined with one of the following:
- night sweats
- swelling in the groin
- runny nose
The remaining participants did not report early symptoms prior to their diagnosis of monkeypox.
All participants went on to develop the following:
- lesions suggestive of monkeypox; subsequent swabs of these lesions tested positive for monkeypox virus
- all people had monkeypox virus DNA detected in their nasal and throat swabs
Also, six people had their blood samples test positive for monkeypox virus, and four people had their urine samples also test positive for this virus.
Focus on lesions
The lesions developed on the following parts of the body:
- face
- chest and abdomen
- legs
- arms
Three men developed lesions on their penis and two on their scrotum.
One woman developed lesions on her labia.
The number of lesions people had on their bodies varied from as few as 10 lesions on one person to as many as 150 on another person.
Swabs of fluid in the lesions tested positive for monkeypox virus.
Complications
Patient 1 – This man developed what doctors referred to as “low mood.” The doctors stated that this could have been a biological consequence of monkeypox or it could have resulted from being isolated for weeks in a hospital. The patient received psychological counselling; he was apparently the only person in the study to receive this intervention.
This patient also had a persistent ulcer in this groin. According to the researchers, fluid from this lesion tested positive for monkeypox virus “several weeks [after his other bodily fluids tested negative] and after healing of all other skin lesions.” No other germ was identified in swabs of fluids from this lesion. He was hospitalized for a total of 26 days.
Patient 2 – Doctors stated that this person had a number of complications, including “low mood,” alcohol withdrawal (upon hospitalization and isolation), severe nerve pain that required opioids, and abscesses on the left side of his body on the ankle and in the thigh. The abscesses tested negative for bacteria and were not resolving, so doctors drained them. Fluid from the abscesses tested positive for monkeypox virus. After this drainage occurred, the patient subsequently tested negative for the virus. He was hospitalized for a total of 27 days.
Patient 3 – This woman developed eye inflammation and a painful thumbnail because of a lesion in the skin. A swab of the affected eye tested negative for monkeypox virus and doctors then prescribed antibiotic (chloramphenicol) eye drops, administered four times daily until she recovered. Her monkeypox rash resolved after two weeks but swabs taken from her nose and throat remained positive for monkeypox virus for several weeks after. (We will return to this point later in this bulletin.) After a total of 35 days in the hospital, this patient was sent home and was asked to remain isolated there. Swabs from her nose and throat were regularly assessed, and on days 45 and 48 after her diagnosis these swabs tested negative for the virus and she was considered recovered.
Patient 4 – This man had an ulcer in his groin that persisted for weeks despite the clearance of his other lesions. Fluid from the ulcer tested positive for monkeypox virus. He was treated with a one-gram dose of the antibiotic azithromycin in case the ulcer became infected with bacteria (it had the appearance of a lesion caused by a sexually transmitted infection). This man remained in hospital for 39 days until the lesion completely healed.
It is noteworthy that after this patient’s rash healed he had persistently swollen lymph nodes in his groin. This suggests that his immune system had detected a germ (or remnants of a germ) and had mobilized to fight it. However, tests taken prior to his hospital discharge suggested that he no longer had monkeypox.
About six weeks after being released from hospital, this patient had intercourse for the first time since his illness was diagnosed. Subsequently, his lymph nodes became even larger and he developed what researchers described as “shallow ulcerating skin lesions” in his groin. Swabs of fluid from the lesions and his nasal passages and throat tested positive for monkeypox virus. He stayed at his local hospital for a few days until he tested negative for monkeypox virus. Doctors described the return of the ulcers and the increased size of his lymph nodes after he left the hospital for the first time as a “relapse.”
Patient 5 – This patient had no complications; he was hospitalized for 13 days.
Patient 6 – This patient was an infant. She had 30 lesions and developed itchiness from skin-cleansing products. Doctors used the over-the-counter remedy calamine lotion and a short course of antibiotics as treatment. She was hospitalized for 22 days.
Patient 7 – Though this patient only developed 10 monkeypox lesions, she experienced low mood and a prolonged course of illness (mentioned later). She was hospitalized for 10 days.
Antiviral treatment
Although antiviral drugs have been approved in many high-income countries for the treatment of smallpox and/or monkeypox virus infection, they were approved on the basis of studies in animals. They have not been tested in large numbers of people (as is the case with most other drugs). Therefore, doctors discussed the risks and benefits of using these drugs with some of the patients whom they thought would benefit from them.
Patients 1, 2 and 3 were given 200 mg of the drug brincidofovir, once weekly, as capsules. They were all expected to take the drug for three consecutive weeks. However, after one or two doses, all three people developed abnormally elevated levels of liver enzymes in their blood, which suggested liver injury. Further use of brincidofovir ceased. Their liver enzyme levels took about one month to normalize. Furthermore, the researchers stated, “brincidofovir was not observed to confer any convincing clinical benefit.”
Patient 7 had been in isolation at home and in hospital for a total of 35 days. In the hope of accelerating her recovery, doctors offered her a two-week course of the antiviral drug tecovirimat, 600 mg twice daily taken orally. Within 48 hours after this patient began therapy with tecovirimat, swabs from her nose and throat tested negative for monkeypox virus and remained negative for the next 72 hours (testing ceased after that). No new lesions developed after she began antiviral therapy. Extensive analysis of her blood and urine samples as well as questioning revealed no tecovirimat-related toxicity. The patient was sent home after completing a one-week course of tecovirimat in the hospital and completed the other week of antiviral therapy at home. Subsequently, she remained well.
All participants were ultimately deemed to have fully recovered.
Bear in mind
This series of cases provides some insight into the course of monkeypox in people hospitalized in recent years in the UK. Although no one died, lesions, and in some cases complications, were obviously very painful for some people.
Numbers
It is important to note that the number of people hospitalized was small and definitive conclusions about the effect of antiviral therapy or the course of monkeypox itself cannot be drawn.
However, the results from the use of brincidofovir give one pause for thought. In an experiment with prairie dogs with severe monkeypox, brincidofovir given one day after infection “conferred a modest survival benefit,” according to the researchers. This conclusion was arrived at because 29% of the animals who received brincidofovir survived vs. 14% of them who were given placebo.
Although the results from the patient who received tecovirimat are promising, this is just one person and researchers cannot be certain that the effects seen were a result of the drug. It may have simply been due to the natural course of the disease.
A missing link
Large, randomized clinical trials are needed to better understand tecovirimat’s promise and its future role in treating people with monkeypox. Scientists also need to study the potential of monkeypox virus to develop resistance to tecovirimat.
Complications
The researchers stated that other reports of monkeypox have featured data from people who had severe inflammatory reactions due to overwhelming bacterial infections that occurred once they had developed monkeypox. Previous reports indicated that some people with monkeypox also developed severe lung inflammation. None of these complications were found in the present study.
Positive PCR and virus
The fact that patients 2 and 3 may have had positive PCR test results from throat and/or nasal swabs after their lesions cleared is interesting. However, in future studies, positive PCR test results need to be paired with viral co-culture assays (growing virus in the lab) to determine if having a positive PCR result means that active virus is present. It is possible that the PCR tests detected residual fragments of viruses that were still present rather than the active production of viruses. This could have occurred because fragments of the virus persisted in some tissues for days or weeks after the infection was brought under control.
Mental health issues
The low mood reported in at least three patients in this study could have been due to prolonged isolation in a hospital and the refusal of hospital authorities to allow visitors in order to help restrict the spread of the virus. However, it is also possible that the stigma and fear of having a strange and relatively new (to the UK) disease could have contributed to their mood. The researchers noted that one person’s “landlord attempted to evict them during [hospital] admission.” Therefore, stigma from a diagnosis of monkeypox could also have contributed to their low mood. Hopefully, doctors and nurses caring for people with monkeypox in the current outbreak (or in the future) will be vigilant for changes in mood and will intervene when necessary.
—Sean R. Hosein
Resources
An outbreak of monkeypox in Canada and other countries – CATIE News
Montreal’s response to an international outbreak of monkeypox virus: First steps towards action – CATIE blog
Monkeypox: symptoms and management – Public Health Agency of Canada
Monkeypox – Centers for Disease Control and Prevention
REFERENCE:
Adler H, Gould S, Hine P. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infectious Diseases. 2022; in press.