On the Heels of COVID, ID Confronts Monkeypox
August 18, 2022 | Molly Bowen
It was mid-May when Dr. Matthew Hamill first learned of reports of a monkeypox outbreak in his native UK. WHO had issued a situation report about a person who arrived in the UK from Nigeria, where monkeypox is endemic, noting “Since the case was immediately isolated and contact tracing was performed, the risk of onward transmission related to this case in the United Kingdom is minimal. However, as the source of infection in Nigeria is not known, there remains a risk of ongoing transmission in this country.” On May 15, four more cases had been confirmed in the UK in men who have sex with men (MSM). According to Hamill, who is Assistant Professor of Infectious Diseases and Clinical Director for STI Services at the Baltimore City Health Department, “It was just a matter of time before we would start to see cases.” Indeed, Maryland’s first case was reported June 16, and as of August 17, CDC’s website notes that 349 cases have been confirmed statewide, 13,517 have been reported nationally, and there have been 39,434 cases confirmed internationally in 94 locations—87 of which have not historically reported cases of monkeypox.
ID Division care providers and researchers have sprung into action locally through clinical support, community outreach, health system infection control guidance, in-house PCR testing capacity, and a streamlined process for prescribing the monkeypox antiviral medication Tecovirimat. The Division is also responding to broader issues associated with an emerging disease, jumping on needs for development of rapid testing and on planning for studies and the establishment of infrastructure for conducting them.
SYMPTOMS, TRANSMISSION, INFECTION CONTROL
Monkeypox is an orthopox virus, which is in the same family of the now eradicated smallpox virus, and it’s characterized by its notable rash that can first present as macules, papules, or blisters and then scab over. Lesions at different stages of evolution can occur in the same individual. A consistent finding in the 2022 epidemic is of rectal infection causing proctitis which may be very painful and require careful pain management. Typically, those infected with monkeypox experience a prodrome consisting of chills, fever, swollen lymph nodes, and other flu-like symptoms before the onset of the rash. However, in the 2022 monkeypox epidemic the prodrome has been observed not to occur before the rash appears, or even at all. It is also manifested in some new ways from what is considered the classical presentation. Symptoms of rectal pain, also known as proctitis, or throat pain have been observed. Several studies have now indicated that the average duration from exposure to symptom onset (the incubation period) is 7 days (range, 3 to 20). According to CDC’s website, disease generally starts within 3 weeks of exposure, and it’s transmissible from the onset of symptoms until the rash has totally healed and “a fresh layer of skin has formed.” However, a recent, very small retrospective study in Lancet suggests that the virus can linger in the upper respiratory tract after skin lesions have healed. The viability of respiratory tract virus was not established, but this small study points to a need for more research on clinical illness. Viable monkeypox has also been demonstrated in semen in one case report.
While to date this outbreak of monkeypox has been prevalent among MSM, cases are now starting to be seen in other adults, adolescents, and children. Monkeypox is transmitted through direct person-to-person contact (including, but not limited to, sexual activity), contaminated objects and surfaces, and contact with skin lesions and respiratory droplets. Respiratory secretions such as saliva can be spread during kissing. However, it’s not clear how often the virus may be spread, or at what point during infection a person with monkeypox symptoms might be more likely to spread the virus, from respiratory secretions. There have been no reports to date of transmission during brief interactions between people in close proximity, such as a brief conversation, or for a longer duration, such as passengers seated near a person with monkeypox on an airplane.
With a charter of crafting procedures and policies that keep patients and healthcare workers safe, the Hospital Epidemiology and Infection Control team is addressing monkeypox in accordance CDC guidelines and getting them out to frontline clinical workers. “While monkeypox is less transmissible than COVID, what we address in infection control remains the same for both inpatient and ambulatory settings throughout our facilities: what to look for in clinically evaluating patients, where to put them, what PPE and safety measures to take,” Dr. Clare Rock noted. Both Dr. Joyce Jones, Clinic Director for the Bartlett Specialty Practice, and Dr. Liz Gilliams, Clinical Associate and Medical Director for STI Services at BCHD Sexual Health Clinics, indicated that healthcare workers are protected with N95 masks, face shields, gowns, and gloves.
COMMUNITY ENGAGEMENT & RESPONSE
With men who have sex with men and transgender people as sentinel cohorts, the epidemiology recalls the early days of HIV. According to Hamill, “concern among BCHD clientele has grown steadily in recent weeks as cases have risen, and phone inquiries now are quite heavy. People are approaching this with a sense of activism to stop it from impacting the community.” Gilliams noted that “The HIV and STI health care community in Baltimore is a closely knit outreach network for affected communities. Raising awareness, engaging people in what measures they can take to prevent monkeypox, and registering people to be vaccinated at the first possible opportunity are outreach measures that are being conducted across Baltimore.”
Jones has observed that “the number of people seeking testing among our clientele has been steadily increasing. We have also observed that monkeypox-related stigma is a significant issue for many of our clientele due to the presence of an infectious rash, the need for lengthy isolation, and the current higher incidence of infection in LGBTQI communities. Stigma is a real issue that we are addressing directly and compassionately.”
PREVENTION
JYNNEOS, the FDA-approved vaccine to prevent monkeypox in people aged 18 and over, is a live non-replicating vaccine manufactured by Bavarian Nordic A/S; 2 doses are currently recommended. A global supply shortage is currently hampering efforts to preemptively vaccinate people who are at risk, and the timeline for increased availability is uncertain. Local health departments are prioritizing vaccination for close contacts of people with confirmed monkeypox diagnosis. BCHD is preemptively vaccinating at-risk populations as vaccine supplies become available.
DIAGNOSIS
At BCHD, clients are clinically evaluated and PCR testing is administered, but it can take days to get results. As Hamill explained, “Samples are sent to Maryland State Lab for orthopox testing.” In accordance with the HEIC guidelines, the Bartlett Specialty Practice has established a process for outpatient clinical evaluation and, if indicated, treatment for its clients. The team in Dr. Heba Mostafa’s Clinical Microbiology lab mobilized quickly to develop a PCR assay that replicated an orthopox assay made years ago by CDC. According to Mostafa, “the team ordered the same primers and probes, which arrived quickly, and the assay came online in the last week of June.” They also worked with the Maryland State Lab to develop a process to deliver results to the state and to CDC. And the HEIC team, Mostafa’s team, CEPAR, and the Epic team worked to harmonize ordering requirements across Johns Hopkins Health System and to set up the new test in Epic that includes links to clinical guidance and resources. The assay, which delivers results in 24 hours, is now being used systemwide, and its use is unrestricted; it does not require approval from the Division.
TREATMENT
Hamill noted that “People who are really unwell, beyond just the painful lesions, are prescribed the antiviral tecovirimat (or TPOXX), which is approved for treatment of smallpox. According to the CDC, tecovirimat is approved under an Expanded Access-Investigational New Drug (EA-IND) protocol for treatment of monkeypox among people who have severe disease or are at high risk of severe disease, or among people who have lesions on the body in places “where infection might constitute a special hazard.” Tecovirimat’s EA-IND status means that its efficacy for monkeypox is largely undocumented. One patient case published in Lancet “suggests that tecovirimat may shorten the duration of illness and viral shedding.” But there’s no published data on shortening the course or lessening the symptoms of monkeypox. To address the need, the ACTG Network is developing a multi-center, Phase 3, randomized control trial to assess whether tecovirimat does shorten the time patients experience lesions and pain. Dr. Hamill is the proposed local site PI from Hopkins.
Jones, who is prescribing TPOXX under the EA-IND, noted challenges in prescribing. At first, both the CDC and the Maryland State Department of Health had to approve use in each patient and it could take hours from healthcare provider recommendation to prescription. Hopkins now has TPOXX on hand and prescription does not require pre-approval from the CDC, but the process remains time consuming for prescribers. This is due to the EA-IND designation and CDC protocol for prescription that requires individual consent and mandatory follow up with paperwork submission to the CDC for each individual patient. Jones indicated that the Bartlett Specialty Practice is supporting the hospital system to develop a more efficient process for prescribing tecovirimat for patients who need it.
RESEARCH IN THE WORKS
Dr. Kelly Gebo notes that “research study developments are moving quickly.” Mostafa’s lab is establishing a monkeypox sample repository, and Drs. Joel Blankson and Andrea Cox are establishing a repository for additional biospecimens from monkeypox patients. The Precision Medicine in ID team is establishing a data registry for Johns Hopkins Health system patients who are tested for monkeypox, irrespective of test result. Data include demographics, comorbidities, viral testing and result, treatment, vaccination status, and health care utilization. For patients who test positive, one study is underway, and two are planned:
• Dr. Joyce Jones is leading JHH availability of TPOXX through the CDC protocol as the local PI for the EA-IND study (underway).
• ACTG’s planned Phase 3 RCT for TPOXX, for which Dr. Hamill is the proposed PI. The trial proposes evaluating time to clinical resolution.
• There are plans to expand the CCEPSI observational cohort study, developed for COVID by Drs. Paul Blair from ID and Bhakti Hansoti of Emergency Medicine, for monkeypox. The study proposes to collect clinical history, samples, and survey data for patients who test positive for monkeypox to assess stigma, quality of life, and pain.
While not nearly as grave as COVID in terms of transmissibility, mortality, or the uncertainties associated with a novel virus, the expertise of ID researchers and care providers is being applied for both local and global response. In many ways, the COVID experience primed the Division for mounting swift response to outbreaks more broadly.
To learn more about the Division’s engagement in monkeypox awareness, visit our News page.
Thanks to Drs. Kelly Gebo, Amita Gupta, Liz Gilliams, Matthew Hamill, Joyce Jones, Heba Mostafa, and Clare Rock for their time and contributions.