Monkeypox in Transplant Recipients: No Breaks Between Outbreaks : Transplantation

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Monkeypox in Transplant Recipients: No Breaks Between Outbreaks

Al Jurdi, Ayman MD1; Kotton, Camille Nelson MD2

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doi: 10.1097/TP.0000000000004337
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Abstract

On July 23, 2022, the World Health Organization declared the monkeypox outbreak to be a public health emergency of international concern with over 16 000 cases reported from 75 countries, including 5 deaths.1 Transplant recipients are at risk for monkeypox infection through contact with infected humans or animals via direct contact with cutaneous lesions, sexual transmission, or respiratory droplets.2 As with other similar pathogens, it could be transmitted from donor to recipient at the time of transplant, especially given the ongoing viremia and shedding in urine and the respiratory tract that can occur after resolution of the rash,3 as well as a prolonged incubation phase when transmission could happen before the rash develops. The transplant community is concerned about the potential for more severe outcomes in transplant recipients who develop monkeypox infection. Prevention and treatment strategies for monkeypox at this time are mostly borrowed from smallpox. Strategies to reduce the risk of developing monkeypox infection include infection prevention measures, vaccination, and Vaccinia immune globulin (Table 1).4 There are 2 available vaccines that can be used for the prevention of monkeypox: (1) ACAM2000, which is Food and Drug Administration (FDA)–approved for the prevention of smallpox but is contraindicated in transplant recipients because it contains a replication-competent live virus‚ and (2) JYNNEOS, which is FDA-approved for the prevention of both smallpox and monkeypox in high-risk individuals. JYNNEOS contains a replication-deficient live virus, has a lower risk of adverse events compared with ACAM2000, and therefore is the preferred vaccine in transplant recipients. Currently, the Centers for Disease Control and Prevention (CDC) recommends post exposure prophylaxis ideally within 4 d, but up to 14 d, after exposure to monkeypox. Pre-exposure vaccination is not yet recommended because of limited vaccine supply. Although these vaccines are expected to be effective, there is no published data yet on their efficacy during this outbreak and clinical trials are still ongoing (Clinicaltrials.gov trials: NCT05438953, NCT02977715). Vaccine efficacy may be diminished in transplant recipients. Vaccinia immune globulin is FDA-approved for the treatment of complications from smallpox live virus vaccines, but whether it may have additional value for postexposure prophylaxis or for treatment of monkeypox is unclear at this time.

TABLE 1. - Prevention and treatment strategies for monkeypox infection
Strategy Composition and mechanism Dosing and administration Indication Notes
Vaccines
ACAM2000 Replication-competent live virus A single percutaneous injection Postexposure prophylaxis Contraindicated in immunocompromised individuals (including transplant recipients) during pregnancy and in those with cardiac disease, atopic dermatitis, eczema, and eye disease treated with topical steroids
JYNNEOS (also known as Imvamune or Imvanex) Replication-deficient live virus Two subcutaneous injections given 4 wk apart Postexposure prophylaxis Can be used in transplant recipients. Cannot be used in those with severe allergies to vaccine components (gentamicin, ciprofloxacin, or egg protein)
Ig
Vaccinia immune globulin Human Ig directed against smallpox antigens One intravenous injection of 6000 U/kg a Severe complications from vaccination or postexposure prophylaxis Can be used in severely immunocompromised people in whom vaccination is contraindicated or in those with severe complications from vaccination
Antiviral agents
Tecovirimat (also known as TPOXX, ST-246) Inhibition of Orthopoxvirus p37 envelope protein Oral: 600 mg every 12 hbIntravenous: 200 mg every 12 h c Treatment Contraindicated in those with severe kidney impairment (creatinine clearance <30 mL/min)
Cidofovir (also known as Vistide) Inhibition of viral DNA polymerase Intravenous: 5 mg/kg weekly for 2 wk then every 2 wk Treatment Associated with nephrotoxicity and neutropenia. Coadministration with intravenous saline and probenecid may reduce the risk of nephrotoxicity
Brincidofovir (also known as CMX001 or Tembexa) Inhibition of viral DNA polymerase Oral: 200 mg once weekly Treatment Less likely to cause nephrotoxicity than cidofovir, but is associated with hepatic toxicity and fetal toxicity in pregnancy
Information obtained from the CDC.4,5
a Higher can be considered if no effect with 6000 U/kg dose.
b Oral dosing listed is applicable only to people who weigh between 40 and 120 kg.
c Intravenous dosing listed is applicable only for people who weigh between 35 and 120 kg.
CDC, Centers for Disease Control and Prevention; Ig, immunoglobulin.

There are currently no FDA-approved treatments for monkeypox infection. Interim clinical guidance from the CDC for the treatment of monkeypox incorporates using antiviral medications that are used for the treatment of smallpox (Table 1).5 The CDC recommends considering antiviral therapy for monkeypox in individuals at high risk of severe disease, including solid organ and hematopoietic stem cell transplant recipients. Antiviral therapies include (1) tecorivimat, an envelope-wrapping protein inhibitor that is FDA-approved for the treatment of smallpox in humans‚ and (2) the viral DNA polymerase inhibitors cidofovir and brincidofovir (experimental). Although there are data from animal models supporting the efficacy of these antiviral agents in treating monkeypox infection, there is limited data regarding their use for the treatment of monkeypox in humans.2,3 There is an urgent need to study the efficacy of currently available vaccines and antiviral agents in transplant recipients and to develop new efficacious alternatives.

REFERENCES

1. World Health Organization. Director-General’s statement at the press conference following IHR Emergency Committee regarding the multi-country outbreak of monkeypox - 23 July 2022. 2022. Available at https://www.who.int/news-room/speeches/item/who-director-general-s-statement-on-the-press-conference-following-IHR-emergency-committee-regarding-the-multi--country-outbreak-of-monkeypox--23-july-2022. Accessed July 25, 2022.
2. Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox virus infection in humans across 16 countries—April–June 2022. New Engl J Med. 2022;387:679–691.
3. 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;22:1153–1162.
4. Centers for Disease Control and Prevention. Considerations for monkeypox vaccination. 2022. Available at https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.html.
5. Centers for Disease Control and Prevention. Treatment information for healthcare professionals. 2022. Available at https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html. Accessed July 25, 2022.

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