What every intensivist needs to know about mpox

Abstract

The mpox virus is a zoonotic orthopoxvirus with a DNA genome. Based on genetic characteristics, the mpox virus is categorized into two main clades: clade I and clade II. Clade I is further subdivided into subclades Ia and Ib [1]. Clade I is predominantly found in Central Africa, while clade II primarily circulates in West Africa [2]. The clade IIb subclade of clade II caused the global mpox outbreak from 2022 to 2023, during which 86% of cases were among men who have sex with men (MSM) [1]. More than half of the reported mpox cases involve individuals who are co-infected with the human immunodeficiency virus (HIV) [3]. The 2024 mpox outbreak in the Democratic Republic of the Congo and neighboring countries is primarily caused by clade Ia [4]. Only in 2024, as of September 15, the Democratic Republic of the Congo has reported 25,757 cases of mpox, with 806 deaths [3]. In April 2024, scientists identified a new variant of clade I, named Ib, by analyzing samples collected in South Kivu Province, Democratic Republic of the Congo, from late 2023 to early 2024. Reports of infections caused by the Ib variant have increased over the past few months. The proportion of women infected with clade Ib was significantly higher (52%), with nearly one-third identifying as sex workers [1]. On August 15, Sweden reported its first case of mpox caused by the Ib variant. Thailand confirmed its first Ib variant mpox case on August 22 [4]. Compared to clade IIb, which caused the global mpox outbreak in 2022, clade Ia exhibits stronger human-to-human transmissibility and higher mortality and severity rates. As for the clade Ib, its characteristics remain unclear [5].

As the mpox outbreak intensifies, by August 31, 2024, a total of 106,310 confirmed cases have been reported across 123 countries worldwide, resulting in 234 laboratory-confirmed deaths [3]. In Africa, the confirmed and suspected mpox cases in 2024 have surpassed 17,500, far exceeding the 15,000 cases reported in 2023. In response to this escalating situation, the Africa Centers for Disease Control and Prevention (Africa CDC) declared mpox a “Public Health Emergency of Security Concern” (PHESC) for the first time on August 13, 2024. The following day, the World Health Organization (WHO) declared the mpox outbreak a “Public Health Emergency of International Concern” (PHEIC), urging global cooperation to prevent further spread [5]. The current mpox outbreak may pose new challenges for intensivists worldwide.

Mpox mainly spreads through transmission between animals and humans or from person to person. Animal-to-human transmission can happen through direct contact with an infected animal, being bitten or scratched, or consuming undercooked meat from an infected animal. Human-to-human transmission primarily occurs through direct contact with an infected individual’s skin or mucous membrane lesions, oral secretions, upper respiratory secretions (such as nasal discharge and mucus), and items contaminated with the virus (such as bedding). Sexual contact, particularly in the context of the clade IIb outbreak and the current Ib outbreak, plays a significant role in transmission. Also, prolonged close exposure to respiratory droplets and mother-to-child transmission are significant transmission routes [6].

When treating mpox patients, intensivists should wear appropriate personal protective equipment (PPE), including N95 respirators or equivalent, eye protection, gloves, and gowns. PPE should be donned correctly, ensuring complete coverage of exposed areas to minimize contamination. In potential aerosol-generating procedures (AGPs), such as bronchoalveolar lavage, intubation, or extubation, powered air-purifying respirators (PAPRs) may be recommended for additional protection. Extra caution should be exercised during these procedures using protective barriers like intubation boxes or video laryngoscopy to minimize exposure. In healthcare settings where prolonged close contact occurs, especially during AGPs, the risk of transmission is heightened. For this reason, adhering to stringent PPE protocols is crucial [7].

Suspected or confirmed mpox patients should be isolated in single rooms with dedicated bathrooms. Airborne infection isolation rooms (AIIRs) with negative pressure are preferred to prevent airborne transmission. Biocontainment units (BCUs) may be employed in high-risk settings, especially for severely immunocompromised patients or those with disseminated disease [7].

Following airway management precautions and guidelines similar to those used during the COVID-19 pandemic is advisable. However, it is essential to note that COVID-19 management varied significantly over time and across regions. Therefore, in mpox, current guidance emphasizes consistent use of respiratory protection (such as N95 or equivalent), minimizing AGPs, and optimizing isolation procedures to reduce nosocomial transmission [7].

Diagnosing mpox involves collecting lesion samples or bodily fluids from suspected cases for polymerase chain reaction (PCR) testing [8]. Patients with mpox who are admitted to the intensive care unit (ICU) for treatment are often those already diagnosed with severe mpox. Mpox should be considered severe when patients exhibit the following conditions: ocular infections; neurologic complications; myopericarditis; complications associated with mucosal (oral, rectal, genital, and urethral) lesions and complications from uncontrolled viral spread due to moderate or severe immunocompromise, particularly advanced HIV infection [9].

Mpox has been reported to potentially cause a range of life-threatening complications, affecting nearly every organ system in the body. These complications include vision-threatening keratitis, conjunctivitis, secondary skin infections with multidrug-resistant bacteria, fungi, or viruses, sepsis, bronchopneumonia, epiglottitis, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), multiple organ dysfunction syndrome (MODS), myocarditis, pericarditis, arrhythmias, Ludwig's angina, cardiac arrest, encephalitis, and encephalomyelitis (Fig. 1) [8, 10]. Intensivists must be vigilant for these potential complications. Additionally, immunocompromised individuals, such as those with advanced HIV infection (CD4 + T cell count < 200 cells/cm³) and organ transplant recipients, are more susceptible to these complications and severe mpox [1].

Fig. 1

Complications of mpox

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Supportive care

For most mild mpox patients with intact immune systems and no skin lesions, supportive care will help them recover independently [9]. Regardless of disease severity, supportive care remains the cornerstone of mpox treatment, with particular attention to skin lesion care, pain management, and fluid management [2, 11]. Pain management is crucial, with primary medications including acetaminophen, ibuprofen, or topical lidocaine for mild cases. ICU patients often require more potent opioid analgesics such as morphine and oxycodone [2]. Intensivists should closely monitor dehydration in mpox patients caused by fever, reduced intake, and other systemic manifestations. Fluid resuscitation, maintenance, and electrolyte balance correction are crucial [11].

Available drug therapeutics for severe mpox

For severe mpox patients, the following medications may be considered:

Tecovirimat (TPOXX or ST-246)

Tecovirimat is an emerging antiviral drug inhibiting the highly conserved viral envelope protein p37 in orthopoxviruses. Note that the optimal bioavailability of tecovirimat depends on the concurrent intake of high-fat foods [12]. It should not be administered intravenously to patients with severe renal impairment (creatinine clearance < 30 mL/min) [11]. Disappointingly, tecovirimat has been reported to be ineffective against the clade Ib in clinical trials [13].

Cidofovir (Vistide)

This drug inhibits DNA synthesis by inserting itself into the DNA chain as replication occurs. Its dose-dependent nephrotoxicity limits its use, so it is usually administered with oral probenecid and hydration [12]. Caution is advised when using cidofovir with tenofovir disoproxil fumarate in HIV patients on antiretroviral therapy (ART). In patients with HIV infection and AKI, it may be necessary to change their ART regimen to one that does not include tenofovir disoproxil fumarate; consultation with an HIV specialist is recommended [10].

Brincidofovir (CMX001 or Tembexa)

Brincidofovir is a prodrug of cidofovir with lower nephrotoxicity but may cause elevated liver enzymes (such as transaminases and bilirubin), necessitating liver enzyme monitoring [10, 12]. However, obtaining brincidofovir can be challenging.

Vaccinia immune globulin intravenous (VIGIV)

VIGIV is primarily used for immunocompromised adults and children or those who cannot receive antiviral treatment (including tecovirimat) or for whom antiviral treatment is ineffective, or in severe cases, in combination with antiviral drugs and/or other therapies [8].

Mpox in patients with HIV

Mpox patients with HIV who have not received ART should start ART as soon as possible to improve immune function, ideally in conjunction with mpox treatment. Based on the severity of immune compromise and uncontrolled viral replication, prompt use of tecovirimat (possibly in intravenous form) may be considered, potentially in combination with cidofovir or brincidofovir and VIGIV. It is important to note that immune reconstitution inflammatory syndrome (IRIS) potentially induced by ART may worsen the condition of mpox patients [14].

Drug interactions

Medications used for severe mpox may interact with some drugs. Intensivists should be aware of these drug interactions; for example, tecovirimat can reduce the concentration of midazolam in the blood, diminishing its effectiveness. Additionally, tecovirimat can increase the concentration of repaglinide in the blood, leading to hypoglycemia [7, 15]. The drug interactions for severe mpox can be found in Table 1 [16,17,18,19].

Table 1 Drug interactions of available drug therapeutics for severe mpox

Full size table

Intensivists who are caring for mpox patients should consider receiving the modified vaccinia Ankara (MVA) vaccine (JYNNEOS, Bavarian Nordic) to reduce the risk of infection [14]. For individuals with compromised immune systems, including those with HIV, primary immunodeficiencies, or those undergoing immunosuppressive therapy, the MVA vaccine is considered safe [20].

No datasets were generated or analysed during the current study.

Africa CDC:

Africa Centers for Disease Control

AGPs:

Aerosol-generating procedures

AIIRs:

Airborne infection isolation rooms

AKI:

Acute kidney injury

ARDS:

Acute respiratory distress syndrome

ART:

Antiretroviral therapy

BCUs:

Biocontainment units

HIV:

Human immunodeficiency virus

ICU:

Intensive care unit

IRIS:

Immune reconstitution inflammatory syndrome

MSM:

Men who have sex with men

MODS:

Multiple organ dysfunction syndrome

MVA:

Modified vaccinia Ankara

OATP:

Organic anion transporting polypeptide

PAPRs:

Powered air-purifying respirators

PCR:

Polymerase chain reaction

PHESC:

Public Health Emergency of Security Concern

PHEIC:

Public Health Emergency of International Concern

PPE:

Personal protective equipment

VIGIV:

Vaccinia immune globulin intravenous

WHO:

World Health Organization

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We are grateful for this study's support provided by the Department of Critical Care Medicine at the Second Affiliated Hospital of Harbin Medical University.

This study was supported by National Natural Science Foundation of China (82472184), National Key Research and Development Program of China (2021YFC2501800), Heilongjiang Provincial Postdoctoral Science Foundation of China (LBH-Q19137), Heilongjiang Province Science Fund for Distinguished Young Scholars (JQ2021H002), Youth Medical Research Special Fund (Z-2018-35-1902) and Harbin Medical University Youth Fund (PYQN2023-9).

Authors and Affiliations

1. Harbin Medical University Graduate School, Harbin Medical University, Harbin, 150086, Heilongjiang Province, China

   Siyao Zeng

2. Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang Province, China

   Yue Li, Zhipeng Yao, Junbo Zheng & Hongliang Wang

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Contributions

SYZ and HLW proposed this study. SYZ searched for literature and obtained information. YL and ZPY have created the figure and table. SYZ drafted the manuscript, and HLW and JBZ revised it. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Junbo Zheng or Hongliang Wang.

Competing interests

The authors declare that they have no conflicts of interest. Figure 1 was created using Figdraw (www.figdraw.com).

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Zeng, S., Li, Y., Yao, Z. et al. What every intensivist needs to know about mpox. Crit Care 28, 356 (2024). https://doi.org/10.1186/s13054-024-05114-8

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• Received: 05 September 2024

• Accepted: 30 September 2024

• Published: 04 November 2024

• DOI: https://doi.org/10.1186/s13054-024-05114-8

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