Mpox in children (2024): New Challenges

Mpox (formerly monkeypox) is a viral zoonotic disease caused by the mpox virus (MPXV), which is part of the same family as the smallpox virus.1 Although milder than smallpox, mpox can still lead to severe health issues, particularly in vulnerable individuals. It primarily transmits through close physical contact with an infected person, bodily fluids or contaminated surfaces.1 Initially, mpox presents with fever, headache, myalgia and fatigue, often followed by lymphadenopathy—a hallmark differentiating it from smallpox. Within a few days, a distinctive rash emerges, progressing from flat lesions to fluid-filled blisters and scabs (figure 1).2 These lesions commonly appear on the face, hands, feet and genital regions and usually last up to 4 weeks. While most cases resolve without treatment, complications can arise, especially for those immunosuppressed, potentially leading to secondary bacterial infections or, in severe cases, even to encephalitis and death.2

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Mpox emerged for the first time as a public health emergency of international concern (PHEIC) in 2022.3 However, a previous outbreak caused a significant impact on some states in the USA in 2003 as a consequence of illegal wildlife trade of prairie dogs (that were in contact with Gambian giant rats, dormice, and rope squirrels), particularly affecting children.4 The study of exotic pet trafficking from Africa is notable due to zoonotic virus transmission from African mammals to humans. The outbreak was the first introduction of Mpox-infected animals to the Americas and then the spillover to humans. While it was historically confined to Africa,3–5 recent outbreaks in non-endemic regions, like the current clade Ib, highlighted their spread and impact across diverse demographics, including children, with more urgent challenges, particularly in low- and middle-income countries (LMICs).6 The paediatric population faces unique issues in mpox, influenced by factors such as immunological vulnerabilities, transmission dynamics, healthcare infrastructure and societal factors.

In 2024, mpox was again declared a PHEIC due to the spread of clade Ib in Africa.5 High transmission rates in children were reported, with 30% of cases in the Democratic Republic of Congo (DRC) (>50% in children <5 years in some areas) (figure 1) and 47% in Burundi, emphasising the need for _targeted paediatric epidemiological attention (https://www.cdc.gov/mpox/php/data-research/clade-i-mpox-in-children-in-africa-and-potential-impacts-on-children-in-the-united-states.html). From 1 January 2022 up to 30 September 2024, 109 699 cases have been reported globally, with 236 deaths in 123 countries. Just in 2024, 14 478 cases were notified, with 51 deaths in 74 countries. In September 2024, 2763 cases were described in 47 countries (https://worldhealthorg.shinyapps.io/mpx_global/).

One of the primary challenges concerning mpox in children is the transmission dynamics.6 7 Younger people tend to have more physical contact with family members, caregivers and peers, which increases the risk of acquiring this virus.7 Unlike adults, children may not be able to adhere to hygiene protocols or social distancing measures, making them more susceptible to close-contact transmission, a significant route for mpox.6 Since mpox can be transmitted through respiratory droplets, lesions and contaminated objects like bedding or clothing, children who live in crowded environments or attend daycare or school settings are at heightened risk, common in impoverished countries.6

Household transmission is a remarkable challenge. Internationally, children live in multigenerational homes, making it easier for mpox to spread among family members.7 Sometimes, adults may become infected through community exposure and bring the virus into the household, where children may be infected. In resource-limited settings, access to adequate sanitation or infection control measures is lacking, exacerbating the risk of transmission.6

The clinical presentation of mpox in children (figure 1) is also challenging as it overlaps with other common infections. Mpox typically presents with similar symptoms to adults in children but can be more severe (figure 1). Early signs include fever, chills, headache, fatigue and lymphadenopathy. Within a few days, a rash develops, often starting on the face and spreading to other areas, including the hands, feet and genitals (figure 1). The rash progresses through stages: macules, papules, vesicles, pustules and, finally, crusts. In severe cases, children may experience respiratory disease, dehydration and secondary bacterial infections. Younger children and those immunosuppressed are at higher risk for complications, including pneumonia and, rarely, encephalitis.2 8 9

At early stages, differential diagnoses should include chickenpox, herpesvirus, enterovirus, measles or other exanthems, usually in children, especially in regions with incomplete vaccinations or outbreaks.4–7 In addition, practitioners attending children commonly lack awareness, as risk perception and education about disease manifestations are very low in many countries.

One of the biggest diagnostic challenges is the limited availability of mpox testing in many regions. Many LMICs, particularly in Africa (historically endemic) or where recently emerged (eg, Latin America or Asia), lack the laboratory infrastructure needed for rapid and accurate diagnosis. In children, timely diagnosis is crucial to prevent complications and reduce the risk of severe disease. Still, the lack of reliable diagnosis in many world areas makes this difficult.3

Paediatric populations are at a higher risk of severe disease from mpox compared with adults, especially with other simultaneous vulnerabilities, such as malnutrition, coexisting infections or immunodeficiencies. This is particularly important in Africa under the current outbreak, where children are most affected and vulnerable simultaneously. Past outbreaks suggested that children under 8 are more likely to experience severe mpox, including pneumonia, encephalitis and secondary bacterial infections.5 Children and adolescents with close contact with people with suspected, probable or confirmed mpox may be eligible for post-exposure prophylaxis (PEP) with vaccination, immune globulin or antivirals (https://www.cdc.gov/mpox/hcp/clinical-care/pediatric.html). Tecovirimat has been used and approved for children >13 kgs (not recommended for those <12 months), showing good outcomes in severe cases, although randomised trials are lacking. Vaccination and PEP are critical prevention components, but some settings have low uptake.

Malnutrition can exacerbate the severity of mpox in children.6 This can lead to prolonged illness, more severe symptoms and higher mortality. Children living with HIV or other immunosuppressive conditions are also at increased risk of severe disease.

Another significant challenge in addressing mpox in paediatric populations is the accessibility and acceptance of vaccines. Their access is globally limited, with paediatric populations in LMICs facing significant challenges obtaining them. Preventive and therapeutic interventions for small children are not universal.

Healthcare systems struggle with mpox in children, often already burdened by HIV, malaria, tuberculosis, pneumonia or diarrhoea in many regions. In the province of South Kivu, DRC, only three deaths occurred in those less than 10 years old and were associated with a coinfection with severe malaria. The sudden rise in mpox cases added a burden, especially in LMICs that cannot respond effectively to simultaneously public health crises. Just in the DRC, as of 13 October 2024, 6962 cases of mpox have been confirmed. However, most cases aged 0–17 since 2022 are reported from the Americas (763/1210; 63%), and even 59 cases were pregnant women (https://worldhealthorg.shinyapps.io/mpx_global/).

Diagnostic capacities in LMICs must improve to identify mpox risks and clades. Effective communication and community engagement are needed to support interventions, including vaccination. Reference laboratories should store clinical samples to track mpox genetics and share data globally.

For children, overstretched healthcare systems can lead to limited access, delays in care, inadequate treatment and poor follow-up, particularly in underserved areas. Many LMICs also lack infection control measures, increasing the risk of mpox spread in hospitals.4–7 Mpox can significantly impact children, causing distress, stigma, bullying and social isolation. Visible lesions may lead to fear, discrimination, shame and anxiety in schools.7

Global inequalities in mpox outbreak responses pose a challenge for children. Wealthier countries contain outbreaks through testing and vaccination, while LMICs struggle due to limited resources, leaving these children at higher risk with less access to healthcare and vaccines.3

Additionally, global funding for mpox is limited, even being declared twice as a PHEIC, compared with other infectious diseases, which hampers the development of _targeted interventions for paediatric populations.3 5 6 While efforts have been made to address this gap, such as through global health initiatives and international partnerships, much more needs to be done to ensure that all children globally are protected from the risks of Mpox.

In conclusion, the challenges of mpox in paediatric populations are multifaceted and global in 2024. Compared with the 2022/2023 outbreaks, the current one in Africa, especially in DRC, is significantly affecting children. Children are at higher risk with the clade Ib, where human-to-human transmission is easier. Those <15 years tend to be more affected in some areas, as occurs in South Kivu province, DRC (even 20% of cases there occur are <1 year) (figure 1). Transmission dynamics, diagnostic difficulties, severe disease outcomes, vaccine accessibility, healthcare system limitations, psychosocial impacts and global inequalities all contribute to the complex landscape of paediatric mpox. Addressing these challenges requires coordinated global efforts, improved healthcare infrastructure, _targeted vaccination campaigns and a commitment to reducing health disparities globally. From a global health perspective, the disease should be controlled in its geographical origin, Africa. More concerted efforts to support the affected areas in that continent are of utmost importance for the rest of the world. Only through these measures can the global community effectively protect paediatric populations from the growing disease threat.5 Overall, while Mpox in children is less common in non-endemic regions, it remains concerning due to potentially severe outcomes, particularly in endemic areas. Additionally, maternal and congenital mpox needs increased local and international understanding, awareness and surveillance; vaccines and treatment options in these last groups should also be a priority.2 Continued research and _targeted interventions are necessary to address these challenges.