Of concern during public health emergencies is the likelihood that vulnerable populations like children may experience delayed and/or inadequate attention (6). Mpox is endemic largely in West and Central Africa (Cameroon, Central African Republic, Cote d'Ivoire, Gabon, Liberia, Nigeria, the Democratic Republic of the Congo, Sierra Leone, and South Sudan) (7). Since the first clinical case was reported in an infant in the Democratic Republic of the Congo in 1970, mpox in Africa has disproportionately affected children under 15 years of age (8) with the risk of death highest among children under 5 years (9–16). Prior to the 2022 global outbreak, children under 18 years comprised up to 80% of all mpox cases reported to the WHO; during the first year of the 2022 outbreak, children still comprised approximately 40% of African cases (15). In addition, transmission occur between caregivers and children, as well as intra-uterine transmission between mothers and their children (17).

The WHO declared the 2022 global mpox outbreak over on May 10, 2023. However, in late 2023, there were reports of new clusters of cases in the Democratic Republic of Congo later identified to be cause by a novel monkeypox virus strain called Clade 1b (18). The novel Clade 1b virus appeared to be more amenable to human-to-human transmission than Clade 1a strains historically reported in the Democratic Republic Congo that affected children even more disproportionately.

During the current outbreak from January to May 2024, 70% of reported cases occurred in children under 15 years of age. Moreover, children accounted for 83% of total fatalities, with the highest mortality observed among infants under 1 year old, who had a case fatality ratio of 8.7%. This rate is more than three times higher than the 2.4% case fatality ratio recorded in individuals aged 15 years and older (18). In the Democratic Republic of the Congo, 47.7% of the cases reported between January 1, 2022, to August 18, 2024 were in children 15 years of age or younger (19). Between January 1, 2010 and December 31, 2023, children in the country younger than 5 years had had the highest incidence rate (46.38 per 100,000) and case-fatality ratio (6.0%) (20). We provide more details of Clade 1b infection in African children in the later section.

Among children, mpox is primarily characterized by a rash that progresses through several stages: macular, papular, vesicular, and pustular, eventually leading to scabbing and desquamation. The lesions are firm or rubbery, well-circumscribed, deep-seated, and often become umbilicated in later stages. The rash can be localized or widespread, affecting different body areas, including the palms and soles, at different times. Lesions are typically painful or itchy. Additional symptoms could include fever, chills or sweats, sore throat, headache, myalgias, and lymphadenopathy (21). Most pediatric complications arise from secondary bacterial infections, including encephalitis, pustular corneal lesions, corneal scarring, submaxillary abscess, retropharyngeal abscess, and bronchopneumonia (21).

Oral manifestations are common in mpox, affecting nearly 70% of clinical cases (22), and 96% of laboratory-confirmed cases (23). Lesions, often preceding skin rashes, may be severe enough to require hospitalization (24), and commonly affects the lips and tongue (25). They include ulcers, pustules, perioral erosions, candidiasis, and oropharyngeal lesions (25). A meta-analysis estimates oral features range from mouth sores (24.80%) to mouth rash (17.99%) (26). Despite their prevalence, documentation in children remains poor (27).

A rapid review of the literature on oral lesions associated with mpox is highlighted in Table 1. The literature search was conducted in Pubmed, Medline, Research4life, EBSCO and AJOL utilizing terms (“Monkeypox” OR “Mpox”) AND (“oral lesions” OR “oral symptoms” OR “mouth ulcers” OR “oral manifestations”). Boolean operators, MeSH terms, and wildcards were used to maximize search sensitivity. The search was conducted for the last 20 years (January 1, 2004–September 30, 2024). The search was for patients of all ages diagnosed with mpox who had oral manifestations. The review included case reports, case series, observational studies, and reviews. The 44 records identified were imported into Rayyan, one duplicate removed, titles and abstracts screened and full texts and their references reviewed. Articles that could not be accessed were excluded. Fourteen articles reported on oral lesions associated with mpox. The data on study location, study design, sample size, and study findings were extracted and collated into a summary as shown in Table 1 (28–40).

Table 1 highlights that oral lesions are common in mpox, with prevalence ranging from 8.5% to 100% (25). Features include buccal ulcers, perioral lesions, tongue sores, and mucosal rashes (25, 29, 33, 36–40), often in individuals aged 10–19 years (37). Cases report fibrinoid-membrane ulcers, perioral erosions with black crusts, and erythematous ulcers (31, 32). Severe cases associate oral sores with prolonged hospitalization and abnormal labs (35). Saliva shows higher viral loads and better diagnostic sensitivity than oropharyngeal swabs (28, 35). Oral ulcers and exanthem are more prevalent in endemic regions, with advanced diagnostics revealing unique patterns (33). However, a significant gap in understanding mpox's oral health impacts in children, with most reports from endemic African regions. In the Democratic Republic of Congo, Pittman et al. found mouth and throat lesions in 24.5% of pediatric cases, highest in ages 5–11 years (36), while Whitehouse et al. reported buccal ulcers in 56% of confirmed cases, with age-based variations (37).

This geographical concentration of data suggests that oral health manifestations in children might be underreported or under-researched in non-endemic regions. The lack of studies outside Africa raises questions about potential disparities in disease recognition, reporting, or clinical presentation in different settings. Furthermore, endemic regions may have unique socio-environmental factors, such as higher exposure risks or limited healthcare access, influencing the frequency and severity of oral health manifestations in children.

The distinct focus on endemic areas also highlights the urgent need for global, region-specific pediatric studies. Such research is critical for understanding whether the observed patterns are consistent worldwide or if they reflect localized factors. Expanding the scope of pediatric oral health studies could also contribute to developing targeted interventions, improving diagnostic capabilities, and addressing potential oral health inequities in mpox management for children globally.

Children in African countries continue to be at high risk of mpox infection, including from Clade 1b virus. Personal communication with Africa CDC indicated that between January and September 2024, 46% of confirmed cases reported in Africa were children less than 15 years. Children less than 15 years constituted 52% of the cases in Burundi, 47% in DR Congo, 37% in Nigeria and 50% in the Congo. The risk of severe mpox is higher among those who are immunocompromised, including from malnutrition and HIV infection (41). Cases of severe mpox have larger, more extensive lesions, particularly affecting the mouth, eyes, and genitals. Complications can also include inflammation of vital organs, such as the heart, brain, or other organs, as well as secondary bacterial infections of the skin, bloodstream, or lungs (42).

The risk of immunosuppression due to malnutrition and HIV are higher for children in African countries. By the end of 2023, an estimated 1.4 million children (ages 0–14 years) were living with HIV globally, with 120,000 newly infected (43). African countries with ongoing mpox outbreaks, such as Nigeria, South Africa, Kenya, Rwanda, Côte d'Ivoire, and Uganda, also have high HIV burdens (44). Advanced HIV disease and low CD4 cell counts are linked to impaired mucosal recognition of the mpox virus, weakened B-cell response, and reduced viral clearance (27). This increases the risk of severe mpox. Mpox can also present as an opportunistic infection or an AIDS-defining illness (45). However, further research is needed to fully understand the host-pathogen interactions of the mpox virus in individuals with immune deficiency due to HIV infection (46). Of concern is that all children younger than five years of age living with HIV are considered to have advanced HIV disease (47). This risk is a concern for African countries, where the burden of new and established HIV infections is still high (48).

Children in African countries additionally face a high risk of immunosuppression due to malnutrition. While global rates of child stunting are declining, the number of stunted children in Africa increased from 54.4 million in 2000 to 61.4 million in 2020, with an estimated 61 million by 2025 (49, 50). Progress in reducing stunting is slow, at 1.5% per year, far below the 5.5% needed to meet global targets (51, 52). East and West Africa, the regions most affected by mpox, also have the highest rates of malnutrition (53). Malnutrition leads to insufficient intake of essential vitamins and minerals, disrupts gut microbial metabolic processes causing chronic low-grade inflammation (54), damages both the innate and adaptive immunity of the host (55, 56), and increases the body's vulnerability to infections including viral infections (57) like mpox (58).

Mpox complicated by HIV and malnutrition creates a challenging clinical scenario, particularly in pediatric patients, due to the compounded effects of the diseases. In addition to HIV and malnutrition causing immune suppression, which weakens the body's ability to fight infections, HIV and malnutrition are also associated with oral lesions, which can further complicate mpox infection. Candidiasis, ulcerations, and gingivitis, which are lesions associated with HIV and malnutrition (59, 60), cause pain and discomfort that impair nutritional intake, worsening malnutrition. In pediatric mpox cases, the presence of these oral manifestations can lead to dehydration, difficulty eating, and a higher susceptibility to bacterial infections. The combined impact of mpox, HIV, and malnutrition significantly heightens the risk of morbidity and mortality in children, emphasizing the need for comprehensive care that addresses both the infectious and nutritional aspects of treatment. Early intervention, supportive care, and multidisciplinary management are critical in improving outcomes for these vulnerable patients.

Primary lesions of mpox often originate in the oropharynx before manifesting on the skin (61), which can lead to the initial presentation of mpox infection to dentists. Oral mpox lesions may resemble herpetic and other vesicular-bullous lesions, complicating differential diagnosis (25). Herpetic simplex infection is common in children (62). These lesions are typically treated conservatively, with symptom resolution expected within 10–14 days (63). This possible risk of misdiagnosis may increase the likelihood of mpox transmission within the community.

In Africa, it is common for children to present with oral lesions co-existing with painful, self-limiting skin lesions (25, 36, 37). Conditions such as chickenpox, shingles, or herpes, which have both oral and skin features, can increase the risk of mpox misdiagnosis (8, 15). There is currently little known about the differential oral features of mpox in children and adults or the prognostic oral lesion markers for mpox in children. Oral lesions may be a valuable indicator of mpox in low-middle income countries.

Although mpox has been documented in Africa since the 1970s, resources for its surveillance, treatment, and prevention have been scarce. Both Clade 1 and Clade 2 mpox infections can affect children and adolescents, potentially leading to significant morbidity and mortality, including hospitalization, visual impairment, critical illness, and death (64). The management of mild ailments like oral and skin lesions are often routinely undertaken by alternative medical care providers like traditional healers and patent and proprietary medicine vendors (private drug retailers) (65, 66). These alternative care providers serve as the first source of care for between 8% and 55% of illnesses occurring among children under five (67) and are a particularly important source of care in rural and lower income communities (68).

The involvement of alternative care providers in Africa's mpox response has been minimal, with their inclusion in outbreak plans and interventions largely overlooked. As a result, the limited focus on frontline carers, including those responsible for children's health and oral health, may negatively impact the quality of care vulnerable children receive during this period. The self-limiting nature of mpox infection, and the absence of easy to administer rapid diagnostic tools that can be purchased in shops like the HIV, malaria, and COVID−19 self-testing tools, further increases the risk for delayed diagnosis and management.

Vaccines and antiviral medications became widely used to prevent and treat mpox for the first time during the 2022 outbreak, but their efficacy in pediatric patients remains unknown (64) and their access in primary health care setting in Africa remains limited. These complexities associated with the appropriate diagnosis of mpox increases the risk of its delayed or non-diagnosis in children in Africa.

The high rates of mpox among children expose the deep inequalities in access to healthcare and nutritional support, with immunosuppression due to HIV and malnutrition further increasing their susceptibility. The intersection of infectious diseases and socioeconomic factors, where under-resourced communities face multiple, overlapping health crises including challenges in receiving timely and accurate diagnoses presents a challenge for children, their oral health and their quality of life. The exclusion of first-line responders to children's health problems—traditional healers and patent medicine vendors—in the mpox response underscores another layer of inequality—children in rural and underserved areas may not receive accurate information or timely care. Worse still, access to mpox vaccines and antiviral treatments is limited, particularly for pediatric populations in Africa (15).

When the focus of care for children and adolescents with oral health problems is dentists—to the exclusion of pandemic preparedness and first-line respondents, the existing inequalities are further exacerbated, especially in rural and underserved areas (69, 70). Focusing only on oral health professionals for the management of oral health care needs during the mpox outbreak further creates missed opportunities to integrate oral health into broader health systems for appropriate pandemic preparedness and response, and to prioritise oral healthcare needs of children and adolescents during health crises. In addition, focusing on dentists to provide care to children during the mpox outbreak overlooks the current oral health crisis precipitated by the limited access to specialized dental care across many parts of Africa (71). Where there is specialized oral health care in Africa, economic and geographic barriers make access challenging (72). Furthermore, in times of crisis, such as pandemics, first-line health responders play a crucial role in maintaining healthcare continuity. Neglecting their involvement in oral health management reduces the system's resilience to health emergencies and deepens disparities.

Furthermore, the global inequality in vaccine distribution during the mpox outbreak echoes similar challenges seen with COVID-19, where wealthier nations had better access to life-saving interventions. The WHO-pre-qualified Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine—currently the most commonly used mpox vaccine globally—was indicated for use for people above the age of 18 years (73), although the was expanded to include it use in individuals aged 12 years and older on 8 October 2024 (74). Recently, the Japanese Government promised to provide around 3.05 million doses of pediatric-indicated, live attenuated LC16 vaccine for children in Africa (75). The vaccine was only granted WHO Emergency Use Listing for use in children on the 17th of November 2024 (74). There is however, little data on the safety and immunogenicity of the LC16 vaccine in immunocompromised individuals (76), with a proviso for the need to screen for HIV and other significant immunosuppression in children before administering the vaccine, because of the risk of adverse reactions.

While the threat of mpox to children and adolescents had been hidden in plain sight (77), that of oral health in children and adolescents with mpox had been largely overlooked. Of concern is the high vulnerability that the triad of being a child, a resident in Africa, and the non-prognostic mpox oral lesions poses. This intersection highlights a pressing need for targeted interventions that address both systemic inequities and the specific clinical challenges associated with mpox.