Clade I Mpox in Children in Africa and Expectations for Transmission in the United States

Introduction

There is currently an ongoing outbreak of clade I monkeypox virus (MPXV) in Central and Eastern Africa. A large proportion of suspected cases in some areas have been reported in children younger than 15 years of age. Historically, pediatric cases of mpox in Western and Central Africa, where mpox occurs regularly, or is endemic, often occur as a result of contact with wild animals that carry the disease, spreading it to humans. Humans can then spread the disease to close household contacts. The high proportion of children with suspected mpox reported in the current outbreak is likely due to a number of factors, including spread within and between close households, younger population demographics in impacted countries, misdiagnosis of other diseases (such as measles), poor sanitary conditions, limited access to health services, and a high level of food insecurity and malnutrition.

Based on what we know today, and based the current characteristics of viral spread, we don't expect a similar age-related proportion of mpox cases in the United States for several reasons. These reasons include smaller household size that includes fewer people, access to cleaning and disinfecting products, and improved access to medical care, equipment, and information about caring for patients. CDC simulated clade I mpox outbreaks resulting from close-contact transmission within and between households (household clusters) in the United States to better understand the potential impact of this transmission route. Modeling results indicate that close-contact transmission among children, within and between households is unlikely to result in many mpox clade I cases in the United States in adults or children. Should pediatric cases of clade I mpox occur in the U.S, however, CDC has clinical and public health guidance for reporting, testing, and effective case management.

Background

Since January 2023, the Democratic Republic of the Congo (DRC) has reported the largest number of yearly suspected clade I mpox cases on record for the country. While clade I monkeypox virus (MPXV) is endemic, or naturally occurring in the DRC, the current outbreak is more widespread than previous DRC outbreaks and has resulted in clade I mpox transmission to several neighboring countries, including Burundi, Central African Republic, Republic of the Congo, Rwanda, Uganda, Kenya, and some travel-associated cases outside of Africa. In early August 2024, both the Africa Centres for Disease Control and Prevention and the World Health Organization (WHO) declared the outbreak a Public Health Emergency of Continental Security and a Public Health Emergency of International Concern, respectively.

MPXV has two distinct genetic clades: clade I (with subclades Ia and Ib) is endemic to some countries in Central Africa, and clade II (with subclades IIa and IIb) is endemic to some countries in West Africa1. Clade II MPXV is responsible for the ongoing global outbreak that started in 2022 and is still circulating at low levels among adults, including in the United States; this outbreak has predominantly affected gay, bisexual, and other men who have sex with men (MSM).2The outbreaks that began in 2023 in Central and Eastern Africa are caused by clade I mpox.

Historically, infections caused by clade I MPXV were often presumed to be associated with direct contact with wildlife followed by limited onward spread (primarily in households). Persons infected by wildlife can infect family members through close contact within households, including direct contact with lesions or other contaminated materials like clothing, bedding, or shared spaces, such as beds. Children were often the largest demographic group impacted, perhaps due to their lack of immunity from prior infection or smallpox immunization. Immediately following smallpox eradication (1981-85), and the end of smallpox vaccination in 1980, the median age of an mpox case was 3.3 years, primarily among unvaccinated young children.13

Person-to-person spread of clade I mpox appears to be a central feature of current transmission dynamics. In DRC, zoonotic spillover may still be a factor, in particular with subclade Ia; this more closely mirrors historical clade I outbreak dynamics where zoonotic spillover and subsequent household transmission are key factors driving outbreaks.

Clade Ib MPXV is a subclade that has been newly reported from eastern DRC. While both clade Ia and clade Ib are spread through close contact (including day-to-day household contact, direct contact with the lesions or other contaminated materials like clothing, bedding, and healthcare-related cases when PPE is unavailable), available data indicate that clade Ib has been spreading primarily in adults through intimate and sexual contact (e.g., kissing, oral-genital, oral-anal, vaginal, or anal sex), including transactional sex. Clade Ib MPXV cases have also spread via travel to some neighboring countries that are not endemic for MPXV, including Burundi, Rwanda, and Uganda. There have also been travel-associated cases in India, Kenya, Sweden, Thailand, but ongoing transmission has not occurred in those countries.

Clade Ib has distinct genetic changes similar to clade IIb that suggest sustained human-to-human transmission.4 Among clade I cases, clade Ib mpox cases appear to be clinically milder than clade Ia cases, and so far, clade Ib has a lower case-fatality rate compared to clade Ia mpox. No deaths have been reported from non-endemic countries with clade Ib infections at this time.

Findings

Clade I Mpox in Children in Africa

Many countries impacted by the current outbreak have very young populations.5 Given the large pediatric populations in these countries, pediatric cases could be expected. Historically, children have been the demographic most impacted during outbreaks of clade I mpox in DRC.67 In the current outbreak, children continue to be impacted. Since the beginning of 2024, 30% of confirmed mpox patients in the DRC have occurred in persons <15 years of age.8 In Burundi, where recent cases are exclusively clade Ib, ongoing mpox surveillance indicates that 47% of confirmed cases are among children under 10 and the median age was approximately 14 years.9

While data on transmission in the current outbreak is limited, some factors may be contributing to the number of reported mpox cases in children in Africa. The health status of children in DRC is impacted by food insecurity and chronic malnutrition, the high prevalence of infectious diseases (measles, malaria, diarrheal disease), limited access to healthcare services, and the lack of access to sanitation products. In 2024 in DRC, 22% of the population will experience high levels of food insecurity and nearly 4.5 million children under five years of age are projected to face acute malnutrition, including approximately 1.4 million cases of severe acute malnutrition, increasing vulnerability to the severity and duration of infectious diseases.910

While an important route of transmission within the affected countries is still suspected to be through sexual activity among teens and adults,41112 community and household transmission among close contacts in affected African nations is also likely contributing to cases among children.8 This may be linked to the demographics of households in DRC, where homes are often densely occupied.

Additionally, other rash-causing illnesses (e.g., measles) may look like mpox, leading to misdiagnosis of mpox in children. Overlapping with the mpox outbreak in time and geographic area, DRC has been experiencing a large measles outbreak. During the first 6 months of 2024, more than 2,000 cases of measles per week were reported, with Equateur province having both the greatest number of measles cases and suspect mpox cases.13 Mpox cases significantly declined after recognition of the measles outbreak and subsequent measles vaccination, indicating that a substantial number of measles cases were misdiagnosed as mpox. Recent investigations have also demonstrated that a high proportion of suspected mpox cases in some children were negative for MPXV. 79

Expectations for Clade I Mpox Transmission in the United States

The cases of children with mpox reported in the outbreak in Central and East Africa likely reflects spread within households under conditions generally different than those experienced in many U.S. households, as well as exposure to infected dead or live wild animal vectors that exist in countries where MPXV is endemic. Numerous factors probably contribute to household spread in Africa, including crowded households, greater proportions of the populations being under 15, being negatively impacted by other diseases and/or food insecurity, and lack of access to disinfecting and hygeine products.

Based on what we know today and the current characteristics of viral spread, we do not expect a similar age-related risk if mpox were introduced in the United States for several reasons. These reasons include smaller, one-generation household sizes, availability of and access to products for cleaning and disinfection, the absence of known animal reservoirs, generally better access to medical care and information for caring for patients, and domestic readiness for local and federal public health interventions.14 During the 2022 clade IIb outbreak, Nigeria had 16% of cases among children while the U.S. had less than 0.01%, highlighting the different experience within two different countries given the same pathogen.715

CDC modeling also suggests that there would not be widespread transmission of clade I mpox disease within and between U.S. households. CDC simulated clade I mpox outbreaks resulting from close-contact transmission within and between households (household clusters) in the United States to better understand the potential impact of this transmission route. This modeling included children and interactions between children in daycare and school settings as well as among household contacts. Modeling results indicate that close-contact transmission within and between households is unlikely to result in a large number (more than 10) of mpox clade I cases in the United States. Even considering a plausible "worst-case" scenario based on existing data for clade Ia —with a 15% household secondary attack risk and a 5% non-household (between-household) secondary attack risk — 95% of resulting outbreaks had 10 or fewer cases, and 93% of resulting outbreaks affected 3 or fewer households.

Similarly, in an unpublished (manuscript in draft) CDC household transmission study from a previous active clade I outbreak in resource-limited areas of DRC, 75% of the households who had at least one person with mpox did not experience onward transmission of MPXV.

There are no consistent reports of schools as drivers of mpox transmission during the recent outbreaks in Africa. U.S. schools generally have routine cleaning and disinfection policies with readily available access to appropriate disinfectants, hygiene materials for students and staff (soap, running water, hand sanitizer, and paper towels), less crowding compared to many resource-limited countries, and in many instances, access to on-site healthcare providers, such as school nurses or school-based health center staff who can evaluate ill children for exclusion when necessary. Although direct skin-to-skin contact during close play or contact sports could theoretically spread mpox, the risk of ongoing spread within U.S. schools (should a case be introduced) is expected to be low. During the clade IIb mpox outbreak in the United States that began in 2022, there were no reported school-related mpox cases.

Frequently Asked Questions

1. Are there special considerations for pediatric clinical care, including testing and treatment?

There are no cases of clade I mpox in the United States at this time, and the risk to the general public, including children and adolescents, is low. Despite this low risk, being prepared is necessary given limited U.S. experience with clade I mpox. Clinicians should maintain a high degree of suspicion for children who have traveled to the DRC or to certain countries sharing a border with the DRC, or who have been in close contact with a confirmed or suspected case of mpox who present with signs and symptoms. Testing recommendations are similar for suspected children and adults based on clinical presentation and epidemiologic criteria. Further testing is required to differentiate the two clades, or the sub-clades, as clinically, clade I MPXV is indistinguishable from clade II MPXV. A suspected pediatric case of mpox should isolate at home or in an alternative location pending results of clinical testing for mpox if their clinical status enables outpatient management. If there is laboratory confirmation of mpox, CDC-recommended mpox activity restrictions should be followed until mpox symptoms have resolved. For more information about clinical care for pediatric cases, visit Clinical Considerations for Mpox in Children and Adolescents in the U.S.

Treatment for mpox is based on clinical presentation and severity, regardless of clade. As with adults, children and adolescents with mpox should be closely monitored throughout their illness and likely will benefit from supportive care and pain control. Decisions about supportive treatment for children closely align with treatment plans for adults. Available and appropriate medical countermeasures (e.g., tecovirimat, cidofovir) should be considered for those with severe disease or life-threatening complications. Additionally, it should also be considered for those with severe immunodeficiency or who are immunocompromised, conditions affecting skin integrity (e.g., eczema), children <1 year, or adolescents who are pregnant or breastfeeding. These medications must be accessed through clinical trials or are available for compassionate use under the expanded access-investigational new drug (IND) protocol. There are currently no FDA-approved therapeutics to treat mpox. For more information visit: Clinical Treatment of Mpox.

For the pediatric population, particular attention should be paid to keeping skin lesions covered and preventing children from scratching lesions or touching their eyes after touching lesions, which may result in autoinoculation and more severe illness. For more information about skin care for individuals with mpox lesions, please see Mpox: Treating severe lesions (aad.org).

High-quality care and supportive measures may help to minimize disease severity among future pediatric patients with clade I mpox in the U.S. The U.S. has advanced medical care that is not widely available in DRC. Supportive care, nutritional supports, wound care, and treatment for superinfections are widely available in U.S. healthcare systems. A study in DRC demonstrated decreased morbidity and mortality for patients with clade I mpox, including children, were observed when high-quality supportive care was provided. Furthermore, the under-five mortality rate per 1,000 live births for all causes of death in the U.S. is 6 as compared to 76 in the DRC, highlighting the relatively healthy state of children with good access to healthcare in the U.S. In Burundi, where the mortality rate of children under five is 50 per 1,000 live births, to date, there is no evidence that any children have died from mpox, further illustrating the likely reduced virulence of clade Ib MPXV circulating there. If clade Ib mpox were to be detected in the U.S., severe cases would be expected to be rare. In certain cases, due to underlying health conditions, severe disease may occur. CDC is available for clinical consultation and to support clinical management by emailing poxvirus@cdc.gov.

2. Should children be vaccinated against mpox?

Currently CDC does not recommend widespread vaccination for mpox in the United States for any age group, including children. CDC does recommend vaccination for those <18 years, (e.g., adolescents), with risk factors for mpox: gay, bisexual or other men who have sex with men, transgender, nonbinary people who in the past six months have any of the following: new diagnosis of ≥1 sexually transmitted disease, more than one sexual partner, sex at a commercial sex venue, or sex in association with a large public event in an area where MPXV transmission is occurring; sexual partners of people with the risks described above, and people who anticipate any of the above. Additionally, CDC recommends prevention strategies, including vaccination, for those traveling to countries with ongoing clade I mpox outbreaks who are at risk via sexual exposure.16

Mpox vaccine may also be offered as post-exposure prophylaxis (PEP) for previously unvaccinated or partially vaccinated (i.e., one dose of JYNNEOS) children or adolescents with high-risk or certain intermediate risk exposures for clade I mpox under an Expanded Access (EA) IND. JYNNEOS utilization as PEP should ideally be provided within 4 days of exposure however vaccination may occur up to day 14. In infants <6 months, vaccinia immune globulin intravenous (VIGIV) which is available through a CDC EA-IND, is preferred in lieu of vaccination.

3. Will schools close due to clade I mpox?

CDC does not recommend school closure as a routine infection control strategy for mpox and does not expect substantial impacts to educational settings from mpox at this time. If there are cases of clade I mpox in an educational setting, short-term partial closures (e.g. a classroom or other area where the child spent time) may be necessary to allow for cleaning and disinfection and contact tracing. Schools and childcare settings can be prepared by following their everyday operational guidance to reduce the transmission of infectious diseases. Among the limited number of mpox cases in children17 attending school during the clade II mpox outbreak in 2022, there were no cases of in-school transmission reported to CDC and minimal impact on school operations with only short-term closures for cleaning & disinfection.

People with mpox should prioritize staying home and following infection control guidance until the mpox symptoms have resolved. A person with mpox can spread it to others from the time symptoms start until the rash has fully healed and a fresh layer of skin has formed. Healthcare providers and the state or local department of health can help determine when a staff member, child, or student can return to the educational setting. Employers should, consistent with applicable law and policy, provide flexible, non-punitive sick leave policies for staff members. Educational settings may provide virtual options when available and appropriate for students able to participate while at home. Schools and childcare settings can support the health department in contact tracing. Consistent with applicable reporting requirements, schools and childcare settings should contact their health department if a person with confirmed mpox has been in their facility and should, consistent with state or local requirements, support efforts to identify individuals who might have been exposed to the virus.