Mpox caused by Clade Ib: Epidemiological characteristics, prevention, and control

Human mpox (formerly known as monkeypox) historically received little attention until its emergence beyond African countries in 2022. As of September 30, 2024, a total of 109,699 laboratory-confirmed mpox cases have been reported to the World Health Organization (WHO).[1] It has been more than one year since the WHO announced on May 11, 2023, that the mpox epidemic did not constitute a public health emergency of international concern (PHEIC). However, on August 14, 2024, the WHO declared that the upsurge of mpox in the Democratic Republic of the Congo (DRC) and an increasing number of countries in Africa constituted a PHEIC once again. Although the WHO has proposed the “Strategic Framework for Enhancing Prevention and Control of Mpox 2024–2027”, controlling and eliminating the mpox from 2024 to 2025, as planned, appears to be a significant challenge.[2] Additionally, various vulnerable populations (such as children, pregnant women, and immunosuppressed individuals), adverse outcomes (such as myocarditis), and hospital management strategies for mpox complicate prevention and control efforts.[3–5] To effectively prevent and control mpox in the public, it is critical to understand the epidemic trends, the threat posed by Clade Ib, and the necessary control measures. Mpox epidemic trends: Over the past two years, the peak of the mpox epidemic has fluctuated across various regions. Since the first mpox case was reported in the UK on May 7, 2022, the epidemic has spread to other continents beyond Africa, including the American region, the Western Pacific region, and the Eastern Mediterranean region.[6] The United States was the first country in the Americas to report an adult male case on May 18, 2022. Two days later, Australia became the first country in the Western Pacific region to report two cases. Subsequently, Morocco reported one case on June 2, 2022, becoming the first country in the Eastern Mediterranean region to do so. At this point, mpox cases have been reported in nearly all five WHO regions.[6] As of September 30, 2024, of the total reported cases, the America region reported the highest total number of cases (65,877), following by European region (28,176), African region (9425), Western Pacific region (4379), South-East Asia region (971), and Eastern Mediterranean region (871).[1] However, it is important not to focus solely on the total number of cases, changes in epidemic trends reflect the current focus and direction of control measures. According to the WHO report, peak time in the European and the Americas regions was July and August in 2022, respectively. Subsequently, the number of cases peaked in Southeast Asia and the Eastern Mediterranean in August 2023, and in the Western Pacific in September 2023. While it appears that the mpox epidemic is no longer as severe, the African region has reported a significant increase in cases during the first half of 2024.[1] As of October 13, 2024, the African region has reported a total of 10,944 laboratory-confirmed cases, with 78.06% of these cases occurring in 2024 across 15 countries.[1] In the first half of 2024 (February 1, 2024 to July 31, 2024), the African region was the most affected, recording 3061 cases and 23 deaths. This was followed by the American region (2236 cases, 0 deaths) and the European Region (837 cases, 2 deaths).[1] The rapidly escalating epidemic in the African region is one of the factors contributing to the renewed declaration of a PHEIC. The population is generally susceptible to mpox. Individuals who have been vaccinated against smallpox may have approximately 85% effectiveness in preventing mpox virus (MPXV) infection.[7] However, during this multi-country mpox outbreak, men who have sex with men (MSM) represent a high-risk population. The MPXV is divided into two distinct clades: Clade I (formerly known as the Congo Basin or Central African clade) and Clade II (formerly known as the West African clade). Furthermore, Clade II is subdivided into two subclades, IIa and IIb. Clade IIb is responsible for the ongoing multicountry outbreak from 2022 to 2024.[8] As of now, Clade IIb remains the predominant epidemic clade affecting MSM through human-to-human sexual contact in countries outside the African continent.[8,9] However, during the years 2022–2023, the initial declaration of a PHEIC was not taken seriously enough, as most MPXV infections were self-limited and characterized by low-level transmission. The rapidly increasing infections in the African region in 2024 suggest that the global transmission dynamics of MPXV are beginning to change. First, the emergence of a new offshoot of Clade I, known as Clade Ib, has complicated the global response to the outbreak. The current outbreak in the DRC is attributed to Clade Ib, which is associated with more severe disease than Clade II.[10] The rapid spread of the Clade Ib, particularly in eastern DRC and neighboring countries, along with its recent detection in Sweden and Thailand, underscores the growing threat of potential international transmission.[8] Up to now, there has been limited research reported on the epidemic characteristics of Clade Ib. The Lancet published an article stating corresponding epidemiological data in the African region is vital for formulating effective mpox prevention plans and policies.[11] According to report from WHO, as of October 13, 2024, the DRC has reported a total of 8207 cases (27 deaths), of which, 6962 cases and 25 deaths occurred in 2024. As of October 13, 2024, 18 countries have reported 8540 confirmed cases and 33 deaths. These data may suggest that Clade Ib had a higher case fatality rate (CFR) and greater transmissibility. However, further research is needed to compare the epidemic characteristics of different clades.[1] Meanwhile, the presence of other spreading clades, including Clade Ia and Clade II in various African countries, indicates that the detection techniques and prognosis assessment need to be more precise.[8] Importantly, the latest study reported that due to the significant mutational potential of MPXV in the future, its spread could be more extensive, potentially affecting demographics beyond the currently impacted.[12] Existing strains and the evolutionary dynamics of MPXV underscore the importance of ongoing surveillance and its implication for public health policy.[12] Additionally, the WHO indicated in 2022 that mpox can be transmitted through respiratory droplets during prolonged face-to-face contact.[13] However, few cases of droplet exposure have been specifically documented, as these are included in the broader category of person-to-person transmission. Some studies have detected the virus in saliva, but the viral load is significantly lower than that found in feces, anal swabs, and crusts, making droplet transmission generally considered less likely.[14,15] Notably, Thailand, as the first Asian country, reported cases of Clade Ib infection through droplet transmission on August 22, 2024. Although more evidence is needed to determine the extent of droplet transmission, the emergence of this case presents a greater challenge to mpox control among the general population. Finally, it is crucial to pay attention to the CFR, particularly among children aged 15 years and younger. During the 2022–2023 period, Laurenson-Schafer et al[16] reported that, compared to the population aged 15–44 years, the risk of hospitalization among children aged 0–4 years increased by 112%. However, this increase was not significant among those aged 5–14 years (adjusted odds ratio [aOR] = 0.81, 95% confidence interval [CI]: 0.44, 1.51).[16] Cases and deaths among adults over 40 years remain infrequent, likely due to residual immunity from the smallpox vaccination campaigns conducted in the 1960s and 1970s.[17] The primary affected population consists of MSM, who exhibit a low CFR; consequently, the CFR among children during the 2022–2023 multicountry outbreak has not received adequate attention. One meta-analysis indicated that, among children under 10 years old, the CFR was nearly 100% from 1970 to 1990.[18] Across all countries, the calculated pooled estimate of the CFR was 8.7% prior to 2022.[18] However, a surge in cases caused by Clade Ib has been associated with a higher CFR (reported to be as high as 10%) compared to the Clade II, which was responsible for the 2022–2023 global outbreak.[17] The deaths are concentrated in children aged 15 years and younger (nearly 78%), and even stillbirths in 2024.[19,20] In contrast, there was 37.5% (6/16) of deaths occurred in children under 10 years old from 2000 to 2019.[18] The higher CFR and the surge in child deaths during the first half of the year are raise concerning. Our focus should not only be on the rapid spread of Clade Ib among adults through close physical contact but also on the shifting affected groups, particularly children, through households transmission.[8] The threat posed by Clade Ib underscores the need for further research on epidemic characteristics (i.e., transmission parameters, risk factors, transmission risks from various types of contact, and severity risk factors), detection methods, and vaccine effectiveness. Prevention and control measures: Important actions must be taken to address this challenge [Supplementary Figure 1, https://links.lww.com/CM9/C292]. First, it is essential to strengthen surveillance, case management, and public health education. The Centers for Disease Control and Prevention (CDC) should enhance the timeliness and accuracy of disease surveillance capacity. In epidemic areas, there is an urgent need for improved surveillance to monitor the growth of mpox epidemics and the transmission dynamics of new virus strains, which is critical for advanced planning and resource allocation, including medical care and vaccination. New surveillance tools, such as environmental monitoring through wastewater analysis, should be consistently developed. Wastewater samples have been utilized to track the presence of the MPXV, drawing on the experience of wastewater monitoring during the coronavirus disease 2019 (COVID-19) pandemic in USA, as proposed by the CDC.[21] Additionally, in non-epidemic countries, customs checkpoints should strictly prevent the importation of the virus and enhance monitoring of individuals traveling from high-risk countries to mitigate the risk of local outbreaks. In line with the previous epidemic trends, it is crucial to emphasize dynamic and timely assessments for evaluating imported risk. Factors such as the volume of exchanges, their nature (travel, work, study, etc.), and the epidemic severity of the area of stay should be considered in the import risk assessment. Given that Cade Ib may have a higher likelihood of droplet transmission and a greater CFR, the case management should be adjusted promptly. Furthermore, hospital-based disease surveillance and case management should be adopted, as they paly critical roles in clinical diagnosis and treatment.[4] Enhancing the capacity for human resource management, healthcare professional education, and facilities and resource management is essential to counteract the upsurge of cases in epidemic area.[4] Additionally, precise clinical diagnosis and laboratory testing, appropriate operational medical equipment, and effective case classification management should be integral components of hospital-based disease surveillance and case management. The WHO has issued guidance on clinical management and infection prevention and control for mpox in 2022.[22] The WHO has also listed the first mpox in vitro diagnostic under its Emergency Use Listing procedure, marking a significant step toward improving global access to mpox testing.[23] Precise clinical assessment tools, such as visual assessment for lesions and robust biological indicators to diagnose Clade I and predict severe outcomes in the early stages, may prove to be more effective than limited point-of-care tests.[24] The most important aspect of public health education is to maintain measures such as reducing travel to affected countries and unsafe sex. Considering the high CFR and the potential for household transmission among children, it is essential to disinfect clothing, supplies, and any potentially contaminated environments before returning home. This practice will help prevent indirect contact with children through contaminated materials and reduce the risk of household transmission. Family members are advised to seek medical care immediately and avoid contact with children if they have been in the DRC or its neighboring countries in the last 21 days and develop suspected symptoms.[25] Secondly, in addition to avoiding close contact with suspected cases, vaccination against mpox remains the most effective strategy for individuals, particularly given the high CFR in children.[26] Several potential vaccine candidates are under consideration, including modified vaccinia Ankara-Bavarian Nordic (MVA-BN), LC16m8, ACAM2000, BNT166a, and BNT166c.[8] On September 13, 2024, the WHO approved an application for emergency authorization for the use of MVA-BN. While MVA-BN is currently not licensed for individuals under 18 years of age, this vaccine may be used in children in outbreak settings where the benefits of vaccination outweigh the potential risks.[27] Meanwhile, the effectiveness and safety of these vaccines, along with their delivery, production scalability, and equitable access, still need to be addressed in the current outbreak.[2,8] More long-term studies are being conducted to monitor the durability of immune responses and to determine the need for booster doses, which will be critical in shaping future vaccination strategies and policies.[8] However, an immediate plan is urgently needed for the development and deployment of a vaccination strategy that prioritizes sex workers and other vulnerable populations at risk.[26] It should be emphasized that there is insufficient evidence to confirm the safety and effectiveness of vaccinations in children. In response to the current outbreak, international cooperation is of utmost importance. Information sharing regarding vaccine development, clinical evaluation, and surveillance methods for Clade Ib, is interconnected. The allocation of medical resources including human resources, pharmaceuticals, and vaccines, through international collaboration among public and private entities is essential to prevent epidemics in low-income countries and to curb the spread to other nations. Urgent action is required to prevent the broader geographic dissemination of Clade Ib, with particular emphasis on addressing the needs of vulnerable populations, especially children. Funding This study was supported by a grant from the National Natural Science Foundation of China (No. 72122001). Conflicts of interest None.