Emergence of mpox in the Eastern Mediterranean Region: Data assessment and implications for a public health response

Abstract

Introduction

Monkeypox (mpox) is an illness caused by the MPX virus and endemic to certain African countries. Historically, sporadic outbreaks have occurred in some non-endemic areas. In 2022, a new variant emerged, clade IIb, causing a global outbreak sustained within sexual networks among men who have sex with men (MSM). To our knowledge, this is the first multi-country study examining mpox epidemiology and clinical features of the 2022–2023 outbreak caused by clade IIb across the Eastern Mediterranean Region (EMR).

Methods

We analyzed datasets of anonymous mpox case-based reports submitted to the World Health Organization (WHO) from May 2022 to December 2023 in the EMR to describe the cumulative incidence, demographics, transmission routes, and clinical outcomes.

Results

By the end of 2022, 95 case reports were submitted to the WHO. The first case of mpox was reported in the United Arab Emirates on May 24, 2022. The highest number of cases were reported from Lebanon (27 confirmed cases). Most cases in the EMR were adult males (92 %), 60 % identifying as MSM, and 10 % living with HIV. Most reported symptoms were rash (95.4 %) and fever (69.6 %). No intensive care unit admissions or deaths were reported.

Conclusion

In this study we investigated the epidemiology, clinical presentation, and outcomes of the mpox outbreak related to clade IIb in the EMR. We raise concerns about the accuracy and completeness of the data, given that the number of cases reported to the WHO from EMR countries appears to be significantly lower than the number of cases documented within the region. This discrepancy could impact the reliability of the reported figures and the region's response strategies. Despite these challenges, collaborative efforts across EMR countries have laid the groundwork for effective outbreak response, underscoring the importance of ongoing regional cooperation to enhance future preparedness strategies.

Introduction

Mpox, previously known as monkeypox, is a viral illness attributed to the orthopoxvirus MPX. This virus is endemic to certain African countries where hundreds of cases are recorded every year. Mpox was first described in 1958 in monkeys and the first human case was reported in 1970 in a 9-month-old boy in Congo [1], [2]. Outbreaks of mpox outside Africa have been linked to international travel from endemic to non-endemic countries [3]. In 2022, a new variant, clade IIb, emerged and caused a global outbreak primarily sustained within sexual networks among men who have sex with men (MSM), and faded away by early 2023. While our study focuses on the outbreak that occurred between 2022 and 2023, the topic remains highly relevant as a new mpox outbreak is currently surging in the Democratic Republic of the Congo (DRC) and is rapidly spreading to neighboring African countries. In August 2024, the WHO, again, declared this a Public Health Emergency of International Concern (PHEIC) [4]. Understanding the dynamics of the past outbreak can provide valuable insights for mitigating this and future outbreaks, and improving symptom reporting and public health responses.

MPX is categorized into two genetic clades: the Congo Basin clade (clade I), from which the current outbreak is emerging, and the West African clade (clade II), from which emerged clade IIb during the 2022–23 outbreak [5]. The emergent variant clade IIb was identified on May 6, 2022 from the first case of mpox in the United Kingdom in a British resident returning from Nigeria, where cases had been increasing since 2017 [6]. This outbreak rapidly spread across Europe, North America, and all six World Health Organization (WHO) regions, and by May 21, 2022, 92 mpox cases had been confirmed across thirteen non-endemic countries [7]. On July 23, 2022, the WHO declared mpox as a PHEIC [8]. By August, 2024 99,518 confirmed cases and 140 deaths across 111 countries were reported [8]. Globally, this outbreak principally affected men who have sex with men (MSM) with few cases documented among healthcare professionals [2]. The PHEIC was lifted following attenuation of the outbreak.

MPX is transmitted by direct contact with droplets from infected humans and animals and through skin-to-skin contact [2]. In endemic Africa, the leading cause of human infection is zoonotic, caused by close contact with diseased animals during activities such as deforestation or hunting [9]. On the other hand, transmission during the 2022 global outbreak was primarily associated with sexual contact (in 70 % of cases) including oral, anal, or vaginal sex as well as hand-to-genital contact [10]. Other routes of transmission included direct non-sexual physical contact, contact with a fomite, mother-to-fetus transmission, and air-borne transmission over short and long distances. MSM, immunocompromised individuals such as persons living with HIV (PLWH), pregnant women, and children are considered high-risk groups vulnerable to mpox infection and may face higher risks of severe illness or death [3]. Symptoms of mpox typically emerge within 7 to 21 days after exposure and last 2 to 4 weeks, but potentially longer in immunocompromised individuals [2]. A systematic review and meta-analysis of 77 studies on the clinical and epidemiological features of mpox revealed that the most commonly reported symptoms in the 2022–23 outbreak were skin lesions, fever, and lymphadenopathy, followed by fatigue, myalgia, headache, chills, sore throat, rectal or anal pain, difficulty swallowing, back pain, and cough [11]. A multicenter cross-sectional study in China, which analyzed the epidemiological characteristics and clinical manifestations of 115 mpox cases, reported that systemic symptoms such as fever, lymphadenopathy, and myalgia were the most common. Skin lesions were observed in all participants, including those in the genital and perianal areas [12]. Infections with the emergent clade IIb variant were rarely fatal, with a global survival rate of over 99 % and a hospitalization rate of 6 % [3], [13].

The mpox outbreak that started in 2022 posed a significant concern to health systems globally as capacity had been exhausted by the COVID-19 pandemic, while vaccination against orthopoxviruses had been abandoned for long since the eradication of smallpox in 1980 [14]. Moreover, in May 2022, cases of mpox were reported in several countries with no historical sustained community transmission of mpox and with no recent travel history to endemic areas [15].

Covering 22 countries and territories across the Middle East, West Asia, North Africa, and the Horn of Africa, the EMR encompasses a population of over 745 million people [16]. In this region, marginalized populations such as MSM, female sex workers, and intravenous drug users often face stigma and are discriminated against. This stigma can be experienced in various settings, including the healthcare system, the legal and political systems and in society at large. A global comprehensive analysis of the outbreak was conducted which identified these groups as among the most vulnerable [15]. However, in the EMR, there is a notable lack of epidemiological data and research on mpox. Critical information regarding transmission routes, case characteristics, hospitalization and mortality rates is lacking. This gap highlights the significance of our investigation into the epidemiology, clinical presentation, and outcomes of mpox cases reported to the WHO from the EMR. To our knowledge, this is the first comprehensive regional analysis of the 2022–23 multi-country mpox outbreak across the EMR.

Materials and methods

This is a retrospective analysis of confirmed mpox cases submitted to the WHO’s Regional Office for the Eastern Mediterranean (WHO EMRO) by the member states [17], [18]. In May 2022, under Article 6 of the International Health Regulations (IHR 2005), in line with recommendations issued by the WHO Director-General in August 2023, the WHO established a global surveillance system with two main components: [1] daily aggregated numbers of mpox cases by country, and [2] a Case Reporting Forms (CRF) capturing key variables for each confirmed and probable mpox case based on standardized case definitions (Appendix 1). The CRF collected data on demographics, medical history, clinical presentation, epidemiological exposure factors, and laboratory testing. Sex data, defined as sex at birth, were reported by clinicians based on patient self-reports, with options including female, male, other, and unknown. The WHO received these reports from May 28, 2022 to December 30, 2023, and the data in these reports were subsequently entered into a database for analysis. Additionally, we reviewed relevant journal articles on PubMed and technical reports on mpox surveillance activities from the assessed countries.

WHO case definitions

Case definitions include confirmed, probable, suspected and discarded cases. A confirmed case is defined as a person with laboratory-confirmed MPX virus (MPXV) infection by detection of unique sequences of viral DNA by PCR and/or sequencing. A probable case would be a person presenting with an unexplained acute skin rash, mucosal lesions or lymphadenopathy. A suspected case is defined as a person with known contact with a probable or confirmed mpox case in the 21 days prior to the onset of signs or symptoms. Lastly, a discarded case is a suspected or probable case for which laboratory testing of lesion fluid, skin specimens or crusts by PCR and/or sequencing is negative for MPXV [17], [19].

Outcomes

The primary outcome of the study to use descriptive analysis in order to characterize the outbreak in the EMR. We reported on the number of cases, their demographic and geographic distribution, transmission routes, clinical presentation, hospitalization rate, and mortality. All mpox cases reported to WHO EMRO were included in this analysis.

Ethical considerations

This analysis is based on anonymous case-based reports. Case-based reports submitted by Member States to WHO as per IHR requirements. Those case-based reports included only the minimum necessary data points such as demographic information, clinical presentation, and exposure history, without any personally identifiable information. As the data were anonymized before analysis and used only for public health purposes, individual informed consent and ethical approval were not required.

Results

By the end of 2023, 95 confirmed cases were reported to the WHO, of which 71 had detailed reports of varied completeness, representing a 73.7 % data completeness level [10].

Time trends in case reporting

The first case of mpox in the EMR was reported from the United Arab Emirates (UAE) on May 24, 2022. Subsequently, from May to September 2022, the WHO consistently received between one and six case reports of mpox per week from the region, then peaking at 13 cases during the week of September 30, 2022 (Fig. 1). Following this peak, cases became sporadic, with intermittent increases observed in late spring (April and May 2023) and late fall (October 2023). The last reported case occurred during the final week of October 2023.

Fig. 1.

Weekly case reports of mpox Clade IIb in the Eastern Mediterranean Region.

Demographic distribution

Among the 64 case reports that contained information on age and gender, 58 (91 %) were male, 59 (92 %) were aged 16 – 50 years, and 3 (5 %) were children (Table 1). In the region, Lebanon experienced the highest case count, with 27 laboratory-confirmed cases. Notably, among these cases, 78 % fell within the age range of 25 to 44 years old, with 60 % identifying as MSM. Only one pediatric case was recorded, involving an eight-year-old.

Table 1.

Demographic characteristics of reported cases.

Characteristic	Overall, n (%), (n = 95)
Age, years
< 16	3 (3.2)
16 −25	8 (8.4)
26 −35	36 (37.9)
36 −50	15 (15.8)
> 50	2 (2.1)
Missing	31 (32.6)
Gender
Male	58 (61.1)
Female	6 (6.3)
Missing	31 (32.6)
Sexual Behavior
Heterosexual	42 (44.1)
MSM	25 (26.5)
Unknown	13 (13.7)
Missing	15 (16.2)
Sexually transmitted infection
HIV	10 (10.5)
Syphilis	1 (1.0)
HSV	1 (1.0)
Not Specified	55 (57.9)
Route of Transmission
Sexual transmission	9 (9.0)
Person-to-person contact	6 (5.9)
Contact with fomites	3 (4.4)
Unknown	39 (41.0)
Missing	36 (40.0)
Recent Travel History	45 (47.0)

MSM: men who have sex with men; HIV: human immunodeficiency virus; HSV: herpes simplex virus

d girl. The lowest case counts were from Jordan and Iran (1 case each) (Table 2).

Table 2.

Distribution of cases by country.

Country	Reported cases, n (%)
Lebanon	27 (28.4)
Sudan	19[20]
United Arab Emirates	16 (16.8)
Saudi Arabia	8 (8.4)
Pakistan	7 (7.3)
Qatar	5 (5.2)
Egypt	3 (3.2)
Morocco	3 (3.2)
Oman	3 (3.2)
Bahrain	2 (2.1)
Islamic Republic of Iran	1 (1.05)
Jordan	1 (1.05)
Regional Total	95 (100)

Transmission and sexual behavior

In terms of sexual behavior among the cases, 44.1 % identified as heterosexual, while 26.5 % identified as MSM, 13.2 % marked sexual behavior as “unknown”, and 16.2 % didn’t contain any information on sexual behavior. Regarding the mode of transmission, data on the transmission route were missing for 36 cases (40 %). Among the remaining 59 cases, 41 % reported an unknown route of transmission, 9 % indicated sexual transmission, 5.9 % involved person-to-person contact, and 4.4 % were linked to contact with fomites. Additionally, a recent travel history was reported in 47 % of cases. (Table 1).

HIV and sexually transmitted infection status

Sixty-five of the reports (68 %) provided information on coinfection with a sexually transmitted infection (STIs). Among these, 10 cases (15 %) tested positive for HIV, one for syphilis, and one for herpes zoster virus. Most of those reports (55 cases, 85 %) did not specify the STI. (Table 1).

Clinical presentations and hospitalization

Among the 95 confirmed cases, 66 individuals (about 69 %) reported experiencing symptoms. The predominant symptoms included rash (95.4 %), fever (69.6 %), fatigue (48.5 %), and genital rash (38.9 %). Notably, genital rash was more prevalent among cases involving MSM, with 56 % reporting this symptom, compared to heterosexual cases, where genital rash was reported in 21.8 % of cases (Table 3). Out of the 86 cases for which hospitalization data was available, 46 cases (approximately 53 %) required hospitalization. Among the hospitalized cases, only one individual was also HIV positive. There were no reported admissions to the intensive care unit (ICU), and no deaths were reported to the WHO.

Table 3.

Percentage of reported symptoms, categorized by documented sexual behavior.

Symptoms	Heterosexual, %	MSM, %	Overall, %
Rash	96.87	94	95.43
Fever	78.12	61	69.56
Fatigue	25	72	48.5
Genital Lesions	21.87	56	38.93
Musculoskeletal pain	18.75	50	34.37
Throat pain	15.62	44	29.81
Oral Lesions	3.12	11	7.06
Throat pain	15.6	44	29.8
Headache	15.6	28	21.8
Local lymphadenopathy	9.37	6	7.68
Cough	9.37	6	7.68
Generalized lymphadenopathy	6.25	44	25.12
Conjunctivitis	6.25	0	3.12
Chills	6.25	33	19.62
Vomit	3.12	6	4.56
Back Pain	3.12	0	1.56

Percentages are expressed as column %

MSM: men who have sex with men

Discussion

In this study we investigated the epidemiology, clinical presentation, and outcomes of mpox cases reported to the WHO. We raise key issues for discussion and propose practical steps to improve future responses.

Outbreak larger than reported

An important observation pertains to the reported scale of the mpox outbreak in the EMR. The WHO officially received 95 reports of confirmed mpox cases between May 2022 and December 2023, the lowest case count across all six WHO regions. While these numbers may convey a success story, facility-based reports emerging from Gulf countries have contradicted these findings. For example, while only 16 case reports were submitted from the UAE to the WHO, a prospective study from Abu Dhabi, one of the seven Emirates, had alone reported 174 hospitalized cases of mpox between May and December 2022 [2], [20]. Similarly, while the WHO only received 8 mpox case reports from the Kingdom of Saudi Arabia, a single-center study in Riyadh, the capital, had alone examined 16 cases between June and September 2023 [21], [22]. Such discrepancies suggest limitations in data reports to the WHO. It can be reasonably inferred that the mpox outbreak in the EMR may have been larger and more widespread than reported to the WHO.

Stigma affected reporting, response, and tracing efforts

The impact of stigma on the reporting of the outbreak is noticeable at both the provider level and the level of the population affected by mpox in the EMR.

While other regions data completeness rates exceeded 99 %, the EMR lags at approximately 74 %, with significant gaps in crucial information like sexual behavior, HIV status, and transmission modes. In fact, 81 % of EMR reports either failed to specify the mode of transmission or left the field blank. Of those, only 9 % reported transmission through sexual contact, when global estimates approached 83 % [20], [21], [23]. In our region, discussing sexual health, especially in relation to MSM, remains taboo even within healthcare settings. As a result, healthcare providers may be hesitant to ask about or record information deemed sensitive, and patients, fearing judgment or discrimination, may withhold details about their sexual history or avoid seeking medical care altogether [24]. Stigma may also lead to knowledge gaps concerning mpox management among healthcare providers in the region [24], [25]. This lack in knowledge could result in misdiagnosis, which impacts tracing efforts.

We speculate that most individuals affected by the 2022–2023 mpox outbreak in the EMR belonged to vulnerable populations, similar to trends observed globally. Our analysis shows a stark contrast between the global prevalence of HIV among mpox cases (around 50 %) and the much lower figure reported in the EMR (12 %). In this region, PLWH face discrimination from healthcare workers and report high levels of perceived stigma [26]. In this context, stigma could have contributed to underreporting and misrepresentation of PLWH affected by mpox in the region [22] which distorts the epidemiological picture and impairs the region’s ability to respond effectively to the outbreak [27].

Furthermore, our results indicate higher hospitalization rates in this region. One possible explanation for this could be either attributed to policies of hospital isolation of all cases, or that only the most severe cases presented at hospitals. This may reflect a lack of trust in healthcare systems and the fear of discrimination faced by vulnerable populations, which discourages them from seeking timely medical attention, further contributing to gaps in reporting. Others, possibly experiencing milder symptoms, may have chosen to recover at home to avoid the stigma associated with the disease.

Low reported numbers in the EMR may also reflect the reluctance among key populations to test and seek care due to the fear of the social and personal implications of a positive diagnosis, further exacerbating the challenges in addressing the outbreak [28].

Lebanon experience stood out as an example for countering the effects of stigma and discrimination. The country reported the highest number of cases, of which 60 % were identified as MSM. This could be explained by the fact that Lebanon is the only country that delegated its mpox response to the National AIDS Program (NAP) whose main approach was to engage MSM community organizations in mpox awareness, diagnosis, and support. This approach leveraged the existing trust between the Lebanese NAP with the MSM community and resulted in better reporting [29]. The Lebanese experience highlights the importance of engaging local communities and trusted stakeholders, such as the NAP in Lebanon, who have established relationships with vulnerable populations. These groups often feel alienated by the formal healthcare system, making it essential to involve intermediaries they trust to bridge the gap and ensure more effective outreach and accurate reporting. This can lead the ways towards enhanced data reporting regarding sexual health in the EMR, rectifying the gaps needed to characterize this and future outbreaks of STIs.

Reported symptoms and clinical presentation

The most commonly reported symptoms in our study were rash, fever, fatigue, which is consistent with findings from a large study conducted across 16 countries during the outbreak that reported 95 % of patients experiencing a rash, 62 % fever and 41 % experiencing fatigue, similar to our numbers [30]. Genital lesions were less commonly reported (39 %) in the EMR population compared to 73 %. In our study population symptom patterns did not differ significantly based on sexual behavior, though genital lesions were more common among MSM (56 %) compared to heterosexual individuals (22 %). Similarly, generalized lymphadenopathy was more frequent in MSM than in heterosexuals. These differences may be linked to variations in the route of transmission.

Concomitant HIV and STI infections were significantly lower among the EMR reported cases, 15 % and 1.5 %, respectively. This differs greatly from globally reported figures where 41 % had HIV and 29 % had an STI [29].

Global and Regional collaboration

This study also helped to identify important obstacles for effective collaboration which should be addressed in future outbreaks. The International Health Regulations (IHR) provide a global legal framework for local and international response to outbreaks, defining country core capacities to have the ability to detect, assess, report, and respond to public health events. This is intended to enable effective global collaboration for halting public health events. The weak reporting and, likely weak ability to diagnose cases, in the EMR jeopardizes the regional response and subsequently may weaken the global efforts.

Furthermore, the collaborative efforts across nations in the EMR have laid the foundation for effective response to outbreaks, emphasizing the necessity to strengthen and continue regional cooperation, a stance advocated since the onset of the COVID-19 pandemic [22], [31]. A similar approach in mpox may be imperative to overcoming region-specific challenges such as mitigating stigma and taboos surrounding sexual health and sexual behavior, to improve reporting and access to services for individuals affected by related diseases.

Conclusion

Although the WHO ended the PHEIC notice in May 2023, the re-emergence of mpox in 2024 emphasizes the importance that global health systems integrate mpox in their long-term prevention and preparedness programs. The WHO has effectively managed public health emergencies in this area, as demonstrated by the COVID-19 response. However, the 2022–2023 mpox outbreak highlighted that it under-performs when involving topics that involve higher stigma, particularly around sexual health and behaviors. Stigma led to underreporting, misdiagnosis, and incomplete data which poses significant limitations to thoroughly characterizing the outbreak, which in its turn delays the development of effective and targeted responses. Focusing on better education of healthcare workers may help decrease stigma and improve reporting during future outbreaks. This mpox outbreak also showed the global impact of tropical diseases previously deemed “geographically confined” to certain countries, and highlighted the lack of equity in vaccine distribution, which have not reached the countries most in need of it. Finally, this study highlights the importance of continued collaboration between countries and the need for continued surveillance efforts. Moving forward, regional and global health authorities must prioritize stigma reduction, equitable healthcare access, and collaboration with community organizations to improve data accuracy, reporting, and service access in future public health crises, especially in the wake of the ongoing re-emergent outbreak.

Funding

There is no funding source.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary material

Supplementary material

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