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Mpox (formerly known as monkeypox) is a disease caused by mpox virus. Until recently, mpox cases have been reported in endemic regions in Africa. In 2022, a global outbreak of mpox was a result of human‑to‑human transmission through direct contact. Until 2022, no cases of mpox have been reported in Poland. We analyzed a group of 45 patients diagnosed with mpox in Kraków, which accounted for 21% of all cases in Poland. Mpox spread among the patients primarily through sexual contacts. We noted a high incidence of concomitant sexually transmitted infections (STIs) and common engagement in unsafe sexual practices. Our findings offer valuable insights for developing preventive programs and emphasize the importance of regular screening for STIs.

Introduction

Mpox is a zoonotic viral disease caused by mpox virus (MPXV), an orthopoxvirus belonging to the Poxviridae family. It is endemic to several African countries. In 1958, MPXV was first discovered in Copenhagen in laboratory monkeys,¹ and the first human infection was diagnosed in 1970 in the Democratic Republic of Congo in a 9‑month‑old child with an initial suspicion of smallpox.² Several rodents and small mammals have been identified as potential sources of the virus; however, the natural reservoir remains unknown. The obsolete term “monkeypox” originally referred to macaque monkeys, in which the infection was initially identified.³ The first cases of mpox in humans were linked to animal transmission through direct contact with their body fluids, scratching, biting, or consuming the infected animals’ meat.⁴ Before 2022, sporadic cases were reported in nonendemic regions of North and South America, Europe, and Asia, and they were mostly linked to travels to endemic regions or contacts with animals.⁵ However, since May 2022, there has been a significant surge in mpox cases worldwide. This surge was a consequence of a large‑scale human‑to‑human transmission, and was declared a global health emergency by the World Health Organization (WHO) in July 2022.⁶ Genomic analyses revealed that the MPXV‑2022 strain is closely related to 2018 isolates but contains 46 new nonsynonymous mutations, whose role in the virus transmissibility and pathogenesis remains unclear.¹ According to the Centers for Disease Control and Prevention (CDC), as of December 27, 2023, there have been 92 546 confirmed cases of mpox in 117 countries, 110 of which have never reported mpox before. The highest rates were confirmed in the United States (31 567 cases). In Europe, the highest number of patients was reported in Spain (7647 cases). According to the reports from the National Institute of Public Health – National Research Institute, 217 cases of the disease were confirmed in Poland between May 2022 and December 27, 2023.

In most cases, mpox is a self‑limiting disease with an incubation period ranging from 5 to 21 days. Its clinical course is characterized by prodromal symptoms, such as fever, malaise, headache, and muscle pain, followed by polymorphic skin eruptions and mucosal lesions.⁷ Natural evolution of the lesions involves distinct stages: macule, papule, vesicle, pustule, and eventually a scab that falls off. Skin changes are typically accompanied by local lymphadenopathy.⁶ In most patients, distribution of the skin lesions corresponds to the site of MPXV inoculation.⁸ Given that the current outbreak primarily impacted men who have sex with men (MSM), the rash was frequently noted in the anogenital area.⁹

Patients and methods

We retrospectively analyzed medical records of all mpox cases diagnosed at the University Hospital in Kraków from June to November 2022. The study included patients who were hospitalized in our Department of Infectious Diseases as well as those who were isolated at home. The patients with suspected MPXV infection were referred to the University Hospital by different specialists from outpatient clinics and hospitals in Kraków and the southeast region of Poland. Some patients reported directly to an emergency department. Cases of mpox were confirmed by testing the exudate from the skin or mucosal lesions using the real‑time polymerase chain reaction method for viral DNA.

The epidemiologic data, most probable routes of transmission, and clinical symptoms were retrospectively analyzed from the database of the Department of Infectious Diseases of the University Hospital in Kraków. Additional information regarding risky sexual behavior, including chemsex (sexual activity under the influence of drugs) and group sex, prior history of sexually transmitted infections (STIs), and the use of pre‑exposure prophylaxis for HIV (PrEP), was gathered using consistent interview questionnaires for both hospitalized and ambulatory patients. Any concurrent coinfections diagnosed at the time of mpox diagnosis were recorded and treated.

The study was approved by the local ethics committee (118.6120.201.2023). Informed consent was obtained from some patients to take and publish photos of skin and mucosal changes for scientific purposes.

Statistical analysis

A descriptive analysis of the study group was performed, and percentages, means (SD), and medians (interquartile range [IQR]), when applicable, were used to present the distribution and central tendency in the analyzed group.

Results

Between June and November 2022, the outpatient clinic and Department of Infectious Diseases of the University Hospital in Kraków reported 45 cases of mpox, accounting for 21% of all cases confirmed in Poland until September 2023. Forty‑four patients (98%) were men and 1 was a woman (2%). Median (IQR) age of the patients was 34 (19–48) years. Forty‑two patients (93%) self‑identified as MSM. General characteristics of the group are presented in Table 1.

Concomitant STIs acquired before or simultaneously with mpox were evaluated in detail. Twenty‑six patients (58%) with mpox had HIV, including 4 (15%) who were newly diagnosed. Of these newly diagnosed patients, 1 presented with acute retroviral syndrome and syphilis infection. There were 22 patients (85%) who had already been diagnosed with HIV. All of them were on antiretroviral therapy, and 20 (91%) had an HIV viral load below 50 copies/ml. Only 2 patients had detectable HIV RNA (93 copies/ml and 227 copies/ml, respectively). One of them had been diagnosed with HIV less than 6 months before mpox. Characteristics of the patients with previously diagnosed HIV are presented in Table 2.

Of the 4 patients newly diagnosed with HIV, 1 presented with acute retroviral syndrome along with syphilis infection. He had a history of unprotected anal sex with multiple male partners for 4 weeks prior to diagnosis. Due to extensive ulceration of the penis and local superinfection with Staphylococcus aureus, the patient required an extended hospital stay. The infection was complicated by an abscess in the groin, which required surgical drainage and treatment with intravenous antibiotics (Figure 1).

Apart from newly‑diagnosed HIV coinfection, 12 patients (27%) were diagnosed with other STIs. Of those, 5 patients (38%) had syphilis, 4 (33%) had Chlamydia trachomatis infection, 3 (25%) Neisseria gonorrhoeae infection, and 2 (17%) Ureaplasma urealyticum infection. Four patients were diagnosed with more than 1 STI in addition to mpox. Specifically, 1 patient had syphilis, Ch. trachomatis infection, and newly‑diagnosed HIV. Another patient had N. gonorrhoeae infection and syphilis, while the third had N. gonorrhoeae and U. urealyticum infections. Lastly, 1 patient had acute retroviral syndrome alongside syphilis.

We also evaluated the history of previous STIs. Twenty‑nine patients (64%) reported having other STIs in the past, and 13 of them (29%) had 2 or more STIs. Specifically, 17 patients (59%) had a history of syphilis, 12 (41%) of N. gonorrhoeae infection, 7 patients (24%) had been successfully treated for hepatitis C, 6 (21%) contracted Ch. trachomatis, 1 patient (3%) had hepatitis A, and 1 patient (3%) had U. urealyticum infection.

In the group of 23 patients without HIV infection, 3 individuals (13%) were taking PrEP, and 1 (2%) was receiving postexposure prophylaxis at the time of mpox diagnosis. Among the patients newly diagnosed with HIV, 1 man (2%) had a record of inconsistent adherence to PrEP 3 months before being diagnosed with HIV and mpox.

A total of 13 patients (29%) had a history of engaging in group sex within 1 month prior to diagnosis, 15 patients (33%) reported having sex under the influence of drugs (taken immediately before or during sex), and 5 patients (11%) reported using a sauna before infection. In our cohort, there was only 1 woman (2%); her husband had an infection confirmed 10 days before her symptoms started. Most of our patients contracted mpox in Poland, but 7 of them (16%) had a history of travel abroad in the 4 weeks preceding the onset of symptoms (3 patients traveled to Germany, 2 to Italy, 1 to Spain, and 1 to Egypt). All these patients identified as MSM and reported risky sexual behavior during their travel.

The history of smallpox vaccination was reviewed, revealing that only 1 patient was vaccinated against smallpox in childhood as part of routine immunizations. He was a 47‑year‑old man, the first confirmed case of mpox in our cohort. He presented with mild symptoms of mpox, characterized by single localized penile ulcerations (Figure 2).

Twenty‑six patients (58%) required hospitalization. Initially, hospitalization was mandatory in Poland for individuals with suspected or confirmed mpox. Following confirmation of the infection, the patients were required to continue hospital isolation for up to 21 days after symptom onset. After the legal requirement for hospitalization expired on July 28, 2022, the decision about patient admission and discharge was made individually, based on symptoms, general condition, and current recommendations for isolation in a hospital ward. The mean duration of hospitalization was 7 (range, 1–14) days.

Most patients in the analyzed cohort experienced mild and self‑limiting symptoms of mpox, requiring only supportive treatment. Twenty‑three patients (51%) had fever lasting for a median (IQR) of 4 (2–10) days, while 35 patients (78%) presented with painful lymphadenopathy. Specifically, 20 patients (44%) showed inguinal lymph node involvement, in 12 (27%) cervical lymph nodes were affected, and 3 (7%) had both inguinal and cervical lymph nodes enlarged. Skin changes initially manifested in various parts of the patients’ body. The genital area was the first are affected in 17 men (27%), 12 patients (20%) had lesions primarily in the oral cavity, 9 (14%) in the anorectal region, 4 (9%) on the palms and soles, and 3 (7%) on the chest. Thirty patients (67%) had polymorphic rash spreading across multiple anatomical regions. In addition to typical mpox symptoms, the patients also reported pain in the anal area (n = 13; 29%), sore throat (n = 10; 22%), dysuria (n = 6; 13%), and headache (n = 2; 4%).

Laboratory workup showed elevated levels of C‑reactive protein (10–281 mg/l; reference range <⁠5 mg/l) in 28 individuals (62%). Seven patients (16%) had leukocytosis with neutrophil predominance.

Discussion

MPXV is typically transmitted through direct contact with skin or mucosal lesions, as well as through respiratory droplets.¹⁰ However, in the 2022 outbreak, a distinct transmission pattern has emerged, indicating that the virus is primarily spread through sexual contact. Our report presents the second largest population of Polish patients with mpox. The largest Polish retrospective analysis of 94 patients treated at the Hospital for Infectious Diseases in Warsaw was published in 2023.¹¹ The vast majority of patients treated at the University Hospital in Kraków, similarly to the Warsaw cohort, identified themselves as MSM and reported recent engagement with multiple sexual partners. A similar trend has been observed worldwide, suggesting that mpox should be regarded as an STI, not merely a disease transmitted by close contact.¹²

According to the literature, the prevalence of concurrent STIs diagnosed during mpox management varies between 15% and 29%, and is heavily dependent on the setting in which the patient is treated (primary care, hospital, or infectious disease clinic). This variability is largely due to inadequate testing policies employed by many health care facilities.^13-15 We reported a high incidence of past (64%) and concomitant (27%) STIs, including HIV, syphilis, hepatitis A and C, and N. gonorrhoeae, Ch. trachomatis, and U. urealyticum infections. Due to various reasons, not all of our patients underwent on‑site STI testing. However, a relatively high percentage of STI diagnoses could be explained by the fact that as much as 58% of the patients were treated in a hospital, where more comprehensive diagnostic measures were available.

Altogether, 58% of our patients were diagnosed with HIV; 22 were already on antiretroviral therapy, and 4 were newly diagnosed. A slightly lower prevalence of HIV among mpox patients was reported in a 2023 systematic review and by the WHO (40% and 51%, respectively)¹⁶. This relatively high rate of HIV coinfection in our group can be primarily attributed to the fact that the study was conducted at the referral hospital for people living with HIV. Additionally, higher awareness among infectious diseases specialists regarding the clinical manifestation of mpox likely played a significant role in this outcome. HIV infection, particularly in individuals with low CD4 cell counts, should be recognized as a risk factor for severe mpox infection with an elevated risk of complications and mortality.¹⁷ In our cohort of HIV‑positive patients, only 1 experienced a complicated course of mpox, with bacterial superinfection by S. aureus. This patient presented with acute retroviral syndrome and CD4 cell count of 227 cells/μl (RR, 500–1500 cells/μl). Additionally, another patient had a CD4 count below 350 cells/μl (319 cells/μl) at the time of mpox diagnosis. Nevertheless, he exhibited self‑limiting symptoms and did not require hospitalization.

Supportive treatment is recommended in patients with mild course of the disease. However, for patients with a more severe infection, extensive skin lesions, or those at a risk of complications (such as immunocompromised individuals or pregnant women), antiviral treatment may be warranted. Tecovirimat is the only drug registered to treat mpox in Europe, while brincidofovir, originally developed to treat smallpox, and cidofovir may show some activity against MPXV.⁴ None of our patients required specific antiviral treatment. One patient with the bacterial superinfection was treated with targeted antibiotics.

To date, a specific vaccine against MPXV has not been developed, but due to the virus antigenic similarity to other orthopoxviruses, smallpox vaccines can be utilized and have been registered for protection against mpox.¹⁸ The third‑generation vaccine containing a modified vaccinia strain Ankara (JYNNEOS in the United States, IMVANEX in the European Union, and IMAMUNE in Canada) was approved for protection against mpox by the European Medicines Agency in July 2022.¹⁹ According to the CDC recommendations, the mpox vaccination should be offered to individuals with known or potential exposure to mpox, those engaging in high‑risk sexual behavior, people living with HIV, or those who are immunosuppressed.¹⁸ Promoting vaccines with nonstigmatizing, targeted information in the key populations is very important to effectively manage STIs, such as the recent mpox outbreak.²⁰

Following eradication of smallpox declared by the WHO in 1980, vaccination programs have been discontinued. Our study revealed that only 1 of the patients was vaccinated against smallpox in his childhood. He experienced mild symptoms with genital area involvement.

Health care professionals should work to enhance educational methods regarding vaccinations, safe sexual practices, barrier methods, PrEP, and the importance of regular testing to prevent STI transmission. Our results emphasize the importance of testing for other STIs in patients with mpox, not only as part of a differential diagnosis (with syphilis, herpes simplex virus, or lymphogranuloma venereum) but also as a general epidemiological screening practice. Health care professionals should be aware of the potential emergence of new STIs.