New case study provides comprehensive characterization and follow-up of monkeypox infection

Historically, monkeypox outbreaks have been primarily found in Central and West Africa. This zoonotic infection is caused by the monkeypox virus (MPXV), which belongs to the Poxviridae family of Orthopoxvirus gender. Until 2022, the incidence of monkeypox outside of Africa was a rare event.

The recent detection of monkeypox outside of Africa was found to be linked to household contacts of the patients. Interestingly, a case of monkeypox outside of Africa was reported in 2003 linked to the importation of exotic pets.

Study: Ten-week follow-up of monkeypox case, Sweden, 2022. Image Credit: MIA Studio/Shutterstock

Background

Outbreaks of monkeypox in Australia, Europe, Israel, and the United States were reported in May 2022. This infection was primarily detected in men who have sex with men. Interestingly, compared to previous outbreaks, the new outbreak of monkeypox showed distinct clinical symptoms with localized rashes and mucosal lesions, mainly in the genital area. Besides these clinical manifestations, patients with monkeypox also suffered from lymphadenopathy and fever.

In a recent case of monkeypox in Sweden, scientists focused on clinical symptoms, viral kinetics and microbial diagnostics. In addition, a bioinformatics analysis of the genomic sequences was carried out. This case study is available in Emerging infectious diseases.

Case study

The current study analyzed a male patient with monkeypox from Sweden. He had no history of smallpox vaccination and was otherwise in good health. The patient reported inguinal swelling on day 0, with evidence of a small skin change on his foreskin the following day. This modification of the foreskin quickly transformed into a deeper and well circumscribed lesion with local adenopathy in the following days.

On the 5th and 6th day, fever developed with a peak of 39°C. The patient consulted an outpatient clinic one week after the onset of symptoms. Meanwhile, the fever subsided and no new lesions erupted.

The patient reported having received oral sex from multiple male partners in the three weeks prior to the onset of clinical symptoms. By day 11, the lesions had increased up to 2 cm in diameter. Clinicians performed microbiological testing for syphilis, herpes simplex virus, and Haemophilus ducreyi, and all tests were negative. The patient also underwent MPXV analysis at the Public Health Agency of Sweden.

Real-time PCR analysis for orthopoxvirus DNA and MPXV DNA was performed using the genital swab samples. This test showed a positive result which was reconfirmed using the Sanger sequencing method.

Although the genital lesions healed, the local lymphadenopathy increased. On day 25, the patient suffered a lymph node rupture with discharge. At a follow-up visit on day 25, he was reported to be feeling much better; however, he had enlarged lymph nodes. Additionally, the genital lesions were also reduced to 5mm and bled only slightly when touched. Ruptured lymph nodes also healed during this time.

During the ten-week follow-up, clinicians took repeated samples from the ruptured local lymph node, urine, blood, semen, airway, and genital lesion. MPXV DNA was detected in most samples. Nevertheless, the genital samples, which initially tested positive, showed a rapid decline in viral DNA content. MPXV DNA was detected in samples from ruptured lymph nodes 40 days after symptom onset. Similarly, the virus was found in semen samples after 54 days and in saliva after 76 days.

Electron microscopic analysis of skin lesions revealed characteristics of orthopoxviruses that were 220–450 nm long and 140–260 nm wide. Metagenomic sequencing of the DNA sample extracted from genital lesions aided in viral genomic reconstruction. This analysis strongly indicated that the virus in the case belonged to the West African clade. Additionally, a single nucleotide polymorphism distance of 4nt was observed.

Consequences

Monkeypox is reported every day in different countries. The clinical symptoms and route of transmission of the new cases were found to be different from previous symptoms of monkeypox infection. These new aspects strongly influence the clinical management of the infection and the formulation of public health measures. There is an urgent need to control the monkeypox outbreak at an early stage and prevent further transmission of the infection.

A lot of important information about monkeypox has been highlighted in this case study. For example, the clinical manifestation of single genital lesions and enlargement of local lymph nodes has been observed. These clinical manifestations clearly indicate that the MPXV strain, associated with the monkeypox epidemic of 2022, is different from previous epidemics.

The new strain associated with the incidence of localized lesions is significantly different from the classic generalized rash or blisters that spread over the body. In addition, ruptured lymph nodes are also a new symptom. Interestingly, differential viral kinetics were also observed in different samples over time. The persistence of MPXV DNA in semen and respiratory samples implicates the route of transmission.

Phylogenetic analyzes showed that the new virus strain belongs to the West African monkeypox clade, which showed lower mortality rates than the Central African clade. The current study presented rapid and accurate bioinformatics analysis to classify viruses at a relatively low cost.