Testing for Monkeypox Virus Coinfections

Since the eradication of smallpox in 1980, monkeypox remains the predominant infectious Orthopoxvirus in the areas where it is endemic. However, the recent international spread of the virus has raised great concern in the global scientific and health care communities. Continuous surveillance and epidemiological studies remain important to understand the extent, distribution, and pattern of viral spread. In addition, virological and clinical research is crucial to monitor any mutations or changes to the monkeypox virus genome to prepare for advanced and targeted diagnostics tools and treatments.

"The way monkeypox has spread during the current outbreak differs significantly from previous cases reported in the Western Hemisphere."

Studying coinfections, which can exacerbate disease severity and lead to underreporting cases, is also important, especially when a virus begins to spread to regions where the virus is not usually present. Ultimately, better understanding monkeypox and the frequency and type of coinfections that occur with the virus can help heath care professionals design better disease control measures, including effective testing.

Current status of the monkeypox outbreak

Monkeypox virus (MPXV) is an Orthopoxvirus part of the Poxviridae family that is endemic to West and Central Africa. The first non-endemic outbreak that occurred outside of Africa in 2003 was reportedly due to importing wild rodents to the US. Over the years, other sporadic occurrences of monkeypox cases have been documented in Singapore, the UK, and the US, mainly due to animal-to-human transmission.

In early 2022, while the world was still dealing with the COVID-19 pandemic, monkeypox outbreaks were reported in North and South America, where MPXV infections don’t typically occur. The unexpected outbreaks spread so rapidly that on July 23, the World Health Organization declared monkeypox a global public health emergency.

As of October 20, the Centers for Disease Control and Prevention (CDC) is tracking more than 75,000 global cases of monkeypox, with more than 27,000 cases in the US. In the past, non-endemic outbreaks of MPXV have been associated with travel or attributed to importing infected animals, however, the latest multicountry outbreak has been primarily attributed to human-to-human transmission. According to the CDC, men who have sex with men (MSM) have been disproportionately impacted by the current monkeypox outbreak. However, monkeypox can infect anyone, and the public health initiatives targeting the outbreak should focus on raising awareness while avoiding stigma.

Monkeypox coinfections

Coinfection (i.e., concomitant or secondary infection) with other pathogens often leads to increased disease severity in patients, and in some cases, contributes to the transmissibility of a non-endemic infection. Thus, studying coinfections remains crucial for establishing the epidemiology of an infectious disease. Coinfections are often syndromic in nature, complicating the initial diagnosis. In addition to the increased morbidity and mortality associated with coinfections, they represent a significant economic burden to the health care system.

"People with suspected cases of monkeypox should be screened for other STIs and immunocompromising infections."

Known monkeypox coinfections

Mathematical modeling of HIV–monkeypox coinfections suggest that the presence of one significantly increases infection by the other. This study was conducted in 2012 due to the high prevalence of HIV with concomitant outbreaks of monkeypox in certain regions of Africa (mainly Central and West). The latest epidemiological data published by the CDC during the current outbreak in the US show that 41 percent of the monkeypox positive cases were also HIV positive.

Monkeypox patients may present symptoms (especially skin lesions and rashes) that are very similar to certain sexually transmitted infections (STIs), like herpes and syphilis. Skin rash-based clinical diagnosis of monkeypox is often confounded in areas where monkeypox is endemic by varicella zoster virus (VZV/human herpes 3) infections.

A five-year study in the Democratic Republic of the Congo demonstrated a 12.1 percent coinfection rate of VZV in people positive for monkeypox. Moreover, VZV-positive patients displayed exacerbated symptoms in the presence of monkeypox infection. It’s possible that the actual magnitude of monkeypox infections may go unreported due to VZV coinfections masking symptoms and surveillance of the virus in a population.

In general, monkeypox is a self-limiting infection, and clinical outcomes are very much dependent on a patient's existing health conditions (degree of compromised immunity and extent of pathogen exposure, etc.). E.g., immunocompromising conditions like HIV/AIDS can result in more drastic clinical presentations. And since HIV-positive patients  often show coinfection/comorbidities of HBV, HCV, tuberculosis, and other STIs, patients can often be misdiagnosed, further complicating treatment. Thus, people with suspected cases of monkeypox should be screened for other STIs and immunocompromising infections.

Coinfections during the 2022 monkeypox outbreak

Published in June, a multicenter study of monkeypox cases in Portugal from April 29 to May 23 established that most cases in the country were not linked to travel or contact with symptomatic persons, suggesting that monkeypox virus had been spreading undetected in Europe since at least early April 2022 before spreading to Portugal.

"...monkeypox virus had been spreading undetected in Europe since at least early April 2022."

The recent outbreak has brought forth interesting coinfection cases that will ultimately help define the etiology and clinical manifestation of monkeypox infection in historically non-endemic regions. A confirmed case of monkeypox in the Czech Republic was found to be coinfected with syphilis and HIV. Similarly, in a case report from Italy, a patient with confirmed monkeypox also tested positive for HIV and SARS-CoV-2. This last case highlights the challenges of the emergence of a new infectious disease during a pandemic. In both cases, the patients reported having unprotected sex prior to contracting the infections.

Monkeypox and coinfections in a newborn

Neonatal cases of monkeypox infections are uncommon. However, the pediatric population should always be monitored in the event of any disease spread, especially during outbreaks. In a recent case study in the UK published in the New England Journal of Medicine, the authors discuss a perinatal transmission of monkeypox, where a 10-day-old infant with rashes and pustules was diagnosed with monkeypox and adenovirus coinfection. The authors speculated that the infant acquired the monkeypox–adenovirus coinfection from their father who, a few days prior to the infant’s birth, had signs of a fever and thereafter presented with rashes. Four days after the infant’s diagnosis, the mother also developed rashes. The family had no known contact with any traveler or any travel history to Africa.

A need for robust monkeypox surveillance and STI screening

The way monkeypox has spread during the current outbreak differs significantly from previous cases reported in the Western Hemisphere. Studies related to monkeypox coinfections, although still nascent, underscore the need for a more robust surveillance plan that includes broader STI screening in conjunction with diagnostic tests for monkeypox for at-risk and vulnerable populations.