Atypical Presentation of Monkeypox Creates Confusion in Primary Care

Roxana Tabakman

August 12, 2022

If you haven’t seen a case of monkeypox yet, this is likely to change. In a press briefing on July 13, the Pan American Health Organization (PAHO) announced that there had been a surge in monkeypox cases and that specialists are predicting an even greater increase. On Saturday, July 23, the World Health Organization (WHO) declared the disease a Public Health Emergency of International Concern.

Nearly 14% of all monkeypox cases recorded worldwide are concentrated in the Americas, mainly in the United States and Canada. However, the increase in cases observed in Brazil in recent weeks was also highlighted in the speech made by PAHO Director Carissa Etienne, MD, MPH.

"The public health risk at the global level is assessed as moderate [at present]. It is important to note that no deaths have been reported in the region of the Americas, but that is not to say that the situation is not worrying," said Etienne.

Specialists give two reasons for the increase in cases. The first is increased epidemiologic surveillance and subsequent reporting of cases through the expanded network of diagnostic laboratories equipped to detect the disease. The second is mass gatherings at large LGBTQIA+ Pride Month events held throughout June.

"The focus of our organization is to alert and ensure prevention aimed primarily at more vulnerable populations, in particular, men who have sex with men (MSM)," PAHO officials stated.

Alexandre Naime Barbosa, MD, PhD, infectious disease specialist, vice president of the Brazilian Society of Infectious Diseases (SBI) and head of the Department of Infectious Diseases, Dermatology, Diagnostic Imaging and Radiotherapy of the Botucatu School of Medicine at São Paulo State University (UNESP), São Paulo, Brazil, spoke with Medscape Medical News about the outbreak. "Monkeypox is here to stay and it's going to be a public health problem. It isn't as serious as COVID-19 because it’s a much less lethal disease, but [the virus] is spreading, and we’re only seeing the tip of the iceberg. The number of reported cases is high, but much lower than the real figures must be," he said.

As of July 20, Brazil had more than 1000 reports (592 confirmed cases) recorded in the states of São Paulo, Rio de Janeiro, Minas Gerais, Paraná, Rio Grande do Sul, Ceará, Rio Grande do Norte, Goiás, and the Federal District.

Case Count Underestimated

The WHO warned that the number of cases is being underestimated, due in part to healthcare professionals' lack of clinical experience identifying this infection, which had previously been recorded in only a handful of countries. But that's not the only problem.

The presentation of the disease has been atypical, with many patients exhibiting clinical pictures that stray from the classic description of the disease (ie, fever and swollen lymph nodes, followed by a massive synchronous, centrifugal rash). And now there are reports of asymptomatic infection in individuals in vulnerable populations, with a high viral load in the genital region.

Current clinical pictures are presenting with anal pain and rectal bleeding. And contrary to what one would expect, the genital or perineal/perianal lesions are not spreading further but are appearing at different (asynchronous) stages of development, even without the occurrence of fever, malaise, or other symptoms (absence of prodromal period).

According to Barbosa, some of the underdiagnosed cases are due to the atypical presentation and difficult characterization of the disease. He recounted a recent case in which "a male patient diagnosed with monkeypox had only one vesicular lesion with semi-purulent contents, approximately 0.5 cm in diameter in the infralabial region, a little above the chin, which looked a lot like mild acne. We only suspected monkeypox," Barbosa commented, "because the patient reported having unprotected receptive oral sex with several partners about 15 days earlier at a music festival."

Marilia Santini, MD, PhD, an infectious disease specialist and researcher at the STD and AIDS Clinical Research Laboratory, Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), indicated that healthcare professionals who had never had any contact with monkeypox cases were expecting to treat patients with lesions spread over their entire body and clinical pictures starting with 3 days of fever. "This is not what is happening," she explained. "If a doctor fixates on the idea that a monkeypox patient is going to present with pustules all over their body, the case will go undiagnosed."

She goes on to say that the first patient who sought treatment only had one small lesion and didn't have a fever or a headache. "We didn't think it was monkeypox, but we collected a sample because he was worried. He said he had some friends who were suspected to have the disease and were being tested in England. We believed him and collected the sample. He was indeed positive!"

This was the first of many atypical cases that Santini has treated. The classic differential diagnosis, which she expected to be chickenpox with only a few lesions, became herpes, molluscum, granuloma venereum, and other infections that present with gingival lesions. "Ocular lesions have now been described. We haven't seen any of these [yet], but ophthalmologists also need to be on the alert," Santini added.

In Brazil, the reference materials for healthcare professionals came from the bulletins from the Monkeypox Situation Room, which was activated on May 23 by the Secretariat of Health Surveillance at the Ministry of Health and then discontinued 50 days later. Monitoring for monkeypox has now been incorporated into the Ministry of Health's routine.

However, the last edition of the bulletin (epidemiological week 27: July 3-9, 2022) still mentions the classic signs and symptoms (fever, headache, myalgia, lower back pain, adenomegaly, chills, and exhaustion), but the document reports that there are confirmed cases of the disease recorded globally with no visible rash and with clinical manifestations such as anal pain and rectal bleeding. The State of São Paulo's epidemiological alert, published on July 6, contains guidance regarding the new clinical presentation of the disease.

For probable cases, in addition to one or more sudden rashes on any part of the body, the document specifies the following: multiple or anonymous sexual partners in the 21 days before symptom onset and/or an epidemiologic link to a probable or confirmed case of monkeypox in the same 21 days, such as prolonged face-to-face exposure in close proximity, including health workers without appropriate personal protective equipment (PPE) — gloves, gown, eye protection, and respirator; direct physical contact with skin or skin lesions, including sexual contact; or contact with contaminated materials such as clothing, bedding, or utensils.

In practice, this diagnostic algorithm poses problems. During a medical visit, it’s difficult to determine the exact date when transmission may have occurred.

Other requirements, such as a history of travel or an epidemiologic link to individuals with a history of travel to countries with confirmed cases, are no longer as relevant. As of July 9, of the 218 confirmed cases in Brazil, only 36 reported having traveled outside of Brazil.

"If a doctor is asking whether the person has traveled abroad, they may miss cases, because the cases we have been seeing for 2 weeks are completely local," said Santini.

Sylvain Aldighieri, MD, an incident manager at PAHO, explained that in Mexico, 94% of the 35 patients with confirmed monkeypox were men, and 60% were people living with human immunodeficiency virus (HIV), an association that has not yet been fully explained.

Transmission occurs primarily through personal contact with skin lesions of infected individuals, respiratory secretions, or contaminated objects, but other possibilities are being investigated.

In a study of 12 confirmed cases of monkeypox conducted in Barcelona, Spain, virus DNA was detected in saliva, stool, semen, and urine samples, as well as in rectal swab tests. The infectious potential of these biological materials and their respective roles in disease transmission during sexual activity is still being researched.

To make the situation more difficult, completely asymptomatic cases are beginning to be described, which is something that had not been recorded in this pathology until now.

Retrospective testing of anorectal and oropharyngeal swabs collected to screen for gonorrhea and chlamydia in an MSM population in Belgium identified three positive monkeypox patients who were completely asymptomatic at the time of collection and did not develop any subsequent symptoms.

Cases Among MSM

Monkeypox cases are being diagnosed mainly, but not exclusively, among MSM. 215 of the 218 confirmed cases in Brazil as of July 9 were male patients. Of these patients, 123 self-identified as MSM, 30 as homosexual, and one as bisexual. There is no information on the remaining 64 patients.

"Anyone can contract monkeypox, whether you’re MSM, heterosexual, elderly, young, or a child, but at present, MSM are more vulnerable," said Barbosa. In his assessment, "the recent Belgian study that found monkeypox virus DNA in MSM with no lesions of any type alerts us that we should more readily suspect [monkeypox] in this population and create more sensitive testing protocols."

"Another fundamental and quite urgent point," Barbosa added, "is the need for awareness campaigns to raise the alarm for these populations [that are] more affected right now. We have to do this work at LGBTQIA+ parties, saunas, nightspots, clubs, and locations heavily frequented by this more vulnerable population," he specified, "but without fostering any stigma or prejudice."

"We are working with civil society and LGBTQ+ communities to alert at-risk groups of the symptoms and to provide information about how they can protect themselves," said Etienne.

At the beginning of the summer in Europe, the WHO warned that large gatherings can facilitate transmission of the virus if there are close, prolonged, and frequent interactions among people, particularly in the case of sexual activity. The agency proposed that companies and event organizers participate in awareness-raising and behavior-changing initiatives before, during, and after the summer events.

The initial spread of monkeypox in Europe appears to be related to mass events in Spain and Belgium. Spain is currently the country with the most cases (2447) less than two months after the first reports on May 17. The most likely mechanism of transmission reported by 332 (85.8%) of the 387 case-patients who had available information was intimate and prolonged contact during sex. A total of 31 case-patients reported close contacts unrelated to sex. A large number had attended pride events in different cities in Spain. For that reason, the Spanish Ministry of Health considered it essential to partner with the LGTBQIA+ community.

Effective risk communication strategies are paramount to informing the general population and the most at-risk groups. In Brazil, various campaigns are under way. For example, the SBI and the São Paulo State Secretariat of Science, Research and Development in Health are partnering to prepare a technical report and a campaign to raise awareness for the MSM population.

The information should be clear and contrasted in partnership with the LGBTQIA+ community to minimize risk behaviors and maximize awareness about the importance of following public health control measures. Explicit warnings to avoid any form of stigmatizing the LGBTQIA+ community should frame all interventions.

No Risk Groups

It is important to emphasize that MSM do not constitute a risk group. Transmission is currently centered on, but not exclusive to, that population. Without control, there is a risk of transmission to other population groups. How the current outbreak will evolve is still uncertain and will be influenced by the manner in which the message reaches the population. It is also essential to continue characterizing the dynamics of the outbreak to identify potential changes and adapt recommendations.

Researchers from the Institute of Tropical Medicine in Antwerp, Belgium, wrote the following in their report on asymptomatic cases: "Our findings suggest that identification and isolation of symptomatic individuals may not be enough to contain the outbreak. [These features imply that] an outbreak in the general population tends towards extinction with relatively minor hygienic measures, as observed in several outbreaks in endemic regions. If, however, asymptomatic transmission occurs, the outbreak becomes much more difficult to contain."

Barbosa and Santini reported no conflicts of interest.

Roxana Tabakman is a biologist, freelance reporter, and writer who resides in São Paulo, Brazil. She is the author of the books A Saúde na Mídia, Medicina para Jornalistas, Jornalismo para Médicos (in Portuguese), and Biovigilados (in Spanish). Follow her on Twitter: @roxanatabakman.

This article has been translated from the Medscape Portuguese edition.


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