Monkeypox only assumes relevance affecting rich countries

Publicação: 14 de June de 2022

In the current situation of pandemic threats, the importance of the disease should not be underestimated

To ensure global preparation in the event of smallpox resurgence, new vaccines, diagnostics and antiviral agents are being developed, which may also be useful for the prevention and control of monkey smallpox

Coinciding immunity to monkeypox virus was previously achieved with vaccinia virus (VACV) vaccination; however, eradication of smallpox and subsequent lack of vaccination efforts paved the way for monkeypox to gain clinical relevance. In addition, as most cases of smallpox occur in rural Africa, the suspicion of underreporting may translate into an underestimation of the potential threat of this pathogen, as well as the fact that cases occurring in several locations far from their origin may be misdiagnosed or undiagnosed. A visit to myMisdiagnosis.com, a global database of incorrect diagnoses, on May 30 showed that patients were being misdiagnosed – with chickenpox – when in fact the correct diagnosis in specific cases would be monkeypox. The disease shares many characteristics with the much more common varicella virus, syphilis and herpes. So there is a genuine danger that people will be confused. The risk of misdiagnosis is worrying. Monkeypox can be diagnosed by a PCR test and/or sequencing.

Over the past 5 decades, monkeypox outbreaks have been reported in 10 African countries and 4 countries outside Africa. Interestingly, the infection imported into the UK in May 2021 and into the United States in July 2021 occurred at a time when reported cases of smallpox in Nigeria were at a very low level. The same happened now in 2022. Asked about this, Dr. Jimmy Whitworth, a professor of international public health at the London School of Hygiene and Tropical Medicine (LSTMH), a specialist in infectious diseases, epidemiology and public health, explains that monkeypox has been circulating in a vast area of Nigeria and other West and Central African countries for several years. According to him, the cases reported in the United Kingdom and in the United States represent international travelers who had been exposed to monkeypox and were incubating the infection while traveling. “Usually, person-to-person transmission is limited, but in this outbreak, it seems to be extensive, perhaps because it occurred in a community with intensive close contact and change of partners,” he adds.

Dr. Whitworth recalls that mass vaccination with the smallpox vaccine was discontinued in the 1980s and is believed to have allowed cases of monkeypox in the human population to increase in the following decades. Also according to him, vaccination provides good cross-protection against monkeypox, however, it is likely that the number of confirmed cases will continue to increase for a while. “This is because the transmission chains have not yet been fully discovered, which means that undetected community transmission is still occurring. It is usually a very obvious disease, so we expect cases to be reported to health systems,” he says.

However, despite growing concerns about the geographical spread and resurgence of monkeypox, the disease seems to have taken on relevance only after it affected the rich countries. Asked about the reason for this and whether we live in two (or more) distinct worlds, the LSTMH professor justifies that public health authorities are generally more interested in diseases occurring in their country. “This is natural, and I imagine that the Brazilian health authorities have not, until recently, had much interest in monkeypox because it does not occur within the country and has not yet been imported. But I understand that there are many neglected tropical diseases precisely because they do not pose a threat to the rich Western countries. This is one of the reasons why multilateral support to agencies such as the World Health Organization (WHO) and the Global Fund for AIDS, tuberculosis and malaria is so important, ” concludes Dr. Whitworth.

Virologists on alert

Monkeypox has put virologists on alert, although it causes less serious diseases. In the midst of pandemic threats, their importance should not be underestimated. To ensure global preparedness in the event of smallpox resurgence, new vaccines, diagnostics and antiviral agents are being developed. These may also be useful for the prevention and control of monkeypox.

In an interview published in O Globo, virologist Dr. Clarissa Damaso, from the Federal University of Rio de Janeiro (UFRJ) and a member of the Advisory Committee for Smallpox Research of the WHO, detailed that the smallpox virus is considered a biological weapon and that for reasons of biodefense the vaccine still exists and there are safety stocks. She also reported that a more modern, non-pustular vaccine, made with a more attenuated vaccine virus, BN-MVA, which does not replicate in humans, was recently approved in the United States and Europe, with indication for military personnel and people who research pox viruses. Regarding treatment, the specialist said that there are two new antiviral drugs, also developed for biodefense in military and Pox virus researchers. They were approved in 2019 and 2021 in the US, and, if necessary, can be produced in large scale, as well as the vaccine.

Antiviral can treat monkeypox

A study published in The Lancet titled Clinical features and management of human monkeypox: a retrospective observational study in the UK showed the reduction of symptoms and disease contagion time in a patient treated with a tecovirimat antiviral. The drug is the first with indication for the treatment of common smallpox.

Dr. Hugh Adler, a researcher at the University of Liverpool and one of the authors of the study, said in a press release that the research offers some of the first insights related to the use of antivirals for the treatment of the disease, which can be very useful to tackle the disease. The lack of in-depth knowledge about the disease was an obstacle faced by the British team.

In addition to monkeypox, smallpox, which presents unique challenges, also requires prospective studies of urgent antivirals. While smallpox no longer occurs naturally, the global health sector remains vigilant in the event of reappearance through natural mechanisms, laboratory accident or deliberate release.

Learn more

Zoonotic Orthopoxirus outbreaks have occurred several times worldwide, including monkeypox in Africa and the United States, cowpox in Europe, camel pox in the Middle East and India, buffalo pox in India, vaccinia in South America, and emerging new Orthopoxirus infections in the United States, Europe, Asia, and South America.

The monkeypox virus is an enveloped double-stranded DNA virus that belongs to the genus Orthopoxvirus of the Poxviridae family. There are two distinct genetic clades of monkeypox virus: the Central African clade (Congo Basin) and the West African clade. The clade of the Congo Basin has historically caused more serious diseases and was considered more transmissible. The geographical division between the two clades has so far been in Cameroon, the only country where both clades of viruses have been found.

Monkeypox is a disease of global importance for public health, as it affects not only the countries of West and Central Africa, but also the rest of the world. In 2003, the first outbreak of monkeypox outside Africa was in the United States and was linked to contact with infected pet prairie dogs. These animals had been housed with Gambian and Arganazi pocket rats that had been imported into the country from Ghana. This outbreak has caused more than 70 cases of monkeypox in the US. The disease was also reported in travelers from Nigeria to Israel in September 2018, to the United Kingdom in September 2018, December 2019, May 2021 and May 2022, to Singapore in May 2019, and to the United States in July and November 2021. In May 2022, several cases of monkeypox were identified in non-endemic countries. Currently, studies are underway to better understand epidemiology, sources of infection, and patterns of transmission.

Clinical care for monkeypox should be fully optimized to relieve symptoms, control complications and prevent long-term sequelae. Patients should be given fluids and food to maintain adequate nutritional status. Secondary bacterial infections should be treated as indicated. An antiviral agent known as tecovirimat that was developed to combat smallpox was licensed in 2022 by the European Medical Association for Monkeypox based on animal data and human studies. It’s not widely available yet. If used for treatment, tecovirimat should be monitored in a clinical research setting with prospective data collection.

Useful links

https://www.who.int/news-room/fact-sheets/detail/monkeypox

https://www.cdc.gov/poxvirus/monkeypox/transmission.html

https://pubmed.ncbi.nlm.nih.gov/34563454/

https://pubmed.ncbi.nlm.nih.gov/35148313/

https://pubmed.ncbi.nlm.nih.gov/34662033/

https://pubmed.ncbi.nlm.nih.gov/33012864/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463189/#:~:text=Monkeypox%20could%20therefore%20emerge%20as%20the%20most%20important%20orthopoxvirus%20infection%20in%20humans.&text=We%20use%20mathematical%20modelling%20to,of%20monkeypox%20will%20continue%20increasing.

https://www.who.int/emergencies/disease-outbreak-news/item/monkeypox—united-kingdom-of-great-britain-and-northern-ireland-ex-nigeria

https://www.cdc.gov/media/releases/2021/s0716-confirm-monkeypox.html

https://reliefweb.int/sites/reliefweb.int/files/resources/An%20Update%20of%20Monkeypox%20Outbreak%20in%20Nigeria_210521_21.pdf

https://www.who.int/emergencies/disease-outbreak-news/item/monkeypox—united-kingdom-of-great-britain-and-northern-ireland