Ep93: The rise and fall of mpox

Ep93: The rise and fall of mpox
Date:
16 April 2023
Category:

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The first time most of us heard of monkeypox was in May 2022. The smallpox-like infection appeared to spring from nowhere and make its way through Europe then the Americas, largely within the gay and bisexual community. But the first documented human case of mpox actually occurred in 1970 in Central Africa and it’s been endemic ever since.

Last year’s mpox outbreak eclipsed prior case numbers in just a few months thanks to a newly evolved strain. The count of confirmed cases totalled over 86,000 all around the world and it’s a testament to well-coordinated community health in the developed world that the outbreak was reigned in within a few months of the index case in Europe.

But alongside this success story, there’s also a cautionary tale about global health strategy. Because mpox wasn't taken seriously in endemic countries, an incubator was created for this new strain to emerge. We also discuss the stigma associated with sexually transmitted infections and the pros and cons of applying this label.

Credits

Guests
Dr Vincent Cornelisse FRACGP FAChSHM PhD (Royal Prince Alfred Hospital, Royal North Shore Hospital, Sydney; Kirby Institute, UNSW)
Dr Massimo Giola FRACP FAChSHM PhD (Te Whatu Ora, Tauranga, Rotorua)

Production
Produced by Mic Cavazzini DPhil. Recording assistance in Tauranga from Melissa Cox, Mockingbird Music Studios. Editorial feedback kindly provided by Dr Aidan Tan and Dr David Arroyo.

Music licenced from Epidemic Sound includes ‘Cocktail by Major Tweaks, ‘Broke No More’ by Cushy, ‘Temple of Ruhnha’ by ELFL and ‘Razzamatazz’ by Jules Gaia. Music courtesy of Free Music Archive includes ‘Out of the Skies, Under the Earth’ by Chris Zabriskie, Image by Flashpop licenced from Getty Images.

References

Diagnosis and Treatment of Mpox (monkeypox) [BMJ Best Practice, 2023]
Monkeypox [Lancet, 2023]
Monkeypox in Africa: the science the world ignored [Nature, 2022]
Monkeypox [NEJM, 2022]
2022 Mpox Outbreak Global Map [CDC]
What You Need to Know About the History of Monkeypox [Smithsonian Mag]

Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022 [NEJM, 2022]
Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus [Nat Med, 2022]
Modelling human-to-human transmission of monkeypox [Bull World Health Organ, 2020]
Heavy-tailed sexual contact networks and monkeypox epidemiology in the global outbreak, 2022 [Science, 2022

A Position Statement on Mpox as a Sexually Transmitted Disease [Clin Infect Dis, 2022]
Recent epidemiology of sexually transmissible enteric infections in men who have sex with men [Curr Opin Infect Dis, 2016]  
Antimicrobial resistance in sexually transmitted Shigella in men who have sex with men: A systematic review [Int J STD AIDS, 2023]
Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017 [Euro Surveill, 2018]
Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the United States, 2012–2015 [Clin Infect Dis, 2017]
Mpox in Nigeria: Perceptions and knowledge of the disease among critical stakeholders-Global public health consequences [PLoS One, 2023]

Transcript

MIC CAVAZZINI: Welcome to Pomegranate Health, a podcast about the culture of medicine. I’m Mic Cavazzini for the Royal Australasian College of Physicians. The first time most of us ever heard of monkeypox was in May 2022. The smallpox-like infection appeared to spring from nowhere and make its way through Europe then the Americas, almost entirely within the gay and bisexual community.

The name actually goes back to 1958, when it was identified in a Danish primate facility. But the poor macaque monkeys that got sick were just innocent bystanders, as the reservoir is likely to be rodents in the rainforests of Central Africa. The first documented human case of mpox occurred in 1970 in what we now know as the Democratic Republic of the Congo. It’s been endemic ever since, with tens of thousands of cases suspected to have occurred over the decades.

But last year’s mpox outbreak eclipsed those numbers in just a few months thanks to some newly evolved strains. The confirmed case count totalled over 86,000 all around the world. In Australia there were 140 cases and in Aotearoa-New Zealand a mere 41. It’s a testament to well-coordinated community health in the developed world that the multi-country outbreak was reigned in so quickly. Transmission rates reached their peak only three months after the first breakout case was recognised and were almost back to normal by the end of the year.

But alongside this success story, there’s also a cautionary tale about us being too inward looking for effective global health strategy. At the end of the podcast we’ll talk about the conditions that led to the evolution of today’s highly transmissible strain of mpox. And we’ll discuss the practical and social implications of labelling an infection as sexually transmitted. One specialist who was central to coordinating Australia’s public health response and messaging was Dr Vincent Cornelisse.

VINCENT CORNELISSE:   So, hi, I'm Vincent Cornelisse. I’m a sexual health physician in Sydney. So I work across RPA sexual health and Northern Sydney sexual health. And I have a PhD in sexual health epidemiology.

MIC CAVAZZINI:               Thank you for having me in your office, Vincent. And on our screen from across the ditch is Dr Massimo Giola. Kia ora Massimo.

MASSIMO GIOLA:            Hello. Kia ora, both.

MIC CAVAZZINI:               Do you find that the Italian phonology helps with pronouncing Te Reo Maori?

MASSIMO GIOLA:            Very much so. I’m told by native speakers of Te Reo my pronunciation is quite good.

MIC CAVAZZINI:               It’s all about the R’s. Massimo, please tell me about where you practice and what your special interests are.

MASSIMO GIOLA:            Sure. So I am an infectious disease physician by prior training. I trained in Italy in the 90s. Then I moved to New Zealand in 2009. And I retrained in sexual health in Auckland. I work in Te Whatu Ora which is the new New Zealand-wide Health Organization covering the whole country three days a week in Tauranga and one day a week in Rotorua.

MIC CAVAZZINI:               And thank you, Massimo, for sharing your notes with me, it certainly made it easy for me to get up to speed on this story. Let’s start with the basics of clinical presentation. The symptoms as they’d been observed since the seventies include a prodromal phase lasting a few days with fever, headache, muscle aches. Then a vesiculopustular rash starting from the face and that rash can last a couple of weeks. But the variant from last year’s outbreak did change the script a little bit- Massimo can you explain how the symptoms differed from what we knew about Mpox before?

MASSIMO GIOLA:            Yeah, so the 2022 outbreak immediately presented itself as very different from textbook mpox, in the sense that there were patients who were presenting without any prodromic symptoms, and in fact, without any systemic symptoms at all. But just with the skin or the mucosal lesions. And the lesions did not appear to be synchronous. So they appear to be in different stages of evolution, which again, is very atypical, if you look at the textbook mpox presentation.

MIC CAVAZZINI:               Interesting. And for those of us not afficionados in tropical medicine, mpox really only came onto the scene on May the 6th last year when it was diagnosed in a man who’d travelled to London from Nigeria. On May 14th, two cases were detected who were not travellers, and another two by the 16th.  Vincent, was the connection to sexual transmission—was it made more on the appearance of the lesions or a careful history?

VINCENT CORNELISSE:   Thanks, Mic. I think it was both, really. And it was a really interesting space to sit in at the time. And all we really knew about mpox at that time is what we knew from mpox in endemic countries. And we knew that it could cause severe disease, it had a fairly high complication rate, with cases of mpox encephalitis, for example. But also secondary infections of lesions causing localized cellulitis but also massive systemic sepsis. And as a result, it had a significant mortality rate.

MIC CAVAZZINI:               And I guess it was hard to tell in the early days, but that case fatality rate was something like one per cent?

VINCENT CORNELISSE:   Which doesn't sound terribly high, but if you're looking at thousands and thousands of cases of young people, with a fatality rate of one per cent so that that's a lot of young people at risk. So that's the situation we were in and we were looking at clearly transmission with within a defined population—so gay men. Contact tracing clearly showed that cases were occurring in sexual partners. And lesions were occurring on the genitals, around the anus and around the mouth. And you don't need to be sexual health physician to work out that—that infers that this is a sexually transmitted infection.

MIC CAVAZZINI:               I looked up the World in Data curves and by the 15th of June, the 7 day rolling average of daily confirmed cases had reached 120. A month later it was 500 new cases a day. Massimo, when I asked you how worried you and your colleagues were about this at the time, your response was, “We weren’t just worried– we were scared senseless.”

MASSIMO GIOLA:            Well, I can tell you, I remember exactly the first time mpox entered into my life as a sexual health physician. And I really thought, “Oh my God, here we go.” And the more information we got, it really felt to me like living, again, the HIV pandemic, but at a very accelerated pace. Every week, almost every day, you could see the cases going up, and new countries being involved.

There was also considerable concern among the clinicians in the sexual health clinics because, particularly in New Zealand, we were just coming out of a major Omicron outbreak. And therefore, you know, lots of clinics had staff redeployed, or reduced hours, reduced days. And we were looking at this potential new major outbreak with very, very limited resources. So the mood was very, very concerned.

MIC CAVAZZINI:               In a large case series from July, 13 per cent of patients with this new variant were hospitalised mostly for reasons of pain management and soft-tissue superinfection. But of course as you’ve described, some cases are more severe. Vince what was the mood like in the community? Were people scared? Were they informed?

VINCENT CORNELISSE:   I think, as Massimo alluded to, there were so many unknowns about this situation, and the doubling time was very quick. I mean, we saw at one point, the doubling time was 10 to 14 days. And that's an extraordinarily fast doubling time, this kind of this exponential curve of infections we were seeing across the world. Without really anything we could do about it directly, as in we didn't have any vaccine doses in the country. So I think there was a an atmosphere of, definitely anxiety and I daresay fear, around what this would mean and how this would pan out.

And then on top of that, we didn't know what precautions needed to be taken to keep health workers safe from mpox. And the initial advice was, you know, if you have a patient who you suspect may have mpox, you need to be in a full gown and mask and gloves and goggles. And none of the health workers had been vaccinated yet because the vaccine wasn't available. And it wasn't clear whether this was an airborne infection and hence, in the first few weeks, there were concerns– the first few cases who were diagnosed in Australia had come from overseas and there was concerns about do we need to get everyone who was on that plane into isolation because they might all have been exposed to mpox. There were just so many uncertainties, and that I think, was potentially a hindrance to being able to facilitate people getting access to healthcare if they thought they had an mpox infection.

MIC CAVAZZINI: Yeah that whole PPE headache again from two years back. As Massimo has already alluded to… the harrowing experience of the HIV pandemic over the 80s and 90s has mean that there is a certain degree of health literacy among the community of men who have sex with men. At least in developed and relatively tolerant countries like ours, there is a propensity to seek healthcare, to get tested for STIs. The architecture, to some extent, was already there. Can you tell me more about how that was harnessed? 

VINCENT CORNELISSE:   The gay community is very health aware and very connected to the gay health sector. In Australia, we were in a position with PrEP or HIV pre-exposure prophylaxis, of being able to roll this out very rapidly, through strong partnerships between the health sector and the community sector. And that resulted in Australia having one of the most rapid uptake of HIV pre-exposure prophylaxis in the world. And as a result, we saw a significant decline in new HIV diagnoses in Australia, particularly in Sydney.

MIC CAVAZZINI:               I was very aware of the big billboards targeted at that community saying, “Go and take this up. It’s not a big deal.” I found it very engaging.

VINCENT CORNELISSE:   Yeah and that was all a result of decades of successive governments from a bipartisan approach supporting this really strong community-led HIV response. So that infrastructure had already been built and that same infrastructure was very useful for deploying an mpox response.

MIC CAVAZZINI:               I’ll let Massimo maybe answer the converse question, and that is about stigma. You always worry with a new infection, that that stigma will keep patients away from your clinic. What does that look like? Is it a sense of shame? Does it come from real or perceived judgment from primary care practitioners?

MASSIMO GIOLA:            Yeah, I wouldn't particularly say it comes from primary care. I would say it's a wider societal, cultural phenomenon. So anything that has to do with sex and with sexual “sins” and guilt and shame has got very deep roots in the society. And it's still very difficult for many people to come forward and discuss their sexual behaviours, and their risks for catching infections through sex. And as soon as a disease is labelled as sexually transmitted, it carries with it all that associated stigma and shame and whakama, as it's called in Te Reo Maori. And it's very difficult, for example, to get patients advocating for themselves, for example, with syphilis or other sexually transmissible infections. And so there is always that reluctance that if we call something sexually transmitted, it will carry with it that stigma and that shame.

MIC CAVAZZINI:               We don’t have time to get too deep into the therapy side but I’ll link some great resources at our web page.  Very briefly, there’s no specific treatment approved for mpox but the main antivirals used against smallpox are considered appropriate. So brincidofovir is still stockpiled by the US for against a possible bioterrorism attack, and tecovirimat is another. But there hadn’t been a lot of testing of these antivirals against mpox, had there, Massimo?

MASSIMO GIOLA:            No and again, it was interesting to see how at the beginning of the outbreak, WHO and other international health agencies were willing to set up randomized control trials. Which means obviously giving to some people placebo rather than the active drug. And at some stage, they were even proposing to do a trial for the vaccine. And very quickly, it became obvious that the community was not having any of that.

So I guess it was a very interesting example of how the proper way to make science really clashed with the community on one side, but also with the public health interests on the other side. Because if you have a major outbreak of a tropical zoonosis that maybe can kill, you know, in the worst case scenario, up to ten per cent of the people that it infects do you really want to run an RCT, or are you going to deploy all the public health interventions.

So to me, again, that community debate and claiming very strongly, “We want the drugs we want, the vaccine right now,” reminded me of the fights of the gay community in the 80s and the 90s to get the effective antiretroviral treatment. So it reminded me of ACT-UP and those protests at conferences, people wanting the antivirals right now. So I come back to the parallel with the HIV epidemic, it was really like living it again at a faster speed, including that interesting debate between science and community. It was very, very interesting.

MIC CAVAZZINI:               Yeah I’ve touched on that politics of advocacy on other issues—it’s a difficult one. Sticking with the science, the smallpox vaccine is also at least 85 per cent effective in preventing mpox or use as a post-exposure treatment. Between WHO member countries there are hundreds of millions of doses of the ACAM2000 vaccine, but the live-attenuated virus has a 1 in 175 chance of causing myocarditis. Modified Vaccina Ankara, is much more attenuated and has a better safety profile, but there’s a global shortage. Massimo, you did, in one of your lectures, provide some “hacks” for stretching out available stocks. Do you want to share those?

MASSIMO GIOLA:            Yeah. So monkeypox was happening in Africa, you know, as the immunity for smallpox was vanishing. But sadly, African children dying of monkey pox, no one was paying attention. And the African countries are very upset because as soon as the infection got out of Africa and caused a major outbreak in the Western world, then all resources were mobilized. So the consequence of monkeypox not really being paid much attention is that there was only one manufacturer of this third generation vaccine. And they had very limited resources to manufacture more at a short notice.  

And a number of countries and the number of jurisdictions tried to look into ways of making that limited supply stretch a lot further. So one option was where let's give one dose and the second dose we’ll wait and see what the supply will be and how fast it can be escalated. So normally, it will be given two doses 28 days apart, but the decision was made to roll out first doses and look at the second doses much later.

And then the other option, there was a trial done in the US showing that you could give one fifth of the dose intradermally rather than subcut[aneous] and that will give an equivalent immune response. So quite a few jurisdictions decided to go for intradermal split doses. Which again caused some very interesting challenges because not very many nurses are trained on how to deliver intradermal injections. So it was a matter of, you know, escalating very fast training packages, looking at resources internationally, leveraging on other sectors of the workforce, like the paediatric nurses that were trained how to give BCG vaccination, and ask them to train other nurses to do it. So again, I was amazed from, from this point of view, how responsive and how willing to help everyone was, which was, you know, very, very heartwarming.

MIC CAVAZZINI:               Forgive me now, if I go from this story about gold-standard community intervention to a less heartwarming prelude about missed opportunities in global health strategy. Recall that mpox first appeared in humans in the Congo Basin in 1970. But there were only a few dozen cases over the decade in part because the smallpox vaccination program had been so effective up to its eradication in 1980.

Throughout the eighties, vaccination coverage remained too high for epidemic spread, and case numbers of mpox stayed around 350. By 2010, however, population immunity had dropped to 60 percent and it’s suspected that there were almost 19,000 cases over the following decade. Most infections were in children and the case fatality rate was up to ten per cent.

In parallel, there was also a second genetic lineage of mpox in West Africa that would make the zoonotic jump only very occasionally. This clade II mpox was less lethal and always petered out with little or no community transmission. Until September 2017, that is, when Nigeria reported its first case of mpox in almost forty years. By that stage, only people above the age of 38 were old enough to have been vaccinated against smallpox, making up just ten per cent of the population.

Within a year of the index case, about 270 Nigerian people had been infected with mpox and seven had died. Because resources were so limited, fewer than half were lab-confirmed, but of those, 70 percent had not had contact with animals or known household cases. This was reported by researchers from the Nigerian CDC and the Niger Delta University who recognised that clade II mpox was no longer just a zoonosis.

In an April 2019 article in the PLoS One journal, three years before the global outbreak, lead author Professor Dimie Ogoina made these observations; “it is noteworthy that a substantial number of our cases…were young adults in their reproductive age presenting with genital ulcers, as well as concomitant syphilis and HIV infection…sexual transmission is plausible in some of these patients through close skin to skin contact during sexual intercourse or by transmission via genital secretions.”

Speaking to National Public Radio, Professor Ogoina now says that his warnings were not taken seriously at international conferences, and that health officials in Nigeria stopped looking for new cases. All you’ll find on the WHO bulletins is mention of some training in animal surveillance, despite the fact that on four occasions up to 2021 the virus managed to hitch a ride overseas but without spreading further than the travelers. The Nigerian mpox outbreak likely infected more than 500 people up to last year, and the viral genomes were observed to cluster into a grouping designated clade IIA. But in 2022, one particular lineage developed a handful of new mutations that would bring it international fame.

First in Nigeria, then in Western Europe and the Americas, it underwent further flurries of evolution that ultimately resulted in 46 single-nucleotide polymorphisms, and a group of strains now known as clade IIB. According to a phylogenetic analysis published in Nature Medicine the observed mutation rate is over six times higher than expected from baseline substitutions, indicative of just how many viral copies have been churning away in the human population. Some of the more recent mutations may shield replication from interference by a human antiviral enzyme, but for most, the functional impact on transmission or virulence hasn’t yet been determined.

Had the mpox outbreak in Nigeria been suppressed early, the virus could have been denied the opportunity to train itself on our immune system. We mentioned that there was shortage of the third generation MVA vaccine but that’s not strictly accurate. The USA actually had 28 million doses of this stockpiled against a terror attack that were going to be destroyed because they had a 2020 expiry date. Only when mpox went global were those stocks retested to find that they were still viable.

As reported in Nature magazine, the African Union is now waiting on a donation of 50,000 doses from the South Korean government. Professor Ogoina told reporters that the disease was still proliferating on the content unsurveilled even though worldwide tallies report only a handful of new cases a day.

Let’s move now to a semantic discussion around how we define sexually transmitted infections, and how such terminology can help or hinder public health messaging. As we’ve said, mpox has classically been understood to transmit via close household contact as it’s highly expressed in epithelial cells. Respiratory epithelia and mucosa are also vulnerable and clade 1 mpox has been capable of droplet transmission, though not to the frightening extent of variola virus which causes smallpox.

But as we’ve heard, in the recent outbreak of clade II mpox, it wasn’t household contacts who were getting sick.
It was reported from a case series last August that mpox DNA could be found in the semen of most patients, and sometimes live virus too. While this added weight to the male sexual-transmission model, a more comprehensive review of findings a few months later concluded that semen was not a major mode of transmission.

So the virus is not concentrated specifically in the sex organs or fluids in the same way the gonorrhoeae bacterium is but most people still catch it through sexual intercourse. Is that enough to call it a sexually transmitted infection? Vincent Cornelisse elaborates on some of the considerations in this debate.   

VINCENT CORNELISSE:   One of the key questions at the start of this outbreak was, is this sexually transmitted? And this was a big piece of debate when this outbreak first emerged. Some people were arguing that, “It’s monkey pox, it's a zoonosis, we've seen it in family clusters in Africa.”

And quite soon it became clear, at least to people working in sexual health, it became very clear that lesions were genital, anal and oral, and we weren't seeing random cases pop up in the community. We weren't seeing cases pop up after music festivals where gay men had also attended. This really was only seen amongst sexual contacts.

So it was quite clear, but still this debate raged on and part of the debate then became, can we really say this as a sexually transmitted outbreak? Because if we do so, do we risk stigmatizing gay men? And, you know, it's a valid question to ask, we don't want to do anything that stigmatizes any part of society.

But the flipside to that concern was if we don't call this out, and we don't say, “This is a sexually transmitted outbreak amongst gay men,” then lots of people are going to come forward for vaccination who aren't actually at risk and going to dilute our resources further. And the guys who are at risk won't know that they are at risk and need to come forward for vaccination or to keep an eye out for symptoms so that if they develop mpox that they know to seek medical care urgently, and to isolate themselves from sexual partners urgently to avoid further spread. So that was a debate that was raging at the time. And I think this was all settled with probably by about July, Massimo I think.

MASSIMO GIOLA:            By and large, yes. And then there have been a couple of editorials published on major sexual health journals that clearly make a case that monkeypox it's not only sexually transmissible, but actually at least as the 2022 outbreak variant of it, it is actually a sexually transmitted disease, which means sexual contact is the primary mode of transmission. Absolutely.

MIC CAVAZZINI:               It sort of really made me rethink of what sexual health medicine—that sexually transmitted disease isn't as hard a category as respiratory disease or kidney diseases. And I'd never thought of that. You know, really, this virus is inhabiting, the epidermal cells and it's close contact of that sort, skin-to-skin contact that's transmitting it. So, the definition or the risk to MSM isn't so much about the specific pathology of the disease, but more about the behavioural element too. And Massimo, you've mentioned in one of your talks about how, the gay population being a minority, sexual networks are a lot more dense than they are in the broader population. Can you take us through that mathematical analysis by the London School of Hygiene and Tropical Medicine?

MASSIMO GIOLA:            I'm not sure I'm able to take you through a mathematical analysis, but I'll try my best to put it in simple words.

MIC CAVAZZINI:               Yes, that's, that's what we need.

MASSIMO GIOLA:            So you might have heard it from me previous times this idea that MSM are the “canary in the coal mine” of sexually transmissible infections. So anything that happens in the field happens first among MSM, and then spills over to the general population. And the reasons for that are that, as you said, gay men are a minority in the general population, which means that the sexual health networks are denser and there are less degrees of separations between a gay man and a case of STI than in the general population. So we are all much more connected.

Then we do tend to congregate in what we perceive as safe places. And that's because being gay is still illegal in some countries, or even in the best case scenario potentially a cause for bullying and discrimination. So obviously, that's why we have gay bars and gay saunas, and gay discos and gay parties, because people feel safer. And obviously, those gatherings represent an excellent opportunity for STI and maybe even non-STI pathogens, actually, to spread through the population.

If we go back, summer 2022, in the northern hemisphere; basically COVID was over, or that was the perception, and lots of large gatherings that had been put on hold for a couple of years were being held again. Almost every weekend, there was a major festival or a major Pride event somewhere in Europe. So thousands of gay and bisexual men from Western Europe and the US were attending those events. It was a perfect storm, essentially.

Then there's the issue, you know, are gay men more promiscuous than heterosexuals? And I know, probably the general public that's the kind of knee-jerk reflex they have, every time they see they hear about MSM being associated with an STI. Well, data don't really support that. It looks like the total lifetime number of sexual partners is very comparable between MSM and heterosexuals. Maybe MSM have a slightly higher number of concurrent sexual partnerships, which means more than one sexual partner in a very short amount of time, whereas heterosexuals tend to be more serial monogamists.

I always remember when I asked a young heterosexual man in one of my clinics, “Are you in a regular, long-term relationship?” And he said, “Oh, yes, Doc.” And I replied, “How long have you been together?” “Oh, ages.” “Can you be more precise?” “Oh, maybe three weeks.” So, you know, this in the eye of a young heterosexual men is a long-term relationship. But actually for a bacteria with a short infectious period like, for example, gonorrhea, three weeks are a really long time. It's unusual for the infectivity of gonorrhea to be longer than three weeks—well to be longer than a couple of weeks, really. Which means if you're a serial monogamist, and even if you change partner once a month, for gonorrhea, it's kind of difficult to spread through the population. But if you just have one more sexual partner in those two weeks, that's an excellent opportunity for gonorrhea to spread.

MIC CAVAZZINI:               And there was another—there was a review from the WHO that showed mpox had R values of around 1.3 being reported across 70 countries. The highest was a 1.5 in the US. So I’m guessing that’s within that dense sexual network, and for the rest of the population it would be virtually zero, well below one.

MASSIMO GIOLA:            Yeah. And then for some STIs, there is also the issue of biological factors, biological susceptibilities of gay and bisexual men. And that is the lining of the rectum being very different from the lining of the vagina, that gives to some STI pathogens, an excellent opportunity to spread. So the typical example is HIV. The infectivity if you have an insertive condomless vaginal intercourse as a man, your chance of getting HIV is about one in 2,500,000. But if you have an insertive anal intercourse, as an insertive partner your chance of catching HIV is about one in 250. So it's not just about the lining of the rectum being very thin. It's also about the amount of immune system cells in the lining and that's why even for the insertive partner the risk is much bigger because there's so much more virus around given the rich envelope of immune system in there.

MIC CAVAZZINI:               So that would be true of the transmissibility of mpox through this mode. But there are also conditions that you don't always think of as sexually transmitted diseases at all. Transmission of enteric pathogens like Shigella between MSM has been observed since the 1970s, actually. Vince, tell us why there's been an increased frequency of outbreaks of Shigella in recent years.

VINCENT CORNELISSE:   That’s a good question, Mic. And on this topic, so now in the Australian STI Management Guidelines, we have a section called “sex-associated infections”. We ended up placing mpox in there as well, because this is you know, before it was firmly determined that it was a sexually transmitted infection. But certainly, other bacterial infections can be transmitted sexually, even if that might not be their main mode of transmission in the general community. Shigella is a perfect example.

Another one is meningococcal disease, which of course we often see breakouts amongst schoolchildren, or amongst music festival goers, more recently. But certainly we've seen an meningococcal breakouts amongst gay men, likely through sexual transmission, purely because if you're doing sex well, you're in contact in many different ways and hence there’s lots of opportunity for transmission of organisms.

And where we get into difficulty with organisms such as Shigella is that this is then combining a highly transmissible organism—Shigella is super transmissible—it's transmissible by close contact, but also through fomite transmission, which in the context of sex might include transmission by sharing toys, for example, sex toys, or even surfaces in sex venues.

So it's a highly transmissible organism in a population that's exposed to very large quantities of antibiotics. So we know from ecological data that gay and bisexual men use many more times the amount of antibiotics that the average person uses in Western society. And that's not the fault of gay and bisexual men. That's because we are prescribing these antibiotics to gay and bisexual men to treat other STIs.

And hence, we're now in a situation where, for example, Shigella infections amongst gay men in Australia are very highly likely to be antibiotic resistant. Which we addressed in the guidelines by saying, you know, if you diagnose a gay man with Shigella do not proceed to treat them as a standard Shigella infection in the community. You must speak to your local public health units to find out what the resistance patterns in that community are, because it's highly likely that there'll be resistant to first line, second line and perhaps even third line treatment.

MIC CAVAZZINI:               And even in the general community, it's likely to pass within a few days.

VINCENT CORNELISSE:   Yeah, but again, the problem becomes, as Massimo pointed out, we’re now not just treating that individual. We are also needing to prevent transmission to others, in a community where there's lots of close physical contact with perhaps multiple partners at a time.

MIC CAVAZZINI:               So there's that pressure on physicians, perhaps.

VINCENT CORNELISSE:   The pressure to treat but at the same time balancing that with the problems from overuse of antibiotics in this population already.

MIC CAVAZZINI:               Okay, gastro is not usually life-changing, at least in adults who have access to sanitary hydration. But a more serious infection known for a long time to affect men who have sex with men with higher frequency is hepatitis A. As recently as 2016-2017 there was an outbreak estimated at over 4000 cases across 17 European countries. Of those for whom complete records were available, half were hospitalised for several nights and some proportion of those will experience hepatic failure. Massimo, how do we rank these emerging infections or mutated strains?

MASSIMO GIOLA:            Well, yeah, you know, there are other things, for example, I read recently case series of entamoebiasis, entamoeba histolytica in Japan seems to be a major issue among MSM in Japan, with cases of hospitalization with liver abscesses.

Hepatitis A among MSM is nothing new. There is actually a clade that's called the MSM clade of hepatitis A in Western Europe because it's been circulating among MSM communities for decades. You know, hep A does not frequently kill people and doesn't cause a chronic hepatitis either. But for sure it's not pleasant, and yeah, people can end up in the hospital for considerable amount of time and can be pretty sick.

So I guess us in the sexual health services probably need to have a bit of a broader mindset and make sure we include in our differential diagnosis also other things and not just the usual gonorrhea, chlamydia, and syphilis.

MIC CAVAZZINI:               Let me push that canary in the coal mine analogy. HepA and mpox too have a secondary attack rate in the community and household settings that's significant. How does the canary inform general practice across the community?

MASSIMO GIOLA:            We also need to make sure the wider health community and the funders are aware of these other situations and understanding that the traditional indications, let's say, for free vaccination for Hep A, must be extended to include people at-risk attending the sexual health clinic, for example.

The other thing I would like to link with the canary in the coal mine is something Vince already alluded to, which is the high degree of altruism shown by gay and bisexual men over recent history. And in fact, as soon as I started having conversation with my patients about mpox, and the fact that maybe there was going to be a vaccine which was not registered, but if they really wanted it they could have it—unanimously, the answer I got was, “Oh, yeah, let's do it. We've got to look after ourselves, and the wider community”.

Not only that, that we now have data strongly indicating that gay men bought time for the medical community to roll out the vaccine as they were willing to temporarily put on hold the highest risk behaviours. A recent survey from the US found that 50 per cent of gay men in the US, for a good chunk of 2022, decreased the number of sexual partners, decreased the attendance to sex-on-site venues, decreased the number of partners met on online apps. And that—there was a strong focus about protecting the whole community. And I would say the whole society really at large.

MIC CAVAZZINI:               Yeah, the messaging is very tricky, but it ultimately was effective. Last question, is again that question of the usefulness of the STD label. As Vincent said it will heighten awareness amongst the at-risk population and specific practitioners. But, speaking personally, I found that when this emerged last May, beyond reading the headlines I didn't get particularly interested, I didn’t get particularly worried because, rather than going to wild Pride parties, I was exhausted after looking after a six month old infant at the time.

VINCENT CORNELISSE:   No but that illustrates it perfectly. That's why this was important. If you had gone off to try and get an mpox vaccine our messaging would have been wrong.

MIC CAVAZZINI:               But as a health communicator, and as a general interest, I feel like I should have paid more attention. I feel a bit ashamed that I didn't take it more seriously. And, I laughed a bit when you talked about sex toys before because, you know, Shigella probably obviously gets transmitted between kids toys at daycare.

VINCENT CORNELISSE:   Any toys.

MIC CAVAZZINI:               So these are things that I should be aware of, even at a general community level.

VINCENT CORNELISSE:   Sure, you should be aware but not alarmed and racing off to your doctor, right? So, I think the big philosophical question is not, “Will we stigmatize mpox and people with mpox by labeling it an STD?” The big philosophical question is, how can we destigmatize sex? Because that's really the crux. There's no need for sex to be stigmatized. There's no need for sexually transmitted infections to be stigmatized. There's no need for people who have multiple sexual partners to be stigmatized. And that's where the problem lies not…

MIC CAVAZZINI:               Not the categorization of the disease, which actually is very helpful in the public health response.

MIC CAVAZZINI: Many thanks to Vincent Cornelisse and Massimo Giola for giving their time and expertise to this episode of Pomegranate Health. The views expressed in this podcast may not represent those of the Royal Australasian College of Physicians.

It’s a story rich with scientific findings. If you want to follow anything up, please go to racp.edu.au/podcast where you’ll find all the citations embedded in a transcript. There’s also a reading list and links to other resources including an eLearning course on microbiology designed for Trainees of Infectious Diseases.

If you liked this podcast please share it with your colleagues or leave a review. You can subscribe via an pod-catcher such as Spotify, Apple Podcasts or Castbox. Or for the late adopters, there’s also an email alerts list you can sign up to at our website. Finally, if you have any feedback, or great ideas for new stories, please send an email to podcast@racp.edu.au.

I’m Mic Cavazzini, and this episode was produced on the traditional lands of the Gadigal people of the Eora nation. I pay respect to the storytellers who came long before me. 

 

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01 Mar 2024
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