In the first 6 months of 2022 there have been 240 cases of acute hepatitis of unknown cause in young children in the UK. This may not sound like a large number, but it is, because these are “new” cases of hepatitis caused by something new, not the normal background cases of viral hepatitis we see normally. Most cases of hepatitis in children in the UK are caused by Hepatitis Viruses A-E, but in this outbreak the cause is something different.
 
In fact, the World Health Organisation say there have been over 650 cases reported from 33 countries Worldwide between 5th April and the 26th May, but this is likely to be an underestimate due to many countries not looking for specific causes of hepatitis, but rather assuming it is due to Hepatitis Viruses A-E because the tests to confirm the cause are not always routinely available.
 
The other striking thing about these cases, above and beyond the unknown cause, is that the hepatitis appears to be more severe than hepatitis normally is in children.
 
The UK has been investigating this outbreak for most of the year and has pretty thorough data from 1st January to the 3rd of May. In this period there were 163 cases of which 11 required liver transplants. No patients have died so far in the UK, but in the USA 20 of 109 cases required liver transplants, and 3 died. Needless to say, this is worrying, as severe liver failure or death from acute hepatitis in children is usually very, very, rare.
 
What is hepatitis and how does it present?
Hepatitis is inflammation of the liver. It presents with:

• Jaundice – yellowing of the skin and eyes due to the build up of bilirubin in blood which has a yellow colour (think of The Simpson’s and you won’t be far wrong!)
• Dark urine – as bilirubin gets into urine it makes the urine dark
• Pale grey poo – bilirubin is normally excreted into the gut making poo brown (although there are other reasons as well, but let’s not go there!) but if bilirubin is not excreted by the liver into the gut the poo stays pale and grey
• Itchy skin – caused by the build-up of bilirubin and bile salts in skin
• Muscles and joint pains
• Fever
• Nausea and vomiting
• Tiredness
• Loss of appetite
• Abdominal pain – especially right upper quadrant pain over the liver

 
Normally the liver is very good at recovering and regrowing after damage has been caused. Even the ancient Greeks knew this. In the Greek legends Prometheus was punished by Zeus because he stole fire to give back to mankind. He was chained to a rock in the Caucasus Mountains, and every day an eagle came and ate part of his liver. Each night, his liver would regrow, which meant he had to endure his punishment for eternity. Okay, the liver takes a bit longer than a night to regrow but you get the (very graphic!) picture.
 
In the case of severe liver failure, the damage to the liver is too much for the liver to cope with and it dies completely. In this situation the patient either gets a liver transplant, or they die; we do not have a machine that effectively performs the function of the liver in the way we do with kidneys and dialysis.
 
The other thing that is a bit weird about the current outbreak is that all the cases are in children, with nearly 60% being 3-5 years old. Cases do not appear to be occurring in adults suggesting adults are not susceptible or are immune to whatever is causing the hepatitis.
 
What are the current hypotheses?
A lot of work has been done to try and identify the cause of the hepatitis outbreak. The most common and consistent finding so far is the presence of Adenovirus DNA in the blood of about 70% of the patients. At the moment this is the top of the possible causes although it is not confirmed and Adenovirus infections in children are very common so it is possible this could be coincidental. At the moment nothing will be ruled out until it has definitely been shown to not be the cause.
 
The current possible hypotheses are:

• An unusual Adenovirus infection due to:
  • Abnormal patient response to the Adenovirus leading to hepatitis
  • Very high rates of population Adenovirus infection meaning the outbreak of hepatitis looks bigger than normal (lots of cases means relatively more “rare” complications)
  • Abnormal response to Adenovirus due to immune priming by SARS CoV2 which is also very common at the moment (SARS CoV2 is making patients respond to Adenoviruses in a weird way)
  • Abnormal response to Adenovirus due to coinfection with another as yet unidentified virus
  • Abnormal response to Adenovirus due to exposure to an unidentified toxin, drug or environmental chemical
• A new variant of Adenovirus
• A post-infection syndrome due to past SARS CoV2 infection
• A drug, toxin or environmental exposure (without blaming any viruses)
• A novel unknown pathogen yet to be discovered (oh goody, another new virus!!!)
• A new variant of SARS CoV2

 
Although the list of possible hypotheses is very long, the Adenovirus hypothesis is number 1.
 
Another bit of supporting evidence for the Adenovirus hypothesis is that in 27 of 35 children who had their Adenoviruses typed by molecular methods, the Adenovirus was shown to always be type 41F. Again, this doesn’t prove Adenovirus 41F is the cause, as it could just be the common Adenovirus circulating within the population at the moment, but it is suggestive that there might be something special about this particular virus.
 
So far, no toxin or drug has been found. Some background use of paracetamol (a hepatotoxic drug) has been found, but the levels in the patients is consistent with treatment doses not toxic doses.
 
The most important theory that has been excluded is that the cause might be the Covid vaccinations. IT IS NOT! These children (under 5 years old) are too young to have been vaccinated.
 
So, where are we now?
Well, the hunt for the cause continues. Paediatricians, Virologists and Microbiologists around the UK are on the look out for cases of unexplained hepatitis, especially in children. Any child with hepatitis (whatever the cause) should be notified to the Health Security Agency as soon as possible so they can continue to build up a picture of who is getting hepatitis and what they might have been exposed to. Children with hepatitis should have ALL these tests sent for possible causes:

• Serum for Hepatitis Viruses A-E
• Whole blood (EDTA, normally the purple tube) for Adenovirus PCR
• Throat swab for Adenovirus PCR

 
In the meantime, what can we do?
 
How to prevent infection
Even though we don’t know the cause of these cases of acute hepatitis in children we can have a pretty good guess at how to stop them.
 
Adenoviruses are spread by droplets, in the same way as SARS CoV2… so wash your hands regularly, don’t sneeze in people’s faces and cover your mouth when you cough! Oh, how quickly we forget… 

No, I’m serious… what is Covid? I hear it all the time. Someone coughs, is it Covid? Someone sneezes, is it Covid? Some say they feel a bit under the weather, is it Covid? I even had the discussion with my parents at the weekend… ECIC (aka my wife) has a bit of a cold and they say, “has she got Covid?”
 
So, what is Covid?
To start with, “Covid” isn’t anything. The actual name for the disease cause by the Severe Acute Respiratory Coronavirus type 2 (SARS CoV2) was Covid-19; it was an acronym for COronaVirus Infectious Disease 2019. But now it has been reduced to a snappier “Covid”.
 
I have also been asked if someone has “caught covid”…NO! You cannot catch Covid-19, you can catch SARS CoV2, that is the name of the virus. It is so reminiscent of the horror show that was HIV back in the 1980s… even senior health professionals thought you could catch AIDS (Acquired Immune Deficiency Syndrome) …NO! You cannot catch AIDS, you can catch Human Immunodeficiency Virus (HIV). Covid-19 and AIDS are the names of the clinical diseases, not the causative viruses.
 
So, when we think about Covid-19 being a disease, a group of symptoms if you like, then the question “what is Covid-19?” actually starts to make more sense. 

​What is Covid-19?
The original Covid-19 was a severe infection with SARS CoV2 characterised by high fever, cough, severe shortness of breath and hypoxia often requiring hospitalisation for respiratory support.
 
But we rarely see this pattern of infection with SARS CoV2 anymore. It has been a while since I have seen someone sick enough with SARS CoV2 infection to end up on ITU. Yet there are still about 80 patients a day with positive SARS CoV2 tests around the hospital, so what has happened?
 
The increase in immunity to SARS CoV2 from previous infection or vaccination has changed the symptoms of infection with SARS CoV2. In fact, the NHS website lists lots of symptoms of Covid-19 now… but are they all Covid-19?

• a high temperature or shivering (chills) – a high temperature means you feel hot to touch on your chest or back (you do not need to measure your temperature)
• a new, continuous cough – this means coughing a lot for more than an hour, or 3 or more coughing episodes in 24 hours
• a loss or change to your sense of smell or taste
• shortness of breath
• feeling tired or exhausted
• an aching body
• a headache
• a sore throat
• a blocked or runny nose
• loss of appetite
• diarrhoea
• feeling sick or being sick

 
It seems to me that the list of possible symptoms from infection with SARS CoV2 has become so broad that the term Covid-19 has probably become obsolete. ECIC has tested negative, but she has a new cough, shortness of breath, feels tired, has a sore throat, blocked nose blah blah blah… but she hasn’t got Covid-19 she has one of the many other “cold-like” illnesses we don’t name… she also didn’t get too much mollie-codling or sympathy either! Donuts, ice cream are allowed, and to just watch daytime TV and snooze in the afternoon… she is getting better… it’s probably an unnamed virus… it will pass.
 
Think about it. We don’t normally have a single name for all infections caused by a specific bacterium. We wouldn’t say a patient had “Staphylococciitis” (okay, I have just made that up), we would say they had had cellulitis, or septic arthritis, or osteomyelitis, or endocarditis, or one of the other infections caused by Staphylococcus aureus. The name of the infection is dependent on the symptoms… not the causative microorganism.
 
And we don’t call the other coronavirus related infections by any specific name; we don’t have Covid-92 for what was thought to be the cause of “Russian Flu” back in 1892.
 
I think we need to move on. I think still talking about Covid-19 is damaging. It is damaging because it dilutes our understanding of how severe the infection can be in non-immune people, and it increases the anxiety for those who have a mild or asymptomatic upper respiratory tract infection; some people still think everyone with COVID-19 dies!!!!!!!!
 
Personally, I think it is time to stop using the term Covid-19 EXCEPT as the name for the severe life-threatening acute respiratory infection that leads to people ending up on intensive care units. For everyone else we should use the term for their actual infection; upper respiratory tract infection (URTI), pharyngitis, pneumonia, acute coryzal illness (a cold).
 
To this we can then add the causative virus if we really, really, really, want to:

• URTI caused by SARS CoV2
• Pharyngitis caused by SARS CoV2
• Pneumonia caused by SARS CoV2
• Cold… no, just a cold, eat chicken soup, donuts, ice cream, whatever you like… it’s a cold and as “old housewives” say…you “feed a cold”…

 
But what do you think? Do you think the name Covid-19 still has a wider value? Or do you think it should be restricted to specific patients?
 
Or do you not care… it’s just pedantic Microbiologists who think about these things and everyone else has something better to do? 😊 Okay, fair enough…
 
That’s it, I’m not going to write another blog about Covid-19!

​Back in 2018 I wrote a blog called “Don’t monkey around with the pox”. The subject was a disease called Monkey Pox, and I wrote it because the UK had recently diagnosed the first 2 cases ever in the UK. The patients were both from Nigeria. Monkey Pox is a rare infection though, and it wasn’t clear if we would see other cases again… until now…!

​At the beginning of May this year a new case of Monkey Pox was diagnosed in a patient who had recently come to the UK from Nigeria. Then towards the middle of May 2 further cases of Monkey Pox were diagnosed in the same household, but these patients had no contact with the first case, or any travel history, and in fact it’s not clear where they acquired their infections from. All very worrying…
 
Then a further 4 cases have been diagnosed! Also unrelated to the previous cases and with no obvious source for the infection… however these cases have all occurred in gay or bisexual men who have sex with men (MSM).
 
This is extremely concerning! We have now had 6 cases of Monkey Pox in people who have not been to Africa and who have no obvious source for the infection. This means we have an unknown source of infection in the UK population. On top of this we now have cases in a group of the population where spread may occur more readily through sexual activity. It is very unlikely that these 7 cases are going to be the last cases identified!
 
So, time for an update… what has changed since the blog in 2018?
 
Epidemiology
Monkey Pox is still a rare infection. In the Democratic Republic of the Congo where most cases have been reported, surveillance studies during “outbreaks” have shown an incidence of past infection between 0.001-0.05% of the population, that’s about 1 in 100,000, but that’s when they are looking for cases during an outbreak, not all the time, so the true rate could be lower than this.
 
There are 2 main types of Monkey Pox, West African and Central African. West African causes a milder infection with a mortality of about 1%; Central African is more severe with a mortality of about 10%. Fortunately for us, the cases in the UK so far have all been the West African type and are therefore mild infections.
 
Person-to-person transmission is rare, with a household secondary case rate of 8%, but transmission can still occur from touching infective lesions, respiratory droplets and possibly also sexual contact.
 
Case definition
The current UK case definition for a probable case of Monkey Pox is:

• Symptoms including: fever >38.5oC, headache, myalgia, arthralgia, back pain or lymphadenopathy

PLUS

• Contact with a case of Monkey Pox within 21 days of symptom onset OR travel to West Africa or Central Africa within 21 days of symptom onset OR MSM

 
The rash of Monkey Pox is vesicular (small fluid filled blisters) starting 1-5 days after onset of fever. It usually starts on the face or genitalia and then spreads to the rest of the body. It may look similar to chicken pox. Skin lesions eventually scab over, dry and then fall off.
 
Any patient meeting the case definition should be URGENTLY discussed with the Health Security Agency (HSA) in the UK, previously known as Public Health England, as well as the High Security Infectious Diseases Unit at the Royal Free Hospital London and the Imported Fever Service at Porton Down. This is for a surveillance activity rather than “infection severity” at the moment but as we all know, new infections that can spread can become a problem!
 
Treatment
There is no specific treatment for Monkey Pox, and most cases are mild and self-limiting. In severe cases the drug Cidofovir has been used. Cidofovir is a nucleoside analogue drug; it mimics a component of the virus’s genetics which when incorporated into the new virus particle causes a fault and the virus can’t reproduce. The main problems with Cidofovir are that it is only available intravenously and it is very toxic to kidneys.
 
There are now 2 new experimental drugs for treating pox-illnesses like Monkey Pox (and even Smallpox!) that might be available for very unwell patients in an off-license capacity:

• Brincidofovir is a derivative of Cidofovir which is orally bioavailable and is less toxic to kidneys
• Tecovirimat is a novel drug that is also orally bioavailable but works by preventing newly reproduced virus from wrapping up into a small package prior to release – there is experimental evidence that Tecovirimat and Brincidofovir are synergistic with each other (the combined effect is greater than either on its own)

 
Prevention
The main methods of prevention are avoidance of exposure to infected animals and people, good infection control practice and vaccination (the Smallpox vaccine is 85% effective at preventing Monkey Pox).
 
There are no definitive infection control policies for this infection yet, but in the meantime the following for respiratory spread infections would be appropriate:

​In the event of a sustained outbreak in the UK it is possible that the HSA might start to ring vaccinate at risk people (e.g. MSM population) to prevent spread of the virus within the wider population.
 
Now we wait to see what happens. Will there be further cases? Will the virus become established in the MSM population? If it does we could be in for another viral “pandemic”… oh joy!
 
Oops since writing this on Tuesday we now have 20 cases in the UK… did I say watch this space?!

Doctors love acronyms; they use them all the time. They’re bad enough when they’re talking:

• “What did the patients FBC, U&Es and CRP show?” – translated as “What were the results of the fancy blood tests we sent to the haematology and biochemistry labs?”
• “The patient grew a CNS” – translated as “the bacterium in the patient’s blood was a coagulase negative staphylococcus (a skin contaminant)”
• “The patient is on AMG” – a personal pet hate this one, translated as “the patient has been given the antibiotics Amoxicillin, Metronidazole and Gentamicin”

“Urine bugs may be a sign of aggressive prostate cancer”, that was the headline on the BBC news and so I had to take a look. The BBC reports that “scientists have identified urine bacteria which are linked to aggressive prostate cancer” and that “clearing the infection might prevent bad tumours”; the researchers claim they have demonstrated “an association between the presence of bacteria in urine sediments and higher D’Amico risk prostate cancer patients” and that “specific anaerobic bacteria genera have prognostic potential”

How do you predict that an antibiotic is going to be able to treat an infection caused by a particular bacterium? Easy… you do the antibiotic sensitivities and if it is susceptible you treat. Right?
 
Well, sometimes it isn’t as simple as that. Sometimes you need more than just a standard laboratory investigation… you need to take your antibiotic testing to another level… do you mean levitation?!

I can just imagine the conversation:
 
“Goldberger, I need you to go down South and investigate an outbreak” demanded the Surgeon General.
 
“Yes Sir!”, replied Dr Joseph Goldberger, “Errr, what outbreak am I investigating Sir?”
 
“The leprosy-like skin infection outbreak that no one has ever been able to discover a cause for of course, it’s affecting millions of people down there.”
 
“Yes Sir!” replied Dr Goldberger again, whilst probably thinking with a sinking heart “OMG, this sounds like a nightmare…”
 
But when you work for an organisation such as the US Public Health Service in 1915 and your boss tells you to do something you pack your bags and off you go. So he did…

The Microbiologist listened, getting increasingly confused. The speaker was saying that the newborn needed to drink its mother’s colostrum milk otherwise it wouldn’t have ANY antibodies. But this didn’t make sense to the Microbiologist; transfer of antibodies to the fetus via the placenta is a fundamental aspect of the immune protection a mother can give her newborn baby. We even rely on transfer by immunising in pregnancy for pertussis (whooping cough) and Covid-19 so that IgG antibody can develop in the mother, cross the placenta, and protect the baby after it has been born. It’s a FACT!
 
And yet, there was the speaker saying that this newborn HAD to receive its mother’s colostrum or it would have NO antibody. They even took a blood sample from the newborn to check it had antibodies AFTER it had had the colostrum.
 
“Why are you frowning?” asked the ECIC (AKA Wife).
 
“It doesn’t make sense” muttered the Microbiologist, “you get antibody in babies by transplacental transfer, not drinking milk.”
 
“So, you’re saying the experts are wrong and you’re right?”
 
“No, I’m just confused.”
 
“Well, that’s because you’re not a vet.” Continuing to mutter under her breathe “didn’t I say I’ll marry you ONLY if you NEVER act in a medical manner towards my cats…”
 
She had been “warned” about medical interference and the “know-it-all” attitude of medics by her vet!!!
 
Oh, sorry, did I not say? We were watching This Farming Life (one of our favourite TV shows) and they were talking about Clydesdale foals and whether they must be given the colostrum from the mare!

Sunday night is “Antiques Roadshow night” in our house, every Sunday in the UK the BBC1 broadcast an hour of people bringing their various family heirlooms or jumble sale bargains to antique experts for a brief chat about what they are and how much they are worth. I enjoy the social history side of the show although I find the occasional “money-grabbing” a bit depressing.
 
Last Sunday, 20th February, was a bit different as I saw a trailer showing something unusual and medical… queue my curiosity! I was glued to the program in anticipation.
 
It was the last item on the show, and it had been brought in by some school children and their Headmaster and it was this:

I’ve had to reduce the amount of time I spend watching the news as it’s really not good for my mental health. Not only that, but ECIC is getting increasingly irritated with me muttering and grumbling at the various Covid-19 stories, and she’s right, I should “just let it go”.
 
One (of the many) things that irritates me is when someone says a new variant is “more transmissible”. Why does it irritate me? Well, it’s an incorrect term. Transmissible means “being able to be spread from one person to another”, well we know SARS CoV2 is transmissible… but it cannot be “more transmissible”, it is either transmissible or it is not. More transmissible would mean that it was better able to “move” from one person to another and we have no evidence of that at all… it hasn’t suddenly sprouted wings!