“We want to know whether to stop the Aciclovir”, said the Doctor.
The Microbiologist took a deep breath. This was a surprisingly regular but unhelpful opening gambit from those calling for advice, “would you perhaps like to tell me about the patient?” he asked.
“Oh yeah, sorry! He’s 53 years old; previously fit and well. He returned from trekking in Nepal nearly two weeks ago. He was well whilst on holiday but became unwell four days ago with a flu-like illness which progressed to nausea and vomiting followed by headache, confusion and difficulty speaking. We thought this was encephalitis but his CSF HSV PCR is negative so we wondered whether it is alright to stop the Aciclovir” asked the doctor.
The Microbiologist took a deep breath. This was a surprisingly regular but unhelpful opening gambit from those calling for advice, “would you perhaps like to tell me about the patient?” he asked.
“Oh yeah, sorry! He’s 53 years old; previously fit and well. He returned from trekking in Nepal nearly two weeks ago. He was well whilst on holiday but became unwell four days ago with a flu-like illness which progressed to nausea and vomiting followed by headache, confusion and difficulty speaking. We thought this was encephalitis but his CSF HSV PCR is negative so we wondered whether it is alright to stop the Aciclovir” asked the doctor.
“Encephalitis is a clinical diagnosis not a Microbiology one. A negative PCR doesn’t rule out the diagnosis of encephalitis. Has the patient had an MRI brain scan? Is there any more history? Where in Nepal did the patient go? Any contact with animals? Anyone else on the trip unwell?” the Microbiologist replied.
The doctor didn’t know but went off to speak to the patient’s wife and then call the Microbiologist back.
At the later phone call it turned out that the patient had been trekking in Sagarmatha National Park and had been as high as Namche Bazaar. No one else had been unwell. There had been a number of city trips back in Kathmandu including a visit to Swayambhunath (also known as the Monkey temple because of the hordes of rhesus macaques that live there) where the patient received a small bite from a monkey who got a little too close. The patient had also not had an MRI scan.
“Bitten by a monkey…and that wasn't relevant in your initial history taking?!” Gasped the Microbiologist “No, you cannot stop the Aciclovir” he continued categorically. “You haven’t ruled out encephalitis which is what it sounds like this patient has. In addition, it could still be HSV or it could be Simian B Virus. Does the patient have any lesions at the site where he was bitten? Carry on with the Aciclovir, look at the site of the bite, ask the Radiologists about a MRI scan and I will arrange further testing on the CSF.”
The doctor didn’t know but went off to speak to the patient’s wife and then call the Microbiologist back.
At the later phone call it turned out that the patient had been trekking in Sagarmatha National Park and had been as high as Namche Bazaar. No one else had been unwell. There had been a number of city trips back in Kathmandu including a visit to Swayambhunath (also known as the Monkey temple because of the hordes of rhesus macaques that live there) where the patient received a small bite from a monkey who got a little too close. The patient had also not had an MRI scan.
“Bitten by a monkey…and that wasn't relevant in your initial history taking?!” Gasped the Microbiologist “No, you cannot stop the Aciclovir” he continued categorically. “You haven’t ruled out encephalitis which is what it sounds like this patient has. In addition, it could still be HSV or it could be Simian B Virus. Does the patient have any lesions at the site where he was bitten? Carry on with the Aciclovir, look at the site of the bite, ask the Radiologists about a MRI scan and I will arrange further testing on the CSF.”
The Doctor hung up the phone and turned to their colleague… “The Microbiologist thinks the patient has some kind of monkey flu or something…!” he said. “I bet this another Halloween wind up again…!”
What is Simian B Virus?
Simian B Virus, or B virus as it is sometimes called, really does exist and it can infect humans. It infects all types of macaque monkeys and is a member of the herpes viruses causing similar infections to Herpes Simplex Virus (HSV) in humans, such as oral or genital lesions. Latent infection in monkeys occurs and can either reactivate or cause asymptomatic virus shedding, in the same way as HSV in humans.
Transmission to humans occurs after exposure to oral, genital or ocular secretions and occasionally CSF, either through bites, monkey scratches and cages (from contaminated surfaces) and in rare instances needlestick injuries (usually veterinary staff and people who work with macaque monkeys such as laboratory workers). As in humans with HSV, stressed or immunocompromised macaque monkeys are more likely to reactivate and shed B virus.
Studies have shown that between 20% and 100% of captive macaque monkeys are seropositive for B virus (i.e. they have had B virus in the past and could reactivate it) and up to 2% of seropositive macaque monkeys have active virus shedding at any time. This would suggest a major risk of exposure in people who work with these monkeys and yet there are only about 50 cases of B virus infection reported in the literature. This suggests that most human exposure does not result in infection; asymptomatic infection in humans has not been described although it has been looked for in people who work with monkeys.
How does Simian B Virus present?
There are three main clinical presentations of B virus infection, which occur between 3 days and 3 weeks after exposure:
How do you diagnose Simian B Virus infection?
The most important aspect to diagnosing Simian B Virus infection is to consider it in the first place. This is a rare infection but where there is a history of exposure to macaque monkeys or their environment it should always be one of your differential diagnoses.
Diagnosis is made by PCR on CSF samples or looking for seroconversion in blood. In the UK this is done in the Virus Reference Department at Colindale in London. Given the rarity of such an infection and the specialist nature of the test all patients should be discussed with the laboratory before sending any samples as there are likely to be particular requirements for sampling and transport of specimens.
How is Simian B Virus infection treated?
Without treatment the mortality is 80%, and almost all survivors have permanent neurological damage, whereas with treatment the survival is 80%. Treatment should ideally be guided by an Infectious Diseases Physician because they are more familiar with the antimicrobials used to treat this infection.
The treatment of infection with Simian B Virus is IV Ganciclovir 5mg/kg BD. Note: This is different to the treatment of HSV encephalitis which is IV Aciclovir. The IV Ganciclovir should continue for 2-3 weeks or until symptoms have resolved, whichever is longer.
Most Infectious Diseases Physicians, Virologists and Microbiologists also recommend prolonged oral suppression therapy with Valaciclovir or Aciclovir after the IV treatment in order to prevent reactivation of latent virus. There is no definite duration of this with some experts recommending life-long treatment whilst others would stop after a year and monitor with regular oropharyngeal and conjunctival swabs to detect and treat reactivation.
Can Simian B Virus infection be prevented?
The best ways to prevent B virus infection are to not get bitten in the first place and to wear protective gloves, face masks and protective glasses when handling monkeys or performing procedures in potentially contaminated cages.
If someone is bitten or scratched then the wound should be thoroughly cleaned with a detergent soap (e.g. chlorhexidine or iodine based) and water for at least 15 minutes.
Following exposure either by scratch, bite or mucosal splashing the patient should be given post-exposure prophylaxis with PO Valaciclovir 1g TDS for 14 days. If Valaciclovir is not available then PO Aciclovir 800mg five times a day for 14 days can be used but it is not thought to be as effective as it results in lower blood concentrations than Valaciclovir.
NB Neither drug is actually licensed for this use but as it is a rare situation it is unlikely that any drug company will go through the expense of getting a license when experts agree it should be given anyway.
So the patient was discussed with the Reference Laboratory and CSF and blood samples were sent for Simian B Virus PCR and serology testing. The site of the monkey bite had healed completely and there was no associated lymphadenopathy. The Radiologists did an MRI brain scan which was also reported as normal. The CSF PCR and serology for Simian B Virus were negative but on wider testing for other viruses the cause was found to be an Enterovirus, a much more common cause of encephalitis.
Everyone was relieved that this wasn’t Simian B Virus, although the Doctor was a little disappointed as they were looking forward to the chance to present such an interesting patient at the Grand Round. The patient’s treatment was stopped as there is no specific treatment for Enterovirus, it is a self-limiting infection. The patient rapidly recovered and went home.
P.S. The Editor Chief in Charge (aka my wife) has informed me that King Louie who sang Oo “B” do, I want be like you oo oo, was in fact an orangutan not a rhesus macaque! She is so critical of my work!!!
What is Simian B Virus?
Simian B Virus, or B virus as it is sometimes called, really does exist and it can infect humans. It infects all types of macaque monkeys and is a member of the herpes viruses causing similar infections to Herpes Simplex Virus (HSV) in humans, such as oral or genital lesions. Latent infection in monkeys occurs and can either reactivate or cause asymptomatic virus shedding, in the same way as HSV in humans.
Transmission to humans occurs after exposure to oral, genital or ocular secretions and occasionally CSF, either through bites, monkey scratches and cages (from contaminated surfaces) and in rare instances needlestick injuries (usually veterinary staff and people who work with macaque monkeys such as laboratory workers). As in humans with HSV, stressed or immunocompromised macaque monkeys are more likely to reactivate and shed B virus.
Studies have shown that between 20% and 100% of captive macaque monkeys are seropositive for B virus (i.e. they have had B virus in the past and could reactivate it) and up to 2% of seropositive macaque monkeys have active virus shedding at any time. This would suggest a major risk of exposure in people who work with these monkeys and yet there are only about 50 cases of B virus infection reported in the literature. This suggests that most human exposure does not result in infection; asymptomatic infection in humans has not been described although it has been looked for in people who work with monkeys.
How does Simian B Virus present?
There are three main clinical presentations of B virus infection, which occur between 3 days and 3 weeks after exposure:
- Localised vesicles or ulcers at the site of exposure with pain, tingling, itching and lymphadenopathy
- Influenza-like illness with fever and myalgia followed by numbness at the site of exposure leading to abdominal pain, hepatitis, pneumonitis, conjunctivitis and eventually encephalitis.
- Encephalitis with nausea and vomiting, headache, meningism, cranial nerve defects, dysarthria, dysphagia, seizures, paralysis, respiratory failure, coma and death.
How do you diagnose Simian B Virus infection?
The most important aspect to diagnosing Simian B Virus infection is to consider it in the first place. This is a rare infection but where there is a history of exposure to macaque monkeys or their environment it should always be one of your differential diagnoses.
Diagnosis is made by PCR on CSF samples or looking for seroconversion in blood. In the UK this is done in the Virus Reference Department at Colindale in London. Given the rarity of such an infection and the specialist nature of the test all patients should be discussed with the laboratory before sending any samples as there are likely to be particular requirements for sampling and transport of specimens.
How is Simian B Virus infection treated?
Without treatment the mortality is 80%, and almost all survivors have permanent neurological damage, whereas with treatment the survival is 80%. Treatment should ideally be guided by an Infectious Diseases Physician because they are more familiar with the antimicrobials used to treat this infection.
The treatment of infection with Simian B Virus is IV Ganciclovir 5mg/kg BD. Note: This is different to the treatment of HSV encephalitis which is IV Aciclovir. The IV Ganciclovir should continue for 2-3 weeks or until symptoms have resolved, whichever is longer.
Most Infectious Diseases Physicians, Virologists and Microbiologists also recommend prolonged oral suppression therapy with Valaciclovir or Aciclovir after the IV treatment in order to prevent reactivation of latent virus. There is no definite duration of this with some experts recommending life-long treatment whilst others would stop after a year and monitor with regular oropharyngeal and conjunctival swabs to detect and treat reactivation.
Can Simian B Virus infection be prevented?
The best ways to prevent B virus infection are to not get bitten in the first place and to wear protective gloves, face masks and protective glasses when handling monkeys or performing procedures in potentially contaminated cages.
If someone is bitten or scratched then the wound should be thoroughly cleaned with a detergent soap (e.g. chlorhexidine or iodine based) and water for at least 15 minutes.
Following exposure either by scratch, bite or mucosal splashing the patient should be given post-exposure prophylaxis with PO Valaciclovir 1g TDS for 14 days. If Valaciclovir is not available then PO Aciclovir 800mg five times a day for 14 days can be used but it is not thought to be as effective as it results in lower blood concentrations than Valaciclovir.
NB Neither drug is actually licensed for this use but as it is a rare situation it is unlikely that any drug company will go through the expense of getting a license when experts agree it should be given anyway.
So the patient was discussed with the Reference Laboratory and CSF and blood samples were sent for Simian B Virus PCR and serology testing. The site of the monkey bite had healed completely and there was no associated lymphadenopathy. The Radiologists did an MRI brain scan which was also reported as normal. The CSF PCR and serology for Simian B Virus were negative but on wider testing for other viruses the cause was found to be an Enterovirus, a much more common cause of encephalitis.
Everyone was relieved that this wasn’t Simian B Virus, although the Doctor was a little disappointed as they were looking forward to the chance to present such an interesting patient at the Grand Round. The patient’s treatment was stopped as there is no specific treatment for Enterovirus, it is a self-limiting infection. The patient rapidly recovered and went home.
P.S. The Editor Chief in Charge (aka my wife) has informed me that King Louie who sang Oo “B” do, I want be like you oo oo, was in fact an orangutan not a rhesus macaque! She is so critical of my work!!!
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