The ward doctors rang the Microbiologist for advice as the patient hadn’t responded to antibiotics including IV Ceftriaxone which had been started in case the patient had meningitis. The CSF and blood cultures were negative.
On further questioning it turned out that the patient had returned from North America three weeks earlier where she had been travelling. She had spent time in various places but more recently in Arizona where she had stayed with friends and helped them clean up their old barn on the family farm.
“This might be the nameless virus”, advised the Microbiologist. “Send serum for antibody testing but continue the antibiotics for now in case I’m wrong. Watch out for the patient becoming hypotensive and oliguric. You had probably best let the Critical Care Outreach team know about her, they might admit her to the unit pre-emptively… just in case”.
So the Doctor arranged the blood test and rang Critical Care, “the Microbiologist wants the patient to come to the Critical Care Unit because she might have some virus… I don’t know what virus; they wouldn’t tell me the name!”
So what was the Microbiologist talking about? Let’s discuss the Hantaviruses…
Most Hantavirus infections are asymptomatic but significant Hantavirus infections present in two distinct syndromes: Haemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS). The incubation period is usually 2-4 weeks but can be as long as 2 months.
HFRS presents with acute fever, back pain, bleeding and renal failure. There are five phases which tend to overlap: febrile, hypotensive, oliguric, diuretic and convalescent.
- The febrile phase, including fever, headache, malaise and anorexia, lasts for up to a week. Towards the end of the phase there is severe back pain, nausea, vomiting, facial flushing, a petechial rash and conjunctival redness. The patient usually has a low platelet count and high creatinine.
- In the hypotensive phase the fever settles and the patient’s blood pressure drops, occasionally leading to shock and more severe haemorrhagic features. The hypotensive phase can last up to three days.
- In the oliguric phase the blood pressure returns to normal but urine output falls to the point where the patient may produce no urine at all (oliguria means very low urine output). Haemorrhagic features may become even more severe. The oliguric phase lasts up to 3 days. Up to 15% of patients die during the hypotensive and oliguric phases.
- Survivors enter a diuretic phase and their renal function starts to improve as they over produce urine (diuresis).
- Convalescence follows and can take weeks to months.
HPS begins with fever, myalgia and abdominal pain and diarrhoea. This is followed by rapidly progressive respiratory failure and hypotension. Patients are usually thrombocytopaenic and have a low albumin. Up to 50% of patients die. Survivors tend to have a rapid recovery in respiratory function although full recovery takes weeks to months. Respiratory function tends to return to normal during convalescence.
What are the Hantaviruses called and where do they come from?
The Hantaviruses are a group of RNA viruses from the family Bunyaviridae. There are lots of different Hantaviruses with lots of different names from many different countries. The names often correspond to where the virus was first described rather than where you are likely to catch it! The clinical presentations of HFRS and HPS are caused by different viruses.
- HFRS – Hantaan (from the Hantaan River in South Korea), Dobrava (Slovenia), Puumala (Finland), Saaremaa (an island off Estonia), Seoul (South Korea)
- HPS – Andes (Argentina, Chile), Laguna Negra (Bolivia, Paraguay), Juquitiba (Brazil), Choclo (Panama), Black Creek Canal and Bayou (Southeastern USA), New York-1 and Monongahela (Eastern USA), Sin Nombre (North America)
I particularly like the name Sin Nombre which means “nameless”. I have been told that there was such concern amongst native American Indian residents that "Navajo Flu", as it had been called in the press, should not be “labelled” after the specific area where it was first identified, the four corners area of the USA (where the US states of Arizona, Colorado, New Mexico, and Utah meet). The virus was therefore called the “nameless” virus. I don’t know if that is true but there is a good description of the original outbreak on Wikipedia.
The route of transmission of virus to humans is not completely understood. It is thought to occur via aerosolisation of rodent excreta (faeces, saliva and urine). Person-to-person transmission is very rare, and in the few cases where it is suspected there was very close personal contact in household members.
Each subtype of virus has a specific rodent host. In the UK, Seoul virus is found in rats, Puumala in bank voles and Saaremaa and Dobrava in wild mice. UK acquired Hantavirus infection is very rare, with only about 40 cases diagnosed in the past 30 years; however asymptomatic infection is much more common. Surveillance by Public Health England has shown that 1-3% of the population have serological evidence of past infection whereas 30% of pet rat owners are seropositive. The main people at risk of Hantavirus infection in the UK are those who come in to contact with rodents e.g. pet owners, laboratory animal handlers, veterinary surgeons, sewerage workers, forestry workers and water sport enthusiasts.
How is Hantavirus infection diagnosed?
By the time patients are symptomatic with Hantavirus infection it is very difficult to detect the virus itself. Therefore most cases of Hantavirus infection are diagnosed by detecting the immune response to the virus, acutely with IgM and later with IgG. Serum should be sent for IgM antibody testing with good clinical information, especially a detailed travel history or rodent exposure. A repeat serum sample should then be sent 3-5 weeks later to look for IgG (seroconversion). A positive IgM is diagnostic for acute infection; positive IgG is evidence of recent or past infection.
How is Hantavirus infection treated?
The antiviral Ribavirin has been tried to help treat patients with Hantavirus infection but it has to be started very early to be of any benefit at all. Most patients present too late for Ribavirin to help. The mainstay of management of these patients is supportive care including careful fluid balance, dialysis, respiratory support and control of shock.
Can Hantavirus infection be prevented?
The best way to prevent Hantavirus infection is to avoid exposure to rodents and their excreta but this is easier said than done. Rodents should be kept out of houses and away from human or animal food. Contaminated areas should be cleaned with disinfectants by people wearing respirator masks. If handling infected animals, appropriate personal protective equipment should be worn e.g. gloves, apron/gown, face mask.
There are vaccines available in South Korea and China against Hantaan and Seoul viruses but it is unclear how effective these vaccines actually are.
The following day the Microbiologist was doing the ward round on the Critical Care Unit and the ITU Consultant asked the Microbiologist “why wouldn’t you tell the ward doctors the name of the virus, …the ward doctor was very worried that it might be something deadly or secretive which must remain out of the press!” The Microbiologist laughed, “that’s its name, it’s called Sin Nombre, the nameless virus … and I thought I had an overactive imagination”.
Over the next week the patient had a stormy time of it. They did become hypotensive and needed dialysis for renal failure. The serology confirmed that she did indeed have a Hantavirus infection. After careful attention to fluid balance and cardiovascular support the patient did slowly improve and eventually went home. Much later the Microbiologist heard from colleagues that the patient had told her American friends what had happened and they all got checked for exposure to Hantavirus. Their results showed that they had all been exposed in the past (positive IgG) and were therefore immune.
P.S. I have had to reassure my wife that evicting the mouse who has taken up residence and wreaked havoc in our allotment shed is not sufficient exposure to be deemed a risk!