On the Horizon: Hantaviruses

Posted on October 18, 2016   by Benjamin Thompson

In early 2013, a man in North Wales was rushed to hospital showing symptoms of serious kidney problems. The source of his infection? His pet rats.

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Tests revealed that the causative agent was a rodent virus known as Seoul virus. Epidemiological tracing showed that the virus was present in the pet rats, and also in rats at the breeding farm where they came from. The owner of the breeding colony and her spouse tested positive for antibodies against the virus, and the spouse had in fact been hospitalised in late 2011 with an unidentified viral kidney illness.

In response to this case, and the handful that have happened since, Public Health England performed blood tests of people who kept pet rats. Results showed that nearly a third of those tested contained antibodies against Seoul virus, suggesting a previous exposure to the virus. In the control group, or in groups who only occasionally came into contact with rats (pest control workers, for example) less than 3.3% of people tested positive. In 2015, an outbreak of Seoul virus in South Wales was linked to both pet rats and large-scale commercial breeding of rats for reptile food.

Old and New World

Seoul virus is a member of the genus Hantavirus, made up of 24 related species. These viruses tend to be grouped into two broad categories: Old World, found in Asia or Europe, or New World, found in the Americas. While causing a benign infection in their natural hosts, the two groups broadly cause two different syndromes in humans, although there may be some overlap. Generally, each hantavirus is believed to be restricted to an individual host species – like Seoul virus and brown rats – with other species – in this case humans – being an incidental host.

Humans contract hantaviruses by breathing in aerosolised urine, faeces or possibly saliva from infected animals. This can happen during the cleaning of rodent-infested buildings or rat cages, which explains why people with pet rats are at risk from the virus.

Old World hantaviruses have been shown to cause haemorrhagic fever with renal syndrome (HFRS), a collection of symptoms ranging from fever through to kidney failure. Mortality rates depend on the infecting virus – for Puumala virus-related HFRS, it is around 1% while Hantaan virus-related levels are around 15%.

In Europe, the average annual number of reported human cases increased markedly during the last decade to more than 3,000 cases of HFRS. Thankfully, the majority of these are of the mild Puumala-virus related variety, and are detected widely across Europe, with the exception of the UK and the Southern Mediterranean.

For New World hantaviruses, the situation is worse. These can cause hantavirus pulmonary syndrome (HPS), which begins with mild flu-like symptoms that can rapidly escalate to lethal pulmonary oedema. HPS has mortality rates up to 60%. Currently, there are no vaccines against hantaviruses licensed in Europe, and prevention is centred around rodent control and through limiting exposure to infected excreta.

Voles as vectors

In the case of the Puumala hantavirus, bank voles (Myodes glareolus), found widely across Europe, transmit the disease. In the colder regions of Northern Europe, the natural population density of these voles is cyclical, so in Finland peak infection rates occur every three to four years, normally in the wintertime.

In the warmer climes of Central Europe, vole numbers are related to the quantity of food available. In Germany, an analysis of 12 years of data showed that levels of Puumala infection and vole numbers in a given year are strongly related to the amount of beech fruit produced the previous year.

As with many other emerging diseases, climate change appears to have a role to play in the levels of hantavirus infection. In North America, a large outbreak of the Sin Nombre virus occurred in 1993 , the year after a particularly severe El Niño rain season provided enough food for an explosion in rodent levels.

There is some evidence that milder winters in Central Europe are linked to increased Puumala infections, although the data are not conclusive. Confusingly, milder winters in Northern Europe seem to lower subsequent Puumala infections, as water is frozen into ice rather than a protective covering of snow under which the voles can hide, which makes them easier prey.

One thing that is not well understood is, if Puumala virus is so widespread across Europe and bank voles are found throughout the UK, why has the virus not been found in the British Isles? Research suggests that the lack of detection could be down to the fact that areas of beech forest are more fragmented in the UK than in mainland Europe, preventing a large enough population of bank voles from forming to sustain a viral reservoir.

The situation in the UK

To date, Seoul virus remains the only hantavirus for which there is clear evidence of infection within the UK, but this could be because Puumala virus infection is both mild and obscure in this country, and is being diagnosed as something else, or not diagnosed at all. Having infections going unrecognised makes it difficult for scientists to obtain sufficient samples to perform research on.

“There’s a general acceptance that [hantaviruses] are a nightmare to grow,” explains Dr Lorraine McElhinney, who works at the Animal & Plant Health Agency (APHA). “You can’t look at the properties of viruses if you can’t get optimal models to replicate what you’re seeing in humans.”

Being difficult to grow makes it a challenge to gather enough genetic material to sequence. In 2013, Lorraine’s group published a paper that identified a new hantavirus in the UK, isolated from a wild field vole, suggesting that there are many more of these viruses waiting to be discovered. The team is having trouble getting it to replicate in laboratory cell lines, so we don’t know much about what it is, or if there is a risk to public health. Further studies currently underway at APHA and the University of Liverpool may provide some answers.

Given that the number of rodent species is huge, it’s likely that the more we search, the more of these viruses will be found. Some of the infected – shrews, moles and some bats – are known to feed on insects, so there is the intriguing possibility that there are other non-rodent hosts yet to be found. This makes some sense given that other members of the Bunyaviridae family of viruses, to which the Hantavirus genus belongs, are transmitted by the bites of arthropods such as mosquitoes or ticks.

There remains much we don’t know about hantaviruses, particularly around the complex interactions of climate, habitat and host. However, this complexity should not be a deterrent – prior to 1993, the Sin Nombre virus was unknown, yet its first identified outbreak killed 12 people, showing that this group of microbes is not one that we should ignore.