Microbe of the Month: The microbiologist as Pied Piper: Bernard Dixon on the strange and sometimes lethal hantaviruses, which spread to humans from rodents
Monday 13 December 1993
Those words, from the Nobel prize- winner Sir MacFarlane Burnet, were published in his autobiography only 25 years ago. Yet they can already be consigned to the dustbin of history, alongside the assurance by astronomer royal Sir Richard Woolley in 1956 that space travel was 'utter bilge'. A quarter of a century after Burnet's surprising gaffe, scarcely a week goes by without the announcement of some application of the science whose practical significance he derided.
One wonders what the Australian immunologist would make of developments such as the identification of genes predisposing individuals to inherited diseases, the genetic engineering of pest-resistant crops, and the retrieval of DNA from the tissues of extinct animals.
One advance of which he would surely approve is the dramatic transformation in scientists' tools for investigating infectious diseases. Typical is a mysterious and lethal form of pneumonia that appeared in New Mexico last May. Six months later, scientists at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, have identified the virus responsible by using molecular biology to demonstrate its kinship with one that causes a milder disease in Europe. These and other members of the same family are called hantaviruses, after the Hantaan River in South Korea where yet another family member, Hantaan virus, caused fevers and deaths among troops serving in the Korean war.
Research in Atlanta has now revealed the close relationship between eight known hantaviruses, which are carried by rats, mice and other small rodents and in most cases can be transmitted to humans. The technique used to demonstrate this kinship is called the polymerase chain reaction (PCR), which amplifies tiny quantities of DNA. Although the CDC researchers investigating the New Mexico incident did not originally know what microbe they were dealing with, they applied this method to amplify DNA from the tissues of dead victims. They were thus able to compare the DNA with that of other, familiar microbes. They found that it resembled two other hantaviruses, including Puumala virus, which occurs in Scandinavia and elsewhere in Europe.
The New Mexico virus came to light when a young man died in hospital a few days after attending the funeral of his fiancee. Both had succumbed to sudden, acute chest infection. At least 40 others were attacked by the same virus, now known to be transmitted by deer mice, and 26 of them have died. The other hantaviruses affecting humans produce a condition known as haemorrhagic fever with renal syndrome (HFRS), characterised by haemorrhages and kidney failure. Despite these effects, HFRS is significantly less lethal. Hantaan virus killed 7 per cent of its victims during the Korean war, while Puumala virus has mortality of less than 1 per cent.
Recent recognition of the relationship between the hantaviruses, facilitated by PCR, has coincided with an increasing realisation that they pose a threat to human health in many parts of the world and certainly whenever infected rodents are in contact with humans. The virus appears to be transmitted by aerosol from the animals' urine and faeces.
Any increase in the size of an infected rodent population almost inevitably triggers a rise in human infections. The New Mexico outbreak has been traced to a population explosion in deer mice, caused in turn by an abundance of pine nuts and grasshoppers after heavy snows disturbed the ecology of the deserts and mountains last spring. Dr Peter Kulzer, of the University of Wurzburg, writing recently in the Lancet, reported 40 cases of HFRS in Germany in the first half of 1993 - an unusually large number - which he suggests is related to a proliferation of small rodents.
There is little firm information about hantavirus infections in Britain. There were two cases in Scotland during the 1980s and earlier this year scientists at the public health laboratory in Taunton reported an acute illness in 29 patients with antibodies indicating that they had been infected with hantavirus. The most severely infected individuals developed a high fever, swelling of the face, neck and extremities, malaise lasting for months, and a tendency to haemorrhage. Many of the patients worked in rat-infested areas, and research is now in progress to determine what proportion of rodents in Somerset carry hantavirus.
Worldwide, an estimated 200,000 people are infected with a hantavirus each year, and between 4,000 and 20,000 of them die as a result. With virtually no treatment yet available, the best hope of reducing this toll, and of combating future outbreaks, rests on the development and application of vaccination - which, in turn, requires better definition of high-risk groups and the geography of the infection. And that, despite Sir MacFarlane Burnet's gloomy prognostication, means more applied molecular biology.
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