VIRUS

Family portrait

Research into Type A influenza virus. Clumping of hen red corpuscles (red blood cells) as a result of the influenza virus – total agglutination. © Institut Pasteur
Research into Type A influenza virus. Clumping of hen red corpuscles (red blood cells) as a result of the influenza virus – total agglutination. © Institut Pasteur
Influenza virus cultured in embryonated chicken eggs. © Institut Pasteur
Influenza virus cultured in embryonated chicken eggs. © Institut Pasteur
Chikungunya virus isolated from a patient on Réunion Island. © Institut Pasteur
Chikungunya virus isolated from a patient on Réunion Island. © Institut Pasteur
Example of a polluted site colonised by breeding mosquitoes. © CNRS Photothèque/Nicole Pasteur
Example of a polluted site colonised by breeding mosquitoes. © CNRS Photothèque/Nicole Pasteur
SARS research unit – Centers for Disease Control and Prevention (US). © James Gathany
SARS research unit – Centers for Disease Control and Prevention (US). © James Gathany
Coronavirus identified by Sylvie van der Werf’s team at Institut Pasteur (FR) in March 2003 as responsible for SARS © Institut Pasteur
Coronavirus identified by Sylvie van der Werf’s team at Institut Pasteur (FR) in March 2003 as responsible for SARS © Institut Pasteur

The virus family is a motley crew whose members include RNA and DNA (single- or doublestranded,with or without a protein envelope). Viruses are often classified according to how they look under the electronic microscope, such as the star-shaped Astroviridae viruses. Here we examine three notoriously vicious viruses.

The inexorable rise of H5N1

Since it was first isolated in Scottish chickens in 1959, the H5N1 avian influenza virus has travelled to the four corners of the Earth and raised many questions. According to the June 2007 report by the World Health Organization (WHO), the toll so far is 310 people infected and 189 dead. Although this is far short of the 55 000 rabies victims every year, the H5N1 virus certainly seems to be stealthily honing its weapons with the ultimate aim of adapting to the human race. And the greater the number of human cases, the more likely it becomes that a variant of the virus will succeed in adapting to humans.

On its six-stage scale of pandemic risk, WHO has categorised the current risk from H5N1 at stage 3. While the virus attacks humans incidentally, the main targets of its increased virulence are wildfowl and domestic poultry. The natural reservoirs of a number of influenza viruses, wildfowl have traditionally been asymptomatic carriers. However, the epizootic that began in 1996 has changed all this: since the first case of H5N1 was reported in a goose in the Chinese province of Guangdong, this escalating new virus has notched up a whole string of firsts. 18 first-ever human cases were detected in Hong Kong in 1997, six of which resulted in death. The outbreak was only brought under control by slaughtering 1.5 million chickens on farms and in the city's markets.

The first cases of wildfowl to fall sick from the virus occurred in 2002, also in Hong Kong. The first case of a fatal infection of two tigers and two leopards in a zoo was reported in Thailand in December 2003. The first possible case of person-to-person transmission in September 2004, where a child may have infected its mother, also occurred in Thailand. The first case reported in Western Europe was of an imported parrot in October 2005.

The H5N1 virus is diversifying its victims and undergoing genetic mutations that are making it increasingly virulent. It has become WHO viral public enemy number one, and the Organization has developed a strategic action plan to anticipate a fully-fledged pandemic (stage 6 on the scale of risk). Not all experts share the WHO conviction that such a threat is imminent, and it is difficult to estimate the probability of a global H5N1 pandemic. If the virus were to become humanised, with or without genetic recombination with another virus, would it be as dangerous as the avian influenza virus? In any case, WHO plans the international coordination of H5N1 epidemic surveillance based on the most pessimistic predictions.

Meanwhile, the unpredictable H5N1 virus has prompted feverish research in every field, including the study of wildfowl migration routes, epidemic early warning systems, improvements in specific diagnostic methods, influenza virus genetics and the containment of epidemic outbreaks, to mention but a few.

The main problem with vaccine production is in selecting base strains, as the virus is evolving continuously. On 16 June 2008, Sanofi Pasteur, the vaccine division of the Sanofiaventis Group that created the first human H5N1 vaccine to be licensed by the United States Food and Drug Administration in 2007, announced its commitment to donate 60 million doses of H5N1 vaccine to WHO over three years for the setting up of an H5N1 vaccine global stockpile.

Chikungunya, a virus spread by mosquitoes

The source of the Chikungunya epidemic, which broke out on France's Réunion Island in February 2006, infecting 40% of its population, can be traced back to Kenya in June 2004.

Antoine Flahault, a doctor and biostatistician commissioned by the French government to coordinate an epidemic-control task force, says: "There was a serious drought in Kenya between December 2003 and June 2004.

Usually it is the rains that cause mosquitoes to proliferate but, for the Chikungunya vector (the yellow fever mosquito Aedes aegypti), it was drought." Aedes aegypti tends to live close to human dwellings and the female deposits her larvae in clear water, such as a water jug. "Aedes aegypti is a mosquito that usually lives in our gardens."(1) As a result of the drought, Kenyans were obliged to store their water for several days and this was all the time needed for the larvae to hatch. "You need to understand the life of the Aedes aegypti mosquito: it bites during the day, between a few hours after dawn until an hour or so after sunset, but does not tend to enter people's homes, making a mosquito net futile." The Chikungunya virus was first isolated during an outbreak of the disease in southern Tanzania in 1952. The term ‘Chikungunya' derives from a root verb in the Kimakonde language, meaning ‘to be contorted', and describes the stooped appearance of Chikungunya sufferers with joint pain. From Kenya, where the virus attacked 75% of the population of Lamu and Mombasa, the East African strain of the virus was carried to the Comoro Islands in late 2004, before reaching the coast of Mayotte in February 2005 and travelling from there to Réunion Island. The adaptation of the virus to a cousin of Aedes aegypti, the Asian tiger mosquito Aedes albopictus, has led to an unprecedented spread of the disease that has surprised scientists. "The entomologists consulted in 2005 did not believe it possible for a Chikungunya epidemic to occur in Réunion, because Aedes albopictus is the predominant mosquito on the island and Chikungunya was thought to be a disease specific to Aedes aegypti." The species barrier is fragile indeed...

SARS, the first scare of the millennium

Severe acute respiratory syndrome (SARS) can claim to have thrown early 21st century epidemiologists into a flat spin. The images of Asian's urban populations wearing masks to protect themselves against infection in 2003 are still a raw memory. The SARS virus is highly infectious as it affects the respiratory system. When suffers cough, they infect the people around them. SARS is an entirely new pathology that emerged in the Chinese province of Guangdong in late 2002 and spread to Hong Kong, Taiwan, Singapore and Canada in the ensuing 30 months.

Why so many places at once? In February 2003, a man from Guangdong travelled to the Metropole Hotel in Hong Kong where he infected 17 guests who then continued on their travels.

On China Airlines Flight 112 from Hong Kong to Beijing in March 2003, one passenger infected at least 22 people. In what almost amounted to a criminal investigation to trace the path of the virus, it was revealed that closely- packed urban living played a major role in the epidemic's spread. A total of 8 422 people were infected across 27 countries, with a mortality rate of 11%. Unprecedented international mobilisation led to rapid deployment of a large-scale research effort during the epidemic.

Apart from a few isolated cases in China in 2004, SARS has disappeared from the human landscape. However, there continues to be round-the-clock surveillance, and SARS is one of four diseases (the others being smallpox, poliomyelitis and the human form of H5N1) for which a single case may constitute a public health emergency of international concern and must be reported to WHO immediately.

The culprit was identified in April 2003: an unknown type of coronavirus, a virus family that owes its name to its crown-shaped appearance under the electronic microscope.

Dubbed SARS-CoV, this newcomer was not the product of a mutation of other known coronaviruses, which cause nothing more serious than the common cold. Work on sequencing its genome began in 2003, in parallel with a hunt for its natural reservoir.

Discovering its origin (in all likelihood animal) is seen as the only means to prevent its re-emergence. The suspected involuntary host is the bat, specimens of which were found to be carrying a virus similar to SARSCoV in China in 2005.

Despite rapid containment of the epidemic, results have been mixed. Hospitals served as little more than centres of contamination, as sick people failed to be diagnosed immediately as carriers. A disease of city-dwellers that is intensified by population concentration and movements, SARS is seen as the archetypal epidemic of the new millennium. Not only has it been an intellectual challenge for scientists, who have used the epidemic to draw lessons for the surveillance of a future pandemic, it has also caught the imagination of disaster movie scriptwriters.

Axel Meunier

  1. All quotations are from Antoine Flahault.


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