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19 June 2003 marked 100 days from the World Health Organization (WHO) alert issued in response to an alarming epidemic in humans that had broken out in Hong Kong Special Administrative Region, China. Now that the disease seems to be on the wane, it is an opportune time to review what happened.
In retrospect, as early as November 2002, cases of an atypical acute respiratory disease of unknown aetiology were starting to occur in Guangdong Province in southern China. The epidemic picked up pace from January 2003, and was at its height from March to May 2003. Infection and disease spread across the world, highlighting the extent of international travel. The countries most seriously affected were China, Viet Nam and Canada.
Uninformed conjecture that the virus originated in farmed livestock, combined with conspiracy theories about the large-scale "hiding" of information, caused alarm. This threatened to have a severe impact on trade, food consumption patterns, tourism, and commerce in general. On 5 May, FAO issued a press release in the form of an interview on business and tourist travel to inform member countries that there was “no evidence that SARS stems from farm animals”. There is no reason to amend this information. (The FAO press release is available at http://www.fao.org/english/newsroom/news/2003/17263-en.html.)
Probable cases of SARS worldwide, by date of onset (n = 5 923) 1 November 2002 to 16 June 2003*
* Does not include 2 537 probable cases for which no onset dates are available.
Source: Ministry of Health, China; WHO.
The causative virus was soon identified as a coronavirus, and it was characterized by early May. The results indicate that the SARS coronavirus is not related closely to any of the previously characterized coronaviruses but forms a distinct group within the genus Coronavirus. It is approximately equidistant from all previously characterized coronaviruses, just as the existing groups are all equidistant from one another. It was concluded that: “the genetic distance between the SARS coronavirus and any other coronavirus in all gene regions implies that no large part of the … genome was derived from other known viruses. The … genomic sequence does not provide obvious clues concerning the potential animal origins of this pathogen”; and that: “The genome of SARS-Coronavirus has several unique features that could be of biological significance. The short anchor of the spike-protein, the specific number and location of small open reading frames (ORFs), and the presence of only one copy of the PLPpro provide a combination of genetic features that readily differentiate this virus from previously described coronaviruses” (Rota et al., 2003).
Phylogenetic analysis |
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Similarly, Marra et al. (2003) concluded: “Although morphologically a coronavirus, this SARS virus is not more closely related to any of the three known classes of coronavirus, and we propose that it defines a fourth class of coronavirus (group 4) and that it be referred to as SARS-Coronavirus. Our sequence data do not support a recent interviral recombination event between the known coronavirus groups as the origin of this virus, but this may be due to the limited number of known coronavirus genome sequences. Apart from the s2m motif located in the 3'UTR, there is also no evidence of any exchange of genetic material between the SARS virus and non-Coronaviridae. These data are consistent with the hypothesis that an animal virus for which the normal host is currently unknown recently mutated and developed the ability to productively infect humans. There also remains the possibility that the SARS virus evolved from a previously harmless human coronavirus. However, preliminary evidence suggests that antibodies to this virus are absent in people not infected with SARS-Coronavirus, which implies that a benign virus closely related to the [SARS coronavirus] isolate is not resident in humans.”
WHO carried stories in May that scientists had found a closely related coronavirus infecting a number of viverid and mustelid carnivores |
Following the trail, WHO carried stories in May that scientists had found a closely related coronavirus infecting a number of viverid and mustelid carnivores (masked palm civets, raccoon dogs and ferret badgers), which were on sale in markets. For this reason, they believed that the SARS virus originated from these wild animals. However, elements of the story cast doubt on these animals as the source of the SARS coronavirus. A high proportion of the animals tested were found to be excreting virus, and therefore acutely infected. This suggested that they had acquired infection recently and so were most likely to have picked it up in the market or at assembly points. The true origin of the coronavirus could have been any of a wide spectrum of animals or animal products being sold through markets; it could even have originated in humans. The animals mentioned are distributed primarily in low-altitude mountainous areas in tropical and subtropical regions. Many are reared in captivity and can be purchased live at animal markets and restaurants in the cities of Guangdong Province. Others might be caught in the nearby mountains, and one report claims that trade in these animals from Viet Nam has developed over the last two years.
The virus found in the civet cats (Paguma larvata) is not identical to the coronavirus found in SARS patients; the human virus has 29 fewer nucleotides in the N-protein gene. According to the Chinese People's Daily newspaper, Guan Yi, a doctor at the University of Hong Kong's Department of Microbiology, said: “We have charted a complete genetic map of the SARS-like coronavirus detected in the Himalayan palm civet, which shares 99.8 percent of the genetic code of the human SARS coronavirus.”
In an interview reported in The Scientist, Dr Klaus Stöhr, director of WHO's global SARS laboratory network, said: “The human virus has a deletion. We think the N-protein is attached to the interior of the virus envelope, but our knowledge about this is schematic. We don't know what the protein is doing.” The sequence of the animal virus was compared with 60 sequences of human SARS virus being held in a library to which the Chinese researchers have access. “With the exception of … 29 nucleotides, they were identical,” said Stöhr. “But there was one human virus which didn't have this deletion. This was one called 'GZ1'. But we don't know more about that sample, where it came from, what the person had when he became ill - we have no clue what it means at present.”
Transmission occurs readily from droplets exhaled from the respiratory tract of infected people. However, the virus can survive for days in human diarrhoeic excreta, a fact that was possibly involved in the explosive development of outbreaks in some situations. Epidemiological evidence collated by WHO indicated that infections were primarily nosocomial (acquired in hospital), and - despite initial fears - very few cases were acquired during air travel. Thus, the key to control was realized to be improving the biosecurity and sanitation procedures surrounding patients admitted to hospital. Very few transmission events (fewer than 40) occurred during air travel. Data reported on the WHO network show that all the six index cases from four cities in Guandong Province had either eaten or dealt with wildlife, particularly snakes, ten days before they fell ill. Stöhr went on to say: “We don't know what the snakes mean, but broadly this appears to be another piece fitting into the pattern.”
FAO assisted its sister agency in attempting to gather information on livestock diseases in China that could provide possible clues as to the origin of SARS. To date, no such connection has been ascertained |
Evidence is now emerging that there may have been many subclinical infections with SARS coronavirus during the epidemic of acute disease.
During February, FAO assisted its sister agency in attempting to gather information on livestock diseases in China that could provide possible clues as to the origin of SARS. To date, no such connection has been ascertained.
WHO convened a Global Conference on Severe Acute Respiratory Syndrome from 17 to 18 June 2003 in Kuala Lumpur. The FAO Emergency Prevention System for Transboundary Animal Diseases (EMPRES) was represented by Dr Laurence Gleeson of the Australian Animal Health Laboratory (AAHL). The AAHL is a high-biosecurity laboratory linked to FAO-EMPRES as a collaborating centre.
Clearly, much remains to be understood about this virus and its related disease. The description given here may need to be amended in the near future as additional virological, immunological and epidemiological knowledge accrues.
For more information, see: http://www.who.int/csr/sars/en/index.html and: http://www.cdc.gov/ncidod/sars/
In June 2003, a bizarre sequence of events resulted in the appearance of cases of monkeypox virus in humans in the United States of America. This was the first time that the virus had been reported outside the African continent.
Monkeypox is a rare viral disease caused by Monkeypox virus, which belongs to the orthopoxvirus group of viruses occurring in Central and West Africa |
Monkeypox is a rare viral disease caused by Monkeypox virus, which belongs to the orthopoxvirus group of viruses occurring in Central and West Africa. It is called “monkeypox” because it was first isolated in 1958 from laboratory monkeys. Blood tests of animals in Africa later found that other types of animals had experienced monkeypox virus infection. Scientists also recovered the virus that causes monkeypox from an African squirrel. These types of squirrel might be the common host for the disease, although rats, mice and rabbits can be infected experimentally. Monkeypox was first reported in humans in 1970, and it is an important differential diagnosis for smallpox. The virus does not usually transmit well between humans, although such transmission has featured in recent outbreaks in Africa.
The following notes have been prepared from a collation of newspaper and other media articles; they are believed to be substantially correct.
The virus appears to have been introduced into Wisconsin, the United States, in a consignment of Gambian giant rats (Cricetomys sp.) imported from West Africa for the pet trade. There appear to be few restrictions on such trade other than those regarding the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) legislation. It is believed that the rats infected prairie dogs (Cynomys sp.) in pet shops/markets, and that the dogs then passed the infection on to their owners, often via bites. As of 18 June 2003, a total of 87 cases of monkeypox had been reported to Centers for Disease Control and Prevention (CDCs) in the United States: Wisconsin (38), Indiana (24), Illinois (19), Ohio (4), Kansas (1), and Missouri (1). Of the 75 patients for whom data were available, 20 were admitted to hospital. Most patients were not seriously ill; some were admitted to facilitate proper isolation. Most had had direct or close contact with wild or exotic mammals such as prairie dogs. In one instance, 28 children attending a day-care facility in Indiana were potentially exposed to two prairie dogs that subsequently became ill and died; 12 children reported handling or petting the prairie dogs, and 7 subsequently became ill with symptoms consistent with monkeypox infection.
Trace-back investigations of animals are ongoing to identify how monkeypox virus entered into the United States |
Trace-back investigations of animals are ongoing to identify how monkeypox virus entered into the United States. Preliminary results have determined that an animal vendor in Wisconsin sold prairie dogs to the index patient in Wisconsin; this vendor had obtained prairie dogs from an animal vendor in Illinois, who had housed prairie dogs and Gambian giant rats in close proximity.
Because Gambian giant rats are often imported from regions of Africa where monkeypox is endemic, trace-back investigations of the Gambian giant rats were initiated. These investigations identified a shipment of animals from Ghana, which included Gambian giant rats that were delivered to a Texas animal importer on 9 April 2003. These Gambian giant rats were sold on to an Iowa animal vendor on 15 April 2003, who then supplied them to another distributor. The shipment of animals from Ghana contained about 800 small mammals of nine different species, including six genera of African rodents that might have been the source of introduction of monkeypox. These rodent genera included rope squirrels (Funisciurus sp.), tree squirrels (Heliosciurus sp.), Gambian giant rats, brushtail porcupines (Atherurus sp.), dormice (Graphiurus sp.) and striped mice (Hybomys sp.). Laboratory testing of animals from the 9 April 2003 importation from Africa is under way to determine which, if any, of the animals might have introduced the virus into the United States.
On the basis of the epidemiological link with the shipment from Ghana, trace-forward investigations have been initiated to locate the animal vendors and owners who purchased imported African rodents from the 9 April 2003 shipment, or prairie dogs from linked distributors after 15 April 2003. In addition to routine sales by animal vendors, animals are also sold or traded at “swap meets” (gatherings of animal traders, exhibitors and buyers). Investigation of one distributor revealed that infected prairie dogs from this animal vendor might have been sold or traded to unidentified buyers at swap meets in the United States, in particular at: Schaumburg, Illinois, on 20 April 2003, 3 May 2003 and 18 May 2003; Indianapolis, Indiana, on 27 April 2003 and 18 May 2003; and Columbus, Ohio, on 19 April 2003. In addition, another distributor sold infected prairie dogs at a swap meet in Wausau, Wisconsin, on 11 May 2003. In several instances, it has been impossible to identify the buyers. Invoices and other records are incomplete for many of these sales, especially those transacted at swap meets.
In order to calm fears that a large epidemic may develop, smallpox vaccine could be issued for use in people who are at high risk.
For more information, see: http://www.cdc.gov/ncidod/monkeypox/index.htm.
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Rota, P.A., Oberste, M.S., Monroe, S.S., Nix, W.A., Campagnoli, R., Icenogle, J.P., Peñaranda, S., Bankamp, B., Maher, K., Chen, M., Tong, S., Tamin, A., Lowe, L., Frace, M., DeRisi, J.L., Chen, Q., Wang, D., Erdman, D.D., Peret, T.C.T., Burns, C., Ksiazek, T.G., Rollin, P.E., Sanchez, A., Liffick, S., Holloway, B., Limor, J., McCaustland, K., Olsen-Rasmussen, M., Fouchier, R., Günther, S., Osterhaus, A.D.M.E., Drosten, C., Pallansch, M.A., Anderson, L.J. & Bellini, W.J. 2003. Characterization of a novel Coronavirus associated with severe acute respiratory syndrome. Science, 300: 1394-1399. (Originally published in Science Express as 10.1126/science.1085952 on 1 May 2003)
