AnimalNet Nov. 10/05 -- II

Bird flu spreads further in Asia

Bird flu virus triggers worse inflammation in human lung cells than human flu viruses

Recent outbreak of rabies infections in Brazil transmitted by vampire bats

Can anthrax be controlled?

Bats as the reservoir for outbreaks of emerging infectious diseases

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Bird flu spreads further in Asia
November 10, 2005
Reuters/AP
BEIJING - Three Asian nations were cited as reporting new outbreaks of bird flu in poultry on Thursday, a day after health experts unveiled a $1 billion global plan to halt the spread of the deadly virus.
China, Vietnam and Thailand were cited as saying they had more outbreaks as the region heads into the northern winter, when the H5N1 avian flu virus seems to thrive.
Vietnam, where the virus has killed 42 people, will send soldiers and police to help contain avian flu, and Agriculture Minister Cao Duc Phat was cited as saying in Nong Nghiep Vietnam, a newspaper run by his ministry, that provincial authorities must do more, adding, "We must launch a campaign to build each hamlet, each commune into a stronghold for fighting the epidemic. In an emergency, the army will be deployed to isolate the infected area."
Another Vietnamese official was cited as saying the sudden death of a flock of ducks also suggested a more virulent strain was at work.
Chinese state media reported two new outbreaks in poultry in the northeast, bringing the total number of outbreaks to six since the start of last month. Thailand said tests confirmed the presence of H5N1 in two provinces next to the capital Bangkok, a city of 10 million people.
The World Health Organization said it was sending experts to southern China to help investigate whether bird flu killed a 12-year-old girl last month.



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Bird flu virus triggers worse inflammation in human lung cells than human flu viruses
November 10, 2005
BioMed Central
Scientists might have identified one of the reasons why the bird flu virus H5N1 is so deadly to humans. A study published today in the open access journal Respiratory Research reveals that, in human cells, the virus can trigger levels of inflammatory proteins more than 10 times higher than the common human flu virus H1N1. This might contribute to the unusual severity of the disease caused by H5N1 in humans, which can escalate into life-threatening pneumonia and acute respiratory distress.
Michael Chan and colleagues from the University of Hong Kong and collaborators in Vietnam, studied the levels of a subset of the pro-inflammatory proteins called 'cytokines' and 'chemokines', induced by the virus H5N1 in human lung cells, in vitro. The authors compared protein levels induced by strains of the H5N1 virus that had appeared in Hong Kong in 1997 (H5N1/97) and Vietnam in 2004 (H5N1/04), with levels induced by the human flu virus H1N1.
Their results show that H5N1 is a much more potent inducer of pro-inflammatory proteins than H1N1. Twenty-four hours after infection with H5N1/04, the levels of the chemokine IP-10 in bronchial epithelial cells reach 2200 pg/ml, whereas in cells infected with H1N1 they only reach 200pg/ml. In H5N1/97-infected cells, IP-10 levels reach 1750 pg/ml. Similar results were found for other chemokines and cytokines.
Chemokines and cytokines are the "messengers of the immune system" and are critical in coordinating and regulating the immune response. Altering this balance is likely to lead to an uncontrolled inflammatory response in the lung and probably explains, at least in part, the severe lung inflammation associated with avian flu virus H5N1.



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Recent outbreak of rabies infections in Brazil transmitted by vampire bats
November 10, 2005
Eurosurveillance Weekly Release Volume 10 - issue 45Eurosurveillance Weekly Release Volume 10 - issue 45
Ravindra Gupta (ravi.gupta@hpa.org.uk), Centre for Infections, Health Protection Agency, London, United Kingdom
On 25 October 2005, the Brazilian ministry of health reported a new focus of human rabies infections transmitted by blood eating vampire bats (Desmodus rotundus) in northeast Brazil [1]. Twelve deaths were reported in Turiaçú, in the state of Maranhão in October 2005. Rabies deaths have also been reported in 2005 in Godofredo Viana (3), Cândido Mendes (2) and Carutapera (2) [1], and the local media reports that several hundred may have been bitten by bats. [4]. These areas are in the north of Maranhão, next to the focus of a bat-transmitted human rabies outbreak in the state of Pará in 2004 [1,5]. During the recent outbreak, media reports noted that nocturnal biting coincided with the failure of a regional generator which left people without electricity for six weeks [4].
Between 1986 and 2004, the ministry of health was notified of 743 human rabies cases in Brazil, most of which occurred in the north and northeast of the country [1]. Numbers of cases had been falling steadily from 1980 (over 170 cases) to 2003 (under 20 cases), mainly due to control of rabies in dog populations. Up to 2003, most human rabies infections notified in Brazil were transmitted in an urban setting by cats or dogs, but most infections since 2004 have been transmitted by bats in rural parts of the states of Pará and Maranhão [1,5]. Outbreaks of bat-related rabies have been linked to the continued deforestation of the Amazon region, which has displaced vampire bats across northern Brazil and increased contact with humans [2]. The ministry of health also notes that abandoned gold mines in Maranhão have provided favourable habitats for bat populations [5].
Vaccination and bat-catching teams are working in the region to try to prevent the spread of infection. A meeting between the authorities from two states affected in 2004 and 2005 was held in October to coordinate outbreak control activities.
Worldwide, rabies causes approximately 55 000 deaths per year [6]. Rabies viruses are transmitted to humans via saliva from bites of carnivores and chiropterans (bats). Bats may be frugivorous (fruit eating), hematophagous (blood eating), or insectivorous (insect eating). Transmission from carnivores has been controlled in Europe by vaccination of domestic cats and dogs and oral vaccination of wildlife. Vampire bats (Desmodus rotundus) feed on blood from warm blooded animals such as horses and cattle. They are not native to Europe and other species of bat found in Europe are not known to be reservoirs of classical (genotype 1) rabies. Bats with rabies may behave abnormally, which may partly explain the uncharacteristic behaviour of human biting exhibited in the Brazilian outbreaks.
Current World Health Organization guidelines on rabies pre-exposure prophylaxis state that rabies vaccine should be offered to visitors travelling or living in areas where rabies is endemic. The vaccine is given at 0, 7 and 21 or 28 days [7]. Following a bite or exposure of mucous membrane to saliva, vigorous washing with soap, water and application of ethanol or iodine to the wound is recommended to decrease the risk of rabies transmission. For previously unvaccinated people, the area surrounding the wound should be injected with rabies immunoglobulin (RIG) as soon as possible after washing, followed by intramuscular vaccination with five doses of inactivated cell culture or duck embryo vaccine [8].
The extent of the outbreak in Brazil is not yet fully understood, and therefore the risk to travellers is not completely defined. Vaccination should be considered for travellers to the affected area of the country, especially if they will be in remote areas for a long time [9]. Such travellers should be informed of the need for prompt treatment in the event of a rabies exposure. Sleeping in enclosed areas protected by an intact building structure or screening and netting should decrease exposure. Anyone returning from the Amazon region with a possible animal bite should be immediately referred for a specialist assessment regarding post-exposure prophylaxis.
References:
1. Ministério Da Saúde. Raiva Humana transmitida por morcegos no Estado do Pará e Maranhão. 25 October 2005
2. Promed. Brazil: 23 Deaths in Vampire Bat Rabies Outbreak in Maranhao State. ProMED-mail [online]. Boston US: International Society for Infectious Diseases, archive no. 20051102.3202, 2 November 2005. (http://www.promedmail.org)
3. Rabies, human, vampire bats - Brazil (Maranhao)(02). In: ProMED-mail [online]. Boston US: International Society for Infectious Diseases, archive no. 20051027.3133, 27 October 2005. (http://www.promedmail.org)
4. Rabies, human, vampire bats - Brazil (Maranhao). In: ProMED-mail [online]. Boston US: International Society for Infectious Diseases, archive no. 20051024.3100, 24October 2005. (http://www.promedmail.org)
5. MINISTÉRIO DA SAÚDE, SECRETARIA DE VIGILÂNCIA EM SAÚDE (Brasilia). Raiva humana transmitida por morcegos no estado do maranhão. 25 July 2005 (http://portal.saude.gov.br/portal/arquivos/pdf/Nota%20Tecnica%20%20MA%20surto%20de%20raiva%20humana%2025%2007%2005.pdf)
6. WHO Expert Consultation on Rabies. First report. (WHO technical report series 931 Geneva: World Health Organization; 2004. (http://www.who.int/rabies/trs931_%2006_05.pdf)
7. Vaccine preventable diseases, vaccines and vaccination. In: WHO International Health and Travel Publication. Geneva: World Health Organization; 2005. (http://whqlibdoc.who.int/publications/2005/9241580364_chap6.pdf)
8. Rabies [2005]. In: Immunisation Against Infectious Disease. London: Department of Health; 1996 (new chapters available online, May 2005) http://www.dh.gov.uk/assetRoot/04/11/09/70/04110970.pdf
9. National Travel Health Network and Centre (NaTHNaC, London). Clinical update: rabies in Brazil. 9 November 2005 (http://www.nathnac.org/pro/clinical_updates/rabies_Brazil_091105.htm)



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Can anthrax be controlled?
November 10, 2005
Max-Planck-Gesellschaft
Max Planck Researchers discover a protein which is deadly for anthrax bacteria
Scientists from the Max Planck Institute for Infection Biology in Berlin discovered why lung, but not skin, anthrax infections are lethal. As reported in the newest issue of PloS Pathogen (November 2005) Neutrophils, a form of white blood cells, play a key role in anthrax infections.
They can kill Bacillus anthracis by producing a protein called alpha-defensin. This discovery might now pave the way towards the development of new therapiesfor the fatal lung form of anthrax.
Bacillus anthracis is the causative agent of anthrax. What makes Bacillus anthracis especially dangerous is that these bacteria can form spores. The spores are extremely resistant against environmental stress and can survive for years.Infection with Bacillus anthracis can take place either via the lung or through the skin. Interestingly, the lung form of anthrax is almost always fatal, whereas skin infections remain localized and are rarely lethal. In contrast to the lung form, the skin form of anthrax can be treated without problems and most patients recover. During the past few years, Bacillus anthracis has also been used as a weapon for bioterrorism. Anthrax spores were sent in envelopes and inhaled and resulted in the death of 5 people in the USA.
The findings of the lab of Arturo Zychlinsky now help clarifying why the skin form is harmless in contrast to the lung form. After a skin infection with Bacillus anthracis, neutrophils are recruited to the site of infection. Neutrophils are white blood cells that can identify and kill microbes. In the skin, neutrophils take up the spores, which germinate inside the neutrophil to a vegetative ("growing") bacterium. This vegetative bacterium is then attacked and killed within the neutrophil. The scientists succeeded in identifying the substance responsible for the killing of the bacteria. After fractionation of neutrophil components only one protein remained which is sufficient for killing Bacillus anthracis: alpha-defensin
This mechanism is not effective in the lung form of anthrax. Here, the number of neutrophils recruited to the site of infection is known to be low, and insufficient to kill bacteria. Thus, inhaled spores can germinate and spread through the organism. The scientists in Berlin now hope that their discovery will help to develop new drugs against the lung form of anthrax. There might be the possibility that the inhalation of alphadefensin might kill vegetative bacteria in the lung and prevent dissemination.



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Bats as the reservoir for outbreaks of emerging infectious diseases
November 10, 2005
Eurosurveillance Weekly Release Volume 10 - issue 45Eurosurveillance Weekly Release Volume 10 - issue 45
Chris J Williams (kitwilliams@nhs.net), Health Protection Agency Centre for Infections, London, United Kingdom
A study from China has provided evidence that bats may be the natural reservoir for severe acute respiratory syndrome coronavirus (SARS-CoV) [1]. Bats are already well recognised as a potential source of human rabies cases caused by bat lyssavirus, and of emerging viral infections such as Nipah virus [2]. Bats may also be a host for Ebola virus [3]. Direct interactions between bats and humans are rare, although there are exceptions, such as the trained bat handlers in many countries. However, changing ecology or other circumstances can bring endemic bat infections to humans by means of an intermediary species [4] and this may have occurred in the case of SARS.
Since the emergence of SARS-CoV in 2003, researchers have been seeking the original source of the infection. SARS-CoV was discovered in palm civets in Chinese markets, leading to culling of these cat-like animals. Further studies have shown that civets infected with SARS-CoV show symptoms of disease, and the virus has not been found in other civet populations, suggesting that civets are not the natural reservoir [5,6].
Researchers in China have recently identified viruses similar to human SARS-CoV in three species of horseshoe bat. In four locations in China, they collected blood, faecal and throat samples from 408 bats representing nine species. Three species of horseshoe bat (genus Rhinolophus) showed a high prevalence (28%-71%) of antibodies to SARS-CoV, consistent with their being a wildlife reservoir for this virus. The viruses found in these bats were further characterised using PCR, and putative evolutionary relationships to other coronaviruses were determined, based on conserved and variable viral proteins. These analyses suggested that the viruses were closely related to human SARS-CoV, with 92% sequence identity.
Bats may pass disease onto humans directly through biting or salivary contact (European bat lyssavirus [7]), or through human ingestion of food chewed by the bat (Nipah virus [4]). Another probably more common route is transmission through another species, which is in contact with both bats and humans. Changing circumstances, such as bringing livestock into areas populated by bats, or selling bats or bat products in markets where other animals are present, may cause a ’spillover’ of infection into a new species [4,8]. In the case of SARS this may have been the palm civet [6], sold in markets alongside bats; in the case of Nipah virus, it is domesticated livestock [2]. Transmission of Nipah and Hendra viruses may follow ingestion of insects or fruit partly digested by bats [4], and a similar mechanism is suggested to account for the presence of Ebola virus in primates and duikers following fruiting events [4]. The intermediate animal may amplify the infection, increasing the chances of transmission to humans.
Bats comprise 20% of the diversity of mammalian species, so it should not be surprising that they are the zoonotic host for a number of infections. Expert opinion is that they are not over-represented as hosts for infections [4]. Why infections endemic in bats should be so pathogenic in humans is less clear, but may relate to the (currently poorly understood) bat immune system: bats, lacking bone marrow in their hollow bones, may have different antiviral responses, possibly including viral inhibitors.
What are the implications for humans and bats in Europe? Horseshoe bats are widely distributed from Australia to Europe, but the species cited in the Chinese study are not indigenous to Europe [9]. Bat migration, and trade in bats for traditional medicines, have the potential to introduce new infections into European bat species. There are also risks from the spillover effect: intermediary species may be imported having already acquired infection from bats, or could acquire infections already endemic in European bats [10]. Finally, global travel and migration mean that new human infections arising anywhere in the world could potentially become a problem in Europe.
References:
1. Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH et al. Bats are natural reservoirs of SARS-like coronaviruses. Science 2005;310:676-9. (http://www.sciencemag.org/cgi/content/full/sci;310/5748/676)
2. Field H, Young P, Yob JM, Mills J, Hall L, Mackenzie J. The natural history of Hendra and Nipah viruses. Microbes Infect 2001; 3(4): 307-314
3. Pourrut X, Kumulungui B, Wittmann T, Moussavou G, Delicat A, Yaba P et al. The natural history of Ebola virus in Africa. Microbes Infect 2005;7:1005-1014.
4. Dobson A.P. What links bats to emerging infectious diseases. Science 2005;310:628-9. (http://www.sciencemag.org/cgi/content/full/310/5748/628)
5. Wu D, Tu C, Xin C, Xuan H, Meng Q, Liu Y et al. Civets are equally susceptible to experimental infection by two different severe acute respiratory syndrome coronavirus isolates. J Virol 2005;79:2620-2625.
6. Tu C, Crameri G, Kong X, Chen J, Sun Y, Yu M et al. Antibodies to SARS coronavirus in civets. Emerg Infect Dis 2004;10:2244-2248.
7. Fooks AR, McElhinney LM, Pounder DJ, Finnegan CJ, Mansfield K, Johnson N et al. Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. J Med Virol 2003;71:281-289.
8. Childs JE. Zoonotic viruses of wildlife: hither from yon. Arch Virol Suppl 2004;1-11.
9. EUROBATS secretariat [homepage on the internet]. Bonn: UNEP / EUROBATS Secretariat; c2005 The agreement on the conservation of populations of European bats: Protected species.(http://www.eurobats.org/about/protected_species.htm) [accessed 8 November 2005]
10. Muller T, Cox J, Peter W, Schafer R, Johnson N, McElhinney LM et al. Spill-over of European bat lyssavirus type 1 into a stone marten (Martes foina) in Germany. J Vet Med B Infect Dis Vet Public Health 2004;51:49-54.
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