Saturday, October 13, 2012

Pub Med: H5N1 highly pathogenic avian influenza virus isolated from conjunctiva of a whooper swan with neurological signs

Arch Virol. 2012 Oct 10. [Epub ahead of print]

Affiliation

Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, 2-11 Inada, Obihiro, Hokkaido, 080-8555, Japan.

Abstract

An H5N1 highly pathogenic avian influenza virus was isolated from conjunctiva of a whooper swan with neurological signs, which was captured during the latest H5N1 HPAI outbreak in Japan. The conjunctival swab contained a larger amount of the virus in comparison with the tracheal swab. This is the first report on H5N1 virus isolation from the conjunctiva of a wild bird, and the result may suggest the conjunctival swab to be a critical sample for H5N1 HPAIV detection in waterfowl. Phylogenetic analysis of the HA gene indicated that the virus falls into H5N1 clade 2.3.2.1.

PMID

23053526 [PubMed - as supplied by publisher]
 
[Editing is mine]

Saudi Arabia: Pilgrims’ health satisfactory: MoH

October 12, 2012

RIYADH — The recently detected coronavirus does not pose any threat to the health of pilgrims, Dr. Ziad Memish, Deputy Health Minister for Public Health, announced here Friday. “The virus is not yet a threat to the pilgrims. The health of pilgrims who have arrived as of today (Friday) is satisfactory, and no epidemic or any worrying disease has been detected,” he said.

Dr. Memish said that the ministry is strictly screening all pilgrims at its 16 air, sea, and land ports of entry. It is also monitoring pilgrims compliance with Haj health instructions in their home countries and checking whether the appropriate vaccines have been taken. “Since the ports of entry are the front lines of defense against any passage of infectious diseases, the health authorities at these places have been provided with well-trained healthcare personnel, equipped with the latest devices to detect any symptoms of disease in pilgrims,” he said.

http://www.saudigazette.com.sa/index.cfm?method=home.regcon&contentid=20121013139430

Friday, October 12, 2012

Influenza (98): human-animal interface, WHO

Published Date: 2012-10-11

Date: Mon 1 Oct 2012

Source: WHO, Programmes and Projects [edited]

http://www.who.int/influenza/human_animal_interface/HAI_Risk_Assessment/en/index.html





A. Human infection with avian influenza A(H5N1) virus and associated animal health events:


-----------------------------------------------------


From 2003 through 1 Oct 2012, 608 laboratory-confirmed human cases with avian influenza A(H5N1) virus infection have been officially reported to WHO from 15 countries, of which 359 died. Since January 2012, 30 human cases of influenza A(H5N1) virus infection have been reported to WHO. Since the last update [10 Sep 2012], no new laboratory-confirmed human cases with influenza A(H5N1) virus infection have been reported to WHO. Public health risk assessment for avian influenza A(H5N1) viruses: The public health risk for the virus remains unchanged.



B. Human infection with other non-human influenza viruses


---------------------------------------------------------


A(H3N2) variant virus infection



-------------------------------


The United States of America (USA) reported few additional human cases of influenza A(H3N2)v, and no additional deaths. The large majority of cases have been associated with swine exposure, though instances of likely human-to-human transmission have been identified. No sustained human-to-human transmission has been reported.



Limited serological studies [1-4] indicate that adults may have some pre-existing immunity to this virus but children do not. Seasonal vaccines do not provide cross protection against A (H3N2)v infection. WHO has identified several candidate vaccine viruses specific for A(H3N2)v that could be used to produce an (H3N2)v vaccine if needed [5].



Overall public health risk assessment for influenza A(H3N2)v viruses:

Further human cases and small clusters may be expected as this virus is circulating in the swine population in the USA and people may continue to be exposed, especially through the autumn. Close monitoring of the situation is warranted as schools have started again and changing weather conditions may favor influenza transmission.



A(H1N1) variant virus infections


--------------------------------


As a result of enhanced surveillance around the agricultural fairs, a case of human infection with H1N1 variant influenza virus was detected and reported from the USA [6]. The case occurred in August 2012 in a previously healthy woman. She was not hospitalized and recovered from her illness. The person had direct contact with swine at a State Fair. No further cases were identified. This is the 2nd case of infection with this H1N1v virus in the USA; the previous case occurred in 2011.



Canada also reported a case of human infection with influenza A(H1N1)v in an adult male with underlying risk factors. He developed symptoms at the end of August [2012] and was hospitalized with pneumonia in September. He had occupational exposure to swine. No additional cases have been reported.



The influenza A(H1N1)v viruses isolated from patients in the USA and Canada have an haemagglutinin similar to human seasonal influenza viruses circulating very recently in people, which might suggest some existing population immunity except in young children. Current seasonal vaccines would provide cross protection against these viruses. Available data indicates that the virus would be susceptible to antivirals (neuraminidase inhibitors; oseltamivir and zanamivir).



Overall public health risk assessment for influenza A(H1N1)v viruses:


Further human cases and small clusters of human infection with these viruses may be expected as they are circulating in swine populations. No human-to-human transmission with this virus has been reported. It is expected that the human populations are largely protected by existing immunity except for young children and by the seasonal influenza vaccine.



Because influenza viruses evolve constantly and change characteristics and behavior unpredictably, WHO continues to stress the importance of global monitoring of variant influenza viruses and recommends to all Member States to strengthen routine surveillance activities.



All human infections with non-human influenza viruses as such are reportable to WHO under IHR (2005). More information on influenza at the human-animal interface is available from WHO (http://www.who.int/influenza/human_animal_interface/en/); additional information on influenza in animals is available from OIE (http://www.oie.int/animal-health-in-the-world/web-portal-on-avian-influenza/) and FAO (http://www.fao.org/avianflu/en/index.html), and OFFLU (http://www.offlu.net).



References


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1. CDC. Antibodies cross-reactive to influenza A(H3N2) variant virus and impact of 2010-11 seasonal influenza vaccine on cross-reactive antibodies -- United States. MMWR 2012; 61(14): 237-41; [available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6114a1.htm].

2. Skowronski, et al. Cross-reactive antibody to swine influenza A(H3N2)subtype virus in children and adults before and after immunisation with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010. Euro Surveillance 2012; 17(4); available at http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20066.

3. Waalen et al. Age-dependent prevalence of antibodies cross-reactive to the influenza A(H3N2) variant virus in sera collected in Norway in 2011; Euro Surveillance 2012; 17(19); available at http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20170.

4. Danuta Skowronski, et al. Cross-reactive and vaccine-induced antibody to emerging swine influenza A(H3N2)v, JID 2012; available at http://jid.oxfordjournals.org/content/early/2012/08/07/infdis.jis500.full.pdf+html.

5. WHO. Candidate vaccine viruses for variant influenza A(H3N2); available at http://www.who.int/influenza/vaccines/virus/candidates_reagents/variant_a_h3n2/en/index.html.

6. CDC. H1N2 variant virus detected in Minnesota; available at http://www.cdc.gov/flu/spotlights/h1n2v-cases-mn.htm.



Relevant links


--------------


- WHO table: cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO: http://www.who.int/influenza/human_animal_interface/EN_GIP_LatestCumulativeNumberH5N1cases.pdf

- WHO table: H5N1 avian influenza: timeline of major events http://www.who.int/influenza/human_animal_interface/avian_influenza/H5N1_avian_influenza_update.pdf

- WHO archive: avian influenza situation updates: http://www.who.int/influenza/human_animal_interface/avian_influenza/archive/en/index.html

- World Organisation of Animal Health (OIE) webpage: web portal on avian influenza: http://www.oie.int/animal-health-in-the-world/web-portal-on-avian-influenza/

- Food and Agriculture Organization of the UN (FAO) webpage: avian influenza: http://www.fao.org/avianflu/en/index.html

- Updated unified nomenclature system for the highly pathogenic H5N1 avian influenza viruses: http://www.who.int/influenza/gisrs_laboratory/h5n1_nomenclature/en/index.html



--

communicated by:

ProMED-mail rapporteur Marianne Hopp

[This document includes an epidemiological curve of avian influenza H5N1 cases in humans by country and month of onset, and a useful map of avian influenza H5N1 cases in humans for 2012. Readers are recommended to view these illustrations, which can be accessed, via the source URL above. - Mod.CP]

[all editing is mine]
http://www.promedmail.org/direct.php?id=20121011.1337739

HEALTH HAZARDS - SAUDI ARABIA: UPDATED HAJJ PILGRIMS TRAVEL ADVICE

Published Date: 2012-10-11 17:24:30


This year [2012] the Hajj will take place during [24-29 Oct 2012]. Recent outbreaks of Ebola haemorrhagic fever in Uganda and the Democratic Republic of the Congo, cholera in Sierra Leone, and infections associated with a novel coronavirus in Saudi Arabia and Qatar required review of the health recommendations of the 2012 Hajj. Current guidelines foresee mandatory vaccination with quadrivalent meningococcal vaccine for all pilgrims and yellow fever and poliomyelitis vaccine for pilgrims from high-risk countries. Influenza vaccine is strongly recommended.



The annual Hajj is one of the greatest assemblies of humankind on earth. Each year, 3 million Muslims attend the Hajj in Mecca, Saudi Arabia. Of these, 1.8 million non-Saudi Arabians usually come from overseas countries, and 89 per cent (1.6 millions) of them arrive by air [1]. Pilgrims come from more than 180 countries worldwide, and about 45 000 pilgrims each year arrive to Saudi Arabia from the European Union [2].



Preventive measures during the Hajj:

Saudi Arabia provides free health care to all pilgrims during the Hajj. For the 2012 Hajj, which will take place on [24-29 Oct 2012], the country has prepared 25 hospitals, 4427 beds including 500 critical care beds and 550 emergency care beds. In addition, there are 141 health care centres in the vicinity of the Hajj area with 20 000 specialised health care workers. The planning for the Hajj relies on the coordinated efforts of 24 supervisory committees [2]. The Hajj preventive medicine committee oversees all public health and preventative matters during the Hajj. A large number of public health officers regulate ports of entry for all pilgrims to ensure compliance with the requirements of the Saudi Arabian Ministry of Health. Public health teams are located in various areas of the Hajj, including 21 mobile teams. At each of the 18 hubs at King Abdulaziz International Airport Hajj terminal in Jeddah, 2 clinical examination rooms and a large holding area are dedicated to assess arriving pilgrims, check their immunisation status, and administer the recommended prophylactic medicines [2]. The public health teams and teams at the ports of entry report back to the command centre on 9 communicable diseases using electronic and manual surveillance systems. These diseases are influenza, influenza-like illness, meningococcal disease, food poisoning, viral haemorrhagic fevers, yellow fever, cholera, poliomyelitis, and plague [2].



Pre- and post-Hajj travel advice:

The Hajj is a unique event with possible impact on international public health. Health care practitioners around the world must be attentive to the potential risks of disease transmission during the Hajj. They must recommend appropriate strategies for the prevention and control of communicable diseases before, during, and after the completion of the Hajj. The current international collaboration in planning vaccination campaigns, developing visa quotas, arranging rapid repatriation, and managing health hazards at the Hajj are crucial steps in this process. The Saudi Arabian Ministry of Health publishes the Hajj requirements for each Hajj season. This year's [2012] Hajj recommendations have recently been published [3].



Recent outbreaks of Ebola haemorrhagic fever in Uganda and the Democratic Republic of the Congo (DRC), cholera in Sierra Leone, and infections associated with a novel coronavirus in Saudi Arabia and Qatar required review of the health recommendations of the 2012 Hajj. We present here the changes and additions made in the recommendations for these diseases. For completeness, we also summarise the existing recommendations [3,4].



Meningococcal disease

The risk of the occurrence of meningococcal outbreaks is a real concern during the Hajj seasons. This risk is related to the high carriage rates, with one study from Mecca reporting carriage rate as high as 80 per cent [5]. Due to the previous occurrence of meningococcal outbreaks, the bivalent A and C meningococcal vaccine became a requirement for the attendance of the Hajj in 1986. Two large outbreaks caused by meningococcal serogroup W135 in 2000 and 2001 [6-8] resulted in an extension of the previous requirement to include serogroups Y and W135, and the quadrivalent (A, C, Y, W135) meningococcal polysaccharide vaccine was included as a requirement for a Hajj visa in May 2001 [9]. In addition, visitors arriving from countries in the African meningitis belt receive chemoprophylaxis with ciprofloxacin tablets (500 mg) at the port of entry to lower the rate of meningococcal carriage. It is estimated that about 400 000 to 460 000 pilgrims receive the recommended doses at the port of entry in Saudi Arabia. Compliance with meningococcal vaccination among arriving international pilgrims exceeded 97 per cent in 2011 [1].



Yellow fever

In accordance with the International Health Regulations 2005, all travellers arriving from countries identified by the World Health Organization (WHO) as areas at risk of yellow fever must present a valid yellow fever vaccination certificate showing that the person was vaccinated at least 10 days previously and not more than 10 years before arrival at the border. In the absence of such a certificate, the individual will be placed under strict surveillance for 6 days from the date of vaccination or the last date of potential exposure to infection, whichever is earlier. Health offices at entry points will be responsible for notifying the appropriate director general of health affairs in the region or governorate about the temporary place of residence of the visitor. Aircraft, ships, and other means of transportation arriving from countries affected by yellow fever are requested to submit a certificate indicating that it applied disinfection in accordance with methods recommended by WHO.



Risks of respiratory tract infections

Acute upper respiratory tract infections (URTIs) are the most common disease during Hajj. There are many factors promoting the spread of respiratory pathogens, including close contact among pilgrims, shared sleeping tents, and dense air pollution [2]. The pathogens causing URTIs among pilgrims are respiratory syncytial virus (RSV), parainfluenza virus, influenza virus and adenovirus [10]. The rates of different types of respiratory virus infections are as follows: influenza (9.8 per cent), parainfluenza (7.4 per cent), adenovirus (5.4 per cent) and RSV (1.4 per cent) [11]. Because of overcrowding and the fact that many Muslims come from countries where tuberculosis (TB) is endemic, pulmonary tuberculosis was a leading cause of hospitalisation in patients with community-acquired pneumonia [12]. The estimated risk of tuberculosis acquisition during the Hajj is thought to be around 10 per cent, based on the use of pre-visit and post-visit QuantiFERON TB assay test [13]. In another community-based survey of the epidemiology of tuberculosis in Saudi Arabia, positive tests using purified tuberculin antigens were more frequent in Saudi Arabians living in the Holy cities hosting pilgrims compared to other cities in Saudi Arabia [14]. The development of strategies to reduce the transmission of TB during the Hajj is a challenge for which no evidence-based approved measures are available to date. The Saudi Arabian Ministry of Health continues to recommend wearing face masks in crowded places and changing them frequently to minimise transmission of respiratory infections. Controlling tuberculosis transmission in mass gatherings is an area that needs urgent research studies. [14].



Novel coronavirus infection

Of particular interest is the recent report of 2 cases of acute respiratory failure associated with a novel coronavirus. Both patients were previously healthy adults. The cases occurred a few months before the 2012 Muslim Hajj season. The 1st case of infection with the novel coronavirus was identified in a Saudi Arabian national, who died in June 2012 [15,16]. The 2nd case was a patient from Qatar who was transferred to a hospital in London, United Kingdom in early September 2012 [17]. Available data to date do not support human-to-human transmission of this novel coronavirus, and zoonotic transmission is highly suspected. In the 2nd case of this novel coronavirus infection, none of the 64 close contacts developed severe disease, 13 of them (20 percent) reported mild respiratory symptoms, and the novel coronavirus was not detected in 10 symptomatic contacts who were tested [17].



WHO does not recommend any travel restrictions to or from Saudi Arabia. The current case definitions from WHO [18] and from the Saudi Arabian Ministry of Health can be found on the WHO website (http://www.who.int/csr/disease/coronavirus_infections/case_definition/en/index.html) and in Table 1, respectively. The practice of good hand hygiene and cough etiquette was associated with less respiratory illness among United States travellers to the 2009 Hajj [19]. It is recommended that pilgrims continue to practice proper hand hygiene, protective behaviours and cough etiquette to further decrease the occurrence of respiratory diseases. [see Table 1. Severe respiratory disease associated with novel coronavirus: case definition by the Saudi Arabian Ministry of Health at above given URL link.]



Foodborne diseases and cholera

Diarrhoeal illnesses during mass gathering including Hajj are a potential health hazard. Many factors may contribute to this problem including: inadequate standards of food hygiene, shortage of water, the presence asymptomatic carriers of pathogenic bacteria, and the preparation of large numbers of meals poorly stored by pilgrims. There are only few studies describing the incidence and aetiology of traveller's diarrhoea during the Hajj. In one study, diarrhoea was the 3rd most common cause (6.7 per cent) of hospitalisation [20]. Another study describes an outbreak of diarrhoeal illness in a small number of soldiers during the Hajj season [21]. As a precautionary measure, the Saudi Arabian Ministry of Health strongly enforces that pilgrims are not allowed to bring fresh food into Saudi Arabia. Only properly canned or sealed food or food stored in containers with easy access for inspection is allowed in small quantities, sufficient for one person for the duration of their trip.



Cholera is another risk during the Hajj, especially in light of the continued occurrence of outbreaks in different countries. As of 20 Sep 2012, a total of 19 283 cases, including 276 (1.4 per cent) deaths have been reported in the ongoing cholera outbreak in Sierra Leone since the beginning of the year [2012] [22]. The highest numbers of cases occurred in the western area of the country, where the capital city of Freetown is located. In addition, the WHO reported a sharp increase in the number of cholera cases in July [2012] in the DRC and many other countries [23]. The Ministry of Health of Saudi Arabia has updated its public health staff at all ports of entry for pilgrims, to be observant of all pilgrims coming from areas where cholera has been reported by WHO, and to maintain a high level of vigilance for any signs and symptoms of diarrhoea, and to continue surveillance at their camps and initiate quarantine and contact tracing once a case is suspected. Emphasis is being placed on early detection of cases and timely provision of treatment at all Hajj premises, once pilgrims have passed the ports of entry while incubating the disease.



Poliomyelitis

Poliomyelitis is still predominant in certain countries around the world. The attendance of visitors from these countries to the Hajj may pose a health risk for other visitors. All travellers arriving from polio-endemic countries and re-established transmission countries, namely Afghanistan, Angola, Chad, the DRC, Nigeria and Pakistan, regardless of age and vaccination status, should receive one dose of oral poliovirus vaccine (OPV). Proof of OPV vaccination at least 6 weeks prior departure is required to apply for entry visa for Saudi Arabia. These travellers will also receive one dose of OPV at border points on arrival in Saudi Arabia. The same requirements are valid for travellers from recently endemic countries at high risk of reimportation of poliovirus, i.e. India (Table 2).



Polio cases secondary to wild poliovirus importation or to circulating vaccine-derived poliovirus in the past 12 months have been reported in the following countries: China, Central African Republic, Cote d'Ivoire, Kenya, Mali, Niger, Somalia and Yemen [4]. All visitors aged under 15 years travelling to Saudi Arabia from these countries should be vaccinated against poliomyelitis with the OPV or inactivated poliovirus vaccine (IPV). Proof of OPV or IPV vaccination 6 weeks prior to application is required for entry visa. Irrespective of previous immunisation history, all visitors under 15 years arriving in Saudi Arabia will also receive one dose of OPV at border points (Table 2).



Table 2. Saudi Arabian health requirements and recommendations for entry visas for the Hajj seasons in 2012



Ebola outbreaks

Two large outbreaks of Ebola have been reported by the Ministries of Health of Uganda and the DRC. In Uganda, a total of 24 probable and confirmed cases were reported during the outbreak. Eleven of these 24 cases have been laboratory-confirmed by the Uganda Virus Research Institute in Entebbe. A total of 17 deaths were reported in this outbreak. The last confirmed case was admitted on [3 Aug 2012] and discharged from hospital on [24 Aug 2012] [24,25]. This is twice the maximum incubation period (21 days) for Ebola proposed by the WHO during Ebola outbreak response operations. In the DRC, 46 cases (14 laboratory-confirmed, 32 probable) of Ebola haemorrhagic fever were reported until [15 Sep 2012]. Of these, 19 have been fatal (6 confirmed, 13 probable). The cases occurred in 2 health zones of Isiro and Viadana in Haut-Uele district in Province Orientale. In addition, 26 suspected cases have been reported and are being investigated.



The 2 Ebola outbreaks are not epidemiologically linked and have been caused by 2 different Ebola subtypes: Ebola subtype Sudan in Uganda, and Ebola subtype Bundibugyo in DRC. To avoid global spread of the disease, the Saudi Arabian Ministry of Health decided to exclude pilgrims from these 2 countries for this Hajj season. This restriction is based on the careful review and deliberation of the national committee on communicable disease prevention who felt that it cannot be excluded that new cases may emerge, and on the fact that the risk of disease transmission is thought to be high with potential catastrophic consequences if occurring during the Hajj, as the disease has a high mortality rate, and no therapeutic interventions are available.



[Reported by: J A Al-Tawfiq /1, Z A Memish /2

1. Saudi Aramco Medical Services Organization, Dhahran, Kingdom of Saudi Arabia

2. Public Health Directorate, Ministry of Health, Riyadh, Director WHO Collaborating Center for Mass Gathering Medicine, Professor, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia]

References follow:  http://www.promedmail.org/direct.php?id=20121011.1338172

Disaster & Prepardness Response: WHO’s hospital safety index and emergency checklist rolled out in Europe

12-10-2012

WHO has developed tools, including the index and checklist, helping health authorities to improve hospitals and health systems’ ability to prepare for emergencies and remain resilient during and after disasters.
Assessments using the hospital safety index were made in 9 countries in the WHO European Region. These include training national experts to assess priority hospitals and identifying the most effective mitigation measures for emergencies.
Several countries, including the Republic of Moldova, have integrated the application of the hospital safety index into the processes for accrediting hospitals, or planning new ones, as in Georgia. In Tajikistan, recommendations on structural and other improvements, developed with the Ministry of Health, were used to mobilize donor funding for priority mitigation measures and retrofitting vulnerable facilities. Hospital emergency plans were developed, updated and tested through exercises and drills in Poland and in the Ukraine, and complemented by training of health professionals in emergency management.
To date, more than 140 hospital assessment reports have been produced. Countries shared their experience at a global expert meeting in Istanbul, Turkey in March 2012 and several national and regional meetings.
The WHO tools assess hospitals’ vulnerabilities, promote low-cost/high-impact mitigation measures and strengthen emergency preparedness to ensure that hospitals keep functioning during all emergencies.
13 October 2012 is the International Day for Disaster Reduction.

Need for health services to remain functional in disasters and emergencies

Health services need to keep functioning during and after crises and disasters, when they are needed most. Making sure that hospitals and health facilities are safe and prepared for emergencies is a key priority to ensure community resilience and protect the health of vulnerable groups. Vulnerable groups, particularly women and girls, are often among those most affected in communities hit by disasters.
When hospitals fail, communities are left without critical health services, including basic emergency care. Keeping hospitals safe from natural or human-made threats goes beyond the mere protection of buildings and physical structures. It requires protecting and ensuring the preparedness of the health workforce, and preserving supply lines to keep facilities operational.

http://www.euro.who.int/en/what-we-do/health-topics/emergencies/disaster-preparedness-and-response/news/news/2012/10/whos-hospital-safety-index-and-emergency-checklist-rolled-out-in-europe

Chhattisgarh sounds alert as swine flu claims five lives

October 11, 2012 Click on map to enlarge:

Raipur : The Chhattisgarh government Thursday sounded a high alert after swine flu claimed five lives in the state within less than a fortnight, a health department official here said.
"In less than 15 days, five deaths in the state have been confirmed to swine flu. Dozens of people, including two government doctors in Raipur, are suffering from the disease," a directorate of health services official said.

The state government has instructed hospitals across all the 27 districts to distribute Tamiflu, a drug against H1N1 virus that causes swine flu, free of cost.

The government has also asked people to rush to the nearest hospital in case they detect symptoms of the disease, which include high fever, cough, sore throat, body ache, chills and fatigue that can be extreme. http://twocircles.net/2012oct11/chhattisgarh_sounds_alert_swine_flu_claims_five_lives.html

Singapore: False Tweet on Hospital with Coronavirus Patient

It appears the reason this case made the news is because of the false tweet sent out. 

Woman tests negative for SARS-related bug
By Claire Huang |
Posted: 12 October 2012

SINGAPORE: A woman suspected of being infected with a variant of the influenza bug that caused the SARS epidemic in 2002 does not have the infection.

While she was initially suspected to be infected with the novel coronavirus, the Singapore General Hospital (SGH) said laboratory tests have confirmed that she does not have the infection.

She was admitted to SGH after arriving in Singapore from Kuwait, with a two-hour transit in Qatar.

The hospital said her illness was linked to influenza A or H1N1 infection, which is one of the circulating seasonal influenza strains.

It added that the patient has a history of chronic disease and as such, would be at a higher risk.

A false tweet was circulated online at about 4pm on Thursday telling netizens to stay away from SGH because it has a patient who has the novel coronavirus.

-snip-
http://www.channelnewsasia.com/stories/singaporelocalnews/view/1230965/1/.html

The WHO has declared no new cases since September 22, 2012.


Novel coronavirus infection - update

No new cases of infection with the novel coronavirus have been reported since 22 September 2012. So far, after careful follow-up of close contacts of the two confirmed cases, and a heightened state of global surveillance , there is no evidence of human-to-human transmission of the virus.
The governments of Saudi Arabia, Qatar and the United Kingdom, are continuing their work to gain a better understanding of the disease and the likely source of infection. WHO is supporting the national authorities in their ongoing investigation, and has deployed experts to Saudi Arabia and Qatar as part of an international team. These and future epidemiological and scientific studies will lead to a better understanding of the novel coronavirus.
WHO continues to work with the ministries of health and other international partners to coordinate actions for timely detection, rapid diagnosis and case management of infection caused by the novel coronavirus, should the need arise.
Based on this overall situation, WHO encourages Member States to continue with their routine surveillance to ensure early detection and rapid response to all potential public health threats. WHO will continue to coordinate routine surveillance efforts internationally.
This event was rapidly detected by the international public health community, and notified to WHO under the International Health Regulations (2005). It demonstrates the value of having the appropriate systems and processes in place for early detection, risk assessment and dissemination of information in order to implement appropriate response. 
http://www.who.int/csr/don/2012_10_10/en/index.html

Thursday, October 11, 2012

Germs and money: Where and when will the next pandemic emerge?

Oct 13th 2012

ON OCTOBER 2nd a British traveller, flying home to Glasgow from Afghanistan, began to feel ill. Within hours he was diagnosed with Crimean-Congo Haemorrhagic Fever, a virus nasty enough for him to be put onto a military transport aircraft for transfer to an isolation hospital in London. Less than 24 hours later he was dead.

This outbreak, on top of another death last month in Saudi Arabia from a previously unknown virus, a cousin of the Severe Acute Respiratory Syndrome (SARS), has set global health agencies on edge. Ten years ago the deaths of a couple of travellers from foreign parts might not have been news at all. But the fright of the SARS outbreak in 2003 has left a lasting impression, and scientists and public-health officials now tend to see any putative disease threat through its lens.

Continued:  http://www.economist.com/node/21564529

Vietnam: Received 20,000 equipment protection help prevent disease outbreaks

On 10/10, Vietnam has received 20,000 of labor protection equipment to help vets in new bird flu outbreak may occur and other emerging diseases, by the International Development (USAID) awarded, at the request of the Ministry of Agriculture and Rural Development of Vietnam.
The personal protective equipment consisting of 50,000 masks, 80,000 and 30,000 hooded jacket gloves for protection, worth about $ 200,000, was transferred to the provinces in the risk of the highest bird flu outbreak, or in need urgent protective equipment, to prevent human exposure to highly pathogenic H5N1 avian influenza virus.
The protective equipment will help protect the veterinary staff and others involved in the prevention of and response to the H5N1 virus, or other pandemic risk in medical facilities and in communities in Vietnam

Wednesday, October 10, 2012

Human bocavirus Infections found in Shenzhen

Published Date: 2012-10-09 16:45:16

Entry-exit Inspection and Quarantine Bureau warns the mass travelers to take personal protection measures following the consecutive detection of 4 human Human bocavirus cases at Shenzhen Port.

A baby was taken to a medical inspection room for further temperature monitoring, body examination and epidemic investigation after it was found that its temperature had exceeded normal value through infrared thermal imaging temperature monitoring by personnel from Shenzhen Entry-exit Inspection and Quarantine Bureau at Shenzhen Port. The baby, less than one year old, was from Hong Kong. Its armpit temperature was 37.6 centigrade and it had obvious canker in mouth. After throat swab inspection, the baby was diagnosed as a case of human bocavirus infection, the 4th in Shenzhen within one month. The other 3 cases were respectively found from Huanggang Port and Shenzhen Bay Port.

As a new virus that closely relates to human's acute respiratory infection, bocavirus, through airborne transmission, makes children from 6 months to 3 years old vulnerable to pneumonia, bronchitis, bronchopneumonia and other diseases, with main clinical symptoms of cough, fever, gasping, diarrhoea, and so on. Autumn is high occurrence season for the virus. The virus is not easy to be distinguished [symptomatically] from other respiratory virus infection and has caused great attention of many scholars and experts.

Shenzhen Entry-exit Inspection and Quarantine Bureau warns that travellers should take care of their personal hygiene and avoid going to the public areas with high dense crowds. The children should also be taken good care of. Travellers should make immediate report to an inspection and quarantine department and take hospitalization if finding any above mentioned symptoms before entering Shenzhen.

[byline: Connie and Elaine]

-- communicated by: ProMED-mail from HealthMap alerts

[Although it is clear that influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus are important causes of pneumonia, the role of rhinoviruses and some of the newly described viruses, including human coronaviruses and human bocavirus, is harder to determine.

Human bocavirus is a small single-stranded DNA-containing virus classified in the family _Parvoviridae_. It is one of the many respiratory pathogens affecting infants and young children. 4 species of human bocavirus (HBoV) have been recently discovered and classified in the Bocavirus genus (family Parvoviridae, subfamily Parvovirinae). Although detected both in respiratory and stool samples worldwide, HBoV1 is predominantly a respiratory pathogen, whereas HBoV2, HBoV3, and HBoV4 have been found mainly in stool.

A variety of signs and symptoms have been described in patients with HBoV infection including rhinitis, pharyngitis, cough, dyspnea, wheezing, pneumonia, acute otitis media, fever, nausea, vomiting, and diarrhea. Many of these potential manifestations have not been systematically explored, and they have been questioned because of high HBoV co-infection rates in symptomatic subjects and high HBoV detection rates in asymptomatic subjects. However, evidence is mounting to show that HBoV1 is an important cause of lower respiratory tract illness. The best currently available diagnostic approaches are quantitative PCR and serology. [See: T Jartti, et al. Rev Med Virol. 2012 Jan;22(1):46-64).

The name bocavirus is derived from bovine and canine, referring to the 2 known hosts for other members of this genus; the bovine parvovirus which infects cattle, and the minute virus of canines which infects dogs.[7] Parvoviruses (Latin: small viruses) have a 5 kilobase long single-stranded DNA, and they use some of their host's replication proteins to copy their DNA. - Mod.CP


http://www.promedmail.org/

Cruise ship with meningitis outbreak docks in Spain

10/10/12
MADRID, Oct. 9 (Xinhua) -- The cruise-ship Orchesta arrived in the Spanish port of Valencia on Tuesday after four cases of bacterial meningitis had been reported among members of its crew.
The ship, which has 2,800 passengers onboard arrived after sailing from the Italian port of Liverno.
The four infected crew members, two of whom are said to be in a serious condition, are in hospital, while the passengers and remaining crew have all been prescribed antibiotics as a precautionary measure.
The company MSC, which runs the ship has assured passengers that there is no risk to their health given that those infected were not in contact with passengers and added that nobody else has shown any symptoms of the potentially fatal disease.
"No passaneger and no member of the crew has shown and symptoms of meningitis," said the statement published by MSC.
The Orchestra is now expected to continue with its itinerary, calling in at Ibiza, Tuniz, Catalia and Naples.
The warning of the disease was raised around mid-day on Monday, while the majority of the holidaymakers onboard were visiting Livorno

Tuesday, October 9, 2012

Vietnam: Smuggling chickens raging, the vaccine is disabled

[There have not been any human infections recently in Vietnam, and the vaccine is not working...so it is not easy to contract the H5N1 Avian Influenza]
Translation:
October 8, 2012

Chicken illegally carrying dangerous new strain are local mass influx.
It is worrying that this new virus has appeared and spread rapidly in China since the beginning of the year and we are using the vaccine does not work against them. According to Prof. Dr. Nguyen Tran Hien, Director of the Institute of Hygiene and Epidemiology, with the former group, the injectable flu vaccine for poultry only meet 75% of the variation H5N1 virus in poultry, in the absence of disease vaccine increase the risk of the virus to mutate to spread from person to person. Meanwhile, according to the Department of Animal Health, the country also seven provinces with avian bird deaths, the destruction of more than 180,000 children.
However, the Deputy Director of Animal Husbandry Department Nguyen Thanh Son fear, new branches virus can source from chicken cull China, especially chickens smuggled into Vietnam in recent years. Meanwhile, the Deputy Minister of Agriculture and Rural Development Diep Kinh Tan said: "The disease situation is complicated in the North or Central. 2 months ago, there was a new virus (group C) in China, causing the bird flu with the potential to cause very high death and are at risk of entry into Vietnam. "
Chicken spill massive smuggling into the country through the province of Quang Ninh
While new avian influenza virus with high-risk infectious and high mortality rates are raging, state smuggled poultry (the main cause of spreading dangerous strain) has not been controlled.

Smuggled chickens contain pathogenic strains with stronger, higher ability to infect humans and cause death rate is also higher. This information is the Animal Health Department (MARD) warned at the beginning of the year.
Vaccines disabled with the new strain of bird flu
Talking to us, Acting Director of Animal Health, Hoang Van Nam said the new H5N1 virus appears, but still belongs to the old branch, but had differences with both groups A and B viruses cause disease in Vietnam in 2011. According to Prof. Dr. Long Thanh, director of the Central Veterinary Diagnostic Center, but appear from July, but this group of viruses has spread rapidly and over a wide range from the north into Central. According to experts, the virus is able to cause bird flu continues to spread in the future and this strain highly lethal than the old strain.

Saudi Arabia: Video - Hunting Migratory Birds Prohibited For Fear Avian Influenza

October 10, 2012
Sky News Arabic:
Represents the hunting of migratory birds to the Saudis love did not prevent him laws enacted by the Kingdom banned for fear of transmission of avian influenza infection.

http://www.skynewsarabia.com/web/video/49600/%D8%B5%D9%8A%D8%AF-%D8%A7%D9%84%D8%B7%D9%8A%D9%88%D8%B1-%D8%A7%D9%84%D9%85%D9%87%D8%A7%D8%AC%D8%B1%D8%A9-%D8%A7%D9%84%D8%B3%D8%B9%D9%88%D8%AF%D9%8A%D8%A9

Indonesia: Video in Indonesia: Flu burung teror warga Bandung

http://video.sindonews.com/view/337/flu-burung-teror-warga-bandung

Indonesia: Tia Lestari (8) Update

[I don't recall reading about severe lung disease or pneumonia...]
From the previous article:
The patient became ill on 28 September with intermittent complaints of body heat. "But the family just delivering drugs from the stall. Recent on Tuesday (2/10) brought Lia to the hospital and was subsequently referred to RSHS and while in the ER was vomiting and bloody bowel movements. Lia died the next day, Wednesday (3/10) at 15.00 pm, "he said.


10 October 2012 JAKARTA - The Hasan Sadikin Hospital (RSHS) Bandung ensure the death of the patient Tia Lestari, 8, Bojongsoang origin, Bandung regency is not due to bird flu. Tim Bird Flu Handling RSHS Dr Sri Sudhawati confirmed, the patient died due to pneumonia or severe lung disease. "The patient is not suffering from bird flu, he suffered from severe pneumonia. Because before he had contact with poultry that died suddenly," he said when met at RSHS, yesterday. 

This is known as in any patient who experienced severe respiratory distress or pneumonia, the procedure is always performed. As reported previously, Tia allegedly died of bird flu. While the 15 chickens that died suddenly around the victim's house and her aunt, was examined Department of Animal Husbandry and Fisheries (Disnakkan) Bandung regency. 

Chief Medical Officer (PHO) Bandung regency Ahmad asserted Kustijadi RSHS result of information, the cause of death of the victim is not bird flu," he said yesterday. Although begitun officers Disnakan Bandung District Health Office and also perform related steps anticipation of bird flu.

Indonesia: Bandung to conduct surveillance after Tia Lia (8) Death

 October 9, 2012
Health Office (PHO) Bandung District will conduct disease surveillance for two weeks, in the District Bojongsoang, related to the finding of a chicken H5N1 virus, or bird flu.
Head of DHO Bandung, Kustijadi Achmad said it appealed to the public to immediately see if a fever or flu disease to the nearest health center.
"If there are people who had a fever around the District Bojongsoang, please see a health center. Later when a high fever that does not go away, will be referred to the hospital," he said when met at Soreang Tribune, Tuesday (10/09/2012).
He added, in addition to the medical officer at the health center, five officers on standby for surveillance of health office at any time to the field if there are reports of bird flu. The observation was carried out for two weeks, starting on Monday (10/08/2012).

Indonesia: Little Tia (8) That Died, Had Poultry with #H5N1

[Little Tia (8) from Tia Lia Lestari (8) of Kampung Ciganitri RT 04/04 Village District Cipagalo that enjoyed playing with the poultry at his Aunt's house, posted here, died of dengue hemorrhagic fever, as I posted here.  As it ends up, those poultry were infected with the H5N1 Avian Influenza virus.]


CIPAGALO - DVO Bandung find the chickens tested positive for the virus H5NI in RW 04, Cipagalo Village, District Bojongsoang. Certainty of the existence of the bird flu virus after a quick test on chicken carcasses.
"Mother's pet chicken Oneng positive bird flu.'s Just the tail of the five, the one positive tail yesterday (Monday, Red) died suddenly," said Iman Rahman, officer Paramedics DVO Bandung, Tuesday (9/10 / 2012).
Therefore, Iman said it did not want to risk too much by directly spraying disinfectant into poultry cages citizens. Not just a chicken coop, a few corners of houses are often used where chickens were also sprayed.
The plan the agency will also conduct a mass depopulation of poultry in the region, yesterday. But the plan was canceled because officials and residents can not collect all the fowl in the village.
"Chicken pet citizens were outside the cage, scatter some where looking for food," said Faith.
Depopulation of chickens owned by residents, said Faith, it is important to prevent the spread of bird flus.
Because, in addition to found a single positive chickens infected, from the record it, says Iman, already there are 50 chicken residents who died in the last two weeks. Death of the chickens is not currently indicated as could spread bird flu in the region.
"We are still awaiting the results of lab tests, if convicted of the sample is positive, then the massive depopulation of poultry in these immediate causes lie within the indicated endemic," he said.
-snip-
Euis also confirmed a chicken that died suddenly in Cipagalo positive bird flu.
"Yeah, one positive chickens from bird flu rapid tests that we do. But still tested in the lab first. Region is not endemic bird flu, may not find another similar case afterwards. This is the first case this year. Earlier report of 14 District Bandung, all negative bird flu, "he said.

Recombonics: Increased Discordance Between Human and Swine H3N2v

October 9, 2012 
The USDA has released an series of 2012 H3N2v swine sequences, which includes 15 matches with recent H3N2v human cases.  Although all released human sequences from 2011 and 2012 cases have an H1N1pdm09 M gene, the first 10 cases from 2011 have an N2 lineage that traces back to H1N2v swine.  In contrast, the last 2 cases in 2011 and 89/91 human H3N2v sequences from 2012 have an easily distinguished N2, which is from an H3N2v swine lineage.  The dramatic switch in the N2 lineage in the human cases was not seen in the swine H3N2v, especially those identified by the USDA through their voluntary swine surveillance program.

This discordance has been noted previously, but was increased by the 16 sets of 2012 H3N2v sequences, all of which matched the 2011 human H3N2v cases.  Five of the sets of HA, NA, MP sequences were from isolates discussed previously when the USDA released sequences for the five internal genes.  The five isolates (A/swine/Illinois/A01241469/2012, A/swine/Illinois/A01241840/2012, A/swine/Illinois/A01241842/2012, A/swine/Illinois/A01241871/2012, A/swine/Illinois/A01241916/2012) had internal gene sequences that were closely related to swine matches with the human cases from 2011, and the recently released sequences had an H1N1pdm09 M gene as well as HA and NA genes which matched the human isolates, which was also true of the 11 additional sets of sequences (see list below).  Although most of the new sequences were also from Illinois, the were collected throughout the first five months of 2012, which extended time frame for at least one Illinois H3N2v match to 8 months (at least one Illinois swine sequence was identified for each of the last 3 months of 2011).

In spite of the detection of this sub-clade in Illinois swine, as well as other states, including Ohio and Indiana, only two of the recent human cases match the N2 lineage in these swine isolates (and the two human cases from Michigan also had a PB1 sequence with E618D, as did recent Ohio swine).  The other 88 sets of sequences from July / August human cases matched the lineage with an N2 from H3N2v swine, which was first reported in human cases at the end of 2011 (from a day car center in Mineral County, West Virginia).

This large discordance between human and swine H3N2v lineages suggest the lineage in most 2012 human cases is evolving in humans, and is rarely found in swine not at agricultural fair venues, although the recent swine cases identified in Indiana and Ohio may signal an entry into the swine population which increase frequencies in subsequent USDA samples acquired through its voluntary surveillance system.

The discordance also raises concerns that the CDC focus on agricultural fairs during the influenza off season is creating a serious undercount in H3N2v cases infected via human to human transmission.

Name                                                                Collection
A/swine/Iowa/A01202529/2011                    8/22/11
A/swine/Iowa/A01202530/2011                    8/22/11
A/swine/Iowa/A01202573/2011                    9/07/11
A/swine/NY/A01104005/2011                       9/13/11 
A/swine/Iowa/A01202878/2011                    9/17/11
A/swine/Iowa/A01202879/2011                    9/17/11
A/swine/Indiana/A01202621/2011               9/28/11
A/swine/Iowa/A01202639/2011                    9/30/11
A/swine/Iowa/A01202640/2011                    9/30/11
A/swine/Illinois/A00857138a/2011             10/20/11 
A/swine/Illinois/A00857138b/2011             10/20/11
A/swine/Illinois/A00857300/2011               11/28/11 
A/swine/Illinois/A01202978/2011               12/16/11
A/swine/Illinois/A01240835/2012                 1/03/12
A/swine/Illinois/A01240836/2012                 1/03/12
A/swine/Illinois/A01240908/2012                 1/03/12
A/swine/Illinois/A00857304a/2012               1/05/12  
A/swine/Illinois/A00857304b/2012               1/05/12
A/swine/Ohio/A01203186/2012                    1/24/12
A/swine/Indiana/A01327213/2012                2/06/12
A/swine/Indiana/A01327215/2012                2/06/12
A/swine/Illinois/A01241469/2012                  2/08/12
A/swine/North Carolina/A01203272/2012+  2/13/12
A/swine/Illinois/A00857318a/2012*               2/23/12
A/swine/Texas/A01104013/2012                   2/15/12
A/swine/Illinois/A01241840/2012                   2/27/12 
A/swine/Illinois/A01241842/2012                   2/27/12 
A/swine/Illinois/A01241871/2012                   2/29/12 
A/swine/Illinois/A01241876/2012                   2/29/12 
A/swine/Illinois/A01241916/2012                   3/01/12
A/swine/Illinois/A01327184/2012                   3/15/12
A/swine/Indiana/A01203372/2012                 4/03/12
A/swine/Illinois/A01327629/2012                   4/15/12
A/swine/Illinois/A01327903/2012                   5/08/12 
A/swine/Illinois/A01327905/2012                   5/08/12 
A/swine/Iowa/A01203503/2012                      5/09/12
A/swine/Indiana/A01203509/2012+               5/09/12
A/swine/Indiana/A01203521/2012                 5/15/12
A/swine/Indiana/A01203522/2012                 5/15/12
A/swine/Ohio/1/2012#                                           6/12
A/swine/Ohio/6/2012#                                           6/12
A/swine/Ohio/7/2012#                                           6/12
A/swine/Ohio/9/2012                                             6/12
A/swine/Indiana/A00968380/2012+               7/18/12
A/swine/Iowa/A01243736/2012                      7/25/12 

+ = 2011 WV lineage
* = H1N1pdm09 NP
# = E618D PB1
bolded date = newly confirmed match


http://www.recombinomics.com/News/10091201/H3N2v_Discord_Up.html 

Pets may get the flu more often than thought

By Rachael Rettner
Published October 08, 2012

Humans aren't the only ones at risk for contracting the flu this season: our furry friends can fall ill from the disease as well. In fact, flu infections in cats and dogs may be much more common than thought, experts say. And pets can catch the flu from their owners, research finds. One study of cat blood samples found about 30 percent of cats in Ohio had been infected with seasonal flu, and 20 percent had been infected with the H1N1 flu strain that caused the 2009 pandemic. Studies also suggest there has been an increase in cat flu infections since 2009.

Read more: http://www.foxnews.com/health/2012/10/08/pets-may-get-flu-more-often-than-thought/#ixzz28nrsgPMG

FAO-OIE-WHO Technical Update September 2011

While I understand that this document is dated, I just added it to the right side-bar for future reference. It is located under "H5N1 Information List". It also has a section that discusses the new clade 2.3.2.1. This document has a large list of references to chose from.

WHO Global Statistics of Avian Influenza

Click on Charts to enlarge:
http://www.info.gov.hk/info/flu/eng/global.htm
http://www.chp.gov.hk/files/pdf/2012_avian_influenza_report_vol8_wk40.pdf

Dept. of Health Hong Kong: Suspected case of Severe Respiratory Disease associated with Novel Coronavirus confirmed to be influenza infection

October 8, 2012 
The Centre for Health Protection (CHP) of the Department of Health said today (October 8) that the suspected case of Severe Respiratory Disease associated with Novel Coronavirus affecting a four-year-old boy who came from Jeddah, Kingdom of Saudi Arabia, was confirmed to be an influenza infection.
     A CHP spokesman said that the Centre had carried out an urgent investigation into the case on receipt of notification from Ruttonjee Hospital yesterday. The boy was subsequently admitted to Queen Mary Hospital (QMH) for isolation yesterday. Investigation revealed that the boy has upper respiratory tract symptoms and there is no clinical or radiological evidence of pneumonia. His current condition is stable.
 
     Respiratory specimens taken from the boy at QMH tested positive for influenza A (H1N1) 2009 virus but negative for Novel Coronavirus associated with Severe Respiratory Disease. The patient is not a case of Severe Respiratory Disease associated with Novel Coronavirus infection.
 
     The spokesman advised travellers returning from novel coronavirus-affected countries with repiratory symptoms should wear a facial mask, seek medical attention and reveal the travel history to the doctor.
 
 Citation: Plourde JR, Pyles JA, Layton RC, Vaughan SE, Tipper JL, et al. (2012) Neurovirulence of H5N1 Infection in Ferrets Is Mediated by Multifocal Replication in Distinct Permissive Neuronal Cell Regions. PLoS ONE 7(10): e46605. doi:10.1371/journal.pone.0046605
Editor: Stephen Mark Tompkins, University of Georgia, United States of America
Received: May 9, 2012; Accepted: September 3, 2012; Published: October 8, 2012

Abstract

Highly pathogenic avian influenza A (HPAI), subtype H5N1, remains an emergent threat to the human population. While respiratory disease is a hallmark of influenza infection, H5N1 has a high incidence of neurological sequelae in many animal species and sporadically in humans. We elucidate the temporal/spatial infection of H5N1 in the brain of ferrets following a low dose, intranasal infection of two HPAI strains of varying neurovirulence and lethality. A/Vietnam/1203/2004 (VN1203) induced mortality in 100% of infected ferrets while A/Hong Kong/483/1997 (HK483) induced lethality in only 20% of ferrets, with death occurring significantly later following infection. Neurological signs were prominent in VN1203 infection, but not HK483, with seizures observed three days post challenge and torticollis or paresis at later time points. VN1203 and HK483 replication kinetics were similar in primary differentiated ferret nasal turbinate cells, and similar viral titers were measured in the nasal turbinates of infected ferrets. Pulmonary viral titers were not different between strains and pathological findings in the lungs were similar in severity. VN1203 replicated to high titers in the olfactory bulb, cerebral cortex, and brain stem; whereas HK483 was not recovered in these tissues. VN1203 was identified adjacent to and within the olfactory nerve tract, and multifocal infection was observed throughout the frontal cortex and cerebrum. VN1203 was also detected throughout the cerebellum, specifically in Purkinje cells and regions that coordinate voluntary movements. These findings suggest the increased lethality of VN1203 in ferrets is due to increased replication in brain regions important in higher order function and explains the neurological signs observed during H5N1 neurovirulence.

Introduction 

Highly pathogenic avian influenza A (HPAI), subtype H5N1, has infected humans in 12 countries and has been associated with approximately a 60% mortality rate since 1997 (http://www.who.int/influenza/human_anima​l_interface/EN_GIP_20111010CumulativeNum​berH5N1cases.pdf). Severe disease of H5N1 includes fast-progressing pneumonia, acute respiratory distress syndrome (ARDS), diarrhea, central nervous system (CNS) clinical signs, and multi-organ failure. Death often occurs within ten days of symptom onset [1][3]. Studies to identify virulence factors contributing to these phenotypes have been the focus of many recent investigations [4][8]. However the mechanisms leading to increased pathogenesis by H5N1, particularly non-pulmonary events, remain to be elucidated.

ARDS is a common manifestation of pulmonary influenza infection; however H5N1 has been atypically shown to also infect and damage the CNS. De Jong and colleagues reported acute encephalitis in brains of humans infected with H5N1. These patients did not present with respiratory illness but had severe diarrhea, with early onset of seizures and coma, and death occurring within one to five days post hospital admittance [9]. Murine infection models have illustrated that neurotropic H5N1 strains exhibit higher lethality than those that do not replicate efficiently in the brain [10]. Several groups have investigated possible routes of viral entry into the brain, including the olfactory system as a major route into the brain of experimentally infected ferrets [10][12]. Studies by Park et al. suggested that, in addition to the olfactory nerves, HPAI enters the CNS through the vagal, trigeminal, and sympathetic nerves [12]. Furthermore, the dissemination of H5N1 through the bloodstream is plausible due to the presence of virus in organs such as the spleen apart from the site of initial infection.
While these possible routes of infection in the brain have been identified, little is known regarding HPAI dissemination within the CNS and its contribution to clinical signs and lethality. Therefore, delineating neurotropic features of H5N1 infection in the ferret model could lead to a better understanding of mechanisms responsible for widespread infection throughout the central nervous system.
Herein, we compare two strains of H5N1 with distinct neurotropism and lethality in ferrets to elucidate the temporal-spatial neuroinvasion leading to death. We show that VN1203 resulted in wider dissemination in the brain and associated with higher morbidity and clinical signs of neurological involvement. By comparison, HK483 infection resulted in low mortality, no viable virus recovered from the brain, and a low incidence of brain lesions limited solely to the olfactory system. Furthermore, we identify brain regions and cell types susceptible to VN1203 that explain the myriad of neurological signs during lethal infection. These findings broaden our understanding of the neurovirulence of H5N1 viruses and support further investigation into therapies leading to CNS protection.

[red bold above is mine]
Continued:  http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046605