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April 7th, 2008, 06:54 PM
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Chinese son likely gave bird flu to father: report
Source: http://uk.reuters.com/article/health...29850620080407
Chinese son likely gave bird flu to father: report
Mon Apr 7, 2008 11:32pm BST
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) - A 24-year-old Chinese man who died of bird flu in December passed the virus directly to his father in a rare case of human-to-human transmission of the virus, doctors reported on Monday.
Chinese officials had already said they believed the younger man infected his 52-year-old father, who survived, but genetic sequencing and other checks confirmed this was likely, the researchers said.
"In this family cluster of confirmed cases of infection with highly pathogenic avian influenza A (H5N1) virus in mainland China, we believe that the index case transmitted H5N1 virus to his father while his father cared for him in the hospital," they wrote in the Lancet medical journal.
H5N1 avian influenza is regularly breaking out in birds across Asia, the Middle East, Africa and Europe. It only rarely infects humans but has killed 238 out of 376 people known to have been infected since 2003.
Most have been directly infected by a sick bird, but in a few rare cases, one person appears to have infected another. These have been documented in Indonesia and, just last month, between two brothers in Pakistan.
Most have been among people who are genetically related and this also appears to be the case with the two Chinese men, the researchers said. Some experts believe there may be a genetic susceptibility to H5N1 infection.
The fear is that the virus will acquire changes that allow it to be passed from one person to another more easily. This could cause a pandemic that could kill tens of millions of people globally, so experts are carefully studying every case of transmission.
Yu Wang of the Chinese Centre for Disease Control and Prevention in Beijing and colleagues investigated the cases of the man and his son, who were diagnosed within a week of each other in December 2007 in Jiangsu Province.
They also tested 91 people the two men had come into close contact with. None of these people became infected.
The young man had a high fever, cough and watery diarrhea and his father nursed him intensively in the hospital.
The younger man died but his father got the flu drugs Tamiflu and rimantadine as well as serum from a woman inoculated with an experimental H5N1 vaccine and recovered.
"With the exception of occasional infection in health workers, all published incidents of possible or probable person-to-person transmission report transmission between genetically related individuals," Nguyen Tran Hien of Vietnam's National Institute of Hygiene and Epidemiology in Hanoi, and colleagues wrote in a commentary.
"Although this finding could be related to the intensity and intimacy of contact between family members, host genetic factors might also play a part in susceptibility to H5N1," they added. So anyone in close, prolonged contact with an H5N1 victim should get flu drugs just in case, they said.
Last week the World Health Organization said some human-to-human spread likely occurred when three brothers in Pakistan became infected with H5N1 last year.
The largest known cluster of human bird flu cases occurred in May 2006 in Indonesia when at least 7 family members died.
(Editing by Philip Barbara)
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April 7th, 2008, 06:58 PM
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Editor, Senior Moderator
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Re: Chinese son likely gave bird flu to father: report
Source: http://www.medpagetoday.com/Infectio...theFlu/tb/9041
* Medical News: Flu & URI
Avian Flu Jumped from Dying Son to Caregiver Father
By Michael Smith, North American Correspondent, MedPage Today
Published: April 07, 2008
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine. Earn CME/CE credit
for reading medical news
BEIJING, April 7 -- A man who died late last year of highly pathogenic avian flu infected his father in one of the few "probable" cases of human-to-human transmission that have been reported, researchers here said.
The infection likely occurred while the 52-year-old father cared for his 24-year-old son, who was severely ill, according to Yu Wang, Ph.D., of the Chinese Center for Disease Control and Prevention, and colleagues.
Although nearly 100 close contacts were tested for the H5N1 virus, the outbreak was limited to the father and son, suggesting a potential genetic susceptibility to infection, Dr. Wang and colleagues said online in The Lancet.
Only a few cases of suspected human-to-human transmission of the virus have been reported -- the largest series in Indonesia in 2006, when seven members of the same family became infected and six died (See: Indonesian Bird Flu Outbreak Raises Pandemic Fears Anew).
But public health authorities worry that small genetic changes in the virus, now widespread among poultry, might one day allow it to pass easily from one person to another, setting the stage for an influenza pandemic.
In most cases, people are infected after prolonged contact with infected poultry. As of April 3, the World Health Organization had reported 378 confirmed cases, 238 of them fatal.
In the first Chinese case, Dr. Wang and colleagues said, there was no obvious link to infected poultry. The young man visited a market six days before the onset of illness, but had not been within 10 meters of the poultry, they said.
A later investigation showed no sign of infected poultry at that market or at another, visited later by his father.
The man developed transient chills and sweats in the fall of 2007 and on Nov. 24 he developed a fever of 38.8°C, malaise, and chills, and was treated with oral antibiotics as an outpatient the next day.
Three days later, he was hospitalized with persistent fever, chills, headache, myalgia, sore throat, cough, and sputum production. On admission, he had lymphopenia, moderate thrombocytopenia, and left-lower-lobe pneumonia.
A blood culture taken on Nov. 28 yielded Salmonella choleraesuis, so he was treated for bacterial infection.
The man developed progressive dyspnea, copious frothy sputum production, watery diarrhea, and pneumonia and despite broad-spectrum antibiotics, corticosteroids, and mechanical ventilation, died of acute respiratory distress syndrome, disseminated intravascular coagulation, and multiorgan failure on the fifth day in the hospital.
An endotracheal aspirate obtained, just before death, was positive for H5N1 by real-time polymerase chain reaction, the researchers said, and the virus itself was isolated.
The patient's father helped care for him in the hospital, without respiratory protection until the last day, Dr. Wang and colleagues reported. He was exposed to frequent coughing, helped to dispose of soiled clothes and bedsheets, and cleaned a toilet and spittoon used by his son.
The man, a retired engineer, developed a fever of 38.1°C, chills, and cough on Dec. 3. He took one 75-mg dose of oseltamivir (Tamiflu) that had been distributed to contacts of his son for prophylactic purposes.
The next day, he was hospitalized with fever, mild thrombocytopenia, and bilateral pneumonia, and treated with levofloxacin (Levaquin), corticosteroids, and oseltamivir. Rimantadine (Flumadine) was started on the third day.
Despite treatment, he required positive pressure ventilation. On Dec. 7, he received two transfusions of plasma from a 30-year-old woman who had received two doses of inactivated whole-virion H5N1 vaccine in a phase I clinical trial.
The patient's fever resolved that night and a chest radiograph on Dec 12 showed improvement in the right upper and bilateral lower lobes.
H5N1 virus was isolated from a throat swab collected on day four of the patient's illness, and H5N1 viral RNA was detected in throat and stool specimens up to 10 days after the onset of illness.
The patient was discharged 22 days after admission with a full recovery.
As in the case of his son, researchers could find no evidence that the man had been in contact with infected poultry.
While the initial source of the infection remains a mystery, Dr. Wang and colleagues said there's little doubt that the son infected the father, because genomic sequencing showed that viral strains isolated from the two were identical but for one non-synonymous coding change.
The researchers said the case does not imply that the virus has acquired the ability to transmit more easily from person to person.
Indeed, with the exception of occasional infections of healthcare workers, all cases of "possible or probable person-to-person transmission" have been among genetically related individuals, according to Jeremy Farrar, M.D., Ph.D., of the Hospital for Tropical Diseases in Ho Chi Minh City and Oxford University, and colleagues.
The authors noted several limitations including the inability to elicit a complete exposure history from the index case and the fact that it was difficult to trace all contacts who came within one meter of the cases.
In an accompanying commentary, Dr. Farrar and colleagues said that might be explained by continued close contact among infected and non-infected family members.
But "host genetic factors might also play a part in susceptibility to H5N1," they said.
Studying such factors, they said, might "help to clarify the nature of the species barrier and the conditions necessary for widespread transmission between people."
The study was supported by the Chinese Ministry of Science and Technology, the NIAID, and the China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases. The researchers reported no conflicts.
Dr. Farrar and colleagues reported no conflicts.
Primary source: The Lancet
Source reference:
Wang H, et al "Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China" The Lancet 2008; DOI: 10.1016/S0140-6736(08)60493-6.
Additional source: The Lancet
Source reference:
Hien NT, et al "Person-to-person transmission of influenza A (H5N1)" The Lancet 2008 DOI: 10.1016/S0140-6736(08)60494-8.
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April 8th, 2008, 03:37 AM
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Re: Chinese son likely gave bird flu to father: report
Interestingly, today, all my feeds heads with probable 2h2 Chinese event and NO ONE talks about Indonesia (or Pakistan!). Is it a breakthrough news? I think that most of cases of 2h2 are overlooked in the media, at least in recent weeks or months. Since 1997, H5N1 tends to cluster into familiar group and this news - a part for its renowned review origin - is not unexpected at all.
If a more transmissible viral strain was emerged in souther China - densely populated - at this point there would be hundreds of thousands of cases, or millions.
Calm down, press!
China is a hot spot these days, Olympic torch permits.
__________________
GIMI69 (IRONOREHOPPER)
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People come and go, but the creative force of great historical events, as well as important ideas and actions remain. (Aleksandr Romanovic Lurija, 1976)
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A TIME'S MEMORY (Blog)
ATTRAVERSO QUESTI GIORNI (Blog)
tracciatore_traccia@libero.it
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April 8th, 2008, 07:28 AM
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Retired
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by ironorehopper
Interestingly, today, all my feeds heads with probable 2h2 Chinese event and NO ONE talks about Indonesia (or Pakistan!). Is it a breakthrough news? I think that most of cases of 2h2 are overlooked in the media, at least in recent weeks or months. Since 1997, H5N1 tends to cluster into familiar group and this news - a part for its renowned review origin - is not unexpected at all.
If a more transmissible viral strain was emerged in souther China - densely populated - at this point there would be hundreds of thousands of cases, or millions.
Calm down, press!
China is a hot spot these days, Olympic torch permits.
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doi:10.1016/S0140-6736(08)60493-6 
Copyright © 2008 Elsevier Ltd All rights reserved.
Fast track — Articles
Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China
Hua Wang MDa, ‡, Zijian Feng MDb, ‡, Yuelong Shu PhDc, ‡, Hongjie Yu MDb, ‡, Lei Zhou MDb, Rongqiang Zu MDa, Yang Huai MDb, Jie Dong MDc, Changjun Bao MDa, Leying Wen MDc, Hong Wang MDd, Peng Yang PhDb, Wei Zhao MDe, Libo Dong PhDc, Minghao Zhou MDa, Qiaohong Liao MDb, Haitao Yang MDa, Min Wang MDc, Xiaojun Lu MDf, Zhiyang Shi MDa, Wei Wang MDc, Ling Gu MDa, Fengcai Zhu MDa, Qun Li MDb, Weidong Yin MBAg, Weizhong Yang MDb, Prof Dexin Li MDc, Timothy M Uyeki MDh and Prof Yu Wang PhDb,  , 
aJiangsu Provincial Centre for Disease Control and Prevention, Nanjing, China
bOffice for Disease Control and Emergency Response, Chinese Centre for Disease Control and Prevention (China CDC), Beijing, China
cState Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
dJiangsu Provincial People's Hospital, Nanjing, China
eNanjing Secondary People's Hospital, Nanjing, China
fNajing Centre for Disease Control and Prevention, Nanjing, China
gSinovac Biotech Co, Beijing, China
hInfluenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
Available online 7 April 2008.
| Refers to: |  | Person-to-person transmission of influenza A (H5N1)
The Lancet, In Press, Corrected Proof, Available online 7 April 2008
Nguyen Tran Hien, Jeremy Farrar and Peter Horby
SummaryPlus | Full Text + Links | PDF (39 K) | | | Referred to by: | | Person-to-person transmission of influenza A (H5N1)
The Lancet, In Press, Corrected Proof, Available online 7 April 2008
Nguyen Tran Hien, Jeremy Farrar and Peter Horby
SummaryPlus | Full Text + Links | PDF (39 K) | |
Summary
Background
In December, 2007, a family cluster of two individuals infected with highly pathogenic avian influenza A (H5N1) virus was identified in Jiangsu Province, China. Field and laboratory investigations were implemented immediately by public-health authorities. Methods
Epidemiological, clinical, and virological data were collected and analysed. Respiratory specimens from the patients were tested by reverse transcriptase (RT) PCR and by viral culture for the presence of H5N1 virus. Contacts of cases were monitored for symptoms of illness for 10 days. Any contacts who became ill had respiratory specimens collected for H5N1 testing by RT PCR. Sera were obtained from contacts for H5N1 serological testing by microneutralisation and horse red-blood-cell haemagglutinin inhibition assays. Findings
The 24-year-old index case died, and the second case, his 52-year-old father, survived after receiving early antiviral treatment and post-vaccination plasma from a participant in an H5N1 vaccine trial. The index case's only plausible exposure to H5N1 virus was a poultry market visit 6 days before the onset of illness. The second case had substantial unprotected close exposure to his ill son. 91 contacts with close exposure to one or both cases without adequate protective equipment provided consent for serological investigation. Of these individuals, 78 (86%) received oseltamivir chemoprophylaxis and two had mild illness. Both ill contacts tested negative for H5N1 by RT PCR. All 91 close contacts tested negative for H5N1 antibodies. H5N1 viruses isolated from the two cases were genetically identical except for one non-synonymous nucleotide substitution. Interpretation
Limited, non-sustained person-to-person transmission of H5N1 virus probably occurred in this family cluster. Funding
Chinese Ministry of Science and Technology; US National Institute of Allergy and Infectious Diseases, National Institutes of Health; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases.
Article Outline
- Introduction
- Methods
- Patients and procedures
- Role of the funding source
- Results
- Discussion
- Acknowledgements
- References
Introduction
As of April 2, 2008, 376 cases of infection with highly pathogenic avian influenza A (H5N1) virus, with 238 deaths, had been reported from 14 countries since November, 2003. 1 Although most cases have been sporadic, about 25% have occurred in clusters of two or more epidemiologically linked people. [2] and [3] Clusters occurred in 1997 4 and 2003 5 in Hong Kong (special administrative region [SAR] of China), and during 2004–07 in Indonesia, [6], [7] and [8] Turkey, 9 Azerbaijan, 10 Vietnam, 11 and Thailand. [11] and [12] Limited person-to-person transmission of the virus has been strongly suggested in the largest cluster in Indonesia 6 and in Thailand. 12 Previous cluster investigations did not adequately assess whether person-to-person transmission had occurred among exposed contacts. Illness surveillance combined with seroepidemiological investigations in exposed contacts allows a comprehensive assessment of H5N1 virus transmission.
In December, 2007, two cases of infection with H5N1 virus in one family were identified within a week in Nanjing, Jiangsu Province, China. Field and laboratory investigations were implemented immediately by public-health authorities. We report the epidemiological, clinical, and virological findings of this family cluster of confirmed H5N1 cases, including assessment of potential spread to exposed contacts. Methods
Patients and procedures
Epidemiological and clinical data were collected through interviews and review of medical records. Investigation staff interviewed case two and relatives of both cases to verify reported exposure histories during the 2 weeks before the onset of symptoms, to validate timelines of events, and to identify close contacts. We were unable to interview the index case (case one) because he was severely ill at the time of diagnosis and died on the next day. Households and places known to have been visited by the cases in the 2 weeks before the onset of illness were investigated to assess poultry and environmental exposures.
Respiratory and stool specimens were collected from the two patients during hospitalisation and placed in sterile viral transport medium for H5N1 testing. 13
RNA was extracted from specimens with the RNeasy mini kit (Qiagen, Valencia, CA, USA) as per the manufacturer's protocol and tested by conventional reverse transcriptase (RT) PCR as recommended 14 and by real-time RT PCR with H5N1-specific primers and probes. 15 These assays were done in biosafety level (BSL) 2 facilities at Jiangsu Centre for Disease Control and Prevention (CDC), Nanjing, China, and the National Influenza Centre of the Chinese CDC (China CDC) in Beijing. Respiratory specimens were inoculated in amniotic cavities of pathogen-free embryonated chicken eggs for viral isolation 16 in enhanced BSL 3 facilities at the National Influenza Centre.
Full genomic sequencing was done on extracted viral RNA. cDNA synthesis and PCR amplification of the coding region of the eight gene segments were done with a one-step RT PCR kit (Qiagen) with gene specific primers (available on request from the authors). The PCR products were purified with the Qiagen QIAquick gel extraction kit and used as templates for nucleotide sequencing. Sequencing reactions were done with the ABI BigDye terminator sequencing kit with reaction products resolved on an ABI 3730XL DNA sequencer (Applied Biosystems, Foster City, CA, USA). Nucleotide sequences were analysed with the DNASTAR package (Lasergene, Madison, WI, USA). Phylogenetic analysis was done by neighbour-joining method with MEGA version 4. The nucleotide sequences obtained from this study are available from GenBank (accession number EU434686-EU434701).
Close contacts were placed under daily surveillance—by telephone or in person—for fever and respiratory symptoms for 10 days after their last exposure to a patient infected with H5N1 virus. Close contacts were defined as individuals known to have been within 1 m, or had contact with respiratory secretions or faecal material, of a patient with H5N1 any time from the day before the onset of illness to when the index case died or during the period that case two was hospitalised. Chemoprophylaxis with oseltamivir (75 mg orally once a day for 7 days) was recommended and distributed to contacts.
Following written informed consent, a structured questionnaire was used to gather demographic information and data on use of personal protective equipment, oseltamivir chemoprophylaxis, illness symptoms, and potential H5N1 risk factors (eg, poultry contact, visiting poultry markets, contact with individuals with febrile respiratory symptoms) during the 2 weeks before the last exposure to patients with H5N1.
Respiratory specimens were gathered from close contacts with febrile respiratory illness during the 10-day observation period for H5N1 testing. Contacts were asked to have acute and convalescent sera (≤1 week, and ≥3–4 weeks after the last exposure to a patient with H5N1, respectively) collected for H5N1 serological testing.
H5N1 serological testing was done by microneutralisation assay in a BSL 3 enhanced laboratory at the National Influenza Centre, 17 and modified horse red-blood-cell hamagglutinin inhibition assay in BSL 2 conditions at the National Influenza Centre. 18 Antigens for the assays were produced from the index case's virus isolate. Sera were tested in duplicate by two separate microneutralisation assays done on different days. An individual was deemed to be seropositive for H5N1 antibody if H5N1 neutralising antibody titres of 1:80 or greater were detected for single serum, or four-fold or greater rises for paired sera, and confirmed by horse red-blood-cell haemagglutinin inhibition assay. [14] and [19]
Data collection for H5N1 cases was determined by the Chinese Ministry of Health to be part of a continuing public-health outbreak investigation and exempt from institutional review board assessment. Case two granted permission for data collection on him and his son (case one) for research purposes. The protocol for collection of epidemiological data and serological testing of close contacts was approved by the China CDC institutional review board. Written, signed, informed consent was obtained from 91 adult contacts to participate in the study. Role of the funding source
The study sponsors had no role in the design or conduct of the study, or in the collection, analysis, or interpretation of the data. Hongjie Yu had full access to all data included in the study and is responsible for the integrity of the data and accuracy of data analyses. Yu Wang made the final decision to submit the manuscript for publication. Results
The index case, a 24-year-old male salesman, was well until August, 2007, when he experienced transient chills and sweats once or twice a month. On Nov 24, he developed fever (38·8°C), malaise, and chills, and was treated with oral antibiotics as an outpatient the next day. On Nov 27, he was hospitalised with persistent fever, chills, headache, myalgia, sore throat, cough, and sputum production. On admission, the patient had lymphopenia, moderate thrombocytopenia, and left-lower-lobe pneumonia ( table 1). A blood culture taken on Nov 28 yielded Salmonella choleraesuis; he was thus treated for bacterial infection. The patient developed progressive dyspnoea, copious frothy sputum production, watery diarrhoea, and pneumonia. Despite administration of broad-spectrum antibiotics, corticosteroids, and mechanical ventilation, the patient died of acute respiratory distress syndrome, disseminated intravascular coagulation, and multiorgan failure on the fifth day in hospital. An endotracheal aspirate obtained on the fifth day of hospitalisation, just before death, was positive for H5N1 by RT PCR and H5N1 virus was isolated.
Table 1.
Clinical features of the two cases  | Index case | Case two |
|---|
| General | | Age (years) and sex | 24, male | 52, male | | Temperature (°C)* | 40·1 (40·4) | 38·9 (40·0) | | Blood counts* | | White blood cells (×109 per L) | 7·1 (0·7) | 6·7 (4·0) | | Lymphocytes (×109 per L) | 0·49 (0·12) | 1·06 (0·5) | | Platelets (×109 per L) | 88 (37) | 99 (54) | | Serum biochemistry* | | Alanine aminotransferase (U/L) | 17·3 (107·0) | 30·7 (110·4) | | Aspartate aminotransferase (U/L) | 43·8 (374·0) | 61·5 (84·7) | | Albumin (U/L) | 36·8 (34·7) | 37·7 (37·7) | | Creatinine (U/L) | 96·8 (367·1) | 98 (98) | | Creatine kinase (U/L) | 85 (341) | 138 (138) | | Lactate dehydrogenase (U/L) | 328 (3036) | 548 (548) | | Coagulation* | | Prothrombin time (seconds) | 16·6 (16·6) | 11·7 (10·06) | | Activated partial thromboplastin time (seconds) | 87·2 (180·1) | 39 (39·0) | | Fibrinogen (g/L) | 2·01 (3·28) | 4·4 (4·02) | | Arterial blood* | | PaCO2 (mm Hg) | 23·3 (36) | 27 (28) | | PaO2 (mm Hg) | 42 (44) | 59 (66) | | Bicarbonate (mEq/L) | 14·6 (26·4) | 20·1 (19·5) | | Alveolar-arterial oxygen gradient (mm Hg) | 79 (83) | 92 (94) | | Other | | Chest radiography | Left lower-lobe infiltrate | Right upper, bilateral lower-lobe infiltrates | | Gastrointestinal symptoms | More than five episodes of watery diarrhoea without blood or mucus on the night of day 4 and ≥15 episodes on day 5 | Two episodes of watery diarrhoea without blood or mucus on day 3 | | Complications | Acute respiratory distress syndrome, respiratory failure, cardiac failure, disseminated intravenous coagulation, liver function impairment, renal dysfunction | Respiratory failure, liver dysfunction | | Treatment | | Mechanical ventilation | Intubation | Mask positive pressure ventilation | | Corticosteroids | Methylprednisolone 40 mg intravenously twice daily on days 6–9 | Methylprednisolone 40 mg intravenously twice daily on days 3–8 | | Rimantadine | No | 100 mg orally twice daily on days 3–7 | | Oseltamivir | No | 75 mg orally daily on day 1 of illness, 150 mg orally twice daily on days 2–6 | | Passive immunotherapy | No | 2×200 mL transfusion of post-vaccination plasma on day 5 | | Days from onset to death or discharge | 8, died | 23, discharge |
* Data are measurement at admission (peak or nadir measurement during hospitalisation).
Case two (the index patient's father), a 52-year-old retired engineer with hypertension, developed fever (38·1°C), chills, and cough on Dec 3. That night he took one dose of oseltamivir (75 mg orally) that had been distributed for chemoprophylaxis to contacts of the index case. The next morning, he was hospitalised with fever, mild thrombocytopenia, and bilateral pneumonia, and treated with levofloxacin, corticosteroids, and oseltamivir (150 mg orally twice daily for 5 days; table 1). Rimantadine (100 mg orally twice daily for 5 days) was started on day 3 of his illness. His respiratory status worsened, requiring positive pressure ventilation. On Dec 7, he received two 200 mL transfusions of plasma at 0100 h and 0500 h from a 30-year-old woman who had received two doses of inactivated whole-virion H5N1 vaccine (days 0 and 28) in a phase I clinical trial. 20 Plasma obtained 280 days after the second vaccine dose was negative for hepatitis B virus, hepatitis C virus, and HIV, and was heat-inactivated at 56°C for 10 h (neutralising antibody titres 1:40 against the clade 1 vaccine strain A/Vietnam/1194/2004-RG and 1:20 against case two's virus strain A/Jiangsu/2/2007). The patient's fever resolved that night. A chest radiograph on Dec 12 (day 10) showed improvement in the right upper and bilateral lower lobes ( figure 1). H5N1 virus was isolated from a throat swab collected on day 4 of the patient's illness, and H5N1 viral RNA was detected in throat and stool specimens up to 10 days after the onset of illness. The patient recovered fully and was discharged 22 days after admission.
Figure 1. Improvement of pulmonary lesions in chest radiographs from case two
(A) Bilateral lower-lobe infiltrates on day 4 of illness. (B) Reduction of pulmonary lesions in the right upper and bilateral lower lobes on day 10 of illness.
Complete genomic sequencing showed that the H5N1 viruses isolated from the index case (A/Jiangsu/1/2007) and case two (A/Jiangsu/2/2007) were identical, except for one non-synonymous nucleotide substitution in the NS gene (glutumate to glycine at aminoacid position 82) coding for the NS2 protein. All genes were entirely of avian origin and both isolates were characterised as H5N1 clade 2.3.4 viruses. 2 Sequence analyses indicated that these two isolates were highly homologous (sharing 97·2–98·9% homology in aminoacid sequences of the haemagglutinin gene) with viruses isolated from H5N1 cases in southern China. The haemagglutinin receptor-binding site was similar to that of other H5N1 viruses, and a polybasic aminoacid cleavage site (LRERRRKRG) was present. Sequencing of the M2 and neuraminidase genes of both viruses suggested susceptibility to adamantane and neuraminidase inhibitor antiviral drugs.
The index case lived with his mother in an apartment located in an urban area 10 km from his father's home, and rarely shared meals with him. No poultry were raised in the home or neighbourhood, and no live poultry were ever brought home. He had been bitten by a healthy pet dog 25 days before the onset of H5N1 illness and received four doses of rabies vaccine. He had consumed cooked poultry four times at restaurants during the 2 weeks before the onset of illness. No live poultry were present or slaughtered at these restaurants. He did not have any known direct contact with live poultry or ill individuals in the 2 weeks before the onset of illness. 6 days before the onset of illness, he visited a market to purchase vegetables and freshly killed pork with his girlfriend. She reported that the index case had not gone near the area where live poultry were sold and slaughtered in the market, 10 m from the section they had visited.
The index case's father did not raise poultry and had not brought live poultry into the home. He visited a market to purchase vegetables and bean curd 15 days and 8 days before the onset of illness. Live poultry were sold and slaughtered at this market, but the patient denied going near this area, which was 20 m from the vegetable stalls. The patient did not have any known contact with ill individuals except for his son during the 2 weeks before the onset of illness. After the index case became ill, the patient had close contact with him five times, including eating dinner together, providing care, and attending his funeral ( table 2). He provided unprotected bedside hospital care for the index case between Nov 27 and 29. The longest continuous time he spent caring for his son was 20 h. During this period, the index case had high fever (40·0°C), frequent coughing, extensive sputum production, and frequent episodes of watery diarrhoea. Case two had helped to change his son's soiled clothes and bedsheets, and had cleaned the toilet that had been used to dispose of diarrhoeal stool and a spittoon that contained copious sputum. The patient did not use personal protective equipment until after H5N1 had been confirmed in the index case late on Dec 1. A summary of the patient's exposure to one another is shown in figure 2.
Table 2.
Detailed exposure of case two to the index case before the onset of illness
Figure 2. Timeline of pertinent exposures and dates of onset of illness
100 close contacts of the H5N1 cases were identified and followed up daily for 10 days. Of these, 91 (91%) gave consent for collection of data, completed a questionnaire, and provided serum specimens, including nine (10%) household contacts, five (5%) social contacts, and 77 (85%) health-care workers who cared for the two cases ( table 3). Eight contacts (the index patient's mother and girlfriend, four family members, one colleague of the mother, and one health-care worker) were exposed to both cases.
Table 3.
Type of exposure and sera collection of 91 close contacts
Data are median (IQR) or n (%).
* Including direct contact (touching), preparation, cooking, and consumption of well-appearing poultry.
† For each of these analyses, data available for one participant only.
The median duration of exposure to at least one of the cases was 7 h (IQR 2–36). 78 (86%) of the close contacts reported taking oseltamivir chemoprophylaxis beginning on Dec 3, and some reported always wearing protective equipment, including surgical masks, N95 respirators, gloves, face shields, glasses, or gowns while caring for the two cases ( table 3). No adverse effects attributed to oseltamivir chemoprophylaxis were reported.
Only two of the 100 close contacts who were followed up—the index patient's girlfriend and one doctor—developed acute respiratory symptoms during the 10-day surveillance period. The girlfriend had a temperature of 37·3°C and onset of cough 5 days after her last known exposure to the index case and 1 day after her last known exposure to the index case's father. The doctor had a temperature of 37·3°C 3 days after the last known exposure to the index case. Both ill contacts had normal chest radiographs, and throat swabs collected from them on the first day of illness were negative for H5N1 by RT PCR.
Paired acute and convalescent sera were collected from 30 (33%) close contacts ( table 3), including from the index case's girlfriend. A convalescent serum specimen was collected from 61 (67%) other close contacts ( table 3), including the ill doctor. All serum tested negative for H5N1 antibodies (ie, all H5N1 neutralising antibody titres <1:10) by microneutralisation and horse red-blood-cell haemagglutinin inhibition assays. Discussion
In this family cluster of confirmed cases of infection with highly pathogenic avian influenza A (H5N1) virus in mainland China, we believe that the index case transmitted H5N1 virus to his father while his father cared for him in the hospital. The index case had high fever, cough, extensive sputum production, and watery diarrhoea while his father had prolonged, direct, and close unprotected contact with him. His father did not have any known exposure to poultry or to any other ill person before the onset of his illness. Possible transmission sources include inhalation of droplets expelled by the index case through coughing or via contact with the index case's clothes that were contaminated with diarrhoeal stool and subsequent inoculation of mucous membranes or the respiratory tract. Unlike in previous reports, [6] and [12] viral isolates were available from all cases. Our epidemiological findings are supported by genetic sequencing data that indicate that both case's H5N1 viral isolates were virtually identical.
We cannot ascertain when person-to-person transmission of H5N1 virus occurred, but the most likely incubation period after the father's unprotected exposure to his severely ill son is 4–5 days (range 3–6). Transmission is unlikely to have occurred during exposure to the index case at a restaurant on the day of fever onset, since the index case had yet to start coughing, or during a final 30-min hospital visit 3 days before the father's illness started. Although the index case's respiratory tract H5N1 viral load was probably high during his hospitalisation, his father wore a surgical mask during his last visit, but did not wear protective equipment during earlier hospital exposures. We doubt that transmission occurred at the funeral of the index case, a day before the onset of the father's illness, when personal protective equipment was used.
The only potential place of exposure to H5N1 virus that we identified for the index case was a market visit 6 days before the onset of illness. Visiting a wet poultry market, where avian influenza A viruses can be maintained and amplified, 21 has been identified as a risk factor for H5N1 infection in Hong Kong SAR 22 and urban China. 23 No outbreaks of H5N1 in poultry were identified in Nanjing before or after the two human cases were detected, and no sick or dead poultry were seen at markets in Nanjing during our investigations. Only H5-vaccinated poultry were sold in the markets visited by the cases. In parallel with our investigations, 540 cloacal, faecal, and environmental specimens were collected from live poultry, wild birds, and surfaces at 23 poultry markets, restaurants (including markets and restaurants visited by both cases), and parks in Nanjing City between Dec 2 and Dec 9. All specimens tested negative by real-time RT PCR for H5N1 and by virus culture at the Jiangsu Provincial Centre for Animal Disease Control and Prevention (Yaoxing Liu, personal communication). With regard to the father, the estimated H5N1 incubation period of 3–6 days after exposure to his son is more plausible 2 than the 8 days that had passed since his last visit to the market. However, we cannot exclude completely the possibility that both cases were infected with virtually the same H5N1 viral strain through exposures to different live poultry markets located 10 km apart with different sources of poultry.
The index case is unlikely to have acquired H5N1 virus infection through consumption of cooked poultry or poultry products, including boiled duck blood. There is no epidemiological evidence to date that H5N1 viruses can be transmitted to human beings by consumption of properly cooked poultry. 24 H5N1 virus infection has been detected in the gastrointestinal tract, but whether this is the site of initial infection is currently unknown. 25 We do not believe that the index case acquired H5N1 virus infection from contact with his pet dog, although infection of dogs with H5N1 virus has been documented. 26 A serum specimen collected from the dog on Jan 7, 2008, tested negative for H5N1 neutralising antibodies (unpublished data).
The index patient's positive bacterial blood culture result on Nov 28 delayed a diagnosis of H5N1 until he deteriorated while receiving broad-spectrum antibiotics. The effect of S choleraesuis infection on susceptibility to infection with H5N1 virus—or the severity of such infection—is unknown, especially since only one colony was found on blood culture, and contamination or partial pretreatment as an outpatient cannot be ruled out. S choleraesuis causes swine paratyphoid, and occasionally infects human beings and can cause bacteraemia. [27] and [28] Transient bacteraemia could explain the occasional febrile episodes he experienced in the 3 months before his H5N1 illness, although the timing of his bacterial infection is unknown. Since this pathogen is usually acquired from pigs, this infection could indicate food or water contamination. 27 However, the index case was reported to have eaten only properly cooked meat.
We found no evidence of transmission of H5N1 virus from the cases to any other close contacts, including the index case's mother and girlfriend, both of whom had prolonged, direct, and close unprotected exposure to both patients. A convalescent serum specimen was available for more than 90% of contacts—including two who had subsequently reported illness—and all were negative for H5N1 antibodies. All 34 individuals who reported visiting a live poultry market in the 2 weeks before the onset of illness in the two cases were also negative for antibodies against the virus. In 1997, one social contact, 29 six (12%) household contacts, 29 and eight (4%) health-care workers 30 exposed to cases had H5N1 neutralising antibodies. Our findings are consistent with studies done among health-care workers exposed to H5N1 cases in Vietnam [31] and [32] and Thailand 33 during 2004.
More than 90% of H5N1 case clusters have occurred in blood-related family members. 2 Although exposures must always be assessed among non-blood-relatives, this observation suggests that research is needed into potential genetic susceptibility to H5N1 virus infection. 34 The major challenge of such a study is the small number of case clusters that have occurred in different countries, which would require close international collaborations.
Unlike the index case, who was not diagnosed with H5N1 until just before death and did not receive oseltamivir, case two received early treatment with oseltamivir and rimantadine. On the fifth day of illness, he was also given post-vaccination plasma from a participant in a clade 1 H5N1 vaccine clinical trial. 20 The plasma showed fairly low cross-reactivity with the clade 2.3.4 H5N1 virus strain isolated from this case. Although case two's treatment with post-vaccination plasma was uncontrolled, as it was when another H5N1 patient also received convalescent H5N1 plasma, 35 survival of both cases warrants research into antiviral treatment combined with passive immunotherapy for individuals infected with H5N1 virus. Corticosteroids were given to both cases here, although WHO recommends against routine corticosteroid treatment for such patients. 36
Our investigations had several limitations. We could not elicit a complete exposure history from the index case before his death, but we interviewed his contacts, including his girlfriend, to verify his activities as much as possible. We also believe that it is difficult to trace all contacts who came within 1 m of the cases. We might have missed seroconversion in the nine contacts that remained healthy during the 10-day surveillance period, but who had declined serum collection. However, we believe that our serological findings from the other contacts, including all household and family contacts, suggest that it is unlikely that any asymptomatic or subclinical H5N1 virus infections were missed. We did not isolate any more than one H5N1 virus from either case to compare isolates during the case's clinical course. Stool specimens were not collected from the index case for H5N1 testing, but H5N1 virus has been detected or isolated from rectal swab and stool specimens from other patients infected with H5N1, 37 including the index case's father. Lastly, we were unable to assess H5N1 viral load in serial clinical specimens from case two because the quality of some of the specimens was suboptimal.
Our conclusion that limited, non-sustained person-to-person transmission of H5N1 virus probably occurred in this family cluster does not imply that H5N1 viruses have attained the ability to transmit more efficiently in human beings. A switch in receptor binding affinity has been suggested as a necessary factor, [38] and [39] but human infection with H5N1 virus that binds to receptors with α2,6-sialic acid linkages has occurred without further spread. 40 Viral characteristics required for sustained person-to-person H5N1 virus transmission remain unknown. H5N1 clusters require urgent investigation because of the possibility that a change in the epidemiology of H5N1 cases could indicate that H5N1 viruses have acquired the ability to spread more easily among people.
Contributors
Yu Wang, Hongjie Yu, Hua Wang, and Zijian Feng designed the protocol of investigation, set up the field epidemiology and clinical investigation, contacted all investigators; Hongjie Yu draft the manuscript; Dexin Li, Yuelong Shu, Jie Dong, Leying Wen, Libo Dong, Min Wang, Zhiyang Shi, and Ling Gu were responsible for virus isolation, microneutralisation, haemagglutination inhibition assay, RT PCR and real-time RT PCR testing, including the experimental design and analysis of data; Timothy Uyeki provided technical assistance for the epidemiological investigations, helped to review the data, and contributed to revising the manuscript. All other co-authors participated in collection and management of data.
Conflict of interest statement We declare that we have no conflict of interest.
Acknowledgments
We thank the local Centres for Disease Control and Prevention of Xuanwu District and Gulou District in Najing City for assistance in coordinating field investigations and provision logistics support. The views expressed in this study are those of the authors and do not represent the policy of China CDC or the US CDC. This study was supported by grants (2004BA519A17, 2004BA519A71, and 2006BAD06A02) from the Chinese Ministry of Science and Technology, the US National Institute of Allergy and Infectious Diseases, National Institutes of Health (CIPRA grant U19 AI51915), and the China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases.
References
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2 Writing Committee of the Second WHO Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus, Update on avian influenza A (H5N1) virus infection in humans, N Engl J Med 358 (2008), pp. 261–273.
3 WHO, WHO guidelines for investigation of human cases of avian influenza A http://www.who.int/csr/resources/publications/influenza/WHO_CDS_EPR_GIP_2006_4r1.pdf (accessed March 3, 2008)..
4 KY Yuen, PK Chan and M Peiris et al., Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus, Lancet 351 (1998), pp. 467–471. SummaryPlus | Full Text + Links | PDF (174 K) | View Record in Scopus | Cited By in Scopus (380)
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7 IN Kandun, H Wibisono and ER Sedyaningsih et al., Three Indonesian clusters of H5N1 virus infection in 2005, N Engl J Med 355 (2006), pp. 2186–2194. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (28)
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10 Anon, Human avian influenza in Azerbaijan, February–March 2006, Wkly Epidemiol Rec 81 (2006), pp. 183–188.
11 S Olsen, K Ungchusak and L Sovann et al., Family clustering of avian influenza A (H5N1), Emerg Infect Dis 11 (2005), pp. 1799–1801. View Record in Scopus | Cited By in Scopus (17)
12 K Ungchusak, P Auewarakul and SF Dowell et al., Probable person-to-person transmission of avian influenza A (H5N1), N Engl J Med 352 (2005), pp. 333–340. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (260)
13 WHO, Collecting, preserving and shipping specimens for the diagnosis of avian influenza A(H5N1) virus infection. Guide for field operations www.who.int/csr/resources/publications/surveillance/WHO_CDS_EPR_ARO_2006_1/en/ (accessed March 3, 2008)..
14 WHO, Recommendations and laboratory procedures for detection of avian influenza A(H5N1) virus in specimens from suspected human cases http://www.who.int/csr/disease/avian_influenza/guidelines/labtests/en/ (accessed March 3, 2008)..
15 E Spackman, DA Senne and TJ Myers et al., Development of a real-time reverse transcriptase PCR assay for type A influenza virus and the avian H5 and H7 hemagglutinin subtypes, J Clin Microbiol 40 (2002), pp. 3256–3260. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (137)
16 WHO, WHO manual on animal influenza diagnosis and surveillance http://www.who.int/vaccine_research/diseases/influenza/WHO_manual_on_animal-diagnosis_and_surveillance_2002_5.pdf (accessed March 3, 2008)..
17 T Rowe, RA Abernathy and J Hu-Primmer et al., Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays, J Clin Microbiol 37 (1999), pp. 937–943. View Record in Scopus | Cited By in Scopus (93)
18 I Stepheson, JM Wood, KG Nicholson and MC Zambon, Sialic acid receptor specificity on erythrocytes affects detection of antibody to avian influenza haemagglutinin, J Med Virol 70 (2003), pp. 391–398.
19 WHO, WHO case definitions for human infections with influenza A (H5N1) virus http://www.who.int/csr/disease/avian_influenza/guidelines/case_definition2006_08_29/en/ (accessed March 3, 2008)..
20 J Lin, J Zhang and X Dong et al., Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase I randomised controlled trial, Lancet 368 (2006), pp. 991–997. SummaryPlus | Full Text + Links | PDF (134 K) | View Record in Scopus | Cited By in Scopus (36)
21 RG Webster, Wet markets—a continuing source of severe acute respiratory syndrome and influenza?, Lancet 363 (2004), pp. 234–236. SummaryPlus | Full Text + Links | PDF (393 K) | View Record in Scopus | Cited By in Scopus (57)
22 AW Mounts, H Kwong and HS Izurieta et al., Case-control study of risk factors for avian influenza A (H5N1) disease, Hong Kong, 1997, J Infect Dis 180 (1999), pp. 505–508. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (93)
23 H Yu, Z Feng and X Zhang et al., Human influenza A(H5N1) cases, urban areas of People's Republic of China, 2005–2006, Emerg Infect Dis 13 (2007), pp. 1061–1064. View Record in Scopus | Cited By in Scopus (1)
24 Scientific Report of the Scientific Panel on Biological Hazards, Food as a possible source of infection with highly pathogenic avian influenza viruses for humans and other mammals, Eur Food Safety Authority J 74 (2006), pp. 1–29.
25 J Gu, Z Xie and Z Gao et al., H5N1 infection of the respiratory tract and beyond: a molecular pathology study, Lancet 370 (2007), pp. 1137–1145. SummaryPlus | Full Text + Links | PDF (381 K) | View Record in Scopus | Cited By in Scopus (6)
26 T Songserm, A Amonsin and R Jam-on et al., Fatal avian influenza A H5N1 in a dog, Emerg Infect Dis 12 (2006), pp. 1744–1747. View Record in Scopus | Cited By in Scopus (15)
27 CH Chiu, LH Su and C Chu, Salmonella enterica serotype Choleraesuis: epidemiology, pathogenesis, clinical disease, and treatment, Clin Microbiol Rev 17 (2004), pp. 311–322. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (29)
28 P Chassagne, MB Perol and J Doucet et al., Is presentation of bacteremia in the elderly the same as in younger patients?, Am J Med 100 (1996), pp. 65–70. SummaryPlus | Full Text + Links | PDF (600 K) | View Record in Scopus | Cited By in Scopus (47)
29 JM Katz, W Lim and CB Bridges et al., Antibody response in individuals infected with avian influenza A (H5N1) viruses and detection of anti-H5 antibody among household and social contacts, J Infect Dis 180 (1999), pp. 1763–1770. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (92)
30 C Buxton Bridges, JM Katz and WH Seto et al., Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong, J Infect Dis 181 (2000), pp. 344–348. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (101)
31 NT Liem and W Lim, Lack of H5N1 avian influenza transmission to hospital employees, Hanoi, 2004, Emerg Infect Dis 11 (2005), pp. 210–215.
32 C Schultsz, VC Dong and NV Chau et al., Avian influenza H5N1 and healthcare workers, Emerg Infect Dis 11 (2005), pp. 1158–1159. View Record in Scopus | Cited By in Scopus (28)
33 A Apisarnthanarak, S Erb and I Stephenson et al., Seroprevalence of anti-H5 antibody among Thai health care workers after exposure to avian influenza (H5N1) in a tertiary care center, Clin Infect Dis 40 (2005), pp. e16–e18. Full Text via CrossRef
34 VE Pitzer, SJ Olsen, CT Bergstrom, SF Dowell and M Lipsitch, Little evidence for genetic susceptibility to influenza A (H5N1) from family clustering data, Emerg Infect Dis 13 (2007), pp. 1074–1076. View Record in Scopus | Cited By in Scopus (2)
35 B Zhou, N Zhong and Y Guan, Treatment with convalescent plasma for influenza A (H5N1) Infection, N Engl J Med 357 (2007), pp. 1450–1451. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (2)
36 WHO, Clinical management of human infection with avian influenza A (H5N1) virus http://www.who.int/csr/disease/avian_influenza/guidelines/clinicalmanage07/en/index.html (accessed March 3, 2008)..
37 MD de Jong, CP Simmons and TT Thanh et al., Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia, Nat Med 12 (2006), pp. 1203–1207. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (72)
38 J Stevens, O Blixt and TM Tumpey et al., Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus, Science 312 (2006), pp. 404–410. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (70)
39 S Yamada, Y Suzuki and T Suzuki et al., Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors, Nature 444 (2006), pp. 378–382. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (48) 40 P Auewarakul, O Suptawiwat and A Kongchanagul et al., An avian influenza H5N1 virus that binds to a human-type receptor, J Virol 81 (2007), pp. 9950–9955. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (3)
Correspondence to: Prof Yu Wang, Chinese Center for Disease Control and Prevention, 27 Nanwei Road, Beijing, 100050, China
‡ Contributed equally
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April 8th, 2008, 11:17 AM
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Re: Chinese son likely gave bird flu to father: report
Leigh Dayton | April 09, 2008
IN a remarkable reversal of policy, Chinese scientists have for the first time reported openly about a case of person-to-person transmission of bird flu.
The scientists collaborated with researchers at the US Centres for Disease Control in Atlanta to confirm the case of a 52-year-old man who contracted bird flu from his 24-year-old son who died. The man survived.
The group - led by Yu Wang, of the Chinese Centre for Disease Control and Prevention in Beijing - reported yesterday in The Lancet that there was no evidence the deadly HVN1 virus had evolved to spread easily between people.
Dominic Dwyer, a medical virologist with the Institute for Clinical Pathology and Medical Research at Westmead Hospital in Sydney, welcomed the findings.
"Fortunately, there's still no (easy) human-to-human transmission," Professor Dwyer said. He noted that, to date, "less than half a dozen" people had died from H5N1 spread by a person, not a bird.
Virologist William Rawlinson, with Sydney's Prince of Wales hospital, said the genetic information provided would help diagnosis.
http://www.theaustralian.news.com.au...-25837,00.html
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April 8th, 2008, 11:21 AM
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by niman
Leigh Dayton | April 09, 2008
Dominic Dwyer, a medical virologist with the Institute for Clinical Pathology and Medical Research at Westmead Hospital in Sydney, welcomed the findings.
"Fortunately, there's still no (easy) human-to-human transmission," Professor Dwyer said. He noted that, to date, "less than half a dozen" people had died from H5N1 spread by a person, not a bird.
http://www.theaustralian.news.com.au...-25837,00.html |
The above comment is beyond absurd. There were six deaths in the Karo cluster alone that were due to H2H. WHO just acknowledged that the two deaths in Pakistan were H2H. The first cluster in Indonesia invovled two deaths due to H2H. The cluster in Azerbaijan involved half a dozen deaths due to H2H. There have been MANY smaller clusters of 2 or 3 involving fatal infections due to H2H, including the Thai cluster published in NEJM (mother and daughter died, aunt recoved from H2H infections).
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April 8th, 2008, 12:06 PM
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Re: Chinese son likely gave bird flu to father: report
Notable points:
Index case blood panel:
Lymphocytes (×109 per L) 0·49 (0·12)
Platelets (×109 per L) 88 (37)
Elevated PPT (nearly double high normal)
Pre-existing systemic infection, 3-month duration prior to acute illness:
The index case, a 24-year-old male salesman, was well until August, 2007, when he experienced transient chills and sweats once or twice a month.
The index case's only plausible exposure to H5N1 virus was a poultry market visit 6 days before the onset of illness. (time frame would be roughly consistent with exposure to airborne feather particulates from infected birds, in a wet-market setting).
He had been bitten by a healthy pet dog 25 days before the onset of H5N1 illness and received four doses of rabies vaccine.
An asymptomatic dog could have had H5N1 infection, an initial source of exposure. Alternatively, the rabies shots may have had an adverse effect on an immune system already taxed by a then chronic infection (viral or bacterial). The standard vaccination series is 5 doses (patient reported to have received four), administered weekly over the course of a month, along with a dose of Human Rabies Immune Globulin.
Possible side effects from HDCV vaccine adminstration:
* Local reactions include pain, redness, swelling, or itching at the injection site. Mild local reactions are reported by 30-74 % of vaccine recipients.
* Systemic reactions, including headache, nausea, abdominal pain, muscle aches, and dizziness, have been reported by 5-40% of people who received the vaccine.
* Six percent have an allergic reaction 2 to 21 days after vaccination.
Signs and symptoms include a generalized pruritic rash, angioedema, arthritis, arthralgias, nausea, vomiting, and malaise.
* Less common reactions are fever and difficulty breathing.
The index case is complicated by symptoms suggesting pre-existing, chronic infection.
The second case is also noteworthy: the patient was a professional in (early?) retirement (at 52), under treatment for hypertension.
Both patients had pre-existing conditions that contributed to H5N1 infectious susceptibility. Case 2 had multiple, extreme exposure events, without protection.
Hospital staff and girl friend had transient indicators of infectious exposure, without development.
I would NOT, repeat, NOT focus on this case as evidence of a family cluster H2H transmission with genetic factors.
There are predisposing conditions indicated, but they are related to geographical locale and ethnic factors, rather than familial susceptibility.
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April 8th, 2008, 12:14 PM
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by Oracle
Notable points:
Index case blood panel:
Lymphocytes (×109 per L) 0·49 (0·12)
Platelets (×109 per L) 88 (37)
Elevated PPT (nearly double high normal)
Pre-existing systemic infection, 3-month duration prior to acute illness:
The index case, a 24-year-old male salesman, was well until August, 2007, when he experienced transient chills and sweats once or twice a month.
The index case's only plausible exposure to H5N1 virus was a poultry market visit 6 days before the onset of illness. (time frame would be roughly consistent with exposure to airborne feather particulates from infected birds, in a wet-market setting).
He had been bitten by a healthy pet dog 25 days before the onset of H5N1 illness and received four doses of rabies vaccine.
An asymptomatic dog could have had H5N1 infection, an initial source of exposure. Alternatively, the rabies shots may have had an adverse effect on an immune system already taxed by a then chronic infection (viral or bacterial). The standard vaccination series is 5 doses (patient reported to have received four), administered weekly over the course of a month, along with a dose of Human Rabies Immune Globulin.
Possible side effects from HDCV vaccine adminstration:
* Local reactions include pain, redness, swelling, or itching at the injection site. Mild local reactions are reported by 30-74 % of vaccine recipients.
* Systemic reactions, including headache, nausea, abdominal pain, muscle aches, and dizziness, have been reported by 5-40% of people who received the vaccine.
* Six percent have an allergic reaction 2 to 21 days after vaccination.
Signs and symptoms include a generalized pruritic rash, angioedema, arthritis, arthralgias, nausea, vomiting, and malaise.
* Less common reactions are fever and difficulty breathing.
The index case is complicated by symptoms suggesting pre-existing, chronic infection.
The second case is also noteworthy: the patient was a professional in (early?) retirement (at 52), under treatment for hypertension.
Both patients had pre-existing conditions that contributed to H5N1 infectious susceptibility. Case 2 had multiple, extreme exposure events, without protection.
Hospital staff and girl friend had transient indicators of infectious exposure, without development.
I would NOT, repeat, NOT focus on this case as evidence of a family cluster H2H transmission with genetic factors.
There are predisposing conditions indicated, but they are related to geographical locale and ethnic factors, rather than familial susceptibility.
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I would say that the two most important phrases (emphasis added) in the paper were:
6 days before the onset of illness, he visited a market to purchase vegetables and freshly killed pork
A blood culture taken on Nov 28 yielded Salmonella cholerae suis
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April 8th, 2008, 12:37 PM
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Membro del Comitato Consultivo, Editore e Direttore del Forum Italiano di FluTrackers
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by niman
I would say that the two most important phrases (emphasis added) in the paper were:
6 days before the onset of illness, he visited a market to purchase vegetables and freshly killed pork
A blood culture taken on Nov 28 yielded Salmonella choleraesuis
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AIV in the pork meat or AIV in vegetables? It is use in backyard farm to collect faecal material from stables to employ as fertilizer for cultivation.
Faecal human material may carry the virus.
In every case, faecal contamination of raw food may lead to infection via oral route - simply touching the vegetables or other uncleaned objects in those markets.
In the past, Italy open-air markets sold vegetables clearly covered by dirt, and chemical fertilizer and sometimes human-faecal-derived fertilizer....
After widespread cholera and salmonella epidemics a strict regulation was imposed. (I talk of late '70).
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April 8th, 2008, 12:41 PM
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Re: Chinese son likely gave bird flu to father: report
Niman, it's OBVIOUS that he had a Salmonella infection (either typhoid or nontyphoidal strains) - but there is more to this story, and it has ZERO to do with pork. This was a prolonged infection, first reported by the patient in August 2007.
"Transient bacteraemia could explain the occasional febrile episodes he experienced in the 3 months before his H5N1 illness, although the timing of his bacterial infection is unknown. Since this pathogen is usually acquired from pigs, this infection could indicate food or water contamination."
Trust me on this one, China has MAJOR water quality issues; it's just as likely that he contracted the Salmonella infection from the water supply as from preparing pork.
Empyema Thoracis from Salmonella choleraesuis.
http://www.cdc.gov/ncidod/EID/vol11no09/05-0030.htm
Note that the cases identifed in this Salmonella empyema article had pre-existing chronic disease (liver, gallbladder).
The index case bicarbonate reading is off; unfortunately, we don't have the data to calculate anion gap.
Also, it's patently obvious that a commercial entity is interested in peddling it's serum product:
author affiliation - Sinovac Biotech Co, Beijing, China - Phase II bird flu vaccine.
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April 8th, 2008, 01:38 PM
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Re: Chinese son likely gave bird flu to father: report
I wouldn't rule out H5N1 in swine. There have been major problems with swine deaths in China for some time (years). Although other pathogens have been isolated, those pathogens previously had been relatively harmless and the involvement in the fatal swine infections remains unclear.
Sequences from H5N1 from 2001/2003 in China swine are at Genbank. A more recent series was submitted, but withdrawn, although they can still be accessed. The public and pulled sequences are from isolates throughout southern China.
| 1: DQ997083 | 
Reports
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Links
| Influenza A virus (A/swine/Anhui/cb/2004(H5N1)) polymerase basic protein 2 (PB2) gene, partial cds
gi|116583267|gb|DQ997083.1|[116583267]
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April 8th, 2008, 01:58 PM
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Re: Chinese son likely gave bird flu to father: report
Quote:
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I wouldn't rule out H5N1 in swine. There have been major problems with swine deaths in China for some time (years). Although other pathogens have been isolated, those pathogens previously had been relatively harmless and the involvement in the fatal swine infections remains unclear.
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Aren't swine the ultimate mixing vessel and the last likely mammalian "set-up" stage for H2H transmisability? There are big implications are there not?
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April 8th, 2008, 02:05 PM
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by Gnosis
Aren't swine the ultimate mixing vessel and the last likely mammalian "set-up" stage for H2H transmisability? There are big implications are there not?
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H5N1 and swine generate a lot of attention. Throw in China and Indonesia and almost anything can happen.
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April 8th, 2008, 02:39 PM
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Re: Chinese son likely gave bird flu to father: report
While Henan cannot be considered Southern China, it is on a direct line through Anhui to Jiangxi. Earlier ingestion of contaminated water or pork certainly would be consistent with a prolonged Salmonella infection.
We have:
Possible underlying disease (my bet is on choleothiasis), clearly linked to the aforementioned but otherwise rare, Salmonella empeyma thoracis, with lack of white blood cell count elevation, indicating immune suppression (that may or may not have been excerbated by HDCV series vaccine in the month before acute infection onset).
I think the index patient didn't die of H5N1 infection (although it was probably present as a secondary infection). He died of late and inappropriate treatment for a long-standing Salmonella infection that had already progressed to rampant pneumonia. Furthermore, in Taiwan cases of Salmonella enterica subtype choleraesuis was found to be drug resistant in more than 2/3rds of thoracic empeyma cases, exhibiting high case mortality as a result of inappropriate drug treatment.
Case 2 is similarly interesting, because of underlying liver disease, but is otherwise a more straightforward direct H5N1 infection.
The real reason for the publication hoopla is the use of anti-sera in Case 2.
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April 8th, 2008, 03:15 PM
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by Oracle
The real reason for the publication hoopla is the use of anti-sera in Case 2.
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The hoopla is the same as each H5N1 H2H publication (in NEJM, JAMA, and now Lancet).
The paper showed that China used two antivirals (Tamiflu and Rimantadine), as well as passive immunotherapy (against clade 1). Since the H5N1 was clade 2.3.4 it is unlikely that the immunotherapy carried the day, but this was publishable because it was clear cut H2H (no direct link for father other than son).
H5N1 H2H happens all the time, but only those without a poultry connection are written up (as has been done for Thailand, Indonesia, and China).
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April 8th, 2008, 03:21 PM
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Re: Chinese son likely gave bird flu to father: report
how can we be sure that we hear about all the H2H occurances in china/pakistan/korea/etc? would there be villages/provinces too afraid to contact authorities about their sick? would there be clusters in remote areas that we would never hear about?
sorry - i'm getting a little paranoid and worried..
Last edited by sharon sanders; April 8th, 2008 at 03:36 PM.
Reason: typo
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April 8th, 2008, 04:03 PM
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by janetney
how can we be sure that we hear about all the H2H occurances in china/pakistan/korea/etc? would there be villages/provinces too afraid to contact authorities about their sick? would there be clusters in remote areas that we would never hear about?
sorry - i'm getting a little paranoid and worried..
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Paranoid! No.... The cases happened in December! With the highest inhabitants density rate of the world, southern China would have accounted an amount of fatalities if a more tansmissible virus was emerged in relation to the discovery of this familiar cluster.
Again, continuing overlooked socio-economical, demographic, and epidemiological evidences lead to improper facts evaluation.
If one decides to start panicking every time media fanfare happens, it is time to stop to read and move further.
Excuse me, but I currently experience a bit of disappoint for these booming news writers (I refer to major press agencies not reviews), too anxious and too little open in geographical, demographic and socio-economics determinants in the background of the facts they are talking.
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April 8th, 2008, 04:20 PM
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Re: Chinese son likely gave bird flu to father: report
wow...i can't tell if you're ticked off at me or someone else...
i'm just going to read posts for awhile...i can see that i'm clearly out of my league...
note: i love reading your posts; even if i don't understand hardly any of them...
Last edited by sharon sanders; April 8th, 2008 at 04:59 PM.
Reason: typo
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April 8th, 2008, 04:57 PM
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by janetney
wow...i can't tell if you're pissed off at me or someone else...
i'm just going to read posts for awhile...i can see that i'm clearly out of my league...
note: i love reading your posts; even if i don't understand hardly any of them...
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Oh no! Please excuse me for the irruence and I hope you will accept this apology. You are welcomed as I was at FT, of course. I would like only to highlight the need to put every event in a correct perspective; often, media reports tend to speculate a bit about promising pieces of news. IoH
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April 8th, 2008, 05:10 PM
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by janetney
wow...i can't tell if you're pissed off at me or someone else...
i'm just going to read posts for awhile...i can see that i'm clearly out of my league...
note: i love reading your posts; even if i don't understand hardly any of them...
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Janetney, I don't think IOH is directing his comments to you. He is speaking about the media reporting process. H2H transmission is regularly occurring in several countries. Only now is it making news in main stream media. IOH is pointing out that the China cases as well as the Pakistan cases of H2H happened several months ago; if it were easily transmissible we would be in the middle of a pandemic right now.
The concern is that reporters and media outlets are twisting the news to sensationalize it and place it in the immediate present. Old news, stale news does not sell.
An increase in main stream news articles about H2H transmission will have no causal affect on a pandemic. The pandemic will occur when all of viral pieces fall into place and it becomes easily transmissible.
Last edited by Laidback Al; April 9th, 2008 at 01:41 AM.
Reason: I'll leave this post, even though IOH has addressed your post.
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April 8th, 2008, 05:23 PM
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Re: Chinese son likely gave bird flu to father: report
i am mortified that you think my feelings were hurt...by no means! i can only imagine your frustration at the MSM and the sensationalization of any news about birdflu...
i love this site...i feel comfort at this site...
i just re-read my post and it DID sound like i was upset...i'm so sorry!
you all are so amazing in your research and knowledge and ability to break down information...i am in awe...
janet
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April 8th, 2008, 05:46 PM
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Re: Chinese son likely gave bird flu to father: report
We like you too Janet. We have many different languages and cultures here which makes for some interesting conversations! Sometimes there are some small misunderstandings. For example, I never knew that there were so many different dialects of English around the world. lol
While we are all from different backgrounds, we speak with the same heart.
The heart of compassion, understanding, and acceptance.
Welcome again.
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April 8th, 2008, 05:57 PM
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Re: Chinese son likely gave bird flu to father: report
what a beautiful post...thank you...
as for the different dialects: i'm from the 'south' (Texas) - right on the gulf coast, and yes, i'm cajun...so, if you were to hear my voice, you would laugh VERY hard....so, i know about sounding different! it's fun, isn't it? ha!
and living in california makes it even more interesting! my own kids make fun of me!
but, thank you for being so welcoming...you don't know how much i appreciate it....
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April 9th, 2008, 12:29 AM
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by Oracle
While Henan cannot be considered Southern China, it is on a direct line through Anhui to Jiangxi. Earlier ingestion of contaminated water or pork certainly would be consistent with a prolonged Salmonella infection.
We have:
Possible underlying disease (my bet is on choleothiasis), clearly linked to the aforementioned but otherwise rare, Salmonella empeyma thoracis, with lack of white blood cell count elevation, indicating immune suppression (that may or may not have been excerbated by HDCV series vaccine in the month before acute infection onset).
I think the index patient didn't die of H5N1 infection (although it was probably present as a secondary infection). He died of late and inappropriate treatment for a long-standing Salmonella infection that had already progressed to rampant pneumonia. Furthermore, in Taiwan cases of Salmonella enterica subtype choleraesuis was found to be drug resistant in more than 2/3rds of thoracic empeyma cases, exhibiting high case mortality as a result of inappropriate drug treatment.
Case 2 is similarly interesting, because of underlying liver disease, but is otherwise a more straightforward direct H5N1 infection.
The real reason for the publication hoopla is the use of anti-sera in Case 2.
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Here is an NA travel log for a wild bird in China. There is an intimate relationship between wild birds and swine alathough its not limited to China (although this travel log includes wild birds in China). Wild bird in black bold (H5N1 from 2005/2006), swine in red, human in red bold
gb|CY030737.1| Influenza A virus (A/swine/Tennessee/9/1978(H1... 36.2 0.005
gb|EU502888.1| Influenza A virus (A/swine/Shanghai/1/2005(H1N... 36.2 0.005
gb|EU429763.1| Influenza A virus (A/duck/Eastern China/51/200... 36.2 0.005
gb|EU429757.1| Influenza A virus (A/duck/Eastern China/40/200... 36.2 0.005
gb|CY028782.1| Influenza A virus (A/swine/California/T9001707... 36.2 0.005
gb|CY028790.1| Influenza A virus (A/swine/Iowa/1/1986(H1N1)) ... 36.2 0.005
gb|CY028437.1| Influenza A virus (A/swine/Tennessee/7/1978(H1... 36.2 0.005
gb|CY028429.1| Influenza A virus (A/swine/Tennessee/4/1978(H1... 36.2 0.005
gb|CY028189.1| Influenza A virus (A/swine/Wisconsin/30747/197... 36.2 0.005
gb|CY028181.1| Influenza A virus (A/swine/Tennessee/3/1978(H1... 36.2 0.005
gb|CY028173.1| Influenza A virus (A/swine/Iowa/2/1987(H1N1)) ... 36.2 0.005
gb|CY027509.1| Influenza A virus (A/swine/Iowa/2/1985(H1N1)) ... 36.2 0.005
gb|CY027525.1| Influenza A virus (A/swine/Tennessee/8/1978(H1... 36.2 0.005
gb|CY027517.1| Influenza A virus (A/swine/Tennessee/5/1978(H1... 36.2 0.005
gb|CY027309.1| Influenza A virus (A/swine/Tennessee/2/1978(H1... 36.2 0.005
gb|CY027301.1| Influenza A virus (A/swine/Tennessee/118/1977(... 36.2 0.005
gb|CY026493.1| Influenza A virus (A/swine/Tennessee/112/1977(... 36.2 0.005
gb|CY026485.1| Influenza A virus (A/swine/Tennessee/106/1977(... 36.2 0.005
gb|CY026477.1| Influenza A virus (A/swine/Tennessee/105/1977(... 36.2 0.005
gb|CY026461.1| Influenza A virus (A/swine/Tennessee/10/1976(H... 36.2 0.005
gb|CY026453.1| Influenza A virus (A/swine/Ontario/6/1981(H1N1... 36.2 0.005
gb|CY026445.1| Influenza A virus (A/swine/Ontario/3/1981(H1N1... 36.2 0.005
gb|CY026437.1| Influenza A virus (A/swine/Ontario/2/1981(H1N1... 36.2 0.005
gb|CY026421.1| Influenza A virus (A/swine/Tennessee/23/1976(H... 36.2 0.005
gb|CY026301.1| Influenza A virus (A/swine/Wisconsin/2/1966(H1... 36.2 0.005
gb|CY026293.1| Influenza A virus (A/swine/Wisconsin/1/1967(H1... 36.2 0.005
gb|CY026285.1| Influenza A virus (A/swine/Wisconsin/1/1957(H1... 36.2 0.005
gb|EU050105.1| Influenza A virus (A/chukkar/Shantou/2888/2003... 36.2 0.005
gb|CY026141.1| Influenza A virus (A/Wisconsin/301/1976(H1N1))... 36.2 0.005
gb|EU139839.1| Influenza A virus (A/swine/North Carolina/3688... 36.2 0.005
gb|EU139837.1| Influenza A virus (A/swine/Minnesota/37866/199... 36.2 0.005
gb|EU139835.1| Influenza A virus (A/swine/Wisconsin/1/1968(H1... 36.2 0.005
gb|CY025207.1| Influenza A virus (A/swine/Tennessee/37/1977(H... 36.2 0.005
gb|CY025012.1| Influenza A virus (A/swine/Kansas/3024/1987(H1... 36.2 0.005
gb|CY025059.1| Influenza A virus (A/swine/Tennessee/48/1977(H... 36.2 0.005
gb|CY024927.1| Influenza A virus (A/Ohio/3559/1988(H1N1)) seg... 36.2 0.005
gb|CY025004.1| Influenza A virus (A/swine/Arizona/148/1977(H1... 36.2 0.005
gb|CY024996.1| Influenza A virus (A/swine/Wisconsin/663/1980(... 36.2 0.005
gb|CY024988.1| Influenza A virus (A/swine/Tennessee/10/1978(H... 36.2 0.005
gb|CY024980.1| Influenza A virus (A/swine/Tennessee/88/1977(H... 36.2 0.005
gb|CY024972.1| Influenza A virus (A/swine/Tennessee/87/1977(H... 36.2 0.005
gb|CY024964.1| Influenza A virus (A/swine/Tennessee/86/1977(H... 36.2 0.005
gb|CY024956.1| Influenza A virus (A/swine/Tennessee/84/1977(H... 36.2 0.005
gb|CY024935.1| Influenza A virus (A/swine/Minnesota/24/1975(H... 36.2 0.005
gb|CY022972.1| Influenza A virus (A/swine/Iowa/31483/1988(H1N... 36.2 0.005
gb|CY022964.1| Influenza A virus (A/swine/Iowa/1/1987(H1N1)) ... 36.2 0.005
gb|CY022996.1| Influenza A virus (A/swine/Wisconsin/629/1980(... 36.2 0.005
gb|CY022980.1| Influenza A virus (A/swine/Ontario/1/1981(H1N1... 36.2 0.005
gb|CY022956.1| Influenza A virus (A/swine/Iowa/1/1977(H1N1)) ... 36.2 0.005
gb|CY022319.1| Influenza A virus (A/swine/Iowa/1/1985(H1N1)) ... 36.2 0.005
gb|CY022327.1| Influenza A virus (A/swine/Iowa/3/1985(H1N1)) ... 36.2 0.005
gb|CY022335.1| Influenza A virus (A/swine/Iowa/17672/1988(H1N... 36.2 0.005
gb|CY022431.1| Influenza A virus (A/swine/Wisconsin/1915/1988... 36.2 0.005
gb|CY022471.1| Influenza A virus (A/swine/Kansas/3228/1987(H1... 36.2 0.005
gb|CY022479.1| Influenza A virus (A/swine/Maryland/23239/1991... 36.2 0.005
gb|CY022463.1| Influenza A virus (A/swine/Wisconsin/8/1980(H1... 36.2 0.005
gb|CY022455.1| Influenza A virus (A/swine/Wisconsin/661/1980(... 36.2 0.005
gb|CY022447.1| Influenza A virus (A/swine/Wisconsin/641/1980(... 36.2 0.005
gb|CY022439.1| Influenza A virus (A/swine/Wisconsin/2/1970(H1... 36.2 0.005
gb|CY022423.1| Influenza A virus (A/swine/Wisconsin/11/1980(H... 36.2 0.005
gb|CY022415.1| Influenza A virus (A/swine/Wisconsin/1/1971(H1... 36.2 0.005
gb|CY022407.1| Influenza A virus (A/swine/Tennessee/11/1978(H... 36.2 0.005
gb|CY022399.1| Influenza A virus (A/swine/Tennessee/1/1975(H1... 36.2 0.005
gb|CY022391.1| Influenza A virus (A/swine/Ontario/7/1981(H1N1... 36.2 0.005
gb|CY022383.1| Influenza A virus (A/swine/Ontario/4/1981(H1N1... 36.2 0.005
gb|CY022375.1| Influenza A virus (A/swine/Nebraska/123/1977(H... 36.2 0.005
gb|CY022367.1| Influenza A virus (A/swine/Minnesota/5892-7/19... 36.2 0.005
gb|CY022359.1| Influenza A virus (A/swine/Minnesota/27/1976(H... 36.2 0.005
gb|CY022351.1| Influenza A virus (A/swine/Kentucky/1/1976(H1N... 36.2 0.005
gb|CY022343.1| Influenza A virus (A/swine/Illinois/1/1975(H1N... 36.2 0.005
gb|CY022303.1| Influenza A virus (A/swine/Tennessee/82/1977(H... 36.2 0.005
gb|CY022295.1| Influenza A virus (A/swine/Tennessee/79/1977(H... 36.2 0.005
gb|CY022287.1| Influenza A virus (A/swine/Tennessee/65/1977(H... 36.2 0.005
gb|CY022143.1| Influenza A virus (A/swine/Tennessee/64/1977(H... 36.2 0.005
gb|CY022135.1| Influenza A virus (A/swine/Tennessee/49/1977(H... 36.2 0.005
gb|CY022127.1| Influenza A virus (A/swine/Tennessee/31/1977(H... 36.2 0.005
gb|CY022119.1| Influenza A virus (A/swine/Tennessee/21/1977(H... 36.2 0.005
gb|CY022111.1| Influenza A virus (A/swine/Tennessee/19/1977(H... 36.2 0.005
gb|CY022103.1| Influenza A virus (A/swine/Iowa/4/1976(H1N1)) ... 36.2 0.005
gb|CY022063.1| Influenza A virus (A/swine/Tennessee/19/1976(H... 36.2 0.005
gb|CY022071.1| Influenza A virus (A/swine/Iowa/1/1976(H1N1)) ... 36.2 0.005
gb|CY022055.1| Influenza A virus (A/swine/Tennessee/17/1976(H... 36.2 0.005
gb|CY022047.1| Influenza A virus (A/swine/Tennessee/15/1976(H... 36.2 0.005
gb|CY022039.1| Influenza A virus (A/swine/Tennessee/7/1976(H1... 36.2 0.005
gb|CY022031.1| Influenza A virus (A/swine/Tennessee/3/1976(H1... 36.2 0.005
gb|CY021959.1| Influenza A virus (A/New Jersey/1976(H1N1)) se... 36.2 0.005
gb|CY021055.1| Influenza A virus (A/Malaya/302/1954(H1N1)) se... 36.2 0.005
gb|DQ835315.1| Influenza A virus (A/China/GD01/2006(H5N1)) se... 36.2 0.005
gb|EF124198.1| Influenza A virus (A/common magpie/Hong Kong/3... 36.2 0.005
gb|EF124197.1| Influenza A virus (A/house crow/Hong Kong/2858... 36.2 0.005
gb|EF124196.1| Influenza A virus (A/house crow/Hong Kong/2648... 36.2 0.005
gb|EF124195.1| Influenza A virus (A/large-billed crow/Hong Ko... 36.2 0.005
gb|EF124194.1| Influenza A virus (A/white-backed munia/Hong K... 36.2 0.005
gb|EF124193.1| Influenza A virus (A/munia/Hong Kong/2454/2006... 36.2 0.005
gb|EF124192.1| Influenza A virus (A/common magpie/Hong Kong/2... 36.2 0.005
gb|EF124191.1| Influenza A virus (A/common magpie/Hong Kong/2... 36.2 0.005
gb|EF124190.1| Influenza A virus (A/Japanese white-eye/Hong K... 36.2 0.005
gb|DQ923509.1| Influenza A virus (A/swine/Korea/CN22/2006(H3N... 36.2 0.005
gb|DQ923508.1| Influenza A virus (A/swine/Korea/PZ72-1/2006(H... 36.2 0.005
gb|DQ150435.1| Influenza A virus (A/swine/IN/PU542/04 (H3N1))... 36.2 0.005
gb|AY207546.1| Influenza A virus (A/duck/New Zealand/76/84(H3... 36.2 0.005
gb|AY207540.1| Influenza A virus (A/mallard/Stralsund/41-6/81... 36.2 0.005
gb|DQ280259.1| Influenza A virus (A/swine/Wisconsin/238/97(H1... 36.2 0.005
gb|DQ280202.1| Influenza A virus (A/swine/Alberta/56626/03(H1... 36.2 0.005
gb|CY009342.1| Influenza A virus (A/Malaysia/54(H1N1)) segmen... 36.2 0.005
gb|AF494254.1| Influenza A virus (A/India/80(H1N1)) neuramini... 36.2 0.005
emb|AJ410559.1|INA410559 Influenza A virus genomic RNA for ne... 36.2 0.005
emb|AJ410558.1|INA410558 Influenza A virus genomic RNA for ne... 36.2 0.005
gb|CY005748.1| Influenza A virus (A/duck/NZL/76/1984(H9N1)) s... 36.2 0.005
gb|AF250363.2|AF250363 Influenza A virus (A/NJ/11/76 (H1N1)) ... 36.2 0.005
gb|U86145.1|IAU86145 Influenza A virus (A/Swine/Quebec/5393/9... 36.2 0.005
gb|U86144.1|IAU86144 Influenza A virus (A/Swine/Quebec/192/81... 36.2 0.005
gb|U47818.1|IAU47818 Influenza A virus (A/swine/Hong Kong/273... 36.2 0.005
gb|U47816.1|IAU47816 Influenza A virus (A/Wisconsin/3523/1988... 36.2 0.005
dbj|D31946.1|FLANANJ76 Influenza A virus (A/New Jersey/8/1976... 36.2 0.005
gb|M27970.1|FLAHANENJ8 Influenza A virus (A/NJ/8/1976(H1N1)) ... 36.2 0.005
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April 9th, 2008, 08:06 AM
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Editor and Director of the China Forum
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Join Date: Feb 2006
Posts: 7,637
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Re: Chinese son likely gave bird flu to father: report
| VN Calm over Neighbor’s Human-To-Human Bird Flu Transmission Report | Amid disturbing news that a Chinese man contracted bird flu directly from his son, a Vietnamese health official affirmed the Southeast Asian nation has yet to receive official confirmation from WHO of human-to-human transmission cases in any country.
 | | Viet Nam has not yet received official confirmation from the World Health Organization about human-to-human transmission of bird flu |
“The Chinese human-to-human transmission case could have happened under rare circumstances due to prolonged exposure to the infected person”, Dr. Nga added.
Doctor Nguyen Tran Hien, director of the Vietnamese Central Institute for Hygiene and Epidemiology, also assured no human-to-human transmission case has ever been detected in the country and that infections all stemmed from contact with sick fowls.
But Hien warned the virus is showing signs of transforming into more lethal forms since the fatality rate from H5N1 infection has jumped to nearly 100% from 55% several years ago. So far this year, five Vietnamese are reported to have contracted bird flu, and all have died.
Yesterday, Channel News Asia (CNA) reported that a 24-year-old man in Nanjing “probably infected his father with the H5N1 strain of bird flu before dying”.
The Singapore-based media corp. said “the case is one of a handful over the last four years in which the H5N1 virus is suspected to have spread from one person to another”.
The article also quoted an epidemiologist as saying such suspected cases have all been "within the family, among blood relatives".
Since 2003, there have been 373 bird flu infections worldwide with 236 fatalities, 52 of which were in Viet Nam. http://www.saigon-gpdaily.com.vn/Health/2008/4/62586/
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April 9th, 2008, 09:30 AM
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Retired
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Re: Chinese son likely gave bird flu to father: report
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April 9th, 2008, 10:51 AM
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Advisory Board
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by niman
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"A great deal of effort focuses on splitting hairs between a familial cluster due to a common source (poultry) and clusters due to H2H transmission. This distinction is not significant, since both signal a more efficient transmission,...."
I'm sorry, but I still don't get it. I keep coming back to this transmission argument, and I must apologize to seeming like a dog with a bone.
How can "both signal a more efficient transmission"?
If I have contact with an infected bird and get sick, and my brother contacts the same infected bird and gets sick, transmission is logically the same in both cases. Bird to human, virus into the lower respiratory tract, twice.
And if I have close contact with an infected bird and get sick, and my brother has close contact with me and gets sick, what's the difference? Neither situtation indicates a more efficient transmission. It's still bird virus to human, virus into the lower respiratory tract, twice.
Yes, I agree that H2H clusters are occuring (and that all the media, WHO and government risk management tactics are merely noise); however, I'm yet to be convinced that the clusters are significantly different in transmission efficiency than any other bird-human transmission that we've previously seen.
Correct me if I'm wrong, but all the h2h clusters seen so far involve intimate circumstances: repeated exposure to blood, sputum, etc. There's not been a case of casual contact (such as we regularly see in normal influenza) leading to h2h, yet.
Perhaps we're at the limit of what epidemiology (or tracking cases) can tell us at the moment. Until we see the logarithmic explosion of cases, epi analysis is at a hiatus, a low spot, a log-jam.
Until we get the logarithmic explosion, we need the surveillance, samples and science results that show us the cones are now umbrellas, or the clear genetic story, in layman's tersm, of the changes that will justify our terror.
J.
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April 9th, 2008, 11:16 AM
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Retired
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Re: Chinese son likely gave bird flu to father: report
Quote:
Originally Posted by cartski
"A great deal of effort focuses on splitting hairs between a familial cluster due to a common source (poultry) and clusters due to H2H transmission. This distinction is not significant, since both signal a more efficient transmission,...."
I'm sorry, but I still don't get it. I keep coming back to this transmission argument, and I must apologize to seeming like a dog with a bone.
How can "both signal a more efficient transmission"?
If I have contact with an infected bird and get sick, and my brother contacts the same infected bird and gets sick, transmission is logically the same in both cases. Bird to human, virus into the lower respiratory tract, twice.
And if I have close contact with an infected bird and get sick, and my brother has close contact with me and gets sick, what's the difference? Neither situtation indicates a more efficient transmission. It's still bird virus to human, virus into the lower respiratory tract, twice.
Yes, I agree that H2H clusters are occuring (and that all the media, WHO and government risk management tactics are merely noise); however, I'm yet to be convinced that the clusters are significantly different in transmission efficiency than any other bird-human transmission that we've previously seen.
Correct me if I'm wrong, but all the h2h clusters seen so far involve intimate circumstances: repeated exposure to blood, sputum, etc. There's not been a case of casual contact (such as we regularly see in normal influenza) leading to h2h, yet.
Perhaps we're at the limit of what epidemiology (or tracking cases) can tell us at the moment. Until we see the logarithmic explosion of cases, epi analysis is at a hiatus, a low spot, a log-jam.
Until we get the logarithmic explosion, we need the surveillance, samples and science results that show us the cones are now umbrellas, or the clear genetic story, in layman's tersm, of the changes that will justify our terror.
J.
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Clusters are more efficientn than sporadic cases. Transmission is not an all or none event.
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April 10th, 2008, 12:55 PM
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Membro del Comitato Consultivo, Editore e Direttore del Forum Italiano di FluTrackers
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Re: Chinese son likely gave bird flu to father: report
[Angus Nicoll - Eurosurveillance Weekly]
(1) [AVIAN INFLUENZA, HUMAN, CLUSTERED CASES, CHINA, UPDATES, ESWI] (Yet) another human A/H5N1 influenza case and cluster when should Europe be concerned?
A Nicoll (angus.nicoll@ecdc.europa.eu)
European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
A Chinese report of a case from Jiangsu province of an almost certain son-to-father transmission of avian influenza type A/H5N1 infection was published this week, along with an accompanying comment [1,2].
The source of the 24-year-old son’s infection was not established, but the authors suggest this might have occurred during a visit to a market where there was live poultry [1].
Such a way of acquiring infection (rather than direct or close contact with sick domestic poultry) has been suggested in a number of the few human cases recently detected in China [3].
However, in the case described in The Lancet, contact with poultry was not certain and, despite some retrospective investigations in the market, no H5N1 viruses were detected in birds.
The son eventually died and his 52-year-old father almost certainly acquired the infection while caring for him in the hospital, as was the case in another probable human–to-human transmission in Thailand in 2004 [1,4].
In the recent Chinese cluster, the cases, their contacts and the circumstances of transmission were well investigated epidemiologically and virologically, with over ninety contacts traced.
Control measures were vigorous, with contacts being treated with chemoprophylaxis, as recommended by the World Health Organization (WHO) [1,5].
The rigour of the investigation contrasts with many earlier outbreaks and is praised in the accompanying comment [2,6].
Only two of the contacts developed illness that was compatible with bird flu by symptoms and timing, but both were negative for markers of A/H5N1 infection (i.e. their illness had to be due to another cause) [1].
Although the viruses in the father and son were almost identical, the authors still could not be entirely certain that this was human-to-human transmission [1], because it was impossible to entirely rule out shared or common exposure to infected birds or environmental contamination.
This explanation is commonly considered in the investigations of human A/H5N1 cases and is the reason why attempts to determine the number of person-to-person transmissions have been unsuccessful.
Their results are lists of clusters with varying levels of probabilities [6,7].
Attempts at modelling these clusters have been made [8], but these cannot substitute proper field and laboratory investigations, such as were carried out in the Chinese cluster [1].
However, it would be unreasonable for anyone to still argue that person-to-person transmission of A/H5N1 has never occurred [5].
Indeed, it probably occurs more often than it seems, simply because of the multiple possible routes of exposure in most clusters.
Usually, where birds could be the source, they are assumed to be the source of all human infections [6].
A cause for concern for epidemiologists in these and other recent cases in China (and Vietnam) is the difficulty in identifying the primary source of infection for the human cases.
How did the viruses get from birds into humans?
This could not be determined in Jiangsu and sometimes cannot be done elsewhere [1,3].
It has been suggested that this may partially reflect the success of the impressive Chinese veterinary campaigns to immunise all domestic poultry.
These have been highly effective in reducing outbreaks in birds and hence much of the need for mass culling of birds.
This in turn has eliminated the economic and social misery that follows for the owners, who may not always be compensated in a timely manner.
However, since poultry immunisation prevents disease but cannot eliminate infection in birds, it probably has left A/H5N1 silently transmitting among poultry, and existing in the environment near poultry albeit at low levels [9].
This is probably also making detection and surveillance for human A/H5N1 cases more difficult.
The previous marker of contact with a die-off in poultry in sick humans with atypical pneumonias as a trigger for testing for A/H5N1 has been lost.
Local officials and clinicians in endemic countries find it hard to test for H5N1 in all people with symptoms compatible with human A/H5N1 infection. This is being attempted in Thailand but not elsewhere, probably because of the costs and logistics [10,11].
Human-to-human transmission of A/H5N1 is not new.
Indeed some of the most certain transmissions occurred from patients to health care workers in Hong Kong when A/H5N1 was first observed in humans in 1997 [12].
This latest Chinese report of human-to-human transmission does not change anything.
It fits with the European Centre for Disease Prevention and Control (ECDC) risk assessment (published in 2005 and revised in 2006) and with the WHO Pandemic Alert Phase 3, which allows for occasional human-to-human transmissions to take place [13,14].
Looking broadly at the recent epidemiology and virology of the A/H5N1 influenza continuously reported by the WHO [15], there is nothing of late to suggest that A/H5N1 has changed its behaviour in a worrying manner.
However, an important caveat to this statement is the case of Indonesia, which accounts for more human cases than any other country (15 of the 28 confirmed human A/H5N1 cases reported for 2008 by WHO to 8 April) and which has seen some of the largest clusters of cases in earlier years, with perhaps third-generation transmission [16,17].
Although the detection and investigation of cases has improved in Indonesia, since early 2007 the authorities have stopped sharing human A/H5N1 viruses with the rest of the world through the WHO-managed Global Influenza Surveillance Network (GISN), despite the 2005 International Health Regulations, whose spirit if not wording dictates transparency and ready sharing of data and specimens [18,19,20].
Hence, it is impossible at present to know in any timely manner whether or not the A/H5N1 viruses are changing virologically in that country.
Yet, if a pandemic is to start in any country, the time factor will be of the essence for early investigation and intervention [21,22].
So should European authorities be concerned about individual human A/H5N1 cases and probable transmissions like the one described in The Lancet and another two reported retrospectively from Pakistan [1,23]?
The time has probably come to be less excited about media or confirmed reports of isolated human cases that occur on almost a daily basis in the media and in newsletters from bodies like the Flu Information Centre in China (FIC, http://www.flu.org.cn/en/default.html.
The virus remains highly pathogenic to humans (the most recent review undertaken by WHO still reports a case fatality rate of over 60 percent [5]), so these cases are often personal and family tragedies.
However, sporadic confirmed cases now seem to represent background incidence in countries where A/H5N1 is entrenched in domestic poultry and there is close contact between birds and humans.
Sporadic cases and small clusters like that in Jiangsu are common and, unless A/H5N1 fades away (as some other avian influenza viruses have), the world may remain in the Pandemic Alert Phase 3 (as defined by WHO [14]) for some years.
What European authorities must be concerned about are any ominous changes in the behaviour and the virology of the A/H5N1 viruses in humans, but also in poultry.
In particular, more clusters of human A/H5N1 cases, larger clusters and lengthening chains of transmission which could indicate that these viruses are acquiring pandemic qualities (Pandemic Alert Phase 4 and 5 in WHO parlance [14]).
That has not happened as yet.
If anything, clusters seem to be less common and smaller at present than they were in 2005 and 2006.
However, it has been pointed out that it would be dangerous to assume that because H5N1 has not yet acquired pandemic characteristics it does not have that potential, which is a point also made in the ECDC’s risk assessment [2,13].
Continuing work by international organisations, governments and veterinarians to root out highly pathogenic avian influenza infections from poultry is fundamental.
Where this is not possible in the short and medium term, it means there will be pressure on clinicians and public health authorities in the countries where the virus is endemic, common or simply regularly occurring in domestic poultry.
It is difficult to know precisely which countries are concerned, but notable are Cambodia, China, Egypt, Laos, Indonesia, Myanmar, South Korea, Thailand and Vietnam, and recently also Bangladesh and Pakistan [24].
However, there are also countries like Nigeria, where A/H5N1 was seen in birds but is currently not reported, and other parts of sub-Saharan Africa where veterinary surveillance for highly pathogenic avian influenza in poultry is patchy (although improving following international investment).
Does no signal mean that the virus has gone or rather that there are problems in surveillance?
Wherever the virus is present in poultry and people come into close contact with them, there needs to be continued detection of potential human cases, viral isolation and rapid sharing of virus through GISN and vigorous investigation around the cases to ensure they are only sporadic, and not part of a large or expanding cluster.
Considering the resources deployed in Jiangsu by the provincial and national specialists [1], it can be seen that this will not be easy for poorer countries, certainly not without support from the rest of the world.
Less sophisticated and resource-demanding investigations will probably need to be developed and made sure to be carried out and sustained at least for some years to come.
References
1) Wang H, Feng Z, Shu Y, Yu H, Zhou L, Zu R, et al. Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. The Lancet. Early Online Publication, 8 April 2008.
2) Hien NT, Farrar J, Horby P. Person-to-person transmission of influenza A (H5N1). Comment. The Lancet. Early Online Publication, 8 April 2008.
3) Yu H, Feng Z, Zhang X, Xiang N, Huai Y, Zhou L, Human influenza A (H5N1) cases, urban areas of People's Republic of China, 2005-2006. Emerg Infect Dis. 2007;13(7):1061-4.
4) Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthavathana P, Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med. 2005;352(4):333-40.
5) Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus, Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z, Hayden FG, Nguyen DH, et al. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med. 2008;358(3):261-73.
6) Nicoll A. Human H5N1 infections: so many cases – why so little knowledge? Euro Surveill 2006;11(5):74-5. Available from: http://www.eurosurveillance.org/em/v11n05/1105-221.asp
7) Olsen SJ, Ungchusak K, Sovann L, Uyeki TM, Dowell SF, Cox NJ, et al. Family clustering of avian influenza A (H5N1). Emerg Infect Dis. 2005;11(11):1799-1801.
8) Uyeki TM, Bresee JS. Detecting human-to-human transmission of avian influenza A (H5N1). Emerg Infect Dis. 2007;13(12):1969-71.
9) Savill NJ, St Rose SG, Keeling MJ, Woolhouse ME. Silent spread of H5N1 in vaccinated poultry. Nature. 2006;442(7104):757.
10) Olsen SJ, Ungchusak K, Birmingham M, Bresee J, Dowell SF, Chunsuttiwat S. Surveillance for avian influenza in human beings in Thailand. Lancet Infect Dis. 2006;6(12):757-8.
11) Ministry of Public Health, Thailand. Avian Influenza (Bird Flu) Control. Available from: http://thaigcd.ddc.moph.go.th/Bird_Flu_main_en.html
12) Buxton Bridges C, Katz JM, Seto WH, Chan PK, Tsang D, Ho W, et al. Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong. J Infect Dis. 2000;181(1):344-8.
13) ECDC. The Public Health Risk from Highly Pathogenic Avian Influenza Viruses Emerging in Europe with Specific Reference to type A/H5N1. June 2006. Available from: http://www.ecdc.europa.eu/Health_topics/Avian_Influenza/pdf/060601_public_health_risk_HPAI.pdf
14) World Health Organization. WHO global influenza preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. Geneva, 2005. Available from: http://www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5.pdf
15) World Health Organization. Situation updates - Avian influenza. Available from: http://www.who.int/csr/disease/avian_influenza/updates/en/index.html
16) World Health Organization. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Accessed on 8 April 2008. Available from: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_04_08/en/index.html
17) Kandun IN, Wibisono H, Sedyaningsih ER, Yusharmen , Hadisoedarsuno W, Purba W, et al. Three Indonesian clusters of H5N1 virus infection in 2005. N Engl J Med. 2006;355(21):2186-94.
18) ECDC. Influenza Virus Sharing – Interim ECDC Briefing. November 2007. Summary. Available from: http://ecdc.europa.eu/pdf/ECDC_influenza_briefing.pdf
19) World Health Organization. Global Influenza Surveillance Network. Available from: http://www.who.int/csr/disease/influenza/influenzanetwork/en/index.html
20) World Health Organization. International Health Regulations (2005). Available from: http://www.who.int/csr/ihr/en Revision of the International Health Regulations. Full text. Available from: http://www.who.int/gb/ebwha/pdf_files/WHA58/WHA58_3-en.pdf
21) Ferguson NM, Cummings DA, Cauchemez S, Fraser C, Riley S, Meeyai A, et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005;437(7056):209-14.
22) World Health Organization. Interim Protocol: Rapid operations to contain the initial emergence of pandemic influenza. Available from: http://www.who.int/csr/disease/avian_influenza/guidelines/draftprotocol/en/index.htm
23) 23. World Health Organization. Avian influenza - situation in Pakistan - update 2. 3 April 2008. Available from: http://www.who.int/csr/don/2008_04_03/en/index.html
24) World Organisation for Animal Health. Update on highly pathogenic avian influenza in animals (type H5 and H7). Available from: http://www.oie.int/downld/AVIAN%20INFLUENZA/A_AI-Asia.htm
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April 10th, 2008, 06:49 PM
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Editor, Senior Moderator
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Re: Chinese son likely gave bird flu to father: report
Source: http://www.newscientist.com/channel/...nfections.html
Bird flu case raises fears of undiagnosed infections
A NEW case of human-to-human transmission doesn't prove that H5N1 bird flu is learning to spread among humans, but it reinforces fears that there could be many more undiagnosed human infections in China. It may also point to a potential cure.
Last November, a salesman hospitalised in Nanjing, China, with fever, diarrhoea and pneumonia was given antibiotics for suspected bacterial infection, but tested positive for H5N1 shortly before he died. The next day his father fell ill with a nearly identical virus, and was given plasma from a woman who had received an experimental whole-virus H5N1 vaccine. He recovered (The Lancet, DOI: 10.1016/S0140-6736(08)60493-6).
The month before, an H5N1 patient in Shenzhen also recovered after receiving plasma from someone who had survived the infection, suggesting that antibodies from such survivors are a promising approach to treating H5N1, and should be investigated further.
However, poultry in Chinese markets are required to be vaccinated, and the fact that the Nanjing salesman had visited a live poultry market shortly before he fell ill reinforces fears that many Chinese could be getting H5N1 from vaccinated poultry, which carry the virus but remain healthy. Like the salesman, such people could be misdiagnosed because they have not been near sick birds.
Jeremy Farrar of the University of Oxford's Clinical Research Unit in Ho Chi Minh City, Vietnam, says scientists should study family clusters of H5N1 to learn what allows the virus to infect humans. Clusters in Thailand, Indonesia, Pakistan and possibly Vietnam have involved only genetically related people. Generally, the virus remains hard to catch - none of other 91 people who'd had contact with the salesman or his father were infected.
“The virus is still hard to catch. None of the other 91 people in contact were infected”
This suggests that "there may be a rare genetic predisposition to the virus", Farrer says.
Bird Flu - Learn more about the flu pandemic that could kill millions in our continually updated special report. ( http://www.newscientist.com/channel/health/bird-flu)
From issue 2651 of New Scientist magazine, 12 April 2008, page 6
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