Avian Flu Jumped from Dying Son to Caregiver Father

By Michael Smith
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.
Caution that the researchers found no evidence in this case that the virus has acquired the ability to pass easily from person to person.
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 LancetSource 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 LancetSource reference: Hien NT, et al "Person-to-person transmission of influenza A (H5N1)" The Lancet 2008 DOI: 10.1016/S0140-6736(08)60494-8.