Feb 16, 2005 (CIDRAP News) – Researchers studying acute encephalitis cases in Vietnam discovered an unexpected cause of death in a 4-year-old boy, and possibly his 9-year-old sister: avian influenza.
The two cases, described in the Feb 17 issue of the New England Journal of Medicine, differ from most other known human cases of H5N1 avian flu, which typically have been marked by fever, respiratory symptoms, and pneumonia. The report was written by Menno D. de Jong, MD, PhD, of the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, and several colleagues.
The findings should prompt healthcare providers to broaden their ideas about the clinical spectrum of H5N1 infection in humans, de Jong and colleagues write.
"These cases emphasize that avian influenza A(H5N1) should be included in the differential diagnosis of a much wider clinical spectrum of disease than previously considered and that clinical surveillance of influenza H5N1 should focus not only on respiratory illnesses, but also on clusters of unexplained deaths or severe illnesses of any kind," the report states. "Awareness of the full clinical spectrum is essential to appropriate management of the illness, since treatment with antiviral agents is likely to be beneficial only when it is started early in the course of illness."
Both children died in hospitals in southern Vietnam in February 2004, the article says. The 9-year-old girl arrived on Feb 1 with a 4-day history of fever, watery diarrhea without blood or mucus, and increasing drowsiness. She had no respiratory symptoms, and her chest radiograph was clear. She became comatose and died the following day; acute encephalitis of unknown origin was listed as the cause. Her body was not autopsied.
The girl's little brother was admitted to the same hospital in Dong Thap province on Feb 12, 2004, having suffered fever, headache, vomiting, and severe diarrhea for 2 days. A chest radiograph was normal.
Within days, his diarrhea and stupor worsened. He was transferred to a hospital in Ho Chi Minh City on Feb 15 but fell into a coma within 12 hours of the transfer. By Feb 16, a chest radiograph showed bilateral infiltrates. He died the next day, with acute encephalitis reported as the cause. No autopsy was performed, but samples were taken for an ongoing study of the causes of acute encephalitis.
When researchers examined those samples at different times over the succeeding months, they ruled out several possible causes before they found the H5N1 virus in the boy's throat, rectal swabs, serum, and cerebrospinal fluid.
Encephalitis and encephalopathy are rare complications of infection with human influenza viruses, and it is extremely rare to isolate flu virus from cerebrospinal fluid, the report states. While certainty isn't possible, the girl's history makes it likely that she died of the same illness as her brother.
The two children had little interaction with poultry, later investigation showed. They used water from a nearby canal for drinking and washing, although they boiled the water before drinking. The family had once owned healthy fighting cocks; they were culled as part of measures to contain an H5N1 outbreak in poultry.
"The source of transmission may have been domestic ducks present in the canal near the children's house," the article says. "Direct transmission from sister to brother appears unlikely considering the interval between their illnesses.
"Further research is needed to determine whether host factors, which may determine a person's susceptibility to disseminated or central nervous system infection, or a particularly neurologically virulent strain of the virus is involved," researchers conclude. "The presence of viable virus in the feces of our patients has important implications for transmission, infection control and public health."
Michael Osterholm, PhD, MPH, director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of this Web site, called the information preliminary but of great concern.
"These cases may represent an 'intermediate human clinical presentation' between the classic gastrointestinal infection in wild waterfowl and the typical human infection," he said via e-mail today. "It is also likely that we are missing a number of similar infections in humans in Southeast Asia as patients presenting with this type of illness would not be typically tested for influenza virus."
de Jong MD, Cam BV, Phan TQ, et al. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med 2005 Feb 17:352(7):686-91 [Abstract]