20 February 2003
Dear Doctor,
In Hong Kong, the Department of Health (DH) operates a highly sensitive influenza surveillance system comprising a network of hospital, laboratories and clinics in the public and private sectors. Through this system, two cases of influenza A(H5N1) infection have recently been detected. The patients were a 9-year-old boy and his 33-year-old father with onset of illness on 9 Feb and 7 Feb 03 respectively during their visit to Fujian (福建), China earlier this year. Both had good past health. The boy is in stable condition but his father died on 17 Feb 03. Their nasopharyngeal aspirates were tested positive for influenza A(H5N1) on 19 Feb and 20 Feb 03 respectively.
The 9-year-old boy went to Fujian with his mother and two sisters during the period 25 Jan - 9 Feb 03, his father joined them since 31 Jan. The boy had onset of low grade fever, cough and runny nose on 9 Feb. On 12 Feb, he was admitted into Princess Margaret Hospital (PMH) and chest X-ray showed left lingular lobe consolidation. He was put on intravenous cefotaxime, clarithromycin and oral amantadine. His condition is improving. His father had acute onset of high fever, blood-stained sputum and myalgia on 7 Feb. On admission into PMH on 11 Feb, he also had nose-bleeding, nausea and abdominal pain; his chest X-ray showed right lower zone consolidation. His condition deteriorated progressively and he eventually succumbed on 17 Feb 03.
The boy's younger sister (8-year-old) had onset of pneumonia on 28 Jan and died on 4 Feb while in Fujian. The exact cause of death cannot be identified. The boy's mother developed parainfluenza infection after the trip and has recovered already. His elder sister remains asymptomatic.
The avian influenza virus A(H5N1) was first known to cause human infection in 1997 when 18 cases (including 6 deaths) were identified in Hong Kong. In-depth studies showed that the main mode of transmission of influenza A(H5N1) was from bird to man, and man-to-man transmission was very ineffective. After that outbreak, there has not been any isolate of influenza A(H5) virus in human specimens prior to the recent two cases.
The initial clinical presentation of influenza A(H5N1) infection was similar to that of other influenza viruses, typically with fever, malaise, myalgia, sore throat and cough. The appropriate management consists of adequate rest, fluid replacement and antipyretic as necessary. Aspirin should be avoided. Persistent high fever (>39 C) is a common sign among the cases in 1997. In some cases, influenza A(H5N1) caused a rapid downhill course ending with viral pneumonia, respiratory distress syndrome and multi-organ failure. If there are signs of complications such as pneumonia, the patient should be hospitalized. Nasopharyngeal aspirate should be taken from patients suspected to have severe influenza illness. There are rapid screening tests for detection of influenza A antigen. Virus isolation by culture is required for confirmation and subtyping. A four-fold or greater rise in antibody titre from the acute phase to the convalescent phase serum samples is indicative of recent infection. The use of antiviral therapy such as amantadine is discussed in the attached note .
Appropriate counselling on prevention of influenza should be given to patients and members of general public. Important messages include avoidance of contact with live poultry / birds, wash hands thoroughly after contact with live poultry / birds, observance of good personal hygiene, maintaining good ventilation, no smoking, and have a balanced diet, regular exercise and adequate rest to maintain body immunity.
In light of the recent increase in atypical pneumonia cases in Guangdong Province, the DH has stepped up the local surveillance on severe community acquired pneumonia cases through the network of public and private hospitals. The number of hospital admissions for pneumonia or severe community acquired pneumonia has remained stable. So far, testing of all severe pneumonia cases for H5 has not found any other H5 positive result.
The DH stands ready to offer advice and assistance to medical professionals who detect unusual or unexplained pattern of illnesses. Please notify such incidents to the respective Regional Office of the DH. The contact numbers are as follows :
| Regional Office | Telephone number |
| Hong Kong Regional Office | 2961 8791 |
| Kowloon Regional Office | 2199 9149 |
| New Territories East Regional Office | 2158 5107 |
| New Territories West Regional Office | 2615 8571 |
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Use of Amantadine in the Management of H5N1 Infections
From the drug sensitivity study at Centres for Disease Control and Prevention (CDC) on the isolates from two H5N1 cases in 1997, it has been shown that the H5N1 virus is sensitive to amantadine. This drug is an effective agent for the treatment and prophylaxis of influenza A (but not B). However, it is prudent to note that the influenza viruses can rapidly develop resistance to this drug. Hence, doctors are advised to use the drug appropriately for treatment or prophylaxis of influenza A. The following guidelines which have incorporated the advice from the CDC experts are recommended for doctors' reference.
Confirmed case of H5N1 infection
Amantadine 100mg twice a day for 5 days can be used to treat cases of H5N1 infection. If started within 48 hours of the start of illness, amantadine can reduce the severity and shorten the duration of illness. Doses should be reduced for children and elderly, and those with underlying renal diseases. For children aged 1 to 9, the dosage is 5mg/kg/day in 2 divided doses up to 150 mg. For children aged greater than 9, adult dosage can be used but if the body weight of the child is less than 40kg, use the regime of 5mg/kg/day in 2 divided doses up to 150 mg.
Symptomatic Contacts of H5N1 cases
Close contacts, i.e. home contacts and medical staff providing direct care to patients with H5N1 infection, should be put on medical surveillance. If they develop symptoms compatible with influenza (fever of 38 C or higher, together with cough or sore throat), they should have a throat swab or nasopharyngeal aspirate taken for viral cultures. Treatment with amantadine (100mg twice for 5 days) can be started pending viral culture results.
Side effects
Amantadine can cause neurological and gastrointestinal side effects. In one study of healthy adults, approximately 13% of those treated with amantadine developed side effects. Neurological side effects include nervousness, anxiety, difficulty in concentrating and dizziness. More serious neurological side effects like marked behavioural changes, delirium, hallucinations, agitation and seizures have been observed. Gastrointestinal side effects include nausea, vomiting abdominal pain and constipation. These side effects will stop after the drug has been withdrawn. Cautions must be exercised for people with renal insufficiency and in the elderly age group. The drugs are contraindicated for persons with seizure disorders.