1 table omitted
Since mid-December 2003, eight Asian countries (Cambodia, China, Indonesia,
Japan, Laos, South Korea, Thailand, and Vietnam) have reported an epizootic
of highly pathogenic avian influenza in poultry and various other birds caused
by influenza A (H5N1). As of February 9, 2004, a total of 23 laboratory-confirmed
human cases of influenza A (H5N1) had been reported in Thailand and Vietnam.
In 18 (78%) of these cases, the patients died. Clinical experience with avian
H5N1 disease in humans is limited.1 The
human H5N1 viruses identified in Asia in 2004 are antigenically and genetically
distinguishable from the 1997 and February 2003 viruses. To aid surveillance
and clinical activities, this report provides a preliminary clinical description
of the initial five confirmed cases in Thailand.
Of the five laboratory-confirmed cases in Thailand, four were in male
children aged 6-7 years, and one was in a female aged 58 years; all patients
were previously healthy. Four patients reported deaths in poultry owned by
the patient's family, and two patients reported touching an infected chicken.
One patient had infected chickens in his neighborhood and was reported to
have played near a chicken cage. None of the confirmed cases occurred among
persons involved in the mass culling of chickens.
Patients reported to hospitals 2-6 days after onset of fever and cough.
Other early symptoms included sore throat (four), rhinorrhea (two), and myalgia
(two). Shortness of breath was reported in all patients 1-5 days after symptom
onset. On admission, clinically apparent pneumonia with chest radiograph changes
was observed in all patients, with patchy infiltrates in four and interstitial
infiltrates in one. Diarrhea and vomiting were not reported. Peripheral leukocytes
were normal or decreased, and four patients had lymphopenia (<1,000/µL).
Mild-to-moderate elevations in hepatic transaminases were found in four patients.
All patients had respiratory failure and required intubation a median
of 7 days (range: 4-10 days) after onset of illness. Two patients had a pneumothorax.
Three patients required inotropic support for decreased cardiac function;
two patients had renal impairment as a later manifestation. None had documented
evidence of secondary bacterial infection.
Late in the course of illness, three patients were treated with oseltamivir
for 3-5 days. All received empiric broad-spectrum antibiotics for community-acquired
pneumonia while the cause of illness was under investigation. Four were treated
with systemic steroids for increasing respiratory distress and clinically
diagnosed acute respiratory distress syndrome (ARDS) with compatible chest
Three children died 2-4 weeks after symptom onset, and one child and
the adult died 8 days after symptom onset. All patients had laboratory evidence
of influenza A (H5N1) by reverse transcriptase–polymerase chain reaction.
In three cases, the virus was isolated in tissue culture, and in three cases,
the viral antigens were identified by immunofluorescent assay.
T Chotpitayasunondh, S Lochindarat, P Srisan, Queen Sirikit National
Institute of Child Health; K Chokepaibulkit, Faculty of Medicine, Siriraj
Hospital, Mahidol Univ, Bangkok; J Weerakul, Buddhachinaraj Hospital, Phitsanulok;
M Maneerattanaporn, 17th Somdejprasangkaraj Hospital, Suphanburi; P Sawanpanyalert,
Dept of Medical Sciences, Ministry of Public Health, Thailand. World Health
Organization, Thailand. CDC International Emerging Infections Program, Thailand.
The 1997 outbreak of influenza A (H5N1) in Hong Kong established that
highly pathogenic avian influenza viruses can infect humans directly, with
resulting illness that was fatal in six (33%) of 18 patients. The viruses
were not transmitted efficiently from person to person, and human infections
stopped after the culling of poultry.2 The
2003-2004 avian outbreak is more widespread, with poultry disease reported
across much of east and southeast Asia. Direct infection of humans with H5N1
viruses has been confirmed in Thailand and Vietnam. However, no evidence of
sustained person-to-person transmission has been identified.
Despite the antigenic and genetic differences in the H5N1 viruses causing
the current Asian outbreaks, certain clinical features of the five human cases
described in this report are similar to those of severely affected patients
from the 1997 outbreak in Hong Kong.3 In
all five cases, disease was severe, with pneumonia progressing to respiratory
failure and death. Early distinguishing features included fever, sore throat,
cough, and lymphopenia. Other organ involvement included mild-to-moderate
hepatitis and later cardiac and renal impairment. In contrast with the cases
reported from Hong Kong, gastrointestinal symptoms were not prominent features.
Because of the severity of disease and the concern for the safety of
health-care personnel, the Ministry of Public Health in Thailand recommends
that hospitalized patients with suspected avian influenza be cared for by
using precautions to minimize the risk for airborne transmission. Broad-spectrum
antibacterial drugs should be used as empiric treatment for the major causes
of pneumonia (e.g., Streptococcus pneumoniae), including
possible superinfection with Staphylococcus aureus.
Testing of a limited number of human isolates demonstrates resistance to amantadine
and rimantadine.4 For this reason, treatment
with neuraminidase inhibitors should be initiated early. The effectiveness
of antiviral drugs against H5N1 infections and the period after which these
drugs will provide little or no benefit is not known. A more detailed understanding
of the pathogenesis is needed to direct therapeutic approaches such as the
use of immunomodulating drugs. Updated recommendations for hospital infection
control and treatment are available from the World Health Organization at http://www.who.int/csr/disease/avian_influenza/en.
The epidemiology of influenza A (H5N1) in Thailand and neighboring countries
remains incompletely described, but the confirmed human infections have occurred
in geographic areas with recognized avian disease, and two patients reported
direct physical contact with ill or dead chickens. Of the five laboratory-confirmed
cases in Thailand, four were in boys aged 6-7 years, which suggests that boys
in this age group might be subject to particular high-risk exposures. Case-control
studies in Thailand and Vietnam should help define specific risk factors for
infection and allow for the development of evidence-based public health interventions.
Control of highly pathogenic avian influenza should include surveillance
for affected flocks, aggressive culling on the basis of international guidelines
to eradicate foci of infection, careful protection of cullers through the
use of personal protective equipment, and use of the currently licensed human
trivalent influenza vaccine to reduce the risk for co-infection in poultry
workers and cullers, which might lead to genetic reassortment of avian and
human influenza viruses.2,3 In
recent weeks, Thailand has moved aggressively to (1) identify geographic areas
with confirmed H5N1 disease in poultry (e.g., cull-affected flocks and flocks
within a 5-kilometer radius), (2) establish controls on the transport of poultry
and poultry products out of affected areas, and (3) promote safe food-handling
Clinicians should be aware of the clinical features of the current human
influenza A (H5N1) disease and the potential risk factors for infection so
that health-care workers are protected and patients can be identified quickly
and managed appropriately. Interim U.S. recommendations for infection-control
precautions and the diagnostic evaluation of persons with specific epidemiologic
and clinical criteria have been developed.4 Additional
information is available from CDC at http://www.cdc.gov/flu/avian/index.htm.
Cases of Influenza A (H5N1)—Thailand, 2004. JAMA. 2004;291(9):1059-1060. doi:10.1001/jama.291.9.1059