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NEJM - 3 Indonesian Clusters -H5N1 - 2005

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  • NEJM - 3 Indonesian Clusters -H5N1 - 2005

    Three Indonesian Clusters of H5N1 Virus Infection in 2005
    <CENTER>I. Nyoman Kandun, M.D., M.P.H., Hariadi Wibisono, M.D., Ph.D., M.P.H., Endang R. Sedyaningsih, M.D., D.P.H., Yusharmen, M.D., Widarso Hadisoedarsuno, M.D., Wilfried Purba, D.V.M., M.P.H., Hari Santoso, M.Epid., Chita Septiawati, M.D., Erna Tresnaningsih, M.D., Ph.D., Bambang Heriyanto, M.Epid., Djoko Yuwono, M.S., Syahrial Harun, M.S., Santoso Soeroso, M.D., M.H.A., Sardikin Giriputra, M.D., M.H.A., Patrick J. Blair, Ph.D., Andrew Jeremijenko, M.B., B.S., M.H.A., Herman Kosasih, M.D., Shannon D. Putnam, Ph.D., Gina Samaan, M.App.Epid., Marlinggom Silitonga, M.D., M.Epid., K.H. Chan, Ph.D., Leo L.M. Poon, Ph.D., Wilina Lim, M.D., Alexander Klimov, Ph.D., D.Sc., Stephen Lindstrom, Ph.D., Yi Guan, M.D., Ph.D., Ruben Donis, Ph.D., Jacqueline Katz, Ph.D., Nancy Cox, Ph.D., Malik Peiris, D.Phil., M.D., and Timothy M. Uyeki, M.D., M.P.H. </CENTER>
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    <TABLE cellSpacing=0 cellPadding=0><TBODY><TR><TD> Deutsch
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    </CENTER> --><!-- <CENTER></NOBR><NOBR>I. Nyoman Kandun, M.D., M.P.H.</NOBR>, <NOBR>Hariadi Wibisono, M.D., Ph.D., M.P.H.</NOBR>, <NOBR>Endang R. Sedyaningsih, M.D., D.P.H.</NOBR>, <NOBR> Yusharmen, M.D.</NOBR>, <NOBR>Widarso Hadisoedarsuno, M.D.</NOBR>, <NOBR>Wilfried Purba, D.V.M., M.P.H.</NOBR>, <NOBR>Hari Santoso, M.Epid.</NOBR>, <NOBR>Chita Septiawati, M.D.</NOBR>, <NOBR>Erna Tresnaningsih, M.D., Ph.D.</NOBR>, <NOBR>Bambang Heriyanto, M.Epid.</NOBR>, <NOBR>Djoko Yuwono, M.S.</NOBR>, <NOBR>Syahrial Harun, M.S.</NOBR>, <NOBR>Santoso Soeroso, M.D., M.H.A.</NOBR>, <NOBR>Sardikin Giriputra, M.D., M.H.A.</NOBR>, <NOBR>Patrick J. Blair, Ph.D.</NOBR>, <NOBR>Andrew Jeremijenko, M.B., B.S., M.H.A.</NOBR>, <NOBR>Herman Kosasih, M.D.</NOBR>, <NOBR>Shannon D. Putnam, Ph.D.</NOBR>, <NOBR>Gina Samaan, M.App.Epid.</NOBR>, <NOBR>Marlinggom Silitonga, M.D., M.Epid.</NOBR>, <NOBR>K.H. Chan, Ph.D.</NOBR>, <NOBR>Leo L.M. Poon, Ph.D.</NOBR>, <NOBR>Wilina Lim, M.D.</NOBR>, <NOBR>Alexander Klimov, Ph.D., D.Sc.</NOBR>, <NOBR>Stephen Lindstrom, Ph.D.</NOBR>, <NOBR>Yi Guan, M.D., Ph.D.</NOBR>, <NOBR>Ruben Donis, Ph.D.</NOBR>, <NOBR>Jacqueline Katz, Ph.D.</NOBR>, <NOBR>Nancy Cox, Ph.D.</NOBR>, <NOBR>Malik Peiris, D.Phil., M.D.</NOBR> and <NOBR>Timothy M. Uyeki, M.D., M.P.H.</NOBR></CENTER>
    -->ABSTRACT
    Background Since 2003, the widespread ongoing epizootic of avian<SUP> </SUP>influenza A (H5N1) among poultry and birds has resulted in human<SUP> </SUP>H5N1 cases in 10 countries. The first case of H5N1 virus infection<SUP> </SUP>in Indonesia was identified in July 2005.<SUP> </SUP>
    Methods We investigated three clusters of Indonesian cases with<SUP> </SUP>at least two ill persons hospitalized with laboratory evidence<SUP> </SUP>of H5N1 virus infection from June through October 2005. Epidemiologic,<SUP> </SUP>clinical, and virologic data on these patients were collected<SUP> </SUP>and analyzed.<SUP> </SUP>
    Results Severe disease occurred among all three clusters, including<SUP> </SUP>deaths in two clusters. Mild illness in children was documented<SUP> </SUP>in two clusters. The median age of the eight patients was 8.5<SUP> </SUP>years (range, 1 to 38). Four patients required mechanical ventilation,<SUP> </SUP>and four of the eight patients (50%) died. In each cluster,<SUP> </SUP>patients with H5N1 virus infection were members of the same<SUP> </SUP>family, and most lived in the same home. In two clusters, the<SUP> </SUP>source of H5N1 virus infection in the index patient was not<SUP> </SUP>determined. Virus isolates were available for one patient in<SUP> </SUP>each of two clusters, and molecular sequence analyses determined<SUP> </SUP>that the isolates were clade 2 H5N1 viruses of avian origin.<SUP> </SUP>
    Conclusions In 2005 in Indonesia, clusters of human infection<SUP> </SUP>with clade 2 H5N1 viruses included mild, severe, and fatal cases<SUP> </SUP>among family members.<SUP> </SUP>
    <SUP></SUP>
    <HR>The avian influenza A (H5N1) epizootic has resulted in sporadic<SUP> </SUP>human cases and case clusters. Previously, H5N1 case clustering<SUP> </SUP>was observed in cousins in 1997<SUP>1</SUP> and in a father and son in<SUP> </SUP>2003.<SUP>2</SUP> H5N1 clustering was described in 2004?2005 but<SUP> </SUP>without sufficient information to assess whether human-to-human<SUP> </SUP>transmission had occurred.<SUP>3</SUP> Although only one likely instance<SUP> </SUP>of limited human-to-human transmission of H5N1 virus was detailed<SUP> </SUP>in Thailand in 2004,<SUP>4</SUP> the investigation of case clusters is<SUP> </SUP>critically important, since an increase in clusters could suggest<SUP> </SUP>greater transmissibility of H5N1 viruses.<SUP> </SUP>
    Since 2003, H5N1 outbreaks in poultry have occurred throughout<SUP> </SUP>Indonesia.<SUP>5</SUP><SUP>,</SUP><SUP>6</SUP><SUP>,</SUP><SUP>7</SUP> Indonesia's first human H5N1 case was confirmed<SUP> </SUP>in July 2005, and three clusters were noted among H5N1 cases<SUP> </SUP>through October 2005. In this report, we describe the epidemiologic,<SUP> </SUP>clinical, and virologic findings of the three H5N1 case clusters.<SUP> </SUP>
    Methods
    Epidemiologic and Clinical Investigation
    After notification of a suspected case of H5N1, the Ministry<SUP> </SUP>of Health in Indonesia initiated an investigation with the assistance<SUP> </SUP>of public health authorities and the World Health Organization<SUP> </SUP>(WHO). Investigators collected nasal and throat swabs, tracheal<SUP> </SUP>aspirates (if available), and serum specimens from patients<SUP> </SUP>who were suspected of having the disease; all specimens were<SUP> </SUP>tested for the presence of H5N1 virus. Laboratory evidence of<SUP> </SUP>H5N1 was defined as virus isolation or detection of H5N1 viral<SUP> </SUP>RNA by testing of respiratory specimens or serologically by<SUP> </SUP>detection of H5N1 neutralizing antibodies. Cases were classified<SUP> </SUP>as suspected, probable, or confirmed H5N1 virus infection, according<SUP> </SUP>to WHO definitions.<SUP>8</SUP><SUP> </SUP>
    We collected epidemiologic and clinical data for patients with<SUP> </SUP>confirmed H5N1 virus infection and their contacts through interviews<SUP> </SUP>and a review of medical records. Contacts of patients with H5N1<SUP> </SUP>infection were followed for illness. Environmental, poultry,<SUP> </SUP>and other avian specimens, if available, were tested for H5N1<SUP> </SUP>virus. Clinical, epidemiologic, and laboratory data were analyzed<SUP> </SUP>with the use of descriptive statistics. We defined a cluster<SUP> </SUP>of H5N1 cases as consisting of at least two persons who had<SUP> </SUP>disease with laboratory evidence of H5N1 virus among household<SUP> </SUP>members, relatives, or other contacts. This study was part of<SUP> </SUP>an ongoing public health investigation of outbreaks of H5N1<SUP> </SUP>virus infection and was determined by the Ministry of Health<SUP> </SUP>to be exempt from approval from institutional review boards<SUP> </SUP>in Indonesia.<SUP> </SUP>
    Laboratory Investigation
    Indonesian laboratories screened clinical specimens from patients<SUP> </SUP>with suspected H5N1 infection for the virus. Respiratory and<SUP> </SUP>serum specimens were shipped frozen to WHO H5 Reference Laboratories<SUP> </SUP>for H5N1 testing by real-time reverse-transcriptase polymerase<SUP> </SUP>chain reaction (RT-PCR), viral culture, molecular sequencing,<SUP> </SUP>antiviral resistance testing, microneutralization, and Western<SUP> </SUP>blot analyses (see the Supplementary Appendix, available with<SUP> </SUP>the full text of this article at www.nejm.org).<SUP> </SUP>
    Results
    Among eight previously healthy patients in three unrelated clusters,<SUP> </SUP>there were seven confirmed cases of H5N1 virus infection and<SUP> </SUP>one probable case (Figure 1). The median age of the patients<SUP> </SUP>was 8.5 years (range, 1 to 38), and four of the eight patients<SUP> </SUP>(50%) died, including two adults and two children.<SUP> </SUP>
    <!-- null --><TABLE cellSpacing=0 cellPadding=0><TBODY><TR bgColor=#e8e8d1><TD><TABLE cellSpacing=2 cellPadding=2><TBODY><TR bgColor=#e8e8d1><TD vAlign=top align=middle bgColor=#ffffff>
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    </NOBR> </TD><TD vAlign=top align=left>Figure 1. Time Lines for Indonesian Case Clusters of H5N1 Virus Infection. ICU denotes intensive care unit.
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    Cluster 1
    This cluster included three of five family members living together<SUP> </SUP>in a suburb west of Jakarta. Patient 1A, an 8-year-old girl<SUP> </SUP>in whom fever, headache, nausea, vomiting, and rhinorrhea developed,<SUP> </SUP>was hospitalized with pneumonia 6 days after the onset of symptoms.<SUP> </SUP>She was treated with albuterol, fluticasone, ceftriaxone, meropenem,<SUP> </SUP>ciprofloxacin, vancomycin, gentamicin, amikacin, linezolid,<SUP> </SUP>and mechanical ventilation for respiratory failure, but she<SUP> </SUP>died on the 26th day of illness. Serum specimens collected late<SUP> </SUP>in her illness showed evidence of acute H5N1 virus infection<SUP> </SUP>on microneutralization assay.<SUP> </SUP>
    Patient 1B was a 1-year-old girl in whom fever developed 1 week<SUP> </SUP>after the onset of illness in her sister (Patient 1A). On the<SUP> </SUP>ninth day of illness, Patient 1B was hospitalized with fever,<SUP> </SUP>rhinorrhea, cough, diarrhea, and vomiting, and she received<SUP> </SUP>the diagnosis of pneumonia. She was placed on mechanical ventilation<SUP> </SUP>but died on the 12th day of illness. No specimens were available<SUP> </SUP>for H5N1 testing.<SUP> </SUP>
    Patient 1C, who worked as a government auditor, was the 38-year-old<SUP> </SUP>father of Patients 1A and 1B. He had close contact with his<SUP> </SUP>sick daughters at home and during their hospitalizations. He<SUP> </SUP>had onset of fever 3 and 9 days, respectively, after the onset<SUP> </SUP>of his daughters' illnesses. On the seventh day of illness,<SUP> </SUP>he was hospitalized with pneumonia and was treated with albuterol,<SUP> </SUP>budesonide, aminophylline, dexamethasone, meropenem, ceftriaxone,<SUP> </SUP>and linezolid. Despite mechanical ventilation, he died on the<SUP> </SUP>11th day of illness. H5N1 virus was isolated from a throat swab<SUP> </SUP>collected on day 7.<SUP> </SUP>
    The three patients in cluster 1 reported having had no contact<SUP> </SUP>with poultry, wild birds, other animals, or any sick persons<SUP> </SUP>besides family members before the onset of illness. Family members<SUP> </SUP>shared a bed after the onset of illness and before hospitalization.<SUP> </SUP>Patient 1C's wife, son, and two housekeepers living in the home<SUP> </SUP>remained well. Of the 173 contacts who were followed for 2 weeks<SUP> </SUP>(8 household members and neighbors, 143 health care workers,<SUP> </SUP>and 22 coworkers), no other ill persons were identified.<SUP> </SUP>
    Cluster 2
    This cluster included two relatives living near south Jakarta.<SUP> </SUP>On August 31, fever, rhinorrhea, and cough developed in a 37-year-old<SUP> </SUP>woman (Patient 2A). On the seventh day of illness, she was hospitalized<SUP> </SUP>with fever, shock, and respiratory failure requiring mechanical<SUP> </SUP>ventilation. Methylprednisolone, levofloxacin, and meropenem<SUP> </SUP>were administered, and oseltamivir was given on the 10th day<SUP> </SUP>of illness. She died 11 days after the onset of illness; H5N1<SUP> </SUP>virus was isolated from tracheal aspirate.<SUP> </SUP>
    Patient 2B was a 9-year-old boy who lived temporarily with Patient<SUP> </SUP>2A (his aunt) during her illness. Three days after his aunt<SUP> </SUP>was hospitalized, he had onset of fever. He was hospitalized<SUP> </SUP>on the ninth day of illness, with persistent fever, sore throat,<SUP> </SUP>and tachypnea. No supplemental oxygen, antibiotics, or antiviral<SUP> </SUP>treatment was administered, and his fever resolved on the 10th<SUP> </SUP>day of illness. The presence of H5N1 virus was confirmed by<SUP> </SUP>RT-PCR in respiratory specimens obtained on the fourth day of<SUP> </SUP>illness.<SUP> </SUP>
    Patients 2A and 2B did not report having had contact with poultry,<SUP> </SUP>wild birds, other animals, or other ill persons, but chickens<SUP> </SUP>died nearby, and poultry were slaughtered daily approximately<SUP> </SUP>50 m from the home. In her home garden, Patient 2A used fertilizer<SUP> </SUP>containing poultry feces that tested positive for H5N1 by RT-PCR.<SUP> </SUP>Of the 132 contacts of Patients 2A and 2B (76 household members<SUP> </SUP>and neighbors and 56 health care workers), no other ill persons<SUP> </SUP>were identified.<SUP> </SUP>
    Cluster 3
    Three relatives living in the same rural village in southern<SUP> </SUP>Sumatra made up the third cluster. In mid-September 2005, backyard<SUP> </SUP>chickens started dying in the village. Three days after holding<SUP> </SUP>two dead chickens, Patient 3A, a 21-year-old man with a history<SUP> </SUP>of smoking cigarettes, had an onset of fever, chills, rhinorrhea,<SUP> </SUP>cough, and headache. On the fifth day of illness, he was hospitalized<SUP> </SUP>with pneumonia and treated with ceftriaxone. Oseltamivir was<SUP> </SUP>started on the seventh day of illness. One week later, his respiratory<SUP> </SUP>status worsened, requiring supplemental oxygen, and a pleural<SUP> </SUP>effusion was noted on chest radiography. His condition improved,<SUP> </SUP>and he was discharged on day 25 of illness. A throat swab that<SUP> </SUP>was collected on admission tested positive for H5N1 by RT-PCR.<SUP> </SUP>H5N1 virus was isolated from a lung specimen obtained from a<SUP> </SUP>chicken close to the home.<SUP> </SUP>
    Patient 3B, the 5-year-old brother of Patient 3A, had an onset<SUP> </SUP>of illness (fever, rhinorrhea, and cough) on the same day as<SUP> </SUP>Patient 3A, was hospitalized on the fifth day of illness, recovered<SUP> </SUP>without treatment, and was discharged 9 days later. Serologic<SUP> </SUP>confirmation of H5N1 virus infection was made more than 3 months<SUP> </SUP>later for Patient 3B. Patient 3C was the 4-year-old son of a<SUP> </SUP>sister of Patient 3A and Patient 3B. He lived in a separate<SUP> </SUP>home and did not have contact with his uncles during their illnesses<SUP> </SUP>but moved to their home after they were hospitalized. Patient<SUP> </SUP>3C did not have any known contact with ill persons or with sick<SUP> </SUP>or dead poultry, but his mother had handled dead chickens and<SUP> </SUP>buried them. On October 4, fever, rhinorrhea, and dry cough<SUP> </SUP>developed in Patient 3C, but the fever lasted only 2 days. After<SUP> </SUP>a throat specimen tested positive for H5N1 by RT-PCR, he was<SUP> </SUP>hospitalized on day 5 and treatment with oseltamivir was started.<SUP> </SUP>A chest radiograph on day 7 revealed mild bilateral perihilar<SUP> </SUP>and interstitial infiltrates. He remained afebrile, received<SUP> </SUP>oseltamivir for 7 days, and was discharged 17 days after the<SUP> </SUP>onset of illness. Of the 33 household and neighborhood contacts<SUP> </SUP>that were followed for 2 weeks, all others remained well.<SUP> </SUP>
    Clinical Findings
    The median time from the onset of illness to hospitalization<SUP> </SUP>was 7 days (range, 5 to 9) (Table 1). All patients with fatal<SUP> </SUP>disease presented with fever, bilateral pneumonia, and respiratory<SUP> </SUP>distress, and three patients presented with leukopenia, lymphopenia,<SUP> </SUP>and moderate thrombocytopenia. In all five patients with severe<SUP> </SUP>disease, including four who required mechanical ventilation,<SUP> </SUP>hypoxemia or hypoxia either was present on admission or developed<SUP> </SUP>later, requiring supplemental oxygen. None of the three mild<SUP> </SUP>cases required supplemental oxygen. Patients 2B and 3C had normal<SUP> </SUP>leukocyte, lymphocyte, and platelet counts on admission and<SUP> </SUP>had fever for 2 and 10 days, respectively. Only Patients 2A,<SUP> </SUP>3A, and 3C received treatment with oseltamivir, beginning on<SUP> </SUP>illness days 10, 7, and 5, respectively. Six patients received<SUP> </SUP>antibiotics to treat possible bacterial coinfection, but no<SUP> </SUP>invasive bacterial infections were identified.<SUP> </SUP>
    <!-- null --><TABLE cellSpacing=0 cellPadding=0><TBODY><TR bgColor=#e8e8d1><TD><TABLE cellSpacing=2 cellPadding=2><TBODY><TR bgColor=#e8e8d1><TD vAlign=top align=middle bgColor=#ffffff>View this table:
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    </NOBR> </TD><TD vAlign=top align=left>Table 1. Clinical Data for Patients from Three Indonesian Clusters of H5N1 Virus Infection in 2005.
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    Of six patients whose serum albumin levels were measured either<SUP> </SUP>at or close to their hospital admission, four patients with<SUP> </SUP>fatal disease had hypoalbuminemia (albumin range, 2.2 to 3.1<SUP> </SUP>g per deciliter). One patient with severe but nonfatal disease<SUP> </SUP>had an albumin level of 2.4 g per deciliter, and one patient<SUP> </SUP>with very mild disease had a level of 4.3 g per deciliter. Four<SUP> </SUP>patients with severe disease had moderately elevated levels<SUP> </SUP>of aspartate aminotransferase and alanine aminotransferase,<SUP> </SUP>with levels of aspartate aminotransferase higher than those<SUP> </SUP>of alanine aminotransferase, at or shortly after admission,<SUP> </SUP>as compared with one patient with mild disease who had normal<SUP> </SUP>levels.<SUP> </SUP>
    H5N1 Testing
    H5N1 virus was isolated from a throat swab from Patient 1C on<SUP> </SUP>illness day 7 and from a tracheal aspirate from Patient 2A on<SUP> </SUP>day 10 (Table 2). Molecular sequencing of H5N1 viruses isolated<SUP> </SUP>from Patient 1C (A/Indonesia/5/2005) and Patient 2A (A/Indonesia/6/2005)<SUP> </SUP>indicated that both H5N1 viruses were of the Z genotype. In<SUP> </SUP>addition, all eight genes of both H5N1 viruses were of avian<SUP> </SUP>origin and were clade 2 viruses, as defined previously.<SUP>9</SUP> Both<SUP> </SUP>A/Indonesia/5/2005 and A/Indonesia/6/2005 had M2 gene sequences,<SUP> </SUP>indicating susceptibility to adamantanes. Sequencing of the<SUP> </SUP>neuraminidase genes and assaying for susceptibility to neuraminidase<SUP> </SUP>inhibitors found that both H5N1 viruses were sensitive to such<SUP> </SUP>agents. Of the five patients whose disease was confirmed by<SUP> </SUP>RT-PCR, the same specimens tested negative by rapid antigen<SUP> </SUP>testing. Throat swabs had a higher yield for detection of H5N1<SUP> </SUP>virus by RT-PCR assay and viral isolation than did nasal swabs.<SUP> </SUP>A throat swab from Patient 3B was positive on RT-PCR assay on<SUP> </SUP>illness day 8, even though the patient had fever for only 2<SUP> </SUP>days and began receiving oseltamivir on day 5.<SUP> </SUP>
    <!-- null --><TABLE cellSpacing=0 cellPadding=0><TBODY><TR bgColor=#e8e8d1><TD><TABLE cellSpacing=2 cellPadding=2><TBODY><TR bgColor=#e8e8d1><TD vAlign=top align=middle bgColor=#ffffff>View this table:
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    </NOBR> </TD><TD vAlign=top align=left>Table 2. Results of Laboratory Testing for H5N1 Virus Infection from Patients in Three Indonesian Clusters in 2005.
    </TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE>
    Discussion
    Our study documents clusters of clade 2 H5N1 virus infection<SUP> </SUP>among Indonesian families. These findings and other reports<SUP> </SUP>of clusters among family members and relatives in Hong Kong,<SUP> </SUP>Vietnam, Thailand, China, Azerbaijan, and Turkey<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>3</SUP><SUP>,</SUP><SUP>4</SUP><SUP>,</SUP><SUP>10</SUP><SUP>,</SUP><SUP>11</SUP><SUP>,</SUP><SUP>12</SUP><SUP>,</SUP><SUP>13</SUP><SUP>,</SUP><SUP>14</SUP><SUP> </SUP>raise questions as to whether genetic or other factors may predispose<SUP> </SUP>some persons to H5N1 virus infection or to severe disease. Since<SUP> </SUP>the completion of this investigation, additional H5N1 case clusters<SUP> </SUP>have been identified in Indonesia, including a large cluster<SUP> </SUP>in northern Sumatra in May 2006. WHO recommends close follow-up<SUP> </SUP>and oseltamivir chemoprophylaxis for household members and relatives<SUP> </SUP>of patients with H5N1 virus infection who had close contact<SUP> </SUP>either with the patient with the disease or with sick or dead<SUP> </SUP>poultry.<SUP>15</SUP> Prompt antiviral treatment of any associated identified<SUP> </SUP>ill persons is also recommended.<SUP> </SUP>
    We identified three pediatric patients with clinically mild<SUP> </SUP>disease in two clusters. This finding is consistent with data<SUP> </SUP>from 1997, when most pediatric patients with H5N1 virus infection<SUP> </SUP>in Hong Kong had relatively mild disease.<SUP>16</SUP><SUP>,</SUP><SUP>17</SUP> Another study<SUP> </SUP>identified mild and asymptomatic H5N1 virus infection in two<SUP> </SUP>adult health care workers in 1997.<SUP>18</SUP> Identification of three<SUP> </SUP>mild H5N1 cases in this study and one case in Turkey (as reported<SUP> </SUP>by Oner et al.<SUP>12</SUP> elsewhere in this issue of the Journal) has<SUP> </SUP>implications for surveillance, since most H5N1 case findings<SUP> </SUP>have focused on patients who were hospitalized with severe pneumonia.<SUP> </SUP>
    We were not able to determine the source of H5N1 virus infection<SUP> </SUP>for the index patients in two clusters, and transmission through<SUP> </SUP>contact with environmentally contaminated material remains a<SUP> </SUP>possibility. In the first cluster, a caged bird with H5N1 virus<SUP> </SUP>infection near the home suggested the possibility of environmental<SUP> </SUP>contamination with H5N1 virus, although no virus was detected<SUP> </SUP>around the residence. The index patient in the second cluster<SUP> </SUP>could have acquired infection through contact with fertilizer<SUP> </SUP>containing H5N1-contaminated poultry feces. The presence of<SUP> </SUP>a poultry-slaughtering operation approximately 50 m from the<SUP> </SUP>home and dead chickens in the neighborhood also suggests that<SUP> </SUP>H5N1 environmental contamination could have been a source.<SUP> </SUP>
    Limited person-to-person H5N1 transmission could not be excluded<SUP> </SUP>in two clusters among patients who had no known contact with<SUP> </SUP>poultry or other animals. Although Patient 1B was not tested,<SUP> </SUP>her clinical characteristics and evidence that her sister (Patient<SUP> </SUP>1A) and her father had acute H5N1 virus infection all strongly<SUP> </SUP>suggest she also had H5N1 virus infection. Both Patient 1B and<SUP> </SUP>her father had close contact with Patient 1A before their illnesses.<SUP> </SUP>Similarly, the only identified exposure for Patient 2B was close<SUP> </SUP>contact with his aunt (Patient 2A) during her illness. Limited,<SUP> </SUP>nonsustained H5N1 virus transmission from Patient 1A to her<SUP> </SUP>sister and father, from Patient 1B to her father, and from Patient<SUP> </SUP>2A to her nephew remain possible explanations given the epidemiologic<SUP> </SUP>investigation.<SUP> </SUP>
    As compared with nasal swabs, throat specimens provided the<SUP> </SUP>highest yield for the detection of H5N1 virus. Rapid antigen<SUP> </SUP>testing did not detect any H5N1 cases, which is consistent with<SUP> </SUP>data reported for clade 1 infections<SUP>19</SUP> and supports guidance<SUP> </SUP>against using such tests for the detection of H5N1 virus.<SUP>20</SUP><SUP> </SUP>
    Few Indonesian patients with clade 2 H5N1 virus infection in<SUP> </SUP>these clusters had diarrhea, unlike patients with clade 1 H5N1<SUP> </SUP>virus infection.<SUP>19</SUP><SUP>,</SUP><SUP>21</SUP><SUP>,</SUP><SUP>22</SUP> Most patients with H5N1 virus infection<SUP> </SUP>had hypoalbuminemia at or close to the time of hospital admission,<SUP> </SUP>which has not been reported previously. Whether this finding<SUP> </SUP>is related to viral, renal, hepatic, gastrointestinal, iatrogenic,<SUP> </SUP>or other factors is unknown. The effects of corticosteroid therapy<SUP> </SUP>or late oseltamivir treatment could not be determined. Both<SUP> </SUP>H5N1 clade 2 viral isolates were sensitive to adamantanes and<SUP> </SUP>neuraminidase inhibitors, although adamantanes are not recommended<SUP> </SUP>by the WHO owing to a high frequency of H5N1 viruses that are<SUP> </SUP>resistant to amantadine and rimantadine.<SUP>15</SUP> Resistance to oseltamivir<SUP> </SUP>has been reported in patients with clade 1 H5N1 virus infection.<SUP>13</SUP><SUP>,</SUP><SUP>14</SUP><SUP> </SUP>A recent study showed a correlation between a high H5N1 viral<SUP> </SUP>load and hypercytokinemia, and the investigators concluded that<SUP> </SUP>early antiviral treatment is needed to suppress viral replication<SUP> </SUP>and to prevent the overwhelming inflammatory response implicated<SUP> </SUP>in H5N1 pathogenesis.<SUP>23</SUP> Therefore, much more research is needed<SUP> </SUP>to define optimal treatment for patients with H5N1 virus infection.<SUP> </SUP>
    Our findings of a wide range of clinical features and outcomes<SUP> </SUP>associated with clade 2 H5N1 virus infection in Indonesia highlight<SUP> </SUP>the importance of careful clinical examination, laboratory diagnosis,<SUP> </SUP>and sequential monitoring of all patients with suspected H5N1<SUP> </SUP>virus infection and their close contacts. Further research is<SUP> </SUP>needed to understand the role of mild cases in the epidemiology<SUP> </SUP>of this disease and whether genetic, behavioral, immunologic,<SUP> </SUP>and environmental factors may contribute to case clustering<SUP> </SUP>of H5N1 virus infection.<SUP> </SUP>
    <SUP></SUP>
    <SUP></SUP>
    All authors report receiving financial support from their respective<SUP> </SUP>institutions. No potential conflict of interest relevant to<SUP> </SUP>this article was reported.<SUP> </SUP>
    The views expressed in this article are those of the authors<SUP> </SUP>and do not reflect the official policy or position of the Indonesian<SUP> </SUP>National Institute of Health Research and Development and Directorate<SUP> </SUP>General of Disease Control and Environmental Health (Ministry<SUP> </SUP>of Health), the U.S. Department of Defense, the U.S. Department<SUP> </SUP>of the Navy, or the Centers for Disease Control and Prevention<SUP> </SUP>(CDC).<SUP> </SUP>
    We thank our many colleagues at the Directorate General of Disease<SUP> </SUP>Control and Environmental Health and the National Institute<SUP> </SUP>of Health Research and Development, Ministry of Health, Jakarta;<SUP> </SUP>the provincial, district, and subdistrict health offices; the<SUP> </SUP>health care providers at Indonesian hospitals who cared for<SUP> </SUP>patients with H5N1 virus infection; the U.S. Naval Medical Research<SUP> </SUP>Unit 2; the WHO in Indonesia; Hong Kong University; Hong Kong<SUP> </SUP>Government Virus Unit; and the CDC, for their contributions<SUP> </SUP>to our epidemiologic, clinical, virologic, and immunologic investigations.<SUP> </SUP>

    Source Information
    From the Directorate General of Disease Control and Environmental Health (I.N.K., H.W., Y., W.H., W.P., H.S., C.S.) and the National Institute of Health Research and Development (E.R.S., E.T., B.H., D.Y., S.H.), Ministry of Health, Jakarta; the Infectious Disease Hospital Rumah Sakit Penyakit Infeksi Sulianti Saroso, North Jakarta (S.S., S.G.); the U.S. Naval Medical Research Unit 2, Jakarta (P.J.B., A.J., H.K., S.D.P.); and the World Health Organization, Jakarta (G.S., M.S.) ? all in Indonesia; the University of Hong Kong (K.H.C., L.L.M.P., Y.G., M.P.) and the Department of Health (W.L.) ? both in Hong Kong; and the Centers for Disease Control and Prevention, Atlanta (A.K., S.L., R.D., J.K., N.C., T.M.U.).
    Address reprint requests to Dr. Uyeki at the Influenza Division, Mail Stop A-32, Centers for Disease Control and Prevention, Atlanta, GA 30333, or at tuyeki@cdc.gov<SCRIPT type=text/javascript><!-- var u = "tuyeki", d = "cdc.gov"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></SCRIPT> .
    References
    1. <!-- null --><LI value=1>Isolation of avian influenza A(H5N1) viruses from humans -- Hong Kong, May-December 1997. MMWR Morb Mortal Wkly Rep 1997;46:1204-1207.<!-- HIGHWIRE ID="355:21:2186:1" --> [Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=2>Peiris JS, Yu WC, Leung CW, et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 2004;363:617-619.<!-- HIGHWIRE ID="355:21:2186:2" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=3>Olsen SJ, Ungchusak K, Sovann L, et al. Family clustering of avian influenza A (H5N1). Emerg Infect Dis 2005;11:1799-1801.<!-- HIGHWIRE ID="355:21:2186:3" --> [ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=4>Ungchusak K, Auewarakul P, Dowell SF, et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005;352:333-340.<!-- HIGHWIRE ID="355:21:2186:4" --> <NOBR>[Abstract/Full Text]</NOBR><!-- /HIGHWIRE --><!-- null --> <LI value=5>Office International des Epizooties. Highly pathogenic avian influenza in Indonesia. Jakarta, Indonesia: Department of Agriculture, February 6, 2004. (Accessed October 30, 2006, at ftp://ftp.oie.int/infos_san_archives/eng/2004/en_040206v17n06.pdf.)<!-- HIGHWIRE ID="355:21:2186:5" --><!-- /HIGHWIRE --><!-- null --> <LI value=6>Avian influenza ? situation in Indonesia ? update 32. Geneva: World Health Organization, September 29, 2005. (Accessed October 30, 2006, at http://www.who.int/csr/don/2005_09_29/en/index.html.)<!-- HIGHWIRE ID="355:21:2186:6" --><!-- /HIGHWIRE --><!-- null --> <LI value=7>Smith GJD, Naipospos TSP, Nguyen TD, et al. Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam. Virology 2006;350:258-268.<!-- HIGHWIRE ID="355:21:2186:7" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=8>WHO case definitions for human infections with influenza A (H5N1) virus. Geneva: World Health Organization, August 29, 2006. (Accessed October 30, 2006, at http://www.who.int/csr/disease/avian_influenza/guidelines/case_definition2006_08_29/en/index.html.)<!-- HIGHWIRE ID="355:21:2186:8" --><!-- /HIGHWIRE --><!-- null --> <LI value=9>World Health Organization Global Influenza Program Surveillance Network. Evolution of H5N1 avian influenza viruses in Asia. Emerg Infect Dis 2005;11:1515-1521.<!-- HIGHWIRE ID="355:21:2186:9" --> [ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=10>Yu H, Shu Y, Hu S, et al. The first confirmed human case of avian influenza A (H5N1) in Mainland China. Lancet 2006;367:84-84.<!-- HIGHWIRE ID="355:21:2186:10" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=11>Human avian influenza in Azerbaijan, February-March 2006. Wkly Epidemiol Rec 2006;81:183-188.<!-- HIGHWIRE ID="355:21:2186:11" --> [Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=12>Oner AF, Bay A, Arslan S, et al. Avian influenza A (H5N1) infection in eastern Turkey in 2006. N Engl J Med 2006;355:2179-2185.<!-- HIGHWIRE ID="355:21:2186:12" --> <NOBR>[Abstract/Full Text]</NOBR><!-- /HIGHWIRE --><!-- null --> <LI value=13>Le QM, Kiso M, Someya K, et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature 2005;437:1108-1108. [Erratum, Nature 2005;438:754.]<!-- HIGHWIRE ID="355:21:2186:13" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=14>de Jong MD, Tran TT, Truong HK, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005;353:2667-2672.<!-- HIGHWIRE ID="355:21:2186:14" --> <NOBR>[Abstract/Full Text]</NOBR><!-- /HIGHWIRE --><!-- null --> <LI value=15>WHO rapid advice guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus. Geneva: World Health Organization, 2006. (Accessed October 30, 2006, at http://www.who.int/csr/disease/avian_influenza/guidelines/pharmamanagement/en/index.html.)<!-- HIGHWIRE ID="355:21:2186:15" --><!-- /HIGHWIRE --><!-- null --> <LI value=16>Chan PK. Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clin Infect Dis 2002;34:Suppl 2:S58-S64.<!-- HIGHWIRE ID="355:21:2186:16" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=17>Yuen KY, Chan PK, Peiris M, et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 1998;351:467-471.<!-- HIGHWIRE ID="355:21:2186:17" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=18>Buxton Bridges C, Katz JM, Seto WH, 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;181:344-348.<!-- HIGHWIRE ID="355:21:2186:18" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=19>The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian influenza A (H5N1) infection in humans. N Engl J Med 2005;353:1374-1385.<!-- HIGHWIRE ID="355:21:2186:19" --> <NOBR>[Full Text]</NOBR><!-- /HIGHWIRE --><!-- null --> <LI value=20>WHO recommendations on the use of rapid testing for influenza diagnosis. Geneva: World Health Organization, July 2005. (Accessed October 30, 2006, at http://www.who.int/csr/disease/avian_influenza/guidelines/RapidTestInfluenza_web.pdf.)<!-- HIGHWIRE ID="355:21:2186:20" --><!-- /HIGHWIRE --><!-- null --> <LI value=21>Tran TH, Nguyen TL, Nguyen TD, et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 2004;350:1179-1188.<!-- HIGHWIRE ID="355:21:2186:21" --> <NOBR>[Abstract/Full Text]</NOBR><!-- /HIGHWIRE --><!-- null --> <LI value=22>Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis 2005;11:201-209.<!-- HIGHWIRE ID="355:21:2186:22" --> [ISI][Medline]<!-- /HIGHWIRE --><!-- null -->
    2. de Jong MD, Simmons CP, Thanh TT, et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 2006;12:1203-1207.<!-- HIGHWIRE ID="355:21:2186:23" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE -->

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    This article has been cited by other articles:
    • (2006). Avian Flu: Deadly, and Difficult to Diagnose. Journal Watch (General) 2006: 1-1 <NOBR>[Full Text] </NOBR>
    • Oner, A. F., Bay, A., Arslan, S., Akdeniz, H., Sahin, H. A., Cesur, Y., Epcacan, S., Yilmaz, N., Deger, I., Kizilyildiz, B., Karsen, H., Ceyhan, M. (2006). Avian Influenza A (H5N1) Infection in Eastern Turkey in 2006. NEJM 355: 2179-2185 <NOBR>[Abstract] [Full Text] </NOBR>

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    Re: NEJM - 3 Indonesian Clusters -H5N1 - 2005

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