Seroprevalence of Antibodies to Highly Pathogenic Avian Influenza A (H5N1) Virus among Close Contacts Exposed to H5N1 Cases, China, 2005–2008

<div><p>To assess the extent of highly pathogenic avian influenza (HPAI) A (H5N1) virus transmission, we conducted sero-epidemiologic studies among close contacts exposed to H5N1 cases in mainland China during 2005–2008. Blood specimens were collected from 87 household members and 332 social contacts of 23 H5N1 index cases for HPAI H5N1 serological testing by modified horse red-blood-cell hemagglutinin inhibition and microneutralization assays. All participants were interviewed with a standardized questionnaire to collect information about the use of personal protective equipment, illness symptoms, exposure to an H5N1 case during the infectious period, and poultry exposures. Two (2.3%) household contacts tested positive for HPAI H5N1 virus antibody, and all social contacts tested negative. Both seropositive cases had prolonged, unprotected, close contact with a different H5N1 index case, including days of bed-care or sleeping together during the index case’s infectious period, and did not develop any illness. None of the 419 close contacts used appropriate personal protective equipment including 17% who reported providing bedside care or having physical contact with an H5N1 case for at least 12 hours. Our findings suggest that HPAI H5N1 viruses that circulated among poultry in mainland China from 2005–2008 were not easily transmitted to close contacts of H5N1 cases.</p></div

Demographic characteristics, exposure history, use of personal protective equipment, and serum collection of 419 close contacts exposed to HPAI H5N1 case-patients, China, 2005–2008.

<p>Data are no. (%) of close contacts, unless otherwise indicated. Percentages may not total 100 because of rounding.</p>#<p>Contact with well-appearing or sick/dead poultry was defined as direct contact (e.g. touching), or indirect contact which was defined as no physical contact, but being within 1 meter of poultry, poultry products, or poultry feces.</p>*<p>A wet poultry market was defined as a place where small animals and poultry may be purchased live or slaughtered at the market.</p

Flowchart of H5N1 serological testing for 419 close contacts exposed to HPAI H5N1 cases, China, 2005–2008.

<p>Flowchart of H5N1 serological testing for 419 close contacts exposed to HPAI H5N1 cases, China, 2005–2008.</p

Survey sites, study population and antigens used in seroprevalence survey among close contacts exposed to HPAI H5N1 case-patients, China, 2005–2008.

#<p>A/CK/HN/21/05(H5N1) and A/CK/LN/23/05(H5N1) isolated from poultry epidemiologically linked to case-patient 1 and case-patient 2 respectively, were used as antigens in the serological assays for close contact exposed to the matched H5N1 case; these two patients were confirmed by serology only.</p>*<p>For serological testing of exposed contacts without isolation of H5N1 viruses from either human cases or poultry epidemiologically linked to cases, a representative H5N1 virus strain [clade 2.3.4, A/Anhui/1/2005(H5N1)] was used as the antigen.</p

Comparison of demographic and clinical features of 17 fatal and 9 nonfatal H5N1 cases, China.

*<p>Medians were compared between fatal and survival cases with the Wilcoxon rank sum test. For categorical variables, percentages of cases in each category were compared with Fisher's exact test.</p>†<p>NA demotes not applicable.</p>‡<p>Two fatal H5N1 cases had underlying medical conditions, including a 24-year-old pregnant woman <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002985#pone.0002985-Shu1" target="_blank">[28]</a> and a 16-year-old male with a 10-year history of minimal change glomerulopathy. Two surviving H5N1 cases had underlying medical conditions, including a 26-year-old pregnant woman and a 44-year-old female with a ten-year history of chronic bronchitis [unpublished data, China CDC].</p>#<p>A higher proportion of cases survived that received any antiviral treatment compared to those that did not receive antivirals (67% [8/12 patients] vs 7% [1/14 patients], p = 0.003), and with a positive linear association: the Gamma coefficient equals 0.664 (p = 0.005) which indicate a positive correlation between antiviral therapy and disease outcome.</p>$<p>High-dose corticosteroid use was defined as ≥250 mg hydrocortisone or equivalent intravenous (IV) administration daily. For children <13 years old, high-dose corticosteroid use was defined as ≥5 mg hydrocortisone or equivalent IV/kg/day.</p>¶<p>[]: Indicates denominators for testing of fewer cases than full group.</p

Laboratory findings of 26 H5N1 cases^* on initial testing, at hospital admission, and during hospitalization, China.

*<p>Indicates denominators for testing of fewer cases than full group.</p>†<p>Abbreviations and normal range: WBC, white blood cell, 4.0–10.0×10⁹ cells per L, leukopenia (abnormal) was defined as leukocyte count less than 4×10⁹ per L; LYM, lymphocyte count, 0.8–4.0×10⁹ cells per L, lymphopenia (abnormal) was defined as lymphocyte count less than 0.8×10⁹ per L; PLT, platelet count, 100–300×10⁹ platelets per L, thrombocytopenia (abnormal) was defined as platelet count less than 100×10⁹ per L.</p>‡<p>Abbreviations and normal range: ALT, alanine aminotrasferase, 0.0–45.0 U/L; AST, aspartate aminotransferase, 0–45 U/L; Albumin, 35.0–55.0g/L; Creatinine, 36.0–144.0 µmol/L; CK, creatine kinase, 25–190 U/L, abnormal was defined as >130 IU/L for males and >110 IU/L for females; CK-MB, creatine phosphokinase isoenzymes, 0–25 U/L; LDH, Lactic dehydrogenase, 110–250 U/L; Plasma glucose concentration, 3.33–5.55 mmol/L for <15 years, 3.89–5.83 mmol/L for adults (16–59 years), 4.44–6.38 mmol/L for age >60 years, hyperglycemia (abnormal) was defined as plasma glucose concentration above the upper limit.</p>#<p>Abbreviations and normal range: PT, prothrombin time, 11–13 second, abnormal was defined as 3 seconds longer than the upper range of normal; APTT, activated partial thromboplastin time, 26–36 second, abnormal was defined as 3 seconds longer than the upper range of normal; FIB, fibrinogen, 2.0–4.0 g/L, abnormal was defined as <2.0 g/L.</p>§<p>Normal ranges: total protein (below 120 mg/L); red blood cells (0 to 1 per average high powered field [HPF×400)); white blood cells (1–4 per HPF×400)</p>¶¶<p>NA demotes not applicable.</p

Initial chest radiographic findings and progression during hospitalization of 26 H5N1 cases, China.

*<p>NA demotes not applicable</p

Progression of pulmonary disease in chest radiographs from adult (35-year-old male, Panels A day 6 and B day 23 of illness) and pediatric (6-year-old male, Panels C day 6 and D day 14 of illness) H5N1 cases.

<p>Progression of pulmonary disease in chest radiographs from adult (35-year-old male, Panels A day 6 and B day 23 of illness) and pediatric (6-year-old male, Panels C day 6 and D day 14 of illness) H5N1 cases.</p