RESEARCHHighly pathogenic avian infl uenza A (HPAI) subtype H5N1 has caused family case clusters, mostly in Southeast Asia, that could be due to human-to-human transmission. Should this virus, or another zoonotic infl uenza virus, gain the ability of sustained human-to-human transmission, an in-fl uenza pandemic could result. We used statistical methods to test whether observed clusters of HPAI (H5N1) illnesses in families in northern Sumatra, Indonesia, and eastern Tur-key were due to human-to-human transmission. Given that human-to-human transmission occurs, we estimate the in-fection secondary attack rates (SARs) and the local basic reproductive number, R0. We fi nd statistical evidence of hu-man-to-human transmission (p = 0.009) in Sumatra but not in Turkey (p = 0.114). For Sumatra, the estimated household SAR was 29% (95% confi dence interval [CI] 15%–51%). The estimated lower limit on the local R0 was 1.14 (95% CI 0.61–2.14). Effective HPAI (H5N1) surveillance, contain-ment response, and fi eld evaluation are essential to monitor and contain potential pandemic strains.Highly pathogenic avian infl uenza A (HPAI) subtype H5N1 is repeatedly crossing the species barrier to humans. Since December 2003, a total of 291 cases of HPAI (H5N1) have been reported in humans, resulting in 172 deaths (i.e., 59% case-fatality ratio) in 12 countries, mostly in Southeast Asia (1). Among these cases, 31 fam-ily clusters have been documented, ranging in size from 2 to 8 family members. How many of these clusters are due to a common avian source and how many are due to human-to-human transmission are important facts to deter-mine. Should one of these HPAI (H5N1) strains gain the capacity for sustained human-to-human transmission, the resulting outbreak, if not contained, would spread world-wide through the global transportation network more rap-idly than adequate supplies of vaccine matched to the new variant could be manufactured and distributed (2,3). We analyzed data from 2 of the largest of the familial clusters to ascertain if human-to-human transmission took place, and if so, how transmissible the strain was.MethodsMay 2006 Human Avian Infl uenza Family Cluster, IndonesiaDuring late April and early May 2006, a cluster of 8 cases of HPAI (H5N1) was detected and investigated by the Indonesian public health surveillance system in north-ern Sumatra (4–6). All case-patients were members of the same extended family. Seven of them resided within 3 ad-jacent houses in the village of Kubu Sembilang. The re-maining patient resided with his immediate family in the village of Kabanjahe (≈10 km away).The index patient was a 37-year-old woman, thought to have been exposed to dead poultry and chicken fecal mate-rial before onset of illness. She also reportedly maintained a market stall that sold live chickens. Although her illness was not confi rmed to have been caused by avian infl uenza (H5N1), her death on May 5, 2006, is suspected to be the result of HPAI (H5N1) infection because of her reported symptoms, illness progression, and prior contact with dis-eased or dead poultry.Twenty members of her extended family are suspected to have been in contact with her, many during a family gath-ering on April 29, 2006 (7). At that time, she was manifest-ing symptoms (i.e., she had a heavy cough, was severely ill, and was prostrate). That night, 9 of these members slept in the same small room as she did (indicated by a black trian-gle in online Appendix Figure 1, available from www.cdc.Detecting Human-to-Human Transmission of Avian Infl uenza A (H5N1) Yang Yang,* M. Elizabeth Halloran,*† Jonathan D. Sugimoto,*† and Ira M. Longini, Jr.*†1348 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 9, September 2007*Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; and †University of Washington, Seattle, Washington, USADetecting Transmission of Avian Infl uenza A (H5N1) gov/EID/content/13/9/1348-appG1.htm). Of these 9 family members, 2 of her sons (15 and 17 years of age) and her 25-year-old brother, who lived in Kabanjhe, became ill in the next 3 weeks. The sons died. The brother was the only person from this family cluster to recover.Of the remaining 11 family members, 4 became ill and died. The 29-year-old sister of the index patient, who lived in an adjacent house, became ill after she provided direct personal care to her ill sister (7). The 18-month-old daugh-ter of this sister also became ill after she was in the pres-ence of the index patient with her mother. The 10-year-old nephew of the index patient, who lived in the other house adjacent to hers, became ill after he attended the fam-ily gathering and frequently visited his aunt’s house. The nephew’s father became ill after he personally cared for his son. The possibility that HPAI (H5N1) was transmitted from the nephew to his father is also supported by genetic sequencing data (4). Though symptoms did not develop in the mother of the nephew, she was directly exposed to her husband during his illness. All case-patients, except for the index patient, were confi rmed as infl uenza (H5N1) positive by PCR. The nephew’s mother was confi rmed as infl uenza (H5N1) negative. As an intervention, 54 surviving rela-tives and close contacts were identifi ed and placed under voluntary quarantine (7). All of these persons, except for pregnant women and infants, received oseltamivir prophy-lactically.December 2005 Human Avian Infl uenza Family Cluster, Eastern TurkeyFrom December 18, 2005, (8) to January 15, 2006 (9), a cluster of 8 confi rmed infl uenza (H5N1) cases was de-tected in Dogubayazit District in eastern Turkey (online Appendix Figure 2, available from www.cdc.gov/EID/con-tent/13/9/1348-appG2.htm) (10–13). These case-patients were among 21 members of 3 households located within 1.5 km of each other (14). All confi rmed case-patients were hospitalized after onset of symptoms (9). Four of the con-fi rmed case-patients died; the other 4 recovered (9). Ten of the remaining 14 household residents were hospitalized with avian infl uenza-like symptoms but were never con-fi rmed to be infected with infl uenza (H5N1) (9). All but one of the hospitalized residents were children (6–15 years of age) (9).Before onset of symptoms, 4 children from 1 house-hold, 3 of whom had confi rmed cases (including the index patient), were reported to have had close contact with the dead bodies of sick chickens (15). The 2 confi