NEWS SCAN: H5N1 death of Indonesian mother, asymptomatic H5N1, smallpox drug controversy, swine-origin flu

Nov 14, 2011

Indonesia confirms H5N1 death in mother of 2 earlier victims
Indonesia's Ministry of Health has confirmed H5N1 avian flu in the death of a 29-year-old mother of two children who also died of the disease, according to a report today from Bird Flu Information Corner, an Internet message board operated by Kobe University in Japan and Airlangga University in Indonesia. The report said the patient, from the resort island of Bali, felt weak, was coughing, and had breathing difficulty on Oct 15, when she was hospitalized. However, she escaped just before she was to be transferred to a referral hospital and was found in a place of alternative healing the next day. Her condition deteriorated, and she died at home on Oct 17. Her 5-year-old daughter and 10-year-old son died Oct 9 and Oct 10, respectively, of H5N1 avian flu. Many poultry deaths had been recently reported in the family's flocks and those of their neighbors. If the woman's death is confirmed by the World Health Organization (WHO), it would bring Indonesia's official H5N1 case count to 182, including 150 deaths.
Oct 26 WHO report on children's deaths

Study says T-cell response may help identify subclinical H5N1
A research group from Oxford University exploring the prevalence of asymptomatic H5N1 avian influenza infections in an area of Vietnam that had experienced outbreaks found that T-cell interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assays could be a useful adjunct to serology, which has low sensitivity for detecting antibodies to the virus. They reported their findings in the Journal of Infectious Diseases. They obtained 747 blood samples from a community in northern Vietnam that had reported poultry outbreaks and human infections over the past decade. For a control group, they obtained serum samples from patients in the United Kingdom, as well an area of Vietnam where the virus has not been known to circulate. Twenty four (3.2%) participants in the exposed community had responses to the H5 hemagglutinin peptide pool, with little or no response to H1 or H3. They confirmed the responses by culturing ELISPOT assays and growing antigen-specific short-term T-cell lines and clones. Nearly 5% (37) of participants had antibody titers suggestive of H5N1 exposure. Only four had evidence exposure on both tests. The group concluded that although ELISPOT testing may be useful, more research is needed with cohorts in different geographic areas. They also studied 19 recovered H5N1 patients, only 3 of whom (16%) had H5-specific T-cell responses. They say this may be so "because T-cell responses are short-lived, as seen with seasonal influenza, and it is not known how long specific H5 T-cell responses may persist."
Nov 11 J Infect Dis study abstract
In a commentary on the study in the same issue, Susan Epstein, PhD, with the US Food and Drug Administration's cellular and gene therapy division, said the study raises compelling questions, such as whether or not asymptomatic infections with H5 viruses not well adapted to humans stimulate T-cell, but not antibody, responses. She wrote that T-cell testing is still too cumbersome and expensive for widespread screening, though it may be useful for certain diagnostic purposes, such as testing family contacts in transmission studies.
Nov 11 J Infect Dis commentary extract

Newspaper report raises questions about contract for smallpox drug
A Los Angeles Times report published yesterday has raised questions about the US government's handling of a $433 million contract awarded in May to Siga Technologies Inc. for an antiviral to treat smallpox, saying the price of $255 per dose is well above what federal officials earlier said was reasonable. Siga announced in October 2010 that the Department of Health and Human Services (HHS) intended to give it a contract worth up to $2.8 billion for its drug, ST-246. But the contract required that the winner be a small business, and Chimerix Inc., maker of a competing antiviral, protested, saying Siga was too big, according to the Times report. The federal Small Business Administration agreed, but the Obama administration decided to block all firms except Siga from bidding for the contract, asserting that it was the only firm capable of delivering a product within 5 years. The final contract for 1.7 million doses of ST-246 was awarded in May, after negotiations described as contentious. The story said that in March, Dr. Richard Hatchett, chief medical officer for HHS's Biomedical Advanced Research and Development Agency, complained that Siga's projected profit on the product at that point was 180%, which he considered "outrageous." In April, after Siga complained about HHS's approach to profit, Dr. Nicole Lurie, HHS assistant secretary for preparedness and response, replaced the lead HHS negotiator on the deal, according to the story. Lurie told the Times that the contract was awarded strictly on merit. The story also says that billionaire Ronald O. Perelman, Siga's controlling shareholder, is a longtime Democratic Party donor. In addition, the report raises questions about the need for the drug, noting that the government has enough smallpox vaccine for the entire population. The vaccine is regarded as likely to provide some protection if given within 4 days after exposure to the virus.
Nov 13 LA Times story
Jun 29 CIDRAP News item about change in Siga contract
Feb 16 CIDRAP News item about contract award to Chimerix

Analysis shows diversity of swine-origin flu in humans
US swine-origin influenza viruses (SOIVs) collected from humans over the past two decades have been antigenically and genetically diverse, with only triple-reassortant SOIVs occurring since 1998, according to a study in Virology. Researchers analyzed 27 cases of SOIV reported to the Centers for Disease Control and Prevention from 1990 through 2010. All 6 of the viruses isolated from 1990 through 1995 were categorized as classical SOIVs, whereas all 21 isolated since 1998 have been triple-reassortant SOIVs. Of those 21, 13 were classified as H1N1, 1 as H1N2, and 7 as H3N2. The authors say the SOIVs were antigenically and genetically closely related to flu viruses circulating in pigs but not to those circulating in people. They write that their findings highlight "the importance of continued surveillance at the animal-human interface." Their analysis did not include eight US cases identified since September of human infections with H3N2 SOIVs that contain genetic material from the 2009 H1N1 flu virus.
Nov 10 Virol abstract

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