EINet Alert ~ Sep 01, 2006

*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- Global: Human avian influenza – transfusion treatment
- Cyprus: Duck die-off not due to avian influenza
- Netherlands: Suspicion of H5N1 in Blijdorp zoo withdrawn
- Indonesia: No cluster of bird flu in Cikelet
- Indonesia: Suspected cases of bird flu in Central Sulawesi and Palu
- Indonesia: Pregnant woman treated with Tamiflu
- Thailand: Avian influenza human disease situation in 2006
- Thailand: Thai researcher says dog had H5N1 avian flu
- Viet Nam: Ducks in Hanoi contract bird flu virus
- USA: New test may enable more labs to subtype flu viruses
- USA: Wild bird surveillance
- USA (Alaska): No highly pathogenic H5N1 avian influenza detected in migratory birds
- USA (Michigan): H5N1 avian influenza virus from mute swans low pathogenic subtype
- South Africa: No outbreak of avian influenza

1. Updates
- Avian/Pandemic influenza updates

2. Articles
- Experimental evaluation of the FluChip diagnostic microarray for influenza virus surveillance
- Low Frequency of Poultry-to-Human H5N1 Virus Transmission, Southern Cambodia, 2005
- Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?

Global: Cumulative number of human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)

Viet Nam / 3 (3)
Total / 3 (3)

Thailand / 17 (12)
Viet Nam / 29 (20)
Total / 46 (32)

Cambodia / 4 (4)
China / 8 (5)
Indonesia / 17 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 95 (41)

Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 12 (8)
Djibouti / 1 (0)
Egypt / 14 (6)
Indonesia / 43 (35)
Iraq / 2 (2)
Thailand / 2 (2)
Turkey / 12 (4)
Total / 96 (64)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 241 (141).
(WHO 8/23/06 http://www.who.int/csr/disease/avian_influenza/country/en/index.html )


Global: Human avian influenza – transfusion treatment
Should the world be caught without an effective vaccine or antiviral treatment for an avian flu pandemic, a last-ditch option may be to inoculate the sick with antibodies from the blood of those who are able to recover from the disease, according to a review of studies published after the 1918 Spanish influenza pandemic.

The H5N1 virus has killed 141 of the 241 people reported to have contracted it. Current manufacturing capacity could vaccinate less than 5 per cent of the world's population in the event of a pandemic, however, making alternative treatments extremely desirable. One method known to work in other viral diseases such as rabies and measles is to transfer the blood of a recovered patient to a sick one, giving the latter antibodies against the pathogen.

Transfusions were also tried in the 1918 flu pandemic but hadn't been studied extensively, so US military and biotech researchers searched the medical literature published between 1918 and 1925 for reports of the treatment. Those who received blood transfusions were 21 per cent more likely to survive a case of influenza-induced pneumonia than those who didn't receive the treatment, they found in a survey of 8 studies. Of 336 total people treated, 16 per cent died from the pneumonia compared with 37 per cent of those in control groups. Of the treated individuals, those who had received a transfusion within the first 3 days of contracting pneumonia were 41 per cent more likely to survive than those treated afterward.

"Our analysis suggests that patients with Spanish influenza pneumonia who received transfusion may have experienced a clinically important reduction in the risk for death and improvements in clinical signs and symptoms," the researchers report in a paper published online on 29 Aug 2006 in the Annals of Internal Medicine (Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influnza pneumonia: a future H5N1 treatment? Ann Intern Med 2006; 145(8) http://www.annals.org/cgi/content/full/0000605-200610170-00139v1). "Our findings are provocative, but our review has important limitations," they point out. The old studies were small and poorly done by current standards.

Nevertheless, "the concept is important and it should be explored further, especially given our lack of proven interventions to prevent or treat illness due to H5N1 influenza," writes John Treanor of the University of Rochester in an accompanying editorial. Serum from recovered patients would be technically simple to prepare and presumably in ample supply, he says, although researchers don't know if those who recover from H5N1 produce copious antibodies. He notes that "controlled clinical studies done now will probably pay a considerable dividend when the pandemic begins."
(Promed 8/31/06)


Europe/Near East
Cyprus: Duck die-off not due to avian influenza
The Agriculture Ministry yesterday reassured the public that ducks found dead at the Athalassa Lake in Nicosia were not infected with bird flu. The ducks are believed to have died after being infected by Clostridium botulinum, a soil bacterium that cannot be spread from animal to animal or from animal to humans.
(Promed 8/26/06)


Netherlands: Suspicion of H5N1 in Blijdorp zoo withdrawn
Dr Veerman, the Minister of Agriculture, Nature and Food Safety, has decided today [25 Aug 2006] to revoke the suspicion of avian influenza infection in the Blijdorp zoo [Rotterdam]. Final results of laboratory investigations of samples from the 2 northern hawk owls found dead in the zoo have been obtained today. According to their outcome, it could not be confirmed with certainty that the birds died due to H5N1.

The initial suspicion of H5N1 was raised at the beginning of August 2006, following tests which were carried out within the avian influenza surveillance undertaken by the Wild Life Health Centre (Erasmus MC Rotterdam/Utrecht University). Further investigations at the Lelystad Laboratory [The Central Institute for Animal Disease Control, CIDC] confirmed the above initial suspicion. However, the investigators have not been able to isolate the virus.

The [Dutch] Food and Consumer Product Safety Authority has sent various [additional] samples from birds in the Blijdorp zoo for [laboratory] investigations. The avian influenza virus could not be detected in any of these samples, including the ones coming from the direct vicinity of the 2 dead young owls.
(Promed 8/27/06)


Indonesia: No cluster of bird flu in Cikelet
According to health officials in Indonesia, no evidence has been found of human-to-human transmission of H5N1 bird flu in the remote villages of West Java which have witnessed the latest outbreak of the deadly virus.

Experts are always concerned when there appears to be a cluster of infection, i.e. when a group of people are infected from the same source. Scientists believe clusters of cases raise the likelihood of H5N1 mutating into a form easily passed between humans that could spark a global flu pandemic with a the potential to kill millions. A total of 3500 poultry had been culled in 5 areas within a one-kilometer radius of Garut and tests have confirmed that half of the poultry were infected by H5N1.

The Cikelet region of Indonesia`s West Java province is remote and inaccessible and the population have had no experience with the disease, and high-risk behaviors occurred during the disposal of carcasses or the preparation of sick or dead birds for consumption, says the WHO. In order to contain the virus, Indonesian authorities are testing all those who were in contact with the bird flu victims and so far all tests have been returned negative.
(Promed 8/25/06)


Indonesia: Suspected cases of bird flu in Central Sulawesi and Palu
Five people have been admitted to hospital on Indonesia's Sulawesi island with bird flu-like symptoms and local authorities have sought funds from the government to help cull poultry, officials said on Wed 30 Aug 2006.

Samples from the patients in Palu, the capital of Central Sulawesi province, have been sent to a government laboratory in Jakarta to be tested for bird flu, said Runizar Ruesin, head of the Ministry's bird flu information centre. No further details about the 5 people were available.

Indonesia has so far recorded 60 bird flu cases, 46 of them fatal. The country's death toll is the highest in the world.

Zulkarnain Hassan, a coordinator at the agriculture ministry's Avian Influenza Crisis Centre, said that there had been bird flu cases in poultry in West and South Palu district and the provincial capital of Palu city. An official of the agriculture ministry in Palu said the local government did not have enough money to compensate farmers for culling their birds and had asked Jakarta for more funds.

"(Culling) is something that must be done," he said, adding that some slaughtering had started in the region on Wed 30 Aug 2006. He did not say how many chickens needed to be killed or how much the work would cost. Bayu Krisnamurthi, head of the national bird flu control commission, said the central government would reimburse funds spent by local governments or compensate farmers.

Separately, the government will on Fri 1 Sep 2006 embark on a new campaign to raise awareness about bird flu through television and radio advertisements, leaflets, posters and billboards, said Tri Satya Naipospos, deputy chief of the National Committee for Avian Influenza Control and Pandemic Preparedness. "So far our campaign has been spotty. We realise that human cases have occurred in regions where people are ignorant about bird flu and they don't have the means to support our efforts," she said, declining to give the cost of the campaign.
(Promed 8/25/06, 8/30/06, 8/31/06)


Indonesia: Pregnant woman treated with Tamiflu
A pregnant woman in Indonesia with symptoms of avian influenza agreed to receive Tamiflu (oseltamivir). The medicine, recommended by the World Health Organization (WHO) to treat the lethal virus, may be a risk to her unborn fetus, a doctor said. The 35 year old woman, 2 months pregnant, began a course of Roche Holding AG's antiviral to treat an infection possibly caused by the H5N1 avian influenza [virus], said Luhur Soeroso, a doctor at the Adam Malik Hospital in Medan on Sumatra island.

Clinicians have had little experience treating H5N1 in pregnant women, and if the woman has the disease, her case may provide needed information. There is no adequate data on the use of Tamiflu in pregnant women, according to WHO. Animal studies don't indicate direct or indirect harmful effects on pregnancy or fetal development, the health agency said in March [2006]. "Our priority is to save her life," Soeroso said. The woman is aware of the unknown risks [to] her fetus caused by oseltamivir and by the antibiotics she is also taking, he said.

WHO recommends that in patients with confirmed or strongly suspected H5N1 infection, doctors should give oseltamivir as soon as possible. The recommendation applies to adults, including pregnant women and children, the health agency said in guidelines for the medical treatment of H5N1 cases, released in May [2006]. There has been "no evidence of a significant risk of fetal abnormalities" caused by Tamiflu treatment during pregnancy, based on clinical trials and post-marketing surveillance, said Alexander Klauser, a spokesman for Roche in Basel, Switzerland. "The majority of women who have taken Tamiflu during pregnancy have given birth to a healthy baby," Klauser said in an email on Friday [25 Aug 2006]. "However, given that there are no well-controlled studies in pregnant women, Tamiflu should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus."
(Promed 8/28/06)


Thailand: Avian influenza human disease situation in 2006
From 1 Jan 2006 to 26 Aug 2006, the Bureau of Epidemiology has received reports of influenza or pneumonia cases in the Avian Influenza Surveillance Network from Provincial Health Offices and Disease Prevention and Control Regional Offices. The investigation and analysis can be summarized as follows: Cumulative number of patients under surveillance has totaled 4434 cases located throughout 71 provinces. [Thailand is subdivided into 75 provinces. - Mod.CP]

A total of 33 cases have been reported today [Sat 26 Aug 2006]: 10 cases from the province of Loei, 3 each from Sukhothai, Phitsanulok, and Uthaithani, 2 each from Nonthaburi, Angthong, Nakhonpathom, Prachaubkirikhan, Nakhonsawan, and Phichit, and one each from Bangkok metropolis, and Uttharadit.

There have been 2 confirmed cases of avian influenza (both fatal) during 2006 up to the present. One of these was a 17 year old male. He became ill on 15 Jul 2006 and died on 24 Jul 2006. The other case was a 27 year old male reported from the Sawang Arom district of Uthai Thani province. He became ill on 24 Jul 2006 and died on 3 Aug 2006. Results for 74 suspected cases are pending.

Conclusions: (1) In 2005, there are 5 confirmed human cases of avian influenza, with 2 fatalities. (2) In 2006, there are 2 confirmed human cases of avian influenza, both fatal.
(Promed 8/28/06)


Thailand: Thai researcher says dog had H5N1 avian flu
A dog in Thailand's central Suphan Buri province contracted avian influenza after eating infected ducks, according to a Thai researcher quoted in a newspaper.

Yong Pooworawan, a lecturer at Chulalongkorn University, disclosed the case yesterday at a university seminar. He said a researcher at Kasetsart University had discovered the case and that it would be described soon in an American medical journal, according to a report today in The Nation, a Thai daily newspaper. Yong did not elaborate on the findings.

If confirmed, the Thai report apparently would be the first known case of H5N1 infection in a dog. The medical literature contains reports of the H5N1 virus in domestic cats, leopards, tigers, and civets, but none involving dogs.
(CIDRAP http://www.cidrap.umn.edu)


Viet Nam: Ducks in Hanoi contract bird flu virus
Two ducks in Viet Nam's capital, Hanoi city, have been infected with the bird flu virus, local newspaper Labor reported on Wednesday [29 Aug 2006]. Specimens from the ducks in a market in Thanh Tri district have tested positive for the bird flu virus strain H5, the paper quoted sources from the country's Central Veterinary Center as saying. Recently, Viet Nam has also detected some waterfowl in the 3 southern provinces of Ben Tre, Long An and Tien Giang as having contracted bird flu viruses, including the strain H5.

Viet Nam will form anti-bird flu task forces at both the central and local levels to stamp out any disease outbreaks in a timely and comprehensive manner. Bird flu outbreaks, starting in Viet Nam in December 2003, have killed and led to the forced culling of dozens of millions of fowl. The last outbreak of bird flu among poultry in the country was in December 2005, according to the Department of Animal Health under the Vietnamese Ministry of Agriculture and Rural Development.
(Promed 8/30/06)


USA: New test may enable more labs to subtype flu viruses
Government-funded researchers say they have developed a test that may enable more laboratories to fully identify influenza viruses than is possible with existing tests.

The FluChip test involves a microarray of genetic material—hundreds or thousands of short sequences of known DNA or RNA deposited on a microscope slide, according to a news release from the Centers for Disease Control and Prevention (CDC). The sequences are used to "capture" matching sequences from viruses in samples gathered from patients.

In a study reported in the Journal of Clinical Microbiology, the test determined the type and subtype of more than 70% of 72 flu viruses, including H5N1 avian flu, in less than 12 hours. The study was led by Kathy L. Rowlen, PhD, of the University of Colorado, with assistance from the CDC and funding from the National Institute of Allergy and Infectious Diseases (NIAID).

The test doesn't require the same level of biological security as other tests used to gather detailed information on flu viruses, including the subtype and clade, or family, according to the CDC. That means more labs can use the test.

"Because the sample is inactivated and you're not amplifying the virus, you don't have to use a BSL-3 [biosafety level 3] lab to do the diagnosis," Dr. Nancy Cox of the CDC, a coauthor of the study, told CIDRAP News. The test can be used in BSL-2 labs, a category that includes many clinical labs, said Cox, who is director of the CDC's influenza division.

Rapid tests now used in clinical practice can identify flu viruses in less than 30 minutes, but, at best, they can only detect a virus and determine whether it is type A or type B; they can't identify the subtype, such as H3N2. More sophisticated tests, such as polymerase chain reaction, immunofluorescence, and viral culture, provide more information but are more difficult to conduct and take from several hours to several days, according to the CDC.

The developers of the FluChip test hope to reduce the time required to subtype a flu virus to less than an hour, the news release said. Their journal article says the methods most widely used to subtype flu viruses typically take about 4 days.
(CIDRAP 8/29/06 http://www.cidrap.umn.edu)


USA: Wild bird surveillance
The public can now view a Web site showing current information about wild bird sampling for early detection of highly pathogenic avian influenza (HPAI) in the United States: http://wildlifedisease.nbii.gov/ai/

Scientists are now using the newly developed database and Web application called HEDDS (HPAI Early Detection Data System) to share information on sample collection sites, bird species sampled, and test results.

The database is available to agencies, organizations, and policymakers involved in avian influenza monitoring and response. Scientists will use the data to assess risk and refine monitoring strategies should HPAI be detected in the United States. Public access is more limited, but shows the states where samples have been collected and includes numbers of samples collected from each state.
(Promed 8/26/06)


USA (Alaska): No highly pathogenic H5N1 avian influenza detected in migratory birds
Secretary Mike Johanns and Interior Secretary Dirk Kempthorne today announced that their departments and the State of Alaska have tested more than 13,000 wild migratory birds for highly pathogenic avian influenza (HPAI) H5N1 in Alaska. No HPAI H5N1-a virus that has killed wild birds, commercial poultry and more than 140 people in Asia, Europe and Africa-has been detected in any of the Alaska samples.

The U.S. Department of Interior (DOI), USDA, the State of Alaska, and the University of Alaska have been involved with sampling wild birds in Alaska since April 2006. The sampling program includes a goal to sample and test 75,000 to 100,000 migratory birds across the United States this year.

So far DOI (including the U.S. Fish and Wildlife Service and the U.S. Geological Survey) has tested more than 11,000 samples and USDA has tested more than 2,000 samples-for a total of more than 13,000. Of those tested by DOI, approximately 113 have tested positive for some form of avian influenza. This is to be expected since there are 144 subtypes of "bird flu," most of which pose no threat to domestic poultry or humans and do not produce noticeable symptoms in wild birds. Of the 113 samples, all tested negative for the highly pathogenic H5N1 virus.
(USDA 8/29/06 http://www.usda.gov, CIDRAP 8/30/06 http://www.cidrap.umn.edu)


USA (Michigan): H5N1 avian influenza virus from mute swans low pathogenic subtype
The United States Department of Agriculture (USDA) today announced final test results, which confirm that an H5N1 avian influenza virus detected in samples collected earlier [in August 2006] from 2 Michigan wild mute swans is a low pathogenic subtype. This strain has been detected several times in wild birds in North America and poses no threat to human health.

The USDA National Veterinary Services Laboratories (NVSL) confirmed the presence of the "North American strain" of low pathogenic H5N1 avian influenza in one of 20 samples collected from the 2 wild mute swans. Preliminary test results announced on 14 Aug 2006 indicated that an H5N1 strain could be present in 2 of the collected samples. Only one of the samples contained high enough levels of the virus to conduct confirmatory testing. As previously announced, genetic testing ruled out the possibility that either of the samples carried the highly pathogenic strain of H5N1 avian influenza that is circulating overseas.

Low pathogenic strains of avian influenza commonly occur in wild birds and typically cause only minor sickness or no noticeable signs of disease in birds. Low pathogenic H5N1 is very different from the more severe highly pathogenic H5N1 circulating in parts of Asia, Europe and Africa. Highly pathogenic strains of avian influenza spread rapidly and are often fatal to chickens and turkeys.
(Promed 8/30/06, USDA 8/28/06 http://www.usda.gov, CIDRAP 8/29/06 http://www.cidrap.umn.edu)


South Africa: No outbreak of avian influenza
The Department of Agriculture wants to assure the public that there is no outbreak of avian influenza (H5N1) in the country.

South Africa is determined to maintain its avian influenza free status and does not allow the importation of any live birds, poultry or poultry products from any country that has not been free for at least the past 3 months.

Smuggling of live birds, eggs or poultry products pose a serious danger to the poultry and ostrich industries in this country. Human health could also be at risk.
(Promed 8/26/06)


1. Updates
Avian/Pandemic influenza updates
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html. See updated case definitions for human infections with influenza A(H5N1) virus (August 29, 2006)
- UN FAO: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html
- OIE: http://www.oie.int/eng/en_index.htm See the update on avian influenza in animals (8/29/06)
- US CDC: http://www.cdc.gov/flu/avian/index.htm
- The US government’s web site for pandemic/avian flu: http://www.pandemicflu.gov/
- CIDRAP: http://www.cidrap.umn.edu/. Frequently updated news and scholarly articles.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm
- American Veterinary Medical Association: http://www.avma.org/public_health/influenza/default.asp
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp See the expansion of disease mapping services at http://diseasemaps.usgs.gov


2. Articles
Experimental evaluation of the FluChip diagnostic microarray for influenza virus surveillance
MB. Townsend, et al.
Abstract: Global surveillance of influenza is critical for improvements in disease management and is especially important for early detection, rapid intervention, and a possible reduction of the impact of an influenza pandemic. Enhanced surveillance requires rapid, robust, and inexpensive analytical techniques capable of providing a detailed analysis of influenza virus strains. Low-density oligonucleotide microarrays with highly multiplexed "signatures" for influenza viruses offer many of the desired characteristics. However, the high mutability of the influenza virus represents a design challenge. In order for an influenza virus microarray to be of utility, it must provide information for a wide range of viral strains and lineages. The design and characterization of an influenza microarray, the FluChip-55 microarray, for the relatively rapid identification of influenza A virus subtypes H1N1, H3N2, and H5N1 are described here. In this work, a small set of sequences was carefully selected to exhibit broad coverage for the influenza A and B viruses currently circulating in the human population as well as the avian A/H5N1 virus that has become enzootic in poultry in Southeast Asia and that has recently spread to Europe. A complete assay involving extraction and amplification of the viral RNA was developed and tested. In a blind study of 72 influenza virus isolates, RNA from a wide range of influenza A and B viruses was amplified, hybridized, labeled with a fluorophore, and imaged. The entire analysis time was less than 12 h. The combined results for two assays provided the absolutely correct types and subtypes for an average of 72% of the isolates, the correct type and partially correct subtype information for 13% of the isolates, the correct type only for 10% of the isolates, false-negative signals for 4% of the isolates, and false-positive signals for 1% of the isolates. In the overwhelming majority of cases in which incomplete subtyping was observed, the failure was due to the nucleic acid amplification step rather than limitations in the microarray.
(Journal of Clinical Microbiology, August 2006, p. 2863-2871, Vol. 44, No. 8)


Low Frequency of Poultry-to-Human H5N1 Virus Transmission, Southern Cambodia, 2005
Vong S, et al.
Emerg Infect Dis [serial on the Internet]. 2006 Oct [date cited].
Available from http://www.cdc.gov/ncidod/EID/vol12no10/06-0424.htm Summary: To understand transmission of influenza A H5N1 virus, we conducted a retrospective survey of poultry deaths and a seroepidemiologic investigation in a Cambodian village where a 28-year-old man was infected with H5N1 virus in March 2005. Poultry surveys were conducted within a 1-km radius of the patient's household. Forty-two household flocks were considered likely to have been infected from January through March 2005 because >60% of the flock died, case-fatality ratio was 100%, and both young and mature birds died within 1 to 2 days. Two sick chickens from a property adjacent to the patient's house tested positive for H5N1 on reverse transcription–PCR. Villagers were asked about poultry exposures in the past year and tested for H5N1 antibodies. Despite frequent, direct contact with poultry suspected of having H5N1 infection, none of 351 participants from 93 households had neutralizing antibodies to H5N1. H5N1 virus transmission from poultry to humans remains low in this setting.
(CIDRAP 8/31/06 http://www.cidrap.umn.edu/)


Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?
Luke TC, et al. Ann Intern Med. 2006 Aug 29; [Epub ahead of print]
BACKGROUND: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics. PURPOSE: To see whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia. DATA SOURCES: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched. STUDY SELECTION: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group. DATA EXTRACTION: Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality. DATA SYNTHESIS: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% CI, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after >/=4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41% [CI, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients. Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed. CONCLUSIONS: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.