Thomas C. Luke, MD, MTMH; Edward M. Kilbane, MD, MPH; Jeffrey L. Jackson, MD, MPH; Stephen L. Hoffman, MD, DTMH
Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of the Army, Department of Defense, or the U.S. government.
Acknowledgments: The authors thank Jan K. Herman, PhD, and Andre B. Sobocinski of the U.S. Navy Bureau of Medicine and Surgery Historical Office for assistance with the search; Lieutenant Laura L. Jensen, USN, for translation of the Russian medical literature referenced in this article; Commander Steven E. Allen, USN, of the U.S. Navy Bureau of Medicine and Surgery Blood Program Office for assistance in blood component collection and therapy regulations; Dr. Judith Epstein of the Naval Medical Research Center for manuscript review; and Merissa Henry of Protein Potential LLC for editorial assistance.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Stephen L. Hoffman, MD, DTMH, Protein Potential LLC, 12111 Parklawn Drive, Rockville, MD 20852; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Luke and Kilbane: Public Health, Bureau of Medicine and Surgery, U.S. Navy, 2300 E Street NW, Washington, DC 20372-3000.
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.
To determine whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia.
Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched.
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.
Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality.
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.
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.
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.
Studies of Spanish influenza that evaluated effects of transfusion with influenza-convalescent blood products might offer insights regarding potential treatments for H5N1 influenza.
This review of 8 controlled studies published in English-language medical literature between 1918 to 1925 found that transfusion with influenza-convalescent human blood products may have reduced risk for death in hospitalized patients with Spanish influenza complicated by pneumonia. Transfusions caused some chill reactions.
Studies had many methodologic limitations.
Studies from the Spanish influenza era support the idea that convalescent human H5N1 plasma could be an effective, accessible treatment that should be studied in clinical trials.
Flow diagram of trial identification and selection.
*Most of these studies were excluded on the basis of multiple criteria.
Absolute risk differences in mortality among patients treated with convalescent blood products and controls.
Results favor treatment with convalescent blood products (z = 7.1; P < 0.001), and there was no statistical evidence of large heterogeneity (Q = 7.0; I2 = 29.3%; P = 0.22). The pooled estimate should be interpreted with caution and should not be generalized to other strains of virulent influenza without further study. Percentages have been rounded to the nearest whole integer. *In 2 studies with low mortality rates in the treatment group, the majority of patients were treated within 48 hours after pneumonia complicating influenza was diagnosed (18, 23, 24). McGuire and Redden (23, 24) reported a range of mortality rates of 30% to 60% among controls, and 30% was used in the analysis.
Absolute risk difference in mortality among patients who received early versus late treatment with convalescent blood products.
Results favor treatment with convalescent blood products (z = 6.50; P < 0.001), and there was no statistical evidence of heterogeneity (Q = 2.76; I2 = 0%; P = 0.43). The pooled estimate should be interpreted with caution and should not be generalized to other strains of virulent influenza without further study. Percentages have been rounded to the nearest whole integer. *The treatment day of a fatal case could not be determined and was excluded from analysis of early versus late treatment (19, 20).
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Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?. Ann Intern Med. 2006;145:599–609. doi: 10.7326/0003-4819-145-8-200610170-00139
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Published: Ann Intern Med. 2006;145(8):599-609.
Infectious Disease, Influenza, Pneumonia, Pulmonary/Critical Care.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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