Tamiflu
[Avian influenza and oseltamivir; a retrospective view]

[Article in Dutch]

Galama JM.

Universitair Medisch Centrum St Radboud, Nijmeegs Universitair Centrum voor Infectieziekten (NUCI), afd. Medische Microbiologie, Postbus 9101, 6500 HB Nijmegen. j.galama mmb.umcn.nl

The outbreak of avian influenza A due to an H7N7 virus in Dutch poultry farms turned out to have public-health effects for those who were involved in the management of the epidemic and who were thus extensively exposed to contaminated excreta and dust. An outbreak-management team (OMT) of experts in virology, infectious diseases and public health advised the Dutch government with respect to the potential health effects on humans. Strict hygiene measures were advised. Moreover, vaccination against human influenza was advised to prevent emergence of a new pandemic virus in humans. Since the human influenza virus H3N2 circulated at the same time, a double infection and emergence of a new human virus was the main fear on which prevention was focused. Conjunctivitis was observed in about 10% of the people involved. The conjunctivitis was sometimes accompanied by mild flu-like symptoms and incidental transmission between humans occurred as well. Because of the unexpected high incidence of symptomatic infections, proven to be caused by the H7N7 strain, oseltamivir was advised as an additional control measure, both for the treatment of symptoms and prophylactically for those with prolonged occupational exposure. After the unfortunate death of a veterinarian due to pneumonia caused by the avian virus, the preventive policy was further extended to people with short and incidental exposure to infected flocks. It is concluded that the policy was adequate, in spite of the unforeseen victim.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12822517&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Oseltamivir: new preparation. An antiviral agent with little impact on influenza.

[No authors listed]

(1) Oseltamivir, an oral antiviral agent, has been marketed in the European Union for the prevention and treatment of suspected influenza during epidemics. (2) Three prevention trials done in the general population showed moderate effects, with a 3.5-4% reduction (in absolute values) in serologically confirmed episodes of 'flu. According to one trial, oseltamivir was moderately effective as a prophylactic for close contacts of 'flu cases (6.6% in absolute values). (3) There are three placebo-controlled double-blind trials evaluating oseltamivir as a treatment for 'flu, two in adults and one in children. (4) At a dose of 75 mg twice a day, oseltamivir shortened symptoms by about 24 hours. There was no evidence that oseltamivir prevented complications that need antibiotic therapy. Influenza virus isolates from adult patients belonged to type A in more than 90% of cases. There is no sound evidence that oseltamivir is effective against type B influenza virus. (5) There was no reduction in the frequency of complications in a trial in at-risk adults with chronic respiratory or cardiovascular disorders, or in a trial in asthmatic children. (6) Patients receiving oseltamivir in clinical trials were more likely to suffer nausea and vomiting than patients given placebo. (7) Oseltamivir has not been compared with oral amantadine or inhaled zanamivir. (8) It is best to use amantadine when prophylaxis is needed during epidemics. In the curative setting, the poor risk-benefit ratio of oseltamivir, zanamivir, and amantadine, argues against the use of these drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12825569&dopt=Abstract oseltamivir Tamiflu



Tamiflu
[Effectiveness of oseltamivir on influenza and influencing factors: age of patients, type of influenza virus and timing of initial administration]

[Article in Japanese]

Kawai N, Iwaki N, Kawashima T, Satoh I, Tsuchimoto T, Shigematsu T, Kondoh K, Maeda T, Hirotsu N, Kunishima O, Kashiwagi S.

National Kyushu Medical Center.

A multi-center open study using the internet was performed during the influenza season of 2001-2002 to evaluate the effectiveness of the anti-influenza agent, oseltamivir, on influenza in relation to: (1) age of patients; (2) type of influenza virus; and (3) timing of initial administration after the onset of the first symptoms of influenza. The study comprised of 779 cases of influenza confirmed by rapid detection tests from 44 clinics in Japan. Patients consisted of 4 age groups, 0-6, 7-15, 16-64 and 65-85 years. All patients were administered oseltamivir within 24 hours, at 25-48 or after 48 hours from the onset of the first symptoms of influenza. Data collected from each age group were the highest body temperature and duration of fever (> or = 37.5 degrees C). The percentage of afebrile patients was calculated at 24, 48 and 72 hours after the initial administration; data were also evaluated by the type of influenza virus A and B. The highest body temperature was higher with statistical significance as patients' age decreased. The duration of febrile period (days) was significantly longer in 0-6 years (2.57 +/- 0.95) than in 65-85 years (2.18 +/- 0.93). Evaluation of the percentage of afebrile patients revealed: the percentage at 24 hours was significantly lower in 0-6 years (28.4%) than in 16-64 years (44.0%); the percentage at 48 and 72 hours showed similar results in each age group; the percentage at 48 and 72 hours was significantly higher when administered initially within 24 hours than over 48 hours after the onset of the first symptoms of influenza; the percentage at 24 and 48 hours was significantly higher when administered within 24 hours than at 25-48 hours; and the type of influenza virus did not affect the percentage. In conclusion, effectiveness of oseltamivir seemed to be affected to an extent by the patients' age and little by the type of influenza virus. Oseltamivir was more effective when administered as early as possible after the onset of the symptoms of influenza.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12872691&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Quantification of the influenza virus load by real-time polymerase chain reaction in nasopharyngeal swabs of patients treated with oseltamivir.

Boivin G, Coulombe Z, Wat C.

Research Center in Infectious Diseases of CHUQ-CHUL and Laval University, Quebec City, Quebec, Canada. guy.boivin crchul.ulaval.ca.

Influenza A virus load was assessed by real-time polymerase chain reaction (PCR) in nasopharyngeal swabs of infected patients treated with oseltamivir. The mean pretreatment virus load was significantly lower in the 24 patients (group A) who initiated treatment within 24 h of the onset of symptoms than it was in the 26 patients (group B) who initiated treatment between 24 and 48 h (1.6x105 vs. 8.4x105 copies/600 ng of total RNA, P=.04); after 48 h of treatment, twice as many patients in group B still had a positive PCR result, compared with patients in group A (42.3% vs. 20.7%). These virological results support the clinical benefit provided by early therapeutic intervention of influenza illness.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12898446&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Management of influenza in adults older than 65 years of age: cost-effectiveness of rapid testing and antiviral therapy.

Rothberg MB, Bellantonio S, Rose DN.

Division of General Medicine and Geriatrics, Baystate Medical Center, Springfield, MA 01199, USA. Michael.Rothberg bhs.org

BACKGROUND: Although antiviral therapy is cost-effective in adults, its cost-effectiveness in older adults has not been studied. OBJECTIVE: To determine the cost-effectiveness of influenza testing and treatment strategies for older adults. DESIGN: Cost-utility decision model. DATA SOURCES: Clinical trials of antiviral drugs and epidemiologic data. TARGET POPULATION: Noninstitutionalized adults older than 65 years of age with influenza-like illness. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Rapid diagnostic testing or empirical therapy with antiviral drugs. OUTCOME MEASURES: Cost per quality-adjusted life-year (QALY) saved. RESULTS OF BASE-CASE ANALYSIS: Compared with no intervention, empirically treating an unvaccinated 75-year-old patient with amantadine increased life expectancy by 0.0014 QALY at a cost of 1.57 dollars, a cost-effectiveness ratio of 1129 dollars per QALY saved. Compared with amantadine, rapid diagnostic testing followed by treatment with oseltamivir cost 5025 dollars per QALY saved and empirical treatment with oseltamivir cost 10,296 dollars per QALY saved. Testing and treatment strategies were less cost-effective if the patient was vaccinated, ranging from 2483 dollars per QALY saved with amantadine to 70,300 dollars per QALY saved with oseltamivir. RESULTS OF SENSITIVITY ANALYSIS: The decision was sensitive to the probability of influenza, the efficacy of oseltamivir in preventing hospitalizations, and hospitalization and case-fatality rates. The decision was not sensitive to the probability or severity of medication side effects, the quality of life for influenza illness or hospitalization, the efficacy of antiviral therapy in shortening influenza illness, or the rapid diagnostic test characteristics. CONCLUSIONS: For unvaccinated or high-risk vaccinated patients during the influenza season, empirical oseltamivir treatment is cost-effective. For other patients, rapid diagnostic testing followed by treatment with oseltamivir is cost-effective. Empirical amantadine treatment offers a low-cost alternative if patients cannot afford oseltamivir.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12965940&dopt=Abstract oseltamivir Tamiflu