Efficacy and safety of low dosage amantadine hydrochloride as prophylaxis for influenza A. Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine. The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home. Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia. [Therapeutic efficacy of amantadine hydrochloride in patients with epidemic influenza A virus infection]. Effectiveness of virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years: a prospective cohort study. Effectiveness of inactivated influenza vaccine for prevention of otitis media in children. Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial. Safety, efficacy, and effectiveness of cold-adapted influenza vaccine-trivalent against community-acquired, culture-confirmed influenza in young children attending day care. Prevention of Russian influenza by amantadine. Administration of amantadine for the prevention of Hong Kong influenza. Amantadine therapy of epidemic influenza a(2) (Hong Kong).
The efficacy and safety of prophylactic low dose amantadine hydrochloride was assessed in two double-blind, placebo-controlled, randomized studies. In a study of 476 subjects aged 18 to 55 years, adverse reactions were not significantly different between the group receiving 100 mg/day amantadine and the placebo group but significantly greater in the group given 200 mg/day (P less than 0.009). The influenza attack rate in this study was too low to assess efficacy. In an experimental challenge study of influenza A/Beth/1/85 in 78 subjects of similar age the prophylactic administration of 50 mg, 100 mg or 200 mg/day doses of amantadine were more effective than placebo in preventing influenza illness (P less than 0.02, 66, 74 and 82% protection, respectively), and in suppressing viral replication (P = 0.02). There was no significant difference between amantadine groups in influenza illness or viral shedding. Compared with the placebo group the 100 and 200 mg amantadine groups showed a significant decrease in infection rate (100 mg: 40% protection: P = 0.012; 200 mg: 32% protection: P = 0.045) whereas the 50 mg group did not (20% protection: P = 0.187). These results suggest that 100 mg/day of amantadine will reduce toxicity but maintain the prophylactic efficacy seen with 200 mg/day. During an outbreak of influenza A/Brazil/78 H1N1 infection, 47 volunteers with clinical and virological influenza of less than 2 days duration were treated in a randomized double-blind fashion for 5 days with 100 or 200 mg of amantadine daily or with 3.25 g of aspirin daily. The aspirin treatment group defervesced more rapidly (10.3 h versus 21.5 h and 23.6 h; P less than 0.01), but by the second daily follow-up visit, both groups of amantadine recipients exhibited greater symptomatic improvement. Bothersome side effects resulted in discontinuation of therapy by 35% of the aspirin treatment group but only 3% of the amantadine treatment group (P less than 0.05). Individuals who present to a physician during an influenza A epidemic with characteristic symptoms will experience symptomatic benefit from amantadine treatment, with negligible toxicity. An outbreak caused by influenza A/Philippines/2/82 (H3N2)-like viruses occurred in a partially vaccinated nursing home population in January 1985. During the first six days of the outbreak, 14 (25%) of 55 residents developed influenzalike illness. The risk of illness was most strongly associated with undetectable levels of antibody against the epidemic strain, with unvaccinated case-patients having more severe illnesses and a higher rate of hospitalization than vaccinated case-patients (5/8 vs 0/6). During the period of amantadine hydrochloride prophylaxis (100 mg/d) from days 7 to 35, only two (5%) of the remaining 41 residents became ill, even though 11 (27%) had no detectable antibody. Serum amantadine levels obtained on day 35 ranged from 117 to 737 ng/mL (mean 309 ng/mL), similar to therapeutic levels documented in younger adults who have taken the standard regimen of 200 mg/d; there were few clinically significant side effects. These findings illustrate the benefits of influenza vaccination and support the use of amantadine hydrochloride at a dosage of 100 mg daily for outbreak control among elderly persons. This study was designed to evaluate the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) against culture-confirmed influenza in children 12 to <36 months of age during 2 consecutive influenza seasons at multiple sites in Asia.
                In year 1, 3174 children 12 to <36 months of age were randomized to receive 2 doses of CAIV-T (n = 1900) or placebo (n = 1274) intranasally > or =28 days apart. In year 2, 2947 subjects were rerandomized to receive 1 dose of CAIV-T or placebo.
                Mean age at enrollment was 23.5 +/- 7.4 months. In year 1, efficacy of CAIV-T compared with placebo was 72.9% [95% confidence interval (CI): 62.8-80.5%] against antigenically similar influenza subtypes, and 70.1% (95% CI: 60.9-77.3%) against any strain. In year 2, revaccination with CAIV-T demonstrated significant efficacy against antigenically similar (84.3%; 95% CI: 70.1-92.4%) and any (64.2%; 95% CI: 44.2-77.3%) influenza strains. In year 1, fever, runny nose/nasal congestion, decreased activity and appetite, and use of fever medication were more frequent with CAIV-T after dose 1. Runny nose/nasal congestion after dose 2 (year 1) and dose 3 (year 2) and use of fever medication after dose 3 (year 2) were the only other events reported significantly more frequently in CAIV-T recipients.
                CAIV-T was well tolerated and effective in preventing culture-confirmed influenza illness over multiple and complex influenza seasons in young children in Asia. A virus infection was studied using half of the normal oral dose of amantadine hydrochloride-100 mg/d instead of 200 mg/d. The patients in this study, who visited the clinics during January and February 1999, were confirmed within 48 hours to have influenza A virus infections by the Directigen FluA test. Using a quasi-randomized controlled trial, 26 patients were treated with amantadine hydrochloride in addition to the usual medication, while 23 were treated with only the ordinary medication. There were no significant differences in the mean age, 35.6 years old, or in clinical features between the two groups. The period of fever over 38 degrees C in the amantadine treated group was 1 day while that in the control group was 1.7 days, which shows a significant difference (p = 0.049). There was no significant difference in the duration of aching, such as arthralgia, or of general fatigue. There was no significant difference in the appearance of subsequent new symptoms after the onset of influenza A virus infection. In conclusion, it is expected that oral amantadine hydrochloride, 100 mg/d, together with the ordinary medication, will reduce the duration of the period of fever over 38 degrees C. To evaluate the effectiveness of a virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years, a prospective cohort study was carried out during the 2004-2005 influenza season in 11 private pediatric clinics in the Barcelona metropolitan area. One dose of a virosomal subunit inactivated influenza vaccine (Inflexal V Berna) was given during September and October 2004 to healthy children aged 3-14 years attended in 5 of the 11 clinics. Who comprised the vaccinated cohort (n=966). The non-vaccinated cohort (n=985) was comprised of children attended in the other six clinics. Informed consent was obtained from all parents. The follow up was performed between 1 November 2004 and 31 March 2005. Using a self-administered questionnaire, information was collected from parents or guardians on any type of acute, febrile respiratory illness suffered by their children during the study period, including antibiotic use, and absence from school or work-loss of parents as a result of the illness. RT-PCR (influenza A+B+C) was carried out on pharyngeal and nasal samples obtained from children attended by pediatricians during this period in these clinics with the following symptoms: fever> or =38.5 degrees lasting at least 72h, cough or sore throat (influenza-like illness). Adjusted vaccination effectiveness was 58.6% (95% CI 49.2-66.3) in preventing acute febrile respiratory illnesses, 75.1% (95% CI 61.0-84.1) in preventing cases of influenza-like illnesses and 88.4% (95% CI 49.2-97.3) in preventing laboratory-confirmed cases of influenza A. The adjusted vaccination effectiveness in reducing antibiotic use (18.6%, 95% CI -4.2 to 3.64), absence from school (57.8%, 95% CI 47.9-65.9) and work-loss of parents (33.3%, 95% CI 8.9-51.2) in children affected by an acute febrile respiratory illness was somewhat lower. Vaccination of children aged 3-14 years in pediatric practices with one dose of virosomal subunit inactivated influenza vaccine has the potential to considerably reduce the health and social burdens caused by influenza-related illnesses. The objective of this study was to evaluate the effectiveness of inactivated influenza vaccine in preventing acute otitis media (AOM) and otitis media with effusion (OME) in children aged 6 to 60 months who attend day care.
                This prospective, single-blind study was conducted in 8 day care centers in Ankara, Turkey. One hundred nineteen (61 vaccinated and 58 unvaccinated against influenza) healthy children were examined at study entry and at 6-week intervals for 6 months by the same 2 otorhinolaryngologists who were blinded about the vaccination status of the children. The frequency of AOM and OME is compared between the 2 groups and the effect of influenza season on frequency of episodes was evaluated. Based on national influenza laboratory data, the influenza season was determined to be the period between December 15, 2003, and January 31, 2004.
                The frequencies of AOM, OME and total otitis media episodes in vaccinated children were 2.3%, 22.8% and 25.2%, respectively, and these frequencies were 5.2%, 31.1% and 36.3% in the unvaccinated group. The difference was statistically significant (P < 0.01). This difference was especially prominent in the influenza season (P < 0.05).
                Influenza vaccine is effective in reducing AOM and OME episodes in 6- to 60-month-old day care children, especially during influenza season. To assess the efficacy of three days versus five days of treatment with oral amoxicillin for curing non-severe pneumonia in children.
                Randomised, double blind, placebo controlled multicentre trial.
                Outpatient departments of seven referral hospitals in India.
                2188 children aged 2-59 months, 1095 given three days of treatment and 1093 given five days.
                Oral amoxicillin 31-54 mg/kg/day in three divided doses.
                Treatment failure: defined as development of chest indrawing, convulsions, drowsiness, or inability to drink at any time; respiratory rate above age specific cut points on day 3 or later; or oxygen saturation by pulse oximetry < 90% on day 3.
                The clinical cure rates with three days and five days of treatment were 89.5% and 89.9%, respectively (absolute difference 0.4 (95% confidence interval--2.1 to 3.0)). Adherence to treatment regimen was 94% and 85% for three day and five day treatments, respectively. Loss to follow up was 5.4% by day 5. There were no deaths, 41 hospitalisations, and 36 minor adverse reactions. There were 225 (10.3%) clinical failures and 106 (5.3%) relapses, and rates were similar in both treatments. At enrollment, 513 (23.4%) children tested positive for respiratory syncytial virus, and Streptococcus pneumoniae and Haemophilus influenzae were isolated from the nasopharynx in 878 (40.4%) and 496 (22.8%) children, respectively. Clinical failure was associated with isolation of respiratory syncytial virus (adjusted odds ratio 1.95 (95% confidence interval 1.0 to 3.8)), excess respiratory rate of > 10 breaths/minute (2.89 (1.83 to 4.55)), and non-adherence with treatment at day 5 (11.57 (7.4 to 18.0)).
                Treatment with oral amoxicillin for three days was as effective as for five days in children with non-severe pneumonia. The goal was to evaluate the safety, tolerability, and efficacy of an investigational, refrigerator-stable formulation of live attenuated influenza vaccine (cold-adapted influenza vaccine-trivalent) against culture-confirmed influenza, acute otitis media, and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons.
                Children 6 to <36 months of age who were attending day care were assigned randomly in year 1 to receive 2 doses of vaccine or placebo intranasally, 35 +/- 7 days apart. In year 2, subjects received 1 dose of the same treatment as in year 1.
                A total of 1616 subjects (vaccine: 951 subjects; placebo: 665 subjects) in year 1 and 1090 subjects (vaccine: 640 subjects; placebo: 450 subjects) in year 2 were able to be evaluated for efficacy. The mean age at first vaccination was 23.4 +/- 7.9 months. In year 1, the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4%; efficacy was 91.8% against A/H1N1 and 72.6% against B. In year 2, the overall efficacy was 88.7%; efficacy was 90.0% against H1N1, 90.3% against A/H3N2, and 81.7% against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6% in year 1 and 97.0% in year 2. Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent (82.3%) than placebo (75.4%).
                Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care. We tested the effectiveness of amantadine hydrochloride in prevention of illness and infection caused by Russian (h1n1) influenza. The trial lasted seven weeks and was double-blind and placebo controlled. The dosage used was 200 mg daily. Efficacy in prevention of serologically confirmed clinical influenza was 70.7%. Efficacy in prevention of infection, symptomatic or asymptomatic, was 39.4%. Side effects seen were all mild, began within two days of the start of the trial, and terminated rapidly on cessation of prophylaxis. The withdrawal rate attributable to use of amantadine was 6.2%. Those who continued to receive prophylaxis for the remainder of the trial did not exhibit excess side effects. It is concluded that amantadine is safe and effective in prophylaxis of H1N1 strains, as has been shown previously for other subtypes of A influenza. The prophylactic effectiveness of amantadine against A2/Hong Kong influenza was investigated in the course of a double-blind trial in Braşov, Romania, during an epidemic due to the Hong Kong virus that started there in March 1969.Altogether 215 subjects were included in the trial; 112 received 100 mg of amantadine twice daily for 20 days and the remaining 103 received inert placebo tablets. Of the amantadine-treated group, 2 had clinical symptoms diagnosed as influenza (1 of these was a doubtful diagnosis), whereas 20 (1 doubtful) of the placebo group had such symptoms. No case with both clinical symptoms and serologically confirmed influenza (>/=4-fold increase in haemagglutination-inhibition titre) occurred among 77 amantadine-treated subjects for whom paired sera were available but there were 13 such cases among the 74 placebo subjects with paired sera. These differences are statistically highly significant. No serious side-effects were recorded.The authors conclude that amantadine was highly effective in preventing overt disease and discuss indications that suggest that it did not interfere with the development of immunity in persons treated during the incubation period. In a double-blind comparison of the therapeutic effect of amantadine in a natural outbreak of Hong Kong influenza in January 1969 near Houston, Texas, the decrease in titers of virus in throat swabs from 12 treated patients during the first 10 hr of treatment was appreciably greater than similar titers of virus from 16 untreated patients (P = 0.06). The titer of shed virus decreased significantly more rapidly (P < 0.05) among amantadine-treated patients ill more than 48 hr before treatment than among five control patients who had been ill more than 48 hr. Cough, sore throat, and nasal obstruction cleared more rapidly in treated patients (P < 0.05), and decline of fever in 6 treated patients sick for less than 48 hr before treatment was more rapid than among 13 untreated patients who had been ill for less than 48 hr. These findings are considered to be consistent with a limited therapeutic effect of the drug.
AMT is effective in preventing influenza A in children but the NNTB is high (NNTB: 12 (95% CI 9 to 17). RMT probably helps the abatement of fever on day three of treatment, but the quality of the evidence is poor. Due to the small number of available studies, we could not reach a definitive conclusion on the safety of AMT or the effectiveness of RMT in preventing influenza in children and the elderly.