Children with influenza A infection: treatment with rimantadine. Inhaling to mitigate exhaled bioaerosols. Correlated studies of a recombinant influenza-virus vaccine. IV. Protection against naturally occurring influenza in military trainees. Influenza B in households: virus shedding without symptoms or antibody response. Correlated studies of a recombinant influenza-virus vaccine. 3. Protection against experimental influenza in man. Complement is activated in the upper respiratory tract during influenza virus infection.
Treatment with rimantadine of influenza in children and the potential development of resistance in clinical isolates associated with therapy have not been previously studied . We compared rimantadine to acetaminophen therapy in a controlled , double-blind study of 91 children with influenza-like illness . Of 69 children with proven influenza A/H3N2 infection , 37 received rimantadine and 32 received acetaminophen for five days . Children receiving rimantadine showed significantly greater reduction in fever and improvement in daily scores for symptoms and severity of illness during the first three days . Viral shedding also diminished significantly during the first two days but subsequently increased such that by days 6 and 7 the proportion of children shedding virus , as well as the quantity of virus shed , was significantly greater in the rimantadine group . During the seven-day study , of the 22 children in the rimantadine group with serial isolates tested , ten ( 45.5 % ) had resistant isolates compared with two ( 12.5 % ) of those with serial isolates in the acetaminophen group ( P less than .03 ) . Thus , of the total 37 children in the rimantadine group , 27 % were found to have resistant isolated compared with 6 % in the total group receiving acetaminophen ( P less than .04 ) . Furthermore , the mean inhibitory concentration of rimantadine increased with time in the rimantadine group ( r = .4 , P = .002 ) but not in the acetaminophen group . Rimantadine therapy , thus , appears to be significantly more effective than acetaminophen in ameliorating the clinical signs and symptoms of influenza in children . Treatment with rimantadine was also associated with increased viral shedding after the medication was discontinued and with the development of resistance in the clinical isolates , the significance of which is unknown Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing . These " exhaled bioaerosols " may carry airborne pathogens and thereby magnify the spread of certain infectious diseases , such as influenza , tuberculosis , and severe acute respiratory syndrome . We hypothesize that , by altering lung airway surface properties through an inhaled nontoxic aerosol , we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy . We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols . Administering nebulized isotonic saline to these " high-producer " individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 + /- 8.19 % for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid , notably surface tension Albert Leibovitz , * Raymond L. Coultrip , Edwin D. Kilbourne , Llewellyn J. Legters , Creed D. Smith , James Chin , and Jerome L. Schulman From the Sixth U.S. Army Medical Laboratory , Fort Baker , California ; Preventive Medicine Division , Office of the Surgeon , Fort Ord , California ; Department of Microbiology , Mount Sinai School of Medicine , City University of New York , New York ; and the Infectious Disease Element , California State Department of Public Health , Berkeley , In the fall of 1983 , 53 households were enrolled in a double-blind trial of alpha 2-interferon as an intranasal spray to prevent common colds . During the winter/spring of 1984 , 26 households were infected with influenza type B , as shown by isolation of the virus ( 19 households ) and /or significant antibody titer rises ( seven households ) . Interferon did not prevent influenza B infection or modify result ing illness . Of 37 persons shedding virus , 12 were asymptomatic . All were older than age 12 years , and 10 did not respond with antibody by any of the five test methods employed ( complement fixation , hemagglutination inhibition , enzyme-linked immunosorbent assay ( ELISA ) , neutralization , and Western blot ) . In contrast , of 13 symptomatic persons shedding virus from whom sera were available , 11 had significant antibody titer rises . Infection rates were highest among teenagers , but also surprisingly high among the 11 persons observed who were aged 50 years or older , four of whom were infected . The case-to-case interval in household transmission varied between one and nine days . Longer intervals of one , two , and four months between infections among family members were also observed , suggesting repeated introduction s. Neither virus isolation alone nor serologic tests was sufficient to estimate infection rates A recombinant ( X-31 ) influenza A2 vaccine ( Hong Kong variant ) and a st and ard A2 vaccine ( Hong Kong variant ) were given to 51 normal adult volunteers . One month later , 29 vaccinated and 14 control volunteers were challenged with an infectious strain of the Hong Kong variant . The other 22 volunteers were given a second vaccination . All vaccinated volunteers developed a rise in neutralizing antibody in serum , and a minimal increase was noted from the second vaccination . Twenty-five of the 29 volunteers who were challenged with live virus showed a significant rise in neuraminidase-inhibiting ( NI ) antibody from vaccination . A rise in neutralizing antibody in nasal secretions was seen in 14 of 29 , but only five subjects developed a rise in NI antibody . For each type of antibody in each location , the recombinant vaccine was slightly more antigenic , a finding compatible with the suggestion that it contained slightly more antigen ( 556 versus 503 chickcell-agglutinating units ) . After challenge with live virus , a reduction in frequency of infection and illness was noted in both vaccinated groups when compared to controls . Quantification of virus in specimens of nasal wash revealed an association between quantity of virus shed and clinical illness . Titers of NI antibody in serum correlated best with reduced shedding of virus , but an effect of neutralizing antibody could not be excluded . From the serologic responses to vaccination and the protection afforded against live-virus challenge , it was concluded that the recombinant vaccine was as effective as a st and ard A2 influenza vaccine The purpose of this pilot study was to determine whether complement is activated in the upper respiratory tract during experimental influenza virus infection in human volunteers . Seven subjects were challenged with influenza A/Bethesda/1/85 ( H3N2 )  , and four subjects received placebo .  C3a and C5a concentrations were measured by radioimmunoassay in nasal lavage fluids before challenge and for 8 days after challenge . A significant increase ( p less than 0.05 ) in C3a and C5a concentrations was demonstrated in lavage fluids from subjects who developed influenza illness as compared with uninfected control subjects and infected subjects who remained asymptomatic . Maximal levels of C3a and C5a were detected during the recovery phase of illness . These results suggest that complement is activated in the airway in response to influenza illness
A better underst and ing of transmission dynamics is essential in influenza p and emic planning .
If a substantial proportion of transmissions were to occur during the presymptomatic phase or from asymptomatic individuals , then infection control measures such as contact tracing and quarantine of exposures would be of limited value .
Infectiousness has been inferred based on the presence of influenza in the upper respiratory tract rather than from transmission experiments .
Although asymptomatic individuals may shed influenza virus , studies have not determined if such people effectively transmit influenza .