Appendix. Presymptomatic or asymptomatic influenza viral shedding and relationship of shedding with symptoms, as determined in representative studies

First author

Nature of study

Pertinent results

Pertinent conclusions

Frank (1)

Surveillance in families, Houston, Texas, 1975–1979

In a study of 50 influenza A illnesses in 41 children <4 years of age, presymptomatic viral shedding was noted in 4 (8%) from whom positive samples were obtained 6, 4, 3, and 3 days, respectively, before symptom onset. Samples were not cultured for most children before symptom onset. Peak shedding occurred during week 1 of illness, when 73% of cultures were positive; 10% were positive on days 8–11, 5% on days 12–15, and 0% days 16–19. Illness duration and shedding were not correlated.

In children, at least 8% of illnesses in a seasonal outbreak were associated with presymptomatic shedding, which was noted up to 6 days before illness; 5% continued to shed at the end of week 2. Peak rates of shedding correlated with symptoms.

Hall (2)

Children with respiratory illness seeking medical care during influenza outbreaks, Rochester, New York, 1977 and 1986

In an influenza B study of 43 children (mean age 8 y), 74% had typical influenzalike illness, 7% had afebrile upper respiratory infections, and 19% had croup. Peak virus titers occurred on day 1 of illness, and 93% of children shed virus on days 1–3, 75% on day 4, and 30% on day 6. Severe illness and prolonged fever were associated with higher virus titers, and a trend (p<0.07) for younger children to shed higher-titer virus occurred. In an influenza A study, symptoms and the highest viral shedding occurred early in illness; 30% of patients still shed at day 7.

Peak shedding early in illness, correlated with symptoms and fever.

Davis (3)

Surveillance in families, Washington, DC area, 1951–1956

Influenza A virus was recovered from 0/4 and 2/3 throat swab samples obtained 3–5 and 1–2 days, respectively, before symptoms, compared with 75 (59%) of 127 swab specimens collected within 3 days after onset of illness.

Shedding at low levels occurred 1–2 days before symptoms

Foy (4)

Surveillance in families, Seattle, Washington, 1984

12/37 persons, all >12 y of age, from whom influenza B virus was isolated were asymptomatic. Virus cultures from asymptomatic persons required longer incubation time than those from symptomatic persons to become positive (12.7 vs. 8.7 days, p<0.007), suggesting low titers of virus in these specimens. The study design did not permit assessment of whether asymptomatic persons transmitted influenza.

Asymptomatic shedding at a low titer may be common during a seasonal outbreak.

Murphy (5)

In the control arm of a study, 7 adult volunteers were nasally infected with wild-type H3N2 virus

Peak virus shedding occurred 2 days after nasal inoculation, and shedding ceased by day 6. Titer of virus shed and daily fever score (reflects height and duration of fever) were strongly correlated (p<0.001). 1/7 study participants had mild symptoms without fever and shed less virus.

Fever score and quantity of virus shed were strongly correlated.

Couch (6)

In a vaccine study, 29 adults received vaccines, and 11 controls received saline. All were nasally infected with H3N2

The vaccinated group had a reduced rate and severity of illness. Among controls (without specific antibody), titer of virus shed and daily severity of illness scores (p<0.001) were strongly correlated. In the combined group, peak viral shedding occurred 3 days after infection. Virus was shed a mean of 5.7 days. 6/29 vaccine recipients and 5/11 controls shed low levels of virus but did not become ill.

Severity of illness and quantity of virus shed were strongly correlated; a substantial rate of asymptomatic shedding occurred at low titer.

Khakpour (7)

Daily cultures of 29 adult prisoners after natural exposure to influenza, Iran, 1968

Virus was isolated from 5/29 contacts. One person had influenza isolated from a throat washing and blood, which is rare, 12 h before symptoms. Four persons had virus isolated from throat washings but never had symptoms; acute antibody titer was high in 2. Virus titrations were not performed.

Presymptomatic and asymptomatic shedding can occur.

Philip (8)

Surveillance in families, Washington, DC area, 1952–1955

In households with proven influenza illness, influenza A was isolated from 8 (38%) of 21 contacts with acute afebrile respiratory illness and 2 (5%) of 40 healthy contacts. Influenza B virus was isolated from 2 (11%)  of 19 contacts with acute afebrile respiratory illness and 0 of 47 contacts. Age distribution of culture-positive contacts was not reported.

Symptomatic household contacts commonly shed influenza A virus. Asymptomatic shedding of influenza A and B viruses was uncommon.

Monto (9)

Surveillance in families, Tecumseh, Michigan, 1976–1981

During seasonal epidemics among persons with serologically proven influenza A (H3N2) infection, at least 15%–25% were ill. Among persons with serologically proven influenza B, at least 19%–34% were ill. Among persons with febrile respiratory illness, influenza virus was isolated from 19.7%.

≈60% of seasonal infections were asymptomatic. (This includes persons with partial immunity due to infection with the same subtype as in previous years; the percentage of asymptomatic infections would be lower in a pandemic.) Viral shedding in asymptomatic persons is likely to be quite low.

Hayden (10)

19 volunteers infected with influenza A H1N1

All study participants were symptomatic, and symptom scores peaked on day 2 and returned to normal by day 8. Virus titers correlated with symptoms.

Viral shedding was correlated with symptoms.