WHO cites more evidence of H5N1's bias toward young

Feb 14, 2007 (CIDRAP News) – The World Health Organization's (WHO's) latest analysis of human H5N1 avian influenza cases adds to previous evidence that young people are more susceptible to the virus and more likely to die of it than older people.

In examining 256 confirmed cases over 3 years, the WHO found that 89% of patients were younger than 40, and the case-fatality rate for patients older than 50 was 40%, versus 76% for 10- to 19-year-olds and 60% for all ages. The findings were reported in the Feb 9 issue of the WHO's Weekly Epidemiological Record.

The agency said the reason for the skewed age distribution is unknown and does not appear to be entirely a result of the preponderance of young people in the affected countries.

Analysts looked at all human H5N1 cases reported to the WHO that had onset dates between Nov 25, 2003, and Nov 24, 2006. The report updates a previous analysis that covered the 205 cases up to Apr 30, 2006. Findings concerning fatality rates, age distribution, and other major variables were similar in the earlier study and the new one.

The 256 cases came from 10 countries, with Vietnam and Indonesia together accounting for 165. The median age of case-patients was 18, and slightly more than half were younger than 20, the report says. The sex balance was nearly even (129 males, 127 females).

By age, the toll was highest among those younger than 20, with about 65 cases each among children under 10 and in 10- to 19-year-olds, according to a graph in the report. It shows about 53 cases among 20- to 29-year-olds, 41 cases among people in their 30s, 14 among those in their 40s, and 15 in those over 50.

The overall 60% case-fatality rate broke down by age-group as follows: under 5 years, 44%; 5 to 9 years, 49%; 10 to 19 years, 76%; 20 to 29 years, 63%; 30 to 39 years, 66%; 40 to 49, 43%, and over 50, 40%.

The fatality rate was higher among women than men—65% versus 55%—but the difference was not statistically significant. However, the difference reached significance for patients in their 20s and 30s, with a 75% fatality rate for women and 52% for men.

A count of cases by year (November to November) showed that cases doubled in the second year of the 3-year period (93 versus 45) and increased by more than 25% in the third year (118 versus 93).

The median time from onset of symptoms until hospitalization was 4 days (range, 0 to 18). In fatal cases, patients lived a median of 9 days from onset of illness until death (range, 2 to 31 days).

The WHO calculated the age-related incidence of cases in Vietnam and Indonesia in an effort to determine if the skewed age distribution of cases simply reflects more people in the younger age brackets. In Vietnam, the incidence was roughly the same for all age-groups (about 11 to 14 cases per 10 million people) up to age 40 and then dropped off. In Indonesia the incidence was about the same up to age 30 (about 4 to 5 cases per 10 million people) and declined in the older groups.

"The relatively small number of cases precludes the drawing of definite conclusions, although the analysis seems to suggest that the higher number of cases among young people is not solely due to the age structure of the population," the report says. "In both Indonesia and Viet Nam, there appears to be a higher incidence among younger people. However, detection bias cannot be ruled out since children and young adults might be more likely to be diagnosed than younger people."

Two British scientists have hypothesized that most people older than 35 have some unexplained immunity to H5N1 avian flu. Matthew Smallman-Raynor of the University of Nottingham and Andrew D. Cliff of the University of Cambridge offer the suggestion in a letter in the March issue of Emerging Infectious Diseases, published early online.

The two researchers looked at age data for 169 patients whose cases were confirmed between January 2004 and May 2006 (they say age information for another 47 patients was not available from published sources). The median age of patients was 18, the same as in the WHO report.

The researchers reported the following estimated age-group case rates per million population: 0 to 9 years, 0.15; 10 to 19 years, 0.15; 20 to 29 years, 0.13; 30-39 years, 0.08; and 40 and older, 0.02. In looking at 30- to 39-year-olds, they found that 21 patients were 30 to 35, while only six were between 36 and 39.

Smallman-Raynor and Cliff note that case rates are about the same in all age groups under 30 and that few people older than 35 have been infected. They also conclude that "the skewed distribution of cases toward children and young adults transcends sex, reporting period, patient outcome, geographic location, and, by implication, local cultural and demographic determinants."

These observations, they suggest, "are consistent with a biological model of geographically widespread immunity to avian influenza A (H5N1) in persons born before 1969, i.e., about 35 years before the onset of the currently recognized panzootic in domestic poultry."

"If an element of immunity to avian influenza A (H5N1) does exist in older populations, its possible association with geographically widespread (intercontinental) influenza A events before the late 1960s merits further investigation," they conclude.

The WHO report says a deeper analysis of the clinical data from human H5N1 cases will be conducted at an international meeting scheduled for Mar 19 to 21 in Turkey.

See also:

Feb 9 WHO Weekly Epidemiological Record
http://www.who.int/wer/2007/wer8206.pdf

Jun 30, 2006, WHO Weekly Epidemiological Record
http://www.who.int/wer/wer8126.pdf

Letter from Smallman-Raynor and Cliff in Emerging Infectious Diseases
http://www.cdc.gov/eid/content/13/3/06-0849.htm

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