Update:Influenza Activity

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Update: Influenza Activity --- United States, 2003--04 Season

Influenza began circulating in the United States unusually early this season,

and influenza activity nationwide is expected to increase. Cases of severe

disease, including deaths, have been reported in children. This report

summarizes influenza activity in the United States during the weeks ending

October

4--December 6, 2003*. During the week ending December 6, influenza activity was

reported to CDC as widespread in 24 states (Figure). The early season and the

unusually high and persistent demand for vaccine have resulted in a decreasing

supply of trivalent inactivated vaccine. Emphasis should be placed on

vaccinating persons at high risk for complications from influenza, including

healthy

children aged 6--23 months. Healthy persons aged 5--49 years who wish to receive

vaccine should consider being vaccinated with the intranasally administered

live, attenuated influenza vaccine (LAIV), a substantial supply of which

remains available. National Surveillance

CDC conducts national influenza surveillance by monitoring 1) viruses through

a system of approximately 120 World Health Organization (WHO) and National

Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories, 2)

visits for influenza-like illness (ILI)† through the U.S. Influenza Sentinel

Providers Surveillance Network, 3) the percentage of U.S. deaths attributable to

pneumonia and influenza (P & I) reported through the 122 Cities Mortality

Reporting System, and 4) estimated levels of influenza activity reported to CDC

by

state and territorial epidemiologists. CDC also receives reports from clinicians

and local health officials on influenza outbreaks and cases nationwide.

Influenza Virus Surveillance

For the weeks ending October 4--December 6, WHO and NREVSS collaborating

laboratories in the United States tested 24,906 respiratory specimens for

influenza viruses; 6,751 (27.1%) were positive. During the same period, the

weekly

percentages of respiratory specimens testing positive for influenza viruses

increased from 1.4% to 37.1%. During the 2000--01, 2001--02, and 2002--03

influenza

seasons, the peak percentages of specimens testing positive for influenza

ranged from 23.2% to 26.4%. During the 1999--00 influenza season, when influenza

A (H3N2) viruses predominated, the peak weekly percentage of specimens testing

positive was 30.9% (1; CDC, unpublished data, 2003).

Of the 6,751 positive isolates, 6,716 (99.5%) were influenza A viruses, and

35 (0.5%) were influenza B viruses. Of the 6,716 influenza A viruses, 1,255

(18.7%) have been subtyped; 1,254 (99.9%) were influenza A (H3N2) viruses, and

one (0.1%) was an influenza A (H1) virus. As of December 6, a total of 47 states

and all nine surveillance regions had reported laboratory-confirmed

influenza.

CDC has characterized antigenically 215 influenza viruses that were collected

and submitted by U.S. laboratories since October 1. Of these, 212 were

influenza A (H3N2) viruses, and one was an influenza A (H1) virus. Of the 212

influenza A (H3N2) viruses, 54 (25%) were similar antigenically to the vaccine

strain A/Panama/2007/99 (H3N2), which is contained in this season's vaccine,

whereas 158 (75%) were similar antigenically to A/Fujian/411/2002, a drift

variant

of A/Panama/2007/99. ILI Surveillance

During the weeks ending October 4--December 6, the weekly percentages of

patient visits§ to approximately 1,000 sentinel providers nationwide for ILI

increased from 0.9% to 5.1%, which is above the national baseline¶ of 2.5%.

During

the 2000--01, 2001--02, and 2002--03 influenza seasons, the peak weekly

percentages of patient visits for ILI ranged from 3.3% to 4.4%. During the

1999--00

season, the peak weekly percentage for patient visits for ILI was 7.1% (1;

CDC, unpublished data, 2003). P & I Mortality Surveillance

During the week ending December 6, P & I accounted for 7.0% of all deaths

reported through the 122 Cities Mortality Reporting System. The epidemic

threshold** for that week was 7.6%. Since the week ending October 4, the weekly

percentage of P & I deaths has been below the epidemic threshold. The percentage

of P & I

deaths exceeded the epidemic threshold for zero weeks during the 2002--03

influenza season, for 9 weeks during the 2001--02 season, and for 10 weeks

during

the 2000--01 influenza season. During the 1999--00 influenza season, the

percentage of P & I deaths exceeded the epidemic threshold for 15 weeks (1; CDC,

unpublished data, 2003). Activity Reported by State and Territorial

Epidemiologists

During the week ending December 6, influenza activity†† was reported as

widespread in 24 states (Alaska, Arizona, Arkansas, Colorado, Idaho, Indiana,

Iowa, Mississippi, Missouri, Montana, Nebraska, Nevada, New Mexico, North

Carolina, Oklahoma, Oregon, Pennsylvania, Rhode Island, Tennessee, Texas, Utah,

Virginia, Washington, and Wyoming), regional in 15 states (Alabama, California,

Connecticut, Florida, Georgia, Illinois, Kansas, Kentucky, land, Minnesota,

New York, North Dakota, Ohio, South Carolina, and West Virginia) and New York

City, and local in six states (Louisiana, Massachusetts, Michigan, New Jersey,

South Dakota, and Vermont) and the District of Columbia. Sporadic influenza

activity was reported in five states (Delaware, Hawaii, Maine, New Hampshire,

and

Wisconsin) and Guam. Reports of Severe Illness and Deaths

Pediatric cases. CDC has received reports of severe complications of

influenza occurring in young infants, school-age children, and adolescents.

Complications have included encephalopathy, seizures, dehydration with severe

hypotension, respiratory failure requiring mechanical ventilation, and secondary

bacterial pneumonia, including necrotizing pneumonia with community-associated

methicillin-resistant Staphylococcus aureus (CA-MRSA). Three deaths (an infant

aged

20 months with underlying reactive airways disease, a previously healthy

infant aged 22 months, and a previously healthy child aged 16 years) have been

associated with secondary pneumonia caused by CA-MRSA. Other influenza-related

deaths not related to CA-MRSA in children have occurred. Fatal cases reported to

CDC are being investigated by local and state health authorities. Laboratory

testing has confirmed influenza A virus infection in these fatal cases;

antigenic characterization is pending. The vaccination status of the majority of

the

deceased children has not been determined.

Pregnant women. In Texas, 88 pregnant women had laboratory-confirmed

influenza A infections. Symptoms included fever, cough, and profound sinus

tachycardia

(i.e., 150--170 beats per minute) that resolved subsequently. One patient

required intensive care for bilateral pneumonia and myocarditis. Of the 88

patients, two (2.3%) had been vaccinated 2 and 10 days before admission,

respectively. No influenza-associated maternal deaths occurred; one case of

fetal loss

occurred but was not attributed to maternal influenza infection. The majority of

the 88 cases were associated with influenza A infection; however, influenza B

viruses also were detected.

Reported by: S Harper, MD, T Uyeki, MD, E Murray, MSPH, L Brammer, MPH, J

, DVM, K Fukuda, MD, N , PhD, Div of Viral and Rickettsial Diseases; C

Mc, Div of Healthcare Quality Promotion, National Center for Infectious

Diseases; M Wharton, MD, Epidemiology and Surveillance Div, National

Immunization Program, CDC. Editorial Note:

Influenza seasons can vary substantially in terms of timing and pattern of

onset, peaking, decline, and overall severity. In the United States, the

2003--04 influenza season began unusually early, with community activity first

reported in early October, followed by continued spread of influenza activity

during

the weeks ending October 4--December 6. National activity levels have not yet

peaked, and neither the duration of activity nor the season's eventual

magnitude is known. As of December 6, influenza A (H3N2) viruses predominated in

the

United States, but different influenza viruses might predominate later in the

season. Influenza seasons dominated by A (H3N2) viruses (e.g., those in

1996--97, 1997--98, and 1998--99) typically are associated with high levels of

severe illness and deaths (3). No evidence exists to indicate that the

A/Fujian-like viruses in circulation are more virulent than other influenza A

(H3N2)

viruses. However, reports of severe pediatric illnesses and deaths underscore

the

severe consequences that influenza infections can cause in children (4).

Cases of sudden death associated with influenza in previously healthy

children also were reported in the United States during the 2002--03 season (4;

CDC

unpublished data, 2003). Although the pathophysiology of sudden deaths

associated with influenza in children is unknown, atypical symptoms (e.g.,

abdominal

pain, absence of fever, and mild respiratory symptoms) have been reported.

Encephalopathy is another severe and potentially under-recognized

complication of influenza in children (5). One case so far this season has

resulted in

the death of a patient (CDC, unpublished data, 2003). Patients might report high

fevers, seizures, headaches, abnormal mental status, and/or confusion and do

not always exhibit classic influenza symptoms. Cases have been reported among

young children and school-aged children, including adolescents. Suspected

cases should be reported to CDC at telephone, 404-639-0277 or 404-639-2893; fax,

404-639-3866; or e-mail, tmu0@... or nib9@....

Although secondary bacterial pneumonia is a common complication of influenza

infection, S. aureus typically occurs in a minority of such cases. Clinical

and laboratory features of S. aureus pneumonia are similar to other types of

community-acquired pneumonia (6,7). Clinicians should be aware that CA-MRSA can

be a cause of community-acquired pneumonia. Treatment for pneumonia after

influenza infection should be guided by bacterial culture results when possible.

Aspirin and other salicylate-containing medications should not be administered

to children with fever and respiratory illness (1).

Pregnant women are at higher risk than nonpregnant women for having

complications secondary to influenza. Pregnant women who will be in their second

or

third trimester during influenza season should be vaccinated against influenza

(8

).

So far this season, influenza A/Fujian/411/2002-like viruses are

predominating in the United States. This strain differs from the influenza A

(H3N2) virus

contained in the 2003--04 vaccine (i.e., A/Panama/2007/99). The A/Fujian-like

viruses are antigenic drift variants of the A/Panama strain and were detected

by global surveillance early this year but too late for inclusion in the

current influenza vaccine. Hemagglutination inhibition testing using

postinfection

ferret sera indicates that antibodies to the A/Panama vaccine virus

cross-react with A/Fujian-like viruses; therefore, current influenza vaccines

should

provide some protection against A/Fujian-like viruses. However, the level of

protection remains uncertain until vaccine effectiveness studies are completed.

The vaccine also contains A/New Caledonia/20/99 (H1N1)-like and B/Hong

Kong/330/2001-like viruses and should protect persons who are vaccinated against

these

viruses if they circulate more widely later in the season.

Approximately 83.4 million doses of influenza vaccine, including inactivated

influenza vaccine made by two manufacturers and LAIV made by a third

manufacturer, were produced for the 2003--04 influenza season. All doses of

trivalent

inactivated vaccine appear to have been sold by the manufacturers and their

major distributors. Trivalent inactivated vaccine remains available from

physicians' offices and in other settings. As of December 9, a total of 3.9

million

doses of LAIV were available from the manufacturer (Wyeth Pharmaceuticals,

Collegeville, Pennsylvania, telephone 800-358-7443).

To ascertain the availability of influenza vaccine, CDC conducted a survey of

state and urban area immunization programs. As of December 3, a total of 28

states had redistributed influenza vaccine from health-care providers and

public immunization clinics that had excess supplies to those that needed

vaccine.

In addition, 34 states had influenza vaccine inventory that had not been

distributed. However, in an average year, <10% of influenza vaccine is purchased

by

state health departments.

Influenza antiviral medications are available for use in adults and children.

Four prescription antiviral medications (i.e., amantadine, rimantadine,

oseltamivir, and zanamivir) are approved for treatment of influenza A virus

infections. Oseltamivir and zanamivir also are approved for treatment of

influenza B.

The costs, routes of administration, adverse effects, contraindications,

approved ages, and potential for antiviral resistance differ among the four

drugs.

When administered within 48 hours of symptom onset, antiviral treatment of

influenza can reduce the duration of illness by approximately 1 day in healthy

adults (9). Data on the use of any of the four antiviral agents during

pregnancy are not available. Amantadine, rimantadine, and oseltamivir also are

approved for chemoprophylaxis of influenza A virus infections and can be used

for

control of institutional influenza outbreaks. When used for chemoprophylaxis,

antivirals can be approximately 70%--90% effective in preventing illness in

healthy adults (9,10). To obtain information about approved age groups, dosing,

and

adverse effects, clinicians should consult antiviral drug package inserts

(available from the Food and Drug Administration at

http://www.fda.gov/cder/drug/antivirals/influenza/default.htm#drugs).

CDC has published recommendations for prevention and control of influenza

(available at http://www.cdc.gov/mmwr/PDF/rr/rr5208.pdf). Supplemental

recommendations have been released for the 2003--04 influenza season (Box).

Influenza

surveillance reports for the United States are published weekly during

October--May and are available from CDC at http://www.cdc.gov/flu or through

CDC's

voice (telephone, 888-232-3228) and fax (telephone, 888-232-3299, document

number

361100) information systems.

Acknowledgments

This report is based on data contributed by A Tulu, K Hankins, Dallas County

Health and Human Svcs Office; G Wendell, J Sheffield, Parkland Memorial

Hospital, Dallas; J Siegel, Children's Medical Center, Dallas; N Pascoe, S

Avashia,

Texas Dept of Health. K Gershman, Colorado State Dept of Public Health and

Environment. Participating state and territorial epidemiologists and state

public

health laboratory directors. WHO collaborating laboratories. National

Respiratory and Enteric Virus Surveillance System collaborating laboratories,

U.S.

Influenza Sentinel Provider Surveillance System. Div of Public Health

Surveillance and Informatics, Epidemiology Program Office; DJ O'Mara,

Immunization Svcs

Div, National Immunization Program, CDC. References

CDC. Update: influenza activity---United States and worldwide, 2002--03

season, and composition of the 2003--04 influenza vaccine. MMWR 2003;52:516--21.

CDC. Surveillance for influenza---United States 1997--98, 1998--99, and

1999--00 seasons. In: CDC Surveillance Summaries (October 25). MMWR 2002;51(No.

SS-7).

WW, Shay DK, Weintraub E, et al. Mortality associated with influenza

and respiratory syncytial virus in the United States. JAMA 2003;289:179--86.

CDC. Severe morbidity and mortality associated with influenza in children and

young adults---Michigan, 2003. MMWR 2003;52:837--40.

Morishima T, Togashi T, Yokata S, et al. Encephalitis and encephalopathy

associated with an influenza epidemic in Japan. Clin Infect Dis 2002;35:512--7.

Mandell LA, Bartlett JG, Dowell SF, File TM, Musher DM, Whitney C. Update of

practice guidelines for the management of community-acquired pneumonia in

immunocompetent adults. Clin Infect Dis 2003;37:1405--33.

ston BL. Methicillin-resistant Staphylococcus aureus as a cause of

community-acquired pneumonia---a critical review. Semin Respir Infect

1994;9:199--206.

CDC. Prevention and control of influenza: recommendations of the Advisory

Committee on Immunization Practices (ACIP). MMWR 2003;52(No. RR-8).

Demicheli V, Jefferson T, Rivetti, Deeks J. Prevention and early treatment of

influenza in healthy adults. Vaccine 2000;18:957--1030.

Hayden FG, Atmar RL, Schilling M, et al. Use of the selective oral

neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med

1999;341:1336--43. * Data reported as of December 5.

† Temperature of >100.0º F (37.8º C) and cough and/or sore throat in the

absence of a known cause other than influenza.

§ National and regional percentages of patient visits for ILI are weighted on

the basis of state population.

¶ Calculated as the mean percentage of visits for ILI during noninfluenza

weeks, plus two standard deviations. Wide variability in regional data precludes

calculating region-specific baselines and makes it inappropriate to apply the

national baseline to regional data.

** The expected baseline proportion of P & I deaths reported by the 122 Cities

Mortality Reporting System is projected by using a robust regression procedure

that applies a periodic regression model to the observed percentage of deaths

from P & I during the previous 5 years; the epidemic threshold is 1.645

standard deviations above the seasonal baseline percentage (2).

†† Levels of activity are 1) no activity, 2) sporadic---small numbers of

laboratory-confirmed influenza cases or a single influenza outbreak reported but

no increase in cases of ILI, 3) local---outbreaks of influenza or increases in

ILI cases and recent laboratory-confirmed influenza in a single region of a

state, 4) regional---outbreaks of influenza or increases in ILI cases and

recent laboratory-confirmed influenza in at least two but less than half the

regions of a state, and 5) widespread---outbreaks of influenza or increases in

ILI

cases and recent laboratory-confirmed influenza in at least half the regions of

a state.