Influenza Update: Focus on Children

Author: Stephen R. Luber, MD, FAAP, Pediatrician, Rockwood Clinic, Spokane, WA.

Peer Reviewer: Theodore C. Chan, MD, FACEP, Associate Professor of Clinical Medicine, Emergency Medicine, University of California, San Diego.

The annual flu season places dramatically increased demands on emergency department and urgent care facilities. Public health programs and staff physicians have long focused on the diagnosis and treatment of influenza in high-risk adults. While no one questions the efficacy of annual targeted immunization efforts and treatment of compromised adults, it has become increasingly evident that current programs miss important opportunities to reduce community exposure and control morbidity by not focusing on children. Recent advances in epidemiology, immunization, treatment, and chemoprophylaxis force clinicians to focus their attention on children as important adjuncts to influenza control.— The Editor

Epidemiology

Children account for nearly two-thirds of diagnosed cases of influenza during a typical season.1 More than 30% of children living in communities will be affected.1 The first sign of a typical flu season is increased school absenteeism;1 only later does the increased hospitalization of the vulnerable elderly occur. Adults contract the illness from children, and infection rates dramatically increase in households with school-age children.

Two recent, population-based studies highlighted the direct effect of influenza on children. Evaluation of hospitalization rates in Group Health Seattle and Kaiser Northern California indicated dramatically increased rates of hospitalization in healthy children younger than age 2.2 Analysis of Tennessee Medicaid patients indicated hospitalization rates of children younger than age 2 that were similar to high-risk adults with substantive excess use of antibiotics.3 An accompanying editorial in the New England Journal of Medicine suggested strong consideration and further study of universal childhood immunization.4

Influenza strikes hard in Japan. The population is long-lived and many elderly live in homes with schoolchildren present. From 1962 to 1987, most Japanese schoolchildren were vaccinated against influenza. The vulnerable elderly were considered secondary targets for immunization. Excess influenza and pneumonia deaths dropped 40%, with between 37,000 and 49,000 excess deaths per year averted. The laws mandating this effort were relaxed in 1987 and repealed in 1994. Subsequent vaccination rates dropped to low levels, leading to a sharply rising number of deaths.5

Similar findings are emerging from a study of immunizing school children with attenuated live vaccine in a Texas community. Immunization rates of 50% have demonstrated the ability to prevent community epidemics and dramatically reduce excess mortality in the elderly. Immunization of school children was shown to be cost effective when considering indirect costs of illness.6 In another, less recent study by Monto and colleagues in Tecumseh, MI, school-age immunization reached 85% and the incidence of influenza-like illness was one-third that of neighboring communities.7

Immunization

The Centers for Disease Control and Prevention (CDC) recommendations for annual flu vaccination target high-risk patients, health care personnel, and the elderly. The program is not designed to control epidemics of influenza but to reduce the affect of the illness on vulnerable populations.8 (See Table 1.) A trivalent, inactivated virus vaccine confers protection from disease of nearly 80% to those younger than 65 years and declines with age.8 Although of declining efficacy in preventing illness in the frail elderly, vaccinations maintain effectiveness for the prevention of complications, hospitalizations, and death in nursing home populations. Production of vaccine was limited and delayed in flu season 2000-2001. The vaccine often went to mass distribution centers and was unavailable to physicians and clinics seeing targeted, high-risk populations. While the vaccine supply appears better this year, there are only three manufacturers and delayed deliveries are expected. Significant efforts to distribute vaccine to targeted, high-risk groups have been cited but lack of formal controls will cause physicians, once again, to be unable to acquire needed vaccines.

Table 1. Influenza Vaccine* Dosage By Age Group—United States, 2001-2002 Season
Age group Product† Dose Number
of doses
Route §
6-35 mos Split virus only 0.25 mL 1 or 2 Intramuscular
3-8 yrs Split virus only 0.50 mL 1 or 2 Intramuscular
9-12 yrs Split virus only 0.50 mL 1 Intramuscular
> 12 yrs Whole or split virus ** 0.50 mL 1 Intramuscular

* Contains 15 mg each of A/New Caledonia/20/99 (H1N1)-like, A/Moscow/10/99 (H3N2)-like, and B/Sichuan/379/99-like strains. For the A/Moscow/10/99 (HeN2)-like antigen, manufacturers will use the antigenically equivalent A/Panama/2007/99 (H3N2) virus. For the B/Sichuan/379/99- like antigen, manufacturers will use one of the antigenically equivalent viruses B/Johannesburg/5/99, B/Victoria/504/2000, or B/Guangdong/120/2000.
† Because of their decreased potential for causing febrile reactions, only split-virus vaccines should be used for children. The vaccines might be labeled as "split," or "subvirion," or purified-surface-antigen" vaccine.
Immunogenicity and side effects of split- and whole-virus vaccines are similar among adults when vaccines are administered at the recommended dosage.
§ For adults and older children, the recommended site of vaccination is the deltoid muscle. The preferred site for infants and young children is the anterolateral aspect of the thigh.
¶ Two doses administered > 1 month apart are recommended for children ages < 9 years who are receiving influenza vaccine for the first time.
** No whole virus vaccine will be distributed in the U.S. during the 2001-2002 influenza season.

Source: Bridges CB, Fukuda K, Cox NJ, et al. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2001;50(RR-4):1-44.

A live attenuated, cold-adapted, trivalent, intranasal virus vaccine has undergone successful trials with efficacy as good or greater than traditional inactivated vaccines.9,10 No adverse events were reported. Developed by Aviron, the live virus vaccine stimulates cellular immunity in addition to humeral immunity, leading to a robust flexible immunity. The intranasal delivery is particularly attractive for the pediatric population. The vaccine targets healthy recipients. Acceptance of this vaccine, combined with increased childhood immunizations, may have a significant effect on propagation of annual epidemics. The new vaccine complements, rather than replaces, the use of inactivated vaccines for high-risk patients. Approval had been sought for the coming 2001-2002 flu season but on July 27, the Food and Drug Administration (FDA) held off on approval; it recognized efficacy but cited the need for more safety data.

Clinical Picture and Diagnosis

The clinical picture of influenza in young children often is subtle, with signs and symptoms mimicking other common childhood diseases. The clear and distinctive clinical picture of adult influenza often is muddied by the subjective nature of the pediatric history and its interpretation by concerned parents. The child’s ability to describe the myalgias, headache, and malaise of influenza is limited. Gastrointestinal symptoms of vomiting and diarrhea occur in up to one-third of children. The infection may present as acute laryngotracheitis/croup or classic bronchiolitis. Infants may present with severe bronchiolitis progressing to respiratory failure. Differentiation from parainfluenza or respiratory syncytial virus (RSV) infections requires culture or immunoassay. The very young infant/neonate may appear moribund and require a septic workup. Febrile seizures are not uncommon in the infant. Physicians must have a strong index of suspicion or diagnostic curiosity to make the correct diagnosis.11,12

Influenza arrives during months in which annual RSV epidemics traditionally have received the primary attention of the pediatrician, and overlap with parainfluenza I croup seasons often direct the physician’s attention away from the primary pathogen. Atypical presentations of croup or RSV-negative bronchiolitis merit diagnostic consideration.

Although some viral pathogens produce a clinical picture so compelling as to permit specific diagnosis, the protean nature of viral respiratory infections has long led to the diagnosis of exclusion: viral syndrome. Pediatricians have long ignored precise identification of the respiratory pathogens affecting their patients. The lack of effective treatment, coupled with delayed laboratory confirmation, limited the necessity of specific diagnosis. The viral diagnosis paradigm was simply an exclusion of treatable bacterial illness in the differential diagnosis. The emergence of effective diagnostic techniques and effective therapy dictates rethinking the clinical approach to the respiratory viral syndrome.

The availability of CLIA (Clinical Laboratories Improvement Act) made rapid diagnostic kits for influenza available for diagnosis and timely intervention. Sensitivity approaches 80% in hospitalized sick children. The use of nasopharyngeal (NP) swabs as opposed to throat swabs also can increase outpatient sensitivity from 60% to 80%. (See Table 2.) Each patient is not necessarily tested. Rather, selective utilization serves to calibrate the clinician’s clinical acumen and to provide office confirmation of local disease presence. The clinician may be more comfortable with a confirmed viral diagnosis and more easily use effective antiviral treatment, while reassuring concerned parents of the lack of indication for antibiotics. Use of diagnostic tests in a children’s hospital emergency department has led to a significant decrease in antibiotic use, while increasing the use of appropriate antiviral medications.13 Reimbursement has been forthcoming, making the tests cost-effective in private and clinic practice.

Table 2. Rapid Diagnostic Tests
CLIA Certified Office-Based Tests* Detect Viral Antigen
Name Cost
(Dollars)
Time
(min.)
Steps Sensitivity‡ Specificity‡ Comment
Directigen Flu A 19.00 15 11 88% 92% Flu A only
Flu OIA 16.50 15 5 95% 64%
QuickVue 20.00 10 3 73% 95%
ZstatFlu 18.00 20 4 62% 98% Pharyngeal swab
Influenza Rapid Test NA 10 4 85% 81%

* = Average reimbursement $35
‡ = Nasopharyngeal swab

Source: Luber S. Influenza year 2000 update: Epidemiology, diagnosis, and outcome-effective guidelines for neuraminidase inhibitor therapy. Emergency Medicine Reports 2000;21:245-256.

The classic diagnostic tradition of history and physical exam can be remarkably accurate in school-age children. When influenza virus is confirmed in a region or community by local or state health departments or by the CDC, persons with fever, muscle aches, and cough most likely have influenza.14 Several studies have shown clinical accuracy of 85% in adults during confirmed outbreaks. During the clinical trials of zanamivir (Relenza), it was found that experienced physicians using key factors in the patient history were as accurate in their diagnoses as they were when they used rapid immunoassay kits.15

Treatment

The opportunity to effectively intervene in viral illness is a new and sometimes uncomfortable concept for physicians, patients, and their parents. Physicians have not had effective agents for a great length of time and may be uncomfortable with new forms of therapy. The need to begin antiviral therapy early contradicts the long-held advice to see the physician only if several days pass without resolution of presenting symptoms. Parents hesitate to seek professional help for potentially mild, self-limited conditions. While this strategy remains effective for dealing with common winter upper respiratory infections, it leaves the physician without the ability to intervene in potentially serious infections. Increasingly broad arrays of antiviral agents recently have been marketed and more are in the drug pipeline. Practitioners need to rethink their service patterns to take advantage of new therapies to relieve significant morbidity and avoid mortality from viral agents.

The treatment of influenza may serve as a model for emerging antiviral therapy. Specific antiviral therapy of influenza began with the introduction of amantadine (Symmetrel) 30 years ago. The drug targets the M2 membrane protein of influenza A and is effective for reducing the duration of symptoms of established illnesses. It also is effective as a prophylactic agent during epidemics in both adults and children.16 A rapid emergence of resistance and lack of activity against influenza type B reduces its usefulness. Neurologic side effects are significant in very young and elderly patients. Resistance has been documented within single households, with treated index cases transmitting resistant virus to other family members.17 Rimantadine (Flumadine) addressed the neurologic toxicity but, like amantadine, it is subject to rapid emergence of resistance, lacks efficacy against type B, and is not FDA-indicated for acute therapy in children. Many experts do support its use in children.

The two prominent surface proteins, hemagglutinin and neuraminidase, have been extensively investigated in the ongoing effort to develop more effective antiviral agents. Hemagglutinin attaches the virus to the epithelial cell membrane and promotes penetration into the cytoplasm; neuraminidase functions in multiple reproductive steps. It degrades the receptor, permitting entry into the cell. After viral replication, it cleaves mucous facilitating, newly formed virions to escape infected cells, separate, and migrate through mucus to infect other epithelial cells. Inhibition of neuraminidase prevents spread of virus within the host and aborts the infection.18

The first active drug developed was zanamivir. Clinical studies in experimental and natural infection demonstrated decreased length of viral shedding, symptoms, and severity in both types A and B influenza diseases.19,20 Ongoing studies of the neuraminidase inhibitors have shown efficacy in childhood. A double-blind, placebo-controlled study of zanamivir in the 1998-1999 Northern Hemisphere flu season recruited 471 children with flu-like symptoms. Three hundred forty-six had culture-proven influenza, and inhaled diskhaler therapy significantly shortened time to alleviation of symptoms and time to resumption of normal activity. The treatment group also used less relief medication. Complications and associated antibiotic use were deceased by 16% and 12%, respectively.21

Questions were raised regarding respiratory function deterioration in patients with existing chronic obstructive pulmonary disease (COPD) and asthma. Bronchospasm has occurred in patients with asthma.20,22 The package insert contains important precautionary information regarding the use of zanamivir with underlying airway disease. The drug is taken as a five-day course using a proven diskhaler design. It is indicated for patients ages 7 and older who have signs and symptoms of influenza A and B of fewer than 48 hours duration.

The desire for an orally active drug led to the development of oseltamivir (Tamiflu). Oseltamivir also has been studied in pediatric populations. A study of 695 patients ages 1-12 years showed a 36-hour or 26% reduction in duration of influenza. The incidence of otitis media was reduced by 44%.23 Specific efficacy was demonstrated with influenza B infection in other studies, with a decrease of symptom duration by 25%.22,24 Oseltamivir was well tolerated in clinical trials, with no safety issues raised. In adult, adolescent, and child studies, nausea was reported, with excess emesis over placebo of 5.8%. The recipients described the gastrointestinal symptoms as transient and mild.25,26 Discontinuance of medication due to adverse events was 1.8% in the oseltamivir group vs. 1.1% with placebo.23 Prior studies with adolescents and adults indicate significant reduction of gastrointestinal symptoms with concomitant consumption of food.25 Resistant strains were uncommon and represented viruses with limited infectivity in humans. Adult and adolescent dosage is 75 mg twice a day for five days. It is approved for children ages 1 and older, and dosing is based on weight; it has a fruit-flavored suspension. Current dosage guidelines and indications are seen in Table 3.

Table 3. Antiviral Agents for Influenza
Generic Name Trade Name Indications Dosage Wholesale Cost - Treatment Comments
M2 Inhibitors — Influenza A
Amantadine Symmetrel Treatment > age 1 100 mg bid × 7 days $6.45
(generic)
CNS side effects
Prophylaxis > age 1 100 mg
qd
$14.38
(branded)
> age 65 — dose decreased to 100 mg
qd
If CrCl < 80 mL/min — decrease dose
Rimantadine Flumadine Treatment > age 14 100 mg bid × 7 days $32.60 If CrCl < 20 mL/min — decrease dose
Prophylaxis > age 1 100 mg
qd
Neuraminidase Inhibitors — Influenza A and B
Zanamivir Relenza Treatment > age 7 2 blisters bid × 5 days $46.18 Dischaler inhalation device
Pending indication: Prophylaxis > age 7
Caution with history of bronchospasm
Oseltamivir Tamiflu Treatment > age 18 75 mg bid × 5 days  $59.54 Pending indications: treatment > age 1; prophylaxis > age 1
Mild GI side effects

Source: Luber S. Influenza year 2000 update: Epidemiology, diagnosis, and outcome-effective guidelines for neuraminidase inhibitor therapy. Emergency Medicine Reports 2000;21:245-256.

Prophylaxis. The neuroaminidase inhibitors have been shown effective for prevention of influenza infection. Zanamivir once a day was 79% effective for the prevention of influenza transmission within families with a confirmed index case.27 Orally administered oseltamivir 75 mg once a day protected close family contacts against influenza by 92% and interrupted transmission within households by 89%.28,29 Post exposure, the placebo group had a 12% incidence of influenza, compared with a 1% incidence in the prophylaxis group. The FDA has indicated oseltamivir for prophylaxis in adolescents and adults ages 13 and older.

It has been suggested that use of family prophylaxis after treatment of the index case may be the most effective use of the medication. It not only protects familial contacts but also can serve to reduce community exposure. Family physicians are in a unique position to treat the whole family when an index case is identified. Pediatricians will need to form effective alliances with internists and family physicians to effectively reach the parents of children with influenza.

Reducing Complications and Antibiotic Use. The serious complications of influenza with bacterial pneumonias, Reye syndrome, and prolonged recovery of high-risk patients are well known. The increased frequency of otitis media and other respiratory infections in children with influenza is under appreciated. Antibiotic usage increases with treatment of the otitis media and for the numerous and gratuitous clinical diagnoses of bronchitis, sinusitis, and pneumonia during the flu season. With proper antiviral treatment of influenza, a substantive reduction of antibiotic usage has been demonstrated. This reflects a real decrease in otitis media occurrence, as well as the desired reduction in the overuse of antibiotics for primary viral infection.

In the oseltamivir trials in children ages 1-12 years, 21% of placebo recipients and only 12% of treated subjects had documented otitis media.22 The 44% reduction in clinical diagnosis was paralleled by a 40% reduction in antibiotic usage.23 The zanamivir trials of children ages 5-12 years showed a 30% reduction in bacterial complications, with a 20% reduction in antibiotic use.21 Effective treatment of primary viral infections can reduce otitis morbidity and antibiotic usage.

In pivotal clinical trials, the neuraminidase inhibitors showed efficacy with one- to two-day decreases in time to alleviation of all significant symptoms of influenza. Early FDA examination and subsequent professional commentary questioned this apparent marginal benefit from therapy. Health maintenance organizations and other third-party payers also questioned utility, and frequently excluded the medications from their panels. This marginality of efficacy contrasted strongly with clinical observations of patients, physicians, and investigators using the medications. In an effort to reconcile clinical impressions in practice with clinical trial data, investigators followed 1408 patients using prescribed zanamivir in Australia during the 1999 flu season.

Symptom relief was reported by more than 50% of patients within 24 hours and by 77% within 48 hours.30 Of the 400 elderly patients, 78% were satisfied with their treatment, with 59% experiencing symptom relief within 24 hours.31 The survey concluded that zanamivir was associated early return to normal activities. They noted the prolonged nature of residual cough in treated influenza after systemic symptoms of fever, headache, myalgia, and malaise had resolved. Investigators speculated that residual cough prolonged the end point in the clinical studies and, thus, caused an underestimation of the clinical effect of treatment.

The identification and treatment of primary viral infections remains a significant challenge to pediatric medicine. It also represents a significant opportunity to reduce an ongoing burden of illness. The technology for effectively preventing, diagnosing, and treating influenza has been demonstrated. Outpatient clinics, emergency rooms, and urgent care centers, as well as private physician offices, need to organize specifically to meet the challenge of early intervention in influenza epidemics. Telephone triage systems need to efficiently screen those with classic symptoms of influenza and promptly direct them to where they can be evaluated and treated with minimal delay.6 Specific time slots dedicated to prompt evaluation and treatment of infectious disease must be set aside during anticipated flu seasons.

The widespread implementation of influenza prevention and treatment in pediatric populations would provide benefit not only to the index cases but also to household contacts and vulnerable fragile elderly in the community. The antiviral treatment and chemoprophylaxis of contacts of influenza victims will serve as a model for treatment of other specific viral illness as newer antiviral agents that are readily visible in the drug pipeline become available to the practitioner. It will help redefine the meaning of antimicrobial therapy from strictly antibacterial to truly broadly antimicrobial.

Post-September 11 Considerations

The advent of biologic terrorism places new strains on the medical delivery systems as we approach the 2001-2002 influenza season. The scattered but real advent of confirmed inhalation anthrax makes the precise identification and treatment of respiratory illness a prime concern for any acute care physician. Unfortunately, the very protean nature of respiratory symptoms makes precise identification unlikely on purely clinical grounds. A detailed history of possible exposure to terrorist agents is a mandatory part of the post-September 11 medical interview. This includes consideration of inhalation toxic agents, as well as communicable disease. Thinking outside the constraints of conventional epidemiology is now mandatory.

The use of real-time influenza reporting systems enables one to either include or exclude the possibility of influenza through community epidemiology. The use of quick diagnostic kits makes a positive diagnosis of the viral infection possible, and increased usage may prevent many needless exposures to unnecessary antibiotics.

The increasing numbers of potentially exposed workers on long courses of broad-spectrum antibiotics also paves the way for proper appreciation of viral respiratory tract infection. While it is certainly possible to contract bacterial illness while on the current recommended regimens for anthrax prophylaxis, a patient with fever, cough, and myalgias while on an established antibiotic course most assuredly will have a viral illness. With proper local epidemiologic surveillance and available laboratory tests, more precise diagnosis will be facilitated, and enhanced use of antiviral agents promoted. More than ever, precision in defining the etiologic agents is not only desirable but also necessary.

References

1. National Institute of Allergy and Infectious Diseases. Fact Sheet: Flu. December 1997.

2. Izurieta HS, Thompson WW, Kramarz P, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000;342:232-239.

3. Neuzil KM, Mellen BG, Wright PF, et al. The effect of influenza on hospitalization, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000;342:225-231.

4. McIntosh K, Lieu T. Is it time to give influenza vaccine to healthy infants? N Engl J Med 2000;342:275-276.

5. Reichert TA, Sugaya N, Fedson DS, et al. The Japanese experience with vaccinating schoolchildren against influenza. N Engl J Med 2001;344:889-892.

6. White T, Lavoie S, Nettleman MD. Potential cost savings attributable to influenza vaccination of school-aged children. Pediatrics 1999;103:e6.

7. Monto AS, Davenport FM, Napier JA, et al. Modification of an outbreak of influenza in Tecumseh, Michigan by vaccination of school children. J Infect Dis 1970;122:16-25.

8. Center for Disease Control and Prevention, Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices. (ACIP). MMWR Morb Mortal Wkly Rep 1999;48(RR-04):1-28.

9. Belshe RB, Gruber WC, Mendelman PM, et al. Efficacy of vaccination with live attenuated, cold adapted, trivalent intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatr 2000;136:168-175.

10. Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated cold-adapted trivalent intranasal virus vaccine in children. N Engl J Med 1998;338:1405-1412.

11. Henderson, F. Viral Respiratory Infection. In: Rudolph A, Hoffman J, Rudolph C. Rudolph’s Pediatrics. 20th ed. Stamford: Appleton & Lange; 1996.

12. Glezen W, Cherry J. Influenza Viruses. In: Feigin RD, Cherry J, eds. Textbook of Pediatric Infectious Diseases. 3rd ed. Philadelphia: Saunders; 1992:1688-1704.

13. Noyola D, Demmler GJ. Effect of rapid diagnosis on management of Influenza A infections. Pediatr Infect Dis J 2000;19: 303-307.

14. Dolin R. Influenza. In: Fauci A, Braunwald E, Isselbacher K, et al. Harrison’s Principles of Internal Medicine. 14th ed. New York: McGraw Hill; 1998.

15. Aoki F, Osterhaus A, Rimmelzwan G, et al. Oral GS4104 successfully reduces duration and severity of naturally acquired influenza [abstract] 38th Interscience Conference of Antimicrobial Agents and Chemotherapy. Sept. 24-27, 1998. San Diego, USA.

16. Amantadine: Does It Have a Role in the Prevention and Treatment of Influenza? NIH Consens Statement 1979 Oct 15-16;2: 51-56.

17. Hayden FG, Belshe RB, Clover RD, et al. Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. N Eng J Med 1989;321:1696-1702.

18. Gubareva LV, Webster RG. Neuraminidase inhibitors: New candidate drugs for influenza. Infect Med 1999;16:345-354.

19. Boivin G, Goyette N Aoki F, et al. Clinical and virological efficacy of zanamivir in the treatment of Influenza A virus infections during the 1997-1998 flu season. Poster Session ICAAC, 1999.

20. Hayden FG, Osterhaus AD, Treanor JJ, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. N Engl J Med 1997;337:874-880.

21. Hedrick J, Barzilai A, Behre U. Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: A randomized controlled trial. Pediatr Infect Dis J 2000;19: 410-417.

22. Monto A, Fleming D, Henry D, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza A and B virus infections. J Infect Dis 1999;180:254-261.

23. Whitley RJ, Hayden FG, Reisinger KS, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001;20: 127-133.

24. Hayden F, Robson R, Jennings L, et al. Efficacy of oseltamivir in experimental human influenza B virus infection, Poster 670. ICAAC 2000.

25. Hayden FG, Atmar RL, Schilling M, et al. Safety and efficacy of a selective oral neuraminidase inhibitor (oseltamivir) to prevent influenza. N Engl J Med 1999;341:1336-1343.

26. Hayden FG, Treanor JT, Fritz RS, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: Randomized controlled trials for prevention and treatment. JAMA 1999;282:1240-1246.

27. Monto A, Robinson D, Herlocher M, et al. Zanamivir in the prevention of influenza among healthy adults: A randomized controlled trial. JAMA 1999;282:31-35.

28. Hayden FG, Atmar RL, Schilling M, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med 1999;341:1336-1343.

29. Oxford J, Jackson H, Ward P. Short term prophylaxis with oseltamivir effectively prevents spread of influenza A and B. Whitechapel, London: Retroscreen Ltd.

30. Silagy C, Watts R. Zanamivir, a new targeted therapy in the treatment of influenza: A patient perspective assessed by questionnaire. Clin Drug Invest 2000;19:111-121.

31. Joseph AM, Neal D. Managing cold and flu: A protocol for the nurse and pharmacist. Federal Practitioner 1999;Nov:23-51.


CME Objectives

To help physicians identify and treat patients with influenza, as well as inform and immunize their patients against this disease to prevent its spread.

Physician CME Questions

1. Gastrointestinal symptoms of vomiting and diarrhea occur in how many children with influenza?

A. Up to one-third

B. More than one-half

C. Three-fourths

D. Almost all


2. The findings of a Texas study with a 50% immunization rate for school children demonstrated:

A. Immunization of school children was shown to be cost effective when considering indirect costs of illness.

B. Immunization made no difference.

C. Immunization prevented community epidemics.

D. Immunization dramatically reduced excess mortality in the elderly.

E. All but B are correct.


3. Which of the following about the presentation of influenza in children is correct?

A. The infection only presents as classic bronchiolitis.

B. Differentiation from parainfluenza or respiratory syncytial virus (RSV) infections may be accomplished without culture or immunoassay.

C. Febrile seizures are not uncommon in the infant.


4. Influenza arrives during months in which annual RSV epidemics traditionally have received the primary attention of the pediatrician.

A. True

B. False


5. Which of the following may be a complication of influenza?

A. Bacterial pneumonias

B. Reye’s syndrome

C. Prolonged recovery of high-risk patients

D. All of the above


6. According to this article, effective treatment of primary viral infections can reduce otitis morbidity and antibiotic usage.

A. True

B. False