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Tex Heart Inst J. 2004; 31(1): 39–41.
PMCID: PMC387431

Control of Influenza

S. Ward Casscells, MD, Section Editor and Mohammad Madjid, MD, Section Editor

Abstract

Influenza is the classic emerging infection. Despite the availability of relatively inexpensive vaccines and specific treatments, influenza is the least controlled vaccine-preventable disease. Vaccination coverage of high-risk patients has improved, but all-cause mortality attributable to influenza continues to increase. A supplemental strategy is to vaccinate the principal disseminators of influenza in the community: school children and working adults. The availability of the live, attenuated, cold-adapted nasal spray vaccine should facilitate this goal.

Key words: Immunization, influenza/complications/epidemiology/prevention & control, influenza A virus, influenza vaccine/immunology, United States/epidemiology, vaccine, intranasal, vaccines, attenuated

Supplemental strategies for the control of influenza are dictated by the sharp increase in all-cause mortality in the United States for the period from 1990 to 1999 compared with that from 1972 to 1992. 1 The annual average jumped from 20,000 to more than 50,000 per year. The numbers were particularly high for 1996–1999, with totals of 65,000 to 71,000 despite the fact that vaccine coverage reached 65% for the most vulnerable group: persons 65 years and older. There is no evidence that the current strategy of focusing vaccine coverage on high-risk patients has any effect on all-cause mortality. If additional control measures are not implemented in the United States, it is projected that the number of deaths due to influenza will double during the next 25 years.

Immunization in High-Risk Patients. It has become increasingly evident that high-risk patients are not easily accessible for influenza vaccination. Immunization rates for the elderly reached a plateau beginning in 1997. 2 Despite the “Healthy People 2010” goals of 90% coverage for persons 65 years and older and for patients in chronic care facilities, no progress has been realized during the first 3 years of this decade. Vaccine coverage for high-risk persons below 65 years of age is considerably worse than it is for the elderly. Children with asthma and women in the 2nd or 3rd trimester of pregnancy have annual immunization rates of less than 15% despite strong recommendations. The “Healthy People 2010” goals for these groups are influenza immunization rates of 60%. The goals for 2010 will not be reached unless considerable effort is devoted to the development of an infrastucture for vaccine delivery. Systematic reminder systems and programs in nonconventional situations are needed.

Influenza in Children. Appreciation of serious morbidity in healthy children has sharpened with the recognition that infants with no chronic underlying condition have influenza-attributable hospitalization rates comparable to those in the elderly. Studies in California 3 and Tennessee 4 have confirmed these high rates of serious, life-threatening morbidity. The highest annual attack rates of influenza virus infection occur in school children. 5 These infections result in high absentee rates that are disruptive not only to the educational process but also to working parents who must miss work to care for ill children. 6

Prevention of febrile respiratory illnesses in children would reduce visits to the doctor for medical care. The resulting reduction of prescriptions for antibiotics would be an added benefit, since unnecessary use of antibiotics leads to the emergence of resistant bacteria and to increases in the cost of treatment of common infections such as acute otitis media. During the winter season of 1996–97, the incidence of acute febrile otitis media was reduced by 30% in a pivotal field trial of the live attenuated, cold-adapted influenza vaccine, CAIV-T. 7

Children with asthma are also vulnerable to influenza virus infection. In a study of viral infections in persons hospitalized with acute respiratory conditions, influenza virus infections were detected in 21% of school-aged children admitted to the hospital during a 4-year period. 8 Studies have shown that influenza vaccine reduces hospitalizations of children for asthma. 9

Bacterial complications of influenza are common. O'Brien and coworkers 10 documented influenza A(H1N1) infections in schoolchildren with severe pneumococcal pneumonia that included empyema and abscess. Australian investigators 11 documented a more frequent occurrence of influenza virus infections among children with meningococcal disease than among controls. Bacterial tracheitis and otitis media are other common bacterial complications. 12,13 Less common complications are febrile seizures and encephalopathy. 14 In addition, pericarditis, myocarditis, and myositis have been reported in children.

The high morbidity in children with influenza has been overlooked in the past; however, renewed interest has led to the encouragement of influenza vaccination for healthy children 6 to 23 months of age and for all household contacts of children less than 2 years of age by the Advisory Committee for Immunization Practices (ACIP) and the American Academy of Pediatrics. 2 The household contacts, of course, would include many healthy school children.

Immunization in School Children and in Working Adults. School children and working adults are the major spreaders of influenza in the community and introducers into the household. 15 Among working adults, health care workers have special priority for influenza vaccination, but only about 35% are immunized annually. These are accessible populations. Children can be immunized in school-based clinics, and working adults can be conveniently immunized at the workplace. Several studies have shown the cost-effectiveness of influenza immunization for work-ing adults. 16–18 Immunization of school children and working adults should have the effect of decreasing absenteeism from school and work, decreasing visits for medical care, and decreasing prescriptions for antibiotics. 6,19

Effectiveness of Influenza Vaccinations. Studies have demonstrated indirect effectiveness (herd immunity) of influenza vaccinations. In 1968, Monto and colleagues 20 delivered a single dose of inactivated vaccine to school children in Tecumseh, Michigan, at the time of emergence of influenza A(H3N2). During that season, the illness rate of adults was significantly lower in Tecumseh than in the neighboring community of Adrian. 20 In Japan, a program of influenza immunization of school children was started in 1962. 21 Two doses of vaccine were recommended each fall, and this procedure was mandatory from 1977 to 1987. With 80% to 85% coverage of children 5 to 15 years of age, a significant decrease in all-cause mortality was noted; that decrease spared 35,000 to 47,000 persons per year. The program became optional in 1987 and was abandoned in 1994. Since that time, the all-cause mortality attributed to influenza has increased considerably. (Note: Japan had no program for the immunization of elderly or high-risk patients at the time of the school program.) These studies demonstrate the effectiveness of inactivated influenza vaccine for reducing the spread of influenza in the community.

Effectiveness of CAIV-T. Recent studies have suggested that CAIV-T, the newly licensed, live attenuated, cold-adapted influenza vaccine given by nasal spray, may be more efficient than the inactivated vaccine for reducing the impact of epidemics in the community. An 8-year field trial is under way in Central Texas to explore the potential of immunizing children 18 months to 18 years of age with CAIV-T. 22 The primary goal of this nonrandomized, open-label trial is to demonstrate herd immunity by measuring the age-specific attack rates for medically attended acute respiratory illness (MAARI) at the intervention site, Temple-Belton, where CAIV-T is offered to age-eligible children. These rates for the first 4 consecutive influenza seasons were compared with the MAARI rates from 2 comparison sites, Waco and Bryan–College Station, where CAIV-T was not offered to children. The 1st year was the baseline year when CAIV-T was not offered. The MAARI rates for adults 35 years and older were essentially identical that year, with 9.3 encounters per 100 at the intervention site and 9.2 per 100 at the comparison sites. Over the next 3 years, 14,699 CAIV-T doses were delivered to a total of 9,765 children. By year, 20%, 25%, and 25% of the target population of age-eligible children in the intervention site received CAIV-T. During those 3 years, MAARI rates for adults 35 years and older at the intervention site decreased by 8%, 18%, and 15%. It is estimated that the number of encounters for MAARI in that age group were reduced by more than 1,000 for year 3 and again for year 4.

To measure direct effectiveness and adjusted efficacy, the MAARI rates for CAIV-T recipients were compared with those of 9,325 age-eligible children in the intervention community who did not receive CAIV-T, and adjusted for the sample with culture-positive MAARI in both groups. 23 In year 4, CAIV-T recipients had 18% fewer MAARIs than did nonparticipants, and adjustment for culture-positive MAARI yielded an adjusted efficacy of 91% for children from 1.5 to 4 years of age, 80% for 5- to 9-year-olds, and 70% for 10- to 18-year-olds. These rates are comparable with the rates observed in the double-blinded, placebo-controlled trials. This experience is remarkable because the prevalent influenza virus was A/New Caledonia (H1N1), and the H1N1 viruses had not circulated since 1995–96, before any of the field trials with CAIV-T. Therefore, this was the 1st natural challenge of CAIV-T with the influenza A(H1N1) virus. Moreover, children who received only 1 dose of the CAIV-T showed protection that carried over to the 2nd season, demonstrating not only persistence of immunity but also heterovariant protection, because the previously administered vaccine contained an earlier variant of influenza A(H1N1). 24

In summary, CAIV-T was found to be safe; no serious adverse effects were attributable to the vaccine, and side effects of the vaccine did not increase direct medical costs. The direct protection was inversely related to age, and ranged from 70% for 10- to 18-year-olds to 91% for children less than 5 years of age. The protection persisted through 2 seasons and was heterovariant. A single dose was sufficient for protection. All of these characteristics support CAIV-T as a good candidate not only for protecting school children and working adults from influenza but also for reducing the spread of influenza in the community. Initial studies have shown a modest, but significant, indirect effect of immunizing up to 25% of the children in the intervention community. These studies were performed before licensure of CAIV-T, and they will be extended with the licensed product, FluMistTM (MedImmune Vaccines, Inc.; Gaithersburg, Md), in the same setting. The CAIV-T is an important addition to our armamentarium against influenza. The advantages of this preparation should be used to the fullest extent possible in order to reduce the impact of influenza. Control of interpandemic influenza is of primary importance, but the lessons learned from controlling interpandemic influenza can be applied to preparation for the next pandemic.

Footnotes

Address for reprints: W. Paul Glezen, MD, Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, MS BCM-280, Houston, TX 77030-3498

E-mail: ude.cmt.mcb@nezelgw

This paper has its basis in a presentation made at the First Symposium on Influenza and Cardiovascular Disease: Science, Practice, and Policy, held on 26 April 2003, at the Texas Heart Institute, Houston, Texas.

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