Empiric therapy with antiviral medication during an influenza epidemic is superior to both rapid diagnostic test-based therapy and no therapy in symptomatic pediatric patients, according to an analysis based on hypothetical scenarios.
“We found no role for rapid diagnostic testing during local outbreaks, because clinical diagnosis is highly predictive, whereas rapid testing leads to frequent false-negative results,” said Michael B. Rothberg, M.D., and colleagues at Baystate Medical Center in Springfield, Mass. (Arch. Pediatr. Adolesc. Med. 2005;159:1055–62).
The analysis included hypothetical patients, 2, 7, and 15 years old, presenting to a primary care physician with fever and cough or coryza within 48 hours of symptom onset in a local influenza outbreak.
The costs and benefits of empiric antiviral therapy, test-guided antiviral therapy, or no antiviral therapy were examined using evidence from all trials of the medications in children. Two treatment choices were included in the analysis: amantadine hydrochloride and oseltamivir phosphate (the only drugs currently licensed for the treatment of influenza in children younger than 7 years), and two rapid diagnostic tests were considered: QuickVue (Quidel Corp., San Diego) and ZstatFlu (ZymeTx Inc., Oklahoma City).
The analysis considered vaccinated and unvaccinated patients separately. Consideration was given to outbreaks that were predominantly influenza A (90%) or a mixture of influenza A (55%) and B.
Compared with no treatment, empiric therapy with antiviral medication improved quality-adjusted life expectancy in all scenarios by both shortening the duration of illness and preventing otitis media.
The choice of which medication and whether it saved money depended on the age of the child and which type of influenza was predominant. “When influenza A predominates, both drugs appear equally effective, but amantadine may be better tolerated and is less expensive,” said the authors. “Because amantadine is not active against influenza B, however, oseltamivir will be more effective when influenza B is prevalent.”
In a scenario where influenza A predominated, empiric amantadine improved quality-adjusted life expectancy for all age groups. It was the least expensive strategy in children under 15 years old, saving $121 per child, compared with no treatment, because of the savings it gave parents who could return to work faster. However, this treatment resulted in no savings if the child was old enough to stay home alone.
During seasons in which influenza B was common, empiric oseltamivir improved quality-adjusted life expectancy in all age groups and was the least expensive option for 2-year-olds. But the cost increased with weight. And vaccinated children had lower costs and better outcomes in all cases.
Rapid testing was useful only in influenza B (or mixed) outbreaks when a patient's likelihood of infection was low. In such cases, a negative test could avoid the higher cost and side effects of oseltamivir.
Otherwise, “because the rate of adverse effects from oseltamivir and the false-negative rate for QuickVue are identical, a child is more likely to be helped than harmed by empirical oseltamivir whenever the probability of influenza is greater than 50%,” the researchers said.
They noted some obstacles to the implementation of their model in clinical practice. First, some practitioners may be uncomfortable with prescribing empiric therapy, although “such caution avoids unnecessary adverse effects, but leads to undertreatment.” Second, parents paying out-of-pocket may be unwilling to purchase the more expensive oseltamivir—especially if a child's illness will not result in loss of parental income. And, despite years of evidence supporting antiviral use, many physicians are unfamiliar with them and many pharmacies may not stock them.
Some potential benefits were not considered in the model, including antivirals' potential to decrease hospitalizations in high-risk children, such as asthma patients.
There also is some suggestion that antiviral therapy can decrease transmission of influenza. The researchers point out that in order to prescribe antivirals in a cost-effective manner, clinicians must be aware of which type of influenza is prevalent. This information is available at state health departments and from the Centers for Disease Control and Prevention (www.cdc.gov