- Email: [email protected]
Pneumococcal vaccination for acute otitis media
Correspondence
Pneumococcal vaccination for acute otitis media Roman Prymula and colleagues (March 4, p 740)1 describe a significant reduction in the incidence of a first episode of acute otitis media (AOM) associated with the use of a new vaccine containing pneumococcal capsular polysaccharides conjugated to Haemophilus-influenzae-derived protein D. They conclude that these results are clinically relevant. We do not agree. The trial showed a 33·6% relative reduction (95% CI 20·8–44·3) for the first episode of AOM, which corresponds to an absolute reduction of 6·7% of all AOM episodes and to a number needed to treat of 15 children. For the strategy to be effective, four doses need to be given, which means that 60 vaccine doses are necessary to prevent one episode of AOM. AOM is certainly one of the most common paediatric diseases, but it recovers without antibiotic treatment in about 80% of children.2 Practice guidelines based on a “wait-andsee” strategy are effective in primary care.2,3 This strategy averts the need for antibiotic treatment in two thirds of children, leading to important cost reductions.3 A systematic review4 of current evidence questioned the beneficial effect of pneumococcal vaccination on AOM prevention, and concluded that large-scale use of pneumococcal polysaccharide and conjugate vaccines for this indication should not be recommended. So far, pneumococcal conjugate vaccinations are not even indicated in high-risk populations (ie, children with recurrent AOM). Before adopting this vaccination, its effectiveness in preventing recurrent episodes of AOM and in reducing rare complications (ie, mastoiditis, need for ventilation tube placement) should be addressed. Additionally, a costbenefit analysis is warranted before www.thelancet.com Vol 367 June 10, 2006
the widespread implementation of pneumococcal vaccine for such a benign clinical condition as AOM. We declare that we have no conflict of interest.
*Federico Marchetti, Jenny Bua, Alessandro Ventura. [email protected] Department of Paediatrics, Institute of Child Health, IRCCS Burlo Garofolo, University of Trieste, Via dell’Istria 65/1, 34100 Trieste, Italy 1
2
3
4
Prymula R, Peeter P, Chrobok V, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet 2006; 367: 740–48. Rovers MM, Schilder AG, Zielhuis GA, Rosenfeld RM. Otitis media. Lancet 2004; 363: 465–73. Marchetti F, Ronfani L, Conti Nibali S, Tamburlini G, for the Italian Study Group on Acute Otitis Media. Delayed prescription may reduce the use of antibiotics for acute otitis media. Arch Pediatr Adoles Med 2005; 159: 679–84. Straetemans M, Sanders EAM, Veenhoven RH, Schilder AGM, Damoiseaux RAMJ, Zielhuis GA. Pneumococcal vaccines for preventing otitis media. Cochrane Database Syst Rev 2004; 1: CD001480.pub2.
Roman Prymula and colleagues1 report the results of a clinical trial to assess the efficacy of an 11-valent pneumococcal vaccine that uses as a carrier a Haemophilus influenzae surface lipoprotein in the prevention of acute otitis media (AOM). Many issues are not clear, particularly the accurate identification of AOM. Making the diagnosis of AOM is not simple and many studies have found limitations in establishing the differential diagnosis between bacterial or viral AOM and otitis media with effusion.2 In Prymula and colleagues’ study, the initial detection of patients was done by paediatricians, Location Prymula and colleagues1
Czech Republic and Slovakia
Teele and colleagues3
Boston
Fireman and colleagues4
California
Eskola and colleagues5
Finland
and if AOM was diagnosed, the patient was referred to the ear, nose, and throat (ENT) department for confirmation and to obtain a sample of middle-ear fluid. Although there was a reduction in culture positive cases in the vaccine group, the report does not specify how many patients, per group, were seen with fever or any other disease by the clinic paediatrician but who were not referred to ENT because a diagnosis of AOM was disqualified at that stage. This information is particularly important since the overall incidence of AOM episodes in the control group is lower than that of other reports (table).3–5 If we assume a realistic incidence of 1·2 episodes per year in the control group, the expected number of cases would have been 2942, which is six-fold greater than the number actually detected in this study (499). The numbers in Prymula and colleagues’ table 3 are difficult to understand and are not consistent. For example, in the control group, there were 474 episodes for which a sample of middle-ear fluid was obtained; however, the table shows 256 episodes with negative cultures and 306 with positive cultures (total: 562 episodes). Prymula and colleagues should indicate the number of patients with first episodes only in each group, and present in a different analysis the number of recurrent episodes. Also, how many patients completed the 24–27-month follow-up period is unclear. Another concern is the number of episodes with negative bacterial cultures (54% in the control group Study population* 2452
e-mail submissions to [email protected]
Episodes per child per year 0·125
877
1·2
16 152
1·8
832
1·2
*Control groups not vaccinated.
Table: Incidence of acute otitis media in control groups of four different studies
1897
Pneumococcal vaccination for acute otitis media Roman Prymula and colleagues (March 4, p 740)1 describe a significant reduction in the incidence of a first episode of acute otitis media (AOM) associated with the use of a new vaccine containing pneumococcal capsular polysaccharides conjugated to Haemophilus-influenzae-derived protein D. They conclude that these results are clinically relevant. We do not agree. The trial showed a 33·6% relative reduction (95% CI 20·8–44·3) for the first episode of AOM, which corresponds to an absolute reduction of 6·7% of all AOM episodes and to a number needed to treat of 15 children. For the strategy to be effective, four doses need to be given, which means that 60 vaccine doses are necessary to prevent one episode of AOM. AOM is certainly one of the most common paediatric diseases, but it recovers without antibiotic treatment in about 80% of children.2 Practice guidelines based on a “wait-andsee” strategy are effective in primary care.2,3 This strategy averts the need for antibiotic treatment in two thirds of children, leading to important cost reductions.3 A systematic review4 of current evidence questioned the beneficial effect of pneumococcal vaccination on AOM prevention, and concluded that large-scale use of pneumococcal polysaccharide and conjugate vaccines for this indication should not be recommended. So far, pneumococcal conjugate vaccinations are not even indicated in high-risk populations (ie, children with recurrent AOM). Before adopting this vaccination, its effectiveness in preventing recurrent episodes of AOM and in reducing rare complications (ie, mastoiditis, need for ventilation tube placement) should be addressed. Additionally, a costbenefit analysis is warranted before www.thelancet.com Vol 367 June 10, 2006
the widespread implementation of pneumococcal vaccine for such a benign clinical condition as AOM. We declare that we have no conflict of interest.
*Federico Marchetti, Jenny Bua, Alessandro Ventura. [email protected] Department of Paediatrics, Institute of Child Health, IRCCS Burlo Garofolo, University of Trieste, Via dell’Istria 65/1, 34100 Trieste, Italy 1
2
3
4
Prymula R, Peeter P, Chrobok V, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet 2006; 367: 740–48. Rovers MM, Schilder AG, Zielhuis GA, Rosenfeld RM. Otitis media. Lancet 2004; 363: 465–73. Marchetti F, Ronfani L, Conti Nibali S, Tamburlini G, for the Italian Study Group on Acute Otitis Media. Delayed prescription may reduce the use of antibiotics for acute otitis media. Arch Pediatr Adoles Med 2005; 159: 679–84. Straetemans M, Sanders EAM, Veenhoven RH, Schilder AGM, Damoiseaux RAMJ, Zielhuis GA. Pneumococcal vaccines for preventing otitis media. Cochrane Database Syst Rev 2004; 1: CD001480.pub2.
Roman Prymula and colleagues1 report the results of a clinical trial to assess the efficacy of an 11-valent pneumococcal vaccine that uses as a carrier a Haemophilus influenzae surface lipoprotein in the prevention of acute otitis media (AOM). Many issues are not clear, particularly the accurate identification of AOM. Making the diagnosis of AOM is not simple and many studies have found limitations in establishing the differential diagnosis between bacterial or viral AOM and otitis media with effusion.2 In Prymula and colleagues’ study, the initial detection of patients was done by paediatricians, Location Prymula and colleagues1
Czech Republic and Slovakia
Teele and colleagues3
Boston
Fireman and colleagues4
California
Eskola and colleagues5
Finland
and if AOM was diagnosed, the patient was referred to the ear, nose, and throat (ENT) department for confirmation and to obtain a sample of middle-ear fluid. Although there was a reduction in culture positive cases in the vaccine group, the report does not specify how many patients, per group, were seen with fever or any other disease by the clinic paediatrician but who were not referred to ENT because a diagnosis of AOM was disqualified at that stage. This information is particularly important since the overall incidence of AOM episodes in the control group is lower than that of other reports (table).3–5 If we assume a realistic incidence of 1·2 episodes per year in the control group, the expected number of cases would have been 2942, which is six-fold greater than the number actually detected in this study (499). The numbers in Prymula and colleagues’ table 3 are difficult to understand and are not consistent. For example, in the control group, there were 474 episodes for which a sample of middle-ear fluid was obtained; however, the table shows 256 episodes with negative cultures and 306 with positive cultures (total: 562 episodes). Prymula and colleagues should indicate the number of patients with first episodes only in each group, and present in a different analysis the number of recurrent episodes. Also, how many patients completed the 24–27-month follow-up period is unclear. Another concern is the number of episodes with negative bacterial cultures (54% in the control group Study population* 2452
e-mail submissions to [email protected]
Episodes per child per year 0·125
877
1·2
16 152
1·8
832
1·2
*Control groups not vaccinated.
Table: Incidence of acute otitis media in control groups of four different studies
1897