Yamanaka Noboru, Hotomi Muneki, Billal Dewan S
Department of Otolaryngology - Head and Neck Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
J Infect Chemother. 2008 Jun;14(3):180-7. doi: 10.1007/s10156-007-0599-3. Epub 2008 Jun 24.
Acute otitis media (AOM) is the most common disease seen in childhood. Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis are the most frequent pathogens of all AOM episodes. The high prevalence of drug-resistant pathogens such as penicillin-resistant S. pneumoniae (PRSP) and betalactamase producing or nonproducing ampicillin-resistant H. influenzae (BLPAR or BLNAR) is causing serious clinical problems worldwide. PRSP and BLNAR have become important risk factors for intractable clinical outcome of AOM. PRSP causes a three times higher incidence of intractable AOM than susceptible strains. BLNAR strains show penicillin-binding protein gene mutation and are not only resistant to ampicillin, but also have reduced susceptibility to cephalosporin. The resistant H. influenzae pathogen has shown clonal dissemination in Japan in ways different from those of penicillin-resistant S. pneumoniae. Protection against AOM due to these pathogens may depend on pathogen-specific antibodies. Pneumococcal capsular polysaccharides (PCPs) are type specific and poorly immunogenic in children younger than 2 years old. Approximately 50% of otitis-prone children showed subnormal levels of anti-PCP IgG2 antibody. In our immunological study in children with otitis media, however, otitis-prone children were not unusually vulnerable to infections except those resulting in otitis media. This fact seems to refute the presence of a broad immunological deficit in these children. Some pathogen-specific antibodies may be directed against protein immunogens such as pneumococcal surface protein A (PspA) of S. pneumoniae, P6 of NTHi, and UspA of M. catarrhalis. The levels of antibody to P6 of NTHi in healthy children were significantly higher than those in the otitis-prone children after the age of 18 months. In general, individual antibody levels in otitis-prone individuals did not have an age-dependent rise. The failure to develop a good antibody response to common antigens such as PspA and P6 may enable the pathogen to cause persistent or recurrent disease.
急性中耳炎(AOM)是儿童期最常见的疾病。肺炎链球菌、不可分型流感嗜血杆菌(NTHi)和卡他莫拉菌是所有AOM发作中最常见的病原体。耐药病原体的高流行率,如耐青霉素肺炎链球菌(PRSP)和产β-内酰胺酶或不产β-内酰胺酶的耐氨苄西林流感嗜血杆菌(BLPAR或BLNAR),正在全球范围内引发严重的临床问题。PRSP和BLNAR已成为AOM难治性临床结局的重要危险因素。PRSP导致难治性AOM的发生率比敏感菌株高3倍。BLNAR菌株显示青霉素结合蛋白基因突变,不仅对氨苄西林耐药,而且对头孢菌素的敏感性也降低。耐药流感嗜血杆菌病原体在日本以不同于耐青霉素肺炎链球菌的方式呈现克隆传播。针对这些病原体预防AOM可能依赖于病原体特异性抗体。肺炎球菌荚膜多糖(PCP)具有型特异性,在2岁以下儿童中免疫原性较差。约50%易患中耳炎的儿童抗PCP IgG2抗体水平低于正常。然而,在我们对中耳炎患儿的免疫学研究中,除了导致中耳炎的感染外,易患中耳炎的儿童对其他感染并无异常易感性。这一事实似乎反驳了这些儿童存在广泛免疫缺陷的观点。一些病原体特异性抗体可能针对蛋白质免疫原,如肺炎链球菌的肺炎球菌表面蛋白A(PspA)、NTHi的P6以及卡他莫拉菌的UspA。18个月龄后,健康儿童中抗NTHi P6抗体水平显著高于易患中耳炎的儿童。一般来说,易患中耳炎个体的个体抗体水平没有随年龄增长而升高。对PspA和P6等常见抗原未能产生良好的抗体反应可能使病原体导致持续性或复发性疾病。