吸气时鸡鸣音是儿童百日咳的典型症状,但这一症状在婴儿、青少年和成人患患者群可没有。鼻腔分泌物百日咳博德特氏菌培养有助于明确诊断,特别是在疾病早期,但阴性培养结果并不能排除诊断。其他辅助检查包括PCR及血清学检查。
病史和检查
关键危险因素包括:年龄不满 6 个月;母体在孕 34 周或更晚曾受到感染的婴儿;未接受或未完全接受免疫接种者;或与感染者(特别是受到感染的兄弟姐妹)亲密接触者。[25]Skoff TH, Kenyon C, Cocoros N, et al. Sources of infant pertussis infection in the United States. Pediatrics. 2015;136:635-641.http://pediatrics.aappublications.org/content/136/4/635.longhttp://www.ncbi.nlm.nih.gov/pubmed/26347437?tool=bestpractice.com某些特定的职业如教师、医护人员也大大增加了百日咳传播的机会。
虽然百日咳的症状和严重性呈多变性,但其典型特征为阵发性咳嗽伴吸气时鸡鸣音(虽然吸气时鸡鸣音在婴儿、青少年及成人患者中不常见)。[41]Cornia PB, Hersh AL, Lipsky BA, et al. Does this coughing adolescent or adult patient have pertussis? JAMA. 2010;304:890-896.http://www.ncbi.nlm.nih.gov/pubmed/20736473?tool=bestpractice.com百日咳初期症状无特异性,类似上呼吸道感染,易延误诊断,直到病程进展至出现更为严重的症状。
在疾病早期(感染后1-2周),患者通常仅有流涕、打喷嚏、咳嗽、无或仅有低热。[33]Centers for Disease Control and Prevention. Pertussis (whooping cough): information for clinicians. July 2014. http://www.cdc.gov (last accessed 14 March 2017).http://www.cdc.gov/pertussis/clinical/index.html[29]Gregory DS. Pertussis: a disease affecting all ages. Am Fam Physician. 2006;74:420-426.http://www.ncbi.nlm.nih.gov/pubmed/16913160?tool=bestpractice.com处于疾病更晚期(感染后 3-10 周)的患者可能会主诉咳嗽加重,首先是阵发性咳嗽的频率增加,接着是咳嗽持续数周不变,继而是咳嗽频率逐渐减少。[33]Centers for Disease Control and Prevention. Pertussis (whooping cough): information for clinicians. July 2014. http://www.cdc.gov (last accessed 14 March 2017).http://www.cdc.gov/pertussis/clinical/index.html[29]Gregory DS. Pertussis: a disease affecting all ages. Am Fam Physician. 2006;74:420-426.http://www.ncbi.nlm.nih.gov/pubmed/16913160?tool=bestpractice.com[42]Tozzi AE, Rava L, Ciofi degli Atti ML, et al, the Progetto Pertosse Working Group. Clinical presentation of pertussis in unvaccinated and vaccinated children in the first six years of life. Pediatrics. 2003;112:1069-1075.http://www.ncbi.nlm.nih.gov/pubmed/14595048?tool=bestpractice.comCDC: pertussis materials
患者可能也有咳嗽后呕吐病史。可能也会出现食欲下降,特别是在婴幼儿中。
体征上,患者可伴有发热或不发热,出现特征性咳嗽伴有吸气相喉鸣音。婴儿表现多不典型,可主要表现为阵发性窒息、轻度咳嗽或其他呼吸系统症状。
临床病史有助于诊断疾病。[43]Centers for Disease Control and Prevention. Pertussis (whooping cough): treatment. September 2015. http://www.cdc.gov (last accessed 14 March 2017).http://www.cdc.gov/pertussis/clinical/treatment.html在不同的国家和健康机构,疑似及确诊病例诊断标准及实验室确诊方法都不尽相同。下表显示的是英国、[4]Public Health England. Guidelines for the public health management of pertussis in England. December 2016. http://www.gov.uk (last accessed 14 March 2017).https://www.gov.uk/government/publications/pertussis-guidelines-for-public-health-management美国[44]Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. Chapter 10: pertussis. 2015. http://www.cdc.gov (last accessed 14 March 2017).http://www.cdc.gov/vaccines/pubs/surv-manual/chpt10-pertussis.pdf以及世界卫生组织 (WHO) 的病例定义。[45]World Health Organization. WHO-recommended surveillance standard of pertussis. http://www.who.int (last accessed 14 March 2017).http://www.who.int/immunization/monitoring_surveillance/burden/vpd/surveillance_type/passive/pertussis_standards/en/
[Figure caption and citation for the preceding image starts]: 临床疑似及确诊病例的诊断标准Nawal Lutfiyya 起草 [Citation ends].
实验室诊断
细菌学培养有助于明确诊断。[1]Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol Rev. 2005;18:326-382.http://www.ncbi.nlm.nih.gov/pubmed/15831828?tool=bestpractice.com[2]Kretsinger K, Broder KR, Cortese MM, et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. MMWR Recomm Rep. 2006;55:1-33.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/17167397?tool=bestpractice.com[46]Palmer CM, McCall B, Jarvinen K, et al. Bordetella pertussis PCR positivity, following onset of illness in children under 5 years of age. Commun Dis Intell. 2007;31:202-205.http://www.ncbi.nlm.nih.gov/pubmed/17724996?tool=bestpractice.com[47]Loeffelholz MJ, Thompson CJ, Long KS, et al. Comparison of PCR, culture, and direct fluorescent-antibody testing for detection of Bordetella pertussis. J Clin Microbiol. 1999;37:2872-2876.http://jcm.asm.org/cgi/content/full/37/9/2872?view=long&pmid=10449467http://www.ncbi.nlm.nih.gov/pubmed/10449467?tool=bestpractice.com[48]Heininger U, Schmidt-Schlapfer G, Cherry JD, et al. Clinical validation of a polymerase chain reaction assay for the diagnosis of pertussis by comparison with serology, culture, and symptoms during a large pertussis vaccine efficacy trial. Pediatrics. 2000;105:E31.http://www.ncbi.nlm.nih.gov/pubmed/10699133?tool=bestpractice.com近十年来,随着PCR的普及,它已被列为百日咳培养的辅助检查之一。[4]Public Health England. Guidelines for the public health management of pertussis in England. December 2016. http://www.gov.uk (last accessed 14 March 2017).https://www.gov.uk/government/publications/pertussis-guidelines-for-public-health-management[8]Cherry JD. Epidemic pertussis in 2012: the resurgence of a vaccine-preventable disease. N Engl J Med. 2012;367:785-787.http://www.nejm.org/doi/full/10.1056/NEJMp1209051http://www.ncbi.nlm.nih.gov/pubmed/22894554?tool=bestpractice.com血清学检查也可行,但并不常用。[8]Cherry JD. Epidemic pertussis in 2012: the resurgence of a vaccine-preventable disease. N Engl J Med. 2012;367:785-787.http://www.nejm.org/doi/full/10.1056/NEJMp1209051http://www.ncbi.nlm.nih.gov/pubmed/22894554?tool=bestpractice.com值得注意的是,特别是如果在疾病后期培养时,细菌学培养阴性结果并不能排除百日咳诊断,英国和美国的实验室评估方法都不相同,详见下表。[44]Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. Chapter 10: pertussis. 2015. http://www.cdc.gov (last accessed 14 March 2017).http://www.cdc.gov/vaccines/pubs/surv-manual/chpt10-pertussis.pdf[4]Public Health England. Guidelines for the public health management of pertussis in England. December 2016. http://www.gov.uk (last accessed 14 March 2017).https://www.gov.uk/government/publications/pertussis-guidelines-for-public-health-management
[Figure caption and citation for the preceding image starts]: 英美百日咳实验室评估Nawal Lutfiyya 起草 [Citation ends].
百日咳博德特菌为苛养菌,分离培养时易被其他鼻咽部微生物的生长而掩盖。[49]Doern GV. Detection of selected fastidious bacteria. Clin Infect Dis. 2000;30:166-173.http://cid.oxfordjournals.org/content/30/1/166.longhttp://www.ncbi.nlm.nih.gov/pubmed/10619747?tool=bestpractice.com最佳采样和样本处理方法,包括使用聚对苯二甲酸乙二酯(商品名:Dacron®)或藻酸钙拭子而非棉拭子或人造丝拭子,以及缓慢将拭子通过鼻孔插入后咽部,可能有助于提高阳性检出率。[49]Doern GV. Detection of selected fastidious bacteria. Clin Infect Dis. 2000;30:166-173.http://cid.oxfordjournals.org/content/30/1/166.longhttp://www.ncbi.nlm.nih.gov/pubmed/10619747?tool=bestpractice.com理想状况下,拭子最好能在后咽部停留30秒后再撤出。[49]Doern GV. Detection of selected fastidious bacteria. Clin Infect Dis. 2000;30:166-173.http://cid.oxfordjournals.org/content/30/1/166.longhttp://www.ncbi.nlm.nih.gov/pubmed/10619747?tool=bestpractice.com拭子或抽吸物需直接置入选择性培养基中培养,如条件不许可,则应置入转移性培养基中。[49]Doern GV. Detection of selected fastidious bacteria. Clin Infect Dis. 2000;30:166-173.http://cid.oxfordjournals.org/content/30/1/166.longhttp://www.ncbi.nlm.nih.gov/pubmed/10619747?tool=bestpractice.com
全血细胞分析是常规检查项目,白细胞计数可见百日咳患者的外周血中淋巴细胞和中性粒细胞数目均增高。[2]Kretsinger K, Broder KR, Cortese MM, et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. MMWR Recomm Rep. 2006;55:1-33.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/17167397?tool=bestpractice.com[42]Tozzi AE, Rava L, Ciofi degli Atti ML, et al, the Progetto Pertosse Working Group. Clinical presentation of pertussis in unvaccinated and vaccinated children in the first six years of life. Pediatrics. 2003;112:1069-1075.http://www.ncbi.nlm.nih.gov/pubmed/14595048?tool=bestpractice.com[50]Litt DJ, Samuel D, Duncan J, et al. Detection of anti-pertussis toxin IgG in oral fluids for use in diagnosis and surveillance of Bordetella pertussis infection in children and young adults. J Med Microbiol. 2006;55:1223-1228.http://www.ncbi.nlm.nih.gov/pubmed/16914652?tool=bestpractice.com婴幼儿患者中白细胞/淋巴细胞计数升高预示预后不佳,应进行重症监护。[42]Tozzi AE, Rava L, Ciofi degli Atti ML, et al, the Progetto Pertosse Working Group. Clinical presentation of pertussis in unvaccinated and vaccinated children in the first six years of life. Pediatrics. 2003;112:1069-1075.http://www.ncbi.nlm.nih.gov/pubmed/14595048?tool=bestpractice.com