今日の臨床サポート

百日咳

著者: 上原由紀 聖路加国際病院 臨床検査科/感染症科

監修: 上原由紀 聖路加国際病院 臨床検査科/感染症科

著者校正/監修レビュー済:2021/10/27
患者向け説明資料

概要・推奨   

  1. 非流行状態では、百日咳を診断するために有力な手がかりとなる症状はない。非特異的な症状しかなくとも、他の明らかな要因がなければ、積極的に鑑別診断に入れておくことが必要である(推奨度2)。
  1. マクロライド系抗菌薬は、鼻咽頭から百日咳菌を除菌する効果はあるが、症状を軽減させる効果については十分な証拠がない(推奨度3)。
  1. CDCでは、発作期のごく初期から3週目までの患者について、抗菌薬使用を開始してよいとされる。また重症化しやすい妊婦や乳児については、症状出現から6週目まで抗菌薬加療を開始するすることは適切とされている。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
上原由紀 : 特に申告事項無し[2021年]
監修:上原由紀 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、CDCのガイドラインと最新情報が確認できるWebsiteを参考ガイドラインの項に示した。
  1. 日本呼吸器学会による百日咳診断基準フローチャート(咳嗽喀痰の診療ガイドライン2019に掲載)の内容を追加した。
  1. ワクチンの種類、届出基準について加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 百日咳とは、百日咳菌(Bordetella pertussis)による急性感染症で、長期にわたる激しい咳発作の特徴的な疾患である。なお、ワクチンは10年程度しか効果が続かないことがわかっており、近年、思春期、成人期以降の発症が目立ってきている。しかし、多くは症状が非特異的であることが多く、診断は困難である。長期に続く咳をみたら鑑別に挙げることが必要である。
  1. 百日咳は、ヒト-ヒト感染で、感染者の気道粘膜の分泌物による飛沫感染の形式をとる。感染後、通常7~10日の潜伏期間を経て、1~2週間の非特異的な上気道感染症状が主体のカタル期、特徴的な発作性の咳こみ、吸気性笛声(whoop)、咳き込み後の嘔吐(post-tussive emesis)が出現し2~3カ月持続する発作期、それらの症状が1~2週にわたって次第に軽快していく回復期を経て治癒する。
  1. 全体的な経過としては3カ月程度となることが多い。
  1. 小児期とは異なり、青年、成人期では致死的となることはない。喘息、喫煙が重症化に影響を与える。
  1. 基本的には免疫のないものは感染する可能性がある。ワクチンは10年程度しか効果が続かないことがわかっている。
  1. 百日咳は、ワクチン開発前は10歳未満の小児の疾患であったが、ワクチン導入後は米国の統計によると、患者の半数以上は青年期、成人期であり、青年期、成人の疾患に年齢層が移行している。日本国内も思春期、成人の発生は増えている。
  1. 伝染性は、カタル期と発作期のはじめを合わせたトータルほぼ2週間が最も強い。その後伝染力は低下し3週間以内にほぼ伝染性はなくなるとされている。
  1. 百日咳は感染症法の5類感染症に分類されている。青年・成人での感染がみられることから、2018年1月からは年齢にかかわらず全例、診断から7日以内に最寄りの保健所に届け出ることとなった。また、学校保健安全法で第2種感染症に指定されており、「特有の咳が消失するまで、または五日間の適正な抗菌薬療法が終了するまで」を出席停止の期間の基準としている。
問診・診察のポイント  
  1. 感冒様の症状が2週間以内にありませんでしたか?また咳嗽が2週間以上続いていますか?

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Paul B Cornia, Adam L Hersh, Benjamin A Lipsky, Thomas B Newman, Ralph Gonzales
雑誌名: JAMA. 2010 Aug 25;304(8):890-6. doi: 10.1001/jama.2010.1181.
Abstract/Text CONTEXT: Pertussis is often overlooked as a cause of chronic cough, especially in adolescents and adults. Several symptoms are classically thought to be suggestive of pertussis, but the diagnostic value of each of them is uncertain.
OBJECTIVE: To systematically review the evidence regarding the diagnostic value of 3 classically described symptoms of pertussis: paroxysmal cough, posttussive emesis, and inspiratory whoop.
DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: We searched MEDLINE (January 1966-April 2010), EMBASE (January 1969 to April 2010), and the bibliographies of pertinent articles to identify relevant English-language studies. Articles were selected that included children older than 5 years, adolescents, or adults and confirmed the diagnosis of pertussis among patients with cough illness (of any duration) with an a priori-defined accepted reference standard. Two authors independently extracted data from articles that met selection criteria and resolved any discrepancies by consensus.
DATA SYNTHESIS: Five prospective studies met inclusion criteria; 3 were used in the analysis. Presence of posttussive emesis (summary likelihood ratio [LR], 1.8; 95% confidence interval [CI], 1.4-2.2) or inspiratory whoop (summary LR, 1.9; 95% CI, 1.4-2.6) increases the likelihood of pertussis. Absence of paroxysmal cough (summary LR, 0.52; 95% CI, 0.27-1.0) or posttussive emesis (summary LR, 0.58; 95% CI, 0.44-0.77) reduced the likelihood. Absence of inspiratory whoop was less useful (summary LR, 0.78; 95% CI, 0.66-0.93). No studies evaluated combinations of findings.
CONCLUSIONS: In a nonoutbreak setting, data to determine the diagnostic usefulness of symptoms classically associated with pertussis are limited and of relatively weak quality. The presence or absence of posttussive emesis or inspiratory whoop modestly change the likelihood of pertussis; therefore, clinicians must use their overall clinical impression to decide about additional testing or empirical treatment.

PMID 20736473  JAMA. 2010 Aug 25;304(8):890-6. doi: 10.1001/jama.2010.・・・
著者: W Kwantes, D H Joynson, W O Williams
雑誌名: J Hyg (Lond). 1983 Apr;90(2):149-58.
Abstract/Text Some of the factors influencing the isolation rate of Bordetella pertussis during a whooping cough epidemic in West Glamorgan, Wales, are reported. The organism was isolated from 39% of patients with clinical whooping cough, pernasal swabbing being much more successful than cough plates. Isolation rates were increased in the non-immunized, particularly in the first year of life. Erythromycin and co-trimoxazole significantly reduced the isolation rate of B. pertussis but this did not occur with penicillin. In this study 20% of patients were culture positive 6 weeks after the onset of their infection. It is suggested that the Department of Health and Social Security recommendation of a minimum period of three weeks exclusion of children from school is inadequate. During the epidemic, the proportion of strains of B. pertussis containing antigen 2 more than doubled.

PMID 6300227  J Hyg (Lond). 1983 Apr;90(2):149-58.
著者: R Henry, D Dorman, J Skinner, C Mellis
雑誌名: Med J Aust. 1981 Jul 25;2(2):108-9.
Abstract/Text
PMID 6272070  Med J Aust. 1981 Jul 25;2(2):108-9.
著者: S O Bergquist, S Bernander, H Dahnsjö, B Sundelöf
雑誌名: Pediatr Infect Dis J. 1987 May;6(5):458-61.
Abstract/Text In an open randomized study 17 patients with a positive culture for Bordetella pertussis were treated for 10 days with erythromycin (50 mg/kg/day divided in 2 doses). The bacterium could not be isolated during therapy and in only one patient was it isolated 5 days after cessation of treatment. In comparison B. pertussis was isolated 10 and 15 days after diagnosis from 10 and 4 patients, respectively, of a group of 21 untreated controls. The treated group developed significantly fewer whoops than did the control group, even though most of the individuals had reached the paroxysmal stage at diagnosis. The dose of erythromycin (ethylsuccinate and stearate preparations) gave serum concentrations about 100 times larger than the minimal inhibitory concentration of isolated bacteria and was well-tolerated. Thus adequate erythromycin treatment eliminates B. pertussis from the nasopharynx and reduces symptoms in patients having a history of pertussis of less than 14 days. Adequate dosage and length of treatment might be crucial for these results.

PMID 2885802  Pediatr Infect Dis J. 1987 May;6(5):458-61.
著者: J E Hoppe
雑誌名: Pediatr Infect Dis J. 1992 Mar;11(3):189-93.
Abstract/Text In an open randomized multicenter study 190 culture-positive pediatric ambulatory pertussis patients were treated for 14 days with either erythromycin estolate (EST) (n = 93; 40 mg/kg/day divided in 2 doses) or erythromycin ethylsuccinate (ETH) (n = 97; 60 mg/kg/day divided in 3 doses). On day 14 Bordetella pertussis was recovered from cultures of 2 patients (2.2%) treated with EST and 1 patient (1.0%) treated with ETH. Despite the fact that 151 patients (79.4%) had reached the early paroxysmal stage at initiation of antimicrobial therapy, clinical improvement was seen in the majority (reduced frequency and severity of coughing: EST, 77.4 and 67.7%; ETH, 74.2 and 63.9%, respectively). Drug-related side effects were noted in 11 patients (11.8%) treated with EST and 16 patients (16.5%) treated with ETH (P greater than 0.05) and consisted mainly of minor gastrointestinal complaints. Erythromycin estolate in a lower dose administered only twice a day was equivalent to erythromycin ethylsuccinate in all aspects and proved to be adequate antimicrobial treatment for pertussis patients.

PMID 1565532  Pediatr Infect Dis J. 1992 Mar;11(3):189-93.
著者: S Altunaiji, R Kukuruzovic, N Curtis, J Massie
雑誌名: Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004404. doi: 10.1002/14651858.CD004404.pub3. Epub 2007 Jul 18.
Abstract/Text BACKGROUND: Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit.
OBJECTIVES: To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007).
SELECTION CRITERIA: All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough.
DATA COLLECTION AND ANALYSIS: Three to four review authors independently extracted data and assessed the quality of each trial.
MAIN RESULTS: Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis.
AUTHORS' CONCLUSIONS: Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

PMID 17636756  Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004404. d・・・
著者: Tejpratap Tiwari, Trudy V Murphy, John Moran, National Immunization Program, CDC
雑誌名: MMWR Recomm Rep. 2005 Dec 9;54(RR-14):1-16.
Abstract/Text The recommendations in this report were developed to broaden the spectrum of antimicrobial agents that are available for treatment and postexposure prophylaxis of pertussis. They include updated information on macrolide agents other than erythromycin (azithromycin and clarithromycin) and their dosing schedule by age group.

PMID 16340941  MMWR Recomm Rep. 2005 Dec 9;54(RR-14):1-16.
著者: Wayne A Ray, Katherine T Murray, Sarah Meredith, Sukumar Suguna Narasimhulu, Kathi Hall, C Michael Stein
雑誌名: N Engl J Med. 2004 Sep 9;351(11):1089-96. doi: 10.1056/NEJMoa040582.
Abstract/Text BACKGROUND: Oral erythromycin prolongs cardiac repolarization and is associated with case reports of torsades de pointes. Because erythromycin is extensively metabolized by cytochrome P-450 3A (CYP3A) isozymes, commonly used medications that inhibit the effects of CYP3A may increase plasma erythromycin concentrations, thereby increasing the risk of ventricular arrhythmias and sudden death. We studied the association between the use of erythromycin and the risk of sudden death from cardiac causes and whether this risk was increased with the concurrent use of strong inhibitors of CYP3A.
METHODS: We studied a previously identified Tennessee Medicaid cohort that included 1,249,943 person-years of follow-up and 1476 cases of confirmed sudden death from cardiac causes. The CYP3A inhibitors used in the study were nitroimidazole antifungal agents, diltiazem, verapamil, and troleandomycin; each doubles, at least, the area under the time-concentration curve for a CYP3A substrate. Amoxicillin, an antimicrobial agent with similar indications but which does not prolong cardiac repolarization, and former use of erythromycin also were studied, to assess possible confounding by indication.
RESULTS: The multivariate adjusted rate of sudden death from cardiac causes among patients currently using erythromycin was twice as high (incidence-rate ratio, 2.01; 95 percent confidence interval, 1.08 to 3.75; P=0.03) as that among those who had not used any of the study antibiotic medications. There was no significant increase in the risk of sudden death among former users of erythromycin (incidence-rate ratio, 0.89; 95 percent confidence interval, 0.72 to 1.09; P=0.26) or among those who were currently using amoxicillin (incidence-rate ratio, 1.18; 95 percent confidence interval, 0.59 to 2.36; P=0.65). The adjusted rate of sudden death from cardiac causes was five times as high (incidence-rate ratio, 5.35; 95 percent confidence interval, 1.72 to 16.64; P=0.004) among those who concurrently used CYP3A inhibitors and erythromycin as that among those who had used neither CYP3A inhibitors nor any of the study antibiotic medications. In contrast, there was no increase in the risk of sudden death among those who concurrently used amoxicillin and CYP3A inhibitors or those currently using any of the study antibiotic medications who had formerly used CYP3A inhibitors.
CONCLUSIONS: The concurrent use of erythromycin and strong inhibitors of CYP3A should be avoided.

Copyright 2004 Massachusetts Medical Society
PMID 15356306  N Engl J Med. 2004 Sep 9;351(11):1089-96. doi: 10.1056/・・・
著者: J E Hoppe, U Halm, H J Hagedorn, A Kraminer-Hagedorn
雑誌名: Infection. 1989 Jul-Aug;17(4):227-31.
Abstract/Text Fifty-five ambulatory children with early culture-proven pertussis were treated for two weeks either with erythromycin ethylsuccinate (n = 28) (50-80 mg/kg/day in three doses during meals) or with co-trimoxazole (n = 27) (6-10 mg trimethoprim/kg/day in two doses after meals). After completion of treatment, all patients in the erythromycin group were culture-negative, while in the co-trimoxazole group one child was still culture-positive. In this case vomiting may have played a role. Both agents appear to be able to eradicate Bordetella pertussis from the nasopharynx of patients with early whooping cough.

PMID 2548964  Infection. 1989 Jul-Aug;17(4):227-31.
著者: D J Hardy, D M Hensey, J M Beyer, C Vojtko, E J McDonald, P B Fernandes
雑誌名: Antimicrob Agents Chemother. 1988 Nov;32(11):1710-9.
Abstract/Text The in vitro activities of several 14-, 15- and 16-membered macrolides were compared with that of erythromycin. In general, 14-membered macrolides such as erythromycin, clarithromycin, and flurithromycin were more active against streptococci and Bordetella pertussis than was the 15-membered macrolide azithromycin, which was more active than 16-membered macrolides such as miocamycin and rokitamycin. Clarithromycin was the most active compound against Streptococcus pyogenes, pneumococci, Listeria monocytogenes, and Corynebacterium species. Legionella pneumophila was most susceptible to miocamycin, clarithromycin, and rokitamycin. Branhamella catarrhalis, Neisseria gonorrhoeae, and Haemophilus influenzae were most susceptible to azithromycin. Azithromycin and dirithromycin were the most active compounds against Campylobacter jejuni. MICs of 16-membered macrolides for strains expressing inducible-type resistance to erythromycin were less than or equal to 1 microgram/ml, whereas none of the compounds had activity against strains expressing constitutive-type resistance. The MICs of roxithromycin, miocamycin, rokitamycin, and josamycin increased in the presence of human serum, whereas MICs of the other compounds either were unchanged or decreased.

PMID 3252753  Antimicrob Agents Chemother. 1988 Nov;32(11):1710-9.
著者: Silvana Bettiol, Kay Wang, Matthew J Thompson, Nia W Roberts, Rafael Perera, Carl J Heneghan, Anthony Harnden
雑誌名: Cochrane Database Syst Rev. 2012 May 16;5:CD003257. doi: 10.1002/14651858.CD003257.pub4. Epub 2012 May 16.
Abstract/Text BACKGROUND: The worldwide incidence of whooping cough (pertussis) has been estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income countries, the case-fatality rate among infants may be as high as 4%. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta 2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs).
OBJECTIVES: To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults.
SEARCH METHODS: We updated searches of the Cochrane Central Register of Controlled Trials (CENTRAL Issue 2, 2012), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE Issue 2, 2012) accessed from The Cochrane Library, MEDLINE (1950 to January 2012), EMBASE (1980 to January 2012), AMED (1985 to January 2012), CINAHL (1980 to January 2012) and LILACS (January 2012). We searched Current Controlled Trials to identify trials in progress.
SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough.
DATA COLLECTION AND ANALYSIS: Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated search in 2012. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay. 
MAIN RESULTS: Ten trials were included of varying sample sizes (N = 9 to 135) from high-income countries. Study quality was generally poor. Included studies did not show a statistically significant benefit for any of the interventions. Only six trials including a total of 196 participants reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) - 4.7 to 8.5. One study on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours (MD -0.2; 95% CI -4.1 to 3.7). Only one trial comparing pertussis immunoglobulin versus placebo reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site).
AUTHORS' CONCLUSIONS: There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough.

PMID 22592689  Cochrane Database Syst Rev. 2012 May 16;5:CD003257. doi・・・
著者: Linjie Zhang, Sílvio O M Prietsch, Inge Axelsson, Scott A Halperin
雑誌名: Cochrane Database Syst Rev. 2012 Mar 14;3:CD001478. doi: 10.1002/14651858.CD001478.pub5. Epub 2012 Mar 14.
Abstract/Text BACKGROUND: Routine use of whole-cell pertussis (wP) vaccines was suspended in some countries in the 1970s and 1980s because of concerns about adverse effects. Following such action, there was a resurgence of whooping cough. Acellular pertussis (aP) vaccines, containing purified or recombinant Bordetella pertussis (B. pertussis) antigens, were developed in the hope that they would be as effective, but less reactogenic than the whole-cell vaccines.
OBJECTIVES: To assess the efficacy and safety of acellular pertussis vaccines in children.
SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to December week 4, 2011), EMBASE (1974 to January 2012), Biosis Previews (2009 to January 2012), and CINAHL (2009 to January 2012).
SELECTION CRITERIA: We selected double-blind randomised efficacy and safety trials of aP vaccines in children up to six years old, with active follow-up of participants and laboratory verification of pertussis cases.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the studies. Differences in trial design precluded a meta-analysis of the efficacy data. We pooled the safety data from individual trials using a random-effects meta-analysis model.
MAIN RESULTS: We included six efficacy trials with a total of 46,283 participants and 52 safety trials with a total of 136,541 participants. Most of the safety trials did not report the methods for random sequence generation, allocation concealment and blinding, which made it difficult to assess the risk of bias in the studies. The efficacy of multi-component (≥ three) vaccines varied from 84% to 85% in preventing typical whooping cough (characterised by 21 or more consecutive days of paroxysmal cough with confirmation of B. pertussis infection by culture, appropriate serology or contact with a household member who has culture-confirmed pertussis), and from 71% to 78% in preventing mild pertussis disease (characterised by seven or more consecutive days of cough with confirmation of B. pertussis infection by culture or appropriate serology). In contrast, the efficacy of one- and two-component vaccines varied from 59% to 75% against typical whooping cough and from 13% to 54% against mild pertussis disease. Multi-component acellular vaccines are more effective than low-efficacy whole-cell vaccines, but may be less effective than the highest-efficacy whole-cell vaccines. Most systemic and local adverse events were significantly less common with aP vaccines than with wP vaccines for the primary series as well as for the booster dose.
AUTHORS' CONCLUSIONS: Multi-component (≥ three) aP vaccines are effective and show less adverse effects than wP vaccines for the primary series as well as for booster doses.

PMID 22419280  Cochrane Database Syst Rev. 2012 Mar 14;3:CD001478. doi・・・
著者: Michael E Pichichero, Margaret B Rennels, Kathryn M Edwards, Mark M Blatter, Gary S Marshall, Monica Bologa, Elaine Wang, Elaine Mills
雑誌名: JAMA. 2005 Jun 22;293(24):3003-11. doi: 10.1001/jama.293.24.3003. Epub 2005 Jun 2.
Abstract/Text CONTEXT: Increasing reports of pertussis among US adolescents, adults, and their infant contacts have stimulated vaccine development for older age groups.
OBJECTIVE: To assess the immunogenicity and reactogenicity of a tetanus-diphtheria 5-component (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3) acellular pertussis vaccine (Tdap) in adolescents and adults.
DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized, modified double-blind, comparative trial was conducted in healthy adolescents and adults aged 11 through 64 years from August 2001 to August 2002 at 39 US clinical centers.
INTERVENTIONS: A single 0.5-mL intramuscular dose of either Tdap or tetanus-diphtheria vaccine (Td).
MAIN OUTCOME MEASURES: Antibody titers to diphtheria and tetanus toxoids for Tdap and Td were measured in sera collected from subsets of adolescents and adults, before and 28 days after vaccination. For pertussis antigens, titers in sera from Tdap vaccinees were assessed vs those from infants who received analogous pediatric diphtheria-tetanus-acellular pertussis vaccine (DTaP) in a previous efficacy trial. Safety was assessed via solicited local and systemic reactions for 14 days and adverse events for 6 months following vaccination.
RESULTS: A total of 4480 participants were enrolled. For both Tdap and Td, more than 94% and nearly 100% of vaccinees had protective antibody concentrations of at least 0.1 IU/mL for diphtheria and tetanus, respectively. Geometric mean antibody titers to pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3 exceeded (by 2.1 to 5.4 times) levels in infants following immunization at 2, 4, and 6 months with DTaP. The incidence of solicited local and systemic reactions and adverse events was generally similar between the Tdap and Td groups.
CONCLUSIONS: This Tdap vaccine elicited robust immune responses in adolescents and adults to pertussis, tetanus, and diphtheria antigens, while exhibiting an overall safety profile similar to that of a licensed Td vaccine. These data support the potential routine use of this Tdap vaccine in adolescents and adults.

PMID 15933223  JAMA. 2005 Jun 22;293(24):3003-11. doi: 10.1001/jama.29・・・
著者: David P Greenberg, Martha Doemland, Julie A Bettinger, David W Scheifele, Scott A Halperin, IMPACT Investigators, Valerie Waters, Kami Kandola
雑誌名: Pediatr Infect Dis J. 2009 Jun;28(6):521-8. doi: 10.1097/INF.0b013e318199d2fc.
Abstract/Text BACKGROUND: During the decade 1998-2007, a combination DTaP(5)-IPV/Hib vaccine was used exclusively in Canada to immunize infants and young children against diphtheria, tetanus, pertussis, polio, and invasive Haemophilus influenzae type b (Hib) disease.
METHODS: Medline was used to search for publications during 1996-2008 related to the epidemiology and vaccine prevention of pertussis and invasive Hib disease in Canada. Related abstracts and presentations were reviewed, when available, and epidemiologic data since 1985 were obtained from the Public Health Agency of Canada public Web site.
RESULTS: Reports of pertussis have declined substantially in preschool and school-aged children during the past decade, and cyclical peaks in disease incidence have been blunted or eliminated. In provinces and territories where Tdap(5) vaccine has been administered to 14- to 16-year-olds, marked reductions of pertussis have been documented in adolescents as well as younger age groups, possibly due to herd immunity. Incidence rates of invasive Hib disease among Canadian children <5 years declined markedly after introduction of Hib conjugate vaccines, and the disease has remained under control with exclusive use of DTaP(5)-IPV/Hib vaccine. Most cases of invasive Hib disease occur among unimmunized or only partially vaccinated children. The reduction of Hib case reports has been documented throughout Canada, including among Aboriginal children who are at high risk for this disease.
CONCLUSIONS: The Canadian experience with DTaP(5)-IPV/Hib and Tdap(5) vaccines is relevant to the United States because immunization schedules, vaccination coverage rates, and epidemiologic patterns of pertussis and Hib diseases are similar in the 2 countries, and because both vaccines are licensed for use in the United States.

PMID 19436236  Pediatr Infect Dis J. 2009 Jun;28(6):521-8. doi: 10.109・・・
著者: S A Halperin, B Smith, M Russell, P Hasselback, R Guasparini, D Skowronski, W Meekison, R Parker, P Lavigne, L Barreto
雑誌名: Vaccine. 2000 Jan 31;18(14):1312-9.
Abstract/Text Pertussis is increasingly being recognized as an important cause of cough illness in adolescents and adults. To evaluate the safety and immunogenicity of an adult formulation of a five-component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine combined with diphtheria and tetanus toxoids, we randomly allocated 749 healthy adolescents and adults from 12-54 years of age recruited from five Canadian communities to receive either tetanus-diphtheria vaccine (Td), acellular pertussis vaccine (aP) or combined diphtheria-tetanus-acellular pertussis vaccine (TdaP). Subjects and personnel were unaware of the vaccine allocation. Antibody levels were measured before and one month postimmunization; adverse events were collected at 24 and 72 h and 8 to 10 days. Adverse events were reported in similar frequency amongst the three vaccine groups. Moderate pain at the injection site was reported less frequently in the aP group than the TdaP group (10.7% compared to 19.4%; relative risk 0.6, 95% confidence interval 0.3-0.9). Chills were reported less frequently after Td (5.3%) than after TdaP (12.5%; relative risk 0.4, 95% confidence interval 0.2-0.9). There were no statistically significant differences between recipients of Td and TdaP in tetanus and diphtheria antitoxin levels achieved. Antibody response against Bordetella pertussis antigens was vigorous in all groups although recipients of aP alone had higher levels of antibody levels against pertussis toxoid, fimbriae, and agglutinins and lower antibody levels against pertactin than did TdaP recipients. We conclude that this adult formulation 5-component acellular pertussis vaccine is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.

PMID 10618527  Vaccine. 2000 Jan 31;18(14):1312-9.
著者: S A Halperin, R Bortolussi, J M Langley, B J Eastwood, G De Serres
雑誌名: Pediatrics. 1999 Oct;104(4):e42.
Abstract/Text CONTEXT: Household contacts of patients with pertussis are at increased risk of acquiring infection. Chemoprophylaxis has been recommended to decrease transmission, particularly to young infants who are at increased risk of severe disease. Although epidemiologic investigations of outbreaks have suggested a benefit, there have been no prospective studies evaluating the efficacy of chemoprophylaxis in preventing secondary cases of pertussis.
OBJECTIVE: To determine whether erythromycin estolate chemoprophylaxis is effective in household contacts of children with culture-positive pertussis.
DESIGN: Randomized, double-blind, placebo-controlled study.
SETTING: Community based.
SUBJECTS: All household contacts of 152 children with culture-positive pertussis who provided consent (n = 362). After withdrawals, there were 135 households with 310 contacts. Exclusions included pregnancy, age <6 months, already receiving an erythromycin-containing antibiotic, and erythromycin allergy. INTERVENTUINS: Erythromycin estolate (40 mg/kg/day in 3 divided doses; maximum dose 1 g) or placebo for 10 days. Nasopharyngeal cultures, pertussis antibodies, and clinical symptoms were assessed before and after treatment.
PRIMARY OUTCOME: Measure efficacy of erythromycin estolate chemoprophylaxis calculated by the proportion of households in each group with a member who developed a nasopharyngeal culture positive for Bordetella pertussis.
RESULTS: There was no difference in the development of respiratory tract symptoms compatible with a case definition of pertussis in the erythromycin- and placebo-treated groups. There were 20 households with secondary culture-positive cases of pertussis; 4 households in the erythromycin-treated group and 15 in the placebo-treated group (efficacy of erythromycin chemoprophylaxis for bacterial eradication 67.5% [95% confidence interval: 7.6-88.7]). However, medication-associated adverse reactions were reported by 34.0% of erythromycin and 15.7% of placebo recipients.
CONCLUSIONS: Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.

PMID 10506267  Pediatrics. 1999 Oct;104(4):e42.

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから