Plague

Japanese: ペスト

(6) Plague
Definition/Concept Plague is a disease caused by infection with the bacterium Yersinia pestis. Yersinia pestis is a Gram-negative bacillus classified as a member of the Yersinia genus in the Enterobacteriaceae family. This bacterium is primarily carried by rodents such as mice and rats, and is transmitted to humans via fleas. When the plague bacillus infects through a flea bite, it migrates to the lymph nodes and causes bubonic plague, and when it spreads through droplets, it causes pneumonic plague. Plague is designated as a Class 1 infectious disease under the Infectious Diseases Control Act.
Classification Human plague is broadly classified into three types: bubonic plague, septicemic plague, and pneumonic plague. Of these, bubonic plague is by far the most common.
Cause and Etiology Humans become infected with the plague bacterium Yersinia pestis through flea bites, but sometimes the bacteria in the sputum of patients with pneumonic plague can become the source of infection. This bacterium has a history of being used as a biological weapon, and the US CDC classifies it as Category A, with a high probability of being used for bioterrorism.
Epidemiology, incidence rate, and statisticsHistorically , plague has caused many epidemics, resulting in large numbers of deaths and becoming feared as the Black Death. Since 1926, there have been no cases of plague in Japan. More than 2,000 cases of infection occur worldwide each year, with most of these occurring in certain regions, such as Africa.
Pathophysiology: In the case of bubonic plague, when the plague bacillus migrates from the site of invasion to local lymph nodes, the lymph nodes become abscessed and swollen. The bacteria then migrate via lymphatic and hematogenous routes to other organs, such as the spleen, liver, and bone marrow, and in severe cases spread throughout the body, causing sepsis.
Clinical manifestations
1) Bubonic plague:
After an incubation period of 2 to 6 days, a sudden fever (over 38°C) appears, followed by headache, chills, muscle pain, joint pain, and fatigue. The lower limbs are particularly susceptible to flea bites, which are often accompanied by swelling of the inguinal lymph nodes. Papules, pustules, or ulcers may appear at the site of the flea bite. The lymph nodes become increasingly swollen, and spontaneous pain and tenderness increase. If appropriate treatment is not given, sepsis may develop and the condition may become severe. Furthermore, eating meat contaminated with the plague bacillus can cause the pharynx to become the initial site of infection, which can lead to severe tonsillitis and swelling of the cervical lymph nodes.
2) Septicemic plague (plague sepsis):
The patient rapidly goes into shock without showing any local symptoms such as lymphadenopathy, and develops a decreased level of consciousness, necrosis of the distal extremities, purpura, etc., and eventually dies within a few days, accompanied by disseminated intravascular coagulation (DIC) and shock.
3) Pneumonic plague:
In cases of natural infection, pneumonia often develops during the final stages of bubonic plague or during the progression of septicemic plague. In cases of bioterrorism, pneumonia is likely to develop when the plague bacillus is inhaled as an aerosol. Patients begin with symptoms of headache, vomiting, and high fever, and can rapidly progress to a critical condition accompanied by difficulty breathing and bloody sputum.
Test results: Peripheral blood white blood cell count is markedly increased, with neutrophils predominating and accompanied by a shift of the nucleus to the left. Occasionally, a leukemoid reaction is observed in which the white blood cell count exceeds 100,000/μL.
Diagnosis: Lymph node aspirate, blood, sputum, etc. are used as specimens, and smears are stained and cultured. The bacterium is a Gram-negative rod-shaped bacterium, with characteristic clearly visible extremely small bodies at both poles. Other diagnostic methods besides bacterial culture include detection of Yersinia pestis antigens, genetic testing such as PCR, and serological diagnosis by antibody titer measurement.
Differential diagnosis: Bubonic plague must be differentiated from diseases accompanied by acute lymphadenopathy, such as suppurative lymphadenitis and cat scratch disease, while pneumonic plague must be differentiated from fulminant pneumonia caused by Streptococcus pneumoniae or Legionella.
Complications : Rarely, meningitis may occur.
Course and prognosis: Bubonic plague has a poor prognosis if left untreated, but it can be cured if treatment is started early. However, pneumonic plague progresses very quickly, and if appropriate antibiotics are not started immediately after the onset of symptoms, it often leads to death.
Treatment, prevention, and rehabilitation: Yersinia pestis has good drug susceptibility, and aminoglycoside, quinolone, and tetracycline antibiotics are mainly used. Gentamicin or streptomycin is recommended as the first-choice drug. In the case of pneumonic plague, it is essential to administer appropriate antibiotics from the early stage of the disease. For prevention, a formalin-inactivated whole cell vaccine can be used, but it is hardly effective against pneumonic plague. [Tetsuya Matsumoto]
■ References
Longo DL, et al ed: Harrison's Principles of Internal Medicine, 18th ed, McGraw-Hill, 2011.
Mandell GL, Bennett JE, et al: Mandell, Douglas and Bennett's Principle and Practice of Infectious Diseases, 7th ed, Elsevier Churchill Livingstone, 2009.

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

（6）ペスト（plague）
定義・概念
　ペストはペスト菌（Yersinia pestis）の感染によって起こる疾患である．ペスト菌は腸内細菌科のエルシニア属に分類されるGram陰性桿菌である．本菌は主にマウス，ラットなどの齧歯類が保菌し，ノミを介してヒトに感染する．ノミの刺し口よりペスト菌が感染するとリンパ節に移行し腺ペストを発症し，飛沫感染を起こすと肺ペストを発症する．ペストは感染症法で一類感染症に指定されている．
分類
　ヒトペストは，腺ペスト，敗血症ペスト，肺ペストの３つの病型に大別される．この中で腺ペストを起こす頻度が圧倒的に多い．
原因・病因
　ヒトはノミに咬まれてペスト菌に感染するが，ときに肺ペスト患者の痰中の菌が感染源となる．本菌は以前，生物兵器として使用された歴史があり，米国CDCはバイオテロに使用される可能性が高いカテゴリーAに分類している．
疫学・発生率・統計的事項
　歴史上，ペストは何度も流行を繰り返し大量の死者が発生して黒死病として恐れられていた．1926年以降，国内においてペスト患者の発生はみられていない．世界全体で毎年2000例以上の感染症例が発症しているが，その多くはアフリカなど一部の地域に集中している．
病態生理
　腺ペストの場合，侵入部位から局所リンパ節にペスト菌が移行すると，リンパ節は膿瘍化し腫大する．さらにリンパ行性や血行性に菌が脾臓，肝臓，骨髄など他臓器に移行し，重症化すると全身に伝播して敗血症を起こす．
臨床症状
1）腺ペスト（bubonic plague）：
2～6日の潜伏期の後，急激な発熱（38℃以上）が出現し，頭痛，悪寒，筋肉痛，関節痛，倦怠感が現れる．下肢が特にノミに咬まれやすく，鼠径リンパ節の腫脹を伴いやすい．ノミに咬まれた部位は丘疹や膿疱，あるいは潰瘍を認める．リンパ節は腫脹が増強し，自発痛や圧痛が強くなる．適切な治療が施されなければ，その後敗血症に至り，重篤化しやすい．なおペスト菌に汚染された肉などを食べることで，咽頭部が初感染巣となり高度の扁桃炎と頸部リンパ節腫脹を伴うことがある．
2）敗血症ペスト（septicemic plague，plague sepsis）：
リンパ節腫脹などの局所症状を示さないまま急激にショック状態に陥り，意識レベルの低下，四肢末端部の壊死，紫斑などが現れ，DIC（disseminated intravascular coagulation，播種性血管内凝固症）やショックを伴い数日以内に死亡する．
3）肺ペスト（pneumonic plague）：
自然感染の場合，腺ペストの末期や敗血症ペストの経過中に肺炎を発症する場合が多い．バイオテロではペスト菌をエアロゾルとして吸入することで肺炎を発症しやすい．頭痛，嘔吐，高熱を訴えて発症し，呼吸困難，血痰を伴って急激に重篤な状態に至る．
検査成績
　末梢血白血球数は著明に増加し，好中球優位で核の左方移動を伴う．ときに白血球数が10万/μLをこえるような類白血病反応（leukemoid reaction）を認める．
診断
　リンパ節吸引液，血液，痰などを検体として，塗抹標本の染色および培養を行う．本菌はGram陰性桿菌で両極に特徴ある明瞭な極小体が観察される．細菌培養以外の診断法として，ペスト菌の抗原の検出，PCRなどの遺伝子学的検査，および抗体価測定による血清診断も可能である．
鑑別診断
　腺ペストは化膿性リンパ節炎や猫ひっかき病など急性のリンパ節腫脹を伴う疾患，肺ペストは肺炎球菌やレジオネラなどによる激症型の肺炎との鑑別を要する．
合併症
　まれに髄膜炎を伴うことがある．
経過・予後
　腺ペストは無治療の場合は予後不良であるが，早期から治療を行えば治癒も可能である．ただし肺ペストの場合は病気の進行がきわめて速いので，発症後すぐに適切な抗菌薬が開始されないと死に至る場合が多い．
治療・予防・リハビリテーション
　ペスト菌の薬剤感受性は良好であり，おもにアミノグリコシド系，キノロン系，およびテトラサイクリン系の抗菌薬が用いられる．第一選択薬としてゲンタマイシンあるいはストレプトマイシンが推奨されている．肺ペストでは病初期からの適切な抗菌薬の投与が必須である．予防にはホルマリン不活化全菌体ワクチンが使用可能であるが，肺ペストにはほとんど効果が認められない．［松本哲哉］
■文献
Longo DL, et al ed: Harrison’s Principles of Internal Medicine, 18th ed, McGraw-Hill, 2011.
Mandell GL, Bennett JE, et al: Mandell, Douglas and Bennett’s Principle and Practice of Infectious Diseases, 7th ed, Elsevier Churchill Livingstone, 2009.

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