Brucellosis

Japanese: ブルセラ症

(14) Brucellosis
Definition/Concept Brucellosis is an infectious disease caused by bacteria of the Brucella genus. It is a zoonotic disease and causes undulant fever. Brucellosis is also known as an endemic disease with specific names such as Malta fever and Mediterranean fever. This disease is designated as a Class 4 infectious disease under the Infectious Diseases Control Act.
Cause and Etiology Different species of Brucella bacteria infect different animals; Brucella melitensis primarily infects sheep and goats, B. abortus cattle, B. suis pigs, and B. canis dogs. Of these, B. melitensis is the most pathogenic and has the largest number of patients. In endemic areas, infection occurs by eating milk or cheese from infected animals such as goats and cows, or by coming into contact with urine and other excrement.
Epidemiology, incidence, and statisticsThis disease is widely distributed throughout the world, mainly in the Mediterranean region and Central and South America. Infection rates are high among dairy farmers and other people who have frequent contact with animals. It is a rare disease in Japan, but people traveling to endemic areas may develop the disease.
Pathophysiology: This bacterium is an intracellular parasite that is resistant to killing even when phagocytosed by neutrophils or macrophages. The proliferated bacteria are dispersed to organs throughout the body via lymphatic or hematogenous routes, where they cause persistent infection.
Clinical Symptoms: When brucellosis develops, a patient will experience an intermittent flu-like fever that continues for a long period of time. Although the temperature will be normal in the morning, the patient will often experience a fever in the afternoon and evening, and may experience a high fever accompanied by chills. Patients may also complain of gastrointestinal symptoms such as nausea, vomiting, and diarrhea, respiratory symptoms such as sore throat and dry cough, sweating, headache, muscle pain, fatigue, weight loss, and depression. Objective symptoms that may be observed include lymphadenopathy, hepatosplenomegaly, and joint swelling.
Laboratory findings: Peripheral blood white blood cell count is often normal or decreased, while lymphocyte count tends to be slightly increased. Erythrocyte sedimentation rate is normal or slightly increased. Furthermore, decreased platelet count and abnormal liver function may be observed.
In the diagnostic interview, it is important to first confirm the patient's travel history to endemic areas overseas, and whether they have consumed milk or meat from goats or cows in those areas. The incubation period is usually 2 to 8 weeks, but it can be longer. Since there are no specific symptoms of this disease, it may be overlooked as fever of unknown origin without being diagnosed. The diagnosis is confirmed if the bacterium is isolated by blood culture, but if the disease is strongly suspected even if the blood culture is negative, bone marrow aspiration or lymph node biopsy may be performed for culture. Gram-negative short rods are observed in smear staining of the specimen. Although the measurement of serum antibody titers has been pointed out as a problem of cross-reactivity with other bacterial species, it is a useful diagnostic test and can also be used to evaluate the effectiveness of treatment. Bone scintigraphy, CT, and MRI are useful for identifying the site of infection.
Differential diagnosis Clinically, it is necessary to differentiate it from other unknown fever diseases (malaria, typhoid fever, tuberculosis, tularemia, malignant tumors, collagen diseases, etc.). Furthermore, it may be mistaken for Moraxella or Haemophilus influenzae based on the results of staining and culture.
Complications The disease is occasionally complicated by arthritis, endocarditis, osteomyelitis, genitourinary tract infections, encephalitis, and meningitis. Endocarditis is a potentially fatal disease in brucellosis.
Course and prognosis: The mortality rate from this infection is generally low.
Treatment, Prevention, and Rehabilitation: Treatment of this disease requires long-term treatment (6 to 8 weeks or more) to prevent recurrence. Treatment with a combination of two drugs from the following is recommended: tetracycline (doxycycline), aminoglycoside (gentamicin), rifampicin, ST combination drug, and quinolone drugs. Vaccines are used in livestock, but are not used in humans due to their strong side effects. [Matsumoto Tetsuya]
■ References
Corbell JM: Brucellosis: an overview. Emerg Infect Dis, 2: 213-221, 1997.
Longo, DL et al ed: Harrison's Principles of Internal Medicine, 18th ed, McGraw-Hill, 2011.

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

Japanese:

（14）ブルセラ症（brucellosis）
定義・概念
　ブルセラ（Brucella）属の菌による感染症がブルセラ症である．人獣共通感染症の1つであり，波状熱の原因となる．ブルセラ症はマルタ熱（Malta fever）や地中海熱（Mediterranean fever）など固有の名前をもつ風土病としても知られている．なお本疾患は感染症法の四類感染症に指定されている．
原因・病因
　ブルセラ属の菌は種によって感染する動物が異なり，Brucella melitensisがヒツジとヤギ，B. abortusがウシ，B. suisがブタ，B. canisがイヌに主として感染する．この中ではB. melitensisが最も病原性が強く患者数も多い．流行地域において，ヤギやウシなど感染動物のミルクやチーズを食したり，尿などの排泄物に接触して感染する．
疫学・発生率・統計的事項
　本疾患は地中海地方，中南米を中心に世界中に広く分布している．動物と接触する機会が多いため，酪農家などに感染率が高い．国内ではまれな疾患であり，流行地域への渡航者が発症することがある．
病態生理
　本菌は細胞内寄生菌であり，好中球やマクロファージに貪食されても殺菌に抵抗性を示し，増殖した菌はリンパ行性あるいは血行性に全身の臓器に散布され，そこで持続感染を起こす．
臨床症状
　ブルセラ症を発症するとインフルエンザ様の発熱が間欠的に起こるいわゆる波状熱が長期間継続する．朝は平熱にもかかわらず，午後から夕方にかけて発熱がみられるパターンが多く，悪寒を伴う高熱の場合もある．悪心・嘔吐，下痢などの消化器症状や咽頭痛，乾性咳などの呼吸器症状，および発汗，頭痛，筋肉痛，倦怠感，さらに体重減少やうつ状態を訴えることもある．他覚的にはリンパ節腫脹，肝脾腫および関節の腫脹などを認めやすい．
検査成績
　末梢血白血球数は正常あるいは低下している場合が多いが，リンパ球数はやや増加傾向を示す．赤沈は正常かやや亢進している．さらに血小板数の減少や肝機能異常を認めることがある．
診断
　問診では海外の流行地域への渡航歴，さらにその地域でヤギやウシなどの乳汁や肉を摂取したかどうかを確認することがまず重要である．潜伏期間は通常2～8週間とされているが，さらに長期の場合もある．本疾患に特異的な症状はないため，不明熱として診断がつかないまま見過ごされる可能性がある．血液培養によって本菌を分離できれば診断が確定するが，血液培養陰性でも本疾患が強く疑われる場合は，骨髄穿刺やリンパ節生検を行って培養を行うことがある．検体の塗抹染色ではGram陰性の短桿菌が観察される．血清抗体価の測定は，他菌種との交差反応の問題も指摘されているが，診断上有用な検査であり，治療効果の判定にも利用できる．感染部位の検索には，骨シンチグラフィ，CT，およびMRIが有用である．
鑑別診断
　臨床的には他の不明熱疾患（マラリア，腸チフス，結核，野兎病，悪性腫瘍，膠原病など）との鑑別が必要である．さらに染色や培養の結果をもとにモラクセラやインフルエンザ菌などと誤認されることがある．
合併症
　本疾患はときに関節炎，心内膜炎，骨髄炎，泌尿生殖器の感染および脳炎，髄膜炎を併発する．心内膜炎はブルセラ症の死因となり得る疾患である．
経過・予後
　本感染による死亡率は一般的には低率である．
治療・予防・リハビリテーション
　本疾患の治療には，再燃を予防するため長期間（6～8週間以上）の治療が必要とされている．テトラサイクリン（ドキシサイクリン），アミノ配糖体（ゲンタマイシン），リファンピシン，ST合剤，およびキノロン系薬の中から２薬剤を併用した治療が推奨される．ワクチンは家畜には用いられているが，副作用が強いのでヒトには応用されていない．［松本哲哉］
■文献
Corbell JM: Brucellosis: an overview. Emerg Infect Dis, 2: 213-221, 1997.
Longo, DL et al ed: Harrison’s Principles of Internal Medicine, 18th ed, McGraw-Hill, 2011.

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