Case Discussion A 27-year-old man presented to our emergency room on Aug 22, 2000 with a 5-day history of fever, chills, and bilateral calf pain. He also complained of diarrhea and mild cough and hemoptysis. The past history was not remarkable and he had a part-time job at a Chinese desert company during summer vacations. He denied recent travel to other countries. Physical examination revealed a temperature of 38o C and clear breath sounds. Laboratory studies at the emergency room (Aug 23, 2000) showed leukocytosis, anemia, thrombocytopenia, hyperbilirubinemia, and renal insufficiency. The abdominal sonography revealed only a tiny gallbladder polyp. The initial chest radiograph was clear (Figure 1). Unfortunately, respiratory distress occurred 1 day later. Physical examination disclosed icteric sclera, pale conjunctive, coarse breathing sounds and bilateral basal crackle but without heart murmur. There was no skin rash, hepatosplenomegaly or peripheral lymphadenopathy. The follow-up chest radiographs showed diffuse alveolar infiltrates with rapid progression to a pattern compatible with acute respiratory distress syndrome (Figure 2). The computed tomography of the chest also revealed dense alveolar consolidation over the dependent portions of both lungs (Figure 3 ). Severe hypoxemia (PaO2 41.9 mmHg) and hypotension (69/37 mmHg) were noted on Aug 23, so he was intubated and transferred to the intensive care unit. There was rapid deterioration of both renal and liver functions (bilirubin 15.3 mg/dL; AST 162 U/L; ALT 57 U/L; ALP 141 U/L; BUN 91 mg/dL; and Creatinine 6.7 mg/dL). The urine legionella antigen and cultures of blood, urine, and sputum were all negative. Diagnosis of leptospirosis was highly suspected and was confirmed based on an initial microagglutination antibody titer of 1:200 and an 8-fold rise in the paired serum 7 days later. Penicillin G 12 MU/day was administered but was shifted to minocycline 400 mg/day on Aug 29 because of drug allergy. Inverse ratio pressure-controlled ventilation and intermittent prone positioning were required to maintain arterial oxygen saturation >= 90%. His chest radiograph and multi-organ failure improved gradually after Aug 29 and was finally liberated from mechanical ventilation on Sep 6. Minocycline therapy was maintained for 2 weeks and he was discharged in a stable condition on the 20th hospital day. When he was last seen at the outpatient clinic on Oct 2, he was rather well and the chest radiograph and all laboratory data were normal. Laboratory data 1. CBC/DC:   WBC RBC Hb Hct MCV PLT   K/uL M/uL G/dL % fL K/uL 890822 11.10 4.01 11.7 34.6 86.3 27 890828 29.08 3.92 11.7 33.9 86.5 159 890902 9.02 4.58 13.2 40.2 88.2 23.1  2. Coagulation:   PT PT Cont PTT PTT Cont INR   Sec Sec Sec Sec   890823 16.8 11.6 64.8 37.5 1.4 890902 14.7 12.1 42.8 37.9 1.2 3. DIC Profile   3P FDP D-Dimer     ug/ml ug/ml 890824 4+ 40-80 2.38 890828 Negative 20-40 1.16 4. Biochemistry   BUN Cre Na K T-Bil D-Bil GOT GPT   mg/dl mg/dl mmole/l mmole/l mg/dl mg/dl U/l U/l 890822 15 1.4 137 3.6 5.8 890822 183   890823 15 1.4 137 3.6 5.8   168 162 890824 91 6.7 140 3.2 15.3 12.0 162 57 890828 63 2.8 152 3.6 18.7   105 168 890904 34 1.5 141 4.6 3.7 1.1 26 22  5. ABG   pH PCO2 PO2 HCO3- BE condition   * mmHg mmHg mEq/l mEq/l   890823 7.28 38.9 82.5 17.7 -8.0 mask, 10 L, FiO2 = 80% 890830 7.31 59.3 61.0 28.9 2.0 PCV, 80%, I/E:2/1 890831 7.41 46.6 69.2 28.8 4.0 PCV, 45%, I/E:1/1,prone 890907 7.38 38.2 73.8 21.8 -2.5 Mask, 10L, 40% 6. Legionella urinary Antigen: negative 7. Blood cultures: no aerobic and anaerobic pathogens     Urine cultures: no aerobic pathogens     Sputum cultures: no aerobic pathogens 8. Bronchoscopy: bleeding from right B6 and B10;     Cultures of PSB (protected sheath brushing): no growt;     Cultures of bronchoalveolar (BAL) fluid : no growth 9. Leptospira titer: (08-24) 1:200 ; (08-31) 1:1600       本病例為一原本身體健康的年輕人。突然產生高燒、畏寒、雙腿肌肉酸痛，輕微咳嗽及咳血之症狀，且有拉肚子及血尿之現象。可推測大概為一全身性之感染症。後來迅速造成肝、腎功能異常且有嚴重的黃疸、出血傾血及呼吸衰竭，可推測可能為較特殊的致病原之嚴重感染，如寄生蟲、較特殊之細菌或病毒等。有拉肚子、腎功能異常、肺炎及呼吸衰竭應考慮 legionellosis, 但legionellosis 少在初期出現嚴重黃疸及咳血。出現黃疸、發燒、腎功能異常會使人聯想到的致病菌中，鉤端螺旋體是必須列入鑑別診斷的。患者曾任職食品工場業務員，工作場所有不少鼠類出沒。職業上也符合應列入leptospirosis的感染對象。因為能及早診斷，及早治療，此病患能於兩週內出院，為一成功治療之典範。 繼續教育考題 1. (D) Which of the following descriptions of leptospirosis is WRONG? A Is caused by spirochete (or spiral shaped) bacteria B People can catch the disease from direct contact with animals, such as rodents, raccoons, skunks and cattle. The disease can also be spread by indirect contact with the contamination on vegetation, food and water, soil and bedding materials C The bacteria enter the body via cuts to the skin, or via the nose, mouth or other mucous membranes. D Disease can be spread frequently from person to person 2. (C) Which of the following conditions is most compatible with this patient's clinical manifestations? A Good past eur's syndrome B Hemophagocytic syndrome C Weil's syndrome D Hemolytic uremic syndrome 3. (D) Which evidence below is helpful in the diagnosis of the patient's syndrome? (1) fever (2) renal dysfunction (3) jaundice (4) consciousness disturbance (5) cardiovascular collapse A (1), (2), (4) B (2), (3), (4) C (1), (3), (4), (5) D (1), (2), (3), (4), (5) 4. (B) What kind of the following occupations are at risk of getting leptospirosis EXCEPT A Farmers B School teachers C Cattle or pig owners D Occupation involving contact with rats and dogs 5. (D) Which of the following conditions should be listed in the differential diagnosis of leptospirosis? (1) Richettsiosis, (2) Malaria, (3) Yellow fever, (3) Toxic shock syndrome (4) Hantaan virus infection (5) Legionnaires’ disease A (1), (2), (4) B (2), (3), (4) C (1), (3), (4), (5) D (1), (2), (3), (4), (5) 6. (C) Which statement about the laboratory diagnosis of leptospirosis is WRONG? A A common diagnostic method is microscopic agglutination test (MAT), which measures the presence of IgG antibodies. B Positive results of MAT are represented by a rise in antibody titer greater than 4-fold in the paired serum (drawn 2 weeks apart) C A positive blood or urine culture may be obtained within 3 weeks D ELISA to measure IgM antibodies may also be helpful. 7. (C) Which of the following description about the pulmonary involvement of leptospirosis is wrong? A Reported in 20% to 70% of patients. B Symptoms are cough, hemoptysis, and chest pain (usually caused by pulmonary hemorrhage) C Frequently leads to acute respiratory distress syndrome (ARDS) D CxR may show patchy alveolar infiltrates and accentuated lung marking; usually in the lower lung fields 8. (C) From the aspect of public health, which of the following descriptions about leptospirosis is WRONG? A Worldwide, leptospirosis infection increases with flooded conditions B Public health authorities suggest keeping dogs away from children's play areas, including sandboxes and wading pools in areas with risk for leptospirosis C There is still no vaccine for this disease D Farmers or dog owners at risk for this infection may use oral doxycycline for prevention 9. (A) Which kind of drug is recommended for the initial treatment of leptospirosis? A Penicillin G B Third-generation cephalosporins C Ciprofloxacin D Sulfur drugs 10. (D) About the treatment of the leptospirosis, which statement below is WRONG? A Antibiotics should be given early in the course of the disease B Intravenous antibiotics may be required for persons with more severe symptoms. C The recommended duration of treatment is 2 weeks D Drug resistance is seen in about 40% of cases

答案解說 答案解說: 1.(D)   鉤端螺旋體 (leptospires) 是一種細桿狀螺旋形，兩端呈鉤狀的一種細菌。本菌能引起人及動物的鉤端螺旋體病 (leptospirosis)，是一種人畜共同傳染病。本病能感染的宿主範圍相當廣泛，包括許多家畜如牛、馬、羊、豬、犬等等以及野生動物，甚至一些水生動物。狗是鉤端螺旋體血清型canicola、icterohaemorrhagiae、grippotyphosa之自然宿主 (亦即保菌宿主)。犬隻感染這幾種血清型之鉤端螺旋體後，常會演變成慢性帶原狀態，菌體會隨著尿液排出而感染其他的犬隻、老鼠等囓齒類以及人類。貓科動物對本菌較不具有感受性。人與人之間目前沒有報告。 2. (D)   本病初感染時幾乎無臨床症狀，故極不易察覺，症狀出現時呈現虛弱無力、嘔吐、高燒、無食慾、貧血、血尿及黃疸等胃、腸、肝、腎之損害症狀。Weil's syndrome 是指嚴重 Leptospirosis 造成 fever, jaundice, renal dysfunction, consciousness disturbance 等 3. (D)   Leptospirosis急性型感染是由於嚴重的菌血症所致，病患往往在病原菌尚未侵入實質臟器之前，便因急性脫水、血管炎及散播性血管內凝血症候群等原因而死亡。亞急性感染可由急性肝腎功能衰竭之臨床症狀如黃疸、尿毒等。 4. (B)   理由如答案 (1) 解說。會接觸家畜如牛、馬、羊、豬、犬以及野生動物或其排泄物之職業都可能感染。 5. (D)   所列疾病都能造成 fever, renal dysfunction, jaundice, consciousness disturbance, 及cardiovascular collapse, 故應列入 differential diagnosis 6. (C)   鉤端螺旋體病之確診必須基於臨床症狀、臨床病理學檢查、細菌學檢查以及血清學檢查等方面之證據。血清學檢查的方法主要有兩種：顯微凝集試驗(microscopic agglutination test，MAT)以及酵素連結免疫吸附法(ELISA)。其中MAT法是目前來說比較快速且準確的方法，但其缺點是不能在感染初期即測得是否遭感染。細菌學檢查的方法是直接以暗視野顯微鏡觀察血液或尿液中之鉤端螺旋體或由二者中分離細菌、增殖後再觀察。倘使血液、尿液中的細菌數目不多，直接觀察幾乎是不可能；若想以鉤端螺旋體培養之方式來確診又非常耗費時間且頗為困難，因此不適合用來做即時的鑑別診斷方法。近年發展出以聚合鏈反應(PCR)偵測鉤端螺旋體基因核酸之技術來進行本病之確診，提供了臨床上一種既快速又敏感，可靠性及準確性又高的診斷方法，即使是血液或尿液中只有很少量之菌體存在，也能夠偵測得到。利用此方法，可以在本病之早期便得到確診。 7. (C)   Leptospirosis 之Pulmonary involvement包含咳血 、咳嗽、 肺炎等。本病患出現ARDS, 甚為罕見。 8. (C)   由於本病可因污染水源、土壤等周圍環境而感染。因此一定要特別注意個人衛生，以避免本菌之感染。建議病畜主人、獸醫師、動物照顧人員及牧場工作者等高危險群，可服用低劑之doxycyclin。高危險群動物也應接受疫苗施打。由於狗的習性愛四處聞一聞或舔東西，所以很容易接觸到傳染細菌，因此接種疫苗預防本病非常的重要。 9. (A)   Leptospirosis應早期投予 antibiotics (Penicillin G 2.4-3.6 MU/day IV) or Tetracycline (2 g/day PO); Doxycycline 同時有therapeutic及 prophylactic效果。Third-generation cephalosporins 在in vitro 有效但臨床經驗不多 # Current recommendation: Mild case --- doxycycline (100mg BID) or amoxicillin (500 mg TID) for 5 to 7 days; Severe cases ---- Penicillin G (6-10 MU/ day IV for 14 days) or ampicillin (2-4 g/day IV) 10. (D)   理由如答案 (9) 解說; drug resistance不常見 Top of Page