Case Discussion  <Case Presentation >     This 65-year-old man was admitted on October 9th, 2001 because of general malaise and jaundice for half a month, and fever for about 3 days.      He had worked in Nigeria since this February until he returned to Taiwan on September 26th. He was found yellowish looking by his family about half a month ago. He began to experience general malaise and poor appetite gradually. Dark-color urine was also noted. Fever and chills occurred on October 4th. On the following days, he felt nausea, vomiting, and diarrhea about 4 times a day. He went to a local clinic and intravenous fluid was given under the impression of common cold. He visited our Emergency Department on October 9thdue to persistent fever.      He had neither diabetes mellitus, hypertension, nor previous history of hepatitis. He denied the use of alcohol, drugs, or smoking.      At the Emergency Department, his body temperature was 38.1℃, blood pressure was 155/87mmHg, pulse rate was 133/min, and respiratory rate was 24/min. His consciousness was clear. The conjunctiva was pale and sclera icteric. The neck was supple. The breath sounds were clear. The heart beats were regular; no murmurs were heard. His liver was palpable; the liver span was 11 centimeters at the right middle clavicular line. The spleen was palpable. There was right upper quadrant tenderness but no rebound tenderness. Cyanosis, edema, skin rash, petechiae, and ecchymosis were not seen.      The liver function test revealed a total bilirubin of 5.19 mg/dL, a direct bilirubin of 2.0 mg/dL, and mildly elevated AST of 52 IU/L and ALT of 38 IU/L. His renal function was BUN of 34.2 mg/dL and Cre 0.76 mg/dL. The leukocyte count was 5230 /uL (band 37%, segment 43%, monocyte 4%, lymphocyte 13%, and atypical lymphocyte 2%). The hemoglobin was 13.9 g/dL and hematocrit 38.6%. Marked thrombocytopenia was found with a platelet count of 9000/uL. Urinalysis showed that protein was > 300 mg/dL, occult blood, 1+ bilirubin 3+, urobilinogen 1.0 EU/dL, and RBC 0-1 per high power field. His chest radiography on admission was normal.      Infection of Plasmodium falciparum was determined after we obtained a thick blood smear, which disclosed intraerythrocytic malaria parasites with predominantly blue ring forms. The initial treatment included hydration and oral mefloquine (750 mg as a single dose, followed by 500 mg in 6 hours and 250 mg in 12 hours) due to high resistant rate of malaria to chloroquine in Nigeria. He still had fever over the next two days of admission, and anemia due to hemolysis developed progressively. He had received transfusion therapy with packed RBC and platelet for the anemia and thrombocytopenia. On the third day of admission, the blood smear revealed decreased parasite load (less than 5% of erythrocytes were infected). However, the patient suffered from altered mentation, seizure, lactic acidosis and impaired renal function (BUN 71.0 mg/dL and Cre 1.88 mg/dL). The cerebrospinal fluid examination showed that leukocyte count was 2 lymphocyte per high power field, protein was 76.9 mg/dL, and sugar was 81 mg/dL. The magnetic resonance imaging of brain had not disclosed any abnormality. Under the impression of cerebral malaria, he was transferred to intensive care unit, and received intravenous quinidine sulfate 10mg/kg every 8 hours and doxycycline 100 mg every 12 hours. The consciousness recovered on the next day, and renal function improved gradually later. Because the patient had recovered consciousness and could take oral medications, the medications were switched to oral quinine (600 mg tid) and doxycycline (100 mg bid).      The next day after medication switched to oral quinine and doxycycline, sudden onset of generalized tonic-clonic seizures occurred, accompanied with recurrent fever, shock status, and respiratory distress with desaturation. The patient underwent intubation with ventilator support and received vasopressor for hemodynamic maintenance. The chest radiograph revealed diffuse pulmonary infiltrates over bilateral lung fields. The measurements of pulmonary artery catheter favored distributive shock and non-cardiogenic lung edema (pulmonary artery wedge pressure 11 mm Hg, cardiac index 6.36 l/min/m2, and systemic vascular resistance index 704 dyne/sec/cm2/m2). Anemia, thrombocytopenia, and hyperbilirubinemia persisted during this period. Although the blood smear still revealed decreased parasite load (less than 1% of erythrocytes were infected), we switched anti-malaria therapy to intravenous artesunate. An antibiotic with ceftazidime was also used because nosocomial pneumonia could not be ruled out. His condition was stabilized gradually over the next week. The hemodynamics and oxygenation improved, fever subsided, and hemogram recovered. The blood smear showed no more malaria parasites after 5-day use of artesunate. The chest radiograph became clear. He eventually underwent successful extubation on Oct 18th. Liver and renal functions gradually improved and fever subsided. He was transferred to a general ward on Oct 19th and was discharged on Oct 24th. 病案分析      本病例是一境外移入之惡性瘧原蟲(Plasmodium falciparum)感染，併發抽搐(convulsions)、休克(shock)，以及非心因性肺水腫(noncardiogenic lung edema)。病患一開始的症狀是疲倦、胃口變差、發燒、噁心、嘔吐以及腹瀉。因為這些症狀是nonspecific，常常會被誤認為是感冒或者是腸胃炎。      現今是地球村的時代，國人因為多種因素會前往各種疫情的地區，所以醫師應更警覺地追溯病人的travel history。現病史中問到病人剛從奈及利亞回來沒多久，再加上有明顯的發燒及黃疸，此時診斷就呼之欲出。血液抹片的檢查可以確定出是哪一種瘧原蟲的感染。      瘧疾在熱帶地區仍造成相當多人感染及死亡。台灣的瘧疾病患絕大多數是境外移入(imported)。      在過去二十年來，惡性瘧原蟲對chloroquine的抗藥性，已成為一個全球廣泛注意的問題，前往瘧疾疫情地區(endemic areas)，應事先開始預防性的服用抗瘧疾的藥物以防止感染。       惡性瘧是瘧疾感染中症狀最嚴重的一種，然而經過即時的診斷及適當的治療，在沒有併發症下，死亡率約千分之一。但是一旦發生嚴重的併發症（如本例病人），沒有完善的治療，死亡率相當高。受惡性瘧原蟲感染的紅血球會附著於血管壁的內皮細胞，而且紅血球也會相互黏著形成如花束般的一團，如此可能堵住血液循環而造成許多病症。本例病患先發生抽搐經診斷是腦性瘧疾(cerebral malaria)，在病患清醒後於治療過程中，再次發生抽搐並進而發生休克以及非心因性肺水腫。其真正的原因並不清楚，但研究顯示大量釋放出的細胞激素(cytokines)及發炎介子(inflammatory mediators)可能是造成此併發症的原因。      本病例為少見的惡性瘧併發症。在病患發生抽搐後即早住進加護病房小心監測及治療，在發生休克及非心因性肺積水，給予PEEP以及在Swan-Ganz Catheter監測下小心給予輸液治療，而能成功治療病人。 繼續教育考題 1. (A) Which statement about the malarial diagnosis is True: A We should consider a patient with fever and flu-like symptoms in individual returning from a malarious endemic areas to have malarial infection B Malaria could be ruled out if the patient has taken prophylactic drugs during travel in malarious endemic area C If a patient did not go abroad, he would not suffer from malarial infection. D Neither 2. (B) A 30 year-old Taiwanese plans to travel to Africa for 1 month. What is his risk of contracting malaria if he has not taken any preventive antimalarial drugs? A 1:5. B 1:50. C 1:1,000. D 1:10,000. 3. (A) Which plasmodium specie causes the most serious complications? A Plasmodium falciparum B Plasmodium ovale C Plasmodium vivax D Plasmodium malariae 4. (A) When the parasite enters a human where does it immediately congregate? A Liver B Spleen C Salivary gland D Red Blood cells 5. (C) Which statement about Plasmodium falciparum is WRONG ? A It is the only malarial parasite causing greater than 20% parasitaemia B It is the only cause of cerebral malaria C It can cause recurrent relapses after initial treatment because of liver hypnozoites D It causes higher mortality than other species of Plasmodium 6. (B) Which of the following statements is WRONG ? A Adults with severe falciparum malaria may develop noncardiogenic pulmonary edema even after several days of antimalarial therapy. B Plasmodium falciparum is the only specie that can cause noncardiogenic pulmonary edema in malarial infection C The noncardiogenic pulmonary edema in malarial infection is a variant of the adult respiratory distress syndrome (ARDS). D The noncardiogenic pulmonary edema in malarial infection can be aggravated by overly vigorous administration of intravenous fluid. 7. (D) Which statement about the malarial infection is True? A Leukocytosis could exclude the malarial infection. B Blood smears prepared from oxalated samples of blood collected for CBC test are as good as smears taken from a drop of peripheral blood to diagnose malarial infection C We can use Quinine and Mefloquine together to treat chloroquine-resistant malaria. D Chloroquine should not be used in Plasmodium falciparum malaria in patient with complications, such as cerebral malaria, severe anemia, renal failure and lung edema. 8. (D) Adverse effects of quinine includes: A Nausea and vomiting B Hypoglycemia C QTc prolongation D All of the above 9. (D) Which of the following statements is True? A Artesunate is an antimalarial drug originally developed in mainland China. B Artesunate is highly effective against falciparum malaria, including multidrug-resistant strains. C Management of fluid balance is difficult in severe malaria, because of the thin dividing line between overhydration (leading to pulmonary edema) and underhydration (contributing to renal impairment). D All of the above 10. (D) What are the mechanisms that cause hypoglycemia in patients of severe malaria? A Failure of hepatic gluconeogenesis B Increase in the consumption of glucose by both host and parasite C Quinine or quinidine could stimulate insulin secretion if a patient receives quinine or quinidine. D All of the above

答案解說 (B)即使有預防性服用抗瘧藥物，也不一定能100％避免瘧疾感染。 (C)瘧疾仍可能經由血液傳染。 到非洲瘧疾疫區一個月有五十分之一的機率會得到瘧疾。 惡性瘧疾的併發症最嚴重，因為它可以侵入各種年齡層的紅血球，且可造成血管阻塞，引起組織缺氧及酸血症。 瘧原蟲侵入人體後，最先感染肝細胞。 (C) Plasmodium falciparum並不會潛伏在肝臟，引起復發。 (B) Plasmodium malariae也有可能引起非心因性肺水腫。 (A)一般瘧疾病患白血球並不高，但仍有瘧疾病人白血球會升高。 (B) 以新鮮剛抽出的周邊血液做的血液抹片，診斷率較高。 (C) Quinine和Mefloquine不可以同時併用，因為會有藥物交互作用，而造成更大的心臟毒性。 (A)-(C)皆是quinine可能的副作用。 (A)-(C)皆正確。 (A)-(C)皆正確。