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This 65-year-old man was admitted
because of general malaise and jaundice for half a month and
fever for 3 days.
He had been previously well
without other systemic diseases, smoking or consumption of
alcohol or use of illicit drugs. He had stayed in Nigeria for
work since February 2001 until September 26th, 2001 when he
returned to Taiwan. Jaundice was first observed by his family
members. He began to experience general malaise and poor
appetite. Dark-colored urine was also noted. Fever and chills
occurred on October 4th
. Over the next few days, he
felt nausea, vomiting, and diarrhea about 4 times a day.
On arrival
at the Emergency Department on October 9th
, his body temperature was 38.1℃,
blood pressure 155/87mmHg, pulse 133/min, and respiratory rate 24/min. His
consciousness was clear. The conjunctiva was pale and sclera
icteric. His liver was palpable; the liver span was 11
centimeters at the right middle clavicular line. The spleen
was palpable. There was tenderness at the right upper quadrant
but without rebound tenderness. Cyanosis, edema, skin rash,
petechiae, or ecchymosis was not seen.
The urine tested for occult blood
gave a result of (+++) and the urine sediment contained 0 to 1
red cells per low-power field. Other laboratory tests revealed
that white blood cell count was 5,230/mm3 with left shifting,
hematocrit 38.5%, and platelet count 9,000/mm3
. Prothrombin time (PT) and partial-thromboplastin
time (PTT) were normal. Total bilirubin level was
5.19 mg/dl with a conjugated form of 2.0 mg/dl.
The aspartate aminotransferase was 52 IU/L and alanine aminotransferase was
38 IU/L. The results of renal function tests were normal.
Blood smears (Figure )showed
multiple ring-form parasites inside the RBCs, and Plasmodium
falciparum infection was diagnosed. Oral mefloquine was prescribed.
General tonic-clonic seizures and conscious disturbance
occurred at night on Oct 10th. He was transferred to ICU for
further care. Cerebral malaria was suspected although brain
MRI revealed no significant lesions. Fever recurred and blood
testing disclosed leukocytosis, lactic acidosis, anemia, renal
dysfunction, and hyperbilirubinemia. Anti-malarial agents were
shifted to quinidine 10 mg/kg iv drip q.8.h. and minocycline
100 mg iv drip q.12.h.. Blood smears showed decreasing levels
of parasitemia and anti-malarial agents were thus switched to
an oral form on Oct 12th .
However, fever recurred on Oct
13th. He developed a sudden onset of generalized tonic-clonic
seizures which lasted 1 minute. Meanwhile, oxygen desaturation
and hemodynamic instability were noted. He was intubated and
administration of inotropic agents were begun. A Swan-Ganz
catheter was inserted and hemodynamic data showed a cardiac
index of 6.36 and SVRI 704 which were indicative of
cytokine-related vasogenic shock. Follow-up chest radiography
revealed findings consistent with acute pulmonary edema.
Anti-malarial agents were shifted to artesunate 60 mg iv drip
q.d.. He regained consciousness gradually and inotropic agents
were subsequently tapered off. His oxygenation improved and he
was extubated on Oct 18th. Liver and renal functions gradually
improved and fever subsided. He was discharged on Oct 24th.
 案例分析
瘧疾至今仍是全世界最重要之寄生蟲疾病之一。目前，全世界超過40%的人口有感染的危險，大部分集中在非洲地區，其他分佈於中南美洲、東南亞等地。全世界每年約有三億多的病例，其中約有兩百萬人死亡。常見的瘧疾依種類可分為間日瘧、三日瘧、卵形瘧與惡性瘧等四種，而其致病原分別是：Plasmodium
vivax、P. malariae、P. ovale和P.
falciparum。其中只有惡性瘧會產生嚴重的併發症。若符合嚴重瘧疾之定義，死亡率更高達20%以上.
瘧疾感染初期症狀為非特異性，發燒為最常見的症狀。因惡性瘧會對紅血球產生多重性感染，所以，發燒型態並無一定規則。除了發燒外，常伴隨顫抖、肌肉酸痛、頭痛及倦怠。實驗室檢查常可見貧血、溶血性高膽紅素血症；血小板減少亦常見。診斷瘧疾主要仍需要做血液抹片檢查。惡性瘧的血液表徵，為可在同一個紅血球上看到多個環形且週邊血液的寄生蟲濃度(parasitemia)往往超過3%。
嚴重瘧疾的定義為：惡性瘧感染再加上以下其中之一種表徵:瘧疾腦病變 (心智狀態改變、抽筋、甚至昏迷)、低血糖 (
serum glucose < 50 mg/dL
)、肺水腫或成人呼吸窘迫症候群（acute respiratory distress
syndrome；ARDS）、嚴重貧血( hematocrit< 20%
)、腎衰竭 (多為寡尿性
[oliguric])、休克、出血傾向（bleeding
diathesis）、代謝性酸血症 ( pH<
7.25)、血紅素尿（hemoglobulinuria）以及血中寄生蟲濃度超過5%
等。
產生嚴重惡性瘧感染的機制至今未明。大致的病理機轉為：被感染的紅血球因細胞膜的改變，形成cytoadherence的現象，致使組織灌流(perfusion)降低，因而產生乳酸中毒；腎臟血流量降低而造成腎小管壞死，腦部血流改變形成昏迷等。另一方面，瘧原虫的表面抗原會經由一些醣蛋白表現，活化單核球，釋放cytokines。目前已被證實的有：TNF-α
( tumor necrosis
factor-α)、IL-1、IL-6、IL-8
等。這些cytokines的分泌會使血管阻力（vascular
resistance）降低，因而造成急性非心因性肺水腫（non-cardiogenic
lung edmea）、溶血性貧血（hemolytic
anemia）等併發症。
本案例旨在強調，任何一位發燒病患的病史詢問中，一定要問及他過去和最近的旅遊史；對於任何一位從疫區旅遊或工作回來的人，發生發燒腹瀉等病症時，應立即採血作抹片檢驗。
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Case Discussion
繼續教育考題