MENINGOCOCCAL DISEASE流行性腦脊髓膜炎

馬偕醫院小兒感染科紀鑫醫師

It commences suddenly with prostration of strength, often extreme: the face is distorted, the pulse feeble. There appears a violent pain in the head, especially over the forehead; then there comes pain of the heart or vomiting of greenish material, stiffness of the spine, and in infants, convulsions. In cases which were fatal, loss of consciousness occurred. The course of the disease is very rapid, termination by death or by cure. In most of the patients who died in 24 hours or a little after, the body is covered with purple spots at the moment of death or very little time afterward.

The Disease Which Raged During the Spring of 1805 Gaspard Vieusseux

Epidemiology

• In the United States, approximately 3000 sporadic cases occur each year.

• Nasopharyngeal carriage rate: 3-15%

• Belt across sub-Saharan Africa: 1%

• In Taiwan, 81 sporadic cases occurred from 1992 to 2000 including 8 fetal cases.

• In 2001, 30 sporadic cases occurred including 6 fetal cases.

Microbiology

Family Neisseriaceae contains five genera:

• Neisseria

• Kingella

• Eikenella

• Simonsiella

• Alysiella.

Genus of Neisseria

• N. gonorrhoeae

• N. meningitidis

• N. kochii

• N. sicca

• N. lactamica

• N. subflava

• N. flavescens

•N. mucosa

•N. cinerea

•N. polysacchreae

•N. elongata

•N. macacae

•N. canis

•N. dentrificans.

N. meningitidis

• gram-negative diplococcus, kidney beans, encapsulated

• facultatively anaerobic, catalase (+) and oxidase (+)

• autolyse when exposed to drying or sunlight

• 13 serogroups currently are recognized: A, B, C, D, H, I, K, L, X, Y, Z, W135, and 29E.

Group Chemical Composition of Capsule

A

BCDXYZ29EW135

2-Acetamido-2-deoxy-D-mannopyranosylphosphate-2.8 N-acetylneuraminic acid-2,9 O-acetylneuraminic acidComposition not known2-Acetamido-2-deoxy-D-glucopyranosyl phosphate4-O--D-glucopyranosyl-N-acetylneuraminic acidComposition not known3-deoxy-D-manno-octulosonic acid4-O--D-galactopyranosyl-N-acetylneuraminic acid

Chemical Structure of Group-Specific Polysaccharide Capsules of Meningococci

• Serogroups A, B, and C account for more than 90 % of meningococcal disease worldwide.

• Serogroup A: periodic epidemics in developing countries, is responsible for only 3 % of in the United States.

• Serogroup B: sporadic disease but occasionally is associated with outbreaks.

• Serogroup C: associated with numerous outbreaks in the United States, Canada, and Europe.

• Serotype Y: has been associated with meningococcal pneumonia in military recruits.

• The germ is spread by direct contact with secretions from the nose and throat, such as by kissing, coughing, sneezing, and sharing of cigarettes, drinks, and food.

• Prevalence : winter and spring

• Incubation period: 1-10 days, most < 4 days

Risk factors

• inversely to age

• upper respiratory pathogens

• smoke and passive smoke

• family members

• late complement component deficiencies

• alternate pathway (properdin) deficiency

Clinical manifestations

• Serious/Invasive Disease

• Conjunctivitis

• Pharyngitis

• Meningococcal Pneumonia

• Meningococcal Pericarditis

• Mesenteric Adenitis and Peritonitis

• Infections of the Genitourinary Tract

• Chronic Meningococcemia

• Symptoms are usually sudden and initially are like the flu: fever, feeling generally unwell, headache, vomiting, and in some cases a stiff neck.

• People with this disease are visibly sick and may be confused, excited, or drowsy.

• Sometimes a reddish-purple rash that may look like bruises appears.

Symptoms and Signs

• The rash is flat and smooth, does not itch, and may spread quickly once it starts.

• In rare cases, the symptoms are followed by lowered blood pressure, shock, delirium, sudden extreme weakness, coma, and death.

• Because the disease spreads quickly in the body, it is important to see a physician immediately if symptoms suggesting meningococcal disease develop.

Clinical Feature Per Cent at Presentation

Fever 71-88.8Rash 68.4-71Shock 38-42Vomiting 34-67Lethargy 30-55Headache 34Irritability 21-34Poor feeding 18Cough or rhinorrhea 18Seizures 8-10

Signs and Symptoms in Serious Meningococcal Disease

Laboratory findings

• Leukopenia <5000/ mm3 : 21 %

• Thrombocytopenia : 14 %

• Hyponatremia(SIADH): 7%

• DIC

• Acidosis

• Liver function

Diagnosis

• Culture: Gold standardBlood culture alone is positive about 50 %

• Gram stain: Rapid diagnosis

• Counterimmunoelectrophoresis and latex agglutination: Cross reaction to E. coli or bacillus

• Polymerase chain reaction : newer testsSpecificity : 91 %

Case Definitions for Invasive Meningococcal Disease

Therapy• For penicillin-susceptible meningococcemia

or meningitis, iv penicillin G, 250,000 units/kg/day every 4 hours for 7 days.

• Third-generation cephalosporins, ceftriaxone (100 mg/kg/day iv in two divided doses) and cefotaxime (200 mg/ kg/day iv in four divided doses

• Steroid therapy is controversal

Presenting Features of Meningococcal Infection Associated with Poor Prognosis

• Presence of petechiae < 12 hours before admission

• Presence of hypotension (systolic <70 mm Hg) • Absence of meningitis (<20 WBC/mm3) • Peripheral white blood cell count <10,000/mm3

• Erythrocyte sedimentation rate <10 mm/hour

Stiehm, E. R.et al J. Pediatr 1966

Additional prophylactic

• Rifampin, 10 mg/ kg/dose (maximum, 600 mg/dose) every 12 hours for 2 days

• Single ceftriaxone (125 mg IM for children < 12 years of age or 250 mg IM for those > 12 years of age)

Disease Risk for Contacts of Index Cases of Invasive Meningococcal Disease

Drug Age Group Dose Duration

Rifampin <1 month 5 mg/kg q 12 hr 2 days

> 1 month 10 mg/kg q 12 hr 2 days

Adults 600 mg q 12 hr 2 days

Ciprofloxacin Adults 500 mg Single dose

Ceftriaxone <15 years 125 mg IM Single dose

Adults 250 mg IM Single dose

Chemoprophylaxis

Recommendations for Administration of

Meningococcal Vaccine

腦膜炎雙球菌 (Neisseria meningitidis)

• 革蘭氏陰性球菌，成對存在。• 流行性腦脊髓膜炎，法定傳染病。 • 2-30% 正常人的鼻咽部就可能存在。• 到目前為止已經發現有十三種血清群 (serogro

ups) ，其中以 A 、 B 、 C 、 W135 與 Y 等五種血清群最常導致疾病。

• 大多出現於冬天與春天• 容易在開發中國家發生流行

• 菌血症 : 有時只表現出伴隨發燒的上呼吸道感染症狀，這種菌血症有時會自行痊癒，有時則導致腦膜炎。

• 敗血症 : 臨床症狀很像一般的感冒，包括發燒、喉嚨痛、肌肉痛、頭痛與全身無力。

• 腦膜炎 : 出現腦膜炎的時候，會有嚴重頭痛、嘔吐、頸部僵硬等現象。

• 散發性血管內凝血 : 導致全身出血點、敗血性休克、腎上腺出血、腎衰竭、心臟衰竭與昏迷。

• 二歲以下兒童大約佔受感染病例的一半，但成人也會發病，大約四分之一的病例出現於三十歲以上成人。

• 根據美國的統計，當地嚴重感染的發生率為每年每十萬人有 1.1 位病例，中國大陸與非洲的發生率則為每年每十萬人有 10-25 位病例。

• 台灣地區最近十幾年並不常見這種感染，每年的病例數只有個位數或十幾、二十幾位，但從去年開始，病例數有稍微增加的趨勢。