MENINGOCOCCAL DISEASE
流行性腦脊髓膜炎
馬偕醫院小兒感染科
紀鑫醫師
The Disease Which Raged During the Spring of 1805
Gaspard Vieusseux
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.
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
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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.
Chemical Structure of Group-Specific
Polysaccharide Capsules of Meningococci
Group
Chemical Composition of Capsule
A
2-Acetamido-2-deoxy-D-mannopyranosyl
phosphate
-2.8 N-acetylneuraminic acid
-2,9 O-acetylneuraminic acid
Composition not known
2-Acetamido-2-deoxy-D-glucopyranosyl phosphate
4-O--D-glucopyranosyl-N-acetylneuraminic acid
Composition not known
3-deoxy-D-manno-octulosonic acid
4-O--D-galactopyranosyl-N-acetylneuraminic acid
B
C
D
X
Y
Z
29E
W135
• 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
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inversely to age
upper respiratory pathogens
smoke and passive smoke
family members
late complement component deficiencies
alternate pathway (properdin) deficiency
Clinical manifestations
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Serious/Invasive Disease
Conjunctivitis
Pharyngitis
Meningococcal Pneumonia
Meningococcal Pericarditis
Mesenteric Adenitis and Peritonitis
Infections of the Genitourinary Tract
Chronic Meningococcemia
Symptoms and Signs
• 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.
• 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.
Signs and Symptoms in Serious
Meningococcal Disease
Clinical Feature
Per Cent at Presentation
Fever
71-88.8
Rash
68.4-71
Shock
38-42
Vomiting
34-67
Lethargy
30-55
Headache
34
Irritability
21-34
Poor feeding
18
Cough or rhinorrhea
18
Seizures
8-10
Laboratory findings
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Leukopenia <5000/ mm3 : 21 %
Thrombocytopenia : 14 %
Hyponatremia(SIADH): 7%
DIC
Acidosis
Liver function
Diagnosis
• Culture: Gold standard
Blood 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 tests
Specificity : 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
Chemoprophylaxis
Drug
Age Group
Dose
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
Duration
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
(serogroups) ，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。