1. Meningococcal infection
Lecture for students of JSC "MUA"
Department of infectious diseases, epidemiology and
immunology
Made by associated prof. Konkayeva M.E.
3. Definition
Meningococcal infection is an acute infectious
disease caused by meningococcus
Neisseria meningitidis…
with aerosol transmission of causative
microorganism;
which characterized by affection of mucouse
layer of nasopharynx (nasopharyngitis),
generalization in form cepticaemia
(meningococcaemia) and inflammation of pia
mater (meningitis).
4. Meningococcal meningitis
It is known from ancient times
Firstly was described by Celsus (I century
BC), Aretha (II century BC), Pavel Eginsky
(VII century BC).
First scientific description was given by
Willis at 1661.
Causative agent meningococcus
(Neisseria meningitidis) was revealed at
1887 by A.Wekselbaum.
5. Etiology (1)
Causative agent of disease is Wekselbaum
meningococcus — Neisseria meningitidis.
gram-negative diplococci, immovable, with no
filaments and capsule, do not form spores.
It grows in medium which contains human or
animal protein. Grow in optimal temperature —
37°С. Aerobe and facultative anaerobe.
6. Etiology (2)
Meningococci contain endotoxin
Divides into few serogroups from A to Z.
Mostly serogroup A meningococci was
extracted from patients in period of
epidemic raise of morbidity.
Now a days serogroups B and C are
revealed often.
10. Epidemiology
People without any clinical manifestations —
meningococci carriers and patients with not revealed
nasopharyngitis (similar to acute respiratory diseases)
epidemiologically constitute more danger .
The infection occurs in winter-spring periods
predominantly. Children are more sicky to this
infection — about 8-10 % from all generalized forms
occur in children under 14 years.
Epidemic raise of morbidity rate is observed every 10-
15 years which can could be connected with
microorganism alternation and decrease of
community immunity.
11. Meningococcal infection in the world
The highest morbidity is seen in African
countries,
especially in Central and West part (so called
«meningitis belt»).
12. Risk factors
Traditionally, this disease belongs to «military» infections, so
far as incidence rate directly correlates with wars, also with
major disasters and accidents.
Stress from one side and congestion of people with poor living
conditions from the other side are characterized by high risk of
meningococcal infection.
If amount of meningococci carriers in community reaches 20%
and more, this means appearing of clinically manifested forms
of infection.
Physical and mental overwork, also overcooling are
predisposing moments in contraction of disease (decrease of
IgA in secret of mucouse membrane of respiratory tract and
IgG in blood).
14. Infectious element
Сausative agent runs into organism through repiratory system.
After contamination it can persist in mucouse membrane of nasopharynx for
a long time, multuply and discharge with nasopharyngeal mucouse to the
environment which goes with high rate of latent form — meningococci
carrier.
In case of local immunity reduction, disorders of biocenosis meningococcus
runs into submucouse membrane causing inflammation, this goes with
phase of primary focality, and clinically — nasopharyngitis.
Only in 5% of patients with nasopharyngitis meningococcus crosses the
local barriers and runs into vessels of submucouse membrane, spreads
hematogenously turning the diseases into phase of generalization, clinically
this phase is manifested in form of meningococcaemia or bacteraemia.
Hematogeous dissemination of agent in some cases leads to secondary
focality of pathogenesis, gives place to formation of secondary focal form of
infection. Meningococci penetrates meninges, skin, joints, retina, suprarenal
glands, lungs, myocard and other organs.
15. Toxical element
Infectious toxic shock associated with reaction of
immune system to toxinaemia plays main role in
pathogenesis of sever forsm of meningococcal infection.
Alongside shock disseminated intravascular
coagulopathy and deep metabolic disorders may occur
and thus leads to severe and nonreversible damage of
vital organs.
The cause of death in generalized forms of disease
might be acute cardiovascular insufficiency, edema of
brain and lungs and acute renal failure.
Mortality in meningococcal infection reaches 12,5 %.
Type-specific immunity is formed after having illness.
16. Pathogenesis of meningoencephalitis
During the penetration of meningococcus to meninges the clinical and
pathomorphological findings of meningitis are formed. Inflammatory
process is formed in pia mater and pia arachnoid in the beginning
(showing meningitis syndrome) and then can perivascularly spread to
brain substance and often limited by outer layer of cortex reaching white
substance (syndrome of encephalitis).
Inflammation in first hours is serous, then — pyogenic. Location of
exudate: on surface of frontal and parietal area, basal brain and spinal
medulla surface, in tunic of strating sections of cranial nerves and spinal
roots (neuritis). In case of damage of ependyma of ventricles the
ependymitis occurs.
If the disorder of circulation of cerebrospinal fluid takes place, the exudate
might accumulate in ventricls which leads to (in children) hydrocephaly or
pyocephalus. The increasing of intracranial pressure may lead to extrusion
of brain by cerebral axis and tonsillar herniation into foramen magnum with
compression of medulla oblongata (death from respiratory paralysis).
17. Classification (1)
by V.I.Pokrovskyi there are:
Localized forms:
Meningococci carrier and
Acute nasopharyngitis;
Generalized forms:
meningococcaemia,
meningitis,
meningoencephalitis
combined;
Rare forms:
endocarditis,
polyarthritis,
pneumonia,
Iridocyclitis.
The most spread
generalized forms in young
people are meningitis in
combination with
meningococcaemia, rarely
— meningococcaemia
without meningitis, also
meningoencephalitis.
19. Acute nasopharyngitis
It is the primary focalty form
Characterized by high body temperature (till
38,5°С) which lasts 1-3 days.
General intoxication (fatigue,headache,
dizziness) and
Nasopharyngitis (nasal stuffiness, hyperemia,
dryness,swollen pharyngeal walls with
hyperplasia of lymphoid folliculi .
Process can be limited ny primary focalty, but it
also can turn to generalization -
meningococcaemia or secondary focalty.
20. Meningitis
Acute onset with shivering attack and high body temperature (38—40°С).
Expressed general weakness, pain in eyeglobs, then – headache. Headaches raises
rapidly, becomes extended, excruciating, bursting or pressing character.
Vomiting which does not bring relief occurs.
Hyperethesia, photophobia, lethargy, sleep disorders.
In severe cases – alteration of consciousness.
After 12-14 hours from beginning of disease, symptoms of meningeal irritation occur
(neck stiffness, Kernig's symptom, Brudzinskyi's symptom).
Decrease of peritoneal, periostal and tendon reflexes, also their discontinuity
(anisoreflexia).
Damage of cranial nerves from first days — facial nerve, oculomotor nerves (III, IV и
VI pairs), rarely — sublingual and trigeminal nerves.
In blood — high WBS and neutrophil count, left deviation, acceleration of ESR.
Cerebrospinal fluid – high pressure, cloudy, very high neutrophil count, high level of
proteins.
Only in some patients (45%) in 1-5 days the symptoms of nasopharyngitis develops.
24. Meningoencephalitis
To the end of first day and beginning of second day of disease, the
alterations of consciousness like profound sopor, psychomotor agitation,
seizures often with visual and auditory hallucinations.
Alongside meningeal symptoms get raised. After 24 hoursfrom the beginning
of disease most patients have attribute meningeal position (patient lies on
his side with incurvated legs and head back).
There are also cerebral symptoms like pyramidal insufficiency: central
bifacial weakness, expressed anisoreflexia of tendon and periostal reflexes,
sharp pathologic symptoms, spastic hemi- and paraparesis, rarely — palsy
with hyper- or hypoesthesia, coordination disturbances.
Focal damages of brain substance are revealed in form of damage of cranial
nerves. There may be cortical abnormalities like mental disturbance,
incomplete or complete amnesia, visual and auditory hallucinations,
euphoria or depression.
26. Meningococcaemia
In first hours of disease the scanty petechial skin rash with
sporadic starlike elements (with diameter of 2-3 mm, irregulare
shape, above the skin, indurated touch) occurs on lower
extremities and trunk.
In case of advance of disease — increase of body temperature
to 40°С. Hemorrhagic rash is plethorical, petechial and starlike.
Rash elements can enlarge in sizes reaching 5-15 and more
sm in diameter, with skin nesrosis.
There are also scleral, conjuctival hemorrhages and
hemorrhages into mucous membrane. Also other hemorrhagic
findings can be observed: nasal, stomach and uterine
bleedings, micro- and macrohaematuria, subarachnoid
hemorrhage.
29. Complications
The most dangerous and frequent
complications in young people are:
Infectious-toxic shock
DIC syndrome
Brain edema
30. Infectious-toxic shock
There are 3 degrees of shock.
1-degree shock (compensated): severe general
condition, often agitation, motor anxiety; rash is often
small; tachycardia, mild dyspnea; BP is normal; but pulse
pressure might be decreased; urine output is low.
2-degree shock (subcompensated): agitation turns to
lethargy; pallor; acrocyanosis; rash is larger, with
necrosis; tachycardia; dyspnea; BP is decreased no less
than to 1/3 from initial level, which is 85/60 - 60/20
mm.Hg in normotonics; oligoanuria.
3-degree shock (decompensated): total cyanosis ("death
spot"); hypothermia, anuria; filiform or undefined pulse;
BP is 50/20 - 0/0 mm.Hg., consciousness is maintained;
сохранено; in brain edema — loss of consciousness and
seizures.
31. Brain edema
Occurs mostly in the end of first 24 hours and in the beginning of second one.
During the stormy course of meningitis the loss of consciousness develops.
Patients do not react to strong stimulus.
General tonic-clonic muscle activity occurs and develops.
The loss of cornel reflexes, myosis and poor reaction to the light are observed.
Bradycardia turns to tachycardia.
BP is labile in the beginning, with tendency to decrease, in terminal stages — high
and reaches в 150/90-180/110 mm.Hg.
Dyspnea raises to 50—60 breathes per minute, breathing becomes noisy, shallow,
with participation of breathign muscles, then it becomes arythmic.
Meningeal syptoms expire, cerebrospinal fluid pressure decreases. Involuntary
defaecation and urination may be observed.
Pulmonary edema develops, hemiparesis occurs.
Death occurs when breathings stops due to respiratory paralysis, cardiac activity may
last more 5-10 minutes.
32. Diagnosis (1)
Diagnostics is based on clinical and epidemiological
findings.
The most important clinical findings are:
Acute onset of disease,
Expressed sypmtoms of intoxication — high body
temperature, shiver, loss of appetite, sleep disorders,
pain in eyeglobs, muscles of whole body, somnolentia or
agitation;
Developing menigeal symptoms — headache, general
hyperesthesia, nausea, vomiting, changes of peritoneal,
tendon and periostal reflexes, neck stiffness, Kernig's and
Brudzinskyi's symptoms.
33. Diagnosis (2)
Counting the peracute course of meningococcal
infection, the optimal time-line for diagnostics should
be first 12 hours from the beginning of disease;
appropriate treatment which was begun in this time-
line leads to full recovery of patients.
However we must take into account that in first hours
of disease there may be no meningeal symptoms
(neck stiffness, Kernig's and Brudzinskyi's symptoms
and others)
34. Laboratory-clinical study
Lumbar puncture:
The pressure of cerebrospinal fluid is increased.
In the end of first 24 hours it becomes cloudy,
albumino-cytologic dissociation is observed and
globulin-rich reactions (Pandi, Nonna-Appelt) are
sharply positive.
Low level of glucose and chlorides.
Very high neutrophil count
In peripheral blood:
High WBS count, left deviation
From second 24hours— acceleration of ESR.
38. Microscopy of cerebrospinal fluid or blood
Intracellular location
of meningococci
in cerebrospinal
fluid
Gram-negative cocci are found, mostly located
inside neutrophils which is goes with probable
case of meningococcal infection.
39. Serologic study
Based on finding the antibodies in paired
serums with passive hemagglutination
test.
Test becomes confirming in case of rising
antibody titres for4 times and more.
40. Bacteriological study
The main conformative method is bacteriological. Study of:
Cerebrospinal fluid which must be delivered to bacteriological
laboratory as soon as possible after lumbar puncture, not letting
its cooling because meningococci are not resistant in the
environment.
Nasopharyngeal mucus, material is taken by sterile cotton swab
and immediately is being seed on serum agar and medium with
ristomycin (delivery to the laboratory without inoculated cotton
swabs is not admitted).
Blood culture (5-10 ml) taken from vein into matrass with 50 ml
0,1 % of semisolid agar.
42. Differential diagnosis
Held with meningitis caused by various
microbial flora: pneumococci,
H.influenzae, staphylococci, streptococci,
candida and others.
Meningococcaemia should be
differentiated from measles, rubella,
Henoch-Schonlein purpura and etc.
43. Treatment
In acuity of disease the complex therapy is
performed, which includes prescription of:
etiotropic and
pathogenetic agents
44. Management of meningitis
Dehydration therapy.
Low-molecular compounds are used: rheopolyglucin, sorbitol,
sorbite, mannitol. Glycerin is useful for peroral taking. Protein
medications (albumin), diuretics (lasix). Limbar puncture is
performed.
Etiotropic therapy.
The best medicine is penicillinum: cross the blood-brain barrier
not toxic.Dose is 100-500 ths.Un. per kg in 24 hours. Single
dose is 2-3 mil.units by 7-8 times a day.
In severe forms of disease:
Gluco-corticosteroids, but alongside increasing the dose of
antibacterial drugs, because glucocorticoids condense the
blood-brain barrier.
45. Treatment of meningococcaemia
Thsi firstly is the treatment of infectious-toxic
shock.
Prescriptions: detoxication therapy with
glucocorticoids, and artificial diuresis.
Antibiotics with cidal effect (penicillinum) are
useless in this situation, so as their use leads to
massive dying of microorganism and
exacerbates shock.
Chloramphenicol succinate is used i.m. in 1 ml 4
times a day.
46. Treatment of nasopharyngitis
Is being treated only in in-patient hospitals
Peroral antibiotics are used,
cephalosporins
Local treatment, physiotherapy (far
ultraviolet, high-frequency therapy.
47. Etiotropic therapy
Drug of choice - benzylpenicillin, 200 ths. UN/kg/day; every 4 hrs i.m. (might
be interchanged with i.v.).
Combinate with agents which omproves the cross through blood-brain
barrier; they are -
Caffeine sodiobenzoate (single dose 4-5 mg/kg),
furosemide (0,3-0,6 mg/kg) and
NaCl and glucose solutions (15—20 ml/kg);
All these medicine must be given i.v. every 8hrs.
Duration of therapy is 6—7 days. Indication for therapy cancellation is low
decrease of cytosis less than 100 cells in 1mcl in cerebrospinal fluid with
predominantly lymphocytes
Store drugs are used in case of idiosyncrasy of penicillinum, absence of
therapy effect:
Chloramphenicol succinate is used by 1,0—1,5 g i.v.or i.m. every 8hrs
Rifampicin — per os or parenteral taking by 0,6 g every 8hrs
48. BUT the etiotropic treatment of patients
with shock must be started with
chloramphenicol succinate by 1,5 g every
8 hrs parenterally, till the full egestion from
shock.
49. Pathogenetic therapy
Directed to the rehydration and detoxication.
500 ml NaCl is given i.v. (5% glucose solution, Ringer's solution) by using
prednisolone in dose of 120 mg (i.v.) and 5—10 ml 5% ascorbic acid solution
at the same time.
In case of sudden drop of BP - 1 ml 1% mesatone solution in 500 ml of
NaCl.
Use of colloid solutions is inappropriate (hemodez, polyglucin,
rheopolyglucin and etc.) due to high risk of acute cardiovascular insufficiency
and pulmonatu edema (especially during injection of high amount of these
solutions — to 1 liter and more).
For arresting of hypertonic dehydration it is better to use isotonic cristalloid
solutions. The speed and duration of perfusion, total amount of injected fluid,
glucocorticoids, pressor amine must be regulated depending on level of BP
and diuresis.
Regular auscultation of lungs is necessary 9high risk of pulmonary edema!)
In the initial phase of shock it is obligatory to give i.v. 10—20 ths. Units of
heparinfor prevention of disseminated intravascular coagulopathy syndrome.
50. In early recovery period
After cancellation of etiotropic agents the following agents
are prescribed:
- medicine that improves the brain circulation (trantal or
emoxypine by 2 pills 3 times a day or doxium to 0,25 g 3 times a
day during 3 weeks);
- nootropic agents that normalize tussular methabolism of brain
(pantogam by 1 tablet 3 times or piracetam by 2 capsule 3 times
or aminalone by 2 tablets 3 times a day during 6 weeks);
- from 4th week of recovery treatment agents with adaptogenic
activity are prescribed: pantocrine by 30-40 drops 2 times a day or
may chang 30-40 drops 2 times a day or eleuterococcus by 30-40
drops 2 times a day during 3 weeks.
- on duration of whole recovery period patients receive
multivitamins (undevit,hexavit), calcium glycerophosphate by 0,5 g
2 times a day and glutamate 1 g 2 times a day.
52. Prevention and arrangements in
the center of infection
The main preventive arrangements are earlier case
detection and their quarantine
Sanitation of meningococci carriers
(benzylpenicillinum 300 ths.units i.m. every 4 hrs during
6 days or bicillinum-5 by 1,5 mil.units i.m. once, or
chloramphenicol by 0,5 ml 4 times a day during 6 days),
Publicity of personal and social hygiene, tempering
and educative activities.
