HERPETIC DISEASE
MENINGOCOCCAL DISEASE
SEPSIS
Herpes
simplex virus (HSV) infections are among the most common maladies
affecting humans. Often they are annoying and troublesome; occasionally they
are life-threatening.
The term herpes is derived from the Greek word meaning to creep,
and clinical descriptions of herpes labialis go back to the time of
Hippocrates. Astruc, physician to the king of
Etiology
Herpes
simplex virus (herpesvirus hominis) shares many
properties with other members of the herpesvirus groups, which in humans
includes varicella-zoster, cytomegalovirus, Epstein-Barr virus, and human
herpesviruses type 6 and 7. The members of this group have an internal core
containing double-stranded DNA, an icosahedral capsid with 162 hollow
capsomeres, and a lipid-containing laminated membrane or envelope (Fig.1).
The overall diameters of enveloped herpesviruses are 150-200 nm.
Replication occurs primarily within the cell nucleus and is completed by the
addition of protein envelopes as the virus passes through the nuclear membrane.
Complete virus replication is associated with lysis of the productive cell. All
members of the human herpesvirus group can also establish latent states within
certain types of cells they infect, although the physical nature of the viruses
during periods of latency is unclear.
Fig.1. Herpes
simplex virus
The development of monoclonal
antibody and restriction enzyme technologies have permitted an even
finer definition of variations among individual HSV isolates. It is now clear
that HSV-1 and HSV-2 share certain glycoprotein antigens and differ with
respect to others. Serologic differentiation between HSV-1 and HSV-2 infections
can be readily made by detection of type-specific gG antibodies.
Epidemiology
Herpes simplex viruses have a worldwide distribution. There are no known animal
vectors for HSV, and although experimental animals can easily be infected,
humans appear to be the only natural reservoir. Direct contact, with
transmission through infected secretions, is the principal mode of spread.
HSV-1 is transmitted primarily by contact with oral secretions and HSV-2 by
contact with genital secretions. Transmission can occur both from overtly
infected persons and from asymptomatic excretors, although virus titers are
higher in persons with active lesions and thus transmissability may be greater.
Approximately 15 % of the adults may be excreting HSV-1 or HSV-2 at
any given time depending on the population studied. For example, because shedding
of HSV-2 is related to sexual activity, prostitutes may have unusually high
rates of excretion.
The risk of heterosexual acquisition of HSV is greater in women than
men, and previous HSV-1 infection reduces the risk of subsequent HSV-2
infection.
Pathogenesis
On entry into skin sites HSV replicates locally
in parabasal and intermediate epithelial cells, which results in the lysis of
infected cells and the instigation of a local inflammatory response. This feries
of events results in the characteristic lesion of superficial HSV infection,
that is, a thin-walled vesicle on an inflammatory base. Multinucleated cells
are formed with ballooning degeneration, marked edema. Such lesions are
indistinguishable from those caused by varicella-zoster
virus. Lymphatics and regional lymph nodes draining the site of primary
infection become involved. Further virus replication may result in viremia and
visceral dissemination, depending on the immune competence of the host.
In murine models the maturity of macrophages at the site of local
infection helps determine whether virus remains localized or disseminates.
Subsequently, other host defense mechanisms, for example, the production of
interferons, natural killer cells, protective antibodies, and sensitized killer
lymphocytes, are elicited to prevent the spread of infection.
Clinical manifestations
Primary HSV-1 infection is frequently
asymptomatic but may present as gingivostomatitis and pharyngitis most commonly
in children under the age of 5 years but occasionally in older persons.
Incubation periods range from
Fig.2. Vesicles in case of herpetic infection
Fig.3. Herpetic infection of gums
Fever and toxicity may persist for many days, and
the patient complains of severe mouth pain. Breath is fetid, and cervical
adenopathy is present. In children, dehydration may result from poor intake,
drooling, and fever. In college-aged persons, primary HSV infection often
presents as a posterior pharyngitis or tonsilitis. Included in the age-related
differential diagnosis are streptococcal or diphtheritic pharyngitis,
herpangina. aphthous stomatitis. Stevens-Johnson
syndrome, Vincent's infection, and infectious mononucleosis.
Herpes simplex virus infections of the eye are
usually caused by HSV-1 (Fig. 4).
Fig.4. Herpetic infection of eye
Primary infections may be
manifested by a unilateral follicular conjunctivitis with regional adenopathy
and/or a blepharitis with vesicles on the lid margin. Photophobia, chemosis,
excessive tearing, and edema of the eyelids may be present. Some patients
develop dendritic figures or coarse, punctate, epithelial opacities. If disease
is limited to the conjunctiva, healing takes place within 2-3 weeks. However,
if systemic symptoms and signs of stromal involvement are
present, the healing phase may be delayed. Spontaneous healing of the
conjunctiva and cornea is usually complete.
Primary genital infection is most common in
adolescents and in young adults and is usually (in 70-95 % of the cases) caused
by HSV-2 (Fig.5).
Fig.5. Herpes genital infection
The
duration of incubation periods 2-7 days. In men, vesicular lesions on an erythematous base usually appear on the
glans penis or the penile shaft. In the female, lesions may involve the vulva,
perineum, buttocks, cervix, and vagina and are frequently accompanied by a
vaginal discharge). Extra-genital lesions occur during the course of primary
infection in 10-20 % of patients. Primary infection in both sexes may be
associated with fever, malaise, anorexia, and tender bilateral inguinal
adenopathy. Although vesicular lesions may persist for several days in men, in
women they rapidly ulcerate and become covered by a grayish-white exudate. Such
lesions may be exquisitely tender, and urethral involvement may result in
dysuria or urinary retention. Herpetic sacral radiculomyelitis
accompanying genital infection may also lead to urinary retention, neuralgias,
and obstipation; in such patients a loss of anal tone, diminished
bulbocavernosus reflex, and cystometrographic evidence of lower motor neuron
dysfunction can sometimes be demonstrated. Lesions of primary genital herpes
may persist for several weeks before healing is complete. Previous HSV-1
infection may reduce the severity and duration of a first episode of genital
herpes caused by HSV-2. In the diagnosis of genital herpes other sexually
transmitted infections such as chancroid or syphilis, erosions secondary to
excoriation, genital manifestations of Behcet syndrome or erythema multiforme,
and local candidiasis must all be distinguished.
Although primary infections are usually in
perioral, ocular. or genital
areas, any skin site may be initially involved. Primary HSV skin infections may
be extensive and mimic herpes zoster.
Although a dermatomal distribution is not usually maintained
and the pain is less severe.
Primary perianal and anal HSV-2 infection is becoming increasingly well
recognized, both in women and in male homosexuals. Pain is the primary symptom,
with itching, tenesmus, and discharge also noted. Systemic complaints of fever,
chills, malaise, headache, difficulty in urinating, and sacral paresthesias may
be present. On examination, vesicles and ulcerations may be seen in perianal
and sometimes in anal areas. They may become confluent and result in a grayish
ulcerating cryptitis surrounded by a red edematous mucosa. Bilateral inguinal
adenopathy is common. The course is generally self-limited unless bacterial
infection supervenes, with healing occurring in 1-3 weeks. However, in the
setting of the acquired immunodeficiency syndrome (AIDS), herpes proctitis as
well as other cutaneous manifestations of HSV infection may be prolonged and
progressive.
Recurrent infections
Recurrent herpes labialis is
frequently heralded by prodromal symptoms (pain, burning, tingling, or itching)
generally lasting for less than 6 hours but occasionally as long as 24-48
hours. Vesicles appear most commonly at the vermillion border of the outer lip
and are associated with considerable pain. The lower lip is more frequently
involved, although individual patients may have stereotyped lesions at similar
sites during each recurrence. The lesion area is usually less than 100 mm, and
lesions progress from the vesicle to the ulcer/crust stage within 48 hours.
Pain is most severe within the first 24 hours after the appearance of lesions.
Healing is generally complete within 8-10 days. Rarely, recurrences may occur
in the mouth or on the nose, chin, or cheek. Systemic complaints do not usually
accompany recurrent herpes labialis, although local adenopathy may occur.
Ocular infection may recur as keratitis, blepharitis, or kerato-conjunctivitis.
Recurrent keratitis is usually unilateral but is rarely (in 2-6 % of the cases)
bilateral. Two main types of keratitis may develop: dendritic ulceration or
stromal involvement. Branching dendritic ulcers that strain with fluorescein
are virtually diagnostic and are often accompanied by a loss in corneal
sensation. Visual acuity may be decreased because the ulcers frequently involve
the pupillary portion of the cornea. They may be accompanied by minimal
anterior opacification or deep stroma involvement. Occasionally, extensive
ameboid corneal ulcers may evolve, particularly if topical steroids have been
applied. Superficial keratitis usually heals, but recurrent infection may lead
to deep stromal involvement and uveitis, which may in part be mediated by
hypersensitivity reactions to viral or altered cellular antigens. A gradual
diminution in visual acuity takes place, and individual attacks may last for
several months with the formation of dense scars, corneal thinning, and
neovascularization. Permanent visual loss may result, and rarely, rupture of
the globe develops.
Recurrent genital lesions in both sexes are generally associated with
less severe systemic symptoms and less extensive local involvement than are
primary attacks. A prodrome of tenderness, itching, burning or tingling is
often noted for several hours before a recurrence. Lesions in women are most
often noted on the labia minora, labia majora, and perineum and less commonly
on the mons pubis or buttocks. Lesions in men are most often found on the glans
or penile shaft. In women recurrences tend to be more severe. Healing generally
occurs in 6-10 days. Virus shedding diminishes more slowly in women and can
occur between recurrences in both sexes. Occasionally, genital recurrences are
associated with headache and even with aseptic meningitis. Urethral stricture
and labial fusion have also been reported after recurrent genital infections.
Recurrent HSV-1 or HSV-2 infections may develop on extremities; occasionally
such lesions are associated with severe local neuralgia. Local edema and
lymphangitis may also occur during recurrences on extremities.
Complications
Herpes
simplex encephalitis is a rare complication of herpetic
infection and yet is one of the most common acute sporadic viral diseases of
the brain. Although little is known about the pathogenesis of HSV-1
encephalitis in humans, the virus is believed to spread by neural routes into
the brain during either primary or recurrent infection. Temporal lobes are the
principal target areas of the virus, and a necrotizing hemorrhagic encephalitis
results.
Herpes simplex
encephalitis occurs at all ages in both sexes, and in all seasons. The clinical
course may begin suddenly or after a brief influenzalike prodrome. Headache,
fever, behavioral disorders, speech difficulties, and focal seizures are
prominent features; olfactory hallucinations may be present. Cerebro-spinal
fluid examination is variable but frequently shows a moderate pleocytosis with
mononuclear and polymorphonu-clear leukocytes: protein levels are slightly
elevated, and glucose is generally normal. Infectious virus is rarely present
in cerebrospinal fluid during encephalitis, and brain biopsy with appropriate
histologic and cultural techniques is currently the most reliable way to make
the diagnosis. Although various antibody and antigen assays may provide
adjunctive information. they are not sensitive enough
to provide a sufficiently early diagnosis. Rapid diagnosis of herpes simplex
encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid
has been reported by certain research laboratories. Herpes simplex virus
encephalitis must be distinguished from other forms of viral encephalitis,
tuberculous and fungal meningitis, brain abscesses, cerebrovascular accidents,
and brain tumors.
The course in untreated patients is usually one
of rapid deterioration over several days that progresses to coma and death.
Mortality in untreated biopsy-proven cases is 60-80 %, and fewer than 10 % of
the patients are left without significant neurologic sequelae.
Relationship to Other Diseases
Erythema Multiforme.
Allergic cutaneous and mucous membrane disorders may accompany or follow acute
HSV infections. Up to 75 % of all cases of erythema multiforme are regularly
preceded by an attack of herpes simplex. Both HSV-1 and HSV-2 may be involved,
and the cutaneous manifestations range from mild to severe (Stevens-Johnson
syndrome) and may be recurrent. Inactivated HSV antigens injected intra-dermally
into persons subject to erythema multiforme have induced such attacks, and HSV
antigen has been identified in skin biopsy specimens from affected lesions.
Cancer. Although HSV
has been suspected as a cause of cervical and other cancers on the basis of both
epidemiologic and laboratory studies, many recent studies do not support its
etiologic role in human cancers.
Idiopathic Neurologic Syndromes. Herpes simplex virus infections have
been implicated as possible factors involved in the pathogenesis of various
neurologic disorders of unknown etiology, including idiopathic facial paralysis
(Bell's palsy), multiple sclerosis, atypical pain syndromes, ascending
myelitis, trigeminal neuralgia, Mollaret's meningitis, and temporal lobe
epilepsy. The associations are based on the known predilection of HSV for nerve
tissue, on serologic or nucleic acid studies, and on the occasional
observations of temporal relationships between attacks of herpes labialis or
genitalis and attacks of the neurologic syndrome.
Diagnosis
Although experimental animals
and embryonated eggs are susceptible to infection with HSV strains, tissue
cultures have largely replaced these hosts for diagnostic purposes. Primary
human embryonic kidney, rabbit kidney, and human amnion cells readily support
the replication of HSV. Continuous cell strains or cell lines of human diploid
origin and certain continuous monkey kidney cell lines also support HSV
replication, but to a lesser extent. Cytopathic effects usually appear rapidly,
within 24-48 hours if the virus inoculum is high. Cells become rounded and
clump, with rapid progression of cytopathic effects throughout the cell
monolayer. Ballooning degeneration and the formation of multinucleated
syncytial giant cells may be observed, particularly with HSV-2 isolates.
Vesicles contain their highest tilers of virus within the first
24-48 hours, and specimens should be collected early and promptly inoculated
into tissue cultures. If a delay is unavoidable, specimens can be stored in
appropriate carrying medium at 4-9°C for a few hours. but
for longer periods they should be stored at -70°C. Typing of isolates can be
accomplished by using a variety of serologic techniques including
immunohistochemistry or microneutralization. When tissue specimens such as neural
ganglia are being studied for the presence of virus, tissue explanation or cell
cocultivation techniques have proved useful in facilitating virus isolation.
The recent development of monoclonal antibodies to individual herpes
virus antigens should allow for the more precise identification and typing of
HSV isolates. HSV-1 and HSV-2 have both type-specific and cross-reactive
antigens that are useful for both grouping and type discrimination. Moreover
the cloning of herpes DNA fragments in recombinant bacteria may permit the
production of probes to identify herpes genomes in the absence of infectious
virus.
For a rapid diagnosis of skin or mucous membrane
lesions, scrapings from suspect lesions may be smeared, fixed with ethanol or
methanol and stained with Giemsa or Wright preparation. The presence of
multinucleated giant cells indicates infection with HSV or varicella-zoster virus. When using cytologic techniques, the
Papanicolaou cervicovaginal stain or the Paragon multiple stain, intranuclear
inclusions may also be seen. Alternatively, such material can be examined for
herpes antigens by immunohistochemical techniques or by in situ DNA
hybridization.
Serologic techniques may be helpful in diagnosing
primary HSV infections but are rarely of value in recurrent infections. A
variety of assays have been used including neutralization, complement fixation,
passive hemagglutination, indirect immunofluorescence, radioimmunoassay, enzyme
immunoassays, complement-mediated cytolysis, and antibody-dependent cellular cytolysis.
During primary infections, a fourfold or greater rise in titer is observed
between acute and convalescent sera. In recurrent infections such rises may or
may not be observed. Many licensed enzyme immunoassays appear to give
inaccurate information concerning HSV-infecting subtypes.
Measurement of IgM HSV antibodies in infants may be helpful in the
diagnosis of neonatal infection. Such antibodies usually appear within the
first 4 weeks of life in infected infants and persist for many months. Measurement
of IgM antibodies in older persons has not proved useful in separating primary
from recurrent infections.
Approaches to detect specific HSV antigens,
antibodies, or DNA in cerebrospinal fluid are under development. Such
techniques may circumvent the need for invasive procedures such as brain biopsy
to make the diagnosis of herpes encephalitis.
Treatment
A number of nucleoside derivatives interfere with
the synthesis of HSV DNA. Some of these (trifluorothymidine, vidarabine) are
useful in and licensed for the topical treatment of herpes keratitis.
Vidarabine and acyclovir are also useful for systemic HSV infections. None of
these agents affects latent virus.
In the immunocompromised host, acyclovir is
useful as both treatment and suppression of recurrent mucocutaneous HSV
lesions. For the treatment of acute episodes, virus shedding, local symptoms,
and time to healing can be reduced by intravenous or oral regimens (400 mg five
times per day). Acyclovir is also useful in the prevention of herpetic recurrences
in immunocompromised hosts including transplant recipients, leukemics
undergoing induction chemotherapy, and patients with AIDS. Regimens of 200-400
mg two to five times per day have been satisfactory in preventing recurrences
among seropositive patients.
Parenteral acyclovir is indicated for
disseminated or central nervous system HSV infections. In patients with
biopsy-proven HSV encephalitis, acyclovir was compared with vidarabine and
found to be superior in reducing mortality. Doses of 10 mg/kg every 8 hours for
14-21 daysare recommended. In newborns with disseminated HSV infections,
acyclovir and vidarabine appear equivalent but because of ease of
administration, acyclovir is recommended.
Acyclovir has little acute toxicity. Drug-related
neurotoxicity (disorientation, hallucinations, tremors, ataxia, and seizures)
has been described rarely, and reversible renal dysfunction may occur,
particularly following a rapid bolus infusion.
Prophylaxis
Experimental vaccines against HSV have shown promise
in animal models, and some are undergoing human trials. Limited trials in
humans, however, have been unsuccessful, and it is unlikely that a human HSV
vaccine will be generally available in the near future.
The prevention of neonatal disease in the offspring of mothers with
genital infection presents special problems.
MENINGOCOCCAL INFECTION
Definition
Meningococcal
infection is an
acute infectious disease
of the human,
caused by meningococcous Neisseria
Meningitigis. The mechanism of
the transmission of the infection
is air-drop. The disease
is characterized by
damage of mucous
membrane of nasopharynx (nasopharingitis), generalization of
the process in form
of specific septicemia (meningococcemia) and inflammation
of the soft
cerebral membranes (meningitis).
History and geographical
distribution
Epidemic cerebrospinal
meningitis (one of the
most clinically expressive
forms of the
disease) was known else
in profound antiquity. The description
of outbreaks of
this infection is
contained in reports
of Areteus (III century
of our era), Egynsky (VII century).
Epidemic
cerebrospinal meningococcal meningitis was first described by Vieusseaux in
1805. Subsequent reports throughout the nineteenth century confirm its episodic
epidemic nature with a propensity for affecting young children and military
recruits assembled in stationary barrack situations. In 1887, Weichselbaum
isolated the meningococcus from the cerebrospinal fluid, and the etiologic
relationship between this organisms and epidemic meningitis was firmly
established.
Kiefer in 1896 and Albrecht and Ghon
in 1901 found that healthy persons could become carriers of the meningococcus.
Serotypes of the meningococcus were first recognized by Dopter in 1909. This
laid the basis for serum therapy in the treatment of meningococcal infection. The agent was
isolated from the
blood by V. Osler in
1899. It had an
important meaning, because many
problems of pathogenesis
of the disease
were explained. It was
evidence that meningitis
is not single
manifestation of the
disease.
In 1937, sulfonamide therapy
radically altered the outcomes of meningococcal infection. With the advent of
antibiotic agents, treatment of meningococcal infection became more effective,
and mortality declined. With the subsequent world wide emergence of resistant
strains and with the absence of effective chemoprophylaxis, renewed interest in
immunoprevention has occurred and has led to the development of safe and
effective vaccines against the groups A, C, Y and W-135 meningococcal group.
Meningococcal infection
occurs on the
all continents. It is serious
problem for public
health. It is registered
in 170 countries
of the world.
Etiology
The causative agent is Neisseria meningitidis. It is small
gramm-negative diplococcus, aerobic, catalise and oxidase-positive, not-motile
and possess a polysaccharide capsule, which is the main antigen and determines
the serotype of the species. Meningococcus
may be seen inside and outside of neutrophills (Fig.6). The main serogroups of
pathogenic organisms are A, B, C, D, and W135, X, Y, Z and L. The bacterial
membrane is a lipopolysaccaride.
Fig.6. Neisseria meningitidis
The
pathogenic properties of
meningococcus are known
insufficiently, because
meningococcal infection is
anthroponosis. The factors of
pathogenic action of
meningococcus are biological
properties, promoting its attachment
on the mucous
membrane of nasopharynx, depression symbiotic
microflora, penetration
through mucous barriers, toxic properties
and other.
One
of such properties
is specific attachment
or adhesion of
meningococcous to the
cells of epithelium
of respiratory tract. Adhesion is
phenomenon, promoting to colonization
of meningococcus on
the mucus. Physical factors
(adsorption of microbes
on the surface
of the cell)
and fermentative processes
have the meaning
in the appearance
of adhesion.
Meningococci are very exacting
to composition of nutritive mediums. Its
reproduction may be
only in presence
of human’s protein
or animal’s protein. Due
to destruction of the
microbe’s cell endotoxin
is delivered (of lipopolysaccharide origin). Exotoxin is no produced. The agent
of meningococcal infection
is characterized by
low resistance in
the environment.
Meningococci perish during
temperature 50°C through 5
minutes, during temperature 100°C – through
30 seconds. Meningococci have a little
resistance to low temperature.
Epidemiology
Meningococcal infection is typical
anthroponosis. The sourses of infection are
healthy carriers of
meningococcus, the patients with
meningococcal
nasopharingitis and the
patients with generalized forms of
the disease.
The patients with generalized
form are more
dangerous. It is proved
that they are
dangerous for surrounding
persons in 6
times than healthy
carriers. However, the main sources
of the infection
are carriers, because 1200-1800
(according other data – 50000)
carriers have occasion
to one patients
with generalized form
of the disease.
Thus, the patients
with generalized form
of the disease
are the source
of infection for
1-3 % of infected
persons, the patients with
meningococcal nasopharingitis –
for 10-30 %, carriers are
the sources of
infection for 70-80 %
from general number
of infected.
The
level of healthy
carriers promotes the
level of morbility
in certain region. So, carriers may
compose 3-12 %. It is temperate
sporadic morbility. Carriers may achieve
20 %. This
situation is marked
as unsatisfactory. The outbreaks are
observed. Carriers may
achieve 30-40 %. In this case
epidemic of meningococcal
infection arises.
The mechanism of transmission of the infection
is air-drop. The infection is
realized during cough, sneezing. In this
the narrow contact
and sufficient exposition
are necessary. It is
proved by A.A. Favorova (1976)
that the
infection is realized
on the distance
less 0,5 meter.
The
wide distribution of
meningococcal infection is
promoted some causes
in the countries
of equatorial Africa. The
main causes are
connected with social
factors (unsatisfactory
sanitary-hygienic conditions of the life
of the majority
part of the
population, high density of
the population and
other).
In meningococcal
infection one of an important
characteristic of epidemic
process is periodical
rise and fall
of the morbidity. The duration of
the period with
high morbidity is
different. It
may be 5-10
years and more. Then the
period of the
fall of the
morbidity becomes. It is continued
from 5 till
20 years.
In meningococcal
infection epidemic process
is characterized by seasonal
spread. It is manifested
especially during epidemics. The morbidity
may compose 60-70%
from year’s morbidity
during seasonal rise. The
onset of the
seasonal rise is
in quanuary in
the countries with temperate clinimate. It achieves of
maximum in march – april.
The
estimate of the
age morbidity of
meningococcal infection testifies
about that 70-80 %
of the cases
of the diseases
have occasion to
children. Children
of the age
1-5 years compose 50 %. Meningococcal infection
is marked rarely
at the first
three month of
the life.
The
persons of the
young age (15-30 years)
compose the majority
among adult patients. It
is explained by
social factors and
features of the
life young people (service in
the army study
in the educational
establishments, living in the
hostel). These factors explain
predomination of men in the
structure of the
morbidity.
The
age of carriers
of meningococcal infection
is different from
the age of
the patient. The larger part
of carriers is
reveled among adults. The portion of
the children is
a little. The morbidity is
higher in the towns
then rural locality.
The considerable
outbreaks of the
diseases were described
in the educational
establishments of the
closed type and
especially among military (as
at peaceful time
such as during
war).
Pathogenesis
In meningococcal
infection entrance gates
are mucous membrane
of nasopharynx. It is place
of primary localization
of the agent. Further meningococci
may persist in
epithelium of nasopharynx
in majority of
the cases. It is
manifested by asymptomatic
healthy carriers. In some
cases meningococci may
cause inflammation of mucous
membrane of upper
respiratory tract. It leads to
development of nasopharingitis.
The
localization of meningococcus on
mucous membrane of
nasopharynx leads to
development of inflammation
in 10-15 % of
the cases.
The
stages of inculcation
on the mucous
membrane of nasopharynx
and penetration of
meningococcus into the
blood precede to
entrance of endotoxin
into the blood and
cerebrospinal fluid. These stages are
realized with help
of factors of
permeability. It promotes of the resistance
of the meningococcus
to phagocytosis and
action antibodies.
Meningococci are able
to break local
barriers with help
of factors of
spread (hyaluronidase). Capsule protects meningococci from
phagocytosis. Hematogenous
way is the
principal way of
the spread of
the agent in
the organism (bacteremia,
toxinemia). Only the agent
with high virulence
and invasive strains
may penetrate through
hematoencephalitic barrier. The strains of serogroup A high invasivicity.
Meningococci penetrate into
the blood after
break of protective
barriers of mucous
membrane of upper
respiratory tract. There is hematogenous
dissemination (meningococcemia). It
is accompanied by
massive destruction of
the agents with
liberation of endotoxin. Meningococcemia and
toxinemia lead to
damage of endothelium
of the vessels. Hemorrhages are
observed in mucous
membrane, skin and parenchymatous organs. It may
be septic course
of meningococcemia with formation of the secondary metastatic
focuses in the endocardium, joints, internal mediums of the eyes.
In most of the cases penetration of meningococci in the cerebrospinal fluid
and the soft cerebral covering is fought about by hematogenous ways through the
hematoencephalic barrier. Sometimes meningococci
may penetrate into the skull through perineural, perilymphatic and the
perivascular way of the olfactory tract, through the enthoid bone.
Thus the meningococci enter into subarachnoid space, multiply and course serous-purulent
and purulent inflammation of the soft cerebral coverings. The inflammatory
process is localized on the surface of the large craniocerebral hemispheres,
and rarely, on the basis, but sometimes it may spread in the
covering of the spinal cord. During severe duration of the inflammatory process
the cranium is covered by purulent mather (so-cold “purulent
cap”). It may lead
to involvement of
the brain’s matter
into inflammatory process
and meningoencephalitis.
The process may engulf the
rootlets of – VII, VIII, V, VI, III and XII pairs of cranial nerves.
Pathogenic properties
of the agent, state
of macroorganism, state of
immune system, functional state
of hematoencephalitic barrier
have the meaning
in the appearance
of meningitis of
any etiology.
Endothelium of
capillaries, basal membrane,
“vascular pedicles” of
glyocytes and basic
substance of mucopolysaccharide origin
are the morphologic
basis of hematoencephalic barrier. Hematoencephalic barrier regulates metabolic
processes between blood
and cerebrospinal fluid. It
realizes protective function
from the alien
agents and products
of disorder of
metabolism. The most alterations
are observed in
reticular formation of
the middle brain.
In
purulent meningitis some pathogenic
moments are promoted
by rows of
paradoxical appearances in hematoencephalic barrier
and membranes of
the brain. In physiological
conditions hematoencephalic
barrier and brain’s
membranes create closed
space, preventing brain’s tissue
from influence of
environment. In this case
secretion and resorbtion
of cerebrospinal fluid
are proportional. In meningitis
closed space leads
to increased intracranial
pressure due to
hypersecretion of cerebrospinal
fluid and to
edema of the
brain. The degree of swelling-edema of
the brain is
decisive factor in
the outcome of
the disease.
The next
stages may single
out in pathogenesis
of purulent meningitis:
1.
Penetration of
the agent through hematoencephalic barrier, irritation of
receptors of soft
cerebral membrane of
the brain and
systems, forming cerebrospinal fluid.
2.
Hypersecretion of
cerebrospinal fluid.
3.
Disorder of
circulation of the
blood in the
vessels of the
brain and brain’s
membranes, delay of resorbtion
of cerebrospinal fluid.
4.
Swelling-edema of
the brain hyperirritation of the
brain’s membranes and
radices of cerebrospinal
nerves.
Besides that,
intoxication has essential
meaning in pathogenesis
of purulent meningitis. Vascular plexuses
and ependime of
ventricles are damaged
more frequently. Then the
agent enters in
to subarachnoid space
and brain’s membranes
with the spinal
fluid flow.
In some cases, especially in
increated patients the process
may turn
into ependima of
the ventricles. As a
result it may
be occlusion of
the foramina of Lushka, Magendie, the aqueduct of Sylvius. It leads to development
to hydrocephaly.
In the pathogenesis of
meningococcal infection toxic and allergic components play an important role.
Thus, in fulminate forms
of meningococcal infection
infectious-toxic shock develops
due to massive
destruction of meningococcus
and liberaton of
considerable quantity of
endotoxin. In infectious-toxic shock
the development of
thrombosis, hemorrhages, necrosis
in different organs
are observed even
in the adrenal
glands (Waterhause - Fridrechsen
syndrome).
The
severe complication may
develop as a
result of expressive
toxicosis. It
is cerebral hypertension, leading frequently
to lethal outcome, cerebral coma. This
state develops due
to syndrome of
edema swelling of
the brains with simultaneous
violation of outflow
of cerebrospinal fluid
and its hyperproduction. The increased
volume of the
brain leads to
pressure of brain’s
matter, its removement and
wedging of medulla
oblongata into large
occipital foramen, pressure of
oblong brain, paralysis of
breath and cessation
of cardiovascular activity.
Morbid anatomy
In meningococcal infection
pathologoanatomical changes depend on form and duration of the disease.
Nasopharingitis is
characterized by hyperemia of the pharyngeal walls, edema of the epithelial
cells, regional infiltration, hyperplasion and hyperthophy of lymphoid
follicles. Signs of catarrhic inflammation are found in trachea and bronchi.
Cases
of fulminate meningococcal infection is characterized by blood vessels disorders and severe impairments of blood
circulation. The main target are the microcirculation
vessels. The vascular lumen turns narrow, thrombs are found. Thrombs are usually found in small veins.
Hemorrhages into skin, subcutaneous tissue, lungs, myocardium, subendocardial
hemorrhages, hemorrhages into renal parenchyma,
adrenals, brain (Fig.7) and subarachnoidal space are typical.
Fig.7. Hemorrhages into brain
Fig.8. Purulent inflammation
Meningococcous meningitis is
characterized by serous or purulent inflammation of pia mater (Fig.8).
Clinical manifestation
The incubation period is 1-10
days, more frequently
5-7 days.
Classification of the clinical
forms of meningococcal infection:
I. Primarily localized forms:
a) meningococcal
carrier state
b) acute
nasopharyngitis;
c) pneumonia.
II. Gematogenously generalized forms:
a) meningococcemia:
typical acute meningococcal sepsis; chronic;
b) meningitis;
meningoencephalitis;
c) mixed forms (meningococcemia + meningitis,
meningoencephalitis).
d) rare
forms (endocarditis, arthritis, iridocyclitis).
In meningococcal carriers the clinical
manifestations are absent.
Meningococcal nasopharingitis
The most common complains of
the a patients are headache, mainly in the frontal-parietal region, sore
throat, dry cough, blocked nose, fatigue, weakness, loss of appetite,
violation of the
sleep. In most of the patients body temperature rises
upto subfebrile and lasts for not more than 3-7 days, sometimes 5-7 days. The
skin is pale, conjunctival vessels and sclera are
injected. There are
hyperemia and edema of the mucous
membrane of the nose. In many patients the posterior wall of
the pharynx seem to be covered by mucous or mucous – purulent exudation.
Inflammatory changes in the
nasopharynx can be noticed after 5-7 days, hyperplasion of lymphoid follicles
lasts longer (till 14-16 days). In the peripheral blood temperate leukocytosis
with neutrophylosis and a shift of leukocytaric formula to the left, increase
in ERS may be revealed. Nasopharyngitis precedes
to development of
generalized forms of
the disease.
Meningitis
It may
start after meningococcal
nasopharyngitis, but
sometimes primary symptoms
of the disease
arise suddenly. In meningitis
three symptoms are revealed constantly: fever, headache and
vomiting. Temperature is increases
quickly with chill
and may reach
40-41°C
during few hours. Intermittent, remittent, constant, double waved
types of the
temperature occur in
meningitis. The patients
suffer from severe
headache, having diffuse or
pulsatory character.
Headache is very
intensive at the
night. It increases due
to change of
body position, sharp sounds, bright light. Vomiting arises
without precedent nausea. There
is no connection
with food and
relief after vomiting. It
is rule abundant, by “fountain”, repeated. Sometimes,
vomiting arises on
the peak of
headache.
In meningitis
hyperthermia, hyperkynesia, photophobia, hyperalgesia, hyperosmia are
noticed. These symptoms are
revealed more frequently
in children. The severe
convulsions arise in
the many patients
at the first
hours of the
disease (clonic, tonic or mixed
types). In small children
meningococcal meningitis may
start with convulsions.
The
disorders of consciousness occupy
the great place
in clinical picture (from
sopor till coma). The
loss of consciousness develops
after psychomotoric excitement. The loss
of consciousness at the
first hours of
the disease is
unfavorable sign.
During objective
examination meningeal symptoms
stand at the
first place. It is
described near 30
meningeal signs. A few
meningeal signs are
used in practice: rigidity of
occipital muscles, Kernig’s symptom, Brudzinsky’s symptom (upper, middle and
lower). The estimate of
state of fontanelle
is very important
in infants. There are
three symptoms of
meningitis in infant: swelling, tension and
absence of fontanelles
pulsation.
There
is no accordance
between expression of
meningeal syndrome and severity
of the disease. The
expression of different symptoms
is no similar
at the same
patient. The patient has
compulsory pose during
serious cases. He lays
on side with
deflection of the
head backwards
(Fig.9). The legs
are curved in
knee-joint and pelvic-femoral joint. The
legs are pulled
to abdomen. Asymmetry and increased
tendinous, periostal and dermal
reflexes are observed
in the patients. These reflexes
may be decreased
during expressive intoxication. Pathological reflexes
may be revealed (such as
Babinski’s, Hordon’s,
Rossolimo’s reflexes, foot’s
clones), and also symptoms
of damage cranial
nervous (more frequently III, VI, VII, VIII pairs).
Fig.9. Patient’s
specific pose in case of meningitis
The multiple
symptoms of the lesion of
the other organs
and systems are
connected with intoxication. There is
tachycardia at the
first hours of
the disease. Then it
may be bradycardia. Arrhythmia, tachypnoea (30-40
times in minute)
are possible. The tongue
is covered by
dirty brownish coat. It
is dry. Abdomen is
pulled inside. There is
tension of abdomen muscles.
The
external appearance of
the patients is
very typical. There is
hyperemia of the
face and neck. Sclera’s vessels
are injected.
In
hemogram high leukocytosis, neuthrophylosis with
shift of formula
to the left, increased ERS
are observed. Small proteinuria, microhematuria,
cylinderuria are marked
in urine.
Fulminate course of
meningitis
With syndrome of
brain’s swelling and
edema is the
most unfavorable variant. There is
hypertoxicosis during this
form and high
percentage of mortality. The main
symptoms are consequence
of inclination of
the brain in
to foramen magnum
and strangulation of
medulla oblongata by
tonsils of cerebellum.
Immitant symptoms from
cardiovascular and respiratory
systems develop quickly. Bradycardia appears. Then
it is changed
by tachycardia. Arterial pressure
may fall catastrophically, but it
increases more frequently
till high level. Tachypnoea arises (till
40-60 times/min) with
help of axillary
muscles. The disorders of
breath lead to
its sudden interruption. These symptoms develop in hyperthermia, clonic cramps
and loss of
consciousness. Cyanosis of the
skin, hyperemia of the
face are marked. Pyramidal signs,
sometimes symptoms of
damage of cranial
nerves, decreased corneal reflexes
contraction of pupils
and its decreased
reaction on light
are determined. Death occurs
due to respiratory
failure at the
first hours of
the disease, rarely on
2-3 day or
on 5-7 day.
Meningitis with syndrome
of cerebral hypotension
It is
rare variant of the
course of meningococcal
meningitis. It is observed
principally in children.
The
disease develops impetuously, with sharp
toxicosis and exicosis. Stupor develops
quickly. Cramps are possible. Meningeal signs
are no expressive,
because, the diagnostics is
difficult. Intracranial
pressure rapidly falls. In
this case the
volume of the
fluid in the
brain’s ventricles decreases. Ventricular collapse
develops. In infant the
large fontanelle is
depressed. In adults and
children supporting moments
in diagnostics are
clinical signs of
dehydration and hypotension
of cerebrospinal fluid, which
flows out by
rare drops. The fall
of intracranial pressure
may lead to
development of severe
complication – subdural hematoma.
Meningitis with syndrome
of ependimatitis (ventriculitis)
Now it
is rare form
of meningitis. This form
develops during late
or insufficient treatment
of the patients. Especial severity
of the disease
is connected with
spread of inflammation
on ventricles membranes (ependime) and
involvement of brain’s
substance in to
pathological process.
The
principal clinical symptoms
are total and
expressive muscular rigidity. The
patients accept the
particular pose. The disorder
of psychic, sleeping, tonic
and clonic cramps
are observed. The body temperature is
normal or subfebrile
during general severe
state of the
patient. Vomiting is constant
symptom. Hydrocephalia and cachexia
develop due to prolonged
course and (or)
noneffective therapy of
ependimatitis.
Meningoencephalitis
It is rare form of meningococcal infection. In this case the symptoms of encephalitis predominate, but meningeal syndrome is weakly expressed. Meningococcal encephalitis is characterized by rapid onset and impetuous cramps, paresises and paralyses. Prognosis is unfavorable. The mortality is high and recovery is incomplete even in modern conditions.
Meningococcemia (meningococcal sepsis)
The disease is more impetuous,
with symptoms of toxicosis and development of secondary metastatic foci. The onset of the disease is an acute. Body temperature may
increase upto 39-41 0C and lasts for 2-3 days. It may be continous, intermittent,
hectic, wave-like. It is possible the course of the disease without fever. There
is no accordance
between degree of
increasing of the
temperature and severity
of the course
of the disease.
The other
symptoms of intoxication
arise simultaneously with
fever: headache, decreased
appetite or its absence,
general weakness, pains in
the muscles of
the back and
limbs. Thirst, gryness
in the mouth, pale skin or cyanosis,
tachycardia and sometimes
dysphnoea are marked. The arterial pressure increases in
the beginning of
the disease. Then it decreases. It may
be decreased quantity
of urine. Diarrhea may
be in some
patients. It is more
typical for children.
Exanthema is more clear, constant and
diagnostically valuable sign
of meningococcemia.
Fig.10. Exanthema in case of
meningococcemia
Dermal
rashes appear through 5-15
hours, sometimes on the
second day from
the onset of
the disease. In meningococcal
infection rash may
be different over
character, size of
rash’s elements and
localization. Hemorrhagic rash
is more typical (petechias, ecchymosis and
purpura).
The elements
of the rash
have incorrect (“star-like”) (
Fig.10) form, dense, coming out over
the level of
the skin. Hemorrhagic rash is
combined inrarely with
roseolous and papulous rash.
The severe
development of the
rash depends from
the character, size and
depth of the
its elements. The deep
and extensive hemorrhages
may be necrosed. Then it
may be formation
of deep ulcers. Sometimes deep
necrosis is observed
on the limbs
and also, necrosis of
the ear, nose and
fingers (Fig.11) of the
hands and legs (Fig.12).
Fig.11. Necrosis of fingers
Fig.12. Zones of leg necrosis
During biopsy meningococci are
revealed. Exanthema
is
leucocytaric-fibrinous
thrombosis, contained the agent
of meningococcal infection. Thus,
in meningococcal infection
rash is the
secondary metastatic foci
of the infection.
Joints occupy
the second place
over localization of
metastases of the
agent. At the last
years arthritises and
polyarthritises are marked
rarely (in 5 %
of the patient
during sporadic morbidity
and in 8-13 %
of the patient
during epidemic outbreaks). The small
joints are damaged
more frequently. Arthritis is
accompanied by painful
motions, hyperemia and edema
of the skin
over joints.
Arthritises appear
later then rash
(the end of the
first week – the beginning of
the second week
of the disease).
Secondary
metastatic foci of the infection
may appear rarely
in the vascular
membrane of the
eye, in myocardium, endocardium,
lungs and pleura. Similar foci
arise very rarely
in kidneys, liver, urinary tract, borne
marrow.
In the
peripheral blood high
leukocytosis, neuthrophillosis
with shift of
the formula to
the left aneosinophyllia, increased
ESR are observed. Thrombocytopenia develops inrarely.
There are
alterations in urine
as during syndrome
of “infectious-toxic kidneys”. Proteinuria, microhematuria,
cylinderuria are marked.
Meningococcal sepsis is
combined with meningitis in majority cases. In
4-10 % of the
patients meningococcemia may
be without damage
of the soft
cerebral covering. Frequency of
meningococcal sepsis is
usually higher in
the period of
epidemic.
Fulminate meningococcemia ( acutest
meningococcal sepsis, Waterhause-Friedrichen syndrome)
It is the
more severe, unfavorable form of
meningococcal infection. Its base
is infectious-toxic shock.
Fulminate sepsis is characterized by
acute sudden beginning and impetuous
course. Temperature of body rises up to 40-41 oC. It is accompanied by chill. However, hypothermia may be
observed through some
hours. Hemorrhagic plentiful rash
appears at the
first hours of
the disease with
tendency to confluence
and formation large
hemorrhages, necroses. A purple-cyanotic spots arise on the skin
(“livors mortalis”). The skin is pale,
but with a total cyanosis. Patients are anxious and excited. The cramps
are observed frequently, especially in children. The
recurrent blood vomiting arise inrarely. Also, a bloody diarrhea may be
too. Gradually, a prostration becomes more excessive and it results is a
loss of the consciousness.
Heat’s activity decreases catastrophically. Anuria develops
(shock’s kidney). Hepatolienalic syndrome is
revealed frequently. Meningeal syndrome is
inconstant.
In the
peripheral blood hyperleukocytosis (till 60*109/l),
neutrophylosis, sharp shift
leukocytaric formula to
the left, thrombocytopenia,
increased ESR (50-70 mm/h) are
reveled. The sharp disorders
of hemostasis are
marked - metabolic acidosis, coagulopathy of
consumption, decrease of fibrinolitic
activity of the
blood and other.
Mixed forms (meningococcemia
+ meningitis)
These forms occur in 25-50 % cases of generalized meningococcal
infection. In the last years there is
tendency of increase frequency of mixed forms in general structure of the
disease, especially in periods of epidemic outbreaks. It is characterized by
combination of symptoms of meningococcal sepsis and damage of cerebral
membranes.
Rare forms of meningococcal infections
These forms (arthritis, polyarthritis, pneumonia, iridocyclitis) are consequence of
meningococcemia. Prognosis is favorable
in opportune and
sufficient therapy.
Diagnostics
The diagnosis
of all forms of meningococcal infection is based on the complex of
epidemiological and clinical data. The
final diagnosis is
established with help
of the laboratory
examination. Separate
methods have different diagnostical significance in various
clinical forms of meningococcal infections.
The diagnosis of meningococcal carrier is
possible only by use of bacteriological method. The material for analysis is the mucus
from proximal portions of upper respiratory tract. In diagnostics of
meningococcal nasopharyngitis epidemiological and bacteriological methods occupy the main
place. Clinical
differention of meningococcal nasopharyngitis from
nasopharyngitis of the other genesis is
no possible or very difficult.
In recognition of generalized forms,
anamnestical and clinical methods of diagnostics have real diagnostic
significance, mainly in combination of meningococcemia and meningitis.
The
examination of cerebrospinal
fluid (CSF) has great
meaning in diagnostics
of meningitis. In lumbar
punction cerebrospinal fluid flows
out under high
pressure and by
frequent drops. The cerebrospinal fluid
may flow out
by rare drops
only due to
increased viscosity of
purulent exudation or
partial blockade of liquor’s
ways. Cerebrospinal
fluid is opalescent
in initial stages
of the disease. Then it
is turbid, purulent,
sometimes with greenish
shade (Fig.13).
Fig.13. Cerebrospinal fluid
in meningococcal meningitis
Pleocytosis achieves till 10-30 103 in
1 mcl. Neuthrophils leukocytes predominate
in cytogram. Neuthrophilous compose 60-100%
of all cells. In microscopy neuthrophils
cover intirely all
fields of vision, inrarely. Quantity of
protein of cerebrospinal
fluid increases (till 0,66-3,0 g/l). There is
positive Nonne-Appelt’s reaction. The reaction of
Pandy composed (+++). Concentration of glucose
and chlorides are
usually decreased.
In generalized forms the
final diagnosis is
confirmed by bacteriological method. In diagnostics immunological
methods are used too. Reactions of hemagglutination, latex agglutination
are more sensitive.
Differential diagnosis
In
meningococcemia the presence
of rash requires
of differential diagnostics
with measles, scarlet fever, rubella, diseases of
the blood (thrombocytopenic purpura Werlgoff’s disease; hemorrhagic vasculitis – Sheinlein-Henoch’s disease).
Sometimes it is
necessary to exclude
epidemic typhus, grippe,
hemorrhagic fevers.
It
is necessary to
differentiate meningococcal meningitis
with extensive group
of the diseases:
1. Infectious
and noninfectious diseases
with meningeal syndrome
but without organic
damage of central
nervous system (meningismus).
Meningismus may be
in grippe, acute shigellosis, uremia, lobar pneumonia, toxical food-borne infectious, typhoid fever, epidemic typhus, infectious mononucleosis, pielitis, middle otitis.
2. Diseases
with organic damage
of central nervous
system, but without meningitis (brain abscess, tetanus, subarachnoid hemorrhage).
3. Meningitis of other etiology. In
purulent meningitises etiological
factors may be
pneumococci, staphylococci, streptococci, bacterium coli, salmonella, fungi, Haemophilus influenzae. In purulent
meningitis nonmeningococcal etiology
it is necessary
to reveal primary
purulent focus(pneumonia,
purulent processes on
the skin, otitis, sinusitis,
osteomyelitis).
Treatment
The therapeutic
tactics depends from
the clinical forms, severity of the
course
of the disease, presence of
complications, premordal state.
In serious and
middle serious course
of nasopharyngitis antibacterial
remedies are used. Peroral antibiotics oxacillin, ampyox,
chloramphenicol, erythromycin are used.
The duration of the
therapy is 3-5 days
and more. Sulfonamides of
prolonged action are
used in usual
dosages. In light duration
of nasopharyngitis the
prescription of antibiotics
and sulfonamides is
no obligatory.
In therapy of
generalized forms of
meningococcal infection the
central place is
occuped by antibiotics, in which
salt benzil penicillin
stands at the
first place. Benzyl penicillin is used
in dosage of
200,000-300,000 IU/kg/day. In
serious form of
meningococcal infection daily
dosage may be
increased to 500,000 IU/kg/day. Such doses
are recommended particularly
in meningococcal meningoencephalitis. In presence
of ependimatitis or
in signs of
consolidation of the puss the
dose of penicillin increases to 800
000 IU/kg/day.
In similar
circumstances it is necessary
to inject sodium
salt of penicillin
by intravenously in
dose 2 000 000-12 000 000 units
in day. Potassium salt
of penicillin is
no injected by
intravenously, because it is
possible the development
of hyperkalemia. Intramuscular dose
of penicillin is
preserved.
Endolumbar injection of penicillin
is no used
practically last years. Daily dose
is injected to
the patient every
3 hours. In some
cases interval between
injections may be
increased up to
4 hours. The duration
of the therapy
by penicillin is
decided individually depending on
clinical and laboratory
data. The duration of penicicllin therapy usually 5-8
days.
At the
last years increased
resistant strains of
meningococcus are marked (till
5-35%). Besides that, in some
cases the injection of
massive doses of
penicillin leads to
unfavorable consequences and
complications (endotoxic shock,
hyperkalemia due to
using of potassium salt of
penicillin, necroses in the
places of injections
and other). Also, the
patients occur with
allergy to penicillin
and severe reactions
in anamnesis. In such
cases it is
necessary to perform
etiotropic therapy with
use other antibiotics. In meningococcal infection
semisynthetic penicillins are
very effective. These remedies
are more dependable
and preferable for
“start-therapy” of the
patients with purulent
meningitis till
establishment etiological diagnosis. In
meningococcal infection ampicillin
is the best
medicine, which is prescribed
in dosage 200-300 mg/kg/day intramuscularly every
4 hours.
In the
most serious cases
the part of
ampicillin is given
intravenously. Daily dose is
increased to 400 mg/kg/day. Oxacillin is
used in dose
not less than
300 mg/kg/day every 3
hours. Metycyllin is prescribed
in dose – 200-300 mg/kg
every 4 hours. In
meningococcal infection chloramphenicol is
highly effective. It is the
medicine of the
choice in fulminate
meningococcemia. It is shown, that
endotoxic reactions arise
more rarely during treatment of
the patients by
chloramphenicol than during therapy
by penicillin. In cases
of meningoencephalitis chloramphenicol is not prescribed
due to its
toxic effects on
neurons of brain. Chloramphenicol is
used in dose
50-100 mg/kg 3-4 ties
a day. In fulminate
meningococcemia it is
given intravenously every
4 hours till stabilization
of arterial pressure. Then chloramphenicol is
injected intramuscularly.
The duration of
the treatment of
the patients by
this antibiotic is
6-10 days.
There are
satisfactory results of the treatment
of meningococcal infection
by remedies from
the group of
tetracycline. Tetracycline is
injected in dose
25 mg/kg intramuscularly and
intravenously in the cases
of resistant agents
to the other
antibiotics.
Pathogenetic therapy
has exceptional significance
in therapeutic measures. It
is performed simultaneously with
etiotropic therapy. The basis
of pathogenetic therapy
is the struggle
with toxicosis. Salt solutions, macromolecular colloid
solutions, plasma, albumin
are used. Generally 50-40 ml of
fluid is injected on 1 kg of body’s mass per day in adults under the control of
diuresis. Prophylaxis of hyperhydratation of the
brain is
performed simultaneously.
Diuretics (lasix, uregit) are injected.
In serious cases
glucocorticosteroids are prescribed. Full doses
is determined individually. It depends
on dynamics of the main
symptoms and presence
of complications. Generally hydrocortisone is
used in dose
of 3-7 mg/kg/day, prednisolone – 1-2 mg/kg/day. Oxygen therapy
has great significance
in the treatment
of the patients
The therapy
of fulminate meningococcemia includs
the struggle with
shock. Adrenaline and adrenomimetics are
not used due
to possibility of
capillary spasm, increased
hypoxia of the
brain and kidneys
and development of
acute renal failure. The
early hemodialysis is
recommended in the
case of acute
renal failure due
to toxicosis.
The basis of the therapy of
infectious-toxic shock is complex of measures, including application of
antibiotics, improvement of blood circulation. The course of infectious-toxic
shock is very serious, with high mortality (50% of the patient die during the
first 48 hours of the disease). Because, it is necessary to
prescribe intensive therapy immediately. Antibiotics of wide spectrum of
action are prescribed. Steroid hormones have important meaning in the treatment
of infectious-toxic shock. Hormones decrease general reaction of the organism
on toxin, positively act on hemodynamics. Treatment by glucocorticoids is
conducted during 3-4 days.
Prophylaxis
Prophylactic measures, directional on the sources
of meningococcal infection
include early revelation
of the patients,
sanation of meningococcal
carriers, isolation and treatment
of the patients. Medical observation
is established in
the focuses of
the infection about
contact persons during
10 days.
The
measures against of the
transmissive mechanism, are
concluded in performance
of sanitary and
hygienic measures and
disinfection. It is necessary
to liquidate the
congestion, especially in the
closed establishments
(children’s establishments,
barracks’s and other). The
humid cleaning with
using of chlorcontaining disinfectants, frequent ventilation, ultra-violet radiation
are performed at
the lodgings.
The measures, directional on
receptive contingents,
include increase nonspecific
resistance of the people
(tempering, timely treatment of
the diseases of respiratory tract, tonsils) and formation
of specific protection
from meningococcal infection. Active immunization
is more perspective
with help of
meningococcal vaccines. There
are several vaccines, for
example, polysaccharide
vaccines A and C.
Vaccine from
meningococcus of the
group B was also
obtained. However, the group B capsular polysaccharide is not
sufficiency immunogenic to produce a reliable antibody response in humans to be
effective, several solutions to this problem are being studied, including the
chemical alterations of the capsular B antigen to make it more immunogenic and
the search for other cell wall antigens that
are capable of eliciting
bactericidal antibodies against B meningococci with a minimum of serious side
effects. New vaccines against meningococcus are under development.
SEPSIS
The term sepsis has been used
for a clinical situation in which there is evidence of infection plus a
systemic response as manifested by an elevated temperature, tachycardia,increased respiration, leukocytosis or an impaired
peripheral leukocyte response, and/or the presence of immature band forms of
peripheral circulation.
Sepsis has some
differences from the
other infectious diseases:
1.
Sepsis is
polyetiological disease. The agents of
sepsis may be different microorganisms –aerobic and
anaerobic.
2.
There is no united
entrance gates.
3.
There is no cyclicy
of the course.
4. Immunity don’t form in
sepsis.
Etiology
The most frequent etiologic
factor of sepsis is auto- or external microflora. These agents are a
staphylococcuses, streptococcuses, colibacilluses and other so called
conditionally pathogenic microorganisms. Rarely, a reason of the sepsis may be
obligate parasites. Blue pus bacillus,
gonococcus, meningococcus, bacillus anthracis, salmonella, fungi and others may
caused sepsis. But, at last time staphylococcus
is found more often than others, so it should be on the first place by
significance. In according to international
classification 3 types
of staphylococcus are detached: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus. Staphylococcus aureus
plays the most important
role in the
pathology of human.
Epidemiology
Staphylococcus infection
is widely spread
among hospitalized persons. Intrahospital distribution
is typical feature
of epidemiology of staphylococcus infection.
Intrahospital infections
are characterized by
large quantity of
the sources of
infection, multiply ways and
factors of transmission
of the agent
multiply persons with
increased risk of the infection. The sources
intrahospital infection are
patients with different
forms of staphylococcus purulent infection, carriers of staphylococcus.
Carriers of staphylococcus from medical
personnel play an
important role in
the conditions of
the hospital.
The ways and
factors of transmission
of staphylococcus infections
are different: respiratory-drug,
contact and alimentary. Transmission of
the agent may be realized
by alimentary way. For
example, it is possibly
infection of infants
in born-hause by
solutions for drink
and milk, using for
supplementary nourishment. Staphylococcus infection
have sporadic character
in observance of
sanitary-antiepidemic regime.
Epidemic outbreaks of
intrahospital
staphylococcous infections may be in
violation of regime.
Staphylococcus
infection develops as
rule in persons
with decreased nonspecific
resistance, with different infectious
diseases (especially, viral
etiology), after chronic diseases, in
persons after massive doses of
immunodepressors, antibiotics, hormones, X-ray therapy.
Pathogenesis and pathologic anatomy
The factors of
risk, , promoting the penetration of normal germs of skin and mucous
membranes into internal mediums of
the macroorganism system, may be different causes injuries, inflammations, trophic
disorders, aggression of different microflora, congenital anomalies. The
following distribution of microbes in macroorganism may go by different ways –
via blood, lymph and direct methastasing. The intermediate localization
of the process
appears. It may
be phlegmona, abscess or other destructive processes. The process
is sepsis, when it
has generalized character
with damage liver, spleen, lungs, kidneys, vessels and
other organs and systems.
The agents of sepsis, penetrating into
tissues, causes an inflammatory process. In some
cases the process
develops impetuously. The purulent
inflammatory focus arises
on he place
of the penetration
with reproduction of
microbes (primary focus). But in
other cases
inflammatory manifestations are less expressive and rapidly disappear, but agent
penetrates inside tissues by lymphatic
and blood ways and causes inflammatory focus
in distant place. These inflammatory focus may lead to development of
sepsis, in corresponding
change of reactivity
and resistance of
the organism.
Entrance dates
of infection may be in
any organ and
tissue. The primary focus
is in tissues
with large quantity
of lymphatic and
blood vessels more
frequently. For example, in
wound sepsis the
skin is entrance
gates more frequently. In urosepsis
and gynecological sepsis
mucous membranes are entrance gates. Prolonged course of sepsis is marked in patients with
localization septic and primary foci in bones, muscles, urogenital system. In
some cases, there are no visual foci, except the primary septic focus. These
forms are called septicemia. But in other
cases, metastatic secondary purulent foci are formed. These forms are named pyemia. But,
also there is possible a transitional form – septicopyemia.
The distribution
of infection is
realized from the
primary focus by
blood and lymphatic
ways. The distribution of
the agents is
realized by veins too, with formation
of thrombosis and thrombophlebitis. Microbes and their
toxins may penetrate to lymphatic vessels and cause lymphangites and
lymphadenites. Metastases may be as an infiltrations, phlegmons, abscesses. Purulent infiltrates may appear in intestine too.
In the serous cavities they are characterized by purulent exudations
(arthritis, pleurisy, peritonitis, pericarditis).
The localization
of metastases in the
lungs is on
the first place, kidneys are
on the second
place, then – other organs.
Allergic component has an
important role in pathogenesis of the septic process. Primary and secondary
septic foci transfer into a source of sensibilisation of human organism.
In
sepsis the violations
of metabolism, acid-alkaline balance, deep
changes of balance
of proteins and
vitamins are observed. Anemia develops due
to damage of
bone marrow.
DIC–syndrome plays an important role in the development
of septic state and complications. In some cases of sepsis DIC–syndrome comes
out on the first plan and cause fatal outcome in considerable degree.
DIC-syndrome is “proteolytic
explosion” with activation and following exhaustion of coagulation, fibrinolytic,
kallekrein-kinine systems and system of complement.
In sepsis dysbalance of immune system
has the pathogenetic meaning. Immune deficiency is manifested by decrease of
quantity of T-helpers, reduce of activity natural
killers and phagocytic activity of granulocytes. These changes lead to
development of generalized infectious inflammatory process.
In sepsis pathologoanatomy alterations are very various. Petechial rash is
marked on the
skin. Hemorrhages
are observed in
organs and tissues, especially on
mucous membranes. The alteration
of myocardium are
marked from turbid
swelling till excessive
lipid dystrophy. Erosions are revealed
in endocardium. Thrombosis of veins
are often observed. Spleen is
enlarged. There is a turbid swelling or lipid infiltration in
liver. Lymphatic nodes are increased. There are a
plural hemorrhages in kidneys. Also, they are marked in the
gastrointestinal tract. Hemorrhages are observed in the suprarenal glands.
There is edema in the lungs. Sometimes there are foci of bronchopneumonia. The infarction foci are not rare. There are edema
and hyperemia of
brain’s substance. In sepsis
with metastases (pyemia) purulent
process are observed
in brain (purulent meningoencephalitis), lungs (like
abscessing infarctions), kidneys,
thyroid gland. Besides that, purulent pleurisies, peritonitis, pericarditis,
phlegmons are observed
in different places.
Classification
1.
Purulent – resorptive fever
is characterized by
presence of purulent
foci, wave-like course,
general intoxication.
2.
Septicemia is characterized by
severe general state, hectic
temperature, severe
disorders of central
nervous system and
cardiovascular system.
3.
Septicopyemia.
This is
combination of septicemia
and presence of
secondary purulent foci
in different organs.
4.
Chronic sepsis. There is
purulent foci in
anamnesis during this
form. The diseases is accompanied by
prolonged wave-like fever, presence of
period of remission
and relapses, periodical formation
of purulent foci.
II.
According to prolongation
of course the
next form of
the diseases are differed:
1.
Fulminant
sepsis (24-48 hours)
2.
Acute sepsis (from
5-7 days till
some weeks)
3.
Subacute sepsis (3-4
months)
4.
Chronic sepsis (from
some month till
one year and
more)
III.
According to date
appearance of process
the next variants
are differed:
1.
Early sepsis (till
3 months from
appearance of the
primary focus)
2.
Late sepsis ( later than
3 months)
IV. According to
character of microorganism
sepsis is differed
on:
Sepsis, caused by
gram-positive flora. It leads, inrarely, to
development of septicopyemia.
Sepsis, caused by gram-negative
flora. Infectious-toxic
shock may be in
such cases.
Clinical manifestation
There is no any specific
incubation in septic patients. In one cases, septic process develops through
weeks and months after localized focus (abscess), but in
other cases sepsis
may be on
its background.
Complains of these patients
are different as a clinical manifestations – weakness, headache, pain in
joints, chill with following sweats or chilling, dry mucous
membrane of the
mouth, poor appetite, sometimes – diarrhea.
Fever is frequently of hectic character in
patients with sepsis. Different variants of the temperature
may be –
remittent and intermittent types, sometimes, – the temperature is more
high in
the morning (the reversal type).
The temperature may be not high in
weak, cachestic patients and
elders, but it doesn’t report about light course of sepsis.
Patient’s skin is pale, moist,
even icteric in severe cases. Different rashes
are observed. Rash of
hemorrhagic type is
marked more frequently, sometimes – pustules, ulcers,
erythema. Eruption may be on skin of trunk, limbs and face.
Mucous membranes of lips, oral
cavity are dry and may have erosions, ulcers, fissures, bleeding sickness.
Often, there are hemorrhages of conjunctiva.
Pulse is frequent. Arterial pressure decreases. Heart is enlarged. There
are a systolic murmur above cardiac apex, tachycardia and “pendulous” rhythm
during auscultation the alterations of
myocardium are revealed during
cardiogram. The type
of these alteration
is diffuse or
diffuse-focal. Sometimes, the
sighs of damage
of endocardium and
large peripheral vessels
are revealed (arteritises,
phlebitises).
The alterations
of respiratory tract
are revealed frequently
in the patients
with sepsis: dyspnoe, bronchitis
and pneumonia. Pneumonia has tendency to formation to abscesses. Inrarely,
serous, purulent, hemorrhagic and mixed pleurisy arise
in the patients.
There is a dry coated tongue in these
patients. Appetite is decreases. Sometimes, vomiting arises. Spleen is frequently enlarged,
soft consistention. Liver also increases and painful during palpation. The
abscesses may arise inside abdominal cavity.
Septic patient, often, have a
disorders of kidneys and urinary track. Sometimes toxic nephrites, purulent
paranephrites arise. The alterations of uterus, perimetrium may
be in women. The
primary location of
inflammatory process is
marked inrarely in
urogenital organs. It may give
generalization of the
process.
Osseous-muscular system is
involved to pathologic process, too. There are reports about the serous and
purulent mono- and polyarthritis, foci of osteal destruction, degeneration of born
marrow, myocytes. Also, the osteal tissue may be
site of the primary foci (osteomyelitis).
Different manifestations may be
from nervous system, such as – a meningismus, purulent meningitis,
cerebral and spinal hemorrhages, hemorrhages into the vegetative ganglions.
The signs of anemia
are revealed in
the blood – decreasing quantity of erythrocytes, hemoglobin. Also,
there are a signs of the anisocytosis, poikilocytosis, thrombocytopenia.
Neutrophilic leukocytosis with shift to myelocytes, increased ESR are marked leukopenia may be in
cachestic patients with
fulminate forms of
sepsis.
Biochemical changes
of the blood
are expressive in
the patient with sepsis. Increased content of
bilirubin and increased activity
of transaminases are
marked.
In
sepsis the proteins
of serum blood
are sharply changed. A quantity of
albumines decreases and
globulines increased. The changes of
concentration of IgA, IgG, IgM
depend upon gravity
of the course and
outcomes of sepsis.
Fulminant sepsis
is a rare form, for example, of meningococcal sepsis. It has several
synonyms. There are – fulminate meningococcemia, acutest meningococcal sepsis,
Waterhouse-Friedrichen syndrome.
It is the more
severe, unfavorable form of meningococcal
infection. Its base is infectious-toxic shock. Fulminate sepsis
is characterized by
acute sudden beginning and impetuous
course. Temperature of body rises up to 40-41oC. It is
accompanied by a chill. However, hypothermia
may be through
some hours. Hemorrhagic plenty
rash appears at
the first hours
of the disease
with tendency to
confluence and formation
large hemorrhages, necroses. A
purple-cyanotic spots arise on the skin (“cadaveric spots”). The skin is pale, but with a total cyanosis.
Moist, covered with a clammy sweat. Patients are anxious and excited. The cramps
are observed frequently, especially in children. The
recurrent bloody vomiting arises inrarely. Also, a bloody diarrhea may be
too. Gradually, a prostration becomes more excessive and it results in a
lose of the consciousness.
Acute sepsis is the most frequent form of sepsis. Staphylococcus sepsis
is occurred more
frequently. It is
accompanied by considerable
fatal outcomes. In majority of
the cases the
onset of disease
is an acute
with chill and
increase of the temperature. Fever may be of different character: constant, intermittent ,
remittent and incorrect. Sometimes sepsis
may be with
subfebril temperature.
Anemia increases in majority of
the patient, because the
skin is pale. Sometimes skin
has jaudiwish shade
due to haemolysis
or toxic hepatitis.
The rash is in the
shape of petechial. Rash is
localized on the
skin of the
chest, forearms, hands, upper
extremities, on the mucous
membrane of the mouth, conjunctiva and
all gastrointestinal tract. Hemorrhages on the
mucous membrane of
gastrointestinal tract may
evoke bloody vomiting and
diarrhea. The sizes of
hemorrhages are different – from small
points till large
hemorrhages. An appearance of hemorrhagic
rash is explained
by present of
hemorrhagic vasculitis. Rash may be
purulent or erythematosus character due to infectious-allergic dermatitis. The damage
of joints is
observed in 25-30%
of the causes. The
large joints are
damaged more frequently, but small
joints may be
damaged too. The joints
are edematous. There is
hyperemia of the
skin over joints. The motions are
painful.
In sepsis symptoms, connecting with
damage of different
organs and system
are always expressed. They appear
as a result
of expressive intoxication,
or as
primary or secondary
purulent inflammatory process.
The symptoms, connecting with
damage of cardiovascular system
is revealed more
frequently. Staphylococcous sepsis
may be without
damage of endocardium. In this
case the clinical
symptoms are evoked
by distrophic changes
of myocardium. Tachycardia,
decreased arterial pressure, pains in
the heart of
indefinite character,
enlargement of the
borders of the
heart, mulffeled heart sounds are observed. The
damage of the
vessels may be
manifested in form
of phlebitis, development of
thromoembolism and also
embolism of small
vessels of the
skin and internal
organs, in this violation
of coronaric circulation.
Oxygenic insufficiency
and damage of
respiratory center leads
to breathlessness. In some patient
bronchitis, pneumonia, abscesses
and pleurisy are
observed. Hemorrhagic
pleurisy is more
typical for staphylococcus sepsis.
In staphylococcous sepsis
the typical sign
is increased liver. The
severe septic hepatitis may
be observed with
development of jaundice
and violation of
all functions of
liver and also
cholangitis, abscesses. Enlarged spleen (septic mesenchymic
spleenitis) is frequent
symptom. Spleen is soft
in an acute
period, because it
is difficulty to
define spleen in pulpation. However, enlarged spleen is clearly
defined in percussion. During prolonged course
of sepsis spleen
becomes dense. The damage
of kidneys has
essential meaning in
clinic of sepsis. In
acute process the
local nephrite of
microbial embolic origin
develops diffusive nephritis develops later.
The
symptoms of damage
of nervous system
are the principal
clinical manifestations in the
patient
with sepsis. In acute
sepsis consciousness is
preserved even in
high temperature. In this
period severe headache, sweat, violation of
the sleep and
dizziness are usual
complaints of the
patients. In severe
cases depression,
irritation, sometimes excitement are
observed in the
patients. Due
to edema of
the brain meningeal
syndrome may be too. It is possible
development of secondary
purulent meningitis. The appearance
of meningitis is
characterized by intensification of
headache, addition of vomiting, development of
meningeal symptoms.
Meningoencephalitis, arachnoiditis and
abscess may developed. The course
of acute sepsis
is from 2
weeks till 3
months.
Thus, clinic of acute sepsis
is characterized by
severe course, expressive symptoms
of intoxication and
symptoms of damage
of separate organs. Frequent manifestation
of acute sepsis
is development of bacterial
endocarditis and purulent
inflammatory focuses in
different organs (phlebitis,
abscesses, pneumonia, pleurisy, pancreatitis, cholangitis, osteomyelitis,
otitis, cystitis, violations of brain’s
blood circulation, hemorrhage into
retina of the
eye and other.
Subacute sepsis. The
course of this
sepsis is 3-4
month. It is differented
from acute sepsis by
lesser intensity of
symptoms. Metastases appear more
rarely than in
acute sepsis. The prognosis
is better in
this form. This form
of sepsis arises
in damage of
the heart by
rheumatic process.
Chronic sepsis is characterized
by prolonged course (till
one year and
more).
This form is accompanied with
remissions and aggravations with a severe morphologic alterations. Chronic
sepsis has a wound origin, for example, the septic process in inflammatory of
the billiary tract and portal vein. In
some cases, billiary tract is secondary infected due to of any general cyclic infectious disease.
In other cases, billiary tract may be as septic focus.
Outcomes of
the disease it depends from the premorbid condition, opportunity, of the
therapy and its effectiveness. Prognosis of a sepsis is frequently
unfavourible, especially for an infants and elder patients.
Diagnostics
Bacteriologic investigations is an important
diagnostic test in sepsis. The results of the bacteriologic investigations
never must be account without a data of history, clinical features and other
laboratory tests. The positive bacteriologic results are not always in a septic
patients. The negative results are especially
frequent in sowing
of the blood.
In sepsis the excretion of the agent
and estimate of received results are inrarely complicated problem. It is
connected with that in sepsis the circulation of agent in the blood is no
constant. A quantity of the agent in the blood is oscillated and may be
insignificant. The treatment by antibiotics has a large influence on
bacteremia.
It is
necessary to perform a differentiation with different diseases accompanied
with prolonged fever, rigors, sweating,
various eruptions.
Typhoid fever and paratyphoid remind
sepsis by fever, pale skin, increased liver and spleen. But, they are
differented from septic process by
cyclic course, not so excessive anemia and rarity of the hemorrhagic eruptions.
Detachment of the
agent of typhoid
fever and paratyphoid, result of
IHA-test (indirect
hemagglutination reaction)
help in
decision of problem.
In some cases, tuberculosis,
especially its milliary forms in young patients, is difficult for diagnostics.
During this, fever, sometimes of hectic type, dyspnoe, sweating may
be as in
sepsis. It is necessary carefully to study of the epidemiological data, repeated
radiological investigation and
sowings of the
blood.
Also, the hectic fever, sweating may
be in acute period of brucellosis. In
brucellosis there are a little
violations of the
general state of
the patients. There is no the hemorrhagic syndrome. During the
second stage there are signs of the locomotor system infractions. In the early
stages of the brucellosis, positive result
of Wright reaction are
marked. Positive intracutaneous
allergic test is observed
some later.
Sepsis should be differentiated with
a pneumonia, because pneumonia may be a result
of sepsis. The following
systematic observation and the metastatic foci in joints, endocardium and
brain’s membranes are usually helpful for decision of this problem.
In epidemic typhus there are
typical clinical symptoms. They are jary-Auvcyne’s symptom, Govorov-Godelyae ’s symptom,
Rosenberg ’s symptom early enlargement of spleen. Typical eruption appears on
the 4-5 day
of the disease. Serologic methods are very useful, especially for the
final diagnosis.
Tropical malaria, also, is accompanied
by a prolonged fever and hepatosplenomegaly. The typical features of the
fever in tropical
malaria are prolonged paroxysms (to 24-36 hours and over), poorly
excessive an apyrexia periods. Rigor and sweating are less excessive, that is
caused by some fluctuation of temperature. These attacks are accompanied by
severe headache, low back pain, nausea and sometimes by vomiting.
Abdominal pains and watery stools appear
inrarely. The indications of
the patients about location in focus of
malaria, depart to tropical
countries have an
important epidemiological meaning. Microscopic blood examination (blood
smear and voluminous drop) are needful and reliable laboratory methods to
diagnostics of malaria.
Four
diseases are problems
for differential diagnostics tuberculosis, collagenoses (a
lupus erythematosus and so called “non-differentiated” collagenoses or diffuse
diseases of connective tissue), malignant neoplasm (especially hepatomas and
hypernephromas, also as a lymphogranulomatosis and leukemia).
At
the last time
it is necessary
to allow for
increased rate of
fungal infections in
diagnostics of sepsis. In the main, they are candidoses of
the bronchopulmonal, intestine, urogenital and osseous systems. Fungi of
genus Candida albicans
have the most
meaning among fungal
damages. Fungi Candida albicans
are revealed in
the normal flora
of the oral
cavity, intestine.
It
is necessary to
perform differential diagnosis of sepsis with intestine yersiniosis.
This disease may have prolonged (more 3
months), relapsing course. In
prolonged yersiniosis alteration
of periods of
relapses and remissions is observed. The period of relapse
is characterized by prolonged fever, reactive polyarthritis, myocarditis,
prolonged gastroenteritis, hepatolienal syndrome, erythema.
The
repeated sowings are produced
on special mediums
for determination of the agent’s
origin: blood, sugar, billiary broth. It is recommended to take the blood
in a quantity 15-20 ml on 80-100 ml of the medium. The agent
may be revealed
from hemorrhagic elements, sputum, urine, content of abscess and other
materials.
Treatment
Therapy of
a sepsis should include at least two obligatory components - suppression of the
originator and restoration of immunity.
Principles
of a etiotropic treatment of sepsis:
Basis
of sepsis therapy - is oppression and liquidation of the agent. There should
not be ignored means of syndromes treatment which restore immunity, all others
if in them there is a necessity, but all of them can not cure the patient on
with sepsis without appropriate ethiotropic therapy.
Antibiotic
therapy of sepsis may be successful, if:
1)
It is carried out by address, that is after revealing
the agent definition of its antibiotic sensivity;
2)
It will be carried out (spent) by bactericidal drugs bacteriostatic drugs are
used only as address;
3)
It is applied at early septicemia (at this stage of illness recovery is
achieved in 100 % with
one antibiotic without all other means of treatment);
4)
Dozes of antibiotics maximum high, and β-lactamic antibiotics
(penicillines, cephalosporines) are used in megadozes;
5)
Empirical antibiotic therapy (if the agent is unknown) is carried out on the
basis of the clinical supposition about a nature of the agent (empirical
antibiotic therapy is should not be carried out by random);
6)
Combination of antibiotics is carried out by a rule: bactericidal drugs with the various mechanism of
action;
7)
Usage of more than two preparations in one combination is not expedient, as
with increase of number of drugs harmful actions grow faster, than therapeutic
effect;
8)
It is not necessary to start antibiotic therapy from reserve antibiotics
(carbopenems, cephalosporines of 4-th generation).
If treatment
is successful, antibiotic therapy is cancelled last, after liquidation of all
infection foci, but not earlier 5-th day of a normal body temperature. Sepsis
is a general clinical
problem. Comprehension of sepsis should become the common medical property
because such patients are in all medical establishments without exception.
Among
various combinations of antibiotics the greatest recognition has received
combination of 3-rd generation cephalosporines (Ceftriaxoni, Cefotaximi, Ceftazidimi) with Aminoglicosides (Gentamicini, Amikacinum).
All these combinations are effective enough at patients with sepsis without a
neutropenia. Appreciable interest to Ceftriaxoni is caused by duration of its
period of semiconclusion, that allows to apply
preparation once per day. Other preparations have shorter period of
semiconclusion and demand repeated injection during day. At sepsis caused by Pseudomonas aeruginoza, high efficiency
of combination of Penicillinums with
antipyocyanic activity (Ticarcilini, Clavulanati, Aztreonami) and
Aminoglicosides is marked.
At sepsis caused by Gram-positive
flora (Meticilini-resistant staphylococcus,
coagulasenegative staphylococcuses, enterococus), using of Vancomycinum,
Rifampicinum is effective.
Carbapenemes (Tienamicines) - Special group of β–lactames antibiotics
(Imipenicemi, Tienami, Meropenemi, Biapenemi), the infections created for
empirical therapy with serious current, including leukopenia. Very wide
spectrum of action, high bactericides, that is not accompanied by superfluous
remission of endotoxins at destruction of bacteria, allow
to use with success Carbapenemes as monotherapy at the most serious infections,
including sepsis.
After allocation and identification
of the originator, definition of antibioticogram the choice of effective
antibacterial therapy is considerably facilitated. In such cases monotherapy is
frequently used. Nevertheless, the question of indication of monotherapy or a
combination of antibacterial preparations remains debatable and, apparently,
should be discussed in each concrete case. Determining arguments, probably,
will be estimation of gravity of infectious process and condition of reactivity
of organism, danger of occurrence of hospital infections in connection with
invasive methods of diagnostics and treatment, transplantation of extraneous
bodies. Nevertheless, at Gram-negative infections, in opinion of many
scientists, the combined therapy is more expedient.
Antibiotics,
as a rule, do not suppress immunity. It is proved, that Lincosamides and
Macrolides have immunomodulative properties and are capable to stimulate the
certain parts of the immune answer.
Duration of antibiotic therapy is determined by course of inflammatory
process. As a rule, preparations cancel at proof normalization of temperature
(absence of attributes of generalized process), absence of the clinical and
laboratory data on presence of the localized center of an infection or joining
of nosocomial infections. At average therapy lasts 2-3 weeks. At revealing
clinical efficiency of empirical or purposeful therapy by antibiotics change of
a combination or separate preparation is inexpedient during all period of
treatment.
The immunotherapy should be directed on blocking of effects of endotoxin
and citocines. Application of Pentoxifilini is perspective, that brakes the formation of FNO, has protictive influence on
lungs, systemic hemodynamics, improves microcirculation and oxygenation of
tissues, stabilizes electrolytic balance, preventing occurrence of
hyponatremia.
Citoprotective antioxidantes (vitamin E, Acetylcysteinum) oppress
activity of free radicals and may improve the forecast at sepsis.
Hyperproduction of free radicals which are metabolites of an arachidonic acid
is lowered also by Ibufrofenum.
Efficiency
of polyclonal antibodies to bacteria E.
coli and Salmonella which at
septic shock caused by Gram-negative bacteria’s, reduce a
lethality almost on 50 % was proved. Now polymyxin B or neutrophile bactericidal
penetrating protein is used.
Efficiency
of application for prophylaxis of the systemic answer on inflammation of
vactination of patients by derivative of endotoxin – monophosphorolipides A is
now studied. Monoclonal antibodies to interleucines, phospholipase, to adhesive
molecules and contact factors are received and pass clinical approbation of
antibody to lipid A, to endotoxin and PNO. It is possible, that in future by
identification of mediators it will be possible to create “ cocktail “ from
antibodies which block receptors and enable to stop progresive process at the
systemic inflammatory answer.
Interferons - native and genoinginering preparations which concern
mainly to IFN (Roferoni A, Introni A, Realdironi, Laferoni etc.) - natural ways
of imunocorection and protection against infections, with success are applied
at present of acute and chronic infectious diseases.
Combined using of Carbapenemes, Roncoleucines- or interferons is
advanced achievement of modern therapy of septic diseases.
At serious course of a sepsis
stabilization of hemodynamics has crucial importance .
First of all it is necessary to restore volume of circulating blood. For this
purpose infuse cristaloides and colloid solutions in the ratio 2-4:1 under the
control of parameters of hemodynamics, including the central venous pressure.
The proof hypotension, even
after fast restoration of blood volume circulation, may be connected with
disorders of
regulation of vascular
tone. Application of inotropic preparations - Dopaminum, Dobutaminum, Dobutrexi in this case is expedient. The clinical effect
from Dopaminum will increase the cardiac emission (B adrenergic effect), rising
of peripheric vessels tone (A-adrenergetic effect), improvement of circulation
in parenchymatous bodies, first of all in kidneys (dopamineergetic effect).
Using of A-adrenomimetics (epinephrine) may be necessary only in case of inefficiency of
high doses of Dopaminum.
Respiratory support is necessary for
significant amount of patients with sepsis, however
application of different methods of artificial ventilation of lungs is limited
to cases of disease with development of acute respiratory insufficiency. In a
combination of inotropic therapy ventilating support promotes decrease of work
of muscles, improvement of oxygenation of blood and function of systemic
circulation.
In support of appropriate level of
metabolic and immune processes the important value has a feed of patients. The
early high-caloric enteroalimentation with the enlarged contents of fibers and
amino acids (an arginine, an ornithine) reduces frequency of complications and
duration of treatment. It is necessary to use enteral alimentary admixtures
(enpites), balanced under the contents of fibers, Adepses and carbohydrates.
It is expedient to use solutions of
amino acids for parenteral feeding (Alvesini, Aminosoli-600, Aminosoli-800,
Aminosoli KE, Infesoli 40 and etc.), Dextrosum, lipide emulsions (Intralipid).
DVS demands correction only in stage
of a decompensation.
Prophylaxis
It is necessary to
perform reatment of
primary foci. The measures, directing on
increase of resistance
of the organism have
an important meaning. These measures
are rational diet, regime
of work and
rest, physical tempering.
Staphylococci
are more frequent
etiological factor of
sepsis, that’s why the prophylaxis of
intrahospital staphylococcal infection
is necessary. The early
revealing and prohibition
of work of
medical personnel with
purulent inflammatory diseases (sore throat,
pyodermia) and opportune
hospitalization of the
patients with staphylococcal infection
in special departments
or wards. It is
necessary the revealing
of prolonged bacteriocarriers of
hospital strains
of staphylococces and
its sanation for
patients with immunodeficiency and
operating-room.
The
maintenance of sanitary-hygienic regime
has leading meaning
in the hospitals
of different profile.
It
is necessary to
use remedies, increasing nonspecific
resistance of the
organism of the
patients in the
groups of risk (infants,
patients with immunodeficiency and
other).