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 to 12 days and are followed by fever and sore throat with pharyngeal edema and erythema. Shortly after its onset, small vesicles develop (Fig.2) on the pharyngeal and oral mucosa: these rapidly ulcerate and increase in number, often involving the soft palate, buccal mucosa, tongue, and floor of the mouth. Gums are tender and bleed easily, and lesions may extend to the lips and cheeks (Fig.3).
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).