nHERPETIC DISEASE
MENINGOCOCCAL DISEASE
SEPSIS
Herpes nsimplex virus (HSV) infections are among the most common maladies naffecting humans. Often they are annoying and troublesome; occasionally they nare life-threatening.
The term herpes is derived from the Greek word meaning to creep, nand clinical descriptions of herpes labialis go back to the time of nHippocrates. Astruc, physician to the king of France, nis credited with the first description of genital herpes in 1736. Between 1910 nand 1920, the infectious nature of herpes lesions was demonstrated by producing ncorneal lesions in rabbits with material derived from herpes keratitis and nlabialis. As techniques for isolating and characterizing the virus became more nsimplified and serologic procedures were developed, our understanding of the nHSV clinical spectrum has greatly expanded. Studies during the past two decades nhave brought insights into the molecular biology of HSV. the nmechanisms of HSV latency and recurrence, and the first successful approaches nto therapy for certain types of HSV infections.
Etiology
Herpes nsimplex virus (herpesvirus hominis) shares many nproperties with other members of the herpesvirus groups, which in humans nincludes varicella-zoster, cytomegalovirus, Epstein-Barr virus, and humaherpesviruses type 6 and 7. The members of this group have an internal core ncontaining double-stranded DNA, an icosahedral capsid with 162 hollow ncapsomeres, and a lipid-containing laminated membrane or envelope (Fig.1).
The overall diameters of enveloped herpesviruses are 150-200 nm. nReplication occurs primarily within the cell nucleus and is completed by the naddition of protein envelopes as the virus passes through the nuclear membrane. nComplete virus replication is associated with lysis of the productive cell. All nmembers of the human herpesvirus group can also establish latent states withicertain types of cells they infect, although the physical nature of the viruses nduring periods of latency is unclear.
Fig.1. Herpes nsimplex virus
The development of monoclonal nantibody and restriction enzyme technologies have permitted an evefiner definition of variations among individual HSV isolates. It is now clear nthat HSV-1 and HSV-2 share certain glycoprotein antigens and differ with nrespect to others. Serologic differentiation between HSV-1 and HSV-2 infections ncan be readily made by detection of type-specific gG antibodies.
Epidemiology
Herpes simplex viruses have a worldwide distribution.There are no known animal nvectors for HSV, and although experimental animals can easily be infected, nhumans appear to be the only natural reservoir. Direct contact, with ntransmission through infected secretions, is the principal mode of spread. nHSV-1 is transmitted primarily by contact with oral secretions and HSV-2 by ncontact with genital secretions. Transmission can occur both from overtly ninfected persons and from asymptomatic excretors, although virus titers are nhigher in persons with active lesions and thus transmissability may be greater. nApproximately 15 % of the adults may be excreting HSV-1 or HSV-2 at nany given time depending on the population studied. For example, because shedding nof HSV-2 is related to sexual activity, prostitutes may have unusually high nrates of excretion.
The risk of heterosexual acquisition of HSV is greater in women thamen, and previous HSV-1 infection reduces the risk of subsequent HSV-2 ninfection.
Pathogenesis
On entry into skin sites HSV replicates locally nin parabasal and intermediate epithelial cells, which results in the lysis of ninfected cells and the instigation of a local inflammatory response. This feries nof events results in the characteristic lesion of superficial HSV infection, nthat is, a thin-walled vesicle on an inflammatory base. Multinucleated cells nare formed with ballooning degeneration, marked edema. Such lesions are nindistinguishable from those caused by varicella-zoster nvirus. Lymphatics and regional lymph nodes draining the site of primary ninfection become involved. Further virus replication may result in viremia and nvisceral dissemination, depending on the immune competence of the host.
In murine models the maturity of macrophages at the site of local ninfection helps determine whether virus remains localized or disseminates. nSubsequently, other host defense mechanisms, for example, the production of ninterferons, natural killer cells, protective antibodies, and sensitized killer nlymphocytes, are elicited to prevent the spread of infection.
Clinical manifestations
Primary HSV-1 infection is frequently nasymptomatic but may present as gingivostomatitis and pharyngitis most commonly nin children under the age of 5 years but occasionally in older persons. nIncubation periods range from 2 nto 12 days and are followed by fever and sore throat with pharyngeal edema and nerythema. Shortly after its onset, small vesicles develop (Fig.2) on the npharyngeal and oral mucosa: these rapidly ulcerate and increase iumber, noften involving the soft palate, buccal mucosa, tongue, and floor of the mouth. nGums are tender and bleed easily, and lesions may extend to the lips and cheeks n(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 nthe patient complains of severe mouth pain. Breath is fetid, and cervical nadenopathy is present. In children, dehydration may result from poor intake, ndrooling, and fever. In college-aged persons, primary HSV infection oftepresents as a posterior pharyngitis or tonsilitis. Included in the age-related ndifferential diagnosis are streptococcal or diphtheritic pharyngitis, nherpangina. aphthous stomatitis. Stevens-Johnsosyndrome, Vincent’s infection, and infectious mononucleosis.
Herpes simplex virus infections of the eye are nusually caused by HSV-1 (Fig. 4).
Fig.4. Herpetic infection of eye
Primary infections may be nmanifested by a unilateral follicular conjunctivitis with regional adenopathy nand/or a blepharitis with vesicles on the lid margin. Photophobia, chemosis, nexcessive tearing, and edema of the eyelids may be present. Some patients ndevelop dendritic figures or coarse, punctate, epithelial opacities. If disease nis limited to the conjunctiva, healing takes place within 2-3 weeks. However, nif systemic symptoms and signs of stromal involvement are npresent, the healing phase may be delayed. Spontaneous healing of the nconjunctiva and cornea is usually complete.
Primary genital infection is most common iadolescents and in young adults and is usually (in 70-95 % of the cases) caused nby HSV-2 (Fig.5).
Fig.5. Herpes genital infection
The nduration of incubation periods 2-7 days. In men, vesicular lesions on an erythematous base usually appear on the nglans penis or the penile shaft. In the female, lesions may involve the vulva, nperineum, buttocks, cervix, and vagina and are frequently accompanied by a nvaginal discharge). Extra-genital lesions occur during the course of primary ninfection in 10-20 % of patients. Primary infection in both sexes may be nassociated with fever, malaise, anorexia, and tender bilateral inguinal nadenopathy. Although vesicular lesions may persist for several days in men, iwomen they rapidly ulcerate and become covered by a grayish-white exudate. Such nlesions may be exquisitely tender, and urethral involvement may result idysuria or urinary retention. Herpetic sacral radiculomyelitis naccompanying genital infection may also lead to urinary retention, neuralgias, nand obstipation; in such patients a loss of anal tone, diminished nbulbocavernosus reflex, and cystometrographic evidence of lower motor neurodysfunction can sometimes be demonstrated. Lesions of primary genital herpes nmay persist for several weeks before healing is complete. Previous HSV-1 ninfection may reduce the severity and duration of a first episode of genital nherpes caused by HSV-2. In the diagnosis of genital herpes other sexually ntransmitted infections such as chancroid or syphilis, erosions secondary to nexcoriation, genital manifestations of Behcet syndrome or erythema multiforme, nand local candidiasis must all be distinguished.
Although primary infections are usually iperioral, ocular. or genital nareas, any skin site may be initially involved. Primary HSV skin infections may nbe extensive and mimic herpes zoster. nAlthough a dermatomal distribution is not usually maintained nand the pain is less severe.
Primary perianal and anal HSV-2 infection is becoming increasingly well nrecognized, both in women and in male homosexuals. Pain is the primary symptom, nwith itching, tenesmus, and discharge also noted. Systemic complaints of fever, nchills, malaise, headache, difficulty in urinating, and sacral paresthesias may nbe present. On examination, vesicles and ulcerations may be seen in perianal nand sometimes in anal areas. They may become confluent and result in a grayish nulcerating cryptitis surrounded by a red edematous mucosa. Bilateral inguinal nadenopathy is common. The course is generally self-limited unless bacterial ninfection supervenes, with healing occurring in 1-3 weeks. However, in the nsetting of the acquired immunodeficiency syndrome (AIDS), herpes proctitis as nwell as other cutaneous manifestations of HSV infection may be prolonged and nprogressive.
Recurrent infections
Recurrent herpes labialis is nfrequently heralded by prodromal symptoms (pain, burning, tingling, or itching) ngenerally lasting for less than 6 hours but occasionally as long as 24-48 nhours. Vesicles appear most commonly at the vermillion border of the outer lip nand are associated with considerable pain. The lower lip is more frequently ninvolved, although individual patients may have stereotyped lesions at similar nsites during each recurrence. The lesion area is usually less than 100 mm, and nlesions progress from the vesicle to the ulcer/crust stage within 48 hours. nPain is most severe within the first 24 hours after the appearance of lesions. nHealing is generally complete within 8-10 days. Rarely, recurrences may occur nin the mouth or on the nose, chin, or cheek. Systemic complaints do not usually naccompany recurrent herpes labialis, although local adenopathy may occur.
Ocular infection may recur as keratitis, blepharitis, or kerato-conjunctivitis. nRecurrent keratitis is usually unilateral but is rarely (in 2-6 % of the cases) nbilateral. Two main types of keratitis may develop: dendritic ulceration or nstromal involvement. Branching dendritic ulcers that strain with fluoresceiare virtually diagnostic and are often accompanied by a loss in corneal nsensation. Visual acuity may be decreased because the ulcers frequently involve nthe pupillary portion of the cornea. They may be accompanied by minimal nanterior opacification or deep stroma involvement. Occasionally, extensive nameboid corneal ulcers may evolve, particularly if topical steroids have beeapplied. Superficial keratitis usually heals, but recurrent infection may lead nto deep stromal involvement and uveitis, which may in part be mediated by nhypersensitivity reactions to viral or altered cellular antigens. A gradual ndiminution in visual acuity takes place, and individual attacks may last for nseveral months with the formation of dense scars, corneal thinning, and nneovascularization. Permanent visual loss may result, and rarely, rupture of nthe globe develops.
Recurrent genital lesions in both sexes are generally associated with nless severe systemic symptoms and less extensive local involvement than are nprimary attacks. A prodrome of tenderness, itching, burning or tingling is nofteoted for several hours before a recurrence. Lesions in women are most nofteoted on the labia minora, labia majora, and perineum and less commonly non the mons pubis or buttocks. Lesions in men are most often found on the glans nor penile shaft. In women recurrences tend to be more severe. Healing generally noccurs in 6-10 days. Virus shedding diminishes more slowly in women and caoccur between recurrences in both sexes. Occasionally, genital recurrences are nassociated with headache and even with aseptic meningitis. Urethral stricture nand labial fusion have also been reported after recurrent genital infections.
Recurrent HSV-1 or HSV-2 infections may develop on extremities; occasionally nsuch lesions are associated with severe local neuralgia. Local edema and nlymphangitis may also occur during recurrences on extremities.
Complications
Herpes nsimplex encephalitis is a rare complication of herpetic ninfection and yet is one of the most common acute sporadic viral diseases of nthe brain. Although little is known about the pathogenesis of HSV-1 nencephalitis in humans, the virus is believed to spread by neural routes into nthe brain during either primary or recurrent infection. Temporal lobes are the nprincipal target areas of the virus, and a necrotizing hemorrhagic encephalitis nresults.
Herpes simplex nencephalitis occurs at all ages in both sexes, and in all seasons. The clinical ncourse may begin suddenly or after a brief influenzalike prodrome. Headache, nfever, behavioral disorders, speech difficulties, and focal seizures are nprominent features; olfactory hallucinations may be present. Cerebro-spinal nfluid examination is variable but frequently shows a moderate pleocytosis with nmononuclear and polymorphonu-clear leukocytes: protein levels are slightly nelevated, and glucose is generally normal. Infectious virus is rarely present nin cerebrospinal fluid during encephalitis, and brain biopsy with appropriate nhistologic and cultural techniques is currently the most reliable way to make nthe diagnosis. Although various antibody and antigen assays may provide nadjunctive information. they are not sensitive enough nto provide a sufficiently early diagnosis. Rapid diagnosis of herpes simplex nencephalitis by nested polymerase chain reaction assay of cerebrospinal fluid nhas been reported by certain research laboratories. Herpes simplex virus nencephalitis must be distinguished from other forms of viral encephalitis, ntuberculous and fungal meningitis, brain abscesses, cerebrovascular accidents, nand brain tumors.
The course in untreated patients is usually one nof rapid deterioration over several days that progresses to coma and death. nMortality in untreated biopsy-proven cases is 60-80 %, and fewer than 10 % of nthe patients are left without significant neurologic sequelae.
Relationship to Other Diseases
Erythema Multiforme. nAllergic cutaneous and mucous membrane disorders may accompany or follow acute nHSV infections. Up to 75 % of all cases of erythema multiforme are regularly npreceded by an attack of herpes simplex. Both HSV-1 and HSV-2 may be involved, nand the cutaneous manifestations range from mild to severe (Stevens-Johnsosyndrome) and may be recurrent. Inactivated HSV antigens injected intra-dermally ninto persons subject to erythema multiforme have induced such attacks, and HSV nantigen has been identified in skin biopsy specimens from affected lesions.
Cancer. Although HSV nhas been suspected as a cause of cervical and other cancers on the basis of both nepidemiologic and laboratory studies, many recent studies do not support its netiologic role in human cancers.
Idiopathic Neurologic Syndromes. Herpes simplex virus infections have nbeen implicated as possible factors involved in the pathogenesis of various nneurologic disorders of unknown etiology, including idiopathic facial paralysis n(Bell’s palsy), multiple sclerosis, atypical pain syndromes, ascending nmyelitis, trigeminal neuralgia, Mollaret’s meningitis, and temporal lobe nepilepsy. The associations are based on the known predilection of HSV for nerve ntissue, on serologic or nucleic acid studies, and on the occasional nobservations of temporal relationships between attacks of herpes labialis or ngenitalis and attacks of the neurologic syndrome.
Diagnosis
Although experimental animals nand embryonated eggs are susceptible to infection with HSV strains, tissue ncultures have largely replaced these hosts for diagnostic purposes. Primary nhuman embryonic kidney, rabbit kidney, and human amnion cells readily support nthe replication of HSV. Continuous cell strains or cell lines of human diploid norigin and certain continuous monkey kidney cell lines also support HSV nreplication, but to a lesser extent. Cytopathic effects usually appear rapidly, nwithin 24-48 hours if the virus inoculum is high. Cells become rounded and nclump, with rapid progression of cytopathic effects throughout the cell nmonolayer. Ballooning degeneration and the formation of multinucleated nsyncytial giant cells may be observed, particularly with HSV-2 isolates. nVesicles contain their highest tilers of virus within the first n24-48 hours, and specimens should be collected early and promptly inoculated ninto tissue cultures. If a delay is unavoidable, specimens can be stored iappropriate carrying medium at 4-9°C for a few hours. but nfor longer periods they should be stored at -70°C. Typing of isolates can be naccomplished by using a variety of serologic techniques including nimmunohistochemistry or microneutralization. When tissue specimens such as neural nganglia are being studied for the presence of virus, tissue explanation or cell ncocultivation techniques have proved useful in facilitating virus isolation.
The recent development of monoclonal antibodies to individual herpes nvirus antigens should allow for the more precise identification and typing of nHSV isolates. HSV-1 and HSV-2 have both type-specific and cross-reactive nantigens that are useful for both grouping and type discrimination. Moreover nthe cloning of herpes DNA fragments in recombinant bacteria may permit the nproduction of probes to identify herpes genomes in the absence of infectious nvirus.
For a rapid diagnosis of skin or mucous membrane nlesions, scrapings from suspect lesions may be smeared, fixed with ethanol or nmethanol and stained with Giemsa or Wright preparation. The presence of nmultinucleated giant cells indicates infection with HSV or varicella-zoster virus. When using cytologic techniques, the nPapanicolaou cervicovaginal stain or the Paragon multiple stain, intranuclear ninclusions may also be seen. Alternatively, such material can be examined for nherpes antigens by immunohistochemical techniques or by in situ DNA nhybridization.
Serologic techniques may be helpful in diagnosing nprimary HSV infections but are rarely of value in recurrent infections. A nvariety of assays have been used including neutralization, complement fixation, npassive hemagglutination, indirect immunofluorescence, radioimmunoassay, enzyme nimmunoassays, complement-mediated cytolysis, and antibody-dependent cellular cytolysis. nDuring primary infections, a fourfold or greater rise in titer is observed nbetween acute and convalescent sera. In recurrent infections such rises may or nmay not be observed. Many licensed enzyme immunoassays appear to give ninaccurate information concerning HSV-infecting subtypes.
Measurement of IgM HSV antibodies in infants may be helpful in the ndiagnosis of neonatal infection. Such antibodies usually appear within the nfirst 4 weeks of life in infected infants and persist for many months. Measurement nof IgM antibodies in older persons has not proved useful in separating primary nfrom recurrent infections.
Approaches to detect specific HSV antigens, nantibodies, or DNA in cerebrospinal fluid are under development. Such ntechniques may circumvent the need for invasive procedures such as brain biopsy nto make the diagnosis of herpes encephalitis.
Treatment
A number of nucleoside derivatives interfere with nthe synthesis of HSV DNA. Some of these (trifluorothymidine, vidarabine) are nuseful in and licensed for the topical treatment of herpes keratitis. nVidarabine and acyclovir are also useful for systemic HSV infections. None of nthese agents affects latent virus.
In the immunocompromised host, acyclovir is nuseful as both treatment and suppression of recurrent mucocutaneous HSV nlesions. For the treatment of acute episodes, virus shedding, local symptoms, nand time to healing can be reduced by intravenous or oral regimens (400 mg five ntimes per day). Acyclovir is also useful in the prevention of herpetic recurrences nin immunocompromised hosts including transplant recipients, leukemics nundergoing induction chemotherapy, and patients with AIDS. Regimens of 200-400 nmg two to five times per day have been satisfactory in preventing recurrences namong seropositive patients.
Parenteral acyclovir is indicated for ndisseminated or central nervous system HSV infections. In patients with nbiopsy-proven HSV encephalitis, acyclovir was compared with vidarabine and nfound to be superior in reducing mortality. Doses of 10 mg/kg every 8 hours for n14-21 daysare recommended. Iewborns with disseminated HSV infections, nacyclovir and vidarabine appear equivalent but because of ease of nadministration, acyclovir is recommended.
Acyclovir has little acute toxicity. Drug-related nneurotoxicity (disorientation, hallucinations, tremors, ataxia, and seizures) nhas been described rarely, and reversible renal dysfunction may occur, nparticularly following a rapid bolus infusion.
Prophylaxis
Experimental vaccines against HSV have shown promise nin animal models, and some are undergoing human trials. Limited trials ihumans, however, have been unsuccessful, and it is unlikely that a human HSV nvaccine will be generally available in the near future.
The prevention of neonatal disease in the offspring of mothers with ngenital infection presents special problems.
MENINGOCOCCAL INFECTION
Definition
Meningococcal ninfection is an nacute infectious disease nof the human, ncaused by meningococcous Neisseria nMeningitigis. The mechanism of nthe transmission of the infection nis air-drop. The disease nis characterized by ndamage of mucous nmembrane of nasopharynx (nasopharingitis), generalization of nthe process in form nof specific septicemia (meningococcemia) and inflammation nof the soft ncerebral membranes (meningitis).
History and geographical ndistribution
Epidemic cerebrospinal nmeningitis (one of the nmost clinically expressive nforms of the ndisease) was known else nin profound antiquity. The description nof outbreaks of nthis infection is ncontained in reports nof Areteus (III century nof our era), Egynsky (VII century).
Epidemic ncerebrospinal meningococcal meningitis was first described by Vieusseaux i1805. Subsequent reports throughout the nineteenth century confirm its episodic nepidemic nature with a propensity for affecting young children and military nrecruits assembled in stationary barrack situations. In 1887, Weichselbaum nisolated the meningococcus from the cerebrospinal fluid, and the etiologic nrelationship between this organisms and epidemic meningitis was firmly nestablished.
Kiefer in 1896 and Albrecht and Ghoin 1901 found that healthy persons could become carriers of the meningococcus. nSerotypes of the meningococcus were first recognized by Dopter in 1909. This nlaid the basis for serum therapy in the treatment of meningococcal infection. The agent was nisolated from the nblood by V. Osler in n1899. It had an nimportant meaning, because many nproblems of pathogenesis nof the disease nwere explained. It was nevidence that meningitis nis not single nmanifestation of the ndisease.
In 1937, sulfonamide therapy nradically altered the outcomes of meningococcal infection. With the advent of nantibiotic agents, treatment of meningococcal infection became more effective, nand mortality declined. With the subsequent world wide emergence of resistant nstrains and with the absence of effective chemoprophylaxis, renewed interest iimmunoprevention has occurred and has led to the development of safe and neffective vaccines against the groups A, C, Y and W-135 meningococcal group.
Meningococcal infection noccurs on the nall continents. It is serious nproblem for public nhealth. It is registered nin 170 countries nof the world.
Etiology
The causative agent is Neisseria meningitidis. It is small ngramm-negative diplococcus, aerobic, catalise and oxidase-positive, not-motile nand possess a polysaccharide capsule, which is the main antigen and determines nthe serotype of the species. Meningococcus nmay be seen inside and outside of neutrophills (Fig.6). The main serogroups of npathogenic organisms are A, B, C, D, and W135, X, Y, Z and L. The bacterial nmembrane is a lipopolysaccaride.
Fig.6. Neisseria meningitidis
The npathogenic properties of nmeningococcus are known ninsufficiently, because nmeningococcal infection is nanthroponosis. The factors of npathogenic action of nmeningococcus are biological nproperties, promoting its attachment non the mucous nmembrane of nasopharynx, depression symbiotic nmicroflora, penetration nthrough mucous barriers, toxic properties nand other.
One nof such properties nis specific attachment nor adhesion of nmeningococcous to the ncells of epithelium nof respiratory tract. Adhesion is nphenomenon, promoting to colonization nof meningococcus on nthe mucus. Physical factors n(adsorption of microbes non the surface nof the cell) nand fermentative processes nhave the meaning nin the appearance nof adhesion.
Meningococci are very exacting nto composition of nutritive mediums. Its nreproduction may be nonly in presence nof human’s protein nor animal’s protein. Due nto destruction of the nmicrobe’s cell endotoxin nis delivered (of lipopolysaccharide origin). Exotoxin is no produced. The agent nof meningococcal infection nis characterized by nlow resistance in nthe environment. nMeningococci perish during ntemperature 50°C through 5 nminutes, during temperature 100°C – through n30 seconds. Meningococci have a little nresistance to low temperature.
Epidemiology
Meningococcal infection is typical nanthroponosis. The sourses of infection are nhealthy carriers of nmeningococcus, the patients with nmeningococcal nnasopharingitis and the npatients with generalized forms of nthe disease.
The patients with generalized nform are more ndangerous. It is proved nthat they are ndangerous for surrounding npersons in 6 ntimes than healthy ncarriers. However, the main sources nof the infection nare carriers, because 1200-1800 n(according other data – 50000) ncarriers have occasion nto one patients nwith generalized form nof the disease.
Thus, the patients nwith generalized form nof the disease nare the source nof infection for n1-3 % of infected npersons, the patients with nmeningococcal nasopharingitis – nfor 10-30 %, carriers are nthe sources of ninfection for 70-80 % nfrom general number nof infected.
The nlevel of healthy ncarriers promotes the nlevel of morbility nin certain region. So, carriers may ncompose 3-12 %. It is temperate nsporadic morbility. Carriers may achieve n20 %. This nsituation is marked nas unsatisfactory. The outbreaks are nobserved. Carriers may nachieve 30-40 %. In this case nepidemic of meningococcal ninfection arises.
The mechanism of transmission of the infection nis air-drop. The infection is nrealized during cough, sneezing. In this nthe narrow contact nand sufficient exposition nare necessary. It is nproved by A.A. Favorova (1976) nthat the ninfection is realized non the distance nless 0,5 meter.
The nwide distribution of nmeningococcal infection is npromoted some causes nin the countries nof equatorial Africa. The nmain causes are nconnected with social nfactors (unsatisfactory nsanitary-hygienic conditions of the life nof the majority npart of the npopulation, high density of nthe population and nother).
In meningococcal ninfection one of an important ncharacteristic of epidemic nprocess is periodical nrise and fall nof the morbidity. The duration of nthe period with nhigh morbidity is ndifferent. It nmay be 5-10 nyears and more. Then the nperiod of the nfall of the nmorbidity becomes. It is continued nfrom 5 till n20 years.
In meningococcal ninfection epidemic process nis characterized by seasonal nspread. It is manifested nespecially during epidemics. The morbidity nmay compose 60-70% nfrom year’s morbidity nduring seasonal rise. The nonset of the nseasonal rise is nin quanuary in nthe countries with temperate clinimate. It achieves of nmaximum in march – april.
The nestimate of the nage morbidity of nmeningococcal infection testifies nabout that 70-80 % nof the cases nof the diseases nhave occasion to nchildren. Children nof the age n1-5 years compose 50 %. Meningococcal infection nis marked rarely nat the first nthree month of nthe life.
The npersons of the nyoung age (15-30 years) ncompose the majority namong adult patients. It nis explained by nsocial factors and nfeatures of the nlife young people (service in nthe army study nin the educational nestablishments, living in the nhostel). These factors explain npredomination of men in the nstructure of the nmorbidity.
The nage of carriers nof meningococcal infection nis different from nthe age of nthe patient. The larger part nof carriers is nreveled among adults. The portion of nthe children is na little. The morbidity is nhigher in the towns nthen rural locality.
The considerable noutbreaks of the ndiseases were described nin the educational nestablishments of the nclosed type and nespecially among military (as nat peaceful time nsuch as during nwar).
Pathogenesis
In meningococcal ninfection entrance gates nare mucous membrane nof nasopharynx. It is place nof primary localization nof the agent. Further meningococci nmay persist in nepithelium of nasopharynx nin majority of nthe cases. It is nmanifested by asymptomatic nhealthy carriers. In some ncases meningococci may ncause inflammation of mucous nmembrane of upper nrespiratory tract. It leads to ndevelopment of nasopharingitis.
The nlocalization of meningococcus on nmucous membrane of nnasopharynx leads to ndevelopment of inflammation nin 10-15 % of nthe cases.
The nstages of inculcation non the mucous nmembrane of nasopharynx nand penetration of nmeningococcus into the nblood precede to nentrance of endotoxin ninto the blood and ncerebrospinal fluid. These stages are nrealized with help nof factors of npermeability. It promotes of the resistance nof the meningococcus nto phagocytosis and naction antibodies.
Meningococci are able nto break local nbarriers with help nof factors of nspread (hyaluronidase). Capsule protects meningococci from nphagocytosis. Hematogenous nway is the nprincipal way of nthe spread of nthe agent in nthe organism (bacteremia, ntoxinemia). Only the agent nwith high virulence nand invasive strains nmay penetrate through nhematoencephalitic barrier. The strains of serogroup A high invasivicity.
Meningococci penetrate into nthe blood after nbreak of protective nbarriers of mucous nmembrane of upper nrespiratory tract. There is hematogenous ndissemination (meningococcemia). It nis accompanied by nmassive destruction of nthe agents with nliberation of endotoxin. Meningococcemia and ntoxinemia lead to ndamage of endothelium nof the vessels. Hemorrhages are nobserved in mucous nmembrane, skin and parenchymatous organs. It may nbe septic course nof meningococcemia with formation of the secondary metastatic nfocuses in the endocardium, joints, internal mediums of the eyes.
In most of the cases penetration of meningococci in the cerebrospinal fluid nand the soft cerebral covering is fought about by hematogenous ways through the nhematoencephalic barrier. Sometimes meningococci nmay penetrate into the skull through perineural, perilymphatic and the nperivascular way of the olfactory tract, through the enthoid bone.
Thus the meningococci enter into subarachnoid space, multiply and course serous-purulent nand purulent inflammation of the soft cerebral coverings. The inflammatory nprocess is localized on the surface of the large craniocerebral hemispheres, nand rarely, on the basis, but sometimes it may spread in the ncovering of the spinal cord. During severe duration of the inflammatory process nthe cranium is covered by purulent mather (so-cold “purulent ncap”). It may lead nto involvement of nthe brain’s matter ninto inflammatory process nand meningoencephalitis.
The process may engulf the nrootlets of – VII, VIII, V, VI, III and XII pairs of cranial nerves.
Pathogenic properties nof the agent, state nof macroorganism, state of nimmune system, functional state nof hematoencephalitic barrier nhave the meaning nin the appearance nof meningitis of nany etiology.
Endothelium of ncapillaries, basal membrane, n“vascular pedicles” of nglyocytes and basic nsubstance of mucopolysaccharide origin nare the morphologic nbasis of hematoencephalic barrier. Hematoencephalic barrier regulates metabolic nprocesses between blood nand cerebrospinal fluid. It nrealizes protective function nfrom the alien nagents and products nof disorder of nmetabolism. The most alterations nare observed in nreticular formation of nthe middle brain.
In npurulent meningitis some pathogenic nmoments are promoted nby rows of nparadoxical appearances in hematoencephalic barrier nand membranes of nthe brain. In physiological nconditions hematoencephalic nbarrier and brain’s nmembranes create closed nspace, preventing brain’s tissue nfrom influence of nenvironment. In this case nsecretion and resorbtion nof cerebrospinal fluid nare proportional. In meningitis nclosed space leads nto increased intracranial npressure due to nhypersecretion of cerebrospinal nfluid and to nedema of the nbrain. The degree of swelling-edema of nthe brain is ndecisive factor in nthe outcome of nthe disease.
The next nstages may single nout in pathogenesis nof purulent meningitis:
1. nPenetration of nthe agent through hematoencephalic barrier, irritation of nreceptors of soft ncerebral membrane of nthe brain and nsystems, forming cerebrospinal fluid.
2. nHypersecretion of ncerebrospinal fluid.
3. nDisorder of ncirculation of the nblood in the nvessels of the nbrain and brain’s nmembranes, delay of resorbtion nof cerebrospinal fluid.
4. nSwelling-edema of nthe brain hyperirritation of the nbrain’s membranes and nradices of cerebrospinal nnerves.
Besides that, nintoxication has essential nmeaning in pathogenesis nof purulent meningitis. Vascular plexuses nand ependime of nventricles are damaged nmore frequently. Then the nagent enters in nto subarachnoid space nand brain’s membranes nwith the spinal nfluid flow.
In some cases, especially in nincreated patients the process nmay turn ninto ependima of nthe ventricles. As a nresult it may nbe occlusion of nthe foramina of Lushka, Magendie, the aqueduct of Sylvius. It leads to development nto hydrocephaly.
In the pathogenesis of nmeningococcal infection toxic and allergic components play an important role. nThus, in fulminate forms nof meningococcal infection ninfectious-toxic shock develops ndue to massive ndestruction of meningococcus nand liberaton of nconsiderable quantity of nendotoxin. In infectious-toxic shock nthe development of nthrombosis, hemorrhages, necrosis nin different organs nare observed even nin the adrenal nglands (Waterhause – Fridrechsen nsyndrome).
The nsevere complication may ndevelop as a nresult of expressive ntoxicosis. It nis cerebral hypertension, leading frequently nto lethal outcome, cerebral coma. This nstate develops due nto syndrome of nedema swelling of nthe brains with simultaneous nviolation of outflow nof cerebrospinal fluid nand its hyperproduction. The increased nvolume of the nbrain leads to npressure of brain’s nmatter, its removement and nwedging of medulla noblongata into large noccipital foramen, pressure of noblong brain, paralysis of nbreath and cessation nof cardiovascular activity.
Morbid anatomy
In meningococcal infectiopathologoanatomical changes depend on form and duration of the disease.
Nasopharingitis is ncharacterized by hyperemia of the pharyngeal walls, edema of the epithelial ncells, regional infiltration, hyperplasion and hyperthophy of lymphoid nfollicles. Signs of catarrhic inflammation are found in trachea and bronchi.
Cases nof fulminate meningococcal infection is characterized by blood vessels disorders and severe impairments of blood ncirculation. The main target are the microcirculatiovessels. The vascular lumen turns narrow, thrombs are found. Thrombs are usually found in small veins. nHemorrhages into skin, subcutaneous tissue, lungs, myocardium, subendocardial nhemorrhages, hemorrhages into renal parenchyma, nadrenals, brain (Fig.7) and subarachnoidal space are typical.
Fig.7. Hemorrhages into brain
Fig.8. Purulent inflammation
Meningococcous meningitis is ncharacterized by serous or purulent inflammation of pia mater (Fig.8).
Clinical manifestation
The incubation period is 1-10 ndays, more frequently n5-7 days.
Classification of the clinical nforms of meningococcal infection:
I. Primarily localized forms:
a) meningococcal ncarrier state
b) acute nnasopharyngitis;
c) pneumonia.
II. Gematogenously generalized forms:
a) meningococcemia: ntypical acute meningococcal sepsis; chronic;
b) meningitis; nmeningoencephalitis;
c) mixed forms (meningococcemia + meningitis, nmeningoencephalitis).
d) rare nforms (endocarditis, arthritis, iridocyclitis).
In meningococcal carriers the clinical nmanifestations are absent.
Meningococcal nasopharingitis
The most common complains of nthe a patients are headache, mainly in the frontal-parietal region, sore nthroat, dry cough, blocked nose, fatigue, weakness, loss of appetite, nviolation of the nsleep. In most of the patients body temperature rises nupto subfebrile and lasts for not more than 3-7 days, sometimes 5-7 days. The nskin is pale, conjunctival vessels and sclera are ninjected. There are nhyperemia and edema of the mucous nmembrane of the nose. In many patients the posterior wall of nthe pharynx seem to be covered by mucous or mucous – purulent exudation.
Inflammatory changes in the nnasopharynx can be noticed after 5-7 days, hyperplasion of lymphoid follicles nlasts longer (till 14-16 days). In the peripheral blood temperate leukocytosis nwith neutrophylosis and a shift of leukocytaric formula to the left, increase nin ERS may be revealed. Nasopharyngitis precedes nto development of ngeneralized forms of nthe disease.
Meningitis
It may nstart after meningococcal nnasopharyngitis, but nsometimes primary symptoms nof the disease narise suddenly. In meningitis nthree symptoms are revealed constantly: fever, headache and nvomiting. Temperature is increases nquickly with chill nand may reach n40-41°C nduring few hours. Intermittent, remittent, constant, double waved ntypes of the ntemperature occur in nmeningitis. The patients nsuffer from severe nheadache, having diffuse or npulsatory character. nHeadache is very nintensive at the nnight. It increases due nto change of nbody position, sharp sounds, bright light. Vomiting arises nwithout precedent nausea. There nis no connection nwith food and nrelief after vomiting. It nis rule abundant, by “fountain”, repeated. Sometimes, nvomiting arises on nthe peak of nheadache.
In meningitis nhyperthermia, hyperkynesia, photophobia, hyperalgesia, hyperosmia are nnoticed. These symptoms are nrevealed more frequently nin children. The severe nconvulsions arise in nthe many patients nat the first nhours of the ndisease (clonic, tonic or mixed ntypes). In small children nmeningococcal meningitis may nstart with convulsions.
The ndisorders of consciousness occupy nthe great place nin clinical picture (from nsopor till coma). The nloss of consciousness develops nafter psychomotoric excitement. The loss nof consciousness at the nfirst hours of nthe disease is nunfavorable sign.
During objective nexamination meningeal symptoms nstand at the nfirst place. It is ndescribed near 30 nmeningeal signs. A few nmeningeal signs are nused in practice: rigidity of noccipital muscles, Kernig’s symptom, Brudzinsky’s symptom (upper, middle and nlower). The estimate of nstate of fontanelle nis very important nin infants. There are nthree symptoms of nmeningitis in infant: swelling, tension and nabsence of fontanelles npulsation.
There nis no accordance nbetween expression of nmeningeal syndrome and severity nof the disease. The nexpression of different symptoms nis no similar nat the same npatient. The patient has ncompulsory pose during nserious cases. He lays non side with ndeflection of the nhead backwards n(Fig.9). The legs nare curved in nknee-joint and pelvic-femoral joint. The nlegs are pulled nto abdomen. Asymmetry and increased ntendinous, periostal and dermal nreflexes are observed nin the patients. These reflexes nmay be decreased nduring expressive intoxication. Pathological reflexes nmay be revealed (such as nBabinski’s, Hordon’s, nRossolimo’s reflexes, foot’s nclones), and also symptoms nof damage cranial nnervous (more frequently III, VI, VII, VIII pairs).
Fig.9. Patient’s nspecific pose in case of meningitis
The multiple nsymptoms of the lesion of nthe other organs nand systems are nconnected with intoxication. There is ntachycardia at the nfirst hours of nthe disease. Then it nmay be bradycardia. Arrhythmia, tachypnoea (30-40 ntimes in minute) nare possible. The tongue nis covered by ndirty brownish coat. It nis dry. Abdomen is npulled inside. There is ntension of abdomen muscles.
The nexternal appearance of nthe patients is nvery typical. There is nhyperemia of the nface and neck. Sclera’s vessels nare injected.
In nhemogram high leukocytosis, neuthrophylosis with nshift of formula nto the left, increased ERS nare observed. Small proteinuria, microhematuria, ncylinderuria are marked nin urine.
Fulminate course of nmeningitis
With syndrome of nbrain’s swelling and nedema is the nmost unfavorable variant. There is nhypertoxicosis during this nform and high npercentage of mortality. The main nsymptoms are consequence nof inclination of nthe brain in nto foramen magnum nand strangulation of nmedulla oblongata by ntonsils of cerebellum. nImmitant symptoms from ncardiovascular and respiratory nsystems develop quickly. Bradycardia appears. Then nit is changed nby tachycardia. Arterial pressure nmay fall catastrophically, but it nincreases more frequently ntill high level. Tachypnoea arises (till n40-60 times/min) with nhelp of axillary nmuscles. The disorders of nbreath lead to nits sudden interruption. These symptoms develop in hyperthermia, clonic cramps nand loss of nconsciousness. Cyanosis of the nskin, hyperemia of the nface are marked. Pyramidal signs, nsometimes symptoms of ndamage of cranial nnerves, decreased corneal reflexes ncontraction of pupils nand its decreased nreaction on light nare determined. Death occurs ndue to respiratory nfailure at the nfirst hours of nthe disease, rarely on n2-3 day or non 5-7 day.
Meningitis with syndrome nof cerebral hypotension
It is nrare variant of the ncourse of meningococcal nmeningitis. It is observed nprincipally in children.
The ndisease develops impetuously, with sharp ntoxicosis and exicosis. Stupor develops nquickly. Cramps are possible. Meningeal signs nare no expressive, nbecause, the diagnostics is ndifficult. Intracranial npressure rapidly falls. In nthis case the nvolume of the nfluid in the nbrain’s ventricles decreases. Ventricular collapse ndevelops. In infant the nlarge fontanelle is ndepressed. In adults and nchildren supporting moments nin diagnostics are nclinical signs of ndehydration and hypotension nof cerebrospinal fluid, which nflows out by nrare drops. The fall nof intracranial pressure nmay lead to ndevelopment of severe ncomplication – subdural hematoma.
Meningitis with syndrome nof ependimatitis (ventriculitis)
Now it nis rare form nof meningitis. This form ndevelops during late nor insufficient treatment nof the patients. Especial severity nof the disease nis connected with nspread of inflammation non ventricles membranes (ependime) and ninvolvement of brain’s nsubstance in to npathological process.
The nprincipal clinical symptoms nare total and nexpressive muscular rigidity. The npatients accept the nparticular pose. The disorder nof psychic, sleeping, tonic nand clonic cramps nare observed. The body temperature is nnormal or subfebrile nduring general severe nstate of the npatient. Vomiting is constant nsymptom. Hydrocephalia and cachexia ndevelop due to prolonged ncourse and (or) nnoneffective therapy of nependimatitis.
Meningoencephalitis
It is rare nform of meningococcal ninfection. In this case nthe symptoms of nencephalitis predominate, nbut meningeal syndrome nis weakly expressed. Meningococcal encephalitis nis characterized by nrapid onset and nimpetuous cramps, paresises and nparalyses. Prognosis is unfavorable. The mortality nis high and nrecovery is incomplete neven in modern nconditions.
Meningococcemia (meningococcal sepsis)
The disease is more impetuous, nwith symptoms of toxicosis and development of secondary metastatic foci. The onset of the disease is an acute. Body temperature may nincrease upto 39-41 0C and lasts for 2-3 days. It may be continous, intermittent, nhectic, wave-like. It is possible the course of the disease without fever. There nis no accordance nbetween degree of nincreasing of the ntemperature and severity nof the course nof the disease.
The other nsymptoms of intoxication narise simultaneously with nfever: headache, decreased nappetite or its absence, ngeneral weakness, pains in nthe muscles of nthe back and nlimbs. Thirst, gryness nin the mouth, pale skin or cyanosis, ntachycardia and sometimes ndysphnoea are marked. The arterial pressure increases in nthe beginning of nthe disease. Then it decreases. It may nbe decreased quantity nof urine. Diarrhea may nbe in some npatients. It is more ntypical for children.
Exanthema is more clear, constant and ndiagnostically valuable sign nof meningococcemia.
Fig.10. Exanthema in case of nmeningococcemia
Dermal nrashes appear through 5-15 nhours, sometimes on the nsecond day from nthe onset of nthe disease. In meningococcal ninfection rash may nbe different over ncharacter, size of nrash’s elements and nlocalization. Hemorrhagic rash nis more typical (petechias, ecchymosis and npurpura).
The elements nof the rash nhave incorrect (“star-like”) ( nFig.10) form, dense, coming out over nthe level of nthe skin. Hemorrhagic rash is ncombined inrarely with nroseolous and papulous rash.
The severe ndevelopment of the nrash depends from nthe character, size and ndepth of the nits elements. The deep nand extensive hemorrhages nmay be necrosed. Then it nmay be formation nof deep ulcers. Sometimes deep nnecrosis is observed non the limbs nand also, necrosis of nthe ear, nose and nfingers (Fig.11) of the nhands and legs (Fig.12).
Fig.11. Necrosis of fingers
Fig.12. Zones of leg necrosis
During biopsy meningococci are nrevealed. Exanthema nis nleucocytaric-fibrinous nthrombosis, contained the agent nof meningococcal infection. Thus, nin meningococcal infection nrash is the nsecondary metastatic foci nof the infection.
Joints occupy nthe second place nover localization of nmetastases of the nagent. At the last nyears arthritises and npolyarthritises are marked nrarely (in 5 % nof the patient nduring sporadic morbidity nand in 8-13 % nof the patient nduring epidemic outbreaks). The small njoints are damaged nmore frequently. Arthritis is naccompanied by painful nmotions, hyperemia and edema nof the skin nover joints.
Arthritises appear nlater then rash n(the end of the nfirst week – the beginning of nthe second week nof the disease).
Secondary nmetastatic foci of the infection nmay appear rarely nin the vascular nmembrane of the neye, in myocardium, endocardium, nlungs and pleura. Similar foci narise very rarely nin kidneys, liver, urinary tract, borne nmarrow.
In the nperipheral blood high nleukocytosis, neuthrophillosis nwith shift of nthe formula to nthe left aneosinophyllia, increased nESR are observed. Thrombocytopenia develops inrarely.
There are nalterations in urine nas during syndrome nof “infectious-toxic kidneys”. Proteinuria, microhematuria, ncylinderuria are marked.
Meningococcal sepsis is ncombined with meningitis in majority cases. In n4-10 % of the npatients meningococcemia may nbe without damage nof the soft ncerebral covering. Frequency of nmeningococcal sepsis is nusually higher in nthe period of nepidemic.
Fulminate meningococcemia ( acutest nmeningococcal sepsis, Waterhause-Friedrichen syndrome)
It is the nmore severe, unfavorable form of nmeningococcal infection. Its base nis infectious-toxic shock. nFulminate sepsis is characterized by nacute sudden beginning and impetuous ncourse. Temperature of body rises up to 40-41 oC. It is accompanied by chill. However, hypothermia may be nobserved through some nhours. Hemorrhagic plentiful rash nappears at the nfirst hours of nthe disease with ntendency to confluence nand formation large nhemorrhages, necroses. A purple-cyanotic spots arise on the ski(“livors mortalis”). The skin is pale, nbut with a total cyanosis. Patients are anxious and excited. The cramps nare observed frequently, especially in children. The nrecurrent blood vomiting arise inrarely. Also, a bloody diarrhea may be ntoo. Gradually, a prostration becomes more excessive and it results is a nloss of the consciousness.
Heat’s activity decreases catastrophically. Anuria develops n(shock’s kidney). Hepatolienalic syndrome is nrevealed frequently. Meningeal syndrome is ninconstant.
In the nperipheral blood hyperleukocytosis (till 60*109/l), nneutrophylosis, sharp shift nleukocytaric formula to nthe left, thrombocytopenia, nincreased ESR (50-70 mm/h) are nreveled. The sharp disorders nof hemostasis are nmarked – metabolic acidosis, coagulopathy of nconsumption, decrease of fibrinolitic nactivity of the nblood and other.
Mixed forms (meningococcemia n+ meningitis)
These forms occur in 25-50 % cases of generalized meningococcal ninfection. In the last years there is ntendency of increase frequency of mixed forms in general structure of the ndisease, especially in periods of epidemic outbreaks. It is characterized by ncombination of symptoms of meningococcal sepsis and damage of cerebral nmembranes.
Rare forms of meningococcal infections
These forms (arthritis, polyarthritis, pneumonia, iridocyclitis) are consequence of nmeningococcemia. Prognosis is favorable nin opportune and nsufficient therapy.
Diagnostics
The diagnosis nof all forms of meningococcal infection is based on the complex of nepidemiological and clinical data. The nfinal diagnosis is nestablished with help nof the laboratory nexamination. Separate nmethods have different diagnostical significance in various nclinical forms of meningococcal infections.
The diagnosis of meningococcal carrier is npossible only by use of bacteriological method. The material for analysis is the mucus nfrom proximal portions of upper respiratory tract. In diagnostics of nmeningococcal nasopharyngitis epidemiological and bacteriological methods occupy the main nplace. Clinical ndifferention of meningococcal nasopharyngitis from nnasopharyngitis of the other genesis is nno possible or very difficult.
In recognition of generalized forms, nanamnestical and clinical methods of diagnostics have real diagnostic nsignificance, mainly in combination of meningococcemia and meningitis.
The nexamination of cerebrospinal nfluid (CSF) has great nmeaning in diagnostics nof meningitis. In lumbar npunction cerebrospinal fluid flows nout under high npressure and by nfrequent drops. The cerebrospinal fluid nmay flow out nby rare drops nonly due to nincreased viscosity of npurulent exudation or npartial blockade of liquor’s nways. Cerebrospinal nfluid is opalescent nin initial stages nof the disease. Then it nis turbid, purulent, nsometimes with greenish nshade (Fig.13).
Fig.13. Cerebrospinal fluid nin meningococcal meningitis
Pleocytosis achieves till 10-30 103 in n1 mcl. Neuthrophils leukocytes predominate nin cytogram. Neuthrophilous compose 60-100% nof all cells. In microscopy neuthrophils ncover intirely all nfields of vision, inrarely. Quantity of nprotein of cerebrospinal nfluid increases (till 0,66-3,0 g/l). There is npositive Nonne-Appelt’s reaction. The reaction of nPandy composed (+++). Concentration of glucose nand chlorides are nusually decreased.
In generalized forms the nfinal diagnosis is nconfirmed by bacteriological method. In diagnostics immunological nmethods are used too. Reactions of hemagglutination, latex agglutination nare more sensitive.
Differential diagnosis
In nmeningococcemia the presence nof rash requires nof differential diagnostics nwith measles, scarlet fever, rubella, diseases of nthe blood (thrombocytopenic purpura Werlgoff’s disease; hemorrhagic vasculitis – Sheinlein-Henoch’s disease). nSometimes it is nnecessary to exclude nepidemic typhus, grippe, nhemorrhagic fevers.
It nis necessary to ndifferentiate meningococcal meningitis nwith extensive group nof the diseases:
1. Infectious nand noninfectious diseases nwith meningeal syndrome nbut without organic ndamage of central nnervous system (meningismus). nMeningismus may be nin grippe, acute shigellosis, uremia, lobar pneumonia, toxical food-borne infectious, typhoid fever, epidemic typhus, infectious mononucleosis, pielitis, middle otitis.
2. Diseases nwith organic damage nof central nervous nsystem, but without meningitis (brain abscess, tetanus, subarachnoid hemorrhage).
3. Meningitis of other etiology. In npurulent meningitises etiological nfactors may be npneumococci, staphylococci, streptococci, bacterium coli, salmonella, fungi, Haemophilus influenzae. In purulent nmeningitis nonmeningococcal etiology nit is necessary nto reveal primary npurulent focus(pneumonia, npurulent processes on nthe skin, otitis, sinusitis, nosteomyelitis).
Treatment
The therapeutic ntactics depends from nthe clinical forms, severity of the n course nof the disease, presence of ncomplications, premordal state. nIn serious and nmiddle serious course nof nasopharyngitis antibacterial nremedies are used. Peroral antibiotics oxacillin, ampyox, nchloramphenicol, erythromycin are used.
The duration of the ntherapy is 3-5 days nand more. Sulfonamides of nprolonged action are nused in usual ndosages. In light duration nof nasopharyngitis the nprescription of antibiotics nand sulfonamides is nno obligatory.
In therapy of ngeneralized forms of nmeningococcal infection the ncentral place is noccuped by antibiotics, in which nsalt benzil penicillistands at the nfirst place. Benzyl penicillin is used nin dosage of n200,000-300,000 IU/kg/day. In nserious form of nmeningococcal infection daily ndosage may be nincreased to 500,000 IU/kg/day. Such doses nare recommended particularly nin meningococcal meningoencephalitis. In presence nof ependimatitis or nin signs of nconsolidation of the puss the ndose of penicillin increases to 800 n000 IU/kg/day.
In similar ncircumstances it is necessary nto inject sodium nsalt of penicillin nby intravenously in ndose 2 000 000-12 000 000 units nin day. Potassium salt nof penicillin is nno injected by nintravenously, because it is npossible the development nof hyperkalemia. Intramuscular dose nof penicillin is npreserved.
Endolumbar injection of penicillin nis no used npractically last years. Daily dose nis injected to nthe patient every n3 hours. In some ncases interval between ninjections may be nincreased up to n4 hours. The duration nof the therapy nby penicillin is ndecided individually depending on nclinical and laboratory ndata. The duration of penicicllin therapy usually 5-8 ndays.
At the nlast years increased nresistant strains of nmeningococcus are marked (till n5-35%). Besides that, in some ncases the injection of nmassive doses of npenicillin leads to nunfavorable consequences and ncomplications (endotoxic shock, nhyperkalemia due to nusing of potassium salt of npenicillin, necroses in the nplaces of injections nand other). Also, the npatients occur with nallergy to penicillin nand severe reactions nin anamnesis. In such ncases it is nnecessary to perform netiotropic therapy with nuse other antibiotics. In meningococcal infection nsemisynthetic penicillins are nvery effective. These remedies nare more dependable nand preferable for n“start-therapy” of the npatients with purulent nmeningitis till nestablishment etiological diagnosis. In nmeningococcal infection ampicillin nis the best nmedicine, which is prescribed nin dosage 200-300 mg/kg/day intramuscularly every n4 hours.
In the nmost serious cases nthe part of nampicillin is given nintravenously. Daily dose is nincreased to 400 mg/kg/day. Oxacillin is nused in dose nnot less than n300 mg/kg/day every 3 nhours. Metycyllin is prescribed nin dose – 200-300 mg/kg nevery 4 hours. In nmeningococcal infection chloramphenicol is nhighly effective. It is the nmedicine of the nchoice in fulminate nmeningococcemia. It is shown, that nendotoxic reactions arise nmore rarely during treatment of nthe patients by nchloramphenicol than during therapy nby penicillin. In cases nof meningoencephalitis chloramphenicol is not prescribed ndue to its ntoxic effects on nneurons of brain. Chloramphenicol is nused in dose n50-100 mg/kg 3-4 ties na day. In fulminate nmeningococcemia it is ngiven intravenously every n4 hours till stabilization nof arterial pressure. Then chloramphenicol is ninjected intramuscularly. nThe duration of nthe treatment of nthe patients by nthis antibiotic is n6-10 days.
There are nsatisfactory results of the treatment nof meningococcal infection nby remedies from nthe group of ntetracycline. Tetracycline is ninjected in dose n25 mg/kg intramuscularly and nintravenously in the cases nof resistant agents nto the other nantibiotics.
Pathogenetic therapy nhas exceptional significance nin therapeutic measures. It nis performed simultaneously with netiotropic therapy. The basis nof pathogenetic therapy nis the struggle nwith toxicosis. Salt solutions, macromolecular colloid nsolutions, plasma, albumin nare used. Generally 50-40 ml of nfluid is injected on 1 kg of body’s mass per day in adults under the control of ndiuresis. Prophylaxis of hyperhydratation of the nbrain is nperformed simultaneously. nDiuretics (lasix, uregit) are injected. nIn serious cases nglucocorticosteroids are prescribed. Full doses nis determined individually. It depends non dynamics of the main nsymptoms and presence nof complications. Generally hydrocortisone is nused in dose nof 3-7 mg/kg/day, prednisolone – 1-2 mg/kg/day. Oxygen therapy nhas great significance nin the treatment nof the patients
The therapy nof fulminate meningococcemia includs nthe struggle with nshock. Adrenaline and adrenomimetics are nnot used due nto possibility of ncapillary spasm, increased nhypoxia of the nbrain and kidneys nand development of nacute renal failure. The nearly hemodialysis is nrecommended in the ncase of acute nrenal failure due nto toxicosis.
The basis of the therapy of ninfectious-toxic shock is complex of measures, including application of nantibiotics, improvement of blood circulation. The course of infectious-toxic nshock is very serious, with high mortality (50% of the patient die during the nfirst 48 hours of the disease). Because, it is necessary to nprescribe intensive therapy immediately. Antibiotics of wide spectrum of naction are prescribed. Steroid hormones have important meaning in the treatment nof infectious-toxic shock. Hormones decrease general reaction of the organism non toxin, positively act on hemodynamics. Treatment by glucocorticoids is nconducted during 3-4 days.
Prophylaxis
Prophylactic measures, directional on the sources nof meningococcal infection ninclude early revelation nof the patients, nsanation of meningococcal ncarriers, isolation and treatment nof the patients. Medical observation nis established in nthe focuses of nthe infection about ncontact persons during n10 days.
The nmeasures against of the ntransmissive mechanism, are nconcluded in performance nof sanitary and nhygienic measures and ndisinfection. It is necessary nto liquidate the ncongestion, especially in the nclosed establishments n(children’s establishments, nbarracks’s and other). The nhumid cleaning with nusing of chlorcontaining disinfectants, frequent ventilation, ultra-violet radiation nare performed at nthe lodgings.
The measures, directional on nreceptive contingents, ninclude increase nonspecific nresistance of the people n(tempering, timely treatment of nthe diseases of respiratory tract, tonsils) and formation nof specific protection nfrom meningococcal infection. Active immunization nis more perspective nwith help of nmeningococcal vaccines. There nare several vaccines, for nexample, polysaccharide nvaccines A and C. n
Vaccine from nmeningococcus of the ngroup B was also nobtained. However, the group B capsular polysaccharide is not nsufficiency immunogenic to produce a reliable antibody response in humans to be neffective, several solutions to this problem are being studied, including the nchemical alterations of the capsular B antigen to make it more immunogenic and nthe search for other cell wall antigens that nare capable of eliciting nbactericidal antibodies against B meningococci with a minimum of serious side neffects. New vaccines against meningococcus are under development.
SEPSIS
The term sepsis has been used nfor a clinical situation in which there is evidence of infection plus a nsystemic response as manifested by an elevated temperature, tachycardia,increased respiration, leukocytosis or an impaired nperipheral leukocyte response, and/or the presence of immature band forms of nperipheral circulation.
Sepsis has some ndifferences from the nother infectious diseases:
1. nSepsis is npolyetiological disease. The agents of nsepsis may be different microorganisms –aerobic and nanaerobic.
2. nThere is no united nentrance gates.
3. nThere is no cyclicy nof the course.
4. Immunity don’t form isepsis.
Etiology
The most frequent etiologic nfactor of sepsis is auto- or external microflora. These agents are a nstaphylococcuses, streptococcuses, colibacilluses and other so called nconditionally pathogenic microorganisms. Rarely, a reason of the sepsis may be nobligate parasites. Blue pus bacillus, ngonococcus, meningococcus, bacillus anthracis, salmonella, fungi and others may ncaused sepsis. But, at last time staphylococcus nis found more often than others, so it should be on the first place by nsignificance. In according to international nclassification 3 types nof staphylococcus are detached: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus. Staphylococcus aureus nplays the most important nrole in the npathology of human.
Epidemiology
Staphylococcus infection nis widely spread namong hospitalized persons. Intrahospital distribution nis typical feature nof epidemiology of staphylococcus infection.
Intrahospital infections nare characterized by nlarge quantity of nthe sources of ninfection, multiply ways and nfactors of transmission nof the agent nmultiply persons with nincreased risk of the infection. The sources nintrahospital infection are npatients with different nforms of staphylococcus purulent infection, carriers of staphylococcus. nCarriers of staphylococcus from medical npersonnel play an nimportant role in nthe conditions of nthe hospital.
The ways and nfactors of transmission nof staphylococcus infections nare different: respiratory-drug, ncontact and alimentary. Transmission of nthe agent may be realized nby alimentary way. For nexample, it is possibly ninfection of infants nin born-hause by nsolutions for drink nand milk, using for nsupplementary nourishment. Staphylococcus infection nhave sporadic character nin observance of nsanitary-antiepidemic regime. nEpidemic outbreaks of nintrahospital nstaphylococcous infections may be in nviolation of regime.
Staphylococcus ninfection develops as nrule in persons nwith decreased nonspecific nresistance, with different infectious ndiseases (especially, viral netiology), after chronic diseases, in npersons after massive doses of nimmunodepressors, antibiotics, hormones, X-ray therapy.
n
Pathogenesis and pathologic anatomy
The factors of nrisk, , promoting the penetration of normal germs of skin and mucous nmembranes into internal mediums of nthe macroorganism system, may be different causes injuries, inflammations, trophic ndisorders, aggression of different microflora, congenital anomalies. The nfollowing distribution of microbes in macroorganism may go by different ways – nvia blood, lymph and direct methastasing. The intermediate localization nof the process nappears. It may nbe phlegmona, abscess or other destructive processes. The process nis sepsis, when it nhas generalized character nwith damage liver, spleen, lungs, kidneys, vessels and nother organs and systems.
The agents of sepsis, penetrating into ntissues, causes an inflammatory process. In some ncases the process ndevelops impetuously. The purulent ninflammatory focus arises non he place nof the penetration nwith reproduction of nmicrobes (primary focus). But iother cases ninflammatory manifestations are less expressive and rapidly disappear, but agent npenetrates inside tissues by lymphatic nand blood ways and causes inflammatory focus nin distant place. These inflammatory focus may lead to development of nsepsis, in corresponding nchange of reactivity nand resistance of nthe organism.
Entrance dates nof infection may be in nany organ and ntissue. The primary focus nis in tissues nwith large quantity nof lymphatic and nblood vessels more nfrequently. For example, in nwound sepsis the nskin is entrance ngates more frequently. In urosepsis nand gynecological sepsis nmucous membranes are entrance gates. Prolonged course of sepsis is marked in patients with nlocalization septic and primary foci in bones, muscles, urogenital system. Isome cases, there are no visual foci, except the primary septic focus. These nforms are called septicemia. But in other ncases, metastatic secondary purulent foci are formed. These forms are named pyemia. But, nalso there is possible a transitional form – septicopyemia.
The distribution nof infection is nrealized from the nprimary focus by nblood and lymphatic nways. The distribution of nthe agents is nrealized by veins too, with formation nof thrombosis and thrombophlebitis. Microbes and their ntoxins may penetrate to lymphatic vessels and cause lymphangites and nlymphadenites. Metastases may be as an infiltrations, phlegmons, abscesses. Purulent infiltrates may appear in intestine too. nIn the serous cavities they are characterized by purulent exudations n(arthritis, pleurisy, peritonitis, pericarditis).
The localization nof metastases in the nlungs is on nthe first place, kidneys are non the second nplace, then – other organs.
Allergic component has aimportant role in pathogenesis of the septic process. Primary and secondary nseptic foci transfer into a source of sensibilisation of human organism.
In nsepsis the violations nof metabolism, acid-alkaline balance, deep nchanges of balance nof proteins and nvitamins are observed. Anemia develops due nto damage of nbone marrow.
DIC–syndrome plays an important role in the development nof septic state and complications. In some cases of sepsis DIC–syndrome comes nout on the first plan and cause fatal outcome in considerable degree.
DIC-syndrome is “proteolytic nexplosion” with activation and following exhaustion of coagulation, fibrinolytic, nkallekrein-kinine systems and system of complement.
In sepsis dysbalance of immune system nhas the pathogenetic meaning. Immune deficiency is manifested by decrease of nquantity of T-helpers, reduce of activity natural nkillers and phagocytic activity of granulocytes. These changes lead to ndevelopment of generalized infectious inflammatory process.
In sepsis pathologoanatomy alterations are very various. Petechial rash is nmarked on the nskin. Hemorrhages nare observed in norgans and tissues, especially on nmucous membranes. The alteration nof myocardium are nmarked from turbid nswelling till excessive nlipid dystrophy. Erosions are revealed nin endocardium. Thrombosis of veins nare often observed. Spleen is nenlarged. There is a turbid swelling or lipid infiltration in nliver. Lymphatic nodes are increased. There are a nplural hemorrhages in kidneys. Also, they are marked in the ngastrointestinal tract. Hemorrhages are observed in the suprarenal glands. nThere is edema in the lungs. Sometimes there are foci of bronchopneumonia. The infarction foci are not rare. There are edema nand hyperemia of nbrain’s substance. In sepsis nwith metastases (pyemia) purulent nprocess are observed nin brain (purulent meningoencephalitis), lungs (like nabscessing infarctions), kidneys, nthyroid gland. Besides that, purulent pleurisies, peritonitis, pericarditis, nphlegmons are observed nin different places.
Classification
I. According to spreading of the disease:
1. nPurulent – resorptive fever nis characterized by npresence of purulent nfoci, wave-like course, ngeneral intoxication.
2. nSepticemia is characterized by nsevere general state, hectic ntemperature, severe ndisorders of central nnervous system and ncardiovascular system.
3. nSepticopyemia. nThis is ncombination of septicemia nand presence of nsecondary purulent foci nin different organs.
4. nChronic sepsis. There is npurulent foci in nanamnesis during this nform. The diseases is accompanied by nprolonged wave-like fever, presence of nperiod of remission nand relapses, periodical formation nof purulent foci.
II. nAccording to prolongation nof course the nnext form of nthe diseases are differed:
1. nFulminant nsepsis (24-48 hours)
2. nAcute sepsis (from n5-7 days till nsome weeks)
3. nSubacute sepsis (3-4 nmonths)
4. nChronic sepsis (from nsome month till none year and nmore)
III. nAccording to date nappearance of process nthe next variants nare differed:
1. nEarly sepsis (till n3 months from nappearance of the nprimary focus)
2. nLate sepsis ( later than n3 months)
IV. According to ncharacter of microorganism nsepsis is differed non:
Sepsis, caused by ngram-positive flora. It leads, inrarely, to ndevelopment of septicopyemia.
Sepsis, caused by gram-negative nflora. Infectious-toxic nshock may be in nsuch cases.
Clinical manifestation
There is no any specific nincubation in septic patients. In one cases, septic process develops through nweeks and months after localized focus (abscess), but in nother cases sepsis nmay be on nits background.
Complains of these patients nare different as a clinical manifestations – weakness, headache, pain ijoints, chill with following sweats or chilling, dry mucous nmembrane of the nmouth, poor appetite, sometimes – diarrhea.
Fever is frequently of hectic character in npatients with sepsis. Different variants of the temperature nmay be – nremittent and intermittent types, sometimes, – the temperature is more nhigh in nthe morning (the reversal type). nThe temperature may be not high in nweak, cachestic patients and nelders, but it doesn’t report about light course of sepsis.
Patient’s skin is pale, moist, neven icteric in severe cases. Different rashes nare observed. Rash of nhemorrhagic type is nmarked more frequently, sometimes – pustules, ulcers, nerythema. Eruption may be on skin of trunk, limbs and face.
Mucous membranes of lips, oral ncavity are dry and may have erosions, ulcers, fissures, bleeding sickness. nOften, there are hemorrhages of conjunctiva.
Pulse is frequent. Arterial pressure decreases. Heart is enlarged. There nare a systolic murmur above cardiac apex, tachycardia and “pendulous” rhythm nduring auscultation the alterations of nmyocardium are revealed during ncardiogram. The type nof these alteration nis diffuse or ndiffuse-focal. Sometimes, the nsighs of damage nof endocardium and nlarge peripheral vessels nare revealed (arteritises, nphlebitises).
The alterations nof respiratory tract nare revealed frequently nin the patients nwith sepsis: dyspnoe, bronchitis nand pneumonia. Pneumonia has tendency to formation to abscesses. Inrarely, nserous, purulent, hemorrhagic and mixed pleurisy arise nin the patients.
There is a dry coated tongue in these npatients. Appetite is decreases. Sometimes, vomiting arises. Spleen is frequently enlarged, nsoft consistention. Liver also increases and painful during palpation. The nabscesses may arise inside abdominal cavity.
Septic patient, often, have a ndisorders of kidneys and urinary track. Sometimes toxic nephrites, purulent nparanephrites arise. The alterations of uterus, perimetrium may nbe in women. The nprimary location of ninflammatory process is nmarked inrarely in nurogenital organs. It may give ngeneralization of the nprocess.
Osseous-muscular system is ninvolved to pathologic process, too. There are reports about the serous and npurulent mono- and polyarthritis, foci of osteal destruction, degeneration of born nmarrow, myocytes. Also, the osteal tissue may be nsite of the primary foci (osteomyelitis).
Different manifestations may be nfrom nervous system, such as – a meningismus, purulent meningitis, ncerebral and spinal hemorrhages, hemorrhages into the vegetative ganglions.
The signs of anemia nare revealed in nthe blood – decreasing quantity of erythrocytes, hemoglobin. Also, nthere are a signs of the anisocytosis, poikilocytosis, thrombocytopenia. nNeutrophilic leukocytosis with shift to myelocytes, increased ESR are marked leukopenia may be icachestic patients with nfulminate forms of nsepsis.
Biochemical changes nof the blood nare expressive in nthe patient with sepsis. Increased content of nbilirubin and increased activity nof transaminases are nmarked.
In nsepsis the proteins nof serum blood nare sharply changed. A quantity of nalbumines decreases and nglobulines increased. The changes of nconcentration of IgA, IgG, IgM ndepend upon gravity nof the course and noutcomes of sepsis.
Fulminant sepsis nis a rare form, for example, of meningococcal sepsis. It has several nsynonyms. There are – fulminate meningococcemia, acutest meningococcal sepsis, nWaterhouse-Friedrichen syndrome.
It is the more nsevere, unfavorable form of meningococcal ninfection. Its base is infectious-toxic shock. Fulminate sepsis nis characterized by nacute sudden beginning and impetuous ncourse. Temperature of body rises up to 40-41oC. It is naccompanied by a chill. However, hypothermia nmay be through nsome hours. Hemorrhagic plenty nrash appears at nthe first hours nof the disease nwith tendency to nconfluence and formation nlarge hemorrhages, necroses. A npurple-cyanotic spots arise on the skin (“cadaveric spots”). The skin is pale, but with a total cyanosis. nMoist, covered with a clammy sweat. Patients are anxious and excited. The cramps nare observed frequently, especially in children. The nrecurrent bloody vomiting arises inrarely. Also, a bloody diarrhea may be ntoo. Gradually, a prostration becomes more excessive and it results in a nlose of the consciousness.
Acute sepsis is the most frequent form of sepsis. Staphylococcus sepsis nis occurred more nfrequently. It is naccompanied by considerable nfatal outcomes. In majority of nthe cases the nonset of disease nis an acute nwith chill and nincrease of the temperature. Fever may be of different character: constant, intermittent , nremittent and incorrect. Sometimes sepsis nmay be with nsubfebril temperature.
Anemia increases in majority of nthe patient, because the nskin is pale. Sometimes skin nhas jaudiwish shade ndue to haemolysis nor toxic hepatitis.
The rash is in the nshape of petechial. Rash is nlocalized on the nskin of the nchest, forearms, hands, upper nextremities, on the mucous nmembrane of the mouth, conjunctiva and nall gastrointestinal tract. Hemorrhages on the nmucous membrane of ngastrointestinal tract may nevoke bloody vomiting and ndiarrhea. The sizes of nhemorrhages are different – from small npoints till large nhemorrhages. An appearance of hemorrhagic nrash is explained nby present of nhemorrhagic vasculitis. Rash may be npurulent or erythematosus character due to infectious-allergic dermatitis. The damage nof joints is nobserved in 25-30% nof the causes. The nlarge joints are ndamaged more frequently, but small njoints may be ndamaged too. The joints nare edematous. There is nhyperemia of the nskin over joints. The motions are npainful.
In sepsis symptoms, connecting with ndamage of different norgans and system nare always expressed. They appear nas a result nof expressive intoxication, nor as nprimary or secondary npurulent inflammatory process. nThe symptoms, connecting with ndamage of cardiovascular system nis revealed more nfrequently. Staphylococcous sepsis nmay be without ndamage of endocardium. In this ncase the clinical nsymptoms are evoked nby distrophic changes nof myocardium. Tachycardia, ndecreased arterial pressure, pains in nthe heart of nindefinite character, nenlargement of the nborders of the nheart, mulffeled heart sounds are observed. The ndamage of the nvessels may be nmanifested in form nof phlebitis, development of nthromoembolism and also nembolism of small nvessels of the nskin and internal norgans, in this violation nof coronaric circulation.
Oxygenic insufficiency nand damage of nrespiratory center leads nto breathlessness. In some patient nbronchitis, pneumonia, abscesses nand pleurisy are nobserved. Hemorrhagic npleurisy is more ntypical for staphylococcus sepsis.
In staphylococcous sepsis nthe typical sign nis increased liver. The nsevere septic hepatitis may nbe observed with ndevelopment of jaundice nand violation of nall functions of nliver and also ncholangitis, abscesses. Enlarged spleen (septic mesenchymic nspleenitis) is frequent nsymptom. Spleen is soft nin an acute nperiod, because it nis difficulty to ndefine spleen in pulpation. However, enlarged spleen is clearly ndefined in percussion. During prolonged course nof sepsis spleen nbecomes dense. The damage nof kidneys has nessential meaning in nclinic of sepsis. In nacute process the nlocal nephrite of nmicrobial embolic origin ndevelops diffusive nephritis develops later.
The nsymptoms of damage nof nervous system nare the principal nclinical manifestations in the n patient nwith sepsis. In acute nsepsis consciousness is npreserved even in nhigh temperature. In this nperiod severe headache, sweat, violation of nthe sleep and ndizziness are usual ncomplaints of the npatients. In severe ncases depression, nirritation, sometimes excitement are nobserved in the npatients. Due nto edema of nthe brain meningeal nsyndrome may be too. It is possible ndevelopment of secondary npurulent meningitis. The appearance nof meningitis is ncharacterized by intensification of nheadache, addition of vomiting, development of nmeningeal symptoms. nMeningoencephalitis, arachnoiditis and nabscess may developed. The course nof acute sepsis nis from 2 nweeks till 3 nmonths.
Thus, clinic of acute sepsis nis characterized by nsevere course, expressive symptoms nof intoxication and nsymptoms of damage nof separate organs. Frequent manifestation nof acute sepsis nis development of bacterial nendocarditis and purulent ninflammatory focuses in ndifferent organs (phlebitis, nabscesses, pneumonia, pleurisy, pancreatitis, cholangitis, osteomyelitis, notitis, cystitis, violations of brain’s nblood circulation, hemorrhage into nretina of the neye and other.
Subacute sepsis. The ncourse of this nsepsis is 3-4 nmonth. It is differented nfrom acute sepsis by nlesser intensity of nsymptoms. Metastases appear more nrarely than in nacute sepsis. The prognosis nis better in nthis form. This form nof sepsis arises nin damage of nthe heart by nrheumatic process.
Chronic sepsis is characterized nby prolonged course (till none year and nmore).
This form is accompanied with nremissions and aggravations with a severe morphologic alterations. Chronic nsepsis has a wound origin, for example, the septic process in inflammatory of nthe billiary tract and portal vein. In nsome cases, billiary tract is secondary infected due to of any general cyclic infectious disease. nIn other cases, billiary tract may be as septic focus.
Outcomes of nthe disease it depends from the premorbid condition, opportunity, of the ntherapy and its effectiveness. Prognosis of a sepsis is frequently nunfavourible, especially for an infants and elder patients.
Diagnostics
Bacteriologic investigations is an important ndiagnostic test in sepsis. The results of the bacteriologic investigations nnever must be account without a data of history, clinical features and other nlaboratory tests. The positive bacteriologic results are not always in a septic npatients. The negative results are especially nfrequent in sowing nof the blood.
In sepsis the excretion of the agent nand estimate of received results are inrarely complicated problem. It is nconnected with that in sepsis the circulation of agent in the blood is no nconstant. A quantity of the agent in the blood is oscillated and may be ninsignificant. The treatment by antibiotics has a large influence obacteremia.
It is nnecessary to perform a differentiation with different diseases accompanied nwith prolonged fever, rigors, sweating, nvarious eruptions.
Typhoid fever and paratyphoid remind nsepsis by fever, pale skin, increased liver and spleen. But, they are ndifferented from septic process by ncyclic course, not so excessive anemia and rarity of the hemorrhagic eruptions. nDetachment of the nagent of typhoid nfever and paratyphoid, result of nIHA-test (indirect nhemagglutination reaction) nhelp in ndecision of problem.
In some cases, tuberculosis, nespecially its milliary forms in young patients, is difficult for diagnostics. nDuring this, fever, sometimes of hectic type, dyspnoe, sweating may nbe as in nsepsis. It is necessary carefully to study of the epidemiological data, repeated nradiological investigation and nsowings of the nblood.
Also, the hectic fever, sweating may nbe in acute period of brucellosis. In nbrucellosis there are a little nviolations of the ngeneral state of nthe patients. There is no the hemorrhagic syndrome. During the nsecond stage there are signs of the locomotor system infractions. In the early nstages of the brucellosis, positive result nof Wright reaction are nmarked. Positive intracutaneous nallergic test is observed nsome later.
Sepsis should be differentiated with na pneumonia, because pneumonia may be a result nof sepsis. The following nsystematic observation and the metastatic foci in joints, endocardium and nbrain’s membranes are usually helpful for decision of this problem.
In epidemic typhus there are ntypical clinical symptoms. They are jary-Auvcyne’s symptom, Govorov-Godelyae ’s symptom, nRosenberg ’s symptom early enlargement of spleen. Typical eruption appears on nthe 4-5 day nof the disease. Serologic methods are very useful, especially for the nfinal diagnosis.
Tropical malaria, also, is accompanied nby a prolonged fever and hepatosplenomegaly. The typical features of the nfever in tropical nmalaria are prolonged paroxysms (to 24-36 hours and over), poorly nexcessive an apyrexia periods. Rigor and sweating are less excessive, that is ncaused by some fluctuation of temperature. These attacks are accompanied by nsevere headache, low back pain, nausea and sometimes by vomiting. nAbdominal pains and watery stools appear ninrarely. The indications of nthe patients about location in focus of nmalaria, depart to tropical ncountries have an nimportant epidemiological meaning. Microscopic blood examination (blood nsmear and voluminous drop) are needful and reliable laboratory methods to ndiagnostics of malaria.
Four ndiseases are problems nfor differential diagnostics tuberculosis, collagenoses (a nlupus erythematosus and so called “non-differentiated” collagenoses or diffuse ndiseases of connective tissue), malignant neoplasm (especially hepatomas and nhypernephromas, also as a lymphogranulomatosis and leukemia).
At nthe last time nit is necessary nto allow for nincreased rate of nfungal infections in ndiagnostics of sepsis. In the main, they are candidoses of nthe bronchopulmonal, intestine, urogenital and osseous systems. Fungi of ngenus Candida albicans nhave the most nmeaning among fungal ndamages. Fungi Candida albicans nare revealed in nthe normal flora nof the oral ncavity, intestine.
It nis necessary to nperform differential diagnosis of sepsis with intestine yersiniosis. nThis disease may have prolonged (more 3 nmonths), relapsing course. In nprolonged yersiniosis alteration nof periods of nrelapses and remissions is observed. The period of relapse nis characterized by prolonged fever, reactive polyarthritis, myocarditis, nprolonged gastroenteritis, hepatolienal syndrome, erythema.
The nrepeated sowings are produced non special mediums nfor determination of the agent’s norigin: blood, sugar, billiary broth. It is recommended to take the blood nin a quantity 15-20 ml on 80-100 ml of the medium. The agent nmay be revealed nfrom hemorrhagic elements, sputum, urine, content of abscess and other nmaterials.
Treatment
Therapy of na sepsis should include at least two obligatory components – suppression of the noriginator and restoration of immunity.
Principles nof a etiotropic treatment of sepsis:
Basis nof sepsis therapy – is oppression and liquidation of the agent. There should nnot be ignored means of syndromes treatment which restore immunity, all others nif in them there is a necessity, but all of them caot cure the patient owith sepsis without appropriate ethiotropic therapy.
Antibiotic ntherapy of sepsis may be successful, if:
1) nIt is carried out by address, that is after revealing nthe agent definition of its antibiotic sensivity;
2) nIt will be carried out (spent) by bactericidal drugs bacteriostatic drugs are nused only as address;
3) nIt is applied at early septicemia (at this stage of illness recovery is nachieved in 100 % with none antibiotic without all other means of treatment);
4) nDozes of antibiotics maximum high, and β-lactamic antibiotics n(penicillines, cephalosporines) are used in megadozes;
5) nEmpirical antibiotic therapy (if the agent is unknown) is carried out on the nbasis of the clinical supposition about a nature of the agent (empirical nantibiotic therapy is should not be carried out by random);
6) nCombination of antibiotics is carried out by a rule: bactericidal drugs with the various mechanism of naction;
7) nUsage of more than two preparations in one combination is not expedient, as nwith increase of number of drugs harmful actions grow faster, than therapeutic neffect;
8) nIt is not necessary to start antibiotic therapy from reserve antibiotics n(carbopenems, cephalosporines of 4-th generation).
If treatment nis successful, antibiotic therapy is cancelled last, after liquidation of all ninfection foci, but not earlier 5-th day of a normal body temperature. Sepsis nis a general clinical nproblem. Comprehension of sepsis should become the common medical property nbecause such patients are in all medical establishments without exception.
Among nvarious combinations of antibiotics the greatest recognition has received ncombination of 3-rd generation cephalosporines (Ceftriaxoni, Cefotaximi, Ceftazidimi) with Aminoglicosides (Gentamicini, Amikacinum). nAll these combinations are effective enough at patients with sepsis without a nneutropenia. Appreciable interest to Ceftriaxoni is caused by duration of its nperiod of semiconclusion, that allows to apply npreparation once per day. Other preparations have shorter period of nsemiconclusion and demand repeated injection during day. At sepsis caused by Pseudomonas aeruginoza, high efficiency nof combination of Penicillinums with nantipyocyanic activity (Ticarcilini, Clavulanati, Aztreonami) and nAminoglicosides is marked.
At sepsis caused by Gram-positive nflora (Meticilini-resistant staphylococcus, ncoagulasenegative staphylococcuses, enterococus), using of Vancomycinum, nRifampicinum is effective.
Carbapenemes (Tienamicines) – Special group of β–lactames antibiotics n(Imipenicemi, Tienami, Meropenemi, Biapenemi), the infections created for nempirical therapy with serious current, including leukopenia. Very wide nspectrum of action, high bactericides, that is not accompanied by superfluous nremission of endotoxins at destruction of bacteria, allow nto use with success Carbapenemes as monotherapy at the most serious infections, nincluding sepsis.
After allocation and identificatioof the originator, definition of antibioticogram the choice of effective nantibacterial therapy is considerably facilitated. In such cases monotherapy is nfrequently used. Nevertheless, the question of indication of monotherapy or a ncombination of antibacterial preparations remains debatable and, apparently, nshould be discussed in each concrete case. Determining arguments, probably, nwill be estimation of gravity of infectious process and condition of reactivity nof organism, danger of occurrence of hospital infections in connection with ninvasive methods of diagnostics and treatment, transplantation of extraneous nbodies. Nevertheless, at Gram-negative infections, in opinion of many nscientists, the combined therapy is more expedient.
Antibiotics, nas a rule, do not suppress immunity. It is proved, that Lincosamides and nMacrolides have immunomodulative properties and are capable to stimulate the ncertain parts of the immune answer.
Duration of antibiotic therapy is determined by course of inflammatory nprocess. As a rule, preparations cancel at proof normalization of temperature n(absence of attributes of generalized process), absence of the clinical and nlaboratory data on presence of the localized center of an infection or joining nof nosocomial infections. At average therapy lasts 2-3 weeks. At revealing nclinical efficiency of empirical or purposeful therapy by antibiotics change of na combination or separate preparation is inexpedient during all period of ntreatment.
The immunotherapy should be directed on blocking of effects of endotoxiand citocines. Application of Pentoxifilini is perspective, that brakes the formation of FNO, has protictive influence olungs, systemic hemodynamics, improves microcirculation and oxygenation of ntissues, stabilizes electrolytic balance, preventing occurrence of nhyponatremia.
Citoprotective antioxidantes (vitamin E, Acetylcysteinum) oppress nactivity of free radicals and may improve the forecast at sepsis. nHyperproduction of free radicals which are metabolites of an arachidonic acid nis lowered also by Ibufrofenum.
Efficiency nof polyclonal antibodies to bacteria E. ncoli and Salmonella which at nseptic shock caused by Gram-negative bacteria’s, reduce a nlethality almost on 50 % was proved. Now polymyxin B or neutrophile bactericidal npenetrating protein is used.
Efficiency nof application for prophylaxis of the systemic answer on inflammation of nvactination of patients by derivative of endotoxin – monophosphorolipides A is nnow studied. Monoclonal antibodies to interleucines, phospholipase, to adhesive nmolecules and contact factors are received and pass clinical approbation of nantibody to lipid A, to endotoxin and PNO. It is possible, that in future by nidentification of mediators it will be possible to create “ cocktail “ from nantibodies which block receptors and enable to stop progresive process at the nsystemic inflammatory answer.
Interferons – native and genoinginering preparations which concermainly to IFN (Roferoni A, Introni A, Realdironi, Laferoni etc.) – natural ways nof imunocorection and protection against infections, with success are applied nat present of acute and chronic infectious diseases.
Combined using of Carbapenemes, Roncoleucines- or interferons is nadvanced achievement of modern therapy of septic diseases.
At serious course of a sepsis nstabilization of hemodynamics has crucial importance . nFirst of all it is necessary to restore volume of circulating blood. For this npurpose infuse cristaloides and colloid solutions in the ratio 2-4:1 under the ncontrol of parameters of hemodynamics, including the central venous pressure.
The proof hypotension, eveafter fast restoration of blood volume circulation, may be connected with ndisorders of nregulation of vascular ntone. Application of inotropic preparations – Dopaminum, Dobutaminum, Dobutrexi in this case is expedient. The clinical effect nfrom Dopaminum will increase the cardiac emission (B adrenergic effect), rising nof peripheric vessels tone (A-adrenergetic effect), improvement of circulatioin parenchymatous bodies, first of all in kidneys (dopamineergetic effect). nUsing of A-adrenomimetics (epinephrine) may be necessary only in case of inefficiency of nhigh doses of Dopaminum.
Respiratory support is necessary for nsignificant amount of patients with sepsis, however napplication of different methods of artificial ventilation of lungs is limited nto cases of disease with development of acute respiratory insufficiency. In a ncombination of inotropic therapy ventilating support promotes decrease of work nof muscles, improvement of oxygenation of blood and function of systemic ncirculation.
In support of appropriate level of nmetabolic and immune processes the important value has a feed of patients. The nearly high-caloric enteroalimentation with the enlarged contents of fibers and namino acids (an arginine, an ornithine) reduces frequency of complications and nduration of treatment. It is necessary to use enteral alimentary admixtures n(enpites), balanced under the contents of fibers, Adepses and carbohydrates.
It is expedient to use solutions of namino acids for parenteral feeding (Alvesini, Aminosoli-600, Aminosoli-800, nAminosoli KE, Infesoli 40 and etc.), Dextrosum, lipide emulsions (Intralipid).
DVS demands correction only in stage nof a decompensation.
Prophylaxis
It is necessary to nperform reatment of nprimary foci. The measures, directing on nincrease of resistance nof the organism have nan important meaning. These measures nare rational diet, regime nof work and nrest, physical tempering.
Staphylococci nare more frequent netiological factor of nsepsis, that’s why the prophylaxis of nintrahospital staphylococcal infection nis necessary. The early nrevealing and prohibition nof work of nmedical personnel with npurulent inflammatory diseases (sore throat, npyodermia) and opportune nhospitalization of the npatients with staphylococcal infection nin special departments nor wards. It is nnecessary the revealing nof prolonged bacteriocarriers of nhospital strains nof staphylococces and nits sanation for npatients with immunodeficiency and noperating-room.
The nmaintenance of sanitary-hygienic regime nhas leading meaning nin the hospitals nof different profile.
It nis necessary to nuse remedies, increasing nonspecific nresistance of the norganism of the npatients in the ngroups of risk (infants, npatients with immunodeficiency and nother).
