Medicine

HERPETIC DISEASE, MENINGOCOCCAL DISEASE, SEPSIS

             HERPETIC DISEASE

 MENINGOCOCCAL DISEASE

 SEPSIS

 

Herpes simplex virus (HSV) infections are among the most common maladies affecting humans. Often they are annoying and troublesome; occasionally they are life-threatening.

The term herpes is derived from the Greek word meaning to creep, and clinical descriptions of herpes labialis go back to the time of Hippocrates. Astruc, physician to the king of France, is credited with the first description of genital herpes in 1736. Between 1910 and 1920, the infectious nature of herpes lesions was demonstrated by producing corneal lesions in rabbits with material derived from herpes keratitis and labialis. As techniques for isolating and characterizing the virus became more simplified and serologic procedures were developed, our understanding of the HSV clinical spectrum has greatly expanded. Studies during the past two decades have brought insights into the molecular biology of HSV. the mechanisms of HSV latency and recurrence, and the first successful approaches to therapy for certain types of HSV infections.

Etiology

Herpes simplex virus (herpesvirus hominis) shares many properties with other members of the herpesvirus groups, which in humans includes varicella-zoster, cytomegalovirus, Epstein-Barr virus, and human herpesviruses type 6 and 7. The members of this group have an internal core containing double-stranded DNA, an icosahedral capsid with 162 hollow capsomeres, and a lipid-containing laminated membrane or envelope (Fig.1).

The overall diameters of enveloped herpesviruses are 150-200 nm. Replication occurs primarily within the cell nucleus and is completed by the addition of protein envelopes as the virus passes through the nuclear membrane. Complete virus replication is associated with lysis of the productive cell. All members of the human herpesvirus group can also establish latent states within certain types of cells they infect, although the physical nature of the viruses during periods of latency is unclear.

Fig.1. Herpes simplex virus

 

The development of monoclonal antibody and restriction enzyme technologies have permitted an even finer definition of variations among individual HSV isolates. It is now clear that HSV-1 and HSV-2 share certain glycoprotein antigens and differ with respect to others. Serologic differentiation between HSV-1 and HSV-2 infections can be readily made by detection of type-specific gG antibodies.

 

Epidemiology

Herpes simplex viruses have a worldwide distribution.There are no known animal vectors for HSV, and although experimental animals can easily be infected, humans appear to be the only natural reservoir. Direct contact, with transmission through infected secretions, is the principal mode of spread. HSV-1 is transmitted primarily by contact with oral secretions and HSV-2 by contact with genital secretions. Transmission can occur both from overtly infected persons and from asymptomatic excretors, although virus titers are higher in persons with active lesions and thus transmissability may be greater. Approximately 15 % of the adults may be excreting HSV-1 or HSV-2 at any given time depending on the population studied. For example, because shedding of HSV-2 is related to sexual activity, prostitutes may have unusually high rates of excretion.

The risk of heterosexual acquisition of HSV is greater in women than men, and previous HSV-1 infection reduces the risk of subsequent HSV-2 infection.

 

Pathogenesis

On entry into skin sites HSV replicates locally in parabasal and intermediate epithelial cells, which results in the lysis of infected cells and the instigation of a local inflammatory response. This feries of events results in the characteristic lesion of superficial HSV infection, that is, a thin-walled vesicle on an inflammatory base. Multinucleated cells are formed with ballooning degeneration, marked edema. Such lesions are indistinguishable from those caused by varicella-zoster virus. Lymphatics and regional lymph nodes draining the site of primary infection become involved. Further virus replication may result in viremia and visceral dissemination, depending on the immune competence of the host.

In murine models the maturity of macrophages at the site of local infection helps determine whether virus remains localized or disseminates. Subsequently, other host defense mechanisms, for example, the production of interferons, natural killer cells, protective antibodies, and sensitized killer lymphocytes, are elicited to prevent the spread of infection.

 

Clinical manifestations

Primary HSV-1 infection is frequently asymptomatic but may present as gingivostomatitis and pharyngitis most commonly in children under the age of 5 years but occasionally in older persons. Incubation periods range from to 12 days and are followed by fever and sore throat with pharyngeal edema and erythema. Shortly after its onset, small vesicles develop (Fig.2) on the pharyngeal and oral mucosa: these rapidly ulcerate and increase in number, often involving the soft palate, buccal mucosa, tongue, and floor of the mouth. Gums are tender and bleed easily, and lesions may extend to the lips and cheeks (Fig.3).

Fig.2. Vesicles in case of herpetic infection

Fig.3. Herpetic infection of gums

Fever and toxicity may persist for many days, and the patient complains of severe mouth pain. Breath is fetid, and cervical adenopathy is present. In children, dehydration may result from poor intake, drooling, and fever. In college-aged persons, primary HSV infection often presents as a posterior pharyngitis or tonsilitis. Included in the age-related differential diagnosis are streptococcal or diphtheritic pharyngitis, herpangina. aphthous stomatitis. Stevens-Johnson syndrome, Vincent's infection, and infectious mononucleosis.

Herpes simplex virus infections of the eye are usually caused by HSV-1 (Fig. 4).

Fig.4. Herpetic infection of eye

Primary infections may be manifested by a unilateral follicular conjunctivitis with regional adenopathy and/or a blepharitis with vesicles on the lid margin. Photophobia, chemosis, excessive tearing, and edema of the eyelids may be present. Some patients develop dendritic figures or coarse, punctate, epithelial opacities. If disease is limited to the conjunctiva, healing takes place within 2-3 weeks. However, if systemic symptoms and signs of stromal involvement are present, the healing phase may be delayed. Spontaneous healing of the conjunctiva and cornea is usually complete.

Primary genital infection is most common in adolescents and in young adults and is usually (in 70-95 % of the cases) caused by HSV-2 (Fig.5).

Fig.5. Herpes genital infection

The duration of incubation periods 2-7 days. In men, vesicular lesions on an erythematous base usually appear on the glans penis or the penile shaft. In the female, lesions may involve the vulva, perineum, buttocks, cervix, and vagina and are frequently accompanied by a vaginal discharge). Extra-genital lesions occur during the course of primary infection in 10-20 % of patients. Primary infection in both sexes may be associated with fever, malaise, anorexia, and tender bilateral inguinal adenopathy. Although vesicular lesions may persist for several days in men, in women they rapidly ulcerate and become covered by a grayish-white exudate. Such lesions may be exquisitely tender, and urethral involvement may result in dysuria or urinary retention. Herpetic sacral radiculomyelitis accompanying genital infection may also lead to urinary retention, neuralgias, and obstipation; in such patients a loss of anal tone, diminished bulbocavernosus reflex, and cystometrographic evidence of lower motor neuron dysfunction can sometimes be demonstrated. Lesions of primary genital herpes may persist for several weeks before healing is complete. Previous HSV-1 infection may reduce the severity and duration of a first episode of genital herpes caused by HSV-2. In the diagnosis of genital herpes other sexually transmitted infections such as chancroid or syphilis, erosions secondary to excoriation, genital manifestations of Behcet syndrome or erythema multiforme, and local candidiasis must all be distinguished.

Although primary infections are usually in perioral, ocular. or genital areas, any skin site may be initially involved. Primary HSV skin infections may be extensive and mimic herpes zoster. Although a dermatomal distribution is not usually maintained and the pain is less severe.

Primary perianal and anal HSV-2 infection is becoming increasingly well recognized, both in women and in male homosexuals. Pain is the primary symptom, with itching, tenesmus, and discharge also noted. Systemic complaints of fever, chills, malaise, headache, difficulty in urinating, and sacral paresthesias may be present. On examination, vesicles and ulcerations may be seen in perianal and sometimes in anal areas. They may become confluent and result in a grayish ulcerating cryptitis surrounded by a red edematous mucosa. Bilateral inguinal adenopathy is common. The course is generally self-limited unless bacterial infection supervenes, with healing occurring in 1-3 weeks. However, in the setting of the acquired immunodeficiency syndrome (AIDS), herpes proctitis as well as other cutaneous manifestations of HSV infection may be prolonged and progressive.

Recurrent infections

Recurrent herpes labialis is frequently heralded by prodromal symptoms (pain, burning, tingling, or itching) generally lasting for less than 6 hours but occasionally as long as 24-48 hours. Vesicles appear most commonly at the vermillion border of the outer lip and are associated with considerable pain. The lower lip is more frequently involved, although individual patients may have stereotyped lesions at similar sites during each recurrence. The lesion area is usually less than 100 mm, and lesions progress from the vesicle to the ulcer/crust stage within 48 hours. Pain is most severe within the first 24 hours after the appearance of lesions. Healing is generally complete within 8-10 days. Rarely, recurrences may occur in the mouth or on the nose, chin, or cheek. Systemic complaints do not usually accompany recurrent herpes labialis, although local adenopathy may occur.

Ocular infection may recur as keratitis, blepharitis, or kerato-conjunctivitis. Recurrent keratitis is usually unilateral but is rarely (in 2-6 % of the cases) bilateral. Two main types of keratitis may develop: dendritic ulceration or stromal involvement. Branching dendritic ulcers that strain with fluorescein are virtually diagnostic and are often accompanied by a loss in corneal sensation. Visual acuity may be decreased because the ulcers frequently involve the pupillary portion of the cornea. They may be accompanied by minimal anterior opacification or deep stroma involvement. Occasionally, extensive ameboid corneal ulcers may evolve, particularly if topical steroids have been applied. Superficial keratitis usually heals, but recurrent infection may lead to deep stromal involvement and uveitis, which may in part be mediated by hypersensitivity reactions to viral or altered cellular antigens. A gradual diminution in visual acuity takes place, and individual attacks may last for several months with the formation of dense scars, corneal thinning, and neovascularization. Permanent visual loss may result, and rarely, rupture of the globe develops.

Recurrent genital lesions in both sexes are generally associated with less severe systemic symptoms and less extensive local involvement than are primary attacks. A prodrome of tenderness, itching, burning or tingling is often noted for several hours before a recurrence. Lesions in women are most often noted on the labia minora, labia majora, and perineum and less commonly on the mons pubis or buttocks. Lesions in men are most often found on the glans or penile shaft. In women recurrences tend to be more severe. Healing generally occurs in 6-10 days. Virus shedding diminishes more slowly in women and can occur between recurrences in both sexes. Occasionally, genital recurrences are associated with headache and even with aseptic meningitis. Urethral stricture and labial fusion have also been reported after recurrent genital infections.

Recurrent HSV-1 or HSV-2 infections may develop on extremities; occasionally such lesions are associated with severe local neuralgia. Local edema and lymphangitis may also occur during recurrences on extremities.

 

Complications

Herpes simplex encephalitis is a rare complication of herpetic infection and yet is one of the most common acute sporadic viral diseases of the brain. Although little is known about the pathogenesis of HSV-1 encephalitis in humans, the virus is believed to spread by neural routes into the brain during either primary or recurrent infection. Temporal lobes are the principal target areas of the virus, and a necrotizing hemorrhagic encephalitis results.

Herpes simplex encephalitis occurs at all ages in both sexes, and in all seasons. The clinical course may begin suddenly or after a brief influenzalike prodrome. Headache, fever, behavioral disorders, speech difficulties, and focal seizures are prominent features; olfactory hallucinations may be present. Cerebro-spinal fluid examination is variable but frequently shows a moderate pleocytosis with mononuclear and polymorphonu-clear leukocytes: protein levels are slightly elevated, and glucose is generally normal. Infectious virus is rarely present in cerebrospinal fluid during encephalitis, and brain biopsy with appropriate histologic and cultural techniques is currently the most reliable way to make the diagnosis. Although various antibody and antigen assays may provide adjunctive information. they are not sensitive enough to provide a sufficiently early diagnosis. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid has been reported by certain research laboratories. Herpes simplex virus encephalitis must be distinguished from other forms of viral encephalitis, tuberculous and fungal meningitis, brain abscesses, cerebrovascular accidents, and brain tumors.

The course in untreated patients is usually one of rapid deterioration over several days that progresses to coma and death. Mortality in untreated biopsy-proven cases is 60-80 %, and fewer than 10 % of the patients are left without significant neurologic sequelae.

 

Relationship to Other Diseases

Erythema Multiforme. Allergic cutaneous and mucous membrane disorders may accompany or follow acute HSV infections. Up to 75 % of all cases of erythema multiforme are regularly preceded by an attack of herpes simplex. Both HSV-1 and HSV-2 may be involved, and the cutaneous manifestations range from mild to severe (Stevens-Johnson syndrome) and may be recurrent. Inactivated HSV antigens injected intra-dermally into persons subject to erythema multiforme have induced such attacks, and HSV antigen has been identified in skin biopsy specimens from affected lesions.

Cancer. Although HSV has been suspected as a cause of cervical and other cancers on the basis of both epidemiologic and laboratory studies, many recent studies do not support its etiologic role in human cancers.

Idiopathic Neurologic Syndromes. Herpes simplex virus infections have been implicated as possible factors involved in the pathogenesis of various neurologic disorders of unknown etiology, including idiopathic facial paralysis (Bell's palsy), multiple sclerosis, atypical pain syndromes, ascending myelitis, trigeminal neuralgia, Mollaret's meningitis, and temporal lobe epilepsy. The associations are based on the known predilection of HSV for nerve tissue, on serologic or nucleic acid studies, and on the occasional observations of temporal relationships between attacks of herpes labialis or genitalis and attacks of the neurologic syndrome.

 

 

Diagnosis

Although experimental animals and embryonated eggs are susceptible to infection with HSV strains, tissue cultures have largely replaced these hosts for diagnostic purposes. Primary human embryonic kidney, rabbit kidney, and human amnion cells readily support the replication of HSV. Continuous cell strains or cell lines of human diploid origin and certain continuous monkey kidney cell lines also support HSV replication, but to a lesser extent. Cytopathic effects usually appear rapidly, within 24-48 hours if the virus inoculum is high. Cells become rounded and clump, with rapid progression of cytopathic effects throughout the cell monolayer. Ballooning degeneration and the formation of multinucleated syncytial giant cells may be observed, particularly with HSV-2 isolates. Vesicles contain their highest tilers of virus within the first 24-48 hours, and specimens should be collected early and promptly inoculated into tissue cultures. If a delay is unavoidable, specimens can be stored in appropriate carrying medium at 4-9°C for a few hours. but for longer periods they should be stored at -70°C. Typing of isolates can be accomplished by using a variety of serologic techniques including immunohistochemistry or microneutralization. When tissue specimens such as neural ganglia are being studied for the presence of virus, tissue explanation or cell cocultivation techniques have proved useful in facilitating virus isolation.

The recent development of monoclonal antibodies to individual herpes virus antigens should allow for the more precise identification and typing of HSV isolates. HSV-1 and HSV-2 have both type-specific and cross-reactive antigens that are useful for both grouping and type discrimination. Moreover the cloning of herpes DNA fragments in recombinant bacteria may permit the production of probes to identify herpes genomes in the absence of infectious virus.

For a rapid diagnosis of skin or mucous membrane lesions, scrapings from suspect lesions may be smeared, fixed with ethanol or methanol and stained with Giemsa or Wright preparation. The presence of multinucleated giant cells indicates infection with HSV or varicella-zoster virus. When using cytologic techniques, the Papanicolaou cervicovaginal stain or the Paragon multiple stain, intranuclear inclusions may also be seen. Alternatively, such material can be examined for herpes antigens by immunohistochemical techniques or by in situ DNA hybridization.

Serologic techniques may be helpful in diagnosing primary HSV infections but are rarely of value in recurrent infections. A variety of assays have been used including neutralization, complement fixation, passive hemagglutination, indirect immunofluorescence, radioimmunoassay, enzyme immunoassays, complement-mediated cytolysis, and antibody-dependent cellular cytolysis. During primary infections, a fourfold or greater rise in titer is observed between acute and convalescent sera. In recurrent infections such rises may or may not be observed. Many licensed enzyme immunoassays appear to give inaccurate information concerning HSV-infecting subtypes.

Measurement of IgM HSV antibodies in infants may be helpful in the diagnosis of neonatal infection. Such antibodies usually appear within the first 4 weeks of life in infected infants and persist for many months. Measurement of IgM antibodies in older persons has not proved useful in separating primary from recurrent infections.

Approaches to detect specific HSV antigens, antibodies, or DNA in cerebrospinal fluid are under development. Such techniques may circumvent the need for invasive procedures such as brain biopsy to make the diagnosis of herpes encephalitis.

Treatment

A number of nucleoside derivatives interfere with the synthesis of HSV DNA. Some of these (trifluorothymidine, vidarabine) are useful in and licensed for the topical treatment of herpes keratitis. Vidarabine and acyclovir are also useful for systemic HSV infections. None of these agents affects latent virus.

In the immunocompromised host, acyclovir is useful as both treatment and suppression of recurrent mucocutaneous HSV lesions. For the treatment of acute episodes, virus shedding, local symptoms, and time to healing can be reduced by intravenous or oral regimens (400 mg five times per day). Acyclovir is also useful in the prevention of herpetic recurrences in immunocompromised hosts including transplant recipients, leukemics undergoing induction chemotherapy, and patients with AIDS. Regimens of 200-400 mg two to five times per day have been satisfactory in preventing recurrences among seropositive patients.

Parenteral acyclovir is indicated for disseminated or central nervous system HSV infections. In patients with biopsy-proven HSV encephalitis, acyclovir was compared with vidarabine and found to be superior in reducing mortality. Doses of 10 mg/kg every 8 hours for 14-21 daysare recommended. In newborns with disseminated HSV infections, acyclovir and vidarabine appear equivalent but because of ease of administration, acyclovir is recommended.

Acyclovir has little acute toxicity. Drug-related neurotoxicity (disorientation, hallucinations, tremors, ataxia, and seizures) has been described rarely, and reversible renal dysfunction may occur, particularly following a rapid bolus infusion.

 

Prophylaxis

Experimental vaccines against HSV have shown promise in animal models, and some are undergoing human trials. Limited trials in humans, however, have been unsuccessful, and it is unlikely that a human HSV vaccine will be generally available in the near future.

The prevention of neonatal disease in the offspring of mothers with genital infection presents special problems.

 

 

 

 

 

 

 

 

 

MENINGOCOCCAL INFECTION

Definition

 Meningococcal  infection  is  an  acute  infectious  disease  of  the  human,  caused  by  meningococcous  Neisseria Meningitigis. The  mechanism  of  the  transmission  of  the  infection  is  air-drop. The  disease  is  characterized     by  damage  of  mucous  membrane  of  nasopharynx (nasopharingitis),  generalization   of  the  process in  form  of  specific  septicemia (meningococcemia) and  inflammation  of  the  soft  cerebral membranes (meningitis).

 

History and geographical distribution

Epidemic  cerebrospinal  meningitis (one  of  the  most  clinically  expressive  forms  of  the  disease) was  known  else  in  profound  antiquity. The  description  of  outbreaks  of  this  infection  is  contained  in  reports  of  Areteus (III  century  of  our  era), Egynsky (VII century).

Epidemic cerebrospinal meningococcal meningitis was first described by Vieusseaux in 1805. Subsequent reports throughout the nineteenth century confirm its episodic epidemic nature with a propensity for affecting young children and military recruits assembled in stationary barrack situations. In 1887, Weichselbaum isolated the meningococcus from the cerebrospinal fluid, and the etiologic relationship between this organisms and epidemic meningitis was firmly established.

Kiefer in 1896 and Albrecht and Ghon in 1901 found that healthy persons could become carriers of the meningococcus. Serotypes of the meningococcus were first recognized by Dopter in 1909. This laid the basis for serum therapy in the treatment of meningococcal infection. The  agent  was  isolated  from  the  blood  by V. Osler  in  1899. It  had  an  important  meaning, because  many  problems  of  pathogenesis  of  the  disease  were  explained. It  was  evidence  that  meningitis  is  not  single  manifestation  of  the  disease.

In 1937, sulfonamide therapy radically altered the outcomes of meningococcal infection. With the advent of antibiotic agents, treatment of meningococcal infection became more effective, and mortality declined. With the subsequent world wide emergence of resistant strains and with the absence of effective chemoprophylaxis, renewed interest in immunoprevention has occurred and has led to the development of safe and effective vaccines against the groups A, C, Y and W-135 meningococcal group.

Meningococcal  infection  occurs  on  the  all  continents. It  is  serious  problem  for  public  health. It  is  registered  in  170  countries  of  the  world.

 

Etiology

The causative agent is Neisseria meningitidis. It is small gramm-negative diplococcus, aerobic, catalise and oxidase-positive, not-motile and possess a polysaccharide capsule, which is the main antigen and determines the serotype of the species. Meningococcus may be seen inside and outside of neutrophills (Fig.6). The main serogroups of pathogenic organisms are A, B, C, D, and W135, X, Y, Z and L. The bacterial membrane is a lipopolysaccaride.

Fig.6. Neisseria meningitidis

The  pathogenic  properties  of  meningococcus  are  known  insufficiently, because  meningococcal  infection  is  anthroponosis. The  factors  of  pathogenic  action  of  meningococcus  are  biological  properties, promoting  its  attachment  on  the  mucous  membrane  of  nasopharynx, depression  symbiotic  microflora, penetration  through  mucous  barriers, toxic  properties  and  other.

One  of  such  properties   is  specific  attachment  or  adhesion  of  meningococcous  to  the  cells  of  epithelium  of  respiratory  tract. Adhesion  is  phenomenon, promoting  to  colonization  of  meningococcus  on  the  mucus. Physical  factors  (adsorption  of  microbes  on  the  surface  of  the  cell)  and  fermentative  processes  have  the  meaning  in  the  appearance   of  adhesion.

Meningococci are very exacting to composition of nutritive mediums. Its  reproduction  may  be  only  in  presence  of  human’s  protein  or  animal’s  protein. Due  to destruction  of  the  microbe’s  cell  endotoxin  is  delivered (of  lipopolysaccharide  origin). Exotoxin is no  produced. The  agent  of  meningococcal  infection  is  characterized  by  low  resistance  in  the  environment. Meningococci  perish  during  temperature  50°C  through  5  minutes, during  temperature  100°C – through  30  seconds. Meningococci have  a  little  resistance to  low  temperature.

 

Epidemiology

Meningococcal  infection  is  typical  anthroponosis. The  sourses  of  infection  are  healthy  carriers  of  meningococcus, the  patients  with  meningococcal  nasopharingitis  and  the  patients  with  generalized forms  of  the  disease.

The  patients  with  generalized  form  are  more  dangerous. It  is  proved  that  they  are  dangerous  for  surrounding  persons  in  6  times  than  healthy  carriers. However, the  main  sources  of  the  infection  are  carriers, because  1200-1800  (according  other data – 50000) carriers  have  occasion  to  one  patients  with  generalized  form  of  the  disease.

Thus, the  patients  with  generalized  form  of  the  disease  are  the  source  of  infection  for  1-3 %  of  infected  persons, the  patients  with   meningococcal  nasopharingitis – for  10-30 %, carriers  are  the  sources  of  infection  for  70-80 %  from  general  number  of  infected.

The  level  of  healthy  carriers  promotes  the  level  of  morbility  in  certain  region. So, carriers  may  compose  3-12 %. It  is  temperate  sporadic  morbility. Carriers  may  achieve  20 %. This  situation  is  marked  as  unsatisfactory. The  outbreaks  are  observed. Carriers may  achieve  30-40 %. In  this  case  epidemic  of  meningococcal  infection  arises.

The  mechanism  of  transmission of the  infection  is  air-drop. The  infection  is  realized  during  cough, sneezing. In  this  the  narrow  contact  and  sufficient  exposition  are  necessary. It  is  proved  by A.A. Favorova (1976) that  the  infection  is  realized  on  the  distance  less  0,5  meter.

The  wide  distribution  of  meningococcal  infection  is  promoted  some  causes  in  the  countries  of  equatorial  Africa. The  main  causes  are  connected  with  social  factors (unsatisfactory  sanitary-hygienic  conditions  of  the  life  of  the  majority  part  of  the  population, high  density  of  the  population  and  other).

In  meningococcal  infection  one  of  an  important  characteristic  of  epidemic  process  is  periodical  rise  and  fall  of  the  morbidity. The  duration  of  the  period  with  high  morbidity  is  different. It  may  be  5-10  years  and  more. Then  the  period  of  the  fall  of  the  morbidity  becomes. It  is  continued  from  5  till  20  years.

In  meningococcal  infection  epidemic  process  is  characterized  by  seasonal  spread. It  is  manifested  especially  during  epidemics. The  morbidity  may  compose  60-70%  from  year’s  morbidity  during  seasonal  rise. The  onset  of  the  seasonal  rise  is  in  quanuary  in  the  countries  with temperate  clinimate. It  achieves  of  maximum  in  march – april.

The  estimate  of  the  age  morbidity  of  meningococcal  infection  testifies  about  that  70-80 %  of  the  cases  of  the  diseases  have  occasion  to  children. Children  of  the  age  1-5 years  compose  50 %. Meningococcal  infection  is  marked  rarely  at  the  first  three  month  of  the  life.

The  persons  of  the  young  age (15-30  years)  compose  the  majority  among  adult  patients. It  is  explained  by  social  factors  and  features  of  the  life  young  people (service  in  the  army  study  in  the  educational  establishments, living  in  the  hostel). These  factors  explain  predomination  of  men  in  the  structure  of  the  morbidity.

    The  age  of  carriers  of  meningococcal  infection  is  different  from  the  age  of  the  patient. The   larger  part  of  carriers  is  reveled  among  adults. The  portion  of  the  children  is  a  little.  The morbidity  is  higher  in  the towns  then  rural  locality.

The  considerable  outbreaks  of  the  diseases  were  described  in  the  educational  establishments  of  the  closed  type  and  especially  among  military (as  at  peaceful  time  such  as  during  war).

 

Pathogenesis

In  meningococcal  infection  entrance  gates  are  mucous  membrane  of  nasopharynx. It  is  place  of  primary  localization  of  the  agent. Further  meningococci  may  persist  in  epithelium  of  nasopharynx  in  majority  of  the  cases. It  is  manifested  by  asymptomatic  healthy  carriers. In  some  cases  meningococci  may  cause  inflammation  of mucous  membrane  of  upper  respiratory  tract. It  leads  to  development  of  nasopharingitis.

 The  localization  of  meningococcus  on  mucous  membrane  of  nasopharynx  leads  to  development  of  inflammation  in  10-15 %  of  the  cases.

The  stages  of  inculcation  on  the  mucous  membrane  of  nasopharynx  and  penetration  of  meningococcus  into  the  blood  precede  to  entrance  of  endotoxin  into  the blood  and  cerebrospinal  fluid. These  stages  are  realized  with  help  of  factors  of  permeability. It  promotes  of  the  resistance  of  the  meningococcus  to  phagocytosis  and  action  antibodies.

Meningococci  are  able  to  break  local  barriers  with  help  of  factors  of  spread (hyaluronidase). Capsule  protects  meningococci  from  phagocytosis. Hematogenous  way  is  the  principal  way  of  the  spread  of  the  agent  in  the  organism (bacteremia, toxinemia). Only  the  agent  with  high  virulence  and  invasive  strains  may  penetrate  through  hematoencephalitic  barrier. The  strains  of serogroup A high  invasivicity.

 Meningococci  penetrate  into  the  blood  after  break  of  protective  barriers  of  mucous  membrane  of  upper  respiratory  tract. There  is  hematogenous  dissemination (meningococcemia). It  is  accompanied  by  massive  destruction  of  the  agents  with  liberation  of  endotoxin. Meningococcemia  and  toxinemia  lead  to  damage  of  endothelium  of  the  vessels. Hemorrhages  are  observed  in  mucous  membrane, skin  and  parenchymatous  organs. It  may  be  septic  course  of  meningococcemia  with formation of the secondary metastatic focuses in the endocardium, joints, internal mediums of the eyes.

In most of the cases penetration of meningococci in the cerebrospinal fluid and the soft cerebral covering is fought about by hematogenous ways through the hematoencephalic barrier. Sometimes meningococci may penetrate into the skull through perineural, perilymphatic and the perivascular way of the olfactory tract, through the enthoid bone.

Thus the meningococci enter into subarachnoid space, multiply and course  serous-purulent and purulent inflammation of the soft cerebral coverings. The inflammatory process is localized on the surface of the large craniocerebral hemispheres, and rarely, on  the  basis, but sometimes it may spread in the covering of the spinal cord. During severe  duration of the inflammatory process the cranium is covered by purulent mather (so-cold  “purulent  cap”). It  may  lead  to  involvement  of  the  brain’s  matter  into  inflammatory  process  and  meningoencephalitis.

The process may engulf the rootlets of – VII, VIII, V, VI, III and XII pairs of cranial nerves.

Pathogenic  properties  of  the  agent, state  of  macroorganism, state  of  immune  system, functional  state  of  hematoencephalitic  barrier  have  the  meaning  in  the  appearance  of  meningitis  of  any  etiology.

Endothelium  of  capillaries, basal  membrane, “vascular  pedicles”  of  glyocytes  and  basic  substance  of  mucopolysaccharide  origin  are  the  morphologic  basis  of  hematoencephalic  barrier. Hematoencephalic barrier  regulates  metabolic  processes  between  blood  and  cerebrospinal  fluid. It  realizes  protective  function  from  the  alien  agents  and  products  of  disorder  of  metabolism. The  most  alterations   are  observed  in  reticular  formation  of  the  middle  brain.

 In  purulent  meningitis some  pathogenic  moments  are  promoted  by  rows  of  paradoxical  appearances  in hematoencephalic  barrier  and  membranes  of  the  brain. In  physiological  conditions hematoencephalic  barrier  and  brain’s  membranes  create  closed  space, preventing  brain’s  tissue  from  influence  of  environment. In  this  case  secretion  and  resorbtion  of  cerebrospinal  fluid  are  proportional. In  meningitis  closed  space  leads  to  increased  intracranial  pressure  due  to  hypersecretion  of  cerebrospinal  fluid  and  to  edema  of  the  brain. The  degree  of  swelling-edema  of  the  brain  is  decisive  factor  in  the  outcome  of  the  disease.

The  next  stages  may  single  out  in  pathogenesis  of  purulent  meningitis:

1.     Penetration  of  the  agent  through hematoencephalic  barrier, irritation  of  receptors  of  soft  cerebral  membrane  of  the  brain  and  systems, forming  cerebrospinal  fluid.

2.     Hypersecretion  of  cerebrospinal  fluid.

3.     Disorder  of  circulation  of  the  blood  in  the  vessels  of  the  brain  and  brain’s  membranes, delay  of  resorbtion  of  cerebrospinal  fluid.

4.     Swelling-edema  of  the  brain  hyperirritation  of  the brain’s  membranes  and  radices  of  cerebrospinal  nerves.

Besides  that, intoxication  has  essential  meaning  in  pathogenesis  of  purulent  meningitis. Vascular  plexuses  and  ependime  of  ventricles  are  damaged  more  frequently. Then  the  agent  enters  in  to  subarachnoid  space  and  brain’s  membranes  with  the  spinal  fluid  flow.

In some cases, especially  in  increated patients the  process may  turn  into  ependima  of  the  ventricles. As  a  result  it  may  be  occlusion  of  the  foramina  of Lushka, Magendie, the  aqueduct of Sylvius. It leads to development to hydrocephaly.

In the pathogenesis of meningococcal infection toxic and allergic components play an important role. Thus, in  fulminate  forms  of  meningococcal  infection  infectious-toxic  shock  develops  due  to  massive  destruction  of  meningococcus  and  liberaton  of  considerable  quantity  of  endotoxin. In  infectious-toxic  shock  the  development  of  thrombosis, hemorrhages, necrosis  in  different  organs  are  observed  even  in  the  adrenal  glands (Waterhause - Fridrechsen  syndrome).

The  severe  complication  may  develop  as  a  result  of  expressive  toxicosis. It  is  cerebral  hypertension, leading  frequently  to  lethal  outcome, cerebral  coma. This  state  develops  due  to  syndrome  of  edema  swelling  of  the  brains with  simultaneous  violation  of  outflow  of  cerebrospinal  fluid  and  its  hyperproduction. The  increased  volume  of  the  brain  leads  to  pressure  of  brain’s  matter, its  removement  and  wedging  of  medulla  oblongata  into  large  occipital  foramen, pressure  of  oblong  brain, paralysis  of  breath  and  cessation  of  cardiovascular  activity.

Morbid  anatomy

In meningococcal infection pathologoanatomical changes depend on form and duration of the disease.

Nasopharingitis is characterized by hyperemia of the pharyngeal walls, edema of the epithelial cells, regional infiltration, hyperplasion and hyperthophy of lymphoid follicles. Signs of catarrhic inflammation are found in trachea and bronchi.

Cases of fulminate meningococcal infection is characterized by blood vessels disorders and severe impairments of blood circulation. The main target are the microcirculation vessels. The vascular lumen turns narrow, thrombs are found. Thrombs  are usually found in small veins. Hemorrhages into skin, subcutaneous tissue, lungs, myocardium, subendocardial hemorrhages, hemorrhages into renal parenchyma, adrenals, brain (Fig.7) and subarachnoidal space are typical.

Fig.7. Hemorrhages into brain

Fig.8. Purulent inflammation

 

Meningococcous meningitis is characterized by serous or purulent inflammation of pia mater (Fig.8).

 

Clinical manifestation

The incubation period is 1-10 days, more  frequently 5-7 days.

Classification of the clinical forms of meningococcal infection:

I. Primarily localized forms:

a) meningococcal carrier state

b) acute nasopharyngitis;

c) pneumonia.

II. Gematogenously generalized forms:

a) meningococcemia: typical acute meningococcal sepsis; chronic;

b) meningitis; meningoencephalitis;

c) mixed forms (meningococcemia + meningitis, meningoencephalitis).

d) rare forms (endocarditis, arthritis, iridocyclitis).

In meningococcal carriers  the clinical manifestations  are absent.

Meningococcal nasopharingitis

The most common complains of the a patients are headache, mainly in the frontal-parietal region, sore throat, dry cough, blocked nose, fatigue, weakness, loss of appetite, violation  of  the  sleep. In most of the patients body temperature rises upto subfebrile and lasts for not more than 3-7 days, sometimes 5-7 days. The skin is pale, conjunctival vessels and sclera are injected. There  are hyperemia and edema of  the mucous membrane of the nose. In many patients the posterior wall of the pharynx seem to be covered by mucous or mucous – purulent exudation.

Inflammatory changes in the nasopharynx can be noticed after 5-7 days, hyperplasion of lymphoid follicles lasts longer (till 14-16 days). In the peripheral blood temperate leukocytosis with neutrophylosis and a shift of leukocytaric formula to the left, increase in ERS  may  be revealed. Nasopharyngitis  precedes  to  development  of  generalized  forms  of  the  disease.

 

Meningitis

It  may  start  after  meningococcal  nasopharyngitis, but  sometimes  primary  symptoms  of  the  disease  arise  suddenly. In meningitis three  symptoms  are revealed constantly: fever, headache and vomiting. Temperature  is  increases  quickly  with  chill  and  may  reach  40-41°C  during  few  hours. Intermittent, remittent,  constant, double  waved  types  of  the  temperature  occur  in  meningitis. The patients  suffer  from  severe  headache, having  diffuse  or  pulsatory  character. Headache  is  very  intensive  at  the  night. It  increases  due  to  change  of  body  position, sharp  sounds, bright  light. Vomiting  arises  without  precedent  nausea. There  is  no  connection  with  food  and  relief  after  vomiting. It  is  rule  abundant, by “fountain”, repeated. Sometimes, vomiting  arises  on  the  peak  of  headache.

In  meningitis  hyperthermia, hyperkynesia, photophobia, hyperalgesia, hyperosmia  are  noticed. These  symptoms  are  revealed  more  frequently  in  children. The  severe  convulsions  arise  in  the  many  patients  at  the  first  hours  of  the  disease (clonic, tonic  or  mixed  types). In  small  children  meningococcal  meningitis  may  start  with  convulsions.

The  disorders  of  consciousness   occupy  the  great  place  in  clinical  picture (from  sopor  till  coma). The  loss  of consciousness  develops  after  psychomotoric  excitement. The  loss  of consciousness  at  the  first  hours  of  the  disease  is  unfavorable  sign.

During  objective  examination  meningeal  symptoms  stand  at  the  first  place. It  is  described  near  30  meningeal  signs. A  few  meningeal  signs  are  used  in  practice: rigidity  of  occipital  muscles, Kernig’s  symptom, Brudzinsky’s  symptom (upper, middle  and  lower). The  estimate  of  state  of  fontanelle  is  very  important  in  infants. There  are  three  symptoms  of  meningitis  in  infant: swelling, tension  and  absence  of  fontanelles  pulsation.

There  is  no  accordance  between  expression  of  meningeal  syndrome and  severity  of  the  disease. The  expression  of different  symptoms  is  no  similar  at  the  same  patient. The  patient  has  compulsory  pose  during  serious  cases. He  lays  on  side  with  deflection  of  the  head  backwards (Fig.9). The  legs  are  curved  in  knee-joint  and  pelvic-femoral  joint. The  legs  are  pulled  to  abdomen. Asymmetry  and increased  tendinous, periostal  and  dermal  reflexes  are   observed  in  the  patients. These  reflexes  may  be  decreased  during  expressive  intoxication. Pathological  reflexes  may  be revealed (such  as  Babinski’s, Hordon’s,  Rossolimo’s  reflexes, foot’s clones), and  also  symptoms  of  damage  cranial  nervous  (more  frequently III, VI, VII, VIII  pairs).

 

Fig.9. Patients specific pose in case of meningitis

The  multiple  symptoms  of the lesion of the  other  organs  and  systems  are  connected  with  intoxication. There  is  tachycardia  at  the  first  hours  of  the  disease. Then  it  may  be  bradycardia. Arrhythmia, tachypnoea  (30-40  times  in  minute)  are  possible. The  tongue  is  covered  by  dirty  brownish  coat. It  is  dry. Abdomen  is  pulled  inside. There  is  tension  of abdomen muscles.

The  external  appearance   of  the  patients  is  very  typical. There  is  hyperemia  of  the  face  and  neck. Sclera’s  vessels  are  injected.

In  hemogram   high  leukocytosis, neuthrophylosis  with  shift  of  formula  to  the  left, increased  ERS  are  observed. Small  proteinuria, microhematuria, cylinderuria  are  marked  in  urine.

Fulminate  course  of  meningitis

 With  syndrome  of  brain’s  swelling  and  edema  is  the  most  unfavorable  variant. There  is  hypertoxicosis  during  this  form  and  high  percentage  of  mortality. The  main  symptoms  are  consequence  of  inclination  of  the  brain  in  to  foramen  magnum  and  strangulation  of  medulla  oblongata  by  tonsils  of cerebellum. Immitant  symptoms  from  cardiovascular  and  respiratory  systems  develop  quickly. Bradycardia  appears. Then  it  is  changed  by  tachycardia. Arterial  pressure  may  fall  catastrophically, but  it  increases  more  frequently  till  high  level. Tachypnoea  arises (till  40-60  times/min)  with  help  of  axillary  muscles. The  disorders  of   breath  lead  to  its  sudden  interruption. These  symptoms develop in hyperthermia, clonic  cramps  and  loss  of  consciousness. Cyanosis  of  the  skin, hyperemia  of  the  face  are  marked. Pyramidal  signs,  sometimes  symptoms  of  damage  of  cranial  nerves, decreased  corneal  reflexes  contraction  of  pupils  and  its  decreased  reaction  on  light  are  determined. Death   occurs  due  to  respiratory  failure  at  the  first  hours  of  the  disease, rarely  on  2-3  day  or  on  5-7  day.

Meningitis  with  syndrome  of  cerebral  hypotension

It  is  rare  variant  of  the course  of  meningococcal  meningitis. It  is  observed  principally  in  children.

 The  disease  develops  impetuously, with  sharp  toxicosis  and  exicosis. Stupor  develops  quickly. Cramps  are  possible. Meningeal  signs  are  no  expressive,  because, the  diagnostics  is  difficult. Intracranial  pressure  rapidly  falls. In  this  case  the  volume  of  the  fluid  in  the  brain’s  ventricles  decreases. Ventricular  collapse  develops. In  infant  the  large  fontanelle  is  depressed. In  adults  and  children  supporting  moments  in  diagnostics  are  clinical  signs  of  dehydration  and  hypotension  of  cerebrospinal  fluid, which  flows  out  by  rare  drops. The  fall  of  intracranial  pressure  may  lead  to  development  of  severe  complication – subdural  hematoma.

 

Meningitis  with  syndrome  of  ependimatitis (ventriculitis)

Now  it  is  rare  form  of  meningitis. This  form  develops  during  late  or  insufficient  treatment  of  the  patients. Especial  severity  of  the  disease  is  connected  with  spread  of  inflammation  on  ventricles  membranes (ependime)  and  involvement  of  brain’s  substance  in  to  pathological  process.

The  principal  clinical  symptoms  are  total  and  expressive  muscular  rigidity. The  patients  accept  the  particular  pose. The  disorder  of  psychic, sleeping,  tonic  and  clonic  cramps  are  observed. The  body  temperature  is  normal  or  subfebrile  during  general  severe  state  of  the  patient. Vomiting  is  constant  symptom. Hydrocephalia  and  cachexia  develop due  to  prolonged  course  and  (or)  noneffective  therapy  of  ependimatitis.

Meningoencephalitis

It  is  rare  form  of  meningococcal  infection. In  this  case  the  symptoms  of  encephalitis  predominate, but  meningeal  syndrome  is  weakly  expressed. Meningococcal  encephalitis  is  characterized  by  rapid  onset  and  impetuous  cramps, paresises  and  paralyses. Prognosis  is  unfavorable. The  mortality  is  high  and  recovery  is  incomplete  even  in  modern  conditions.

Meningococcemia (meningococcal sepsis)

The disease is more impetuous, with symptoms of toxicosis and development of secondary metastatic foci. The onset  of  the disease is an acute. Body temperature may increase upto 39-41 0C and lasts for 2-3 days. It  may be continous, intermittent, hectic, wave-like. It is possible the course of the disease  without  fever. There  is  no  accordance  between  degree  of  increasing  of  the  temperature  and  severity  of  the  course  of  the  disease.

The  other  symptoms  of  intoxication  arise  simultaneously  with  fever: headache, decreased  appetite  or  its  absence, general  weakness, pains  in  the  muscles  of  the  back  and   limbs. Thirst, gryness  in  the  mouth, pale skin or cyanosis, tachycardia   and  sometimes  dysphnoea  are  marked. The  arterial  pressure increases  in  the  beginning  of  the  disease. Then  it decreases. It  may  be  decreased  quantity  of  urine. Diarrhea  may  be  in  some  patients. It  is  more  typical  for  children.

Exanthema  is  more  clear, constant  and  diagnostically  valuable  sign  of  meningococcemia.

Fig.10. Exanthema in case of meningococcemia

 Dermal  rashes  appear  through 5-15  hours, sometimes  on  the  second  day  from  the  onset  of  the  disease. In  meningococcal  infection  rash  may  be  different  over  character,  size  of  rash’s  elements  and  localization. Hemorrhagic  rash  is  more  typical (petechias, ecchymosis  and  purpura).

The  elements  of  the  rash  have  incorrect (“star-like”) ( Fig.10) form, dense, coming  out  over  the  level  of  the  skin. Hemorrhagic   rash  is  combined  inrarely  with  roseolous and  papulous  rash.

The  severe  development  of  the  rash  depends  from  the  character, size  and  depth  of  the  its  elements.  The  deep  and  extensive  hemorrhages  may  be  necrosed. Then  it  may  be  formation  of  deep  ulcers. Sometimes  deep  necrosis  is  observed  on  the  limbs  and  also, necrosis  of  the  ear, nose  and  fingers (Fig.11)  of  the  hands  and  legs (Fig.12).

 

Fig.11. Necrosis of fingers

Fig.12. Zones of leg necrosis

During  biopsy  meningococci  are  revealed. Exanthema  is  leucocytaric-fibrinous  thrombosis, contained  the  agent  of meningococcal  infection. Thus, in  meningococcal  infection  rash  is  the  secondary  metastatic  foci  of  the  infection.

Joints  occupy  the  second  place  over  localization  of  metastases  of  the  agent. At  the  last  years  arthritises    and  polyarthritises  are  marked  rarely  (in  5 %  of  the  patient  during  sporadic  morbidity  and  in  8-13 %  of  the  patient  during  epidemic  outbreaks). The  small  joints  are  damaged  more  frequently. Arthritis  is  accompanied  by  painful  motions, hyperemia  and  edema  of  the  skin  over joints.

Arthritises  appear  later  then  rash  (the end  of  the  first  week – the beginning  of  the  second  week  of  the  disease).

 Secondary  metastatic  foci  of  the  infection  may  appear  rarely  in  the  vascular  membrane  of  the  eye, in  myocardium, endocardium, lungs  and  pleura. Similar  foci  arise  very  rarely  in  kidneys, liver, urinary  tract, borne  marrow.

In  the  peripheral  blood  high  leukocytosis, neuthrophillosis  with  shift   of  the  formula  to  the  left  aneosinophyllia,    increased  ESR  are  observed. Thrombocytopenia   develops inrarely.

There  are  alterations  in  urine  as  during  syndrome  of  “infectious-toxic  kidneys”. Proteinuria, microhematuria, cylinderuria are marked.

Meningococcal sepsis is combined with meningitis in majority cases. In  4-10 %  of  the  patients  meningococcemia  may  be  without  damage  of  the  soft  cerebral  covering. Frequency  of  meningococcal  sepsis  is  usually  higher  in  the  period  of  epidemic.

Fulminate meningococcemia ( acutest meningococcal sepsis, Waterhause-Friedrichen syndrome)

It is the more severe, unfavorable  form  of  meningococcal infection. Its base  is  infectious-toxic shock. Fulminate sepsis is  characterized  by  acute sudden beginning and impetuous  course. Temperature of body rises up to 40-41 oC. It is accompanied by chill.   However, hypothermia  may  be observed  through  some  hours. Hemorrhagic  plentiful  rash  appears  at  the  first  hours  of  the  disease  with  tendency  to  confluence  and  formation  large  hemorrhages, necroses. A purple-cyanotic spots arise on the skin (“livors mortalis”). The  skin is pale, but with a total cyanosis. Patients are anxious and excited. The  cramps  are  observed  frequently, especially in children. The recurrent blood vomiting  arise  inrarely. Also, a bloody diarrhea  may be  too. Gradually, a prostration becomes more excessive and it results is a loss of the consciousness.

Heat’s  activity decreases  catastrophically. Anuria  develops (shock’s  kidney). Hepatolienalic  syndrome  is  revealed  frequently. Meningeal  syndrome  is  inconstant.  

In  the  peripheral  blood  hyperleukocytosis (till 60*109/l), neutrophylosis, sharp shift  leukocytaric  formula  to  the  left, thrombocytopenia, increased  ESR (50-70 mm/h)  are  reveled. The  sharp  disorders  of  hemostasis  are  marked -  metabolic  acidosis, coagulopathy  of  consumption, decrease  of  fibrinolitic  activity  of  the  blood  and  other.

Mixed  forms (meningococcemia + meningitis)

These forms occur in 25-50 % cases of generalized meningococcal infection. In  the last years there is tendency of increase frequency of mixed forms in general structure of the disease, especially in periods of epidemic outbreaks. It is characterized by combination of symptoms of meningococcal sepsis and damage of cerebral membranes.

Rare forms of meningococcal infections

These  forms (arthritis, polyarthritis, pneumonia, iridocyclitis) are consequence of meningococcemia. Prognosis is favorable   in  opportune  and  sufficient  therapy.

Diagnostics

The diagnosis of all forms of meningococcal infection is based on the complex of epidemiological and clinical data. The  final  diagnosis  is  established  with  help  of  the  laboratory  examination. Separate  methods have different diagnostical significance in various clinical forms of meningococcal infections.

 The  diagnosis of meningococcal carrier is possible only by use of bacteriological method. The  material for analysis is the mucus from proximal portions of upper respiratory tract. In diagnostics of meningococcal nasopharyngitis epidemiological and bacteriological methods occupy  the  main  place. Clinical  differention of meningococcal nasopharyngitis from nasopharyngitis of the  other genesis is no possible or very difficult.

In recognition of generalized forms, anamnestical and clinical methods of diagnostics have real diagnostic significance, mainly in combination of meningococcemia and meningitis.

 The  examination  of  cerebrospinal  fluid (CSF)  has  great  meaning  in   diagnostics  of  meningitis. In  lumbar  punction cerebrospinal  fluid  flows  out  under  high  pressure  and  by  frequent  drops. The cerebrospinal  fluid  may  flow  out  by  rare  drops  only  due  to  increased  viscosity  of  purulent  exudation  or  partial  blockade of  liquor’s  ways. Cerebrospinal  fluid  is  opalescent  in  initial  stages  of  the  disease. Then  it  is  turbid, purulent, sometimes  with  greenish  shade (Fig.13).

Fig.13. Cerebrospinal  fluid  in meningococcal meningitis

Pleocytosis  achieves till  10-30 103  in  1  mcl. Neuthrophils  leukocytes  predominate  in  cytogram. Neuthrophilous  compose  60-100%  of  all  cells. In  microscopy  neuthrophils  cover  intirely  all  fields  of  vision, inrarely. Quantity  of  protein  of  cerebrospinal  fluid increases  (till  0,66-3,0 g/l). There  is  positive  Nonne-Appelt’s  reaction. The  reaction  of  Pandy  composed (+++). Concentration  of  glucose  and  chlorides  are  usually  decreased.

In  generalized forms  the  final  diagnosis  is  confirmed  by  bacteriological  method. In  diagnostics  immunological  methods  are  used too. Reactions of  hemagglutination, latex  agglutination  are  more  sensitive.

 

Differential  diagnosis

 In  meningococcemia  the  presence  of  rash  requires  of  differential  diagnostics  with  measles, scarlet  fever, rubella, diseases  of  the  blood (thrombocytopenic  purpura Werlgoff’s  disease; hemorrhagic  vasculitis – Sheinlein-Henoch’s  disease).   Sometimes  it  is  necessary  to  exclude  epidemic  typhus, grippe, hemorrhagic  fevers.

It  is  necessary  to  differentiate  meningococcal  meningitis  with  extensive  group  of  the  diseases:

1.     Infectious  and  noninfectious  diseases  with  meningeal  syndrome  but  without  organic  damage  of  central  nervous  system (meningismus). Meningismus  may  be  in  grippe, acute  shigellosis, uremia, lobar  pneumonia, toxical food-borne  infectious, typhoid  fever, epidemic  typhus, infectious  mononucleosis, pielitis, middle  otitis.

2.     Diseases  with  organic  damage  of  central  nervous  system, but  without  meningitis (brain  abscess, tetanus, subarachnoid  hemorrhage).

3.     Meningitis  of  other  etiology. In  purulent  meningitises  etiological  factors  may  be  pneumococci, staphylococci, streptococci, bacterium  coli, salmonella, fungi, Haemophilus  influenzae. In  purulent  meningitis  nonmeningococcal  etiology  it  is  necessary  to  reveal  primary  purulent  focus(pneumonia, purulent  processes  on  the  skin, otitis, sinusitis, osteomyelitis).

Treatment

The  therapeutic  tactics  depends  from  the  clinical  forms, severity  of  the  course  of  the  disease, presence  of  complications, premordal  state. In  serious  and  middle  serious  course  of  nasopharyngitis  antibacterial  remedies  are  used. Peroral  antibiotics oxacillin, ampyox, chloramphenicol, erythromycin  are  used.

The  duration  of  the  therapy  is  3-5 days  and  more. Sulfonamides  of  prolonged  action  are  used  in  usual  dosages. In  light  duration  of  nasopharyngitis  the  prescription  of  antibiotics  and  sulfonamides  is  no  obligatory.

In  therapy  of  generalized  forms  of  meningococcal  infection  the  central  place  is  occuped  by  antibiotics, in  which  salt  benzil penicillin stands  at  the  first  place. Benzyl penicillin  is  used  in  dosage  of  200,000-300,000 IU/kg/day. In  serious  form  of  meningococcal  infection  daily  dosage  may  be  increased  to  500,000 IU/kg/day. Such  doses  are  recommended  particularly  in  meningococcal  meningoencephalitis. In  presence  of  ependimatitis  or  in  signs  of  consolidation  of  the  puss  the  dose  of  penicillin increases  to  800 000 IU/kg/day.

In  similar  circumstances  it  is necessary  to  inject  sodium  salt  of  penicillin  by  intravenously  in  dose  2 000 000-12 000 000  units  in  day. Potassium  salt  of  penicillin  is  no  injected  by  intravenously, because  it  is  possible  the  development  of  hyperkalemia.  Intramuscular  dose  of  penicillin  is  preserved.  

Endolumbar  injection  of  penicillin  is  no  used  practically last years. Daily  dose  is  injected  to  the  patient  every  3  hours. In  some  cases  interval  between  injections  may  be  increased  up  to  4  hours. The  duration  of  the  therapy  by  penicillin  is  decided  individually  depending on  clinical  and  laboratory  data. The  duration  of penicicllin  therapy usually  5-8  days.

At  the  last  years  increased  resistant  strains  of  meningococcus  are  marked (till  5-35%). Besides  that, in  some  cases the  injection  of  massive  doses  of  penicillin  leads  to  unfavorable  consequences  and  complications (endotoxic  shock, hyperkalemia  due  to  using  of  potassium salt  of  penicillin, necroses  in  the  places  of  injections  and  other).  Also, the  patients  occur  with  allergy  to  penicillin  and  severe   reactions  in  anamnesis. In  such  cases   it  is  necessary  to  perform  etiotropic  therapy  with  use  other  antibiotics. In  meningococcal  infection  semisynthetic  penicillins  are  very  effective. These  remedies  are  more  dependable  and  preferable  for  “start-therapy”  of  the  patients  with  purulent  meningitis  till establishment  etiological  diagnosis. In  meningococcal  infection  ampicillin  is  the  best  medicine, which  is  prescribed  in  dosage  200-300 mg/kg/day  intramuscularly  every  4  hours.

In  the  most  serious  cases  the  part  of  ampicillin  is  given  intravenously. Daily  dose  is  increased  to  400 mg/kg/day. Oxacillin  is  used  in  dose  not  less  than  300 mg/kg/day  every  3  hours. Metycyllin  is  prescribed  in  dose – 200-300  mg/kg  every  4  hours. In  meningococcal  infection  chloramphenicol  is  highly effective. It  is  the  medicine  of  the  choice  in  fulminate  meningococcemia. It  is  shown, that  endotoxic  reactions  arise  more  rarely  during treatment  of  the  patients  by  chloramphenicol than  during  therapy  by  penicillin. In  cases  of  meningoencephalitis  chloramphenicol  is  not  prescribed  due  to  its  toxic  effects  on  neurons  of  brain. Chloramphenicol  is  used  in  dose  50-100 mg/kg  3-4  ties  a  day. In  fulminate  meningococcemia  it  is  given  intravenously  every  4  hours till  stabilization  of  arterial  pressure. Then chloramphenicol  is  injected  intramuscularly. The  duration  of  the  treatment  of  the  patients  by  this  antibiotic  is  6-10  days.

There  are  satisfactory  results  of  the  treatment  of  meningococcal  infection  by  remedies  from  the  group  of  tetracycline. Tetracycline  is injected  in  dose  25 mg/kg intramuscularly  and intravenously in  the  cases  of  resistant  agents  to  the  other  antibiotics.

Pathogenetic  therapy  has  exceptional  significance  in  therapeutic  measures. It  is  performed  simultaneously  with  etiotropic  therapy. The  basis  of  pathogenetic  therapy  is  the  struggle  with  toxicosis. Salt  solutions, macromolecular  colloid  solutions, plasma, albumin  are  used. Generally 50-40 ml of fluid is injected on 1 kg of body’s mass per day in adults under the control of diuresis. Prophylaxis  of  hyperhydratation  of  the brain  is  performed  simultaneously. Diuretics (lasix, uregit) are  injected. In  serious  cases  glucocorticosteroids  are  prescribed. Full  doses  is  determined  individually. It  depends  on  dynamics  of  the  main  symptoms  and  presence  of  complications. Generally  hydrocortisone  is  used  in  dose  of  3-7  mg/kg/day, prednisolone – 1-2 mg/kg/day. Oxygen  therapy  has  great  significance  in  the  treatment  of  the  patients

The  therapy  of  fulminate  meningococcemia  includs  the  struggle  with  shock. Adrenaline  and  adrenomimetics  are  not  used  due  to  possibility  of  capillary spasm, increased  hypoxia  of  the  brain  and  kidneys  and  development  of  acute  renal  failure. The  early  hemodialysis  is  recommended  in  the  case  of  acute  renal  failure  due  to  toxicosis.

The basis of the therapy of infectious-toxic shock is complex of measures, including application of antibiotics, improvement of blood circulation. The course of infectious-toxic shock is very serious, with high mortality (50% of the patient die during the first 48 hours of the disease). Because, it is necessary to prescribe intensive therapy immediately. Antibiotics of wide spectrum of action are prescribed. Steroid hormones have important meaning in the treatment of infectious-toxic shock. Hormones decrease general reaction of the organism on toxin, positively act on hemodynamics. Treatment by glucocorticoids is conducted during 3-4 days.

Prophylaxis

Prophylactic  measures, directional  on  the  sources  of  meningococcal  infection  include  early  revelation  of  the  patients,  sanation  of  meningococcal  carriers, isolation  and  treatment  of  the  patients. Medical  observation  is  established  in  the  focuses  of  the  infection  about  contact  persons  during  10  days.

The  measures against  of  the  transmissive  mechanism,  are  concluded  in  performance  of  sanitary  and  hygienic  measures  and  disinfection. It  is  necessary  to  liquidate  the  congestion, especially  in  the  closed  establishments (children’s  establishments, barracks’s  and  other). The  humid  cleaning  with  using  of  chlorcontaining  disinfectants, frequent  ventilation, ultra-violet  radiation  are  performed  at  the  lodgings.

 The  measures, directional  on  receptive  contingents, include  increase  nonspecific  resistance of  the  people  (tempering, timely  treatment  of  the  diseases  of respiratory  tract, tonsils) and  formation  of  specific  protection  from  meningococcal  infection. Active  immunization  is  more  perspective  with  help  of  meningococcal  vaccines. There are  several  vaccines, for  example, polysaccharide  vaccines  A  and  C.

Vaccine  from  meningococcus  of  the  group B  was  also  obtained. However, the group B capsular polysaccharide is not sufficiency immunogenic to produce a reliable antibody response in humans to be effective, several solutions to this problem are being studied, including the chemical alterations of the capsular B antigen to make it more immunogenic and the search for other cell wall antigens that  are  capable of eliciting bactericidal antibodies against B meningococci with a minimum of serious side effects. New vaccines against meningococcus are under development.

 

 

SEPSIS

The term sepsis has been used for a clinical situation in which there is evidence of infection plus a systemic response as manifested by an elevated temperature, tachycardia,increased respiration, leukocytosis or an impaired peripheral leukocyte response, and/or the presence of immature band forms of peripheral circulation.

Sepsis has  some  differences  from  the  other  infectious  diseases:

1.     Sepsis  is  polyetiological  disease. The  agents  of  sepsis  may be different  microorganisms –aerobic  and  anaerobic.

2.     There  is  no  united  entrance  gates.

3.     There  is  no  cyclicy  of  the course.

4. Immunity don’t form in sepsis.

 

Etiology

The most frequent etiologic factor of sepsis is auto- or external microflora. These agents are a staphylococcuses, streptococcuses, colibacilluses and other so called conditionally pathogenic microorganisms. Rarely, a reason of the sepsis may be obligate parasites. Blue pus bacillus, gonococcus, meningococcus, bacillus anthracis, salmonella, fungi and others may caused sepsis. But, at last time  staphylococcus is found more often than others, so it should be on the first place by significance. In according  to  international  classification  3  types  of  staphylococcus  are  detached: Staphylococcus  aureus, Staphylococcus  epidermidis, Staphylococcus   saprophyticus. Staphylococcus  aureus  plays  the most  important  role  in  the  pathology  of  human.

Epidemiology

Staphylococcus  infection  is  widely  spread  among  hospitalized  persons. Intrahospital  distribution  is  typical  feature  of  epidemiology  of staphylococcus  infection.

Intrahospital  infections  are  characterized  by  large  quantity  of  the  sources  of  infection, multiply  ways  and  factors  of  transmission  of  the  agent  multiply  persons  with  increased  risk  of  the  infection. The  sources   intrahospital  infection  are  patients  with  different  forms  of staphylococcus  purulent  infection, carriers  of staphylococcus. Carriers  of staphylococcus  from  medical  personnel  play  an  important  role  in  the  conditions  of  the  hospital.

The  ways and  factors  of  transmission  of staphylococcus  infections  are  different: respiratory-drug, contact  and  alimentary. Transmission  of  the  agent  may  be  realized  by  alimentary  way. For  example, it  is  possibly  infection  of  infants  in  born-hause  by  solutions  for  drink  and  milk, using  for  supplementary  nourishment. Staphylococcus  infection  have  sporadic  character  in  observance  of  sanitary-antiepidemic  regime. Epidemic  outbreaks  of  intrahospital  staphylococcous  infections  may  be  in  violation  of  regime.

Staphylococcus  infection  develops  as  rule  in  persons  with  decreased  nonspecific  resistance, with  different  infectious  diseases (especially, viral  etiology), after  chronic  diseases, in  persons after massive  doses  of  immunodepressors, antibiotics, hormones, X-ray  therapy.

 

Pathogenesis  and  pathologic  anatomy

The factors  of  risk, , promoting the penetration of normal germs of skin and mucous membranes into internal mediums of  the  macroorganism system,  may be different  causes injuries, inflammations, trophic disorders, aggression of different microflora, congenital anomalies. The following distribution of microbes in macroorganism may go by different ways – via blood, lymph and direct methastasing. The  intermediate  localization  of  the  process  appears. It  may be phlegmona, abscess or other destructive processes. The  process  is  sepsis, when  it  has  generalized  character  with  damage  liver, spleen, lungs, kidneys, vessels  and  other  organs  and  systems.

The  agents  of  sepsis, penetrating  into  tissues, causes  an  inflammatory process. In  some  cases  the  process  develops  impetuously. The  purulent  inflammatory  focus  arises  on  he  place  of  the  penetration  with  reproduction  of  microbes (primary  focus). But in other cases  inflammatory manifestations are less  expressive and rapidly disappear, but agent penetrates inside tissues by  lymphatic and blood ways and causes inflammatory focus  in distant place. These inflammatory focus may lead to development of sepsis, in corresponding  change  of  reactivity  and  resistance  of  the  organism.

Entrance  dates  of  infection  may  be  in  any  organ  and  tissue. The  primary  focus  is  in  tissues  with  large  quantity  of  lymphatic  and  blood  vessels  more  frequently. For  example,  in  wound  sepsis  the  skin  is  entrance  gates  more  frequently. In  urosepsis  and  gynecological  sepsis  mucous  membranes  are  entrance  gates. Prolonged course of sepsis  is marked in patients with localization septic and primary foci in bones, muscles, urogenital system. In some cases, there are no visual foci, except the primary septic focus. These forms are called septicemia. But in other cases, metastatic secondary purulent foci are formed. These forms are named  pyemia. But, also there is possible a transitional form – septicopyemia.

The  distribution  of  infection  is  realized  from  the  primary  focus  by  blood  and  lymphatic  ways. The  distribution  of  the  agents  is  realized  by  veins too, with  formation  of  thrombosis  and thrombophlebitis. Microbes and their toxins may penetrate to lymphatic vessels and cause lymphangites and lymphadenites. Metastases may be as an infiltrations, phlegmons, abscesses. Purulent infiltrates may appear in intestine too. In the serous cavities they are characterized by purulent exudations (arthritis, pleurisy, peritonitis, pericarditis).

The  localization  of  metastases  in the  lungs  is  on  the  first  place, kidneys  are  on  the  second  place, then – other  organs.

Allergic component has an important role in pathogenesis of the septic process. Primary and secondary septic foci transfer into a source  of sensibilisation of human organism.

In  sepsis  the  violations  of  metabolism, acid-alkaline  balance, deep  changes  of  balance  of  proteins  and  vitamins are observed. Anemia  develops  due  to  damage  of  bone  marrow.

DIC–syndrome plays an important role in the development of septic state and complications. In some cases of sepsis DIC–syndrome comes out on the first plan and cause fatal outcome in considerable degree.

DIC-syndrome is “proteolytic explosion” with activation and following exhaustion of coagulation, fibrinolytic, kallekrein-kinine systems and system of complement.

In sepsis dysbalance of immune system has the pathogenetic meaning. Immune deficiency is manifested by decrease of quantity of T-helpers, reduce of activity natural killers and phagocytic activity of granulocytes. These changes lead to development of generalized infectious inflammatory process.

In  sepsis  pathologoanatomy  alterations are very various. Petechial  rash  is  marked  on  the  skin. Hemorrhages  are  observed  in  organs  and  tissues, especially  on  mucous  membranes. The  alteration  of  myocardium   are  marked  from  turbid  swelling  till  excessive  lipid  dystrophy. Erosions  are  revealed  in  endocardium. Thrombosis  of  veins  are  often  observed. Spleen  is  enlarged. There is a turbid swelling or lipid infiltration  in  liver. Lymphatic nodes are increased. There are a plural hemorrhages in kidneys. Also, they are marked in the gastrointestinal tract. Hemorrhages are observed in the suprarenal glands. There is edema in the lungs. Sometimes there are foci of bronchopneumonia.  The infarction foci are not rare. There  are  edema  and  hyperemia  of  brain’s  substance. In  sepsis  with  metastases (pyemia)  purulent  process  are  observed  in  brain (purulent  meningoencephalitis), lungs (like abscessing  infarctions), kidneys, thyroid  gland. Besides  that, purulent  pleurisies, peritonitis, pericarditis, phlegmons  are  observed  in  different  places.

Classification

I. According to spreading of the disease:

1.     Purulent – resorptive  fever  is  characterized  by  presence  of  purulent  foci, wave-like  course, general  intoxication.

2.     Septicemia  is characterized  by  severe  general  state, hectic  temperature, severe  disorders  of  central  nervous  system  and  cardiovascular  system.

3.     Septicopyemia. This  is  combination  of  septicemia  and  presence  of  secondary  purulent  foci  in  different  organs.

4.     Chronic  sepsis. There  is  purulent  foci  in  anamnesis  during  this  form. The  diseases  is accompanied  by  prolonged  wave-like  fever, presence  of  period  of  remission  and  relapses, periodical  formation  of  purulent  foci.

II. According  to  prolongation  of  course  the  next  form  of  the  diseases are differed:

1.     Fulminant sepsis (24-48 hours)

2.     Acute  sepsis (from  5-7  days  till  some  weeks)

3.     Subacute  sepsis (3-4  months)

4.     Chronic  sepsis (from  some  month  till  one  year  and  more)

III. According   to  date  appearance  of  process  the  next  variants  are  differed:

1.     Early  sepsis (till  3  months  from  appearance  of  the  primary  focus)

2.     Late  sepsis ( later  than  3  months)

IV. According  to  character  of  microorganism  sepsis  is  differed  on:

Sepsis, caused  by  gram-positive flora. It  leads, inrarely,  to  development  of  septicopyemia.

 Sepsis, caused by  gram-negative flora. Infectious-toxic  shock  may  be in  such  cases.

Clinical  manifestation

There is no any specific incubation in septic patients. In one cases, septic process develops through weeks and months after  localized  focus (abscess), but  in  other  cases  sepsis  may  be  on  its  background.

Complains of these patients are different as a clinical manifestations – weakness, headache, pain in joints, chill with following sweats or chilling, dry  mucous  membrane  of  the  mouth, poor appetite, sometimes – diarrhea.

Fever is frequently of hectic character  in patients  with  sepsis. Different variants of the temperature may  be – remittent and intermittent types, sometimes, – the temperature is more high  in  the  morning (the reversal type). The temperature may be not high  in  weak, cachestic  patients  and  elders, but it doesn’t report about light course of sepsis.

Patient’s skin is pale, moist, even icteric in severe cases. Different  rashes  are  observed. Rash  of  hemorrhagic  type  is  marked  more  frequently, sometimes – pustules, ulcers, erythema. Eruption may be on skin of trunk, limbs and face.

Mucous membranes of lips, oral cavity are dry and may have erosions, ulcers, fissures, bleeding sickness. Often, there are hemorrhages of conjunctiva.

Pulse is frequent. Arterial  pressure decreases. Heart is enlarged. There are a systolic murmur above cardiac apex, tachycardia and “pendulous” rhythm during auscultation the  alterations  of  myocardium  are  revealed  during  cardiogram.  The  type  of  these  alteration  is  diffuse  or  diffuse-focal. Sometimes, the  sighs  of  damage  of  endocardium  and  large  peripheral  vessels  are  revealed (arteritises, phlebitises).

The  alterations  of  respiratory  tract  are  revealed  frequently  in  the  patients  with  sepsis: dyspnoe, bronchitis and pneumonia. Pneumonia has tendency to formation to abscesses. Inrarely, serous, purulent, hemorrhagic and mixed pleurisy  arise  in  the  patients.

There  is a dry coated tongue  in  these  patients. Appetite is decreases. Sometimes, vomiting  arises. Spleen is frequently enlarged, soft consistention. Liver also increases and painful during palpation. The abscesses may  arise  inside abdominal cavity.

Septic patient, often, have a disorders of kidneys and urinary track. Sometimes toxic nephrites, purulent paranephrites arise. The alterations of uterus, perimetrium  may  be  in  women. The  primary  location  of  inflammatory  process  is  marked  inrarely  in  urogenital  organs. It  may  give  generalization  of  the  process.

Osseous-muscular system is involved to pathologic process, too. There are reports about the serous and purulent mono- and polyarthritis, foci of osteal destruction, degeneration  of   born  marrow, myocytes. Also, the osteal tissue may  be  site of the primary foci (osteomyelitis).

Different  manifestations  may  be  from nervous system, such as – a meningismus, purulent meningitis, cerebral and spinal hemorrhages, hemorrhages into the vegetative ganglions.

The  signs  of  anemia  are  revealed  in  the  blood – decreasing   quantity of erythrocytes, hemoglobin. Also, there are a signs of the anisocytosis, poikilocytosis, thrombocytopenia. Neutrophilic leukocytosis with shift to myelocytes, increased ESR are marked leukopenia  may  be  in cachestic  patients  with  fulminate  forms  of  sepsis.

Biochemical  changes  of  the  blood  are  expressive  in  the  patient with  sepsis. Increased content  of  bilirubin and increased activity  of  transaminases  are  marked.

In  sepsis  the  proteins  of  serum  blood  are  sharply  changed. A  quantity  of  albumines decreases  and globulines increased. The  changes  of  concentration  of  IgA, IgG, IgM  depend  upon  gravity  of  the course  and  outcomes  of  sepsis.

Fulminant sepsis  is a rare form, for example, of meningococcal sepsis. It has several synonyms. There are – fulminate meningococcemia, acutest meningococcal sepsis, Waterhouse-Friedrichen  syndrome.

 It is the more severe, unfavorable  form  of  meningococcal infection. Its base  is  infectious-toxic shock. Fulminate sepsis is  characterized  by  acute sudden beginning and impetuous  course. Temperature of body rises up to 40-41oC. It is accompanied by a chill. However, hypothermia  may  be  through  some  hours. Hemorrhagic  plenty  rash  appears  at  the  first  hours  of  the  disease  with  tendency  to  confluence  and  formation  large  hemorrhages, necroses. A purple-cyanotic spots arise on the skin (“cadaveric spots”). The  skin is pale, but with a total cyanosis. Moist, covered with a clammy sweat. Patients are anxious and excited. The  cramps  are  observed  frequently, especially in children. The recurrent bloody vomiting  arises  inrarely. Also, a bloody diarrhea  may be  too. Gradually, a prostration becomes more excessive and it results in a lose of the consciousness.

Acute sepsis is the most frequent form   of  sepsis. Staphylococcus  sepsis  is  occurred  more  frequently. It is  accompanied  by  considerable  fatal  outcomes. In  majority  of  the  cases  the  onset  of  disease  is  an  acute  with  chill  and  increase of  the  temperature. Fever  may be of different  character: constant, intermittent , remittent  and  incorrect. Sometimes  sepsis  may  be  with  subfebril   temperature.

Anemia  increases  in  majority of  the  patient, because  the  skin  is  pale. Sometimes  skin  has  jaudiwish  shade  due  to  haemolysis  or  toxic  hepatitis.

The  rash  is in  the  shape  of  petechial. Rash   is  localized  on  the  skin  of  the  chest, forearms, hands, upper  extremities, on  the  mucous  membrane of  the  mouth, conjunctiva  and  all  gastrointestinal  tract. Hemorrhages on  the  mucous  membrane  of  gastrointestinal  tract  may  evoke  bloody vomiting  and  diarrhea. The  sizes  of  hemorrhages  are  different – from  small  points  till  large  hemorrhages. An  appearance of  hemorrhagic  rash  is  explained  by  present  of  hemorrhagic  vasculitis. Rash   may  be  purulent  or  erythematosus character  due  to  infectious-allergic  dermatitis. The  damage  of  joints  is  observed   in  25-30%  of  the  causes. The  large  joints  are  damaged  more  frequently, but  small  joints  may  be  damaged  too. The  joints  are  edematous. There  is  hyperemia  of  the  skin  over  joints. The  motions  are  painful.

In sepsis  symptoms, connecting  with  damage  of  different  organs  and  system  are  always  expressed. They  appear  as  a  result  of expressive  intoxication, or  as  primary  or  secondary  purulent  inflammatory  process.  The   symptoms, connecting  with  damage  of  cardiovascular  system  is  revealed  more  frequently. Staphylococcous  sepsis  may  be  without  damage  of  endocardium. In  this  case  the  clinical  symptoms  are  evoked  by  distrophic  changes  of  myocardium. Tachycardia, decreased  arterial  pressure, pains  in  the  heart   of  indefinite  character, enlargement  of  the    borders  of  the  heart, mulffeled heart sounds are observed.  The  damage  of  the  vessels  may  be  manifested  in  form  of  phlebitis, development  of  thromoembolism  and   also  embolism  of  small  vessels  of  the  skin  and  internal  organs, in  this  violation  of  coronaric  circulation.

Oxygenic  insufficiency  and  damage  of  respiratory  center  leads  to  breathlessness. In  some  patient  bronchitis, pneumonia, abscesses  and  pleurisy  are  observed. Hemorrhagic  pleurisy  is  more  typical  for  staphylococcus  sepsis.

In staphylococcous  sepsis  the  typical  sign  is  increased  liver. The  severe  septic  hepatitis may  be  observed  with  development  of  jaundice  and  violation  of  all  functions  of  liver  and  also  cholangitis, abscesses. Enlarged  spleen (septic  mesenchymic  spleenitis) is    frequent symptom. Spleen  is  soft  in  an  acute  period,  because  it  is  difficulty  to  define spleen  in  pulpation. However, enlarged spleen  is  clearly  defined  in  percussion. During  prolonged  course  of  sepsis  spleen  becomes  dense. The  damage  of  kidneys  has  essential  meaning  in  clinic  of  sepsis. In  acute  process  the  local  nephrite  of   microbial  embolic  origin  develops  diffusive  nephritis develops  later.

The  symptoms  of  damage  of  nervous  system  are  the  principal  clinical  manifestations  in  the  patient  with  sepsis. In  acute  sepsis  consciousness  is  preserved  even  in  high  temperature. In  this  period  severe  headache, sweat, violation  of  the  sleep  and  dizziness  are  usual  complaints  of  the  patients. In severe  cases  depression, irritation, sometimes  excitement  are  observed  in  the  patients. Due  to  edema  of  the  brain  meningeal  syndrome  may be too. It  is  possible  development    of  secondary  purulent  meningitis. The  appearance  of  meningitis  is  characterized  by  intensification  of  headache, addition  of  vomiting, development  of  meningeal  symptoms. Meningoencephalitis, arachnoiditis  and  abscess  may  developed. The  course  of  acute  sepsis  is  from  2  weeks  till  3  months.

Thus, clinic  of  acute  sepsis  is  characterized  by  severe  course, expressive  symptoms  of  intoxication  and  symptoms  of  damage  of  separate  organs. Frequent  manifestation  of  acute  sepsis  is  development of  bacterial  endocarditis  and  purulent  inflammatory  focuses  in  different  organs (phlebitis, abscesses, pneumonia, pleurisy, pancreatitis, cholangitis, osteomyelitis, otitis, cystitis, violations  of  brain’s  blood  circulation, hemorrhage  into  retina  of  the  eye  and  other.

Subacute  sepsis.    The  course  of  this  sepsis  is  3-4  month. It  is  differented  from acute  sepsis  by  lesser  intensity  of  symptoms. Metastases  appear  more  rarely  than  in  acute  sepsis. The  prognosis  is  better  in  this  form. This  form  of  sepsis  arises  in  damage  of  the  heart  by  rheumatic  process.

Chronic  sepsis is characterized  by  prolonged  course (till  one  year  and  more).

This form is accompanied with remissions and aggravations with a severe morphologic alterations. Chronic sepsis has a wound origin, for example, the septic process in inflammatory of the billiary tract and portal vein. In  some cases, billiary tract is secondary infected due  to of any general cyclic infectious disease. In other cases, billiary tract may be as septic focus.

Outcomes of the disease it depends from the premorbid condition, opportunity, of the therapy and its effectiveness. Prognosis of a sepsis is frequently unfavourible, especially for an infants and elder patients.

Diagnostics

 Bacteriologic investigations is an important diagnostic test in sepsis. The results of the bacteriologic investigations never must be account without a data of history, clinical features and other laboratory tests. The positive bacteriologic results are not always in a septic patients. The negative results are especially  frequent  in  sowing  of  the  blood.

In sepsis the excretion of the agent and estimate of received results are inrarely complicated problem. It is connected with that in sepsis the circulation of agent in the blood is no constant. A quantity of the agent in the blood is oscillated and may be insignificant. The treatment by antibiotics has a large influence on bacteremia.

It is necessary to perform a differentiation with different diseases accompanied with  prolonged fever, rigors, sweating, various eruptions.

Typhoid fever and paratyphoid remind sepsis by fever, pale skin, increased liver and spleen. But, they are differented  from septic process by cyclic course, not so excessive anemia and rarity of the hemorrhagic eruptions. Detachment  of  the  agent  of  typhoid  fever  and  paratyphoid, result  of  IHA-test (indirect  hemagglutination  reaction) help  in  decision  of  problem.

In some cases, tuberculosis, especially its milliary forms in young patients, is difficult for diagnostics. During this, fever, sometimes of hectic type, dyspnoe, sweating  may  be  as  in  sepsis. It is necessary carefully to study  of the epidemiological data, repeated radiological  investigation  and  sowings  of  the  blood.

Also, the hectic fever, sweating may be in acute period of brucellosis. In  brucellosis  there  are  a  little  violations  of  the  general  state  of  the  patients. There  is no the hemorrhagic syndrome. During the second stage there are signs of the locomotor system infractions. In the early stages of the brucellosis,  positive  result  of  Wright reaction  are  marked. Positive  intracutaneous allergic test  is  observed  some  later.

Sepsis should be differentiated with a pneumonia, because pneumonia may be a result  of  sepsis. The following systematic observation and the metastatic foci in joints, endocardium and brain’s membranes are usually helpful for decision of this problem.

In epidemic typhus there  are  typical clinical symptoms. They are jary-Auvcyne’s  symptom, Govorov-Godelyae ’s symptom, Rosenberg ’s symptom early enlargement of spleen. Typical eruption  appears on  the  4-5  day  of  the  disease. Serologic  methods are very useful, especially for the final diagnosis.

Tropical malaria, also, is  accompanied  by a prolonged fever and hepatosplenomegaly. The  typical features of  the  fever  in  tropical  malaria are prolonged paroxysms (to 24-36 hours and over), poorly excessive an apyrexia periods. Rigor and sweating are less excessive, that is caused by some fluctuation of temperature. These attacks are accompanied by severe headache, low back pain, nausea and sometimes by vomiting. Abdominal  pains and watery stools  appear  inrarely. The  indications  of  the  patients  about location  in  focus  of  malaria, depart  to  tropical  countries  have  an  important  epidemiological  meaning. Microscopic blood examination (blood smear and voluminous drop) are needful and reliable laboratory methods to diagnostics of malaria.

Four  diseases  are  problems  for  differential  diagnostics tuberculosis, collagenoses (a lupus erythematosus and so called “non-differentiated” collagenoses or diffuse diseases of connective tissue), malignant neoplasm (especially hepatomas and hypernephromas, also as a lymphogranulomatosis and leukemia).

At  the  last  time  it  is  necessary  to  allow  for  increased  rate  of  fungal  infections  in  diagnostics  of  sepsis. In the main, they are candidoses of the bronchopulmonal, intestine, urogenital and osseous systems. Fungi  of  genus  Candida  albicans  have  the  most  meaning  among  fungal  damages. Fungi  Candida  albicans  are  revealed  in  the  normal  flora  of  the  oral  cavity, intestine.

It  is  necessary  to  perform differential diagnosis of sepsis with intestine yersiniosis. This disease may have  prolonged (more 3 months), relapsing course. In  prolonged  yersiniosis  alteration  of  periods  of  relapses  and  remissions is observed. The period of relapse is characterized by prolonged fever, reactive polyarthritis, myocarditis, prolonged gastroenteritis, hepatolienal syndrome, erythema.

The  repeated  sowings  are produced  on  special  mediums  for  determination  of  the  agent’s  origin: blood, sugar, billiary broth. It is recommended to take the blood in a quantity 15-20 ml on 80-100 ml of the medium. The  agent  may  be  revealed  from hemorrhagic elements, sputum, urine, content of abscess and other materials.

Treatment

Therapy of a sepsis should include at least two obligatory components - suppression of the originator and restoration of immunity.

Principles of a etiotropic treatment of sepsis:

Basis of sepsis therapy - is oppression and liquidation of the agent. There should not be ignored means of syndromes treatment which restore immunity, all others if in them there is a necessity, but all of them can not cure the patient on with sepsis without appropriate ethiotropic therapy.

Antibiotic therapy of sepsis may be successful, if:

1) It is carried out by address, that is after revealing the agent definition of its antibiotic sensivity;

2) It will be carried out (spent) by bactericidal drugs bacteriostatic drugs are used only as address;

3) It is applied at early septicemia (at this stage of illness recovery is achieved in 100 % with  one antibiotic without all other means of treatment);

4) Dozes of antibiotics maximum high, and β-lactamic antibiotics (penicillines, cephalosporines) are used in megadozes;

5) Empirical antibiotic therapy (if the agent is unknown) is carried out on the basis of the clinical supposition about a nature of the agent (empirical antibiotic therapy is should not be carried out by random);

6) Combination of antibiotics is carried out by a rule: bactericidal drugs with the various mechanism of action;

7) Usage of more than two preparations in one combination is not expedient, as with increase of number of drugs harmful actions grow faster, than therapeutic effect;

8) It is not necessary to start antibiotic therapy from reserve antibiotics (carbopenems, cephalosporines of 4-th generation).

If treatment is successful, antibiotic therapy is cancelled  last, after liquidation of all infection foci, but not earlier 5-th day of a normal body temperature. Sepsis is a general  clinical problem. Comprehension of sepsis should become the common medical property because such patients are in all medical establishments without exception.

Among various combinations of antibiotics the greatest recognition has received combination of 3-rd generation cephalosporines (Ceftriaxoni, Cefotaximi, Ceftazidimi) with Aminoglicosides (Gentamicini, Amikacinum). All these combinations are effective enough at patients with sepsis without a neutropenia. Appreciable interest to Ceftriaxoni is caused by duration of its period of semiconclusion, that allows to apply preparation once per day. Other preparations have shorter period of semiconclusion and demand repeated injection during day. At sepsis caused  by Pseudomonas aeruginoza, high efficiency of combination of Penicillinums with antipyocyanic activity (Ticarcilini, Clavulanati, Aztreonami) and Aminoglicosides is marked.

At sepsis caused by Gram-positive flora (Meticilini-resistant staphylococcus, coagulasenegative staphylococcuses, enterococus), using of Vancomycinum, Rifampicinum is effective.

 Carbapenemes (Tienamicines) - Special group of  β–lactames antibiotics (Imipenicemi, Tienami, Meropenemi, Biapenemi), the infections created for empirical therapy with serious current, including leukopenia. Very wide spectrum of action, high bactericides, that is not accompanied by superfluous remission of endotoxins at destruction of bacteria, allow to use with success Carbapenemes as monotherapy at the most serious infections, including sepsis.

After allocation and identification of the originator, definition of antibioticogram the choice of effective antibacterial therapy is considerably facilitated. In such cases monotherapy is frequently used. Nevertheless, the question of indication of monotherapy or a combination of antibacterial preparations remains debatable and, apparently, should be discussed in each concrete case. Determining arguments, probably, will be estimation of gravity of infectious process and condition of reactivity of organism, danger of occurrence of hospital infections in connection with invasive methods of diagnostics and treatment, transplantation of extraneous bodies. Nevertheless, at Gram-negative infections, in opinion of many scientists, the combined therapy is more expedient.

Antibiotics, as a rule, do not suppress immunity. It is proved, that Lincosamides and Macrolides have immunomodulative properties and are capable to stimulate the certain parts of the immune answer.

Duration of  antibiotic therapy  is determined by course of inflammatory process. As a rule, preparations cancel at proof normalization of temperature (absence of attributes of generalized process), absence of the clinical and laboratory data on presence of the localized center of an infection or joining of nosocomial infections. At average therapy lasts 2-3 weeks. At revealing clinical efficiency of empirical or purposeful therapy by antibiotics change of a combination or separate preparation is inexpedient during all period of treatment.

The immunotherapy should be directed on blocking of effects of endotoxin and citocines. Application of Pentoxifilini is perspective, that brakes the formation of FNO, has protictive influence on lungs, systemic hemodynamics, improves microcirculation and oxygenation of tissues, stabilizes electrolytic balance, preventing occurrence of hyponatremia.

Citoprotective antioxidantes (vitamin E, Acetylcysteinum) oppress activity of free radicals and may improve the forecast at sepsis. Hyperproduction of free radicals which are metabolites of an arachidonic acid is lowered also by Ibufrofenum.

Efficiency of polyclonal antibodies to bacteria E. coli and Salmonella which at septic shock caused by Gram-negative bacteria’s, reduce a lethality almost on 50 % was proved. Now polymyxin B or neutrophile bactericidal penetrating protein is used.

Efficiency of application for prophylaxis of the systemic answer on inflammation of vactination of patients by derivative of endotoxin – monophosphorolipides A is now studied. Monoclonal antibodies to interleucines, phospholipase, to adhesive molecules and contact factors are received and pass clinical approbation of antibody to lipid A, to endotoxin and PNO. It is possible, that in future by identification of mediators it will be possible to create “ cocktail “ from antibodies which block receptors and enable to stop progresive process at the systemic inflammatory answer.

Interferons - native and genoinginering preparations which concern mainly to IFN (Roferoni A, Introni A, Realdironi, Laferoni etc.) - natural ways of imunocorection and protection against infections, with success are applied at present of acute and chronic infectious diseases.

Combined using of Carbapenemes, Roncoleucines- or interferons is advanced achievement of modern therapy of septic diseases.

At serious course of a sepsis stabilization of hemodynamics has crucial importance . First of all it is necessary to restore volume of circulating blood. For this purpose infuse cristaloides and colloid solutions in the ratio 2-4:1 under the control of parameters of hemodynamics, including the central venous pressure.

The proof hypotension, even after fast restoration of blood volume circulation, may be connected with disorders of  regulation of  vascular tone. Application of inotropic preparations - Dopaminum, Dobutaminum, Dobutrexi in this case is expedient. The clinical effect from Dopaminum will increase the cardiac emission (B adrenergic effect), rising of peripheric vessels tone (A-adrenergetic effect), improvement of circulation in parenchymatous bodies, first of all in kidneys (dopamineergetic effect). Using of A-adrenomimetics (epinephrine) may be necessary only in case of  inefficiency of high doses of Dopaminum.

Respiratory support is necessary for significant amount of patients with sepsis, however application of different methods of artificial ventilation of lungs is limited to cases of disease with development of acute respiratory insufficiency. In a combination of inotropic therapy ventilating support promotes decrease of work of muscles, improvement of oxygenation of blood and function of systemic circulation.

In support of appropriate level of metabolic and immune processes the important value has a feed of patients. The early high-caloric enteroalimentation with the enlarged contents of fibers and amino acids (an arginine, an ornithine) reduces frequency of complications and duration of treatment. It is necessary to use enteral alimentary admixtures (enpites), balanced under the contents of fibers, Adepses and carbohydrates.

It is expedient to use solutions of amino acids for parenteral feeding (Alvesini, Aminosoli-600, Aminosoli-800, Aminosoli KE, Infesoli 40 and etc.), Dextrosum, lipide emulsions (Intralipid).

DVS demands correction only in stage of a decompensation.

 

 

Prophylaxis

 It is necessary to  perform  reatment  of  primary  foci. The  measures, directing  on  increase  of  resistance  of  the organism  have  an  important  meaning. These  measures  are  rational  diet, regime  of  work  and  rest, physical  tempering.

Staphylococci  are  more  frequent  etiological  factor  of  sepsis, that’s why the  prophylaxis  of  intrahospital  staphylococcal  infection  is  necessary. The  early  revealing  and  prohibition  of  work  of  medical  personnel  with  purulent  inflammatory  diseases (sore  throat,  pyodermia)  and  opportune  hospitalization  of  the  patients  with  staphylococcal  infection  in  special  departments  or  wards. It  is  necessary  the  revealing  of  prolonged  bacteriocarriers  of  hospital  strains  of staphylococces  and  its  sanation  for  patients  with  immunodeficiency  and  operating-room.

The  maintenance  of  sanitary-hygienic  regime  has  leading  meaning  in  the  hospitals  of  different  profile.

It  is  necessary  to  use  remedies, increasing  nonspecific  resistance  of  the  organism  of  the  patients  in  the  groups  of risk (infants, patients  with  immunodeficiency  and  other).