MENINGOCOCCAL INFECTION

Meningococcal infection is an acute infectious disease of the human, caused by meningococcous Neisseria meningitidis. 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).

Historic reference

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), 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. Osier 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

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polysaccharide capsule, which is the main antigen and determines the serotype of the species. Meningococcus may be seen inside and outside of neutrophills. The main serogroups of pathogenic organisms are A, B, C, D, W135, X, Y, Z and L. The bacterial membrane is a lipopolysaccaride.

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 lipopoly-saccharide origin). Exotoxin is not produced. The agent of meningococcal infection is characterized by low resistance in the environment. Meningococci perish during temperature 50 °Ñ during 5 minutes, during temperature 100 °Ñ - during 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 1,200-1,800 (according other data - 50,000) 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 morbidity in certain region. So, carriers may compose 3-12 %. It is temperate sporadic morbidity. 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

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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 January 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 small. 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

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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 are 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

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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 into 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 Lushka, Magendie, the Sylvius aqueduct. 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 swelling of the brain with simultaneous violation of outflow of cerebrospinal fluid and its hyperproduction. The increased volume of the brain leads to pressure of brain matter, its removement and wedging of medulla oblongata into large occipital foramen, pressure of oblongate brain, paralysis of breath and cessation of cardiovascular activity.

Anatomic pathology

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 hyperthrophy 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

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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 and subarachnoidal space are typical.

Meningococcous meningitis is characterized by serous or purulent inflammation of pia mater.

Clinical manifestations

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 patients are headache, mainly in the frontal-parietal region, sore throat, dry cough, stuffed nose, fatigue, weakness, loss of appetite, sleep disorders. 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 shift of leukocyte 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 increases quickly with chill and may reach 40-41° 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 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, like "fountain", repeated. Sometimes, vomiting arises on the peak of headache.

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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 unfa-vorable 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 seventy 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. 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).

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 per 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 into 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 per min) with help of axillary muscles. The disorders

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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 not 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, pareses 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 °Ñ 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, dryness in the mouth, pale skin or cyanosis, tachycardia and sometimes dysphnoea are marked. The arterial pressure increases in the

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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. 12). 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") 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 on the character, size and depth of 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 of the hands and legs. 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 arthrites and polyarthrites 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.

Arthrites 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, bone marrow.

In the peripheral blood high leukocytosis (20-40 x 109 and more), 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-Friedrichsen syndrome). It is the most 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 °Ñ. It is accompanied by chill. However, hypothermia may be observed through some hours. Hemorrhagic plentiful rash appears at the first hours of the

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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 diarrhea of blood character may be too. Gradually, a prostration becomes more excessive and it results in a loss of the consciousness.

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

In the peripheral blood hyperleukocytosis (till 60 x 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.

Chronic meningococcemia. This form of meningococcal infection is rare. The duration of the disease is from some weeks till some years. One case was described with duration of meningococcemia during 25 years. Fever is usually intermittent. The disease is accompanied by polymorphic exudative erythema. The temperature may be normal during period of the remission. Rash becomes pale. It may disappear. The patient's state is improved. In chronic meningococcemia arthritis and polyarthritis are possible. Splenomegaly is revealed inrarely.

In the peripheral blood leukocytosis, neuthrophylosis, increased ESR are marked. There is temperate proteinuria in urine. Endocarditis (pancarditis) were described in chronic meningococcemia. It is possible the development of meningitis after some weeks or month from the onset of the disease.

»

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

Complications

Meningococcal arthritis occurs primarily in adults. The overall incidence, as a complication of bacteremia, is about 2 to 10 %. There are two forms of meningococcal arthritis. The first is seen within the first few days of treatment and is characterized by severe arthralgias and few objective signs of joint inflammation. The second, more common form appears to be a hypersensitivity phenomenon. It is usually noted three to seven days after the recognition of meningococcemia, often at a time when the patient appears to be improving from the meningitis or sepsis. The knee, wrist, elbow, and ankle joints are most commonly involved.

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Pericarditis, as a complication of meningococcal disease, occurs in 3 to 5 % of cases. It generally occurs in a patient with meningococcemia but has been reported as an isolated event without septicemia or meningitis.

Pericarditis is presumed to be a late complication of meningococcal disease, since clinical symptoms such as fever, dyspnea, or substernal chest pain (or even cardiac tamponade) usually do not appear until the fourth to the seventh day of illness.

Myocarditis was noted at autopsy in 78 % of patients with fatal meningococcal disease. Myocarditis was noted most often in adults, and was more severe than in children.

Numerous other complications include cranial nerve palsies, radiculitis, hemiplegia, seizure disorders,ophthalmic complications, associated herpetic lesions (developing on four or five day of disease), hydrocephalus and arachnoiditis. Orchitis, epididymitis and salpingitis are rare complications.

Diagnosis

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 not possible or very difficult.

In recognition of generalized forms, anamnestic and clinical methods of diagnostics have real diagnostic significance, mainly in case of 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 at the initial stages of the disease. Then it is turbid, purulent, sometimes with greenish shade. Pleocytosis achieves up 10-30 x 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 gm/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.

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

Treatment

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

The duration of therapy is 3-5 days and more. Sulfonamides of prolonged action are used in usual dosages. In mild course of nasopharyngitis the prescription of antibiotics and sulfonamides is not obligatory.

In therapy of generalized forms of meningococcal infection the central place is occuped by antibiotics, in which benzylpenicillin stands at the first place. Benzylpenicillin 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 intravenously in dose 2 to 12 million IU per day. Potassium salt of penicillin is not injected intravenously, because it is possible the development of hyperkalemia. Intramuscular dose of penicillin is preserved.

Endolumbar injection of penicillin is not 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 is usually 5-8 days.

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Recently increase of meningococcus resistant strains is 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 of 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 etiological diagnosis determination. 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 times 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 is concluded in 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.

Meningococcal infection 215

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 impact on hemodynamics. Treatment by glucocorticoids is conducted during 3-4 days.

Prophylaxis

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

The measures, directed on the rupture of the mechanism of the transmission of the infection, consist of 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, ultraviolet 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  was also obtained. However, the group  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  antigen to make it more immunogenic and the search for other cell wall antigens that are capable of eliciting bactericidal antibodies against  meningococci with a minimum of serious side effects. New vaccines against meningococcus are under development.

Control questions:

1. Mechanism of contamination by meningococcous.

2. Localization of infectious agent, meningococcous transmition.

3. The generalized forms of disease, their clinical manifestations.

4. Laboratory diagnosis of meningococcal infection.

5. Differential diagnosis of meningococcous meningitis.

6. Principle of medical treatment of meningococcous infection.

7. Principles of steroid therapy in case of Waterhouse-Friderichsen's syndrome.

8. Criteria of patients discharge from hospital.

9. Duration of supervision and rehabilitation of patiens in polyclinic.

10. Preventive measures in the spot of disease outbreak.

216 Infectious diseases

Date: 2014-12-21; view: 1998