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Coccidioidomycosis

Etiology. A coccidioidomycosis — the infectious disease caused by Coccidioides immitis mushroom living in the soil in the territory of the New World. Its smallest disputes get to a human body at their inhalation or through the injured skin. In a human body the disputes which are in a mitselialny phase (a saprophyte phase) are transformed to sferula, or sporangula. The last will be transformed to endospores which in turn begin to produce new sferula. They, as well as endospores, are not given from one person to another, and also from an animal to the person. immitis find viable S. in pulmonary cavities, they do not constitute special epidemiological danger. Contrary to them artrokonidiya, or the artrospor which are often formed on superficial cultures of a mushroom often cause the expressed disease forms. It is necessary to observe precautionary measures at the processing of clothes, bandage and clinical samples received from patients with open forms of an illness at which education an artrospor is possible. The disease is widespread in the droughty Areas of California, the valley San Joaquin, Northern and South California, the central and southern Regions of Arizona and even southwest part of Texas. In these areas not only the person, but also a cattle, dogs and wild rodents gets sick. The constant infection creates an immune layer among the population and the coccidioidomycosis occurs mainly at children.
Clinical manifestations. At the person it is shown in a look: 1) the benign primary infection inclined to self-healing (at 60% of patients proceeds asymptomatically); 2) residual changes in lungs and 3) the disseminated disease which is quite often coming to an end letalno. At children proceeds easier, than at adults. However at late asked for medical care extensive widespread processes with damage of bones and a meninx can develop that is usually peculiar to persons of more advanced age. Cases of transplacental infection are described.
Primary coccidioidomycosis. The incubation interval varies within 1 — 4 week, most often it makes 10 — 15 days. Can begin imperceptibly or, on the contrary, suddenly with feeling of an indisposition, a fever, fervescence, perspiration at night and anorexias. Sometimes persistent dry cough and pharyngalgias join. There can be headaches, dorsodynias and in a thorax, the pleurae tied with reaction.
For the 1st or 2nd day generalized erythematic or urtikarny rash develops. It can quickly disappear and remains only in inguinal areas. The changes like a knotty erythema which are combined with a polymorphic erythema or without it are very characteristic. Skin changes reach the greatest blossoming during the period with 3 — the 21st day after the beginning of a disease that matches on time the maximum sensitization of an organism to a koktsidioidin. However skin manifestations can appear in the absence of other symptoms of a disease. Along with rashes the phenomena of fliktenulezny conjunctivitis, arthritis and other symptoms of an allergy can develop.
At physical inspection seldom find pathological changes. On roentgenograms of a thorax extensive fields of blackout are usually visible. The percussion sound is in certain cases shortened, the pleural rub and small-bubbling rattles appear. The pleural exudate can be so considerable that breath is broken. As well as at tubercular pleurisy, these changes can precede symptoms of a disease of lungs.
Residual pulmonary coccidioidomycosis. Primary pulmonary koksidioidomikoz seldom is complicated by destruction of fabric and formation of a cavity which in the subsequent is closed. Most often cavities are formed later different periods. In most cases they remain asymptomatic and come to light only on roentgenograms of a thorax. They can sometimes be shown by a pneumorrhagia, sometimes repeated, plentiful, breaking health of the patient which can even lead to a lethal outcome. Bronchogenic planting of healthy sites of a lung is observed extremely seldom. Can remain and it is long to persistirovat focal changes (so-called granulomas) which are not representing danger to the patient, but creating difficulties at differential diagnosis with tuberculosis and new growths in lungs. At some patients the disease takes the form of the chronic progressing fibrous and cavernous process.
The disseminated, or progressing coccidioidomycosis (koktsidioidozny granuloma). At some patients primary infection is not delimited and not stabilized. Within the first 6 months after development of the expressed symptoms of an infection process disseminates and process progresses. On a current she reminds progressing of primary tuberculosis infection. Most often it occurs at males and mainly Philippine and African origin. There are, besides, specific changes in skin, in a bone tissue, cold abscesses are formed. Fungal meningitis, not distinguishable on clinical signs from tubercular belongs to the most serious complications. At Americans of the European race koktsidioidozny meningitis does not represent a big rarity while other extra pulmonary displays of this mycosis at them usually are absent. The miliary centers and peritonitis of a fungal etiology can be distinguished from the corresponding activators, tubercular only on the basis of allocation. Fungal peritonitis proceeds usually rather easily. Koktsidioidozny meningitis in the absence of the corresponding treatment comes to an end letalno in 100% of cases. Outcomes at other forms of the disseminated mycosis depend on character and localization of process.
Diagnosis. Disseminated koksidioidomikoz it is possible to diagnose on the basis of data of a biopsy or autopsy. The sferula revealed at histologic research with double contours and endospores without signs of budding allow to make the diagnosis of a coccidioidomycosis with full confidence. Identification of a mushroom by method of crops or at infection of an animal serves as confirmation of the diagnosis. The phlegm at primary infection usually is absent therefore at children recommend to conduct research of washing waters of a stomach. Mushrooms collapse when processing by the method used for identification of mycobacteria of tuberculosis, hollow clinical samples process penicillin and streptomycin or levomycetinum or 0,05% solution of a copper vitriol for removal of the accompanying bacterial flora. After that it is possible to carry out inoculations of medium or to enter a suspension intraperitoneally to mice or into testicles to Guinea pigs. Anyway at suspicion on a fungal infection it is necessary to carry out a bioassey for identification characteristic sferul. Pure cultures can be also identified by means of serological methods (ekzoantigenny test), but they can be seen off only in specially equipped laboratories in connection with their danger to people around.
Skin test. Test with koktsidioidiny or newer drug sferuliny a vysokospetsifichna, except for cases of cross-reactions at histoplasmosis and a zymonematosis. Positive skin test allows to distinguish a "fresh" infection from "old" only if shortly before it it was negative. At the same time negative skin test does not exclude a koktsidioidozny infection. Koktsidioidin enter vnutrikozhno 0,1 ml in cultivation 1:1000, 1: 100 and even 1:10. Reaction is most expressed in 36 h, read it in 24 and 48 h. Reaction is considered positive at emergence on site of a consolidation not less than 5 mm in size injection. Patients with suspicion on a koktsidioidozny knotty erythema need to enter weak concentration of allergen (1: 1000) because of danger of development in them of giperergichesky reactions. Patients with the disseminated form of a disease are less sensitive to it therefore they can enter solutions in cultivation 1:10, but even in this case reaction on koktsidioidin not always appears. Skin sensitivity to it is less long in comparison with reaction to tuberculine. Allergen does not promote progressing or activation of the main infection even at very considerable general and focal reaction. Under the influence of it synthesis is not stimulated
spetsfichesky antibodies therefore the skin allergy test does not influence results of the serological tests which are carried out further. It can be seen off before the developed immunological research.
Blood analysis and cerebrospinal fluid. Specific reactions of binding complement and pretsiptation appear at patients after development of sensitivity to a koktsidioidin. They    remain positive even in the period of the anergy connected with process dissimination. The caption of reaction of binding complement of subjects is higher, than in more severe form the disease proceeds. At asymptomatically current acute infections specific antibodies in blood usually are absent. Both at primary, and at the disseminated infection SOE increases that helps with an assessment of the clinical status of patients. The eosinophilia meets often. At fungal meningitis of change in cerebrospinal fluid are similar to that at tubercular meningitis. Reaction of binding complement at the same time is positive at 95% of patients and is usually used as diagnostic test. In certain cases similar reactions observe also at patients with epidural koktsidioidozny processes. Fixators can be found in cisternal and lumbar portions of cerebrospinal fluid, but in liquid from ventricles they can be absent. Antibodies do not get through a blood-brain barrier, but in blood of the newborn are present at the same concentration, as at mother's blood. Passively artificial immunity remains at newborns till 6 months of life.
Radiographic research. At primary infection of change in lungs can not receive displays on roentgenograms. Most often note a radical adenopathy, in pulmonary fabric find single or multiple focal and infiltrative changes of different extent, with accurate or indistinct contours, dense and soft. Sometimes they extend to the whole lung lobe. Cavities if are formed, thin-walled. The pleural exudate can collect in a significant amount. In spongy substance of a bone reveal mainly multiple centers of productive character, difficult distinguishable from tubercular.
Prevention. The only method of prevention — minimizing of a possibility of hit in an organism dispute of a mushroom. The available vaccine is inefficient concerning the prevention of a disease at the person.
Treatment. At primary koktsidioidozny infection limit activity of the patient and appoint symptomatic means
until SOE is normalized, precipitant will not disappear and the level of fixators in blood will not decrease, and on roentgenograms of lungs obviously positive dynamics will not be outlined. Cavities in lungs samoizlechivatsya usually. If it does not occur and they are on the periphery, is frequent" cause bleeding or are complicated by consecutive infection, surgical removal of the corresponding site of a lung is shown. Sometimes in the postoperative period complications like residual cavities and bronchial fistulas develop. Also process dissimination is possible. In order to avoid these complications! it is more preferable to perform big thorax operations under cover of an amfoteritsii of Century. It is entered parenterally, it represents choice drug at the disseminated process.
Amphotericinum In possesses nephrotoxicity that is shown in decrease in clearance of creatinine, increase of level of urea in blood and decrease in level of potassium. At depression of function of kidneys on reaching a full dose it begins to be entered every other day or 2 — 3 times a week. Thrombophlebitises can develop even if intravenous injections were carried out very carefully. During treatment anemia, korrigiruyemy by means of hemotransfusions can develop. The agranulocytosis meets seldom, function of a liver is broken mainly at patients with its previous pathology. In the period of primary infection it is not recommended to use Amphotericinum, except for cases of the menacing process dissimination. Despite the frequency and weight of a current of side reactions, treatment by Amphotericinum, especially at the disseminated forms, it is necessary to continue, whenever possible within several months, titrkomplementsvyazyvayushchy antibodies in blood will not decrease yet. Increase of skin sensitivity to a koktsidioidin serves as an indicator of favorable immunological reorganization. Introduction of immunostimulators like a transfer factor of leukocytes is shown to patients with the remaining anergy to allergen (transfer factor). However, its effectiveness is not confirmed yet. Cold abscesses need to be drained, to cut out the synovial membranes and the centers involved in process in bones at their availability. In these cases along with intravenous administration of Amphotericinum also its local use depending on prevalence and disease severity is shown.
Amphotericinum In in therapeutic concentration does not get through a blood-brain barrier, but can mask meningitis at intravenous administration. Treatment of the patient with meningitis needs to be begun perhaps earlier. Intrathecal introduction of Amphotericinum in gradually increasing doses from 0,025 to 0,5 mg 2 — 3 times a week is recommended. The arachnoiditis and a cross myelitis at the same time belong to possible complications.
Treatment at koktsidioidozny meningitis is begun with simultaneous introduction of Amphotericinum intravenously and intratekalno.
Preferably intrathecal administration of drug in the big tank, but its not intra ventricular instillations. The brief experience testifies to a possibility of intra lumbar introduction of Amphotericinum to 10% glucose solution. Patients at the same time lie in a bed which head end is lowered on 30 °. Hard proceeding arachnoiditis at such method of treatment develops a little less than at intrathecal administration of drug. Intravenous administration of Amphotericinum can be stopped after other extra meningeal and extra pulmonary localizations of a coccidioidomycosis when the expressed tendency to normalization of clinical and laboratory indicators is outlined are excluded. Treatment at meningitis has to continue at least within 3 months while in cerebrospinal fluid are not normalized the level of protein, glucose and a cytosis, and reaction of binding complement will not become negative. Further supervision over the patient provides systematic control inspections with an interval of 1 — 3 month within not less than 2 years. At headaches and other suspicious complaints immediately make research of cerebrospinal fluid. Usual clinical supervision over patients has to continue within several years as meningitis can recur in 3 — 5 years after liquid normalization.

Small number of adults and children with fungal meningitis successfully treated by intravenous and intrathecal administration of a mikonzolon. At the disseminated coccidioidomycosis which is not followed by meningitis adults had effective a treatment ketokonazoly inside. Experience of use of drug for children is limited. Rather small toxicity allows to use it at treatment of patients with primary coccidioidosis in the most hard cases when there is a danger of hematogenous dissimination.

 
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