Aspergillosis - Causes, symptoms and treatment. MF.
Aspergillosis is a fungal disease caused by mold fungi of the genus Aspergillus, which affects a person and is manifested by the appearance of primary foci in the lung tissue, a variety of clinical lesions, which in case of severe immunodeficiency can lead to death.
Aspergillus fungi are widespread in nature and are found in soil, in hay, grain, in the dust of various rooms, especially after processing skins and animal wool. An important epidemiological factor is their frequent sowing in dust particles of medical and preventive facilities, which determines the possibility of the emergence of nosocomial fungal infections.
Aspergillosis
Causes of aspergillosis
The causative agent is mold fungi of the genus Aspergillus, the most common of which is Aspergillus fumigatus( 80% of all cases of aspergillosis), less often Aspergillus vlavus, Aspergillus niger and others. Fungi of the genus Aspergillus( or Aspergillus spp.) Belong to the mold fungi, are heat-resistant, a favorable condition for the existence is increased humidity. Fungi of the genus Aspergillus are often present in residential areas, often found on the surface of unsuitable foods. The pathogenic properties of aspergillas are determined by the ability to excrete allergens, which is manifested by severe allergic reactions, lung damage, an example of which can be bronchopulmonary aspergillosis. Also, some of the fungi can release endotoxin, which can cause intoxication. Aspergillus is resistant to drying, and can persist for a long time in dust particles. Destructive for fungi are solutions of formalin and carbolic acid.
The mechanism of infection is aerogenic, and the main way is airborne dust: fungi of this genus enter the respiratory tract with dust particles. There are occupational groups at risk for aspergillosis: agricultural workers;employees of weaving factories and spinning enterprises, as well as immunodeficient patients of medical hospitals, who are exposed to the nosocomial risk of infection.
An additional mechanism of infection is endogenous infection with aspergillas if the fungi of this genus are already present on the mucous membranes. The main factor contributing to the endogenous spread of infection is immunodeficiency, in which 25% of cases develop mycoses of different etiologies, but the major part of which( up to 75%) is aspergillosis.
A person who has aspergillosis, is not contagious to others, such cases have not been described.
The susceptibility of the general population, however, people with weakened immunity during chronic diseases, oncological processes, after organ transplantation and tissues, in HIV infection and others become ill. Seasonality in aspergillosis was not observed.
Immunity after the transferred infection is unstable, there are repeated diseases in the group of immunodeficient patients.
Pathogenic effect of Aspergillus spp.per person
The gateway to infection in the vast majority of cases is the mucosa of the upper respiratory tract. First aspergillas are superficially located, then deepen, causing ulceration of the mucosa.
Aspergillosis, lesion site
1) Even in a healthy person, by inhalation of a large concentration of Aspergillus spores, pneumonia can develop - interstitial pneumonia. A distinctive feature of interstitial pneumonia in aspergillosis is the formation of specific granulomas consisting of giant epithelial cells( the so-called epithelioid cell granulomas).Aspergillosis granulomas( aspergillomas) have a spherical shape and are centrally located foci of purulent inflammation, in which the hyphae of fungi are located, and on the periphery are giant cells. Locations of aspergillus localizations are the upper sections of the lungs, which is confirmed on the roentgenogram. Fungi are found in the affected mucous membrane of the bronchi, in the lung cavity, bronchiectasis foci and cysts, in the lung tissue in this form the fungi do not penetrate( non-invasive aspergillosis).
2) In parallel with the defeat of the respiratory system in aspergillosis, the immunological reactivity of the body( immunodeficiency) decreases. Cases of complications of concomitant diseases of internal organs, mucous membranes and skin are described. Examples are abscesses of the lung, chronic bronchitis, bronchiectatic disease, lung cancer, tuberculosis, against which a pulmonary form of aspergillosis appeared, which, of course, caused a complication of the main process. The last decades show the incidence of aspergillosis in immunocompromised individuals( HIV-infected, cancer patients receiving immunosuppressive therapy, recipients of organs).
3) One of the possible lesions in aspergillosis is the defeat of internal organs and systems( invasive aspergillosis), which occurs in the overwhelming majority of cases against the background of a significant decrease in immunity. Up to 90% of patients with this lesion have two of the possible three features:
• the number of granulocytes in the blood is less than 500 cells per 1 μl;
• therapy with high doses of glucocorticosteroids;
• cytostatic therapy.
In invasive aspergillosis, aspergillomas can form in the internal organs. Drift of fungi occurs hematogenously( with blood flow).First, the lungs are affected, subsequently the pleura, lymph nodes and other internal organs. A feature is the possibility of forming abscesses in place of granulomas in most cases. The nature of the process is similar to septic, in which the lethality is high enough( up to 50%).
4) Allergic alteration of the body - fungal antigens are powerful allergens capable of causing allergic reactions with the primary lesion of the bronchopulmonary tree.
Symptoms of aspergillosis
It is not possible to calculate the incubation period - there is no clear connection between the moment of infection and the appearance of the first symptoms of the disease.
Aspergillosis is classified as invasive( it is more often affected by the sites of the pathogen - the sinuses of the nose, skin, lower respiratory tract), saprophytic( otomycosis, aspergilloma of the lungs) and allergic( bronchopulmonary allergic aspergillosis, aspergillus sinusitis).
Clinically, the following forms of the disease are distinguished:
1) bronchopulmonary form;
2) septic form;
3) eye shape;
4) cutaneous form;
5) defeat of ENT organs;
6) defeat of bones;
7) other more rare forms of aspergillosis( damage to the mucous membranes of the oral cavity, reproductive system and others).
The bronchopulmonary form is the most common form of aspergillosis, characterized by symptoms of tracheitis, bronchitis or tracheobronchitis. Patients complain of weakness, the appearance of a cough with gray phlegm, possibly with blood veins, with small lumps( congestion of fungi).The course of the disease is chronic. Without specific treatment of the disease begins to progress - the lungs are affected with the onset of pneumonia. Pneumonia develops either sharply or complicates the course of the chronic process. In case of acute onset, the patient rises to 38-39 ° C, fever of the wrong type( maximum in the morning or at lunch, and not in the evening, as usual).The patient is shivering, worried with a pronounced cough with viscous sputum mucopurulent or with blood, shortness of breath, chest pain with coughing and breathing, weight loss, lack of appetite, growing weakness, profuse sweating. Upon examination, moist small bubbling rales, a noise of rubbing the pleura, a shortening of the percussion sound are heard.
Aspergillosis, bronchopulmonary form
Sputum microscopy shows greenish-grayish lumps containing mycelium aspergillus accumulations. In peripheral blood, pronounced leukocytosis( up to 20 * 109 / L and higher), increased ESR, increased eosinophils. X-ray - inflammatory infiltrates of round or oval forms with an infiltrative shaft along the periphery, which tend to decay.
In the chronic course of aspergillosis turbulent symptoms do not occur, the fungal process more often overlays the already existing lesions( bronchiectasis, abscess and others).Patients often complain about the smell of mold from the mouth, a change in the character of sputum with greenish lumps. Only radiologically note the occurrence in the existing cavities of spherical shadows with the presence of an air gas layer with the walls of the cavity - the so-called "crescent halo".
Aspergillosis of the lungs, crescent halo
The prognosis of recovery with bronchopulmonary form depends on the severity of the course of the process and the state of immunity and ranges from 25 to 40%.
Septic form of aspergillosis occurs with a sharp depression of immunity( for example, AIDS stage in HIV infection).The process proceeds according to the type of fungal sepsis. Along with the primary lung lesion, the involvement of the patient into the process of internal organs and systems is progressively increasing, the spread of the fungal infection occurs hematogenically. According to the frequency of damage, it is the digestive system - gastritis, gastroenteritis, enterocolitis, in which patients complain about the unpleasant odor of mold from the mouth, nausea, vomiting, stool disorders, with the discharge of a loose stool with foam containing the mycelium of the fungus. Often there are lesions of the skin, eyes( specific uveitis), the brain( aspergilloma in the brain).If aspergillosis develops in an HIV-infected person, the disease is accompanied by other opportunistic infections( candidiasis, cryptosporidiosis, pneumocystic pneumonia, Kaposi's sarcoma, herpetic infection).The prognosis for the disease is more often unfavorable.
Aspergillosis of the ENT of organs proceeds with the development of otitis externa and averages, a lesion of the paranasal sinuses - sinusitis, larynx. When the eyes are affected, specific uveitis, keratitis, and less often endophthalmitis are formed. Other forms of the disease are extremely rare. Aspergillosis of the bone system is manifested by the appearance of septic arthritis, osteomyelitis.
Features of the course of aspergillosis in HIV-infected patients.
Aspergillosis is the most common form of fungal lesions in this group of patients. All patients are in the last stage of HIV infection - the stage of AIDS.Rapidly developing aspergillosis sepsis, which has a severe course and prognosis. The amount of CD4 usually does not exceed 50 / μL.X-ray revealed two-sided focal shading of the globular shape. Along with the lungs, the organs of hearing( otomycosis), vision damage with the development of keratitis, uveitis, endophthalmitis, and the cardiovascular system( fungal lesion of the valvular apparatus of the heart, endocarditis, myocarditis) can often be affected.
Complications of aspergillosis occur in the absence of specific treatment and against the background of immunodeficiency and represent the emergence of extensive abscesses, chronic obstructive pulmonary disease, pulmonary fibrosis, and internal organ damage.
The prognosis of the disease with immunodeficiencies is unfavorable.
Diagnosis of aspergillosis
Preliminary diagnosis - clinical and epidemiological. Occurrence of certain symptoms of the disease in combination with data on the presence of a specific profession, the presence of concomitant disease and immunosuppressive therapy, as well as severe immunodeficiency, persuade the doctor in favor of possible aspergillosis.
The final diagnosis requires laboratory confirmation of the disease.
1) Mycological examination of the material( sputum, bronchus material - flushes, biopsies of affected organs, scrapings of mucous membranes, smears-prints).From the blood, fungi are rarely isolated, so a diagnostic blood test is not valuable.
2) Serological examination of blood for the detection of antibodies to aspergillas( ELISA, RSK), increase in IgE concentration.
3) Paraclinical studies: general blood test: leukocytosis, eosinophilia, increased ESR.
4) Instrumental studies: X-ray examination, CT of the lungs( detection of globular or oval form of bulk infiltrates, one-sided or symmetrical, revealing globular infiltrates in the previously existing cavities with serpovine clarification along the periphery).
5) Special investigations: bronchoscopy, bronchial flushes, bronchoalveolar lavage or transthoracic aspiration biopsy followed by examination of specimens in order to reveal pathomorphological changes: histologically, foci of necrosis, gemmorogic infarcts, invasive vascular involvement, detection of aspergillus hyphae.
Aspergillosis, fungal growth in
material. Differential diagnosis is performed with lung lesions of other fungal etiology( candidiasis, histopalzmosis), pulmonary tuberculosis, lung cancer, lung abscess and others.
Treatment of aspergillosis
Organizational-regime measures include hospitalization according to indications( severe forms of the disease, invasive aspergillosis), bed rest, all feverish period, a full-fledged diet.
Treatment measures include surgical methods and conservative therapy.
1) Conservative drug therapy is a complex task and is represented by the appointment of antimycotics: itraconazole 400 mg / day in long courses, amphotericin B 1-1.5 g / kg / day intravenously with severe immunodeficiency, voriconazole 4-6 mg / kg 2 r/ day intravenously, sppakonazol 200 mg 3 r / day inside, caspofungin 70 mg-50 mg intravenously. Against the background of treatment, antibody titers to aspergillas tend to increase with subsequent gradual decrease. Therapy is supplemented with restorative drugs, vitamin therapy. All drugs have contraindications and are prescribed exclusively by a doctor and under his supervision.
2) Surgical methods: conducting a lobectomy with removal of the affected areas of the lung.
Often, such methods are effective and are confirmed by the absence of recurrence of the disease. When the process is spread, conservative therapy is included.
The effectiveness of treatment is higher when using the possibility of reducing the dosage of concomitant glucocorticosteroid and immunosuppressive therapy.
Prevention of Aspergillosis
1) Timely and early diagnosis of the disease, timely initiation of a specific treatment.
2) Conducting medical examinations in occupational risk groups( agricultural workers, employees of weaving mills and spinning enterprises).
3) Alertness in terms of possible aspergillosis in the group of people suffering from immunodeficiency in the face of immunosuppressive therapy, severe infections( HIV and others).Positive serological responses to antibodies to aspergillas require careful examination of the patient for the disease.
The doctor infektsionist Bykova N.I.