What is Coccidioidomycosis?
Coccidioidomycosis (synonyms: coccidioidomycosis, koktsidioidnaya granuloma, valley fever, desert rheumatism, Pasadasa-Wernicke disease) – a disease related to deep group systemic mycoses, clinically characterized by a primary lesion of the respiratory system, skin and subcutaneous tissue to form the fistula and infiltrates.
Causes of Coccidioidomycosis
The causative agent of coccidioidomycosis is the dimorphic fungus Coccidioides immitis, which occurs in two forms: tissue and culture.
C. immitis is the most virulent infectious agent among mycoses pathogens. Inhalation of one arthroconidia in mice leads to the development of a lethal infection.
Tissue forms – spherules – are considered non-infectious, although they can be transplanted from human to laboratory animals under experimental conditions. The cultural form is pathogenic, it is associated with infection and spread of coccidioid mycosis in endemic foci. In the external environment, the fungus forms colonies consisting of long segmented mycelium filaments, which in young cultures fall into rectangular and barrel arthrospores (2.5-4 microns in diameter). The old culture consists of scraps of mycelium, arthrospor and chlamydospores. Spores of C. immitis during drying can persist for a number of years. Cultures grow well on the environment Saburo, open-hearth broth, etc. The work with the cultures of the fungus is carried out in strict compliance with the rules provided for working with pathogens of especially dangerous infections. Tissue form is very characteristic, widely used in the diagnosis of mycosis. Morphologically, it is quite diverse, especially at different stages of the maturation of the fungus in the tissues. Here there are mainly spherules with a diameter of 15-75 microns. The spherules containing inside the endospores have a dense shell, at the break of which the spores enter the surrounding tissues, where a new spherule develops from each endospore.
The reservoir of infection is the soil in which the fungus develops with the formation of spores. In the dry season spores with dust are spread by air. Infection occurs by inhalation of spore-infected dust. We can not exclude the possibility of the introduction of the dispute through the damaged skin, as well as through the mucous membranes of the digestive tract. Human infection from sick people and animals was not observed. Coccidioidomycosis refers to endemic diseases that are common in semi-desert and steppe areas. In selected endemic areas of the United States, up to 60% of the population is infected with coccidioidomycosis, many of which had some type of infection. According to the intradermal allergy test and the results of serological reactions, about 10 million people are infected with coccidioidomycosis in the USA. Probably, many of them have suffered an infection in the past and only an allergic restructuring of the body to the antigens of the fungus has survived. Isolated cases of coccidioidomycosis are described in Europe. In our country, there were about 50 cases of the disease (Leningrad, Moscow, Vladimir region, Amur region).
Pathogenesis during Coccidioidomycosis
The gates of infection are more often the respiratory organs. In most cases, infection does not lead to severe clinical forms of coccidioidomycosis. Primary infection may be asymptomatic in the form of an allergic restructuring of the body and the appearance of specific antibodies in the serum. In endemic foci, allergy tests with coccidioidin give a positive result in 70% of the population. Some infected develops a kind of pneumonia with the formation of specific granulomas, similar in cell composition to tuberculosis. Granulomas are manifested in numerous small inflammatory foci, which, merging, can form large foci or capture a whole lobe of the lung. The areas of inflammation are often necrotic, forming caverns and abscesses. When lobar lesions can occur areas of caseous pneumonia with extensive cavities. Granulomas as a result of development sometimes lead to fibrosis and calcification. Formed abscesses can be connected with long fistulous passages with the surface of the skin, affecting the path of the pleura, bones, and subcutaneous tissue. In severe cases, hematogenous dissemination may occur, in which endospores from the collapsed spherules penetrate into the bloodstream and spread throughout the body, causing the appearance of secondary foci in various tissues and organs. Hematogenous dissemination of the fungus can occur in any organ, infectious granulomas that are similar in morphology to the primary sites of inflammation are formed. The most frequent outcome of granulomas is necrosis and purulent fusion. The secondary foci in the central nervous system are most severe. Abscesses are most often formed on the basis of the brain and are accompanied by the development of purulent meningitis. Bones are often affected (ribs, vertebrae, small limb bones, tubular bones epiphyses, etc.). Almost always skin is involved in the process. Nodular and ulcerative changes, infiltrates, abscesses are formed. More often they are localized on the head, neck, limbs.
Immunity in coccidioidomycosis is humoral and cellular, however, after the initial transferred disease, the fungus persists for a long time as a latent infection and with a weakening of the body’s defenses, a relapse of the disease may occur.
Symptoms of Coccidioidomycosis
The incubation period varies with inhalation infection from 7 to 18 days. When infected through the skin, it can lengthen to 30-40 days.
According to the clinical course, the following forms of coccidioidomycosis are distinguished:
- primary coccidioidomycosis, which is divided into pulmonary, generalized (septic) and extrapulmonary forms;
- secondary progressive chronic coccidioidomycosis.
Primary infection in 60% of those infected is asymptomatic and is detected when allergic skin tests are made and serologically. Clinically expressed forms with damage to the respiratory system are observed in 25% of those infected. In pulmonary forms, patients complain of cough, chest pain, general weakness, hoarseness. Objectively, there is an increase in body temperature, laryngitis, bronchitis, focal changes in the lungs, a significant increase in the lymph nodes of the root of the lungs, in some patients – symptoms of pleurisy. In the future, cavities are often formed, often in the upper parts of the lungs. The cavity is characterized by a very mild reaction of the surrounding tissue (thin-walled cavity). These cavities (usually single) can persist for many years, periodically opening and disappearing. In 20-40% of patients there are rashes on the skin of the type of erythema nodosum on the 1-2nd (less often on the 3rd) week from the onset of the disease. Occasionally, the rash has an urticar vein and is accompanied by arthralgia, swelling of the joints and eosinophilia.
The generalized (disseminated, septic) form of acute coccidioidomycosis is characterized by hematogenous dissemination with the involvement of a number of organs in the process, the formation of infiltrates and abscesses, especially often in the brain. The disease proceeds hard, intoxication sharply increases, body temperature rises, the temperature curve acquires an irregular (septic) character with large daily sweeps, chills and sweating. In the lungs, radiography can reveal disseminated small miliary foci. Often develops meningitis, meningoencephalitis. Generalization often occurs in the acute period of the disease, but sometimes it occurs 3-4 months after the onset of the disease.
Extrapulmonary forms of coccidioidomycosis are very rare when infected through the skin (possibly through the digestive tract). The course is favorable. It is necessary to differentiate from secondary skin lesions in pulmonary forms of mycosis.
Secondary progressive chronic coccidioidomycosis occurs in 0.5-1% of patients. This is the most severe form with high mortality. Occurs after a few months or years (up to 5 years) after suffering a primary infection. The disease lasts for several months (up to a year, rarely more). Characterized by irregular fever with large daily sweeps, chills, lack of appetite, increasing weakness, weight loss. In the lungs, large infiltrates are detected with necrotization, formation of fistulous passages, damage to the ribs, vertebrae, and infiltrates are formed in the abdominal cavity. In hypodermic cellulose develop congestive. Sometimes there are short-term remissions, which are replaced by new exacerbations and usually end in death.
Complications of coccidioidomycosis. Secondary bacterial purulent infection, tuberculosis can be stratified.
One of the reasons for the dissemination of the fungus may be HIV infection. However, compared with other mycoses, coccidioidomycosis is relatively rare.
Diagnosis of Coccidioidomycosis
The recognition of coccidioidomycosis takes into account the epidemiological background (stay in an endemic area, work with cultures of the fungus) and clinical data.
In the acute phase of disease with pulmonary form diagnostic value imeyutsleduyuschie features: fluktenullezny conjunctivitis, erosive hemorrhagic mucosal changes pharynx, arthralgia, periarthritis, exanthema as nodosum and polymorphic exudative erythema phenomenon tracheo-bronchitis, dyspnea, cough, bloody sputum, physical signs pneumonia. In clinical diagnosis, it is necessary to differentiate from other deep mycoses (histoplasmosis, actinomycosis, nocardiosis), as well as from tuberculosis, syphilis, pulmonary forms of tularemia, osteomyelitis.
From laboratory research methods, the use of the fungus is used, as well as its detection in pathological material (sputum, pus from fistulas, ulcers, pleural cavity, joint fluid, infiltrates, abscesses, cerebrospinal fluid). It is possible to detect the fungus by microscopy using special staining methods (according to the Arabian). To isolate the fungus from pathological materials, they are sown on the Saburo medium and others.
Of the serological reactions used RAC with a specific antigen. Diagnostic captions are 1: 4-1: 32. It is possible to use the precipitation reaction, in which antibody titers increase somewhat faster. In meningeal forms of coccidioidomycosis, it is important to determine the presence of antibodies in the cerebrospinal fluid. Put skin tests with different dilutions of coccidioidin. Usually, the reaction is set at a dilution of 1: 100, for patients with pronounced allergic manifestations, the drug is diluted 1:10 000. Consider the results after 24 and 48 hours. A positive reaction is considered when an erythema with a diameter of 10 mm or more occurs. It should be borne in mind that in coccidioidomycosis patients, the intracutaneous test for a long time (for many years) remains positive. Possible cross-reactions in patients with American blastomycosis.
Treatment of Coccidioidomycosis
Patients with primary pulmonary coccidioidomycosis can be treated symptomatically or prescribed sulfadimezin (1 g 4 times a day) in combination with streptomycin intramuscularly 0.5 g 2 times a day. The duration of the course depends on the course of the disease. Also shown are vitamins, fortifying agents. The most difficult treatment of generalized and especially chronic progressive forms. In this case, the antimycotic drug amphotericin B gives the best results. The antibiotic is used intramuscularly in a 5% glucose solution. The first injection is done at a dose of 250 U / kg body weight. In the future, with good tolerability of the drug, the dose is increased to 1000 U / kg body weight. The drug is administered every other day. The duration of treatment is 4-8 weeks.
Forecast. In primary pulmonary coccidioidomycosis, the prognosis is favorable. With disseminated and chronic progressive forms, the prognosis is serious. Mortality remains high.
Prevention of Coccidioidomycosis
When staying in an endemic area, it is necessary to protect the respiratory tract from dust penetration and to strictly follow the precautions when working with cultures of the fungus in the laboratory. Specific prevention is not developed. Events in the outbreak do not hold.