Diagnosis, Treatment and Prevention of Aspergillosis

Diagnosis of Aspergillosis

If aspergillus is detected in the sputum of immunocompetent individuals, find out:

– the presence of occupational hazard in history;
– the nature of production and living conditions;
– the presence of symptoms of diabetes;
– condition of the nasopharynx;
– Prescription and frequency of antibiotic treatment for other diseases;
– the presence of chronic nonspecific lung diseases, the duration of exacerbation, the presence and nature of anti-inflammatory basic therapy.

When detecting aspergillus in the sputum of immunocompromised individuals, find out:

– the amount and nature of previous antibiotic therapy, corticosteroid and chemotherapeutic agents;
– the level of CD4 + lymphocytes in the blood, the number of neutrophilic granulocytes in the blood;
– the presence of fungal lesions of other organs (ENT pathology, central nervous system, etc.).

Re-isolation of Aspergillus cultures from sputum / ALS in immunocompetent individuals more often reflects colonization of the airways. In cases of unclear pulmonary infiltrates in immunocompromised patients in the absence of the effect of antibiotic therapy, excretion of Aspergillus in sputum should be considered an etiological point and require specific therapy. If there is no dynamics in 7 days of intensive antifungal therapy, then the diagnosis may be considered unconfirmed.

Repeated determination of antigenemia (galactomannan) and the detection of an X-ray “corolla symptom” in patients at risk are considered equivalent to a biopsy with the detection of mycelium, regardless of whether or not pure Aspergillus culture is isolated.

Laboratory research
Required

– Microscopy (sputum / ALS, biopsy, etc.) for the presence of aspergillus:
– microscopy of unpainted preparations by the method of a hanging or crushed drop.
– microscopy of stained preparations (hematoxylin-eosin, Gomorrie-Grocott impregnation, white calcofluor, etc.).
– Cultural diagnostics with repeated studies of the material (to exclude false positive results):
– inoculation of the material on Saburo, Chapek-Doks medium (aspergillos are rarely found in blood, bone marrow and cerebrospinal fluid) – in immunocompromised individuals, the identification of an aspergillus culture most likely indicates invasive aspergillosis.
– Serological diagnostics:
– with the determination of the galactomannan antigen A. fumigatus in blood serum, cerebrospinal fluid, urine, etc.:
using the radioimmunological method (RIA-Radioimmunoassay);
ELISA method (Enzyme-Linked Immunosorbent Assay) (true positive results for the determination of galactomannan are more likely with its high titer in adult patients, and false positive in children).
– Determination of specific antibodies in blood serum:
IgG (in the diagnosis of chronic necrotizing aspergillosis, aspergilloma);
IgG, IgE (diagnosis of ABA).
– Polymerase chain reaction (PCR) method – to determine aspergillus nucleic acid fragments or their metabolic products, for example, glycan and mannitol (up to 25% false-positive results are possible) (additional diagnostics).

If available

– For the purpose of establishing a diagnosis: histological examination of biopsy material with hematoxylin-eosin staining, impregnation according to Gomori-Grocott, calcofluor white, Gribli, McManus, etc.
– Diagnosis of the intensity of exogenous intake of micromycetes: detection of secretory IgA to fungal antigens and mycotoxins in saliva.

Instrumental and other diagnostic methods
Required

– X-ray examination and computed radiography of the chest to determine the presence of lung damage.
– Bronchoscopy with bronchoalveolar lavage for microscopic and cultural studies.

If available

– To obtain material for the purpose of cultural and histological diagnosis – biopsy of lesions.

Expert advice
Required

– Otolaryngologist – to exclude fungal lesions of ENT organs.

Aspergillosis Treatment

Pharmacotherapy
Due to the low efficiency of treatment of invasive aspergillosis, which is on average 35% (when treated with amphotericin B drugs), immunocompromised patients with suspected aspergillosis even before laboratory evidence is often required to conduct empirical antifungal therapy. Anti-aspergillosis treatment must be carried out simultaneously with the normalization of the patient’s immune status (with the elimination of neutropenia, CD4 + lymphocytopenia), as well as the treatment of hemoptysis.

The dosage of antifungal drugs and the duration of treatment are determined individually.

For invasive aspergillosis, the drugs of choice are: Voriconazole (J02AC03) (first 6 mg / kg, then 4 mg / kg 2 times a day, and later 200 mg twice a day in oral form) and Amphotericin B (J02AA01) (1 , 0-1.5 mg / kg / day) or its form – (J02AA01) (3-5 mg / kg / day), (J02AA01) (0.25-1.0-1.5 mg / kg / day ) and etc.

Second-line drugs include Itraconazole (J02AC02) (dosage when taken per os – 400-600 mg / day for 4 days, then 200 mg twice a day; intravenously – 200 mg twice a day, then 200 mg). It is preferred for use in patients with less immunosuppression. Caspofungin (J02AX04) is also used, first 70 mg once a day, then 50 mg per day intravenously. It is effective in the absence of the effect of other antifungal agents.

For brain damage, these drugs are used in combination with flucytosine (J02AX01) (150 mg / kg per day), which penetrates into the cerebrospinal fluid.

After stabilization to persistent relief of clinical, laboratory and instrumental signs (usually at least 3 months), Itraconazole (J02AC02) 400-600 mg / kg / day is indicated.

Fluconazole (J02AC01) is not active when acting on Aspergillus spp.

Short courses of oral corticosteroid drugs in the treatment of ABA (prednisone at 0.5-1 mg / kg / day) eliminate obstruction of the bronchi with mucus in patients with ABA. Consumption of corticosteroid drugs and the number of exacerbations in patients with ABA may decrease with prophylactic treatment with itraconazole (200 mg twice a day). Itraconazole can also be used in the treatment of exacerbations of ABA.

Surgical procedures
Required

Patients with bleeding in the presence of aspergilloma need a lobectomy. With low lung function, ligation or embolization of the bronchial artery is performed (used as a temporary measure). Systemic therapy is ineffective in endobronchial and cavity aspergillosis. Surgical excision of the lesion or curettage of the affected areas is performed. Surgical intervention is also indicated for a centrally located focus of invasive aspergillosis near the mediastinum, when massive bleeding is possible.

In the treatment of aspergilloma, surgery can be carried out under the protection of intravenous use of amphotericin B or their introduction into the cavity (in the amount of 10-20 mg amphotericin B in 10-20 ml of distilled water). Serious postoperative complications (life-threatening pulmonary bleeding) are not uncommon. Therefore, the decision on surgical intervention is very difficult: resection of the aspergilloma is possible only in patients with massive pulmonary hemoptysis and adequate lung function. There is little evidence that in the treatment of aspergilloma, itraconazole is of some effectiveness.

Efficiency criteria and duration of treatment
The duration of treatment for aspergillosis is not strictly limited, since the effect of therapy, expressed in the elimination of fever and positive clinical and radiological dynamics, depends on the state of the immune system, background diseases, the presence of mixt infection (bacterial-fungal). The duration of treatment is individual and ranges from 7 days to 12 months.

Aspergillosis Prevention

Primary prevention
for patients with pronounced immunodeficiency – measures aimed at preventing the entry of conidia aspergillus into the air, which is achieved by using expensive rooms or chambers with laminar air flows, or by installing various gateways between the rooms and air filters.

Since the soil creates favorable conditions for the development of molds, indoor plants should not be placed in the wards of patients with reduced immunity. At the first manifestations of the disease, the patient should be isolated, indoor flowers removed, air ducts, air conditioners and damp surfaces checked. If aspergillus is detected, surfaces should be treated with disinfectants.

Relapse prevention

For immunocompromised individuals – the prohibition of earthwork, agricultural work, contact with animals, the restriction of stay in dusty and humid places, the prohibition of the consumption of stale and moldy foods, cheeses, etc.