Pneumocystis pneumonia is a severe form of interstitial pulmonary inflammation caused by pneumocysts and developing against the background of severe immunodeficiency conditions. The clinical course is characterized by increasing shortness of breath, unproductive cough, febrile fever, chest pain, and the development of cardiopulmonary insufficiency. The diagnosis is made on the basis of radiological signs, the state of the immune status, laboratory identification of the pathogen in blood, BAL, sputum, biopsy (PCR, serological tests). For etiotropic therapy, sulfonamide, antiprotozoal, immunomodulatory agents are used.
Pneumocystis pneumonia (PP) refers to opportunistic infections affecting individuals with immunodeficiency and immunosuppression. At the same time, most people with a normal level of immunity suffer from pneumocystis infection in the form of ARVI. Antibodies to the pathogen have about 90% of the adult population, about 10% are asymptomatic carriers of pneumocysts – they pose the greatest threat to immunocompromised patients. Disease is the most severe clinical form of pneumocystosis.
Causes of pneumocystis pneumonia
Characteristics of the pathogen
Pneumocystis jirovecii is a microorganism that causes pneumocystis pneumonia and other types of pneumocystis in humans. Until recently, pneumocysts were considered the simplest, but in 1988, based on a number of characteristic genetic, morphological and biochemical signs, they were assigned to fungi of the actinomycete family. Pneumocysts have a tropism to the lung tissue, their entire life cycle takes place inside the alveoli and goes through 4 stages:
- Trophozoite. It represents the vegetative stage of P. Jirovecii. It has an amoeboid shape, a diameter of 1-5 microns, a single core and a thin two-layer membrane. It attaches to the alveolocytes, where it increases in size and divides.
- Precista. It has an oval shape, a diameter of 5 microns. In the early stage it contains one nucleus surrounded by mitochondria, in the late stage it contains 2-6 nuclei with membranes.
- Cyst. Mature cyst of rounded shape, with a 3-layer wall, 7-8 microns in diameter. Inside the cyst contains an even number (usually 8 pcs.) of intracystic sporozoite bodies.
- Sporozoite. When mature cysts break, sporozoites are released from them, some of which have a single set of chromosomes (they are haploid). Merging, they form trophozoites again, and the pathogen’s life cycle repeats.
In the described cycle, two phases are distinguished: asexual, or asexual (division of the trophozoite), and sexual, or sexual (sporozoite-trophozoite-precyst-cyst).
The sources of P. jirovecii are carriers (asymptomatic or ARI patients) and patients with pneumocystis infection. In 30% of cases, involvement of medical workers in the epidemic process is revealed. When coughing and sneezing, carriers secrete a fine aerosol containing pathogens. Infection of a susceptible macroorganism occurs when contaminated air is inhaled (by airborne droplets, airborne dust). The gateway for incoming infection is the respiratory tract. A transplacental transmission pathway is rarely implemented.
Intrafamilial and nosocomial epidemic outbreaks of pneumocystis pneumonia are characteristic. The latter occur more often in premature departments, nursing homes, infectious diseases hospitals. The peak of the childhood incidence of pneumocystis pneumonia falls at the end of summer – beginning of autumn, adults are sick all year round.
Pneumocysts are typical opportunists, since they cause manifest infection only with a pronounced deficiency of cellular and humoral immunity in a certain contingent of patients. The risk groups for the incidence of pneumocystis pneumonia include:
- HIV-infected and AIDS patients;
- patients with CMV infection;
- premature babies and infants with ASD;
- children suffering from hypotrophy, rickets;
- patients receiving immunosuppressive therapy (for leukemia, myeloma, other cancers, organ transplantation, collagenoses);
- patients with primary immunodeficiency, blood diseases (anemia, polycythemia), tuberculosis, kidney pathology.
Pathogenesis of pneumocystis pneumonia
Pneumocysts are present in the respiratory tract of healthy people, but cause pneumocystis pneumonia only in persons with impaired humoral and cellular immunity. It has been experimentally proved that the leading role in the mechanism of pneumocystosis is played by a decrease in T-helper cells (a critical decrease is a decrease in CD4+ lymphocytes of 300-200 cells / ml), an increase in the number of cytotoxic CD8+ lymphocytes.
P. Jirovecii attaches to first–order alveolocytes and alveolar macrophages with the help of special outgrowths – filopodia. Cell adhesion is also promoted by glycoproteins of pneumocysts, which interact with phospholipids, apoproteins, mucopolysaccharides, surfactant of the alveolar epithelium. Under conditions of immunocompromization, cysts multiply using surfactant-associated proteins, and release toxic metabolites.
Alveolocytes are destroyed, the alveoli are filled with foamy exudate containing a large number of pneumocysts at different stages of development, inflammatory cells, detritus. Interstitial tissue is infiltrated by plasma cells. Interstitial plasmocellular pneumonia develops. The interalveolar septa hypertrophy, which leads to a sharp decrease in gas diffusion (alveolar-capillary block), the formation of respiratory failure and severe hypoxia.
The lungs of a patient with pneumocystis pneumonia are enlarged in size, have a “rubber” density, pale red or pale purple color. When pressed, a foamy serous-hemorrhagic fluid is released from them. Histological examination shows a thickened alveolar epithelium, infiltration of the interstitium by plasmocytes, cysts and their daughter forms are determined. Small calcifications, alternating areas of atelectasis and emphysematous expansion of lung tissue may be detected.
In accordance with pathomorphological criteria in modern pulmonology, there are three stages of pneumocystis pneumonia:
- Stage I. The pneumocysts attach to the alveolar wall. There is no inflammatory reaction and clinical manifestations.
- Stage II. There is desquamation of alveolocytes, an increase in the number of pathogens in the form of cysts in macrophages. At this stage, the initial clinical manifestations of pneumocystis pneumonia appear.
- Stage III. Alveolitis develops, plasmocytic infiltration of interstitium, giant clusters of pneumocysts in macrophages and alveoli. Corresponds to the height of the disease.
Stages of development of pneumocystis pneumonia:
- edematous phase ‒ lasts 7-10 days, characterized by an increase in symptoms;
- atelectatic phase ‒ lasts for 4 weeks, accompanied by severe pulmonary insufficiency;
- emphysematous phase – has a different duration, is marked by the reverse development of symptoms.
Pneumocystis pneumonia symptoms
The incubation period is variable – from 7-10 days to 2-4 weeks (in AIDS patients – up to 10 weeks). In the edematous stage, the clinical signs of pneumocystis pneumonia are easily confused with a common respiratory infection. Symptoms increase gradually: at first, weakness, malaise, subfebrility worries. Then there is shortness of breath with moderate exertion, chest pain, dry cough.
In the atelectatic stage, fever takes on a febrile character, intoxication syndrome increases (lack of appetite, weight loss, sweating at night). The cough becomes whooping cough-like, constant, especially disturbing at night. Shortness of breath up to 30-50 respiratory movements per minute is expressed at rest. There is pallor of the skin with nasolabial cyanosis, tachycardia. During this period, the patient may die from cardiopulmonary insufficiency (CPN).
The surviving patients have an emphysematous stage. Body temperature decreases, respiratory disorders disappear. In the outcome of pneumocystis pneumonia, emphysema of the lungs, pulmonary heart is formed. Pneumocystis pneumonia often occurs in association with pulmonary tuberculosis.
A clear stage in pneumocystosis can be traced mainly in young children. In HIV-infected people, the disease has an erased protracted course, in HIV-negative people with immunodeficiency, it is more active, with a rapid increase in SLN.
Typical complications that develop in the midst of the disease are pneumothorax, subcutaneous emphysema, pneumomediastinum, resulting from the rupture of small cystic formations. Abscessing pneumonia may develop. These conditions further aggravate respiratory failure, increase mortality. With significant suppression of immunity, generalization of pneumocystis infection with multi-organ damage to the liver, spleen, gastrointestinal tract, thyroid gland, organs of vision and hearing, lymph nodes, bone marrow can occur.
Diagnostics of pneumocystis pneumonia
Due to the nonspecificity and erasure of the symptoms, a significant problem is the underdiagnosis of pneumocystis pneumonia. Sometimes pathology is diagnosed only posthumously. All patients with suspected PP should be urgently consulted by a pulmonologist, an infectious disease specialist. When making a diagnosis, they rely on the following data:
- Physical. During auscultation, breathing is weakened, dry, moist, crepitating wheezes in the lungs are heard.
- Radiological. In the initial stage of pneumocystis pneumonia, infiltrates similar to the outlines of butterfly wings are detected on lung x-ray. In the midst of infection, bilateral symmetrical foci of compaction are noticeable, alternating with areas of swelling (“cotton” lung). The chest CT reveals areas of infiltration of the “frosted glass” type.
- Endoscopic. Bronchoscopy is prescribed to obtain lavage fluid, perform a trans-bronchial biopsy. With the help of light microscopy, various morphological forms of pneumocysts are detected in the obtained material.
- Laboratory. The parasitological study is aimed at the direct search for the pathogen in sputum smears, bronchial flushes, lung biopsy. Indirect RIF makes it possible to identify trophozoites and cysts in biological samples, PCR ‒ DNA sites of pneumocysts in any biomaterial. ELISA is used to detect antibodies to P. jirovecii in blood serum.
- Other. A significant acceleration of ESR (over 40 mm /h), leukocytosis, eosinophilia, an increase in LDH activity, and a decrease in oxygen partial pressure are detected in the blood. A blood test for HIV infection is mandatory. To assess the state of cell-mediated immunity, the number of CD4+ T-lymphocytes is determined.
Comprehensive clinical and laboratory, X-ray and bronchological examination makes it possible to distinguish pneumocystis pneumonia from other lung lesions:
- pulmonary candidiasis;
- cryptococcal pneumonia;
- cytomegalovirus pneumonia;
- mycoplasma pneumonia;
- chlamydial pneumonia;
- tuberculosis of the lungs;
- respiratory cryptosporidiosis;
- Kaposi ‘s sarcoma;
- bacterial pneumonia.
Pneumocystis pneumonia treatment
Standard antibacterial agents for PP are ineffective. Currently, first-line drugs are considered to be combined sulfonamides that have antimicrobial, bactericidal and antiprotozoal effects. They can be prescribed both orally and intravenously. The course of treatment is 1-3 weeks.
With pronounced toxic effects and resistance, other antibiotics active against pneumocysts are selected (lincosamides, anti-leprosy, antimalarial, antiprotozoal drugs). Due to the mass death of pathogens in the first days of therapy, the condition of patients with pneumocystis pneumonia may worsen, and therefore it is advisable to prescribe corticosteroids.
Prognosis and prevention
Mortality from pneumocystis pneumonia reaches 50% among premature infants, 25-40% among AIDS patients. In 10-30% of immunocompromised patients, a few months after treatment, PP relapses occur. In the absence of treatment, the mortality rate is 100%.
Preventive work is carried out in two directions: epidemiological and medicinal. The first aspect involves extensive testing for pneumocystis infection of representatives of risk groups: patients with HIV, oncopathology, immunodeficiency, premature babies, employees of maternity hospitals and hospitals. The second direction is the pharmacoprophylaxis of pneumocystis pneumonia in individuals with 200 CD4+ cells. It consists in taking sulfonamides in prophylactic doses in long courses.
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