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Mustafaeva Dildora Asatovna, doctor, of Philosophy Deputy Director for Medical Issues The Republican Center to fight AIDS, Tashkent, Uzbekistan E-mail: [email protected]
PROGRESSION FEATURES OF PNEUMOCYSTIS PNEUMONIA IN PATIENTS WITH HIV INFECTION
Abstract: Pneumocystis pneumonia is the most common opportunistic infection of the respiratory tract in HIV-infected individuals. The risk of clinical manifestations of pneumocystis pneumonia is especially high when the CD4 cell count is below 200 (^L -1). In patients with HIV, reproduction of P. jirovecii in the alveoli often occurs as a part of a mixed infection (bacterial flora, fungi), which creates a pathomorphological picture of pneumocystis. In connection with the above, it is important to study the features of Pneumocystis pneumonia in patients with HIV infection as a mono infection, as well as the combination of those with other secondary lesions, to develop clinical diagnostic criteria and to identify reliable laboratory diagnostic methods to confirm it.
Keywords: HIV-infection, pneumocystis pneumonia, secondary immunodeficiency.
Introduction to study the features of Pneumocystis pneumonia in patients
According to literature 25-60% of HIV-infected patients with HIV infection as a mono infection, as well as the com-may develop lung damage [9, 10]. Pneumonia of various ori- bination of those with other secondary lesions, to develop
gins is the most common opportunistic infection in this group of patients. The risk of development of pneumonia increases with the aggravation of immunodeficiency, which significantly worsens the long-term prognosis. Consequently the pneumonia that occurs more than once a year is considered to be an AIDS-defining disease [3, 5]. Along with that, the diagnosis of immunodeficient pneumonia is quite difficult due to the absence of alertness among medical professionals towards HIV-infection. From initial referral until the real cause of the disease is identified, the patients with pneumonia are forced to undergo a wide range of diagnostic procedures to exclude various pathologies which leads to their deter ioration
and, often, to unfavorable outcomes [4, 6].
Pneumocystis infection is the most common disease faced by health care professionals in the field of immunodeficient pneumonia of HIV-infected patients.
Pneumocystis pneumonia caused by Pneumocystis carinii/ jirovecii is an opportunistic infection in immunocompromised patients capable of generalization [1, 2]. The number of patients with that kind of pneumonia ranges from 5.6% to 8.5% of all hospitalized patients diagnosed with AIDS [7,8]. The risk of clinical manifestations of pneumocystis pneumonia is especially high when the CD4 cell count is below 200/^l. The reproduction in the alveoli P. carinii/jirovecii in HIV-infected patients often occurs as part of a mixed infection (bacterial flora, fungi), creating a pathomorphologic picture of pneumocystosis [1]. In connection with the above, it is important
clinical diagnostic criteria and to identify reliable laboratory diagnostic methods to confirm it.
Research objective
The objective of this research is to identify the clinical and laboratory features of Pneumocystis pneumonia in patients with HIV infection in order to improve the quality of diagnosis and to optimize the treatment.
Research methods
We examined 47 in-patients between the age of 18 and 57, admitted to the specialized hospital for infectious diseases of the Republican Center to fight against AIDS. The patients included 23 men and 14 women. Along with standard tests (blood and sputum tests, chest X-ray, CT) immunological, viro-logical, microbiological tests and consultation of the specialists of the AIDS centre were performed on all patients. The treatment was carried out in accordance with the national treatment guidelines. After the examination, depending on the number of CD4 cells in the peripheral blood and related opportunistic diseases (oropharyngeal mycosis), patients were divided into 2 groups. The first group consisted of patients diagnosed with only pneumocystis pneumonia and the second group consisted of patients diagnosed with pneumocystis pneumonia combined with mucosal and esophageal candidiasis.
The first group included 19 patients with CD4 cell count below 200/^l, out of those 13 were men and 6 were women. The second group included 28 patients with CD4 cell count below 200/^l, out of those 17 were men and 11 were women.
PROGRESSION FEATURES OF PNEUMOCYSTIS PNEUMONIA IN PATIENTS WITH HIV INFECTION
Results and discussion
The development of Pneumocystis pneumonia in HIV-infected patients in both groups started with the emergence of general weakness, increase in body temperature, which was also accompanied by chills in 18 patients and excessive sweating in 13 patients. The pneumocystis pneumonia proceeded the most heavily in the second group. Febrile temperature for 3.4 ± 2.5 days, severe respiratory distress for 4.1 ± 2.3 days, hypotonia, weight loss, prolonged asthenia predominated in those patients. Patients complained of pain and a feeling of stuck food and tablets when swallowing, therefore there were problems with the administration of tableted form of drugs. In this group of patients, the most frequent concomitant disease was the severe anaemia (14.3 ± 3.9 days). The first group of patients experienced subfebrile temperature which subsequently either rose to febrile temperature or remained subfebrile in the course of 2.3±1.7 days. The conjoining cough in both groups had an unproductive and intrusive nature, and persisted for several weeks (18.2 ± 5.5) or months (4.2 ± 3.1). The shortness of breath, the earliest symptom of pneumocystis pneumonia was observed in all patients both in the first and second group of patients. During the auscultation of the lungs of the first group of patients, due to the weakened vesicular breathing, there were dry rales heard in 9 (22%) patients, crepitant rales in 17 (41%) patients, and in 15 (37%) patients no abnormalities were identified at auscultation. In the second group of patients during the auscultation, in conditions of severe (67%) and diminished (28%) breathing, there were heard crepitant rales in 9(50%) patients, dry rales in 4(22%) patients and in 5(28%) patients no abnormalities were identified. The patients of the first and second groups received long-term oxygen therapy in ICU.
The level of PO2 in the first group amounted to 43.5 ± 4.1 mmHg which was higher than in the second group. The level of PO2 in the blood of the patients of the second group showed on average 28.9 ± 2.6 mmHg which was well below the normal indications and attested to severe respiratory failure.
In the first group the activity of total LDH was significantly lower than in the other group (p < 0.001) and did not exceed 300 IU/l (263.0 ± of 27.09).The average level of CD4 + lymphocytes was 69.2 ± 7.9 cells/^l, reflecting the profound immune deficiency. In the first group of patients, Biseptol (trimethoprim/sulfamethoxazole) was added to antibiotics at the dose of 15mg/kg of body weight, and in the second group Fluconazole/itraconazole at the dose specified in the national protocol for the treatment of the HIV-infected patients with mucosal and esophageal candidiasis. As a result of the treatment all patients had achieved a condition improvement; and when discharged from the hospital, administration of co-trimoxazole was recommended for prophy-
laxis. Remarkable x-ray changes in the lungs in both groups of patients had been observed. In the beginning of the disease almost 13 patients' x-ray picture of the lungs was normal. Later, on chest x-ray revealed reduction of basal pneumatization of the lung tissue, increased interstitial pattern, and in 23 of the patients - bilateral infiltrates in a butterfly pattern. In the second group of patients, in the midst of the disease, often the process was presented by multiple focal shadows ("spongy" lung) (8.1 ± 2.4) than in the first group of patients (6.3 ± 2.1). The spiral computed tomography of the chest revealed bilateral interstitial damage to the lung tissue, "frosted glass"-like zones of fading, alternating sections of normal lung tissue and infiltration in 17 patients.
The results of the immunogram test showed that the level of the white blood cells in the second group (5.5 ± 0.7 cells/^l) was significantly lower than in the first group (7.5 ± 0.6). The absolute number of lymphocytes was higher in the first group (2498.83 ± 290.08) compared to the second group (880.63 ± 183.1)and (1360.59 ± 146.55). The study ofperipheral blood of specific changes and pneumocystis pneumonia were high levels of erythrocyte sedimentation rate (ESR) (which quickly grew and in the midst of the disease reached 60 mm/h and above) in both groups of patients. The absolute value of CD3+ cells was higher in the first group (2036.01 ± 189.76) than in the second group (1136.32 ±1 40.16). The absolute value of CD8+ was higher in the first group (1643.18 ± 178.23) compared with second group (767.99 ± 172.83). The value of the ratio CD4/CD8 was lower only in the first group (0.07 ± 0.02) compared with the second (0.32 ± 0.03) group. The level of activity of total Lactate Dehydrogenase (LDH) in all patients was high, and averaged 743.0 ± 184.5 IU/L. The increased levels of IgG in serum were revealed, which are involved in the formation of immune complexes, activation of the complement system, are deposited on the microbial cells and enhance phagocytosis. Increased levels of IgM indicate a high activity of b-lymphocytes, therefore humoral immunity. IgA is a surrogate marker of progression of HIV-infection, an increase in their level when combined with pneumocystis pneumonia (PCP) with candidiasis of the mouth and esophagus in HIV-infection indicates significant disturbances in the immune system. The level of the absolute number of B lymphocytes, the relative number ofb lymphocytes, the indicators of phagocytosis and immunoglobulins were elevated in both groups but did not differ significantly.
Thus, verification of the diagnosis of PCP is based on identifying the characteristics of the clinical picture (leading syndrome - a progressive respiratory insufficiency); the definition of immunocompromised condition in a patient; high performance ESR, arterial hypoxemia (decrease in PO2); the isolation of the pathogen from biological material of the respi-
ratory tract; x-ray - bilateral interstitial infiltrative changes in the lung; clinical and radiographic effect protivorevmaticski chemotherapy, trimethoprim/sulfamethoxazole.
Therefore, one can say that the levels ofleukocytes, CD3+, CD4+, CD8+, ratio CD4+/CD8+ was significantly lower in the second group of patients, which led to more severe course of the disease when combined with other opportunists. Hyperproduction of immunoglobulins of all classes testified to the inadequacy of the immune response, contributed to the protracted course of the disease in all groups of patients.
Conclusions:
1. Clinically, the diagnostic criteria for PCP is a long gradual onset of increasing respiratory distress, decrease in the content of PO2 in the blood and always with high ESR.
2. The more severe PCP was observed in the group of patients combined with candidiasis of the oral mucosa and esophagus, but kept the patterns, typical of Pneumocystis pneumonia.
3. Pneumocystis pneumonia in HIV infected patients in combination with candidiasis of the oral mucosa and esophagus is manifested by inhibition of the activity of cellular immune responses, a significant increase in the level of the CEC, all major immunoglobulin classes (M, A, G) in the blood serum, which indicates the inadequacy of the immune response to intracellular infection, with the tendency to last longer.
4. Radiological pattern in the majority of patients (63%) is characterized as diffused bilateral interstitial and (or) alveolar infiltration. However, for some patients (15%) the x-ray may remain normal in the acute phase of the disease.
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