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14The efficiency of surgical treatment of the patients with the destructive forms of a pulmonary tuberculosis in combination with chlamydia's and mycoplasma's
infections.
Eugeny A. Danilov (euqeny.dan@rambler.ru ), Alexander M. Kozhemyakin, Sergey D. Yamkovoy.
Central Scientific Research Tuberculosis Institute of Russian Academy of Medical
Sciences, Moscow.
The growth of tuberculosis morbidity rate in the world was marked since 1992 year [1] and more often development of extensive progressing forms of this disease [10,13,14,16,17]. The presence of concomitant non-specific infection of respiratory tract appears to be one of the factors, contributing to progressing course of tuberculosis [4]. Last years the role of Chlamydias and Mycoplasmas increased as the reason of pneumonias and bronchitises [12]. All of them belong to the group of intracellular parasites and are able to generalisation in the organism [2,3,11,18]. The researches which have been carried out during last years, have revealed high rates of infecting of tuberculous patients with Chlamydias and Mycoplasmas - from 43,8 % [15] up to 61,4 % [9]. The research of interaction between pulmonary tuberculosis and Chlamydia's and Mycoplasma's infections (CMI) became one of new directions in scientific researches, however, at present time there are not so many works concerned this problem.
130 cases in Surgical Department of Central Tuberculosis Scientific Research Institute of Russian Academy of Medical Sciences (Moscow) during the period 1998-2003 have been analysed for the goal to estimate the prevalence of CMI among patients with destructive forms of pulmonary tuberculosis and to value their influence on the course of tuberculosis process and results of surgical treatment. The patients had the following clinical forms of a pulmonary tuberculosis: tuberculoma in a phase of destruction - 13 (10 %), infiltrative tuberculosis in a phase of destruction - 10 (7,7 %), fibrous-cavernous tuberculosis within the lobe of lung -15 (11,5 %), fibrous-cavernous tuberculosis more than one lobe of lung - 55 (42,3 %), caseous pneumonia - 10 (7,7 %), tuberculous empyema complicated with bronchial fistula - 27 (of 20,8 %). All patients were examined for pulmonary tuberculosis using traditional methods and, moreover, examined for Chlamydia's and Mycoplasma's infections on admission, before the operation and after the operation. Mycobacterium tuberculosis (MBT) were found out in the sputum of 103 (79,2 %) patients using luminescent microscopy and cultural methods, and at 32 (24,6 %) patients MBT quantity was high (MBT > 100 in a field of vision). Nonspecific microflora was found out in the sputum of 78 (60 %) patients using cultural methods. Streptococcus a-haemolyticus, Streptococcus pneumoniae, Streptococcus ß-haemolyticus and Branchamella catarrhalis were detected in most cases. Taking into account, that CMI are able to generalisation in organism
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[2,3,11,18], material from respiratory tract and, simultaneously, from urogenital tract was examined for CMI at all patients For this purpose, specimens of mucous membrane of bronchuses (brush-biopsy material after bronchoscopy) and specimens of mucous membrane of urethra (in men) and cervix of the uterus (in women) were examined for CMI using a direct immunofluorescence method.
At 65 (50 %) patients CMI were determined in brush-biopsy specimens of bronchuses. At 72 (55,4 %) patients CMI were determined in specimens of urogenital tract. Two kinds of Chlamydias - Chlamydophila pneumoniae and Chlamydia trachomatis, and two kinds of Mycoplasmas - Mycoplasma pneumoniae and Mycoplasma hominis were founded. The coincidence of CMI species in respiratory and urogenital tracts was observed at 87 (67%) patients, at 8(6%) patients CMI species were different in respiratory and urogenital tracts, at 35 (27%) patients CMI have not been founded neither in respiratory, nor in urogenital tracts ( the coefficient of association Q=0,535 (Chlamydia), 0,41 (Mycoplasma), the connection is significant [7]), that confirms CMI generalisation in organism of examined patients. Thus, among 130 examined patients Chlamydias were founded in organism of 31 (23,8 %), Mycoplasma of 37 (28,5 %) and their association of 27 (20,7 %) patients, CMI not found at 35 (27 %). The general CMI rate was 73 % (95 patients).
Table 1. The clinical forms of pulmonary tuberculosis and CMI presence (patient's quantity and percentage in each group *)._
Forms of tuberculosis Chlamydias and Mycoplasmas
not founded founded
Infiltrative 9 (25,7%) 1(1,1%)
Caseous pneumoniae 10 (10,5%)
Tuberculoma 11 (31,5%) 2 (2,1%)
Fibrous-cavernous tuberculosis within the lobe 9 (25,7%) 6 (6,3%)
of lung
Fibrous-cavernous tuberculosis more than one 4 (11,4%) 51 (53,7%)
lobe of lung
Tuberculous empyema complicated with bronchial fistula 2(5,7%) 25 (26,3%)
TOTAL 35 (100%) 95 (100%)
* - difference is significant, p < 0,002
As follows from the table 1, limited forms of destructive tuberculosis -tuberculoma, infiltrative and fibrous-cavernous tuberculosis within the lobe of lung were significantly prevailed among noninfected patients, extensive forms - fibrous-cavernous tuberculosis (uni- and bilateral), tuberculous empyema with bronchial fistula were significantly prevailed among infected patients. Patients with caseous pneumonia were all infected.
Preoperational treatment was performed for all 130 patients, including antituberculous therapy with 4-5 drugs in accordance with MBT strains sensitivities and antibacterial therapy in accordance with sensitivities of non-specific microflora strains. Patients with tuberculous empyema were undergone drainage and open
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treatment of pleural cavity. The treatment of concomitant Chlamydia's and Mycoplasma's infections was a new component of preoperational preparation plan. Apparatus «СТЕЛЛА 1» was used for treatment CMI as alternative method. «СТЕЛЛА 1» - device for phon resonant radiation (PRR) therapy [5,6] with short wave frequency (license of the Ministry of Health of Russia reg. № 42/99-14371532 from 08.11.99г.), that generates holographic spectral analogues [5,6] of antibiotics: azitromicin, claritromicin and lomefloxacin without adverse effects. The course of treatment is 3-4 weeks. 55 patients from 95 infected have passed full course of PRR therapy using «СТЕЛЛА 1». Therefore, three patient's groups were formed: 1 group (experimental) - 40 (30,8 %) CMI infected patients, but haven't passed PRR therapy ; 2 group (experimental) - 55 (42,3 %) CMI infected patients, have passed PRR therapy; 3 group (control) - 35 (26,9 %) patients without CMI. After finishing PRR therapy the full elimination of CMI from organism observed in 2 group, that was confirmed by control immunofluorescence tests. In 1 group CMI agents have remained. The efficiency of preoperational preparation have been estimated on the base of changes of results of control clinical-laboratory and X-ray investigations. Signs of effective preoperational preparation were: positive changes (decrease of intoxication, disappearance of MBT in sputum, diminishing of caverns in quantity and in their sizes, resolution of inflammation in lung, liquidation of a bronchial fistula and resorbtion of necrosis in empyema's cavity) and, also, stabilisation of tuberculous process. Sign of noneffective preoperational preparation was progressing of tuberculosis. The best results of preoperational preparation were developed in 2 and 3 groups - 89,1 % (49 patients) and 94,3 % (33 patients), accordingly. The lowest result was in 1 group - 47,5 % (19 patients). Positive changes in the course of tuberculous process at 40 patients were so significant, so that patients have not been operated. Rest 90 patients (from 130) were operated.
Table 2. Operations in each group (number of the patients).
Operations 1 group 2 group 3 group ALL
Segmental resection -- 2 11 13
Lobectomy -- -- 3 3
Pneumonectomy 22 21 4 47
Thoracoplastic 9 10 2 21
Transsternal transpericardial occlusion of main bronchus 4 2 -- 6
Not operated 5 20 15 40
TOTAL 40 55 35 130
The operations, which have been carried out in three groups of patients, are shown in the table 2. In the nearest postoperational period the pleuropulmonary complications occurred at a part of patients. It were: bronchus stump suture failure and reactivation of purulent inflammatory process in pleural cavity.
Table 3. Results of operations in all groups (patient's quantity and percentage in each group *).
Results 1 group 2 group 3 group
Postoperative complications 23 (65,7%) 9 (25,7%) 2 (10%)
Without complications 12 (34,3%) 26 (74,3%) 18 (90%)
TOTAL 35(100%) 35(100%) 20(100%)
* - difference is significant, p < 0,002.
From the table 3 follows, that in 1 group the postoperational complications occurred much more often, than in 2 group. The frequency of complications in 3 group also was low. The lethal outcomes have not been observed.
Fragments of resected lungs, pleura's and intrathoracic lymphatic nodes of 90 operated patients were used for morphological research. A material was examined with the help of a light and luminescent microscopy. In 1 group the signs of significant progression of tuberculosis process was observed both in the area of main destruction and in a distance from it. The forming tuberculous granulomas had small quantity of epithelioid cells, prevalence of huge cells of foreign bodies, macrophages and lymphocytes, containing inclusions in cytoplasm, similar to elementary bodies of Chlamydias and Mycoplasmas [8]. The inclusions had different optical density. The high dense inclusions looked like dark - violet grains at colouring on Romanovsky-Gimza. The cells with such type of inclusions had positive direct immunofluorescence reaction for Chlamydias. The cells with low dense (optical empty) inclusions had positive direct immunofluorescence reaction for Mycoplasmas. The small quantity of Langhans cells surrounded the central zone of destruction area. The similar picture was observed in granulation stratum of cavities, in pleura's walls. Both in the zones around cavities and in distance the signs of nontuberculous inflammation were observed. There were albuminous exudation in alveoluses, great amount of faded alveolocytes of II type and alveolar macrophages with inclusions in cytoplasm and having positive direct immunofluorescence reaction for CMI. Widespread vasculites with changes in all stratums of vessel's wall were observed in lung and pleura. The affection of bronchus wall in the form of caseous endo- and panbronchitis was observed, including zone of bronchus cutting during the operation. The thickening of capsule was observed in intrathoracic lymphatic nodes, and proliferation of reticular cells with inclusions in cytoplasm, similar to elementary bodies of Chlamydias and Mycoplasmas [8].
We have not observed such morphological reactions in 2 and 3 groups. The granulomas had typical epithelioid cell structure. The vasculites remained only in a zone of active resorbtion of infiltrate, and the inflammatory changes in bronchuses were not caseous-destructive, but had productive epithelioid cell character. Cytoplasmatic inclusions were not observed in all cells. Intrathoracic lymphatic nodes were without changes. Direct immunofluorescence reactions for CMI with tissue samples were negative.
Conclusions:
1) The combination of the destructive forms of pulmonary tuberculosis with Chlamydia and Mycoplasma infections now reaches 73 %.
2) In combination with CMI tuberculous process has tendency to progressing with development of the hard extensive forms of disease.
3) The passing of PRR therapy course for CMI elimination in patients with destructive forms of pulmonary tuberculosis contributes to raise efficiency of complex preoperational preparation up to 89,1 % and to decrease the rate of postoperational complications.
4) Morphological features of tuberculous inflammation in combination with CMI are: prevalence of exudation-necrotic reactions over productive; presence of generalised productive vasculites; significant affection of main bronchuses as caseous endo- or panbronchitis.
The inference: In conditions of high rate of CMI infecting at patients with destructive forms of a pulmonary tuberculosis, the detection of that infections is necessary to be included in preoperational examination plan. If concomitant CMI is detected, PRR therapy is necessary to be included in complex preoperational preparation as alternative method of treatment for elimination CMI from organism and to raise the efficiency of surgical treatment. Literature list:
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