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Mirzadjanova Dono Bahodirovna, Tashkent Medical Academy, candidate of Medical Science
E-mail: Saodat.us@mail.ru
Abdominal typhoid in Uzbekistan (forty year-long observations)
Abstract: Retrospective and prospective studies on the nature of the causative agent of typhoid, clinical presentation and outcome of the disease in the dynamics of a 40 year follow-up (1970-2010 years).
Clinical analysis of case histories of patients with typhoid held for the periods 1979 - 193 patients, 1997 - 61 patients, 2002 - 102 patients and for the period 2007-2010, 112 patients with typhoid fever. Also analyzed hospital records and the results of follow-up for typhoid carriers: 138 carriers in 1973 -1979 years, 52 — bacillicarriers in 1997-2002, and 70 persons in 2003-2010.
It was found that typhoid in Uzbekistan has undergone significant changes in 40 years, which showed an increase in the proportion of cases among children, n the prevalence of antibiotic-resistant pathogens of typhoid, in this regard — weighting of the clinical course of the disease, increasing the formation of acute and chronic bacterial carriage.
During the formation of the various outcomes of typhoid was the most essential dynamics of indicators such as erythrocyte sedimentation rate, immunoregulatory index, the level of antigen-binding lymphocytes, sensitized regarding the specific antigen S. typhi.
Keywords: typhoid, resistance to antibiotics, bacteria carriage.
Despite general decrease of typhoid morbidity, this rate in the Republic of Uzbekistan amounts to 0.3-0.2 per 100 000 of population per year [4]. As is known, in nowadays typhoid has been undergone substantial changes. This is the development of S. Typhi resistance to the most of commonly used antibiotics (including chloramphenicol) with both chromosome and plasmid strains resistance [1; 5]. Such factors as susceptibility ofpopulation to typhoid, alteration of the disease clinical course, increase of incidence of Salmonella typhi carriage are also of importance [3; 7].
The recent literature cites numerous data on various aspects of typhoid (etiology, epidemiology, diagnosis, pathogenesis, clinical course and etc.), but to date there had been no extended analysis of typhoid at the present stage in comparison with that of 30-40 years ago. Available publications reflect inadequate or not fully illuminate the nature of the clinical changes in typhoid as compared to the current and the manifestation of the disease in the past years. This was the subject of the present study.
Object of the study: to analyse dynamic development of typhoid and its outcomes in Uzbekistan for forty-year period.
Materials, methods and volume of study. We conducted a retrospective and prospective studies on the temper of the causative agent of typhoid, clinical course and outcomes of the disease in dynamics was carried out for forty-year period, taking into account the properties of S. typhi (1970-2010).
Case histories, outpatient's cards of patients with typhoid and convalescents from 1973 up to 2010 were analysed, as well as statistic reports of the Department of State Center of Sanitary and Epidemiological Surveillance for 1970-2010. 193 case histories for 1979, 61 — for 1997, 102 — for 2002 and 112 case histories for 2007-2010 were analysed. Diagnosis of typhoid was based on clinical data, results of bacteriological and/or serological (Vidal reaction, ELISA, etc) examination. Bacteriological examination was carried out by standard methods at bacteriological laboratories at the places of study (Samarkand region, Samarkand city, Kashka-Darya region, Tashkent city) and at microbiological department of Research Institute of epidemiology, microbiology and infectious diseases of the Ministry of Health of the Republic of Uzbekistan.
Detection ofantigen-binding lymphocytes (ABL) to S. typhi antigen was carried out by the method of Garib F. Yu. et al. (1995) [2].
T-lymphocytes and T-subsets for estimation of immunoregulatory index (II) were detected by the method of Novikov D. K. et al. in 2000 [6].
Outpatient's cards and results of dispensary observation of S.typhi carriers were analyzed: 138 individuals in 1973-1979, 52 in 1997-2002 and 70 carriers in 2003-2010.
Statistical analyses were performed using programs "Excel" and R-project.
Results and discussion
The first stage of study was analysis of the temper of the causative agent of typhoid to laevomycetinum (chloramphenicol), especially S. typhi susceptibility. It was established, that at the period 1970-1995 most cases of typhoid were caused by laevomycetinum susceptible strains of causative agent but since the end of the nineties up to the present constant increase of the number of laevomycetinum resistant S.typhi strains was observed (fig. 2).
Development of S.typhi resistance to laevomycetinum followed by more frequency and duration of clinical symptoms of the disease, more frequent complications and forming of acute and chronic carriage of S. typhi.
Significant changes were observed in population by typhoid morbidity. If in the seventies individuals at the age 15-45 dominated (94.8 %) and children amounted to only 3.7 %, at the end of the 20th century children rate became 10 times as high as before: 37.7 % of total number of the patients with typhoid (P < 0.05)
Fig. 1. - Typhoid - intensive rate in Uzbekistan for 40 years ( %)
Fig. 2. - Dynamics of frequencylaevomycetinum susceptible (S) and laevomycetinum resistant (R) S. typhi strains isolated from patients in Uzbekistan for 40 years
Irrespectively of the mode oftransmission (via contaminated water or food) at present typhoid is characterized by a severe course with gradual onset of the disease. So, if typhoid in 1979, out of patients in 15.0 % revealed a mild form of the decease, 57.0 % — medium and only 28.0 % were observed severe course of the disease, the patients with typhoid caused by antibiotic resistant strains S.typhi (61 patients, examined in 1997) mild forms of the decease is not detected, in 62.3 % of cases was recorded moderate form, and in 37.7 % of cases develop severe for typhoid. In 2002, 102 patients with typhoid were examined.
Mild, medium and severe course ofthe disease were observed in 5.9 %, 39.2 % and 54.9 % of the cases respectively; severe course rate was 2 times as high as in 1979 and 1.5 times as high as in 1997.
Comparative analysis of clinical symptoms of typhoid at present, as 40 years ago demonstrated similar picture: domination of intoxication syndrome, dyspepsia, violation of stool, indefinite form fevers, and neurologic symptoms with development of typhoid state depending on the disease severity. It was also found, that frequency of typhoid recurrences didn't depend on properties of the causative
agent, mode of transmission and severity of clinical course, but was connected with adequacy and length of etiotropic therapy and presence of inter-current diseases. Frequency of typhoid recurrences was similar in the groups under study (patients in 1979, 1997 and 2002) and varied from 7.8 % to 11.5 % (P > 0.05).
The next stage of the study was analyzing of frequency of acute and chronic bacteria carriage forming in patients with typhoid.
Until recently bacteria carriage forming was observed in 5-6 % of patients with typhoid of Uzbek population, caused by laevomy-cetinum susceptible strains (fig. 3).
Fig. 3. Frequency of bacteria carriage forming (acute and chronic) in patients of compared groups
Increase of typhoid cases polyresistant to antibiotics follows by 1.5-2 fold increase in cases of acute and chronic bacteria carriage.
Thus a high frequency of acute and chronic bacteria carriage forming is one of the peculiarities of outcome of current typhoid.
It gave occasion to analyze frequency of bacteria carriage forming in patients with laevomycetinum susceptible typhoid in 1973-1979 and in patients with laevomycetinum resistant typhoid in 2007. It was established that acute and chronic bacteria carriage forming in these periods amounted to 17.4 % and 6.5 % and 37.5 % and 9.8 % respectively, so the number of acute bacteria carriage in typhoid cases caused laevomycetinum susceptible strains was significantly higher than in typhoid caused by laevo-mycetinum resistant strains.
Analysis of a number of clinical, immunological and cyto-chemical indices allowed to single out some of them with prognostic value for bacteria carriage forming. There were ESR, II (ratio of CD4/CD8 T-lymphocytes) and amount of antigen-binding lymphocytes, sensitizing to S. typhi antigen. Patients with bacteria carriage forming had higher values of ESR at the period of early convalescence (2 times and more as high as the norm). ESR of the patients with outcome in recovery amounted to 30-40 mm/hour at the height of the disease, at the period of early convalescence ESR decreased to 1.5-2 times as high as the norm and to the moment of discharge from the hospital ESR was within normal range. In patients with bacteria carriage forming a high level of ESP (20-25 mm/hour) persisted after temperature normalization.
An expressed immunosuppression was observed at the early stage of the disease in patients with bacteria carriage forming and helper response prevailed at the period of convalescence. It manifested in dynamics of II: in cyclic course of AT with outcome in
convalescence at the initial stage II gradually increased, achieving maximal value (1.8-2.0), at the stage of symptoms relief it decreased to 1.2-1.3 at the period of convalescence II increased to 1.4, approaching the normal value.
In the group of patients with acute and chronic bacteria carriage forming II increased at the initial of the disease, and it sharply decreased to 1.2-1.3 at the height of the disease with subsequent enhancement at the stage of symptoms relief and remained increased at the late stage of convalescence.
The next stage of our study was analysis of changes in content of antigen-binding lymphocytes (ABL), sensitizing to S.typhi antigen. In patients with bacteria carriage forming increase of ABL amount was insignificant, but at the stage of late convalescence a considerable increase of this index was observed, unlike the patients with disease outcome in convalescence characterizing by decrease of this index at the stage of late convalescence (it exceeds values in control group insignificantly).
Conclusion
Thus typhoid in Uzbekistan has undergone substantial changes for last 40 years: enlargement of children proportion in the morbidity structure, more severe course of the disease, domination of antibiotic resistant strains, increase of cases of acute and chronic bacteria carriage.
In the process of forming typhoid outcomes (convalescence or S.typhi carriage) dynamics of the following indices is of great importance: ESR, II, level of antigen-binding lymphocytes, specifically sensitizing to S. typhoid antigen. At present abdominal typhoid is characterized by significant distinctions from the course of the disease 40 years ago and it requires a serious revise of tactics of patient's management.
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Mirrahimova Nargiza Mirzahidovna, Research Institute of Epidemiology, Microbiology and Infectious Diseases Ministry of Health of the Republic of Uzbekistan, Tashkent
E-mail: Saodat.us@mail.ru
Akhmedova Khalida Yuldashevna, Research Institute of Epidemiology, Microbiology and Infectious Diseases, doctor of medical sciences
Abdushukurov Abdurashid Abdurahimovich, Research Institute of Epidemiology, Microbiology and Infectious Diseases, candidate of Medical Science
Antigen-binding lymphocytes for diagnosis organopathology in brucellosis
Abstract: The essential diagnostic method for determining the value of lymphocyte antigen to tissue antigens is its high sensitivity and specificity: ASL content reaches diagnostic levels in the early stages and creates the possibility of preventive treatment of organ damage in brucellosis.
Keywords: brucellosis, antigenbinding lymphocytes, tissue antigens, organopathology.
Brucellosis — a contagious, anthroponotic disease characterized by severe, often chronic course, the possibility of the propagation of the epidemic spread and classified as particularly dangerous infections. The diagnosis of brucellosis is set in the presence of clinical manifestations, epidemiological assumptions, confirmed by laboratory studies [3; 7; 8; 11].
Brucellas are characterized by a high capacity for invasion and intracellular parasitism. When the destruction of their, its released endotoxin. Brucella penetrates through the skin or mucous membranes and lymphatic enter the lymph nodes, where they can be stored for a long time and lead to a restructuring of the body's immune. In most cases, the immune response does not provide sanitation of the organism from the pathogen. Brucella long remain in metastatic lesions from which the re-repeated dissemination of the pathogen in the body with the development of reactive changes and chronic allergic process. It is possible resorption of inflammatory formations or formations persistent irreversible scarring of the affected organs and tissues. The main pathogenetic changes during brucellosis reduced to a non-specific inflammatory and degenerative processes in organs and tissues, hyperergic reaction, cirrhotic changes in organs and tissues [3; 7; 11].
The causative agent of brucellosis, having a high infectivity, causes changes in almost all organs and tissues. First of all, it is the nervous, lymphatic, cardiovascular system and connective tissue [1; 2; 9; 10; 12; 13; 14].
Pathological changes in the brucellosis are found in many organs. In the acute stage in parenchymatous organs found serous inflammation with the subsequent development of degenerative processes. It is develop infectious-reactive reticuloendotheliosis, panangiitis. The defeat ofvessels is the morphological substrate organopathology
when brucellosis. In the lymph nodes, liver and other parenchymal organs observed hyperplasia of reticular cells [2; 3; 10].
In the sub-acute stage of the disease are detected productive inflammatory processes, combined with degenerative processes and changes in infectious-allergic. In chronic brucellosis is prevail proliferative and inflammatory changes of granulomatous character with the formation of granulomas. In the thick connective tissue accumulates a significant amount of serous fluid, there is a loosening and destruction of the fibrous substance. Inflammation completed development of sclerotic tissue. The allergic nature of the systemic nature of the inflammation causes morphopathoge-netic changes.
However, it should be noted that clinically significant signs of organ damage are rare. At the same time, it is necessary to take into account the possibility of "masking" of clinical symptoms other manifestations of disease, typical for brucellosis as neurological and bone and joint pain [1].
The overwhelming number of patients (up to 80 %) increased liver and spleen. In the acute phase may develop specific focal pneumonia, bronchitis sometimes brucellosis.
The defeat of the urinary organs manifests moderate albuminuria, microscopic haematuria, the advent of single cylinders, renal epithelial cells. Rarely develop glomerulonephritis, sometimes with nephrotic component.
In subacute form of brucellosis (suspended after 3 months from the beginning of the disease) in addition to the symptoms of intoxication detected focal lesions in the form of arthritis, neuritis, plexitis and ets.
Conventionally, after 6 months from the onset of the disease is considered chronic brucellosis. For chronic brucellosis is
