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DIAGNOSIS AND TREATMENT OF CHRONIC BRUCELLOSIS
Bukhara State Medical Institute named after Abu Ali Ibn Sina (Bukhara,
Uzbekistan)
Annotation: We followed up 85 patients aged from 17 to 74 years. Standard
general, serological, biochemical and statistical methods were used in all patients.
Patients according to clinical forms were distributed as follows: primary chronic
brucellosis (BCB) - 22 (25,8%) and secondary chronic brucellosis (SCB) - 63
(74,2%). Subcompensation phase was observed in 62,3% of examined patients,
decompensation phase was revealed in 37,7%.
Keywords: Chronic brucellosis, clinic, diagnosis, antioxidant system,
etiopathogenetic treatment
Диагностика и лечение хронического бруцеллеза
Бухарский государственный медицинский институт имени Абу Али
Ибн Сины (Бухара, Узбекистан)
Аннотация: Под наблюдением 85 пациентов в возрасте от 17 до 74
лет. У всех пациентов использовались стандартные общие, серологические,
биохимические и статистические методы. Больные по клиническим формам
распределились следующим образом: первичный хронический бруцеллез (ПХБ) -
22 (25,8%) и вторичный хронический бруцеллез (ВХБ) - 63 (74,2%). Фаза
субкомпенсации наблюдалась у 62,3% обследованных пациентов, фаза
декомпенсации выявлена у 37,7%.
Ключевые слова: хронический бруцеллез, клиника, диагностика,
антиоксидантная система, этиопатогенетическое лечение
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Сурункали бруцеллёз диагностикаси ва даволаш
Абу Али Ибн Сино номидаги Бухоро Давлат тиббиёт институти
(Бухоро, Ўзбекистон)
Аннотация: Назоратимиз остидаги 85 нафар 17-74 ёшгача бўлган
беморни кузатдик. Барча беморларда standart умумий, серологик, биокимёвий
ва статистик усуллар қўлланилган. Клиник шаклларга кўра беморлар
қуйидагича тақсимланди: бирламчи сурункали бруцеллёз (БCБ) - 22 (25,8%) ва
иккиламчи сурункали бруцеллёз (ИСБ) - 63 (74,2%). Субкомпенсация босқичи
кўриб беморларнинг 62,3% кузатилди, декомпенсация босқичи 37,7% нозил
қилинган.
Калит сўзлар: сурункали бруцеллёз, клиникаси, диагностикаси,
антиоксидант тизими, етиопатогенетик даволаш
According to WHO, the annual incidence of brucellosis is 500 million people.
According to M. Avijgan et al., the number of patients with brucellosis is actually 10-
25 times higher than those who were registered with this disease [1]. According to
Academician G.G. Onishchenko, among 100,000 people, the greatest spread of
brucellosis was observed in Nepal, the United Arab Emirates, Jordan, Egypt, and
Turkey [2]. The etymological state of brucellosis in Russia is unstable and the
incidence per 100 thousand of the population is 0.2-0.7 [3]. Among the countries of
the Commonwealth, i.e. in Kyrgyzstan [5], Georgia, Azerbaijan [2], Kazakhstan [4],
Uzbekistan [2], Tajikistan [6] and Turkmenistan, the incidence of brucellosis remains
high, they are among the 25 countries with the highest indicators of the spread of
brucellosis [3]. In Uzbekistan, the incidence of brucellosis per 100 thousand
population is from 1.8 to 2.8 [7; 9].
In chronic active brucellosis (CAB), patients from time to time complain of
fever, trembling, sweating, weakness, shortness of breath, pain in the muscles, joints,
spine, headaches, numbness in the morning, cold on the upper and lower extremities,
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dyspeptic symptoms, weakening cognitive functions [8,10]. According to scientists,
clinical, laboratory and functional examinations are associated with changes and
multifocal fibrosis of organs and tissues of the div, as well as an increase in lymph
nodes, the direct spread of Brucella to all organs and tissues of the div, which will
lead to multiple organ insufficiency [11].
Various infectious factors in the div activate free radical processes. Multiple
organ failure that develops in chronic active brucellosis is largely associated with
increased hemodynamic disorders, lipid peroxidation (LPO). And this requires the
improvement of medical procedures. To date, large-scale measures are being
implemented in our country aimed at providing the population with cheap and high-
quality medicinal and import-substituting drugs produced from local raw materials.
In this direction, it is very important to meet the demand of the population for cheap
pharmaceutical products through the creation of new drugs based on local raw
materials that are not inferior in efficiency to their foreign counterparts.
Purpose:
Evaluation of the effectiveness of the treatment of patients with
chronic active brucellosis with phosphargin succinate.
Research materials and methods used
85 patients aged 17-74 who were treated in the Bukhara Regional Hospital for
Acute Diseases, living in regional endemic areas, were taken as the object of the
study. 64 (75.3%) of them are men and 21 (24.7%) are women. Distribution of
patients by age according to the WHO classification showed that the incidence is
mainly characteristic of young age (78.5%). The average age of the patients was
36.18±1.99 years.
According to the International Classification of Diseases (ICD-10),
brucellosis is included in the "bacterial zoonoses" block and is assigned A23 code
A23.0. Brusella melitensis and A23.1. Brucellosis transmitted by Brusella abortus is
considered [Tenth revision - Geneva, 2003]. When making a diagnosis of chronic
brucellosis used RCHD - Republican Center for Health Development of the Russian
Federation. According to this classification, it was divided into primary chronic
brucellosis (PCHB) and secondary chronic brucellosis. Each patient who came to the
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hospital underwent a clinical examination, an objective examination, and was
diagnosed based on the results of clinical and epidemiological anamnesis and
laboratory tests. Heddelson and Wright agglutination reactions and passive
hemagglutination reaction were used in patients. In patients, we determined the
activity of inflammation in the joints by DAS-28, and the level of general
inflammation in blood serum by the immunoenzyme method of S-reactive protein
(SRB). Private examinations included the amount of malondialdehyde (MDA) in
blood serum by A.I. According to Andreeva's method, catalase activity was
determined by M.Yu. According to Koralik's method and total antioxidant status by
spectrophotometric method was determined. All obtained numbers were statistically
processed.
The obtained results and their analysis
According to clinical forms, patients were divided as follows: primary chronic
brucellosis (PCHB) – 22 and secondary chronic brucellosis (SCHB) – 63. No gender
differences were found in either form.
All of the PCHB group had a disease duration of up to 1 year, while the
majority of SSB patients had a disease duration of 2–3 years (54.1%), up to 1 year
(19.5%), and 4–5 years (1.2%). In 53 (62.3%) patients, the subcompensation stage of
the disease was observed, and in 32 (37.7%) patients, the decompensation stage was
observed.
Patients mainly complained of fever, weakness, headache, loss of appetite,
tremors, sweating and similar manifestations. But their occurrence was different in
primary and secondary chronic brucellosis. In particular, if patients with PCHB are
characterized by weakness, tremors, sweating, fever, headache, sleep disturbances,
loss of appetite, paleness of the skin and hydration, then in SCHB, weakness, fever,
sweating, headache, enlarged lymph nodes are often observed.
It should be noted that musculoskeletal injuries are more characteristic of
SCHB, and the most injuries were observed in the knee joint, while injuries of the
wrist joints were more common in PCHB. According to DAS-28, it was 3.95±0.13
and 4.23±0.12 points in primary and secondary chronic brucellosis, and it was 4.2±0.1
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points in general patients. Their distribution according to the level of activity was as
follows: high activity in PCHB was observed in 9.1% of patients, moderate activity
in 68.2% and low activity in 22.7% of cases. In patients with SCHB, high activity was
observed in 11.1% of patients, moderate activity in 71.4% and low activity in 17.4%
of cases. That is, the activity of joint damage in SCHB was high. At the same time,
gastrointestinal tract lesions were detected in patients, mainly loss of appetite,
covering of the tongue and hepatomegaly. Gastrointestinal damage was observed
more frequently in PCHB.
Damage to the cardiovascular system and respiratory organs was observed in
primary and secondary brucellosis, mainly characterized by muffled heart sounds and
labored breathing. Damage to the nervous system, neuritis, sleep disorders.
In evere forms of brucellosis, damage to the genitals was also observed.
In 62.3% of the patients who participated in the study, the stage of
subcompensation was observed, and in 37.7% - the stage of decompensation was
determined. The decompensation phase was mainly characteristic of PCHB.
In the peripheral blood of most patients, leukopenia, neutropenia,
lymphocytosis, and elevated EChT were found. Heddleson's reaction was positive in
94.7% of patients, Wright's reaction showed high titers.
In order to determine the intensity of inflammatory processes, we determined
the amount of CRP in the blood serum of patients. In the conducted studies, we saw
a sharp increase in its amount from 0.76±0.04 mg/ml to 38.14±2.37 mg/ml (P<0.001).
It was observed that its amount increased to 36.12±2.41 and 39.78±2.19 mg/ml in
PCB and SCB groups. It is worth saying that today attention is being paid to the role
of acute phase proteins in vascular endothelium damage. Among them, CRP is
important, and its amount increases sharply in various inflammatory and necrotic
processes. The synthesis of this protein is accelerated in the liver under the influence
of interleukin 6 and other cytokines. The mechanism of action increases their
functional activity due to binding with T-lymphocytes.
According to the information presented in the literature, if the amount of CRP
is higher than 50 mg/l, it indicates the development of systemic vasculitis. Therefore,
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we tried to gradate the amount of CRP in the blood plasma: moderate - 10-25 mg/l,
average - 26-49 mg/l, and if it is higher than 50 mg/l, we considered it a severe level.
In the studies conducted, high activity in PCB was observed in 9.1% of
patients, while average activity was found in 90.9% of cases. In patients with SCB,
high activity was observed in 11.1% of patients, while moderate activity was found
in 88.1% of cases. That is, there was an activity of the disease in SCB.
We also evaluated the processes of lipid peroxidation in the blood serum of
patients by the content of malondialdehyde. Studies have shown that in patients with
brucellosis, the content of malondialdehyde increases by 1.82 times (P<0.001). If in
primary chronic brucellosis this indicator increased by 1.73 times (P<0.001), then in
secondary chronic brucellosis its increase was 1.87 (P<0.001) times. It should be
noted that in the subcompensation stage of the disease, the content of
malondialdehyde increased by 1.74 (P<0.001) times compared to the normative
indicators, in the decompensation stage- by 2.37 (P<0.001) times. This indicates an
acceleration of free radical processes depending on the stage of the disease.
As we know, the antioxidant defense system plays an important role in
ensuring a critical balance of free oxidation. Currently, when evaluating the serum
antioxidant system, the total antioxidant activity and the activity of the catalase
enzyme are determined. Determination of the total antioxidant activity in the blood
serum of patients with chronic brucellosis showed a decrease in this indicator (see
Table 3). In particular, in primary chronic brucellosis, this indicator decreased by 1.9
(Р<0.001) times, in secondary chronic brucellosis - by 1.46 (Р<0.01) times. The total
antioxidant activity of blood serum decreased by 1.46 (Р<0.01) times in the
subcompensation period of the disease, by 2.08 (Р<0.001) times in the
decompensation period. Detection of catalase activity in blood serum showed a
decrease in this indicator in patients. In particular, in groups of patients with primary
chronic brucellosis and secondary chronic brucellosis, catalase activity decreased by
1.98 (Р<0.001) and 1.85 (Р<0.001) times. In the subcompensation and
decompensation phases, the enzyme activity decreased by 1.41 (Р<0.05) and 1.51
(Р<0.01) times.
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Thus, in chronic brucellosis, there is an acceleration of lipid peroxidation, a
decrease in total antioxidant protection and catalase activity in the blood serum, which
suggests that such changes weaken the compensatory mechanism of the div's
antioxidant system.
Based on the results obtained, we tried to improve the treatment of chronic
brucellosis and used the drug phosphargine succinate, which is produced in our
republic. This drug has antihypoxic and antioxidant properties. The conducted studies
have shown high efficiency in comparison with the traditional treatment used in the
treatment of chronic brucellosis. In particular, traditional medical procedures reduced
the content of malondialdehyde in blood serum by a statistically convincing 1.29
(Р<0.05) times.
But this indicator remained 1.35 (Р<0.05) times higher than in the reference
indicators. In blood serum, the total antioxidant activity and catalase activity were
increased by 1.16 (Р<0.05) and 1.28 (Р<0.05) times, but the control group remained
below 1.45 (Р<0.05) and 1.9 (Р<0.05) times. This activated the compensatory
mechanism of the antioxidant system by 1.5 (Р<0.05) times, but retained values 1.68
(P<0.01) times lower than those of the control group.
Carrying out the proposed therapeutic procedures in the treatment of chronic
brucellosis reduced the content of malondialdehyde in the blood serum by 1.7
(Р<0.01) times (see Table 4). Although it was 1.26 (P <0.05) times lower than in the
group of patients receiving traditional treatment, there was an upward trend compared
to the control group. The total antioxidant activity of blood serum increased by 1.44
(P<0.05) times after treatment in group 2 patients. This indicator was statistically
inconclusively different from the indicators of the 1st and control groups. There was
an increase in catalase activity by 1.63 (P<0.01) times after the proposed treatment.
This is 1.21 (P<0.05) times higher than the indicators of the 1st group, but 1.22
(P<0.05) times lower than the indicators of the control group. Such changes led to an
increase in the compensatory mechanisms of blood serum. Indeed, this indicator
increased by 2.49 (P <0.001) times after the proposed treatment, by 1.36 (P <0.05)
times compared to the indicators of group 1, but remained 1.24 (P<0.05) times lower
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than the reference indicators. Consequently, in the treatment of chronic brucellosis,
traditional and especially recommended methods of treatment increase the activity of
the antioxidant system and slow down the processes of lipid peroxidation.
It should be noted that the treatment of chronic brucellosis statistically
convincingly reduced the level of S-reactive protein. In particular, in patients of group
1, its amount after treatment decreased by 2.79 (P<0.001) times, but remained higher
than in the control group by 17.3 (P<0.001) times, which indicates the preservation
of inflammatory processes in the div of patients. In patients of group 2, 4.75
(P<0.001), maratoba decreased. This indicator turned out to be 1.57 (P<0.01) times
lower than the indicators of the 1st group, but remained 11.02 (P<0.001) times higher
than the standard indicators. This suggests that the foci of inflammation have been
preserved.
Therefore, although the treatment of ChB brucellosis reduces the amount of
acute phase proteins in blood serum, it does not lead to complete normalization. This
indicates that the foci of inflammation are preserved. Compared with conventional
treatment, the proposed treatment regimen more effectively reduced blood serum
CRP levels.
Of course, the positive results noted above also affected the course of the
disease, patients' complaints decreased, and a certain degree of regression of changes
in various systems was observed. In particular, the fever completely disappeared after
traditional treatment, weakness, shivering, and sweating 1.81; 15.36 and 6.03 times
decreased, after the proposed treatment - symptoms such as fever, shivering and
sweating completely disappeared, and weakness was found to decrease by 5.05 times.
Headache, sleep disturbance, skin pallor and skin moisture after conventional
treatment 4.0; 5.02; 3.03 and 9.5 times decreased, insomnia was completely
eliminated after the proposed treatment, headache was 17.2 times, skin paleness and
moisture was found to decrease 30 and 11.11 times. Lymph node enlargement was
reduced from 46.1% to 5.1% with conventional treatment, and from 67.3% to 4.3%
after the proposed treatment.
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The DAS28 index decreased from 4.4±0.1 points to 2.7±0.1 points after
conventional treatment, while it decreased from 4.0±0.1 points to 1.08±0.04 points
after receiving Phospharginine succinate. After conventional treatment, the level of
joint damage according to DAS-28 decreased: no high activity was observed in
patients, moderate activity was detected in 10.2% of patients, low activity and
remission were observed in 46.2 and 43.6% of cases. 4.3% low activity and 95.6% -
transition to remission was observed when phosphargine succinate was added to
conventional treatment. This shows the effectiveness of the proposed treatment.
Polyorgan failure, which develops in chronic brucellosis, leads to
hemodynamic disturbances in many ways, acceleration of PL. This requires
improvement of medical procedures. In order to restore these processes, the use of the
drug Phosphargin succinate, produced in Uzbekistan, increases the capacity of the
antioxidant system compared to traditional treatment, and reduces the peroxide
oxidation of fats, leading to an improvement in the quality of life of patients.
Conclusions
1)
In chronic brucellosis, the amount of acute inflammatory protein
increases sharply.
2)
Inclusion of phosphorgine succinate in the treatment of chronic
brucellosis increases the capacity of the antioxidant system and reduces peroxide
oxidation of fats compared to conventional treatment.
3)
The inclusion of Phosphargine in the treatment of chronic brucellosis
leads to early elimination of clinical symptoms.
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