RU2247373C2 - Method for express-diagnosis and differential diagnosis of urogenital infection - Google Patents

Abstract

FIELD: medicine, laboratory diagnosis.

SUBSTANCE: method involves determination of the patient blood content of globulin-alpha 1, globulin-beta, globulin-gamma and the total bilirubin content followed by calculation of diagnosis indices for the patient (Y₁, Y₂, Y₃) by using the computer program "Statistica 1.5" and introducing values X₁, X₂, X₃ and X₄ in computer wherein X₁ means globulin-alpha 1 value; X₂ means globulin-beta value; X₃ means globulin-gamma value; X₄ means total bilirubin value. Obtained values of diagnosis indices for the individual patient (Y₁, Y₂, Y₃) are compared with average values of diagnosis indices (Y₁', Y₂', Y₃') for different urogenital infections followed by comparison by sign and value. By the maximal coincidence of diagnosis index values for the individual patient with average diagnosis index values urogenital disease is diagnosed and the following diagnosis index average values are used: for chlamydiosis: Y₁' = -2; Y₂' = -0.1; Y₃' = -0.2; for mycoplasmosis: Y₁' = 2; Y₂' = 0.8; Y₃' = -0.04; for ureaplasmosis: Y₁' = 2; Y₂' = -1; Y₃' = 0.02; for health persons: Y₁' = -2; Y₂' = 0.1; Y₃' = 0.2. Invention provides the development of a method for express-diagnosis of infection at initial stage and diagnosis of atypical forms that occur in these diseases, and differential diagnosis of chlamydiosis, mycoplasmosis and ureaplasmosis. Invention can be used for carrying out the differential diagnosis of chlamydiosis, mycoplasmosis and ureaplasmosis.

EFFECT: improved method for express-diagnosis.

2 tbl, 4 ex

Description

The present invention relates to medicine, namely to laboratory diagnostics, and can be used for rapid diagnosis and differential diagnosis of chlamydia, mycoplasmosis and ureaplasmosis.

The widespread prevalence of chlamydia, mycoplasmosis and ureaplasmosis among the population, their role in the etiopathogenesis of a number of obstetric and perinatal diseases require a more detailed study of this problem [3]. Screening for chlamydial and urea-mycoplasma infection with subsequent rehabilitation is one of the reserves to reduce the incidence [1]. The effectiveness of existing diagnostic methods is not the same depending on the clinical form of infection [5]. Often these diseases are hidden under the guise of various therapeutic pathologies and remain undiagnosed, so there is a need for new, more advanced methods for diagnosing these infections.

In the literature, we have not come across methods for the rapid diagnosis of chlamydia, mycoplasmosis and ureaplasmosis by biochemical blood parameters [2].

The traditional, most acceptable methods for diagnosing these diseases are as follows: PCR (polymerase chain reaction), ELISA (enzyme-linked immunosorbent assay), PIF (direct immunofluorescence reaction), bacteriological culture [4].

PCR is based on the detection of genetic material that is specific to each type of microorganism. ELISA is based on the antigen-antibody reaction; antibodies to the pathogen are detected by determining the optical density. The mutual fund is also based on the antigen-antibody reaction; the diagnosticum is an antibody to the components of the pathogen cells labeled with fluorescein. Bacteriological culture on liquid diagnostic media is based on the ability of the medium to change color during the growth of a microorganism due to the manifestation of its enzymatic activity.

Since the ELISA method has one common feature with the proposed invention (blood test), this method can be considered the closest in technical essence.

All these methods have, along with the advantages, also very significant disadvantages. As a rule, they detect diseases in an active or advanced stage, when patients are already difficult to treat [6]. In addition, ELISA, PIF and PCR can give false positive results, and bacteriological culture, on the contrary, does not always reveal an existing infection.

Therefore, the objective of the invention is to develop a method for the rapid diagnosis of infection in its initial stage and the diagnosis of atypical forms that are often found in these diseases, as well as the differential diagnosis of chlamydia, mycoplasmosis, ureaplasmosis.

The task in the method of rapid diagnosis and differential diagnosis of urogenital infections is achieved by the fact that in the blood of the subject determine the value of globulin alpha 1, globulin beta, gamma globulin and total bilirubin, then determine the values of the diagnostic indicators for this subject (Y ₁ , Y ₂ , Y ₃ ) using the computer program “Statistica 1.5” by entering the values into the computer

X ₁ , X ₂ , X ₃ and X ₄ ,

where X ₁ - the value of globulin alpha 1;

X ₂ - the value of globulin beta;

X ₃ - the value of gamma globulin;

X ₄ - the value of total bilirubin;

the obtained values of the diagnostic indicators for this particular patient (Y ₁ , Y ₂ , Y ₃ ) are compared with the average values of the diagnostic indicators (Y ₁ ', Y ₂ ', Y ₃ ') for various urogenital infections, and a comparison is made in sign and magnitude , and by the greatest coincidence of the values of the diagnostic indicators for this subject with the average values of the diagnostic indicators for one of the urogenital diseases, this urogenital disease is diagnosed and the following average diagnostic values are used sticks:

for chlamydia: Y ₁ '= -2, Y ₂ ' = -0.1, Y ₃ '= -0.2;

for mycoplasmosis: Y ₁ '= 2, Y ₂ ' = 0.8, Y ₃ '= -0.04;

for ureaplasmosis: Y ₁ '= 2, Y ₂ ' = -1, Y ₃ '= 0.02;

for healthy: Y ₁ '= -2, Y ₂ ' = 0.1, Y ₃ '= 0.2.

The proposed method was developed by the authors by mathematical processing using the method of multivariate analysis of variance using the computer program “Statistica 1.5” of a large sample of biochemical blood parameters of healthy and sick urogenital infections: chlamydia, mycoplasmosis and ureaplasmosis.

In total, 34 biochemical blood indices were initially studied, but it was found that only four blood indices have informative value for diagnosis and differential diagnosis: globulins alpha 1, globulins beta, gamma globulins and total bilirubin. For each of these four indicators, the coefficients of multivariate analysis of variance were determined using three well-known data processing models by this method using the Statistica 1.5 computer program.

After processing a large sample of indicators of globulins and total bilirubin in patients with urogenital infections, quantitative values of the coefficients of multivariate analysis of variance were obtained, and since processing was carried out using three well-known models of multivariate analysis of variance, for each model, its own value of the coefficients was obtained. Table 1 below shows the coefficient values obtained after data processing. The values of the coefficients were initially calculated to the sixth digit, but then, for the convenience of calculations, the values were rounded. Rounded values are shown in table 1 in parentheses.

Table 1
Standard coefficients of discriminant analysis for the experimental sample Indicators Processing Model 1 Processing Model 2 Processing Model 3 Globulins alpha 1 (B ₁ ) -0.96465 (-1) 1,010827 (1) -0.099244 (-0.1) Globulins beta (B ₂ ) -0.585963 (-0.6) -0.168051 (-0.2) 0.653879 (0.7) Globulins gamma (B ₃ ) -0.581679 (-0.6) -0.066410 (-0.1) 0.030187 (0.03) Bilirubin total (B ₄ ) -0.340574 (-0.3) -0.076411 (-0.1) -0.895842 (-0.9)

Further, taking into account the obtained values of the coefficients of multivariate analysis of variance of Table 1, when computer processing the results of blood tests of a large sample of healthy individuals, as well as patients with chlamydia, myoplasmosis and ureaplasmosis, the average values of the diagnostic indicators (Y ₁ ', Y ₂ ', Y ₃ ') were obtained for each group of subjects (healthy, chlamydia, mycoplasmosis, ureaplasmosis), which are shown below in table 2, moreover, as well as in table 1, the exact values of the indicators are shown first, and then, in parentheses, rounded (tables a 2)

table 2
The average values of diagnostic indicators (Y ₁ ', Y ₂ ', Y ₃ ') for various diseases Patient group Y ₁ ' Y ₂ ' Y ₃ ' Control group (healthy) -1.78066 (-2) 0.11802 (0.1) 0.239081 (0.2) Chlamydia patients -2.21248 (-2) -0.11696 (-0.1) -0.215267 (-0.2) Mycoplasmosis patients 2.16336 (2) 0.84794 (0.8) -0.041503 (-0.04) Patients with ureaplasmosis 2,21792 (2) -1.02909 (-1) 0.021441 (0.02)

We checked the accuracy of the system and, using the Bonferroni correction, narrowed the range of biochemical studies necessary for this.

Further, using the coefficients developed by us (table 1) and four biochemical blood parameters, using the standard discriminant analysis (program "Statistica 1.5"), rapid diagnostics and differential diagnosis of the above diseases can be carried out. For this, the coefficients (table 1) and specific biochemical parameters are entered into the computer, and the values obtained after processing are compared with the average values presented in table 2.

1. For rapid diagnosis and differential diagnosis of diseases of chlamydia, mycoplasmosis and ureaplasmosis, as well as healthy patients, it is enough to use the values of four biochemical parameters of blood composition (presented in table 1).

2. The developed system ensures the theoretical accuracy of the correct diagnosis of at least 0.913 at a 1% confidence level. The actual diagnostic accuracy was 0.975.

The proposed method is as follows. The subject takes blood from a vein for analysis. In the blood, the value of globulin alpha 1 (X ₁ ), globulin beta (X ₂ ), gamma globulin (X ₃ ) and total bilirubin (X ₄ ) are determined. Then determine the values of the diagnostic indicators (Y ₁ , Y ₂ , Y ₃ ) for this particular patient using the computer program “Statistica 1.5” (USA).

Then, the obtained values of the diagnostic indicators for this particular patient (Y ₁ , Y ₂ , Y ₃ ) are compared with the average values of the diagnostic indicators (Y ₁ ', Y ₂ ', Y ₃ ') for healthy individuals and patients with various urogenital infections, and use the following average values of indicators:

for chlamydia: Y ₁ '= -2, Y ₂ ' = -0.1, Y ₃ '= -0.2;

for mycoplasmosis: Y ₁ '= 2, Y ₂ ' = 0.8, Y ₃ '= -0.04;

for ureaplasmosis: Y ₁ '= 2, Y ₂ ' = -1, Y ₃ '= 0.02;

for healthy: Y ₁ '= -2, Y ₂ ' = 0.1, Y ₃ '= 0.2.

Comparison of indicators Y ₁ , Y ₂ , Y ₃ with the average indicators Y ₁ ', Y ₂ ', Y ₃ 'is carried out in sign and magnitude. In this case, as a rule, in comparison with Y ₁ with Y ₁ 'the possibility of two conditions is assumed and then one of them is excluded after comparing Y ₂ with Y ₂ ' and Y ₃ with Y ₃ '(in this sequence, differential diagnostics are performed).

Examples of specific performance are given in the form of extracts from medical records.

Example 1

Patient M., 26 years old, extract from card No. 1. I went to the general practitioner with complaints of joint pain. During the examination, the content of total bilirubin was 8.6 μmol / L, the percentage of globulins alpha was 1-2%, beta - 10.9%, gamma - 18.2%.

To determine the values of diagnostic indicators for this particular patient (ie, Y ₁ , Y ₂ , Y ₃ ), the computer program Statistica 1.5 was used;

As a result, the following values were obtained:

Y ₁ = -3 (exactly: -3.05447)

Y ₂ = -2 (exactly: -2.12643)

Y ₃ = -0.2 (exactly: -0.22242)

Next, we compared the values of Y ₁ with Y ₁ ', Y ₂ with Y ₂ ' and Y ₃ with Y ₃ 'using the data of table 2 of this application for each possible state.

As a result of comparing the obtained data with the average values from table 2, we assigned this patient to the group of patients with chlamydia. So, according to the comparison of Y ₁ with Y ₁ ', this patient can be assigned to the control group or chlamydia (coincidence in the “-” sign), and according to the comparison of Y ₂ with Y ₂ ' and Y ₃ with Y ₃ 'she cannot belong to the control group (has a negative value), and in healthy ones, both Y ₂ 'and Y ₃ ' are positive (i.e., mismatch in sign). Further, the results of our study were confirmed by PCR, SIF and ELISA.

Example 2

Patient K., 27 years old, extract from card No. 8. I went to the doctor for the purpose of preventive examination. In the study of blood biochemical parameters, the following values were obtained: the content of total bilirubin 20.4 μmol / L, globulins alpha 1-2.7%, beta 12.9% and gamma 17.0%. After processing the data to determine Y ₁ , Y ₂ , Y _{3 the} following results were obtained:

Analysis results Y ₁ Y ₂ Y ₃ Patient 2 2.19004 (2) -1.03276 (-1) 0.05153 (0.05)

As a result of comparing the obtained data with the average values from table 2, we predicted ureaplasmosis in the patient. Since, according to the comparison of Y ₁ with Y ₁ ', we can exclude belonging to the control group and chlamydia (since in the control group and with chlamydia Y ₁ ' are negative), and according to the comparison of Y ₂ with Y ₂ 'and Y ₃ with Y ₃ 'cannot be attributed to mycoplasmosis (since with mycoplasmosis, Y ₃ ' is negative, and Y ₂ 'is positive, i.e., mismatch in sign). The results of our study were confirmed by ELISA, UIF and bacteriological culture.

Example 3

Patient F., 33 years old, extract from card No. 4. I went to the doctor with complaints of allergic reactions. Along with other analyzes, a biochemical blood test was performed. As a result of the study, the following values of blood biochemical parameters were obtained: the content of total bilirubin is 20 μmol / L, alpha globulins are 1-7.5%, beta 15.2%, gamma 9.0%. After processing the data using our system, the following results were obtained:

Analysis results Y ₁ Y ₂ Y ₃ Patient 3 2,03285 (2) 1,68617 (1,7) -0.16208 (-0.2)

As a result of comparing the obtained data with the average values from table 2, we diagnosed mycoplasmosis in the patient. Since, according to a comparison of Y ₁ with Y ₁ ', this patient can be classified as mycoplasmosis or ureaplasmosis, and according to a comparison of Y ₂ with Y ₂ ' and Y ₃ with Y ₃ ', we excluded ureaplasmosis. This result is confirmed by PCR, PIF and bacteriological culture.

Example 4

Patient A., 32 years old, extract from card No. 5. During the examination, the content of total bilirubin was 17.0 μmol / L, the percentage of globulins alpha was 1-2.4%, beta 8.9%, gamma 15.6%. After processing the data using our system, the following results were obtained:

Analysis results Y ₁ Y ₂ Y ₃ Patient 4 -1.31743 (-1.3) 0.57285 (0.8) 1.97344 (2)

As a result of comparing the obtained data with the average values from table 2, we diagnosed that patient 4 belongs to the group of practically healthy individuals. Since, according to the comparison of Y ₁ with Y ₁ ', this patient can be assigned to the control group or chlamydia, and according to the comparison of Y ₂ with Y ₂ ' and Y ₃ with Y ₃ 'he cannot be assigned to chlamydia.

40 patients with chlamydia, 40 patients with mycoplasmosis, 40 patients with ureaplasmosis and 40 healthy individuals were examined.

The accuracy of the diagnosis coincidence was: 0.975 at the 1% confidence level.

Sources of information:

1. Adaskevich V.P. Sexually transmitted diseases. - 2nd ed., Rev. and add. - Vitebsk: Publishing House of the Vitebsk Medical Institute, 1997. - 310 p.

2. Komarov F.I., Korovkin B.F., Menshikov V.V. Biochemical studies in the clinic. - Elista: APP Dzhangar, 1998 .-- 250 p.

3. Malinina E.V. Comparative evaluation of various methods of diagnosis and treatment of urogenital chlamydia in women of reproductive age: Author. dis. Cand. honey. sciences. - Moscow, 1997 .-- 22 p.

4. Medical laboratory technology and diagnostics: a Handbook. Medical laboratory technology. / Ed. prof. A.I. Karpishchenko. - St. Petersburg: Intermedika, 1999 .-- 656 p.

5. Nazarenko G.I., Kishkun A.A. Clinical evaluation of laboratory results. - M.: Medicine, 2000 .-- 544 p.

6. Plahotnaya G.A., Ilyina I.N. Mycoplasma and chlamydial infection of the urogenital tract. / Diagnostic and treatment issues // Clinical Pharmacology and Therapy. - 1996. - No. 4. - S. 34 - 39.

Claims (1)

A method for rapid diagnosis and differential diagnosis of urogenital infections, including a blood test, characterized in that in the blood of the subject determine the value of globulin alpha 1, globulin beta, gamma globulin and total bilirubin, then determine the values of the diagnostic indicators for this subject (Y ₁ , Y ₂ , Y ₃ ) using the computer program “Statistica 1.5”, entering into the computer the values X ₁ , X ₂ , X ₃ and X ₄ , where X ₁ - the value of globulin alpha 1; X _{2 is the} value of globulin beta; X ₃ - the value of gamma globulin; X ₄ - the value of total bilirubin; the obtained values of the diagnostic indicators for this particular patient (Y ₁ , Y ₂ , Y ₃ ) are compared with the average values of the diagnostic indicators (Y ₁ ', Y ₂ ', Y ₃ ') for various urogenital infections, and a comparison is made in sign and magnitude , and by the greatest coincidence of the values of the diagnostic indicators for this subject with the average values of the diagnostic indicators for one of the urogenital diseases, this urogenital disease is diagnosed and the following average diagnostic values are used sticks: for chlamydia: Y ₁ '= -2, Y ₂ ' = -0.1, Y ₃ '= -0.2; for mycoplasmosis: Y ₁ '= 2, Y ₂ ' = 0.8, Y ₃ '= -0.04; for ureaplasmosis: Y ₁ '= 2, Y ₂ ' = -1, Y ₃ '= 0.02; for healthy: Y ₁ '= -2, Y ₂ ' = 0.1, Y ₃ '= 0.2.