RU2540912C1 - Method for prediction of neurosyphilis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: diagnostic puncture is preceded by measuring blood antitreponemal titres in flocculation tests; if the titres are not less than 1:32, a high probability of neurosyphilis is stated; if the titres are less than 1:32, blood treponema-specific titres are determined in haemagglutination test, and if the values are not less than 1:40960, a high probability of neurosyphilis is also stated.

EFFECT: method is accessible and simple, and enables achieving the result in a relatively short time.

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Description

The invention relates to medicine, specifically to venereology.

The main role in the diagnosis of neurosyphilis is played by a laboratory study of cerebrospinal fluid obtained by performing lumbar puncture. Clinical indications for performing lumbar puncture in patients with syphilis are very wide. Since lumbar puncture requires special conditions for its implementation, and the complications associated with its implementation are not excluded, criteria are needed that provide an opportunity to further substantiate the need for a patient to perform a puncture due to the high likelihood of neurosyphilis.

There are methods based on laboratory tests of peripheral blood.

The method proposed by de Silva Y et al. (De Silva Y, Walzman M, Shahmanesh M. The value of serum TPHA titers in selecting patients for lumbar puncture. Genitourin Med. 1991; 67: 37-40), is lumbar puncture is recommended for those patients with syphilis who have treponema-specific antibody titers> 1: 2560 in the hemagglutination reaction (Treponema Pallidum Haemagglutination Assay) in the blood. The disadvantage of this method is that treponemal-specific antibody titers> 1: 2560 are detected not only in patients with neurosyphilis, but also in a significant number of patients with an unconfirmed diagnosis of neurosyphilis.

Also known is a forecasting method based on the study of titre of non-treponemal antibodies in the blood in flocculation tests and stating a high probability of damage with titers of at least 1:32 (Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M, Stoner BP , Augenbraun M, Barker DE, Corbett JJ, Zajackowski M, Raines C, Nerad J, Kee R, Barnett SH. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis. 2004; 189 (3) : 369-376.). The disadvantage of this method is that neurosyphilis is also detected in a significant number of patients with titers of less than 1:32, especially in patients with advanced forms of syphilis, as well as in patients with a history of specific therapy failures.

Closest to the claimed is a method for predicting neurosyphilis (patent RU No. 2449286, IPC G01N 33/53, publ. 04/27/2012, priority from 04/15/2011). The essence of the method is as follows: when studying titers of nontreponemal antibodies in the blood in flocculation tests before performing a diagnostic puncture, in addition to stating a high probability of neurosyphilis with titers of at least 1:32, in addition, when detecting titers of nontreponemal antibodies below 1:32, the concentration of total M class immunoglobulins is determined peripheral blood. And at its level below 1.0 g / l, a high probability of neurosyphilis is also diagnosed.

The disadvantage of this method is the fact that although the determination of the concentration of total class M immunoglobulins in the blood is an easily reproducible method, it is not widely available for venereological institutions, since it is not included in the list of methods specified in the medical and economic standards for the provision of medical care for patients with syphilis and its introduction into the diagnostic process is a problem.

The objective of the invention is to develop an affordable method for assessing the likelihood of detecting neurosyphilis while maintaining its sensitivity.

The technical result that will be achieved from the use of the invention is to reduce the complexity, time and cost.

The technical result is achieved by the fact that in the method for predicting neurosyphilis by examining titers of nontreponemal antibodies in the blood in flocculation tests before performing a diagnostic puncture, and if titers of not less than 1:32 are detected, a high probability of neurosyphilis is detected, and if titers lower than 1:32 are detected determination of an additional criterion, as an additional criterion, titers of treponemal-specific antibodies in the blood are determined in the hemagglutination reaction, and with their values not less than 1: 40960, the probability neurosyphilis is also rated as high.

The essence of the invention is to identify neurosyphilis in an additional group of patients with syphilis in a more affordable, simple and cost-effective way.

The definition of an additional criterion - “titre of treponemal-specific antibodies in the blood in the hemagglutination reaction” provides an increase in the sensitivity of the method for assessing the likelihood of detecting neurosyphilis in a more accessible, simple and cost-effective way for practical public health.

The value of the criterion “titers of treponemal-specific antibodies in the blood in the hemagglutination reaction” of not less than 1: 40960 was obtained experimentally. It was found that the likelihood of neurosyphilis is 15.4 times higher in patients with syphilis with treponema-specific antibodies in the blood in a hemagglutination reaction> 1: 40960 compared with patients with titers <1: 40960. The revealed pattern is biologically plausible, since the immune response to syphilitic infection of the central nervous system is accompanied by the synthesis of not only non-treponemal, but also treponemuspecific antibodies, and the immune response to protein antigens is stronger and more obligate.

From an analysis of the scientific, technical and patent literature, the definition as an additional criterion for titre of treponempecific antibodies in the blood in the hemagglutination reaction, which leads to a significant increase in the likelihood of detecting neurosyphilis in a greater number of syphilis patients with an affordable and economical method due to the reduction of labor, time and cost, was not revealed by us, which allows us to conclude that the proposed solutions meet the criteria of "novelty" and "inventive step".

The invention is as follows.

Syphilis patients according to the standard method of one of the flocculation tests with cardiolipin antigen conduct titers of non-treponemal antibodies in the blood (Chereshnev V.A. et al. Syphilis. Immunity and laboratory diagnostics / Chereshnev V.A., Patrusheva NB, Beikin Ya.B., Medvedskaya D.R., Marchenko N.V. // Yekaterinburg, 2006, 387 p.).

With nontreponemal antibody titers below 1:32, additional blood titers of treponemal-specific antibodies in the blood are determined in the hemagglutination reaction, and with values of at least 1: 40960, the likelihood of neurosyphilis is also assessed as high.

Case Studies

Example 1. Patient N-va, 51 years old, medical history (IB) No. 1789, 3 years ago - specific treatment for early latent syphilis. Non-treponemal tests with blood serum are positive in a titer of 1: 8, a titre of treponemal-specific antibodies in the blood in a hemagglutination reaction (RGA) of 1: 80920. An examination of cerebrospinal fluid revealed laboratory signs of neurosyphilis: positive tests with cardiolipin antigen.

Example 2. Patient L., 49 years old, IB No. 1125, had not previously been treated for syphilis. Non-treponemal tests with blood serum are positive in the titer of 1:16, the titer of treponemal-specific antibodies in the blood in the RGA is 1: 327680. The cerebrospinal fluid test data meet the criteria allowing the diagnosis of neurosyphilis: cytosis of 21 cells / μl, positive tests with cardiolipin antigen.

Example 3. Patient M, 49 years old, medical history No. 1674, had not previously been treated for syphilis. Non-treponemal tests with blood serum are positive in a titer of 1: 8, the titer of treponemal-specific antibodies in the blood in the RGA is 1: 163840. In the study of cerebrospinal fluid, laboratory signs of neurosyphilis were detected: cytosis of 43 cells / μl, positive tests with cardiolipin antigen. Diagnosed with asymptomatic neurosyphilis.

The inventive method and, in parallel with it, the method of the prototype was examined 111 syphilis patients with clinical indications for lumbar puncture. High serum titre of non-treponemal antibodies (> 1:32) were detected in 18 people, treponemal-specific antibody titers in the blood in RGA> 1: 40960 in 28 people, IgM levels below 1.0 g / l in 23 people. After a diagnostic puncture, a diagnosis of neurosyphilis was established in 41 patients. Among them, 26 patients had nontreponemal antibodies in the titer> 1:32 and / or IgM level lower than 1.0 g / l, and 29 patients had nontreponemal antibodies in the titer> 1:32 and / or treponemal-specific antibody titers in the blood in the RGA> 1: 40960.

Using the criterion of “titre of non-treponemal antibodies> 1:32” in combination with the criterion of “IgM level below 1.0 g / l” (prototype) allowed us to predict neurosyphilis in 63.4% of patients, and in combination with the criterion of “titer of RGA> 1: 40960 "(the claimed method) - in 70.7% of patients. However, with approximately equal sensitivity, the proposed method is significantly more affordable and simple, allows to achieve a result in much shorter terms, and is more economical (see table).

Table Comparative evaluation of the prototype and the proposed method Prototype The proposed method Availability Available for dermatovenereological institutions level 5 Available for dermatological institutions 3, 4 and 5 levels Labor input High Low Determination of the concentration of total IgM by the method of radial immunodiffusion in a gel according to Mancini Semiquantitative determination of antibodies to Treponema pallidum by passive hemagglutination method 1. Preparation of buffer solution 1. Breeding control samples 2. Preparation of monospecific serum solution 2. Titration of test samples of blood serum of patients 3. Preparation of agar gel in buffer solution 3. The introduction of sensitized red blood cells into the wells of the tablet 4. Filling glass plates with agar gel 4. Incubation 45 minutes 5. The formation of holes in the hardened agar gel 5. Profitability analysis 6. Preparation of standard M class immunoglobulin solutions 7. Dilution of test samples of blood serum of patients 8. The introduction into the wells of standard solutions of immunoglobulin M and test samples 9. Incubation of the plates in a wet chamber for at least 24 hours
10. Profitability analysis The average analysis time until the result 25 hours 60 minutes Expenses, % one hundred 60 The probability of neurosyphilis,% 63,4 70.7

Claims (1)

A method for predicting neurosyphilis by studying titers of nontreponemal antibodies in the blood in flocculation tests before performing a diagnostic puncture, and when titers of at least 1:32 are detected, a high probability of neurosyphilis is found, and if titers lower than 1:32 are detected, an additional criterion is determined, characterized in that that, as an additional criterion, titers of treponone-specific antibodies in the blood are determined in the hemagglutination reaction, and with their values not less than 1: 40960, the likelihood of neurosyphilis is also estimated nyvayut as high.