Method for prediction of developing mixed tick-borne encephalitis and borreliosis infection

FIELD: medicine.

SUBSTANCE: there are involved recording clinical and laboratory manifestations of a CNS injury during the first days of the disease that is followed by the calculation of total diagnostic coefficients related to the detected graduation levels of pathognomonic signs of the disease. Total (+)7 points and more is related to predicting the developing mixed tick-borne encephalitis and borreliosis infection. Total (-)8 points and less shows the developing potential monoinfection of tick-borne encephalitis. If deriving the intermediate values of total diagnostic coefficients when none of said limits is reached, the prognosis is uncertain.

EFFECT: using the method for stating basic tendencies of the developing pathological process at the early stages of the developing disease.

1 tbl, 2 ex

 

The invention relates to medicine, namely to neurology.

Currently there is no way to predict the development of mixed encephalitis-borreliose infection in a patient in the first days of the disease. Known methods of diagnosing mixed encephalitis-borreliose infection: detection of specific antibodies against KE and KB by ELISA in the serum and cerebrospinal fluid of the patient, identification of pathogens by PCR, identification of the clinical picture of illness pathognomonic manifestations, characteristic for each of the infections.

Also known is a method for predicting severity of tick-borne infectious diseases, [EN 2376938 C1 (Kemerovo state medical Academy), 10.06.2008]. The method is based on registration of clinical and laboratory manifestations of CNS involvement in the first days of the disease with subsequent calculation of the amount of diagnostic ratios corresponding to the detected patient values gradations most pathognomonic signs of the disease. The forecast is carried out by comparing the sum of the coefficients of this patient with known average probability risk of developing severe disease. The forecast accuracy is about 90%.

In our opinion, the application of the above method for predicting severity of tick in ektsionnyh disease has the following disadvantages:

1) the Inability to make an exact clinical diagnosis;

2) the Necessity of special diagnostic methods (ELISA);

3) Lack of information content in relation to the dynamics of the patient and the occurrence of specific clinical manifestations;

4) Lack of information content in terms of further pathogenetic treatment (the need for antibiotic therapy).

The purpose of the invention: development of a method for predicting the development of mixed tick-borne encephalitis-borreliose infection, to avoid the above drawbacks.

We propose a new method for predicting the development of mixed tick-borne encephalitis-borreliose infection using diagnostic ratios, which allows it to achieve its goals.

The result provided by the invention, consists in the following: the use of the method of calculating the amount of diagnostic ratios allows to trace the main trends of the pathological process, stretch principle to objectify the assessment of patients in the dynamics of the disease, to identify among patients with tick-borne infectious diseases group of individuals likely to develop mixed encephalitis-borreliose infection, holistic therapy started at the Noi stage of the disease.

Analysis of 418 cases of tick-borne encephalitis (febrile form 180 cases, meningeal form 152 cases, focal form 86 cases), 120 cases Ixodes tick-borne borreliosis (febrile form 53 cases, meningeal form 49 cases, focal form 18 cases), 103 cases of mixed encephalitis-borreliose infection (febrile form 46 cases, meningeal form 33 cases, focal form 24 cases), 136 cases unverified tick-borne infection (febrile form 92 cases, meningeal form 36 cases, focal form 8 cases).

One-factor and two-factor variance analysis were subjected to the following characteristics: gender of patient, age, date of illness, duration of hospitalization, duration of the incubation period of the disease, duration of febrile period of the first, second and third waves of the disease; duration of detection of meningeal syndrome, focal neurological symptoms; epileptic syndrome, peripheral and Central paresis; the presence of lesions of the cranial nerves, breathing disorders; the duration of erythema migrans, the presence of akzente, arthralgia; indicators of the General analysis of blood, urine and cerebrospinal fluid. The timing of the research - the first look no further than the days of the acute period of the disease when odnawialna for, the first days of each exacerbation when multiwave the course of the disease. The confidence level (p<0,05) was achieved on the following parameters: duration of fever the first wave of the disease, duration of meningeal syndrome, the presence of lesions of the cranial nerves, in the General analysis of blood - the amount of hemoglobin and the percentage of monocytes; urinalysis - protein; CSF analysis - the percentage of neutrophils and lymphocytes.

Thus revealed signs of tick-borne infections with differential diagnostic value, were subjected to further statistical processing according to the method of sequential analysis. Selected two groups of patients: group 1 - 53 persons with serologically verified monoinfection tick-borne encephalitis, in group 2 - 41 patients with serologically confirmed mixed encefalite-borreliose infection.

According to the results of sequential analysis revealed levels of vibration (gradation) of the values selected earlier signs of tick-borne infections with determination of significance (informative signs, up to 0.5, attests to their accuracy).

Selected in this way signs used for prediction of the possible development of mixed-tick CNS-infections in the acute period of the disease (is the first four days of illness).

The specificity of the method of prediction is defined as the percentage ratio of the number of coincidences clinical and serologically confirmed diagnoses among patients screened for suspected mixed tick CNS infection. The average is 73,2±8,11%.

To test the accuracy of the forecast of development of mixed tick-borne encephalitis-borreliose infection data were 58 patients with tick-borne CNS, installed: correct diagnoses - 47 (81,03%); incorrect - 5 (8,62%); uncertain - 6 (10,34%). Thus, the accuracy of the forecast of development of mixed encefalite-borreliose infection is quite high.

By results of the carried out researches the table of the diagnostic values of the coefficients assigned to the gradations of the most informative features of the disease.

A method for predicting severity of tick-borne infectious diseases using the proposed diagnostic table of the coefficients is as follows. Find diagnostic coefficients corresponding detected in a patient to treat the symptoms of the disease, summarize the factors to obtain the totals. Sum (+)7 points or more corresponds to the forecast of development of mixed tick-borne encephalitis-borreliose infection. Amount (-)8 points or less indicates the possibility of time the development of monoinfection tick-borne encephalitis. In the case of obtaining intermediate values of the diagnostic factors, when none of the specified threshold is not reached, the prognosis of the disease is determined in repeat surveys.

Possible errors in forecasting: false pre-diagnostics monoinfection tick-borne encephalitis is 15%; the false prediction of the mixed tick-borne infections occur in 20% of cases of application of the diagnostic table.

Example 1. Patient P. (history No. G), diagnosis at admission: tick-borne encephalitis, febrile form. On the first day of a disease marked by high fever up to 39°C, weakness, headache, nausea. On the background of treatment with antipyretics, immunoglobulin from the third day of the disease the body temperature normalized. The period of apyrexia was 6 days, the patient's condition was satisfactory. On the tenth day of the disease had developed a high fever of 39.2°C, had anticipated headache, nausea, joined photophobia. Neurological examination was determined moderately expressed meningeal symptoms, symptoms of Central and peripheral nervous system were observed. In General, the analysis of a blood (the third day of illness) hemoglobin was 120 g/l; monocytes was 4%. In the General analysis of urine (the third day of illness) traces of protein. In CSF (eleventh day of illness)- the percentage of neutrophils was 20%; lymphocyte - 80%. The results of immunological studies confirming the mixed encefalite-borreliose infection in a patient P., obtained at the twenty-second day of the disease: antibodies to TBE virus M class was absent, immunoglobulin G was - 1:1600; index lime - 2,36.

Using the table, we summarize the diagnostic factors prognostic signs on the fourth day of the disease and get the following indicators: duration of fever the first wave of two days (+)1 point; duration meningeal syndrome on the tenth day of the disease - one day - 0 points; the defeat of the cranial nerves is missing - 0 points; hemoglobin 120 - (+)1 point; blood monocytes - 4% - 0 points; in the urine traces of protein - (+)2 points; on the eleventh day of the disease in CSF neutrophil - 20% - (+)1 point, lymphocytes - to 80% (+) 2 points. Finally, on the eleventh day of the disease the sum of the coefficients amounted to (+)7 points.

Thus, the threshold (+)7 points pre-mixed diagnosis of tick-borne infection in a patient with P. was reached on the second day of the second wave of the disease, ten days before the completion of immunological diagnostics.

Example 2. Patient S. (history No. G), diagnosis at admission: tick-borne fever. In the first and second days of the disease was noted fever 38,8°C, headache, myalgia. Was admitted to the hospital on the third day over the no. Increased headache, body temperature increased up to 39.3°C. On the fourth day of the disease in the General analysis of blood hemoglobin was 151 g/l; monocytes was 14%. In the General analysis of urine protein no. In CSF - neutrophils - 3%, lymphocytes - 97%.

The summation of diagnostic factors on the fourth day of the disease: fever lasts the first wave of the unknown (still suffering from a fever) - not evaluated; the duration of meningeal symptoms is unknown - not evaluated; the defeat of the cranial nerves is missing - 0 points; hemoglobin 151 g/l - 0 points, monocytes - 14% - (-)2 points; CSF: neutrophil - 3% - (-)4 points, lymphocytes 97% - (-)2 points. Total - (-)8 points.

Thus, on the fourth day of illness, a decision was made about the likely patients of monoinfection tick-borne encephalitis, which was confirmed later: on the twentieth day of the disease after completion of serological studies.

Thus, on the basis of the proposed method of diagnostic ratios in the early acute period of tick-borne infectious diseases can predict the development of mixed encephalitis-borreliose infection.

The advantages of the proposed method for predicting the development of mixed encephalitis-borreliose infection:

1) identify the main trends in the development of the pathological process;

2) allow yet to establish the diagnosis in the early stages of the disease;

3) allows in the acute period of the disease to determine the need for antibiotic therapy;

4) easy to perform and does not require difficult and economically costly technological processes, which is of advantage for the wide implementation of public health practice.

Thus, the application of the proposed method in the first days of the disease to predict the development of mixed tick-borne encephalitis-borreliose infection with an accuracy of up to 81%.

Sources of information

1. Subbotin A.V., Semenov V.A., Atenco D.A., Zinchuk SF a Method for predicting severity of tick-borne infectious diseases. EN 2376938 C1. Kemerovo state medical Academy. - 2008.

2. Gubler E.V. Computational methods of analysis and recognition of pathological processes / Gevgeli. - L.: Medicine, 1978. - 294 S.

3. Deconinck H.E. the clinical differentiation of tick-borne encephalitis and Lyme borreliosis / Appearance, Kgomotso // Modern problems of epidemiology, diagnosis and prevention of tick-borne encephalitis. - Irkutsk. - 1990. - S.112-113.

4. Korenberg EI the Study and prevention of extincti transmitted by ixodid ticks / Eijkelenborg // Bulletin of the Russian Academy of medical Sciences. - 2001. No. 11. - P.41-45.

5. Korenberg EI Tick-borne borreliosis / Eijkelenborg // Natural focality of diseases: Research Institute of the Gamaleya RAMP, M: "Brown", 2003. - S-122.

6. Sadykov TT Differenziale diagnostic criteria of tick-borne encephalitis and tick-borne borreliosis / Thetradeshow, Toshinaga. Atidegah // Tick-borne borreliosis: proceedings of the scientific.-practical use. Conf., Izhevsk. - 2002. - S-259.

Diagnostic table for the prediction of the development of mixed tick-borne encephalitis-borreliose infection

The signs of the diseaseThe gradation characteristicDiagnostic factor
Duration of fever first wave1-2 days+1
3-6 days0
7-14 days-1
15-25 days-1
26 days or more-3
The duration of meningeal syndromeNo0
1-24 days0
25 days+1
Lesion of cranial nerves No0
There+2
Hemoglobin (g/l)1100
111-120+1
121-1300
131-150-1
151-1600
more than 161+1
The percentage of monocytes in the blood1%-2
2%-3%-1
4%-6%0
7%-9%+1
10%-12%0
13% or more-2
ProteinuriaNo0
There+2
The percentage of neutrophils in CSFPlacito is missing -1
1%-3%-4
4%-10%-1
11%-20%+1
21%-30%-1
31%-40%0
41% or more+2
The percentage of lymphocytes in CSFPlacitas no-1
6%-20%0
21%-40%+1
41%-60%+3
61%-80%+2
81%-90%0
91% or more-2

A method for predicting the development of mixed tick-borne encephalitis-borreliose infection, including evaluation of cumulative results of clinical and laboratory research in disease onset, characterized in that calculate the amount of diagnostic ratios assigned to the most pathognomonic signs of disease: littelest fever first wave, the duration of meningeal syndrome, lesions of the cranial nerves, blood haemoglobin, percentage of blood monocytes, proteinuria, the percentage of neutrophils in the cerebrospinal fluid (CSF), the percentage of lymphocytes in the CSF, and diagnostic factors is determined as follows: diagnostic factor is equal to (+)1 if the duration of the fever of the first wave 1-2 days, with a duration of 3-6 days equal to 0, the duration of 7-14 days is equal to (-)1, the length 15-25 days is equal to (-)1, with a duration of 26 days or more (-)3; diagnostic factor equal to 0 when the absence of meningeal syndrome, the duration of the meningeal syndrome 1-24 day 0, with a duration of 25 days or more (+)1; diagnostic factor equal to 0 in the absence of lesions of the cranial nerves, in the presence of lesion of cranial nerves coefficient is equal to (+)2; diagnostic factor equal to 0 when the content of hemoglobin less than 110 g/l, when the content 111-120 g/l is equal to (+)1, when the content 121-130 g/l equal to 0, when the content 131-150 g/l is equal to
(-)1, when the content 151-160 g/l 0 when the contents of 161 g/l and more equal (+)1; diagnostic factor is equal to (-)2 when the percentage of blood monocytes 1, with a ratio of 2-3 is equal to (-)1, with a ratio of 4-6 0 when the ratio is equal 7-9 (+)1, with a ratio of 10-12 0 when aspect] is to 13 and more equal (-)2; diagnostic factor equal to 0 in the absence of proteinuria, the presence of proteinuria is (+)2; diagnostic factor is equal to (-)1 in the absence of neutrophilic pleocytosis in the CSF, diagnostic factor is equal to (-)4 when the percentage of neutrophils in the CSF of 1-3%, when the content of 4-10% (- ) 1, when the content of 11-20% (+) 1, when the content 21-30% equal (-)1, when the content 31-40% 0 when the content of 41% or more equal (+)2; diagnostic factor equal (-)1 in the absence of lymphocytic pleocytosis in the CSF, diagnostic factor equal to 0 when the percentage of lymphocytes in the CSF 6-20%, when the content 21-40% equal (+)1, when the content of 61-80% equal (+)2, when the content 81-90% 0 when the content of 91% or more is equal to (-)2; and the sum (+)7 points or more predict the development of mixed tick-borne encephalitis-borreliose infection (-)8 points or less - the development of monoinfection tick-borne encephalitis, in the case of obtaining intermediate values these diagnostic ratios, when none of the thresholds are not reached, the prognosis is uncertain.



 

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