RU2814910C1 - Method of differential diagnostics of measles with infectious mononucleosis - Google Patents

Abstract

FIELD: medicine; pediatrics; infectious diseases.

SUBSTANCE: invention can be used for the differential diagnosis of measles with infectious mononucleosis. In the differential diagnosis of measles and infectious mononucleosis, anamnestic data is collected from the patient to determine the presence of a dry cough. A visual examination of the organs of vision is carried out to detect signs of scleritis and/or conjunctivitis. In a general clinical blood test, the level of decrease in leukocytes relative to the age-related physiological norm is determined. Each of the identified symptoms is assigned a score indicating either the presence of the symptom — 1 point or its absence — 0 points. The probability of having measles is calculated by solving the logistic regression equation described by the following formula:

where p is the probability of measles, %; e is the base of the natural logarithm, equal to 2.7; K is constant of the logistic regression equation equal to 3.1; a is the presence or absence of a dry cough in the patient; b is the presence or absence of scleritis and/or conjunctivitis in the patient; c is the presence in a general clinical blood test of a patient of a decrease in the level of leukocytes relative to the physiological norm. If the p value is equal to or more than 50%, the patient is diagnosed with measles, and infectious mononucleosis is excluded. If p is less than 50%, the presence of infectious mononucleosis is confirmed, and measles is excluded.

EFFECT: method provides objectification, increasing the accuracy and quality of diagnosing measles in the shortest possible time, accessibility for research during the initial examination by a pediatrician, an infectious disease specialist in clinical practice, ease of execution with high sensitivity and specificity, no material costs, due to the fact that the patient has suspected measles, according to anamnesis, an objective examination, the presence of a dry cough and scleritis and/or conjunctivitis is established; a general clinical blood test determines the level of leukocytes for subsequent calculation of the probability of measles using the logistic regression formula.

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Description

The invention relates to the field of medicine, namely to pediatrics, infectious diseases, and can be used for timely differential diagnosis of measles infection and infectious mononucleosis in clinical diagnostic practice.

Measles infection is an acute, highly contagious anthroponotic viral disease with an airborne transmission mechanism, manifested by general intoxication, fever, maculopapular exanthema, conjunctivitis and severe catarrhal symptoms of the upper respiratory tract [Gorelov A.V., 2020].

Despite the successes of mass vaccine prevention of measles infection, after global progress achieved between 2010 and 2016. the problem of combating this infection currently continues to remain relevant: there has been an increase in the incidence of measles among the population in many regions of the world and in 2019 the number of cases of the disease amounted to 869,770, which is the highest figure since 1996 [WHO, 2019].

Routine vaccination of the population against measles in decreed age groups, carried out in the Russian Federation since 1967, has made it possible to achieve epidemiological well-being: morbidity and mortality have decreased, the age structure of cases and focality have changed. However, the widespread deterioration of the epidemic situation of measles infection in connection with migration processes significantly increases the risk of measles being imported into the territory of our country [State report “On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2020”]. At the same time, not only children, but also adults, mainly those who have not been vaccinated before, are actively involved in the epidemic process [Platonova T.A., Golubkova A.A., Smirnova S.S., 2021]. In connection with migration processes, this circumstance significantly increases the risk of measles infection in older people and increases the number of sources of the infectious agent among this population, which dictates the need to improve the diagnosis of measles in the conditions of its elimination.

The developed standard definition of a clinical case of measles infection (the presence of a dry cough, conjunctivitis and/or scleritis, leukopenia in a general clinical blood test) excludes pathognomonic symptoms that are clearly considered prognostic and justifies the need to use this model for the differential diagnosis of measles and infectious mononucleosis. This pathognomonic sign, characterized by exanthema on the buccal mucosa (Belsky-Filatov-Koplik spots), occurs in 30-40% of cases or may be absent in patients with an atypical course of measles infection [Usenko D.V., 2020]. In the absence of a pathognomonic symptom, difficulties may arise in clinical practice when making differential diagnoses among patients with exanthemal diseases (for example, in patients with infectious mononucleosis). Previously, we developed a standard definition of a clinical case of measles infection, based on a mathematical model that includes pathognomonic symptoms, which limited the use of the proposed model in a number of differential diagnostic cases of measles infection [Semerikov V.V., 2022]. No other analogues of the standard definition of a clinical case of measles infection have been found in the available scientific and medical literature.

Technical result: objectification of the method, increasing the accuracy and quality of differential diagnosis of measles infection and infectious mononucleosis in the shortest possible time, availability for research during the initial examination by a pediatrician, infectious disease specialist in clinical practice, ease of execution with high sensitivity and specificity, no material costs .

This result is achieved by the fact that in a patient with suspected measles infection, according to anamnesis, objective examination, the presence of a dry cough and scleritis and/or conjunctivitis is established, the level of leukocytes is determined in a general clinical blood test, for the subsequent calculation of the probability of measles using the logistic regression formula.

The diagnostic method is carried out as follows: in a patient with suspected measles, anamnestic data is collected to determine the presence of a dry cough, a visual examination of the organs of vision is carried out in order to detect signs of scleritis and/or conjunctivitis, and capillary or venous blood is taken to determine the level of leukocytes with using general clinical analysis.

The developed standard definition of a clinical case of measles takes into account the presence or absence of pathological clinical symptoms or laboratory parameters (dry cough, conjunctivitis and/or scleritis, leukopenia in a general blood test). Each of the determined indicators is assigned a score indicating its presence - 1 point or its absence - 0 points. The combination of priority clinical and laboratory indicators that have the greatest relationship with the diagnostic probability of a patient having measles infection is used when calculating the probability of measles using a logistic regression equation described by the formula:

p=1/1+e ^{-(K+2.2a+2.2b+0.9 c)} *100%, where p is the percentage probability of measles infection, %; e is the base of the natural logarithm, equal to 2.7; K is the constant of the logistic regression equation equal to 3.1; a - the presence or absence of a dry cough in the patient; b - the presence or absence of scleritis and/or conjunctivitis in the patient; c - the presence in a general clinical blood test of a patient of a decrease in the level of leukocytes relative to the physiological norm.

The presence of significantly more frequently observed clinical and laboratory signs is directly related to the diagnostic probability of measles infection in a patient as a percentage. Thus, with a p value equal to or more than 50%, the patient is diagnosed with measles infection and the absence of infectious mononucleosis; with p less than 50%, the presence of infectious mononucleosis is confirmed, and the diagnosis of measles is excluded.

In conditions of elimination of measles infection, the combination in a patient of a dry cough, inflammation of the sclera and/or conjunctiva, the presence of leukopenia in a general clinical blood test allows for the greatest diagnostic efficiency of the presence of measles infection: the Nigelkerk coefficient of determination [Tashakova M.Kh., 2018] reflects 59% of clinical factors in 86%, sensitivity of the method - 89%, specificity 83% at p <0.001.

The obtained result allows us to establish a clinical diagnosis of measles infection (ICD 10 - B05). This diagnostic method was tested during an in-depth clinical and epidemiological examination of patients with clinical signs of measles (n=28); the comparison group consisted of patients with infectious mononucleosis (n=30).

Application examples

Example 1. Patient A., 17 years old, is admitted to the hospital on the sixth day of illness. The disease began gradually: on the first day weakness, general malaise, and decreased appetite were noted; on the second - runny nose, dry cough, lacrimation; on the third - an increase in temperature to 38 degrees, redness of the conjunctiva; on the fifth - a rash on the face and neck; on the sixth day, the symptoms persisted, coughing became more frequent, and a rash appeared on the chest and limbs. The patient is vaccinated against measles twice, providing a certificate of preventive vaccinations. Denies contact with the patient. Upon admission, the condition is of moderate severity, health suffers, lethargic, pale skin, widespread maculopapular exanthema with single petechiae on the body, prone to fusion, injection of scleral vessels, conjunctival hyperemia, purulent discharge from the eyes, copious mucous discharge from the nose, hyperemia of the pharynx , hard breathing over the lungs, frequent dry cough. During a laboratory examination, a general clinical blood test revealed leukopenia (leukocyte level was 2.9*10 ⁹ /l).

The diagnostic probability of measles infection, based on solving the equation of the mathematical model, was 90% (p=90%). The combination of a dry cough, inflammation of the sclera and/or conjunctiva, the presence of leukopenia in a general clinical blood test indicates a high risk of acute measles infection in the patient, which was subsequently confirmed by the detection of specific antibodies to the measles virus class Ig-M (positivity rate 1.8) and Ig -G (positivity rate 9.5).

Example 2. Patient B., 5 years old, is admitted to the hospital on the third day of illness. The disease began acutely: on the first day there was a headache, general weakness, loss of appetite, low-grade fever, catarrhal manifestations in the form of a dry cough and runny nose, mucous discharge from the eyes; on the second day - deterioration of the condition in the form of an increase in temperature to 39 degrees, an increase in symptoms of conjunctivitis, the cough began to be paroxysmal in nature; on the third day - the appearance of a rash on the face and neck. The patient is vaccinated once against the measles virus. Denies contact with infectious patients. Upon admission, the condition is of moderate severity, health suffers, lethargy, pale skin, maculopapular exanthema on the face and neck, copious mucous discharge from the nose, hyperemia of the pharynx, hard breathing over the lungs, frequent paroxysmal dry cough. Laboratory examination revealed a normal leukocyte level (leukocyte level was 6.1*10 ⁹ /l). The diagnostic probability of measles infection using this mathematical model was 79% (p=79%). The combination of a dry cough, inflammation of the sclera and/or conjunctiva indicates a high risk of measles in the patient. During a serological study, specific antibodies to the measles virus Ig-G were detected (positivity rate 6.9), class Ig-M were absent. A dynamic blood test on the 10th day of hospital stay revealed an increase in specific Ig-G antibodies to the measles virus (positivity rate - 14.2), which made it possible to confirm the etiological diagnosis of the disease.

Example 3. Patient K., 7 years old, is admitted to the hospital on the sixth day of illness. The disease began acutely: on the first day, general weakness, loss of appetite, catarrhal manifestations in the form of a runny nose, and nasal congestion were noted; on the second day - temperature rises to 38 degrees, increasing nasal congestion; on the third and fourth days, the febrile temperature persisted; on the fifth, a rash appeared on the face, neck, and chest; on the sixth - the rash spread throughout the body. The patient is vaccinated once against the measles virus. Denies contact with infectious patients. Upon admission - a state of moderate severity, health suffers, lethargic, pale skin, maculopapular exanthema on the face, neck, chest, upper extremities, moderate nasal congestion, hyperemia of the pharynx, enlarged lymph nodes (anterior cervical - up to 2.0 cm, submandibular - up to 2.0 cm, posterior cervical - up to 1.0 cm, axillary - up to 1.0 cm), hard breathing over the lungs, the liver is palpated 2 cm below the costal arch along the right midclavicular line. During the laboratory examination, leukopenia was not noted (the level of leukocytes was 12.1 * 10 ⁹ /l. The diagnostic probability of measles infection, based on solving the equation of the mathematical model, was 4% (p = 4%). The patient did not have diagnostically significant clinical signs included in the model - laboratory signs indicate a low probability of measles infection.

A serological study revealed specific antibodies to the measles virus of the IgG class (positivity rate 5.8), while the IgM class was absent. During a dynamic blood test on the 14th day of the disease, no increase in specific antibodies of the Ig-G class to the measles virus was detected (positivity rate - 5.8), Ig-M was not detected, which finally made it possible to exclude measles infection in the child. Final clinical diagnosis: infectious mononucleosis (EBV, CMV-associated), moderate severity.

Thus, the use of the proposed diagnostic method will make it possible to diagnose measles infection with a high probability in the early stages of the development of the infectious process, start treatment in a timely manner and monitor its effectiveness.

Claims (3)

A method for the differential diagnosis of measles infection with infectious mononucleosis, which consists in the fact that in the differential diagnosis of measles infection and infectious mononucleosis, anamnestic data is collected from the patient to establish the presence of a dry cough, a visual examination of the organs of vision is carried out in order to detect signs of scleritis and/or conjunctivitis, and also, in a general clinical blood test, the level of decrease in leukocytes relative to the age-related physiological norm is determined, each of the identified symptoms is assigned a point indicating the presence of a symptom - 1 point or its absence - 0 points; Next, the probability of having measles infection is calculated by solving the logistic regression equation described by the formula: where p is the probability of measles infection, %; e is the base of the natural logarithm, equal to 2.7; K is the constant of the logistic regression equation equal to 3.1; a - the presence or absence of a dry cough in the patient; b - the presence or absence of scleritis and/or conjunctivitis in the patient; c - the patient’s general clinical blood test shows a decrease in the level of leukocytes relative to the physiological norm; and if the p value is equal to or more than 50%, the patient is diagnosed with measles infection and infectious mononucleosis is excluded; if p is less than 50%, the presence of infectious mononucleosis is confirmed and measles infection is excluded.