Whooping cough formulation of the diagnosis. On approval of the standard of specialized medical care for children with moderate whooping cough. Typical forms of whooping cough

Stage 1: catarrhal stage
- Typically the duration is 1 to 2 weeks.
- Symptoms are consistent with an upper respiratory tract infection and may include rhinorrhea, sneezing, low-grade fever, and a mild and occasional cough.
Stage 2: paroxysmal
- The typical duration is 1 to 6 weeks, but may last up to 10 weeks.
- The cough gradually becomes more severe. Cough bursts increase in frequency during the first 1-2 weeks, remain constant for the next 2-3 weeks, and then gradually decrease in frequency.
- Patients may have a history of post-cough vomiting and inspiratory cough.
- The symptoms are very characteristic of the disease and most diagnoses are made at this stage.
Stage 3: recovery
- Recovery stage.
- The cough becomes less paroxysmal and usually disappears within 2 to 3 weeks.
- Paroxysms may recur with subsequent respiratory infections for many months after the initial infection.

Diagnostics

Inspiratory cough is a characteristic symptom of whooping cough in children, but may not be present in infants, adolescents and adults. A culture of the bacterium Bordetella pertussis from nasal secretions can confirm the diagnosis, especially in the early stages of the disease, but a negative culture does not exclude the diagnosis. Other diagnostic tests include PCR and serology.

History and clinical examination

The main risk factors include age under 6 months; a child born to a mother who became infected at or after 34 weeks of pregnancy; lack or incomplete immunization; or close contact with an infected person, especially an infected sibling.

Certain occupations, such as school teaching and health care work, may also increase the likelihood of disease transmission. Although the symptoms and severity of whooping cough can vary, the disease is usually characterized by a paroxysmal cough with inspiratory suffocation (although the latter may be absent in infants, adolescents, and adults). Because whooping cough appears similar to the common cold in its early stages, it is often unsuspected and undiagnosed until more severe symptoms appear. In the early stages of the disease (1 to 2 weeks after infection), the patient may have a history of rhinorrhea, sneezing, absent or low-grade fever, and cough.

Patients at a later stage of the disease (3 to 10 weeks after infection) may report progressive cough severity, with paroxysmal cough initially increasing in frequency and then remaining unchanged for several weeks and then gradually decreasing. Coughing attacks may result in vomiting.

On examination, the patient may be febrile or afebrile, may exhibit a characteristic cough, and may have inspiratory stridor on auscultation. Some infants may be atypical and initially have periods of apnea with minimal coughing or other respiratory symptoms.

Diagnosis can usually be made from the medical history. There are different criteria for defining clinical cases (suspected and confirmed) and laboratory confirmation among different countries and health care institutions. The following table provides case definitions for the UK, for the US, and from the World Health Organization (WHO).

Laboratory research

Although culture is the recommended test to confirm diagnosis, polymerase chain reaction (PCR) tests have become increasingly used for diagnosis over the past decade and are recommended as an adjunct to culture. Serology is also available, although it is not often used. It should be noted that a negative culture does not exclude the diagnosis of whooping cough, especially if the culture is taken later in the course of the disease. Recommendations for laboratory evaluation vary between the US and UK, as described in the table below.

B. pertussis is a sophisticated organism, and its isolation in culture is easily obscured by the growth of other microorganisms found in the nasopharynx. Optimal sampling and processing of the sample, including the use of polyethylene terephthalate or calcium alginate swabs rather than cotton or rayon swabs, and slow insertion of the swab through the nostril into the posterior pharyngeal area, may improve the rate of recovery.

Ideally, the tampon should be left in the back of the throat for 30 seconds before being removed. The smear or aspirate should be directly inoculated onto selective media and, if this is not possible, should be placed on transport media. If a CBC is ordered as a general test, a white blood cell count can confirm the leukocytosis and lymphocytosis that are common in whooping cough. High white blood cell/lymphocyte counts are poor prognostic factors in infants and may help inform decisions about intensive care.

Diagnostic tests

Study	Result
Culture of nasopharyngeal aspirate or swab swab from the posterior wall of the nasopharynx The definitive diagnostic test with 100% specificity. However, a negative culture does not exclude whooping cough. Sensitivity is 30% to 60% if culture is collected 2 weeks after the onset of symptoms. Sensitivity is reduced if the culture is collected 3 weeks after the onset of cough. It is recommended to choose a calcium alginate or polyethylene terephthalate swab rather than a cotton swab or rayon swab, as the latter contains fatty acids that are toxic to B. pertussis. The tampon should be inserted slowly through the nostril towards the back of the throat. Ideally, the tampon should be left in the back of the throat for 30 seconds before being removed. The smear or aspirate should be directly inoculated onto selective media and, if this is not possible, should be placed on transport media. Obtaining a positive culture result may be influenced by: how the sample is processed; disease stage at the time of sample collection; use of antimicrobial therapy before culture (treatment with appropriate antibiotics reduces the likelihood of a positive culture); immunity from past infection or vaccination; and the age of the patient (elderly patients are less likely to experience positive results than young children).	May be positive for whooping cough B
PCR of nasopharyngeal aspirate PCR testing has increased sensitivity compared to culture and is recommended as an adjunct to culture. PCR should be performed on nasopharyngeal samples collected 0–3 weeks after the onset of cough. Aspirates are preferred if PCR is to be performed on a sample. Sensitivity 94% and specificity 97%. A positive PCR result in a person without a cough is not a sign of illness. A polyethylene terephthalate smear is preferred; A calcium alginate smear is not used.
Serological study In general, serological tests are useful for diagnosis in later stages of the disease, usually within 2-8 weeks after the onset of cough. However, serology can be performed on a sample collected up to 12 weeks after the onset of cough. Serology is also recommended for individuals who have not been immunized against whooping cough. There is currently no serological test for pertussis available from the US Food and Drug Administration (FDA). Currently available serological tests measure antibodies that may result from either infection or vaccination. A positive serologic response must be interpreted because the person may have had either recent or recent exposure to whooping cough and may have recently been vaccinated. Because vaccination can induce antibodies (ie, IgM, IgA, and IgG antibodies), serological tests cannot distinguish infection from vaccine response. Serological test results should not influence the confirmation of pertussis infection.	Positive or negative
Detailed blood test It is performed primarily to evaluate other etiologies of cough. An elevated white blood cell count may indicate severe whooping cough in infants. High white blood cell/lymphocyte counts are poor prognostic factors in infants and may help inform decisions about intensive care.	Increased white blood cell count

Differential diagnosis

Disease	Differential signs/symptoms	Differential examinations
(IVDP)	Absence of convulsive cough in children. Symptoms may be similar to those of whooping cough in infants, adolescents, and adults.
Community-acquired	Fever, history of productive cough, history of respiratory disease (eg, asthma). Signs of pneumonia on auscultation.	Culture: A negative culture is consistent with URTI but does not exclude whooping cough. A positive result confirms whooping cough. Sputum culture may reveal a bacterial pathogen. X-rays of the GP may indicate the presence of infiltrates in primary CAP or if the patient develops pneumonia as a complication of whooping cough. X-ray of the GP is normal in uncomplicated whooping cough.
Respiratory syncytial virus (RSV) infection	Age extremes (infants and older adults), history of infant prematurity, runny nose, conjunctivitis, sinus/ear involvement, wheezing, shortness of breath, use of accessory muscles of respiration. History of community outbreak	Culture: A negative culture is consistent with RSV but does not exclude pertussis. A positive result confirms whooping cough. Diagnosis of RSV infection can be made by virus isolation, detection of viral antigens, detection of viral RNA, demonstration of elevated serum antibodies, or a combination of these approaches. Most clinical laboratories use antigen tests to diagnose infection.

Treatment

Antibiotic therapy for pertussis and judicious use of antimicrobials for post-exposure prophylaxis will eliminate Bordetella pertussis from the nasopharynx of infected individuals (symptomatic or asymptomatic). However, few data support the impact of antibiotics on the course of the disease.

Antibiotics prescribed after a paroxysm may have no clinical effect. First-line treatment for suspected or confirmed cases is a course of a macrolide antibiotic (eg, azithromycin, clarithromycin, erythromycin). Trimethoprim/sulfamethoxazole (TMP/SMX) is used for patients with macrolide allergy or resistance unless contraindicated. Recommendations for treatment and prevention are the same.

Treatment for older children<1 месяц

Clarithromycin or azithromycin is the preferred treatment for this age group. In the United States, azithromycin is the macrolide of choice in infants aged<1 месяца. Тезисы и опубликованные серии случаев, описывающие использование азитромицина у детей в возрасте менее 1 месяца, показывают меньшее количество побочных эффектов по сравнению с эритромицином. На сегодня имеются только спорадические сообщения о инфантильном гипертрофическом пилорическом стенозе.

Treatment of patients ≥1 month of age

First-line treatment is a macrolide antibiotic. The choice of macrolide should take into account efficacy, safety (including the potential for adverse events and drug interactions), tolerability, and ease of adherence to the prescribed regimen. Azithromycin and clarithromycin are as effective as erythromycin for the treatment of whooping cough in people 6 months of age and older, better tolerated, and associated with fewer and milder side effects than erythromycin.

Studies have shown that treatment is most effective when administered early in the disease (i.e., within 2 weeks of paroxysmal cough). If given after three weeks of cough onset, treatment may have limited benefit. Erythromycin is recommended as an alternative to azithromycin or clarithromycin and is considered the drug of choice in pregnant women (clarithromycin and azithromycin are not recommended for pregnant women). In patients with macrolide allergy, TMP/SMX is the first-line treatment. It is contraindicated in infants under 6 weeks of age (2 months in some countries such as the US), pregnant patients, and nursing mothers. These patients should consult a specialist for treatment recommendations. TMP/SMX is not licensed for chemoprevention. Susceptibility testing is not generally recommended for pertussis-B isolates.

Resistance to clarithromycin and azithromycin has not been reported. During treatment, the development of organisms resistant to erythromycin should be considered if this agent is used. In the United States, isolates obtained from patients who have failed erythromycin therapy must be sent to the CDC for further testing. There are currently no reliable population-based estimates of erythromycin treatment failure rates. TMP/SMX is indicated for erythromycin-resistant organisms unless contraindicated.

3.1.2. RESPIRATORY TRACT INFECTIONS

Diagnosis of whooping cough and parawhooping cough

Date of introduction: from the moment of approval

1. Developed by: Federal Service for Supervision of Consumer Rights Protection and Human Welfare (E.B. Ezhlova, A.A. Melnikova, N.A. Koshkina); Federal Budgetary Institution of Science "St. Petersburg Research Institute of Epidemiology and Microbiology named after Pasteur" (G.Ya. Tseneva, N.N. Kurova); Federal Budgetary Institution of Science "Central Research Institute of Epidemiology" of the Federal Service for Surveillance in the Field of Protection of Consumer Rights and Human Welfare (S.B. Yatsyshina, T.S. Selezneva, M.N. Praded); Federal State Budgetary Institution "Research Institute of Childhood Infections of the Federal Medical and Biological Agency" (Yu.V. Lobzin, I.V. Babachenko).

2. Approved by the Head of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Chief State Sanitary Doctor of the Russian Federation G.G. Onishchenko on May 24, 2013.

3. Entered into force from the moment of approval.

Terms and abbreviations

DTP - adsorbed pertussis-diphtheria-tetanus vaccine

WHO - World Health Organization

GOST - State standard

DNA - deoxyribonucleic acid

ELISA - enzyme immunoassay

KUA - casein charcoal agar

ME - international units

MU - guidelines

ARVI - acute respiratory viral infection

PSK - period of convulsive cough

PCR - polymerase chain reaction

RA - agglutination reaction

RIF - immunofluorescence reaction

RNA - ribonucleic acid

SanPiN - sanitary and epidemiological rules and regulations

ESR - erythrocyte sedimentation rate

SP - sanitary and epidemiological rules

TE - Tris-EDTA buffer

TU - technical conditions

FS - pharmacopoeial monograph

cAMP - cyclic adenosine monophosphate

ELISA - enzyme-linked immunosorbent assay (a type of ELISA)

Ig - immunoglobulin

IL - interleukin

FHA - filamentous haemagglutinin (filamentous hemagglutinin)

NASBA - nucleic acid sequence-based amplification (RNA amplification method)

PT - pertussis toxin (pertussis toxin)

RS infection is an infection caused by respiratory syncytial virus

1 area of use

The methodological recommendations present the modern microbiological characteristics of whooping cough in the context of mass vaccination prevention. They contain a brief description of the genus Bordetella, including new species discovered in the last decade, more detailed characterization of biological properties B. pertussis, B. parapertussis And B. bronchiseptica, description of the bacteriological research method using techniques that increase its information content, modern methods of laboratory diagnostics PCR and ELISA. Algorithms for diagnosing whooping cough are presented depending on the vaccination status, age and duration of the disease of patients. The purpose of these guidelines is to unify approaches to the laboratory diagnosis of pertussis infection.

The methodological recommendations are intended for specialists from Rospotrebnadzor bodies and organizations (microbiologists, epidemiologists), clinical laboratory diagnostic specialists, infectious disease specialists, pediatricians, family doctors and general practitioners.

2. Introduction

In the pre-vaccination era, whooping cough ranked second among childhood droplet infections in terms of morbidity and first in mortality. Currently, several million people fall ill every year in the world, about 200 thousand die (in 2008 - 16 million sick people, 195 thousand deaths).

Specific prevention of whooping cough, carried out in our country since 1959, has clearly influenced the epidemic process, the biological properties of the pathogen and the clinic. The stages of mass immunization were characterized by different levels of coverage of children with vaccinations against whooping cough and, in accordance with this, the epidemiological situation changed. Low immunization levels in the 1990s led to an increase in the incidence of whooping cough. Achieving vaccination coverage of children in the first year of life (more than 95%) in subsequent years and maintaining it at this level ensured not only a decrease in the incidence of whooping cough, but also, since 2001, stabilization of indicators at a minimum level (3.2-5.7 per 100 thousand . population). A feature of the epidemic process of whooping cough against the background of high vaccination coverage among young children is the occurrence of periodic rises. This is explained by the insufficient strength and duration of post-vaccination immunity created in conditions of frequent violations of the vaccination calendar, in particular, non-compliance with vaccination dates and intervals between vaccine doses and revaccination, which contributes to the accumulation of a significant number of non-immune individuals. Increasing vaccination coverage has now led to a change in the age structure of people who develop whooping cough. The majority of cases are schoolchildren aged 7-14 years - up to 50.0%, children aged 3-6 years - up to 25.0%, the smallest proportion are children aged 1-2 years - 11.0% and children under 1 year - 14. 0%. During periods of rising incidence of whooping cough, the intensity of the epidemic process is determined by the incidence of school-age children. The growth rate in this group increases by 2-3 times. Of the people who contract whooping cough, 65% are vaccinated.

Post-vaccination immunity does not protect against the disease. Whooping cough in these cases occurs in the form of mild and erased forms of infection, which are diagnosed mainly retrospectively (serologically). After an illness, longer lasting immunity remains.

The true incidence of whooping cough is much higher due to undiagnosed whooping cough infection (mild and erased clinical forms). Difficulties in the clinical diagnosis of whooping cough in the early stages of the disease, the lack of examination of all long-term (more than 7 days) coughers or its implementation in the later stages of the disease, as well as after prolonged treatment with antibacterial drugs, lead to a low percentage of detection of the infectious agent. The level of bacteriological confirmation of the diagnosis is 10-20%. Modern research methods allow for early diagnosis of the disease (PCR) and significantly facilitate diagnosis (PCR, ELISA).

Thus, whooping cough in our country requires close attention from doctors of various specialties. Timely and high-quality laboratory diagnosis of pertussis infection will avoid errors in diagnosis and will contribute to effective therapy.

3. Characteristics of the genus Bordetella, biological properties of the pathogens of whooping cough and parapertussis

________________
* The word "Bordetella" in the title of section 3 in the original paper is in italics. - Database manufacturer's note.

Genus Bordetella belongs to the family Alcaligenaceae and includes 9 types: IN. ansorpii, B. avium, B. bronchiseptica, B. hinzii, B. holmesii, B. parapertussis, B. pertussis, IN. petrii, B. trematum. The first (in 1908) was described B. pertussis, the bacterium is pathogenic for humans and is the causative agent of whooping cough. B. parapertussis was described in 1938, causes parapertussis (whooping cough-like disease) in humans, and has also been isolated from sheep. B. bronchiseptica was described in 1911, is the causative agent of respiratory tract diseases in many mammals (cough in dogs, atrophic rhinitis in pigs, etc.), but asymptomatic carriage also occurs. It rarely causes disease in humans, but cases have been described in older people infected from domestic animals (rabbits). B. bronchiseptica caused a prolonged cough. B. avium described in 1984, is the causative agent of rhinotracheitis in birds. Several cases of isolation have been described B. avium from elderly patients with a complicated medical history, with a clinical picture of pneumonia. In 1995, two new species were described at once: B. hinzii And B. holmesii. B. hinzii colonizes the respiratory tract of poultry, was isolated from immunocompromised patients, and a case of lethal septicemia was described. B. holmesii isolated only from humans, found in sputum, several times in the blood, the etiological role in the development of infections has not been proven. In 1996 it was allocated B. trematum, the pathogen causes wound and ear infections. In 2001 it was described B. petrii, the only representative of the genus isolated from the environment and capable of living in anaerobic conditions. In 2005 it was allocated B. ansorpii, several cases of isolation from patients with cancer have been described (from the purulent contents of an epidermal cyst, from the blood).

Morphological and cultural properties

Bacteria genus Bordetellae- small (0.2-0.5 µm0.5-2.0 µm) gram-negative coccobacilli. In smears - often bipolar colored, single or in pairs, less often in chains, have a delicate capsule. Everything except B. petrii, - strict aerobes. Bordetella cultivation temperature is +35-37 °C (optimally +35 °C). Bordetella is demanding on growth conditions: 130-150 mg of % amine nitrogen, blood, yeast extract, nicotinic acid, amino acids (cystine, proline, methionine, serine, glutamine, etc.); The causative agent of whooping cough is the most demanding; it grows only on special media, while other members of the genus grow on blood agar. Classic medium for primary isolation B. pertussis is the Bordet-Gengou medium (potato-glycerin agar), later synthetic and semi-synthetic media were proposed, in particular casein-charcoal agar (CCA). On the indicated media, bordetella grow in the form of characteristic colonies: on Bordet-Gengou media - convex, smooth, shiny, silver in color, resembling drops of mercury, surrounded by a hemolysis zone; on KUA - convex, smooth, gray in color with a pearl, yellowish or whitish tint. The colonies are oily and can be easily removed with a loop. B. parapertussis And B. holmesii Due to the formation of pigment, they cause darkening of media with blood and form a brown substrate.

Table 1

Growth characteristics of the main types of Bordetella

B. pertussis

B. parapertussis

B. bronchiseptica

Time required for colonies to appear (days):

At AMC (bordetelagar)

On Wednesday Bordet-Gengou

Colony size on AMC

Growth on plain agar

table 2

Differentiating characteristics of species of the genus Bordetella


	Growth on blood agar	Oxidase	Tirosi- back	Recover update of nitrates	Disposal- tion of citrates	Movable ness
B. pertussis
B. parapertussis
B. bronchiseptica
B. avium
B. hinzii
B. holmesii
B. trematum
B. petrii
B. ansorpii
* - after 4 hours

B. pertussis least active enzymatically (positive oxidase test). B. parapertussis produces the enzymes tyrosinase and urease and does not form oxidase. Tyrosinase catalyzes the production of pigments from tyrosine contained in nutrient media, which causes their darkening. Most active B. bronchiseptica: produces urease, oxidase, utilizes citrates, reduces nitrates to nitrites.

Antigenic structure and serological characteristics

To pathogenicity factors B. pertussis primarily include pertussis toxin . This is an exotoxin, a protein with a molecular weight of 117,000 Da, consisting of two functional parts (A and B) and five structural subunits (S1-S5): fragment A (corresponding to subunit S1) - has enzymatic activity, inhibits cellular adenylate cyclase. Section B (consists of subunits S2-S5) is responsible for the attachment of the toxin to the receptors of target cells. The toxin is highly immunogenic and is included in all acellular pertussis vaccines in its inactivated form. Determination of antibodies to pertussis toxin by ELISA is used to diagnose whooping cough and monitor the effectiveness of vaccination.

Filamentous hemagglutinin - surface protein involved in adhesion has protective properties. Included in acellular pertussis vaccines. A number of commercial ELISA test systems for the diagnosis of whooping cough propose to determine the level of antibodies of various classes to the antigenic complex, which includes hemagglutinin and pertussis toxin. Unlike the toxin, hemagglutinin is not strictly specific for B. pertussis, is also present in B. parapertussis, may cross-react with N. influenzae, C. pneumoniae and a number of other bacteria.

Pertactin - outer membrane protein, belongs to the system of adhesins produced by bacteria when they enter the human body. It has protective properties and is part of a number of acellular pertussis vaccines.

Adenylate cyclase-hemolysin is a complex of the exoenzyme adenylate cyclase, which, when it enters cells, catalyzes the formation of cAMP, with the toxin hemolysin. The toxin is the main pathogenicity factor acting at the initial stage of infection; in addition, the protective properties of the complex are associated with it.

Agglutinogens - surface proteins responsible for the production of agglutinating antibodies. 16 agglutinogens have been isolated from Bordetella (Table 3).

Table 3

Bordetella agglutinogens


	General generic	Intraspecific (strain)
B. pertussis		1, 2, 3, 4, 5, 6, 13, 15, 16
B. parapertussis
B. bronchiseptica

Depending on the presence of agglutinogens 2 and 3 in the bacterial cell, four serotypes are distinguished B. pertussis: 1.2.0; 1.0.3; 1.2.3; 1.0.0. The concept of agglutinogens is closely related to fimbriae (Fim). In the genome of everyone B. pertussis are present and , that is, theoretically, any strain can produce agglutinogens 2 and/or 3. Fimbriae are included in some acellular pertussis vaccines. Serotyping B. pertussis in domestic practice it is based on the agglutination of bacterial cells with monofactorial sera, i.e. antibodies to agglutinogens, in the agglutination reaction (RA) on glass, and in foreign practice - on the agglutination of bacterial cells with monoclonal antibodies to fimbrial antigens in the agglutination reaction in a microplate. To diagnose whooping cough in Russia, RA with a whole cell diagnosticum is still used, in which agglutinating antibodies are determined, primarily to agglutinogens:

lipopolysaccharide : it contains two lipids: A and X. The biological activity of lipopolysaccharide is associated with the X-fraction. It has multiple functions, including pronounced immunogenicity; the reactogenicity of the cell vaccine is associated with it;

tracheal cytotoxin - fragment of peptidoglycan of the cell wall. It has various biological properties: pyrogenicity, adjuvant, arthritogenicity, stimulation of IL-1 production. In vitro the toxin attacks tracheal epithelial cells and causes ciliostasis. This disrupts mucociliary clearance, the first line of defense, and creates conditions for persistent infection;

dermonecrotizing toxin has vasoconstrictor activity, in experimental animals it causes a decrease in body weight gain, spleen atrophy, ischemic damage or skin necrosis. Its role in the disease is unclear.

All of the above factors are present in freshly isolated strains of the pertussis microbe. However, when stored on artificial nutrient media, the variability of the pathogen becomes evident. It has been established that in the process of saprophytization, the pertussis microbe goes through four phases: the freshly isolated microbe (smooth strain), which has high virulent and immunogenic properties, belongs to the first phase. As we move to the fourth phase, immunogenicity and virulence are gradually lost, and cultural and biological properties change.

4. Indications for examination

Whooping cough is a disease that lasts at least two weeks, without symptoms of intoxication and fever, occurring with paroxysmal coughing, intensifying at night and in the morning, accompanied by redness of the face, noisy inhalations (reprises), ending with the discharge of viscous mucus or vomiting at the end of a coughing attack.

Laboratory confirmed case (see clause 5.1).

Epidemiologically linked case : a case in which the patient had (has) contact with one or more whooping cough patients, provided that at least one case in the transmission chain was laboratory confirmed.

Probable case : meets the clinical case definition, is not laboratory confirmed and has no epidemiological link to a laboratory confirmed case.

Confirmed case : Meets the clinical case definition, is laboratory confirmed, and/or has an epidemiological link to a laboratory confirmed case.

The disease occurs cyclically with a succession of periods.

Incubation period lasts from 3 to 14 days (average 7-8 days).

Pre-convulsant period- from 3 to 14 days, manifested by a dry, obsessive cough against a background of normal body temperature.

Period of convulsive cough (CPC)- from 2-3 to 6-8 weeks or more, characterized by typical attacks of convulsive cough, often accompanied by reprises and expectoration or vomiting after coughing.

Period of reverse development (early convalescence)- from 2 to 8 weeks, as the child’s well-being improves, the cough becomes less frequent and gradually loses its typical character.

Period of convalescence (late)- from 2 to 6 months, characterized by a state of hyperreactivity with the possible development of paroxysmal cough during intercurrent illnesses or emotional stress.

4.1. Indications for examination for whooping cough in the preconvulsive period

In the preconvulsive period, laboratory confirmation of the diagnosis by methods of identifying the pathogen (bacteriological, PCR) is mandatory.

Supportive diagnostic signs of whooping cough in the preconvulsive period:

contact with a patient with whooping cough or a child (adult) who has been coughing for a long time in a family or childcare facility;

gradual onset with satisfactory condition and good health of the patient;

normal body temperature;

dry, obsessive cough that gradually intensifies;

absence or mild severity of other catarrhal phenomena other than cough;

absence of pathological auscultation and percussion changes in the lungs;

lack of effect from symptomatic therapy;

the appearance of typical hematological changes - leukocytosis with lymphocytosis (or isolated lymphocytosis) with normal ESR.

4.2. Indications for examination for whooping cough during a period of convulsive cough

The diagnosis is made on the basis of clinical, epidemiological and hematological data, confirmed by laboratory methods for identifying the pathogen and/or specific antibodies.

The main symptom of this period is a paroxysmal convulsive (spasmodic) cough. A coughing attack consists of respiratory shocks following each other on exhalation, interrupted by a whistling convulsive inhalation - a reprise that occurs when air passes through a narrowed (due to laryngospasm) glottis. The attack ends with the discharge of viscous, glassy sputum or vomiting. An attack may be preceded by an aura (a feeling of fear, anxiety, sneezing, sore throat, etc.). Coughing attacks can be short-lived or last 2-4 minutes. Paroxysms are possible - a concentration of coughing attacks over a short period of time. During a typical coughing attack, the patient’s appearance is characteristic: the face turns red, then turns blue, becomes tense, the skin veins of the neck, face, and head swell; lacrimation is noted. The tongue protrudes from the oral cavity to the limit, its tip rises upward. As a result of friction of the frenulum of the tongue on the teeth and its mechanical overstretching, a tear or the formation of an ulcer occurs. A tear or ulcer of the frenulum of the tongue is a pathognomonic symptom of whooping cough. With a smooth course of the disease, the body temperature remains normal.

Characteristic is the gradual development of symptoms of the disease with a maximum increase in frequency and severity of convulsive coughing attacks at the 2nd week of postoperative period; the addition of specific complications at week 3, nonspecific complications against the background of the development of a secondary immunodeficiency state - at week 4 of PSC.

Supportive diagnostic signs of whooping cough during the period of convulsive cough:

characteristic epidemiological history;

paroxysmal convulsive cough is a pathognomonic symptom;

characteristic dynamics of cough from dry obsessive to paroxysmal convulsive;

characteristic appearance of the patient (pasty eyelids, puffiness of the face);

normal body temperature with a smooth course of the disease;

an abundance of large- and medium-bubble moist rales in the lungs, decreasing or disappearing after a coughing attack;

a tear or ulcer of the frenulum of the tongue is possible - a pathognomonic symptom.

Whooping cough severity criteria:

severity of symptoms of oxygen deficiency (hypoxia);

frequency and nature of convulsive cough attacks;

the presence of vomiting after a convulsive cough;

the child’s condition in the interictal period;

severity of edema syndrome;

the presence and timing of development of specific complications;

severity of hematological changes.

Keywords

PERTUSSIS / EPIDEMIOLOGY / DIAGNOSIS / TREATMENT / PREVENTION

annotation scientific article on clinical medicine, author of the scientific work - Nikolaeva Irina Venidiktovna, Shaikhieva Gulnara Sirenevna

Despite high levels of vaccination coverage, pertussis remains an important cause of childhood morbidity and mortality worldwide. In many countries of the world there is an epidemic of whooping cough, and a significant proportion of the sick people are vaccinated people. The goal is to analyze modern data on the reasons for the increase in incidence and characteristics of the course, diagnosis, treatment and prevention of whooping cough in children and adults. Material and methods. A review of publications by domestic and foreign authors, clinical recommendations for the diagnosis, treatment and prevention of whooping cough was conducted, and data from randomized clinical and epidemiological studies were studied. Results and its discussion. Modern data on the epidemiology of whooping cough, features of its clinical manifestations, diagnosis and treatment in different age groups are presented. Conclusions. The increase in the incidence of whooping cough may be associated with changes in the antigenic structure of the pathogen, the short duration of post-vaccination immunity, a decrease in vaccination coverage, and the use of more sensitive laboratory diagnostic methods. Among the patients, teenagers and adults predominate, who suffer from whooping cough mainly in atypical forms. Severe and complicated forms of whooping cough, as well as deaths, are typical for children in the first months of life. The use of modern methods of diagnosis and treatment of whooping cough in clinical practice can reduce the duration and severity of its clinical manifestations, as well as limit the spread of infection. There is a need to improve the vaccination strategy against whooping cough, maintain a high level of vaccination coverage and strictly adhere to anti-epidemic measures in foci of infection.

Pertussis at the present stage

Despite the high level of vaccination coverage, pertussis remains an important cause of child morbidity and mortality worldwide. In many countries, there is an epidemic of pertussis, and a significant proportion among patients are vaccinating people. The aim of the article was to analyze the causes of the growth of incidence today. To review the characteristics of course, diagnosis, treatment and prevention of pertussis in children and adults. Materials and methods. A review publications of domestic and foreign authors, the clinical recommendations for diagnosis, treatment and prevention of pertussis were carried out, data from randomized clinical trials and epidemiological researches were studied. Results and discussion. Modern data on the epidemiology of pertussis, peculiarities of its clinical manifestations, diagnosis and treatment in different age groups are presented. Conclusions. The increased incidence of pertussis may be associated with changes in the antigenic structure of the pathogen, the short duration of post-vaccination immunity, lower vaccination coverage, using more sensitive methods of laboratory diagnostics. Among the cases predominated teenagers and adults who suffer pertussis mainly in atypical forms. Severe and complicated forms of pertussis, as well as lethal outcomes were characteristic of children during the first months of life. The use in clinical practice of modern pertussis diagnosis and treatment methods can reduce the duration and severity of clinical manifestations, as well as limit the spread of infection. There is a need to improve vaccination strategies against pertussis, maintain a high level of vaccination coverage and strict adherence of epidemiology in the nidus of infection.

Text of scientific work on the topic “Whooping cough at the present stage”

UDC 616.921.8(048.8) DOI: 10.20969/VSKM.2016.9(2).25-29

whooping cough at the present stage

Nikolaeva Irina Venidiktovna, Dr. honey. Sciences, Associate Professor of the Department of Children's Infections, Kazan State Medical University, Ministry of Health of Russia, Russia, 420012, Kazan, st. Butlerova, 49, tel. 8-960-037-70-17, e-mail: lrinanicolaeva@ mail.ru Shaikhieva Gulnara Sirenevna, graduate student of the Department of Childhood Infections, Kazan State Medical University, Ministry of Health of Russia, Russia, 420012, Kazan, st. Butlerova, 49, tel. 8-917-245-93-10, e-mail: [email protected]

Abstract. Despite high levels of vaccination coverage, pertussis remains an important cause of childhood morbidity and mortality worldwide. There is an epidemic of whooping cough in many countries around the world, and a significant proportion of the sick people are vaccinated people. The goal is to analyze current data on the reasons for the increase in incidence and features of the course, diagnosis, treatment and prevention of whooping cough in children and adults. Material and methods. A review of publications by domestic and foreign authors, clinical recommendations for the diagnosis, treatment and prevention of whooping cough was carried out, and data from randomized clinical and epidemiological studies were studied. Results and its discussion. Modern data on the epidemiology of whooping cough, features of its clinical manifestations, diagnosis and treatment in different age groups are presented. Conclusions. The increase in the incidence of whooping cough may be associated with changes in the antigenic structure of the pathogen, the short duration of post-vaccination immunity, a decrease in vaccination coverage, and the use of more sensitive laboratory diagnostic methods. Among the patients, teenagers and adults predominate, who suffer from whooping cough mainly in atypical forms. Severe and complicated forms of whooping cough, as well as deaths, are typical for children in the first months of life. The use of modern methods of diagnosis and treatment of whooping cough in clinical practice can reduce the duration and severity of its clinical manifestations, as well as limit the spread of infection. There is a need to improve the pertussis vaccination strategy, maintain a high level of vaccination coverage and strictly adhere to anti-epidemic measures in areas of infection. Key words: whooping cough, epidemiology, diagnosis, treatment, prevention.

pERTussis AT THE pRESENT sTAGE

nicolaevairina v., D. Med. Sci., associate professor of the Department of children infections of Kazan State Medical university, Russia, Kazan, Butlerovstr., 49, tel. 8-960-037-70-17, e-mail: lrinanicolaeva@ mail.ru shaikhieva gulnara s., p. Med. Sci., graduate student of the Department of children infections of Kazan State Medical university, russia, Kazan, Butlerov str., 49, tel. 8-917-245-93-10, e-mail: [email protected]

Abstract. Despite the high level of vaccination coverage, pertussis remains an important cause of child morbidity and mortality worldwide. In many countries, there is an epidemic of pertussis, and a significant proportion among patients are vaccinated people. The aim of the article was to analyze the causes of the growth of incidence today. To review the characteristics of course, diagnosis, treatment and prevention of pertussis in children and adults. Materials and methods. A review publications of domestic and foreign authors, the clinical recommendations for diagnosis, treatment and prevention of pertussis were carried out, data from randomized clinical trials and epidemiological researches were studied. Results and discussion. Modern data on the epidemiology of pertussis, peculiarities of its clinical manifestations, diagnosis and treatment in different age groups are presented. Conclusions. The increased incidence of pertussis may be associated with changes in the antigenic structure of the pathogen, the short duration of post-vaccination immunity, lower vaccination coverage, using more sensitive methods of laboratory diagnostics. Among the cases predominated teenagers and adults who suffer pertussis mainly in atypical forms. Severe and complicated forms of pertussis, as well as lethal outcomes were characteristic of children during the first months of life. The use in clinical practice of modern pertussis diagnosis and treatment methods can reduce the duration and severity of clinical manifestations, as well as limit the spread of infection. There is a need to improve vaccination strategies against pertussis, maintain a high level of vaccination coverage and strict adherence of epidemiology in the nidus of infection. Key words: pertussis, epidemiology, diagnosis, treatment, prevention.

For reference: Nicolaeva IV, Shaikhieva GS. Pertussis at the present stage. The Bulletin of Contemporary Clinical Medicine. 2016; 9 (2): 25-29.

Whooping cough is an acute respiratory disease caused by B. pertussis, the main manifestation of which is a paroxysmal cough. Despite advances in vaccination, whooping cough remains a significant cause of childhood morbidity and

mortality and a serious public health problem worldwide. According to WHO, about 60 million people worldwide fall ill with whooping cough every year and about 1 million children die, mostly under the age of one year.

Currently, in many countries of the world (USA, Australia, the Netherlands, Canada, etc.), despite high vaccination coverage of the child population, there is an epidemic of whooping cough. In Russia in 2014, 4,705 cases of whooping cough were registered (the incidence rate was 3.23 per 100 thousand population). The maximum incidence rates were registered among children under 1 year of age - 54.2 per 100 thousand children. Mortality from whooping cough remains (0.007 per 100 thousand population). The age structure of the cases is dominated by schoolchildren aged 7-14 years (37.9%), children under 1 year old accounted for 25%, children aged 3-6 years old - 18.2%, children aged 1-2 years old - 15.3%. Most of the sick people (65%) were vaccinated! . Official statistics data most likely do not reflect the real situation regarding the incidence of whooping cough, since in practice no more than 10-12% of cases of the disease are diagnosed. Recent reports indicate an 8-10-fold increase in the incidence of whooping cough in 2015 in various regions of Russia (Khabarovsk Territory, Prikamye, Kirov Region, etc.). During 2015, 83 children were hospitalized at the Republican Infectious Diseases Clinical Hospital of Kazan (of which 65 were children in the first year of life), while in 2014 only 10 children were hospitalized. Taking into account the birth of 23 thousand children in Kazan in 2015, the incidence of whooping cough (only taking into account the number of hospitalized children) in children of the first year of life was about 200-250 per 100 thousand!

The increase in whooping cough incidence rates, according to scientists, may be associated with various reasons: the use of more sensitive research methods (polymerase chain reaction), changes in the antigenic structure of the pathogen, the insufficient effectiveness of modern vaccines and the short duration of post-vaccination immunity, a decrease in vaccination coverage, etc.

Despite the fact that whooping cough is a “childhood infection,” the age structure of cases in recent years has been dominated by adolescents and adults, who in most cases suffer from whooping cough in an atypical form. Adolescents and adults are the main source of outbreaks and infection in families of infants who are unvaccinated, in whom whooping cough is very severe and poses a direct threat to life. Transmission of the infection occurs through airborne droplets and is only possible through close contact with a patient or carrier. Vaccinated people can be carriers of the whooping cough pathogen and participate in the epidemic process, spreading the infection. The infectivity index ranges from 0.7 to 1.0. An autumn-winter rise in incidence with a peak in December-January is characteristic.

Currently, whooping cough in unvaccinated people retains all its typical manifestations. The incubation period ranges from 3 to 14 days. The onset of the disease is gradual with increasing dynamics of dry cough (catarrhal period, duration 1-2 weeks), while the symptoms of

There is no toxicity, no fever, and the patients’ well-being is slightly impaired. As a rule, at this stage, patients are diagnosed with ARVI. Next, the cough becomes paroxysmal (the period of spasmodic cough), which lasts from 1 to 6 weeks. A coughing attack with whooping cough consists of a series of short coughing impulses on exhalation, followed by intense inhalation, which is accompanied by a whistling sound (reprise). During an attack, the patient's face turns red or becomes cyanotic, the neck veins swell, the eyes water, the tongue protrudes from the mouth and is curled upward. The attack ends with the discharge of viscous, glassy sputum or vomiting. Vomiting after a coughing attack is very characteristic of whooping cough. Whooping cough cough worsens at night, after physical or emotional stress. The number of coughing attacks during the day ranges from single to 40-50 or more. The patient’s condition between coughing attacks may not be disturbed (except for severe forms of the disease), which can confuse the doctor in assessing his condition. The convalescence phase of whooping cough lasts several weeks and is characterized by a gradual decrease in the frequency and intensity of cough.

In adolescents and adults, whooping cough often occurs in atypical forms and is manifested by a prolonged cough, for which they usually receive ineffective therapy from general practitioners, allergists and otolaryngologists. However, even in these age groups, whooping cough can have a typical course and be complicated by pneumonia (2%), urinary incontinence (28%), collapse (6%), rib fractures (4%), etc. It should be noted that there is “insufficient alertness” regarding whooping cough among doctors in the “adult” network, and therefore the diagnosis in adults is often made in the later stages of the disease.

Whooping cough is most relevant for infants. Most cases of death and severe disease develop in children in the first months of life. Children less than 2 months of age have an increased risk of death. The high-risk group for the development of adverse outcomes includes premature babies, children with intrauterine growth retardation, pathology of the central nervous system, respiratory system and heart. In infants, whooping cough occurs with a short catarrhal period, a longer period of spasmodic cough (up to 2 months), and recurrences may be absent. Coughing attacks may result in apnea. Encephalopathy may develop, which is manifested by loss of consciousness, convulsions, paralysis or paresis of the limbs. According to the literature, in the period from 1997 to 2000, 7203 cases of whooping cough in children in the first six months of life were registered in the United States. Of these, 63.1% of children were hospitalized, 11.8% developed pneumonia, 1.4% had seizures, 0.2% had encephalopathy, and 0.8% of children died. Deaths were mainly associated with the development of severe pneumonia, pulmonary hypertension, encephalopathy and multiple organ failure. Children

with leukocytosis more than 50 0 00*109/l have a 10 times higher risk of death. Rare complications of whooping cough include pneumothorax, emphysema, subarachnoid and intraventricular hemorrhages, subdural and epidural hematomas, lingual frenulum ulcer, rupture of the diaphragm, umbilical and inguinal hernia, rectal prolapse, severe alkalosis and associated tonic convulsions, dehydration.

Diagnosis of whooping cough is based on epidemiological and clinical laboratory data. All patients who have been coughing for more than 7 days are subject to mandatory laboratory testing for whooping cough (2 times bacteriological and/or 1 time polymerase chain reaction). Polymerase chain reaction (PCR) has high sensitivity and is currently the most common method for diagnosing whooping cough. Bacteriological and PCR studies for whooping cough are recommended to be carried out during the first 3 weeks of the disease. In clinically unclear cases, with negative results of bacteriological and PCR studies, late stages of the disease and in vaccinated people, a 2-fold serological examination with an interval of 10-14 days by ELISA is recommended. Confirmation of the clinical diagnosis of “whooping cough” in unvaccinated patients is a single detection of specific IgM and/or IgA and/or IgG (ELISA), or antibodies in a titer of 1/80 or more (RA). In vaccinated people, whooping cough is indicated by an increase or decrease of 4 or more times in the level of specific IgG and/or IgA (ELISA), or the level of antibodies (RA) when studying paired sera taken at an interval of at least 2 weeks. Hematological changes (leukocytosis with lymphocytosis and normal ESR) are of great diagnostic and prognostic importance for whooping cough.

In the treatment of whooping cough, great importance is given to routine measures. Long walks in the fresh air and a protective regime are recommended. Infants are subject to hospitalization regardless of the severity of the disease; patients with severe and complicated forms of whooping cough; children with concomitant pathologies (perinatal encephalopathy, convulsive syndrome, prematurity, degree II-III malnutrition, congenital heart disease, bronchial asthma). According to epidemic indications, children from “closed groups” (orphanages, camps, dormitories, etc.) are hospitalized. Children with apnea, seizures, or respiratory failure should be hospitalized in the intensive care unit.

All patients with suspected whooping cough should begin etiotropic therapy without waiting for examination results. The drugs of choice are macrolides. Azithromycin is prescribed 10 mg/kg per day as a single dose for 5 days. In children over 6 months of age, a clarithromycin suspension can be prescribed at a dose of 7.5 mg/kg per os for 7 days. Macrolides may prevent or reduce the clinical manifestations of whooping cough if they are used during the incubation period or in the early catarrhal stage.

During the paroxysmal phase of the disease, antimicrobial drugs do not change the clinical course, but may eliminate bacteria from the nasopharynx and thus reduce their transmission. If macrolides are contraindicated, trimethoprim-sulfamethoxazole can be prescribed. In severe forms of the disease, the use of 3rd generation cephalosporins is recommended. Antibiotics are most effective when prescribed early in the disease. In the treatment of whooping cough, non-narcotic antitussive drugs (butamirate) are used. For severe whooping cough, mechanical ventilation, oxygen therapy and hormonal therapy (dexamethasone, prednisolone) are performed. There is evidence of the effectiveness of double exchange blood transfusion and extracorporeal membrane oxygenation in severe forms.

Anti-epidemic measures consist of isolating the patient. Patients with whooping cough are isolated for 25 days from the onset of the disease. Contact children under the age of 14 years who have a cough, regardless of vaccination history, are subject to exclusion from attending preschool educational and general education organizations until they receive two negative bacteriological results and/or one negative PCR test result. In family units, contact children are placed under medical supervision for 14 days. Prevention of whooping cough in children in the first months of life involves preventing contact with any “coughing” patients. Newborns in maternity hospitals, children in the first three months of life and unvaccinated children under 1 year of age who have had contact with a patient with whooping cough are injected intramuscularly with normal human immunoglobulin. After isolating the patient, all contacts are recommended to take macrolides for 7 days in an age-appropriate dosage.

Prevention through vaccination remains the most effective means of protection against whooping cough. Vaccination begins at the age of three months and consists of three injections of adsorbed pertussis-diphtheria-tetanus vaccine (DTP) with an interval of 1.5 months. Revaccination is carried out 1.5-2 years after the course of vaccination. DTP is a whole-cell vaccine and consists of a suspension of killed pertussis microbes and purified tetanus and diphtheria toxoids adsorbed on aluminum hydroxide. For vaccination against whooping cough, the whole-cell Tetracok vaccine (an adsorbed vaccine for the prevention of diphtheria, tetanus, whooping cough and polio) is also used. Vaccination with whole-cell vaccines is contraindicated if the child has a progressive pathology of the nervous system, a history of afebrile seizures, complications or a strong general reaction (increase in temperature in the first two days to 40°C or higher) to the previous administration of the vaccine. Currently, acellular (cell-free) vaccines are widely used to prevent whooping cough, which are less likely to cause side effects. Acellular vaccines include: Infanrix (vaccine

for the prevention of whooping cough, diphtheria and tetanus), "Pentaxim" (combined vaccine containing adsorbed acellular pertussis-diphtheria-tetanus vaccine, inactivated polio vaccine and vaccine for the prevention of hemophilus influenzae infection), "In-fanrix HEXA" (recombinant vaccine for the prevention whooping cough, diphtheria, tetanus, polio, Haemophilus influenzae, viral hepatitis B). Vaccination against whooping cough in most cases prevents the disease, however, 3-5 or more years after vaccination, the intensity of post-vaccination immunity decreases, and those vaccinated may become ill. Whooping cough in vaccinated people occurs predominantly in a mild form, specific complications develop 4 times less frequently than in unvaccinated people, and no deaths are observed. In the USA and most European countries, vaccination against whooping cough begins at 2 months of age; in preschool age, a 2nd revaccination with an acellular vaccine is carried out, and adolescents and adults, including pregnant women, are also vaccinated. According to V.K. Tatochenko (2014), to boost immunity from whooping cough, it is necessary to introduce the 2nd revaccination of children aged 4-6 years into the National Vaccination Calendar of our country.

Thus, at present, despite high vaccination coverage, there is a significant increase in the incidence of whooping cough in children and adults around the world. In connection with the current epidemic situation, it is necessary to improve the vaccination strategy against whooping cough, maintain high coverage of timely vaccination and revaccination against whooping cough in children, strictly observe anti-epidemic measures in the foci of infection, and widely use modern methods of laboratory diagnosis of whooping cough in all patients with prolonged cough.

Research transparency. The study had no sponsorship. The authors are solely responsible for submitting the final version of the manuscript for publication.

Declaration of financial and other relationships. All authors participated in the conception, design of the study, and writing of the manuscript. The final version of the manuscript was approved by all authors. The authors received no royalties for the study.

LITERATURE

1. Symptomatic treatment of the cough in whooping cough / S. Bettiol, K. Wang, M.J. Thompson // Cochrane Database Syst. Rev. - 2012. - No. 5 (CD003257).

2. State report on the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2014. - M.: Federal Service for Supervision of Consumer Rights Protection and Human Welfare, 2015. - 206 p.

3. Tatochenko, V.K. Whooping cough is an uncontrollable infection / V.K. Tatochenko // Issues of modern pediatrics. - 2014. - No. 13 (2). - P.78-82.

4. Priming with whole-cell versus acellular pertussis vaccine / J. Liko, G. Robison // N. Engl. J. Med. - 2013. - No. 7. - P.581-582.

5. Cherry, J.D. Why do pertussis vaccines fail? /J.D. Cherry // Pediatrics. - 2012. - No. 129. - P.968-970.

6. Lapiy, F.I. Relevance of effective protection against whooping cough / F.I. Lapiy // Child’s health. - 2010. - No. 3. - P.86.

7. Infant pertussis: who was the source? / K.M. Bisgard, F.B. Pascual, K.R. Ehresmann // Pediatr. Infect. Dis. J. - 2004. - No. 23. - R.985-989.

8. Lobzin, Y.V. Retrospective Study of the Clinical Epidemiological Characteristics of Pertussis in Infants Prior to Their First Vaccination in the Russian Federation / Y.V. Lobzin, N.V. Bakhareva // Infect. Dis. Ther. - 2015. - No. 4 (1). - R. 113-123.

9. Sizemov, A.N. Whooping cough: clinical picture, diagnosis, treatment / A.N. Sizemov, E.V. Komeleva // Attending physician. - 2005. - No. 7. - P.82-87.

10. Centers for Disease Control and Prevention (CDC) Pertussis (Whooping Cough), Clinicians, Clinical Complications Retrieved. - 2012. - July 20. -URL: http:/ www.cdc.gov/pertussis/clinical/features.html

11. Pertussis-United States, 1997-2000 / Centers for Disease Control and Prevention // MMWR. - 2002. - No. 51 (4). - R.73.

12. Kundraft, S.L. Malignant pertussis in the pediatric intensive care unit / S.L. Kundraft, T.L. Wolek, M. Rowe-Telow // Dimens. Crit. Care Nurs. - 2010. - No. 29. - R.1-5.

13. Impact of rapid leukodepletion on the outcome of severe clinical pertussis in young infants / H.E. Rowlands, A.P. Goldman, K. Harrington // Pediatrics. - 2010. - No. 126. - R.816-827.

14. Theilen, U. Rapidly fatal invasive pertussis in young infants—how can we change the outcome? / U. Theilen, E.D. Johnston, P.A. Robinson // BMJ. - 2008. - No. 27. - R.337-343.

15. Prevention of whooping cough: sanitary and epidemiological rules SanPiN 3.1.2.3162-14: approved. Resolution of the Chief State Sanitary Doctor of the Russian Federation dated March 17, 2014 No. 9. - M., 2014. - URL: http://36.rospotrebnadzor.ru/documents/san_nor/14982

16. Tiwari, T. Recommended antimicrobial agents for the treatment and postexposure prophylaxis of pertussis. CDC guidelines / T. Tiwari, T.V. Murphy, J. Moran // Centers for Disease Control. - 2005. - No. 54 (RR-14). - R.1-16.

1. Bettiol S, Wang K, Thompson MJ et al. Symptomatic treatment of the cough in whooping cough. Cochrane Database Syst Rev. 2012; 5 (CD003257).

2. Gosudarstvennyj doklad o sostojanii sanitarno-jepidemiologicheskogo blagopoluchija naselenija v Rossijskoj Federacii v 2014 godu. M: Federal Supervision Agency for Customer Protection and Human Welfare. 2015; 206 rub.

3. Tatochenko VK. Kokljush - nedoupravljaemaja infekcija. Question sovremennoj pediatrii. 2014; 13(2): 78-82.

4. Liko J, Steve G. Robison. Priming with whole-cell versus acellular pertussis vaccine. N Engl J Med. 2013; 7: 581-582.

5. Cherry JD. Why do pertussis vaccines fail. Pediatrics. 2012; 129: 968-970.

6. Lapij FI. Aktual "nost" jeffektivnoj zashhity protiv kokljusha . Zdorov"e rebenka. 2010; 3: 86.

7. Bisgard KM, Pascual FB, Ehresmann KR et al. Infant pertussis: who was the source. Pediatr Infect Dis J 2004; 23: 985-989.

8. Lobzin YV, Bakhareva NV. Retrospective Study of the Clinical Epidemiological Characteristics of Pertussis in Infants Prior to Their First Vaccination in the Russian Federation. Infect Dis Ther. 2015; 4 (1): 113-123.

9. Sizemov AN, Komeleva EV Kokljush: clinic, diagnosis, treatment. Lechashhij vrach. 2005; 7:82-87.

10. Centers for Disease Control and Prevention (CDC). Pertussis (Whooping Cough), Clinicians, Clinical Complications. 2012; Available at: http:/www.cdc.gov/pertussis/clinical/features.html

11. Centers for Disease Control and Prevention. Pertussis-United States, 1997-2000. MMWR. 2002; 51 (4): 73.

12. Kundraft SL, Wolek TL, Rowe-Telow M. Malignant pertussis in the pediatric intensive care unit. Dimens Crit Care Nurs. 2010; 29:1-5.

Project

Approved

Expert advice

Joint Commission

on the quality of medical services

Ministry of Health and

social development

Republic of Kazakhstan

from "" 2016

protocol no.

CLINICAL PROTOCOL FOR DIAGNOSIS AND TREATMENT

PERTOUGH PARACOPTUSIS IN CHILDREN

Paragraph	Section title	page
	Content
	Protocol code
	Date of protocol development/revision
	Protocol users
	Patient category
	Level of evidence scale
	Definition
	Classification
	Diagnostics and treatment on an outpatient basis
9.1	Diagnostic criteria for diagnosis
9.2	Diagnostic algorithm
9.3	Differential diagnosis and rationale for additional studies
9.4	Treatment tactics
9.5
9.6	Preventive actions:
9.7	Patient monitoring
9.8
	Indications for hospitalization indicating the type of hospitalization
10.1	Indications for planned hospitalization
10.2	Indications for emergency hospitalization
	Diagnosis and treatment at the emergency stage
11.1	Diagnostic measures
11.2	Drug treatment
	Minimum list of examinations that must be carried out when referred for planned hospitalization
	Diagnostics and treatment at the hospital level
13.1	Diagnostic criteria at the hospital level
13.2	Diagnostic algorithm
13.3	List of basic diagnostic measures
13.4	List of additional diagnostic measures
13.5	Treatment tactics
13.6	Indications for consultation with specialists
13.7	Indications for transfer to the intensive care unit and resuscitation unit
13.8	Indicators of treatment effectiveness
	Medical rehabilitation
	Palliative care
	Abbreviations used in the protocol
	List of protocol developers with qualification details
	Indication of no conflict of interest
	List of reviewers

	Conditions for reviewing the protocol
	List of used literature

2. Correlation of ICD-10 and ICD-9 codes:

3. Date of development of the protocol: 2016

4. Protocol users: general practitioners, pediatric infectious disease specialists, pediatricians, emergency doctors, pediatric neurologists.

6 . Level of evidence scale:

A	A high-quality meta-analysis, systematic review of RCTs, or large RCTs with a very low probability (++) of bias, the results of which can be generalized to an appropriate population.
IN	High-quality (++) systematic review of cohort or case-control studies, or high-quality (++) cohort or case-control studies with very low risk of bias, or RCTs with low (+) risk of bias, the results of which can be generalized to an appropriate population .
WITH	Cohort or case-control study or controlled trial without randomization with a low risk of bias (+), the results of which can be generalized to the relevant population or RCT with a very low or low risk of bias (++ or +), the results of which cannot be directly distributed to the relevant population.
D	Case series or uncontrolled study or expert opinion.
GPP	Best pharmaceutical practice.

7 .Definition:

Whooping cough – an acute infectious disease with an airborne transmission mechanism caused by Bordetella pertussis, belonging to the genus Bordetella, and characterized by a cyclic course with predominant damage to the mucous membrane of the larynx, trachea, bronchi and the development of convulsive paroxysmal cough.

Parawhooping cough – an acute infectious disease with an airborne transmission mechanism, caused by Bordetella parapertussis, belonging to the genus Bordetella, which manifests itself as a persistent dry cough with attacks, reminiscent of whooping cough in a mild form.

8. Classification:

(N.I. Nisevich, V.F. Uchaikin, 1990)

Type	Heaviness	Flow
1. Typical form 2. Atypical: a) abortive; b) erased; c) subclinical.	· light; · medium-heavy; · heavy.	· acute; · protracted; · mixed infection. By the nature of complications: Specific: Pulmonary emphysema. Emphysema of the mediastinum, subcutaneous tissue. Segmental atelectasis. Pertussis pneumonia. Violation of the breathing rhythm (breath holding - apnea up to 30 s and stopping - apnea more than 30 s). Encephalopathy. Bleeding (from the nasal cavity, posterior pharyngeal space, bronchi, external auditory canal). Hemorrhages (under the skin, in the mucous membranes, sclera, retina, brain, subarachnoid and intraventricular, epidural hematomas of the spinal cord). Hernias (umbilical, inguinal). Prolapse of the rectal mucosa. A tear or ulcer of the frenulum of the tongue. Ruptures of the eardrum. Nonspecific: pneumonia; bronchitis; tonsillitis; lymphadenitis; otitis, etc.

Classification of whooping cough cases:

Clinical definition of the disease:

Cough illness lasting at least 2 weeks, accompanied by one of the following symptoms: coughing fits, noisy inhalation at the end of the attack, vomiting after coughing (Standard case definition for pertussis - Center for Disease Control, US CDC);

Suspicious case of whooping cough– meets the clinical definition of the disease;

Probable case of whooping cough– meets the clinical case definition, is not laboratory confirmed and has an epidemiological link to another suspected or laboratory confirmed case of pertussis.
Confirmed case of whooping cough– a case of pertussis previously classified as “suspicious” or “probable” after laboratory confirmation (with isolation of a culture of the pathogen, or DNA of the pathogen, or identification of specific anti-pertussis antibodies). In the absence of laboratory confirmation of the diagnosis due to the impossibility of conducting research, a “probable” case based on clinical data (manifestations) are classified as “confirmed”.

In atypical forms of the disease, a laboratory-confirmed case of whooping cough does not necessarily meet the clinical definition of the disease.

9. DIAGNOSIS AND TREATMENT AT AN OUTPATIENT LEVEL:

1) Diagnostic criteria:

Complaints:

· increased body temperature (rare);

· cough;

· slight nasal congestion;

· headache;

· anxiety, malaise;

· regurgitation, vomiting after coughing;

· convulsions;

apnea attacks;

· hemorrhages in the sclera, nosebleeds.

Anamnesis:

Gradual onset

· cyclical course of the disease;

· contact with a laboratory-confirmed case of whooping cough 3–14 days before the onset of symptoms of the disease or with a child who has been coughing for a long time;

· dry, increasing cough at normal or subfebrile body temperature, mild and quickly relieved catarrhal symptoms;

· lack of effect from the therapy during the catarrhal period;

· appearance of paroxysmal cough with recurrences, 1 – 2 weeks after the onset of the disease;

· secretion of thick viscous sputum or vomiting after a coughing attack;

· absence of constant changes in the lungs during the period of spasmodic cough;

Possible respiratory dysrhythmia and apnea attacks.

Physical examination:

During the catarrhal period(the duration of the period is from 3 to 14 days (on average 10–13 days), the longest - in vaccinated children, the shortest - in children in the first months of life) :

Cough – persistent, continuously progressing, despite symptomatic therapy;

If there is a cough, there is hard breathing in the lungs, wheezing is not heard, and on percussion there is slight tympanitis;

Paleness of the skin due to spasm of peripheral vessels, slight swelling of the eyelids.

During the period of spasmodic cough:(period duration from 3 weeks to 6-8 weeks or more):

· paroxysmal cough - short coughing impulses follow one after another during one exhalation, followed by an intense and sudden inhalation, accompanied by a whistling sound (reprise);

· the child’s position is forced, his face turns red or becomes cyanotic, his eyes become “bloodshot”, watery, his tongue seems to be pushed out to the limit and hangs down, while its tip is bent upward. The veins of the neck, face, and head swell. As a result of traumatization of the frenulum of the tongue by the lower incisors (or gums), some children experience tearing and the formation of ulcers, which are symptoms pathognomonic for whooping cough. The attack ends with the discharge of viscous, thick, glassy mucus, sputum or vomiting;

· the combination of coughing attacks with vomiting is so typical that whooping cough should always be assumed even in the absence of recurrences. It is possible to concentrate coughing attacks over a short period of time, i.e., the occurrence of paroxysms;

· puffiness and pastiness of the face, swelling of the eyelids, pallor of the skin, perioral cyanosis, signs of pulmonary emphysema;

· subconjunctival hemorrhages, petechial rash on the face and neck;

· tympanic shade of percussion sound, its shortening in the interscapular space and lower sections, dry and moist (medium-, coarse-bubbly) rales are heard over the entire surface of the lungs. Characteristic changes in the lungs are the disappearance of wheezing after a coughing attack and reappearance after a short period of time over other pulmonary fields.