Measles: Clinical Guidelines

List of Abbreviations

ALT – alanine aminotransferase

AST – aspartate aminotransferase

IBDP – immunobiological drug products (ATC J06 Immune sera and immunoglobulins)

EIA – enzyme immunoassay

MoH – Ministry of Health

INR – international normalized ratio

PCR – polymerase chain reaction

RNA – ribonucleic acid

SanPiN – Sanitary Rules and Norms

CRP – C-reactive protein

kg – kilogram

mo – months

mg – milligram

nm – nanometer (10^-9 meters)

day – 24 hours

per os – through the mouth (orally)

Terms and Definitions

This document uses terms interpreted in a way that makes them unambiguous for healthcare professionals. For the purposes of this regulatory document, the following terms, definitions, and abbreviations are used.

Disease – a condition arising from the impact of pathogenic factors, representing a disruption of body function, working capacity, and ability to adapt to changing environmental conditions, accompanied by concurrent changes in the body's protective-compensatory and protective-adaptive reactions and mechanisms.

Instrumental diagnostics – diagnostics using various devices, apparatuses, and instruments to examine a patient.

Disease outcomes – medical and biological consequences of a disease.

Quality of medical care – a set of characteristics reflecting the timeliness of medical care, the correctness of the choice of prevention, diagnosis, treatment, and rehabilitation methods in providing medical care, and the degree of achievement of the planned result.

Clinical practice guidelines for medical care – a regulatory document of the healthcare standardization system that defines the requirements for providing medical care to a patient with a specific disease, syndrome, or clinical situation.

Clinical situation refers to a case requiring the regulation of medical care regardless of the specific disease or syndrome.

Laboratory diagnostics is a set of methods aimed at analyzing test material using various specialized equipment.

Medical intervention encompasses types of medical examinations and/or medical manipulations performed by a medical professional in relation to a patient, affecting their physical or mental state and having a preventive, exploratory, diagnostic, therapeutic, or rehabilitative purpose, as well as artificial termination of pregnancy.

Medical service – a medical intervention or a complex of medical interventions aimed at the prevention, diagnosis, and treatment of diseases, and medical rehabilitation, having an independent completed significance.

Nosological form – a set of clinical, laboratory, and instrumental diagnostic signs that allow a disease (poisoning, trauma, physiological state) to be identified and classified into a group of conditions with common etiology, pathogenesis, clinical manifestations, and general approaches to treatment and condition correction.

Disease complication – the addition of a physiological process disordersyndrome to the disease; impairment of the integrity of an organ or its wall; hemorrhage; developed acute or chronic failure of the function of an organ or organ system.

Primary disease – a disease that, by itself or through its complications, necessitates primary medical care due to the greatest threat to working capacity, life, and health, leads to disability, or causes death.

Patient – an individual who receives medical care or who applies for medical care regardless of the presence of a disease and their condition.

Consequences (results) – disease outcomes, social and economic results of the application of medical technologies.

Symptom – any sign of a disease that can be determined regardless of the method used for this purpose.

Syndrome – a condition developing as a consequence of a disease and defined by a set of clinical, laboratory, and instrumental diagnostic signs that allow it to be identified and classified into a group of conditions with different etiologies but common pathogenesis, clinical manifestations, and general approaches to treatment, which nevertheless also depend on the diseases underlying the syndrome.

Condition is an alteration of the organism arising from the impact of pathogenic and/or physiological factors that requires medical care.

Concomitant disease – a disease that has no causal relationship with the primary disease, is secondary to it in terms of the need for medical care, impact on working capacity, and danger to life and health, and is not the cause of death.

Severity of a disease or condition – a criterion determining the extent of damage to human organs and/or body systems or the impairment of their functions caused by the disease, condition, or their complications.

Level of certainty of evidence – reflects the degree of confidence that the found effect of a medical intervention is true.

Function of an organ, tissue, cell, or group of cells – a property constituting a physiological process that realizes an action specific to the corresponding structural unit of the body.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Measles is an acute, highly contagious viral disease transmitted by airborne droplets and characterized by fever, intoxication symptoms, involvement of the respiratory tract and conjunctiva, and the presence of a maculopapular exanthema progressing to pigmentation [1-4].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The causative agent is the RNA-containing measles virus (Measles morbillivirus), which belongs to the family Paramyxoviridae, genus Morbillivirus. Viral particles are spherical in shape, 120-250 nm in diameter, with an outer villous envelope, a helical nucleocapsid, and hemagglutinin; they do not contain neuraminidase. The virus is characterized by hemagglutinating, hemolyzing, and complement-fixing activity, and it induces the formation of virus-neutralizing antibodies. The measles virus is unstable to physical and chemical factors, persists in the external environment for no more than 30 minutes, is sensitive to sunlight and ultraviolet radiation, and is inactivated by ether and formalin. It dies in saliva droplets within 30 minutes, and instantly upon drying, spreading over significant distances with air currents. It persists for several weeks at low temperatures, and remains active for 5 years at -70°C. The measles virus can be isolated from blood, nasopharyngeal swabs, urine, conjunctival discharge, and cerebrospinal fluid [1, 2].

The portals of entry for the measles virus are the mucous membrane of the upper respiratory tract and the eye conjunctiva. Primary replication of the virus occurs in the epithelial cells of the respiratory tract and regional lymph nodes. Next, the virus enters the bloodstream, resulting in the first wave of viremia during the incubation period. While in the blood, the virus fixes onto cells of the reticuloendothelial system, where its replication and secondary accumulation take place. This leads to a new wave of viremia with the maximum concentration of the virus in the blood, which corresponds to the clinical onset of the disease. The measles virus exhibits tropism for epithelial cells, CNS cells, and vascular endothelium, which determines the involvement of the skin, mucous membranes of the respiratory tract, and eye conjunctiva, as well as the development of meningitis and meningoencephalitis. The virus has a pronounced immunosuppressive effect, reducing the activity of specific and nonspecific defense factors (anergy), which leads to secondary viral or bacterial infection, the development of complications, and the exacerbation of chronic processes. The body's response to measles infection is the mobilization of defense reactions; there is an intensive production of interferons and the formation of cellular and humoral immunity, which leads to a decrease in viremia and the gradual elimination of the virus from the body by the end of the rash period. Specific IgM appear in the first days of the disease, followed shortly by specific IgG, the high titers of which persist for life [1-6].

1.3 Epidemiology of the Disease or Condition

The incidence of measles before the active immunization period was high, ranking among the top air-borne infections. The contagiousness index is very high, at 95-98%. The history of epidemiology preserves numerous examples of measles epidemics with a mortality rate of up to 25%. The viral etiology of measles infection was established in 1911, and the first virus strain was isolated from a patient in 1954 [1-4]. Following the introduction of active immunization into practice, the incidence dropped sharply. According to the World Health Organization, in 2022, following years of declining measles vaccination coverage, the number of measles cases rose by 18%, and deaths from the infection increased by 43% (compared to 2021). A new report by the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) estimates the number of cases at 9 million and deaths at 136,000, the majority of whom are children. The threat of measles to children continues to grow steadily. In 2022, large and severe outbreaks occurred in 37 countries compared to 22 countries in 2021. Twenty-eight outbreak-affected countries are in the WHO African Region, six in the Eastern Mediterranean, two in Southeast Asia, and one in Europe [7].

In 2022, 102 cases of measles were registered in the Russian Federation, with an incidence rate of 0.07 per 100,000 population; in 20% of cases, measles was imported from other countries. In 2022, measles was registered predominantly among children under 18 years of age, whose specific weight accounted for 63.7%, while adults accounted for 36.3% of cases. The measles epidemic process was sustained by unvaccinated individuals and those with unknown vaccination histories, who accounted for 82.4% of cases [8]. In 2023, a sharp increase in measles incidence was noted across all age groups [9].

The source of infection is a sick person who sheds the virus during the last days of the incubation period (the incubation period ranges from 9 to 21 days), during the prodromal period, and in the first 4 days of the rash. From the 5th day after the appearance of the rash, the patient is considered non-contagious. The transmission mechanism is aerosol-based, and the transmission route is airborne. The virus is released from the body during coughing, sneezing, lacrimation, and talking, and is carried by air currents over significant distances, including through ventilation ducts; therefore, infection is possible even without direct contact with a sick person. Lifelong lasting immunity is formed after the disease [1-4].

1.4 Features of Coding the Disease or Condition

International Classification of Diseases 10th Revision (ICD-10) [10].

B05 – Measles

B05.0 – Measles complicated by encephalitis (G05.1)

B05.1 – Measles complicated by meningitis (G02.0)

B05.2 – Measles complicated by pneumonia (J17.1)

B05.3 – Measles complicated by otitis media (H67.1)

B05.8 – Measles with other complications

B05.9 – Measles without complications

1.5 Classification of the disease or condition

There is no single approved classification of measles; the following option is most frequently used in clinical practice:

Clinical classification of measles [2-6]

By type:

1. Typical

2. Atypical:

- Mitigated

- Abortive

- Erased

- Asymptomatic

By severity:

1. Mild

2. Moderate

3. Severe

By clinical course:

1. Uncomplicated

2. Complicated:

- with complications

- with secondary infection superimposition

- with exacerbation of chronic diseases

1.6 Clinical presentation of the disease or condition

In a typical course of measles, four periods are distinguished: incubation, catarrhal (prodromal), rash (exanthem), and pigmentation. The incubation period of measles lasts 9-21 days. The initial period of the disease presents with catarrhal syndrome, typically lasting 3-4 days. The disease begins acutely with an increase in body temperature to 38-40^◦C, upper respiratory catarrhal symptoms (rhinitis, pharyngitis), conjunctivitis, photophobia, increasing signs of intoxication (headache, sharp deterioration in well-being, decreased appetite, sleep disturbance); younger children show pronounced restlessness. Catarrhal symptoms worsen over time, and laryngotracheitis develops. A pathognomonic symptom of the catarrhal period is Koplik spots (Belsky-Filatov-Koplik spots). They appear on the buccal mucosa opposite the molars as small whitish-gray dots surrounded by a hyperemic border. Their formation is associated with the presence of necrosis foci in the basal parts of the mucosa; this symptom appears 1-2 days before the rash and disappears with the development of the exanthem. By the end of the catarrhal period, the patient's well-being may improve slightly.

The rash period begins on days 4-5 from the onset of the disease. The rash appears in stages. The first elements of the rash appear behind the ears and on the bridge of the nose; within the first day, the rash spreads to the face, neck, upper chest, and shoulders; on the 2nd day, the rash covers the torso; and on the 3rd-4th days, the distal parts of the upper extremities and lower extremities. The rash is maculopapular, initially small, then the elements increase in size, merge, become bright, and acquire a typical appearance—irregularly shaped, large maculopapular elements of a bright red color.

The pigmentation period begins on the 3rd-4th day of the rash and also proceeds in stages. The rash begins to acquire a cyanotic-brownish tint. The pigmentation period lasts 7-14 days; fine branny desquamation may occur. The patient's general condition improves, temperature normalizes, and the severity of catarrhal symptoms decreases [2-6, 11].

Severity criteria are presented in the appendix.

Measles anergia (secondary immunodeficiency state) persists for a long time, up to 1 month, which is a risk factor for the superimposition of other viral-bacterial infections and the development of complications [12-14].

Mitigated measles: develops in patients who received immunoglobulins, plasma, blood, and blood products during the incubation period. The duration of periods is shortened, and symptoms are mild. The total duration of the disease is several days.

Abortive form: begins typically; 1-2 days after the onset of the disease, clinical symptoms disappear, and the rash is localized on the face and torso.

Erased form: characterized by mild, rapidly passing symptoms of intoxication and catarrhal phenomena.

Asymptomatic form: disease manifestations are absent.

Atypical forms of the disease are typically detected in outbreak foci when examining contacts.

Features of measles in various age groups: in infants in the first 6 months of life, the catarrhal period is short and less pronounced, Belsky-Filatov-Koplik spots may be absent, the rash period is shortened to 2 days, and the pigmentation period is 5-7 days. Measles anergia is pronounced, and complications develop rapidly (pneumonia, otitis media, encephalitis).

Measles in unvaccinated adults proceeds in a typical form, often with more severe clinical symptoms.

Measles in vaccinated individuals: occurs in individuals in whom specific antibodies have not formed or their levels have dropped below the protective threshold; typically runs a milder course.

Complications: can develop at any stage of the infectious disease. Depending on the etiological factor, proper measles complications caused by the measles virus (primary specific) and non-specific (secondary) caused by other pathogens are distinguished. According to the timing of development, complications are divided into early and late (developing during the pigmentation period).

One of the most frequent complications is pneumonia; acute otitis media and sinusitis frequently develop; furthermore, keratitis/keratoconjunctivitis and gastrointestinal complications may occur. A severe complication is measles encephalitis (meningoencephalitis), which develops on the 4th-5th day after the appearance of the rash or later, and is characterized by a severe course and a high risk of an unfavorable (fatal) outcome [2-6, 15-21].

Differential diagnosis is carried out with the following diseases (conditions): rubella, adenovirus infection, enterovirus infection, parvovirus B19 infection, herpesvirus HHV-6 infection, scarlet fever, toxic-allergic reaction (rash), infectious mononucleosis [2-6, 22].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition:

At the diagnostic stage, measles cases are divided into "suspected", "probable", and "confirmed"^[1]. A "suspected" case is defined as an acute illness with one or more typical clinical signs of measles. A "probable" case is an acute illness presenting with clinical signs of measles and an epidemiological link to another suspected or confirmed case of the disease. A "confirmed" case of measles is classified as "suspected" or "probable" after laboratory confirmation of the diagnosis.

The final diagnosis of measles is established based on clinical data in the presence of laboratory confirmation of the diagnosis.

Comment: Details regarding contact with a measles patient, presence in a measles focus, history of measles vaccination, and administration of immunoglobulin are to be clarified.

^[1]SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" dated January 28, 2021

2.1 Complaints and Anamnesis

Complaints and medical history are described in the section "Clinical Presentation".

2.2 Physical Examination

Comments: A general examination is performed with an assessment of the skin and visible mucous membranes: presence and characteristics of the rash, color (hyperemia, pallor, cyanosis), moisture, edema, presence of Filatov-Belsky-Koplik spots, presence of conjunctivitis, and other symptoms from the respiratory, cardiovascular, and gastrointestinal systems; the severity of the patient's condition is determined based on the aggregate data

Comments: A typical form is characterized by an increase in body temperature up to 38–39˚C from the first days of the illness. On the 2nd–3rd day of the disease, the temperature drops, sometimes to subfebrile levels. On the 4th–5th day, a second wave of fever may occur along with the appearance of the rash.

Comments: the examination is necessary to assess the level of respiratory tract involvement, to identify characteristic changes in bronchitis, bronchoobstructive syndrome, or the appearance of local symptoms typical of pneumonia. In the first 3–4 days, viral lung lesions are possible, while from the 5th day onwards, predominantly bacterial lesions occur.

Comments: Complications of measles include various variants of central nervous system involvement: encephalitis, meningoencephalitis, encephalomyelitis.

Comments: viral infections, including measles, can lead to cardiac damage; these examination methods are necessary to diagnose possible complications of measles: cardiomyopathy, endocarditis, heart rhythm changes due to conduction disorders.

Comments: complications in the form of stomatitis, enteritis, and enterocolitis are possible with measles.

2.3 Laboratory Diagnostics

2.3.1. Nonspecific laboratory diagnostics

Comments: uncomplicated measles is characterized by leukopenia, neutropenia, eosinopenia, relative lymphocytosis, and an unchanged erythrocyte sedimentation rate (ESR). In bacterial complications (pneumonia, sinusitis, etc.), blood tests show increasing leukocytosis, stab neutrophilia, and an elevated ESR.

Comments: in an uncomplicated course of measles, there are no pathological changes; in cases of pronounced fever and intoxication syndrome, there is an increase in urine specific gravity, mild transient leukocyturia, proteinuria, and cylindruria, which disappear when body temperature normalizes and general infectious intoxication symptoms resolve. Persistence of changes requires the exclusion of tubulointerstitial nephritis and other renal disorders.

Comments: in patients with measles infection during the rash period from the 4th to the 8th day of the disease, an increase in liver enzyme activity (ALT, AST) is possible as a manifestation of cytolysis syndrome in the development of a moderately severe and severe course of the disease, with normalization during the convalescence period.

2.3.2. Specific laboratory diagnostics

Specific laboratory testing is performed to identify the pathogen and confirm the diagnosis in individuals with clinical signs of measles ("suspected case") or clinical signs of measles and an epidemiological link to other suspected or confirmed measles cases ("probable measles case"); individuals who have had contact with a measles patient; and newborns whose mothers had measles in the end of the third trimester of pregnancy (2-3 weeks before delivery) [27, 35-37].

Comments: PCR is the most effective laboratory diagnostic method that allows the detection of measles virus RNA in the naso- and oropharynx even during the incubation period, 3-5 days before the clinical signs of the disease (rash) appear. The optimal time for collecting clinical material for molecular biological testing is within 3-5 days after the manifestation of the disease or on the first day of hospitalization. A sample for primary testing using PCR methods is collected from a single patient. For individuals who have been in contact with a measles patient, it is advisable to take the first sample for molecular biological testing 5-7 days after contact in order to identify the pathogen. All types of work are carried out in compliance with the anti-epidemic regime and in strict accordance with the requirements of current regulatory and methodological documents. The rules for swab collection are presented in Appendix A3.

Comments: Since maternal antibodies against measles may be present in the blood of newborns, the use of ELISA to confirm a diagnosis of measles in a child is impractical; the molecular biological method for detecting measles virus RNA is preferred.

Comments: The optimal time for blood collection for testing is on the 4th-5th calendar day from the moment the rash appears (1st blood sample) and no earlier than 10-14 calendar days from the date of collection of the first sample (2nd blood sample). All types of work are carried out in compliance with the anti-epidemic regime and in strict accordance with the requirements of current regulatory and methodological documents.

Comments: performed in addition to the determination of class M antibodies in blood serum by enzyme-linked immunosorbent assay (ELISA). The optimal time for blood sampling is the 4th–5th calendar day from the onset of the rash (1st blood sample) and no earlier than 10–14 calendar days from the date of the first sample collection (2nd blood sample). A 4-fold or greater rise in the titer of specific IgG antibodies upon simultaneous testing of paired blood sera in standard serological tests is the basis for establishing a diagnosis of measles.

In accordance with Order No. 4 of the Chief State Sanitary Doctor of the Russian Federation dated January 28, 2021 (as amended on May 25, 2022) "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'" (together with "SanPiN 3.3686-21. Sanitary Rules and Norms..."), clause 2734: The molecular genetic method is used to determine the genotype of the measles or rubella pathogen to detect imported cases of measles/rubella and prove the elimination of these infections in the country, as well as the absence of circulation of endemic measles/rubella virus genotypes. For this purpose, clinical material samples (urine, nasopharyngeal swabs, cerebrospinal fluid) are collected on the 1st–3rd calendar day from the onset of the patient's rash for testing. Material collection is carried out by medical staff of the medical organization where the patient is hospitalized, or in case of home monitoring, by medical staff of the medical organization that made the diagnosis.

^[1]SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" dated January 28, 2021

2.4 Instrumental Diagnostics

Instrumental diagnostic tests are associated with the specific course of the disease in patients and are most often necessitated by the development of complications and exacerbations of chronic comorbid conditions.

Comments: the test is recommended for patients with moderate and severe measles, a history of congenital heart disease, cardiomyopathies, or myocarditis, as well as those with clinical signs of arrhythmia and other heart diseases.

Comments: Chest X-ray is performed in all cases of suspected pneumonia to confirm the diagnosis.

Comments: In cases of viral pneumonia, the process is interstitial in nature and therefore may not be detected by X-ray examination.

2.5 Other Procedures

Comments: An examination by a neurologist with appropriate diagnostic tests is necessary to rule out neurological complications of measles (encephalitis, meningoencephalitis, encephalomyelitis).

If complications or comorbid conditions are identified, their treatment is carried out in accordance with current clinical guidelines or treatment protocols/methodological recommendations/rules of syndromic therapy for the respective nosological groups.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Specific treatment for measles has not been developed. Treatment tactics are influenced by the following factors: disease severity; leading clinical manifestations and specific features of the disease course, taking into account signs of immunodeficiency; patient age; presence and nature of complications and comorbid conditions; period of the disease; availability and feasibility of providing treatment in accordance with the required type of medical care.

3.1 Conservative Treatment

Bed rest must be maintained throughout the entire febrile period and for the first two days after normalization of body temperature. Failure to comply with bed rest increases the risk of complications.

The diet is prescribed taking into account the patient's age, disease severity, and the presence and nature of comorbid conditions. Fluid intake is prescribed based on physiological needs plus ongoing pathological losses (hyperthermia, tachypnea, etc.). Infants in their first year of life are breastfed or receive adapted formulas as indicated (depending on age and somatic status).

Comments: No special comparative studies have been conducted regarding the treatment efficacy for measles; there are case reports describing the use of these drugs for measles as antiviral treatment. The use of interferons is most effective within the first 3 days of disease onset. (The drug is prescribed at 150,000–500,000 IU for children under 7 years of age, 500,000–1,000,000 IU for children aged 7–12 years, and 1,000,000 IU for children over 12 years and adults, 2 times a day with a 12-hour interval for 5–10 days.)

• To reduce body temperature in patients with measles, nonsteroidal anti-inflammatory and antirheumatic drugs are recommended [2-6].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: In children, nonsteroidal anti-inflammatory and antirheumatic drugs are used exclusively on the basis of preparations containing paracetamol** up to 60 mg/kg/day or ibuprofen** up to 30 mg/kg/day. Paracetamol** and ibuprofen** can be administered per os or as rectal suppositories; paracetamol** for intravenous administration is also available.

Comments: Parenteral fluid administration is carried out based on calculated physiological requirements, ongoing pathological losses, and existing fluid deficits.

• To prevent bacterial superinfection, the use of systemic antimicrobial drugs is not recommended in patients with measles [50, 51].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Antibacterial therapy in uncomplicated viral infection not only fails to prevent bacterial superinfection but actually promotes its development due to the suppression of normal human flora in various biotopes.

3.2 Other Treatment

Patients with measles may receive local treatments in the form of gargles, warm drinks, insufflations, inhalations, lozenges and troches for resorption, and physiotherapeutic procedures to reduce local inflammation, pain severity, prevent secondary infection of the damaged oropharyngeal mucosa, and provide symptomatic therapy.

In addition, therapy taking into account identified complications and comorbid conditions is indicated as prescribed by a physician.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Medical rehabilitation for patients with measles has not been currently developed and is carried out in accordance with the patient's somatic features. Measles, as an acute disease, is a contraindication for sanatorium-resort treatment.

Medical rehabilitation of measles convalescents may be carried out in medical organizations of the state healthcare system or specialized structural subdivisions of medical organizations, including restorative medicine and rehabilitation centers, as well as through sanatorium-resort treatment.

5. Prevention and Dispensary Observation

Comments: Children not vaccinated against measles (under the vaccination age, or who have not received vaccination due to medical contraindications or refusal of vaccination) shall be administered normal human immunoglobulin** (hereinafter referred to as immunoglobulin) no later than the 5th calendar day from the moment of contact with a patient, in accordance with the instructions for its use^[1].

The main method of protecting the population against measles is vaccination prophylaxis.

Dispensary observation is carried out at the place of residence by a district pediatrician / district general practitioner / general physician. The observation plan is drawn up individually depending on the form of past measles, the presence of complications, and the somatic status of the patient.

^[1] SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" dated January 28, 2021

6. Organization of Medical Care

Medical care for patients with measles is provided in the following forms:

• primary health care;

• emergency medical care, including specialized emergency medical care;

• specialized medical care, including high-tech medical care.

Medical care for patients with measles can be provided in the following settings:

• outpatient (in settings not requiring round-the-clock medical observation and treatment)

• day hospital (in settings providing medical observation and treatment during the day, not requiring round-the-clock medical observation and treatment) – at the stage of convalescence (no earlier than the 5th day after the onset of the rash) and rehabilitation;

• inpatient (in settings providing round-the-clock medical observation and treatment, as well as isolation in a Melzer box)

Indications for hospital admission to a medical organization:

Patients with measles are subject to hospitalization in an infectious diseases hospital (infectious diseases department, infectious diseases beds) in cases of:

- severe and/or complicated clinical course of the disease;

- presence of severe chronic diseases;

- regardless of the clinical form of the disease: individuals from organizations with round-the-clock stay for children or adults; individuals living in dormitories and unfavorable living conditions (including communal apartments); if there are individuals from decreed population groups among the patient's family members (workers of medical institutions, public catering, trade, educational organizations, transport, communal and social sectors, shift workers, and employees of state control bodies at checkpoints across the state border of the Russian Federation) who have not had measles and are unvaccinated.

Referrals for the hospitalization of patients with measles (or suspected of this infection), along with personal data, must indicate the initial symptoms of the disease, information on the treatment and preventive vaccinations performed, as well as epidemiological history data.

Patients are hospitalized in infectious diseases hospitals/departments (beds) in Melzer boxes. Children are hospitalized in hospitals equipped with resuscitation and intensive care units.

Indications for hospitalization in a resuscitation and intensive care unit are severe and complicated forms of measles with pronounced symptoms of intoxication syndrome, respiratory and cardiovascular failure, and cerebral disorders.

Indications for discharging a patient from a medical organization:

1) satisfactory patient status

2) no earlier than the 5th day after the onset of the rash

7. Additional Information

Measles is a vaccine-preventable infection. The main method of protecting the population against measles is vaccination prophylaxis [52]. To ensure population immunity against measles sufficient to prevent the spread of infection among the population, the vaccination coverage of the population in the territory of the municipal formation must be: vaccination and revaccination against measles for children at decreed ages – at least 95%; vaccination against measles for adults aged 18-35 years – at least 90%; vaccination against measles for individuals in decreed professions aged 18-55 years – at least 90%^[1].

A decrease in the immune layer leads to the formation of disease outbreaks. Vaccination against measles in the Russian Federation is carried out in accordance with the National Schedule of Preventive Vaccinations.

Routine measles vaccination prophylaxis

• Any vaccines containing the measles component can be used for measles vaccination: monovaccine (measles vaccine**), divaccine (measles and mumps vaccine**), combined vaccines (measles, rubella and mumps vaccine**), regardless of age (but not earlier than 8-12 months of life in accordance with the Instructions for use of the drug), the presence of post-vaccination or post-infection immunity to mumps and/or rubella viruses

• Routine vaccination is carried out in accordance with the national schedule of preventive vaccinations and the schedule of preventive vaccinations according to epidemic indications (Order of the Ministry of Health of the Russian Federation No. 1122-n dated December 6, 2021): vaccination at 12 months of age, revaccination at 6 years.

• Children aged 1 year to 5 years 11 months 29 days who have not had measles, have not been vaccinated against measles, or do not have documentary confirmation must receive one dose of measles vaccine (ATC J07BD Measles vaccines) at any age after 12 months and receive a measles revaccination at age 6 with a minimum interval of 3 months after the first vaccination (Letter of the Ministry of Health of the Russian Federation dated January 21, 2022, No. 15-2/I/2-806 On the distribution of methodological recommendations for conducting preventive vaccinations in accordance with the Order of the Ministry of Health of the Russian Federation dated December 6, 2021, No. 1122n "On approval of the national schedule of preventive vaccinations, the schedule of preventive vaccinations according to epidemic indications and the procedure for conducting preventive vaccinations").

• Children aged 6 years to 17 years 11 months 29 days who have not had measles, have not been vaccinated against measles, or do not have documentary confirmation must be vaccinated with the measles vaccine (ATC J07BD Measles vaccines) twice with a minimum interval of 3 months.

• Children aged 6 years to 17 years 11 months 29 days who have been vaccinated against measles once and have not had measles must receive a second dose of the measles vaccine (ATC J07BD Measles vaccines) with a minimum interval of 3 months after the first administration

• Children born to mothers seronegative for the measles virus are vaccinated at the age of 8 months (with Measles vaccine** as a monopreparation – see the drug instructions) and further at 14-15 months and 6 years (using any vaccines containing the measles component – divaccine, trivaccine). The interval between the first vaccination and the repeat vaccination must be at least 6 months (instructions for Measles vaccine** MA No. LP-No.(001169)-(RG-RU)

• Adults aged 18 to 35 years (inclusive) who have not had measles, have not been vaccinated / in the absence of data on previously performed vaccination / or past measles / or absence of confirmation of robust immunity to measles infection* – must be vaccinated twice with a minimum interval of 3 months; those previously vaccinated against measles once more than 3 months ago must receive one dose of the vaccine.

• Adults aged 36 to 55 years (inclusive) belonging to occupational risk groups (medical workers and employees of educational organizations, employees engaged in trade, transport services, communal and social sectors; shift workers and employees of state control bodies at checkpoints across the border of the Russian Federation), as well as labor migrants, refugees, homeless individuals in the absence of data on previously performed vaccination / or past measles / or absence of confirmation of robust immunity to measles infection* – twice with a minimum interval of 3 months; those previously vaccinated against measles once more than 3 months ago must receive one dose of the vaccine**.

• Children under 8 months of age, as well as children and adults with absolute contraindications to vaccination with live vaccines (primary immunodeficiency, malignant neoplasms, pregnancy), in case of contact with a measles patient, receive normal human immunoglobulin** (solution for intramuscular injection) in accordance with the Instructions for Use.

Vaccination according to epidemic indications

For immunization, immunobiological medicinal products (IBMP) registered and approved for use on the territory of the Russian Federation in accordance with their instructions for use are used.

Information on performed preventive vaccinations is entered into medical accounting documents, on the basis of which federal state observation forms are generated: form No. 5.

• is carried out in accordance with Sanitary Rules and Norms SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases"

• Immunization against measles according to epidemic indications is subject to individuals of any age who have had contact with a patient (suspected of having the disease), have not had measles before, are unvaccinated, have no information about measles vaccinations, as well as individuals over 6 years of age vaccinated against measles once.

• Immunization against measles based on epidemiological indications is carried out within the first 72 hours from the moment a patient is identified. When expanding the boundaries of a measles focus (at the workplace, place of study, within a district or settlement), the immunization timeline may be extended up to 7 calendar days from the moment the first patient in the focus is identified.

• Children and adults not vaccinated against measles (who have not reached the vaccination age or have not received vaccination due to medical contraindications or refusal of vaccination) shall be administered normal human immunoglobulin** (solution for intramuscular injection) (hereinafter referred to as immunoglobulin) in accordance with its instructions for use no later than the 5th calendar day from the moment of contact with a patient.

• Information on vaccinations performed and the administration of immunoglobulin (date, name of the medicinal product, dose, batch number, control number, shelf life, date of manufacture, manufacturing enterprise) is entered into accounting forms in accordance with the requirements for the organization of vaccine prophylaxis.

• Children who received vaccinations within the framework of the National Schedule of Preventive Vaccinations and in whose blood serum antibodies to measles are not detected in standard serological tests undergo additional vaccine administration in accordance with the instructions for use of immunobiological medicinal products (ATC J06 Immune sera and immunoglobulins).

• Considering the possibility of carrying out emergency prophylaxis of measles using monovaccine in children (Measles vaccine**), as a priority under conditions of epidemiological disadvantage for measles infection, subsequent vaccination against rubella and mumps is permitted in accordance with Order of the Russian Ministry of Health No. 1122n dated December 6, 2021, "On Approval of the National Schedule of Preventive Vaccinations and the Schedule of Preventive Vaccinations by Epidemiological Indications" using monovaccines (Measles vaccine** and Rubella vaccine** simultaneously) with a minimum interval of 1 month, or Measles, mumps and rubella vaccine** or Measles and mumps vaccine** combined with rubella vaccine** with a minimum interval of 3 months after the measles vaccine**. In the latter case, vaccination against measles may be counted as routine re-vaccination (V2) (Letter of the Ministry of Health of the Russian Federation dated July 14, 2023, No. 15-2/I/2-12676 On the issuance of recommendations for vaccination against measles in children of various ages using mono- and multicomponent vaccines, August 17, 2023).

^[1]SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" dated January 28, 2021

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Alodzhants E.A. – Assistant at the Department of Adult Infectious Diseases and Epidemiology, Federal State Budgetary Educational Institution of Higher Education "Saint Petersburg State Pediatric Medical University" of the Russian Ministry of Health

2. Babachenko I.V. – D.Sc. in Medicine, Professor, Head of the Research Department of Droplet Infections, Scientific Research Institute of Children's Infections, Federal Medical-Biological Agency of Russia; Professor, Department of Infectious Diseases in Children, Faculty of Postgraduate and Additional Professional Education, Saint Petersburg State Pediatric Medical University, Russian Ministry of Health; Member, Euro-Asian Society for Infectious Diseases

3. Basina V.V. – Ph.D. in Medicine, Associate Professor, Department of Adult Infectious Diseases and Epidemiology, Saint Petersburg State Pediatric Medical University, Russian Ministry of Health

4. Bogoslovskaya E.V. – D.Sc. in Medicine, Head of the Laboratory for Gene Therapy Development Methods, Center for Strategic Planning, Federal Medical-Biological Agency of Russia

5. Gorelov A.V. – D.Sc. in Medicine, Professor, Academician of the Russian Academy of Sciences, Deputy Director for Scientific Work, Central Research Institute of Epidemiology, Rospotrebnadzor; Chairman of the Board, Academician V.I. Pokrovsky National Association of Infectious Disease Specialists; Head of the Department of Infectious Diseases and Epidemiology, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Russian Ministry of Health

6. Gorodin V.N. – D.Sc. in Medicine, Professor, Head of the Department of Infectious Diseases and Epidemiology, Faculty of Advanced Training and Professional Retraining, Kuban State Medical University, Russian Ministry of Health; Chief Physician, Infectious Diseases Hospital No. 2 of the Ministry of Health of Krasnodar Krai; Chief Freelance Specialist in Infectious Diseases of the Ministry of Health of the Russian Federation in the Southern Federal District

7. Zhdanov K.V. – D.Sc. in Medicine, Corresponding Member of the Russian Academy of Sciences, Professor, Director of the Scientific Research Institute of Children's Infections, Federal Medical-Biological Agency of Russia; Chief Freelance Specialist in Infectious Diseases, Healthcare Committee of Saint Petersburg; Deputy President, Euro-Asian Society for Infectious Diseases

8. Lobzin Yu.V. – D.Sc. in Medicine, Academician of the Russian Academy of Sciences, President of the Scientific Research Institute of Children's Infections, Federal Medical-Biological Agency of Russia; Chief Freelance Specialist in Infectious Diseases in Children of the Ministry of Health and Federal Medical-Biological Agency of Russia; President, Euro-Asian Society for Infectious Diseases

9. Novak K.E. – Ph.D. in Medicine, Associate Professor, Department of Adult Infectious Diseases and Epidemiology, Saint Petersburg State Pediatric Medical University, Russian Ministry of Health

10. Nosova A.O. – Junior Researcher, Laboratory for Gene Therapy Development Methods, Center for Strategic Planning, Federal Medical-Biological Agency of Russia

11. Pozdnyakova M.G. – Ph.D. in Medicine, Senior Researcher, Laboratory for Testing New Protective Agents against Viral Infections, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation; Associate Professor, Department of Adult Infectious Diseases and Epidemiology, Saint Petersburg State Pediatric Medical University, Russian Ministry of Health

12. Ponezheva Zh.B. – D.Sc. in Medicine, Associate Professor, Head of the Clinical Department of Infectious Pathology, Central Research Institute of Epidemiology, Rospotrebnadzor

13. Rychkova S.V. – D.Sc. in Medicine, Associate Professor, Head of the Medical Care Organization Department, Scientific Research Institute of Children's Infections, Federal Medical-Biological Agency of Russia

14. Tarasova Zh.E. – Ph.D. in Medicine, Head of the Production Laboratory, Center for Strategic Planning, Federal Medical-Biological Agency of Russia

15. Usenko D.V. – D.Sc. in Medicine, Associate Professor, Leading Researcher, Clinical Department of Infectious Pathology, Central Research Institute of Epidemiology, Rospotrebnadzor; Head of the Educational Center, Executive Director, Academician V.I. Pokrovsky National Association of Infectious Disease Specialists

16. Kharit S.M. – D.Sc. in Medicine, Head of the Research Department of Vaccination and Post-Vaccination Pathology, Scientific Research Institute of Children's Infections, Federal Medical-Biological Agency of Russia; Chief Freelance Specialist in Vaccine Prophylaxis, Healthcare Committee of Saint Petersburg

17. Chulanov V.P. – D.Sc. in Medicine, Professor, Deputy Director for Scientific Work and Innovative Development, National Medical Research Center of Phthisiopulmonology and Infectious Diseases, Ministry of Health of the Russian Federation

18. Shipulin G.A. – Ph.D. in Medicine, Director of the Center for Post-Genomic Technologies, Center for Strategic Planning, Federal Medical-Biological Agency of Russia

19. Esaulenko E.V. – D.Sc. in Medicine, Professor, Head of the Department of Adult Infectious Diseases and Epidemiology, Saint Petersburg State Pediatric Medical University, Russian Ministry of Health; Member, Euro-Asian Society for Infectious Diseases, National Scientific Society of Infectionists; Head of the Laboratory of Viral Hepatitis, Pasteur Research Institute of Epidemiology and Microbiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being

No conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

The evidence base for the recommendations includes publications included in the Cochrane Library, EMBASE, MEDLINE, Clinicalkey ELSEVIER databases, and the electronic library (www.elibrary.ru). The search depth was 20 years

Methods used to assess the quality and strength of evidence: - expert consensus; - assessment of significance in accordance with the levels of evidence and grades of recommendation.

Target audience for these clinical guidelines:

• anesthesiologist-intensivist;

• bacteriologist;

• virologist;

• disinfectologist;

• health station physician;

• infectious disease physician;

• clinical laboratory diagnostics physician;

• clinical pharmacologist;

• laboratory physician;

• neurologist;

• general practitioner (family physician);

• pediatrician;

• municipal (district) pediatrician;

• primary care pediatrician;

• medical prevention physician;

• medical rehabilitation physician;

• admitting department physician;

• internist;

• adolescent therapist;

• district general practitioner;

• epidemiologist.

Table 1. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading levels of recommendation certainty (LRC) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

1. Federal Law No. 52-FZ of March 30, 1999 (as amended on July 24, 2023) "On the Sanitary and Epidemiological Welfare of the Population"

2. Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021 (as amended on May 25, 2022) "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'" (along with "SanPiN 3.3686-21. Sanitary Rules and Norms...") (Registered with the Ministry of Justice of Russia on February 15, 2021, No. 62500), clauses XXXV. Prevention of measles, rubella, mumps.

3. Order of the Ministry of Health of Russia No. 1122n dated December 6, 2021 "On Approval of the National Schedule of Preventive Vaccinations, the Schedule of Preventive Vaccinations by Epidemiological Indications, and the Procedure for Conducting Preventive Vaccinations" (Registered with the Ministry of Justice of Russia on December 20, 2021, No. 66435)

4. Order of the Ministry of Health and Social Development of Russia No. 521n dated May 5, 2012 (as amended on February 21, 2020) "On approval of the Procedure for providing medical care to children with infectious diseases" (Registered with হওয়ার the Ministry of Justice of Russia on July 10, 2012, No. 24867)

5. Order of the Ministry of Health and Social Development of Russia No. 69n dated January 31, 2012 (as amended on February 21, 2020) "On Approval of the Procedure for Providing Medical Care to Adult Patients with Infectious Diseases" (Registered with the Ministry of Justice of Russia on April 4, 2012, No. 23726)

6. Order of the Russian Ministry of Health No. 804n dated October 13, 2017 (as amended on September 24, 2020, with rev. as of October 26, 2022) "On Approval of the Nomenclature of Medical Services" (Registered with the Ministry of Justice of Russia on November 7, 2017, No. 48808)

7. Order of the Ministry of Health of Russia No. 302n dated May 16, 2019 (as amended on November 19, 2020) "On Approval of the Procedure for Minors Undergoing Dispensary Observation, Including During the Period of Education and Upbringing in Educational Organizations" (Registered with the Ministry of Justice of Russia on June 7, 2019, No. 54887)

8. Order of the Ministry of Health of Russia No. 168n dated March 15, 2022 "On Approval of the Procedure for Conducting Dispensary Observation of Adults" (Registered with the Ministry of Justice of Russia on April 21, 2022, No. 68288)

9. MR 4.2.0287-22. 4.2. Methodological Recommendations. Control Methods. Biological and Microbiological Factors. Organization of Internal Quality Control in Laboratories Conducting Testing for Specific Antibodies to Measles Virus by Enzyme-Linked Immunosorbent Assay" (approved by Rospotrebnadzor on May 30, 2022)

10. Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 1 dated February 8, 2023 "On Conducting Catch-Up Immunization Against Measles in the Territory of the Russian Federation" (registered by the Ministry of Justice of Russia on March 7, 2023, reg. No. 72548)

11. Clinical Guidelines – Community-Acquired Pneumonia in Adults – 2021-2022-2023 (August 25, 2021) – Approved by the Ministry of Health of the Russian Federation

12. Clinical Guidelines – Pneumonia (Community-Acquired) – 2022-2023-2024 (January 18, 2022) – Approved by the Ministry of Health of the Russian Federation

Rules for taking nasopharyngeal and oropharyngeal swabs

To study biological material from a patient, nasopharyngeal and oropharyngeal swabs should be taken.

Nasopharyngeal and oropharyngeal swabs are recommended to be combined in a single tube and studied as a single sample. To do this, swabs are taken with different probes, first from the mucous membrane of the inferior nasal meatus and then from the oropharynx; the working ends of the probes after sampling are placed into a single tube containing 0.5 ml of transport medium for the storage and transportation of respiratory swabs and studied as a single sample.

Swabs from the mucous membrane of the inferior nasal meatus.

If the nasal cavity is filled with mucus, it is recommended to blow the nose before the procedure. Dry sterile polystyrene probes with viscose swabs are used for sampling. The probe is inserted with a gentle movement along the outer wall of the nose to a depth of 2-3 cm up to the inferior nasal concha, lowered slightly downward, inserted into the inferior nasal meatus under the inferior nasal concha to the nasopharynx, rotated, and removed along the outer wall of the nose. The total insertion depth should be approximately half the distance from the nostril to the ear opening (5-6 cm). After sampling, the swab (the working part of the probe with the viscose swab) is placed into a tube with 0.5 ml of transport medium for the storage and transportation of respiratory swabs. The end of the probe is broken off while holding the tube cap so that the tube can be tightly closed. The tube containing the solution and the working part of the probe is closed and labeled.

Swabs from the posterior oropharyngeal wall.

Samples are taken with dry sterile probes with viscose swabs using rotational movements from the surface of the tonsils, palatine arches, and the posterior oropharyngeal wall. After sampling, the swab (the working part of the probe with the viscose swab) is placed into a sterile disposable tube containing 0.5 ml of transport medium along with the nasopharyngeal swab probe. The end of the probe is broken off while holding the tube cap so that the tube can be tightly closed. The tube with the solution and the working part of the probe is closed and labeled. Storage of the material prior to testing is permitted for up to 3 days at temperatures from 2 to 8 °C, or long-term at temperatures from minus 24 to minus 16 °C. Storage of the material prior to testing is permitted for up to 3 days at temperatures from 2 to 8 °C, or long-term at temperatures from minus 24 to minus 16 °C.

Immunobiological agents for the prevention of measles registered in the Russian Federation

Table 1

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Measles is an acute, highly contagious viral disease transmitted by airborne droplets and characterized by fever, intoxication symptoms, respiratory tract and conjunctival involvement, and a maculopapular rash progressing to pigmentation. The source of infection is a sick person who sheds the virus in the final days of the incubation period (the incubation period ranges from 9 to 21 days), during the prodromal period, and in the first 4 days of the rash. From the 5th day after the onset of the rash, the patient is considered non-contagious. The transmission route is airborne. The virus is released from the body during coughing, sneezing, and talking, and is carried by air currents over significant distances, including through ventilation ducts; therefore, infection is possible even without direct contact with a sick person. Lifelong lasting immunity is formed after the disease. Complications can develop at any stage of the infection. Depending on the etiological factor, proper measles complications caused by the measles virus (primary specific) and non-specific (secondary) complications caused by other pathogens are distinguished. According to the time of development, complications are divided into early and late (developing during the pigmentation period). One of the most frequent complications is pneumonia; acute otitis media and sinusitis frequently develop, and gastrointestinal complications are possible. A severe complication is measles encephalitis (meningoencephalitis), which develops on the 4th–5th day after the appearance of the rash or later, and is characterized by a severe course and a high risk of an unfavorable outcome. Measles is a vaccine-preventable infection. Both adults and children are affected. Vaccine prophylaxis is performed for children and adults. In vaccinated individuals who contract the disease, measles runs a milder course.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Criteria for assessing the severity of the disease based on clinical signs [43]