Lesson 3

Lesson_2_Differential diagnosis and emergency states in children’s respiratory infectious diseases

 

INFECTIOUS MONONUCLEOSIS (EPSTAIN – BARR VIRUS

INFECTION)

 

Infectious mononucleosis is the best-known clinical syndrome caused by Epstein-Barr virus (EBV). It is characterized by systemic somatic complaints consisting primarily of fatigue, malaise, fever, sore throat, and generalized lymphadenopathy. Originally described as glandular fever, it derives its name from the mononuclear lymphocytosis with atypical-appearing lymphocytes that accompany the illness. Other less common infections may cause infectious mononucleosis–like illnesses.

 

ETIOLOGY. 

 

 

EBV, a member of the Herpesviridae, causes more than 90% of infectious mononucleosis cases. Approximately 5–10% of infectious mononucleosis–like illnesses are caused by primary infection with cytomegalovirus, Toxoplasma gondii, adenovirus, viral hepatitis, human immunodeficiency virus (HIV), and possibly rubella virus. In the majority of EBV-negative infectious mononucleosis–like illnesses, the exact cause remains unknown.

 

EPIDEMIOLOGY.

 

The epidemiology of infectious mononucleosis is related to the epidemiology and age of acquisition of EBV infection. EBV infects up to 95% of the world’s population. It is transmitted in oral secretions by close contact such as kissing or exchange of saliva from child to child, such as occurs between children in out-of-home child care. Nonintimate contact, environmental sources, or fomites do not contribute to spread of EBV.

 

EBV is shed in oral secretions for 6 mo or longer after acute infection and then intermittently for life. Healthy individuals with serologic evidence of past EBV infection excrete virus 10–20% of the time. Immunosuppression may permit reactivation of latent EBV; approximately 60% of seropositive, immunosuppressed patients shed the virus. EBV is also found in the genital tract of women and may possibly be spread by sexual contact.

 

Infection with EBV in developing countries and among socioeconomically disadvantaged populations of developed countries usually occurs during infancy and early childhood. In central Africa, almost all children are infected by 3 yr of age. Primary infection with EBV during childhood is usually inapparent or indistinguishable from other childhood infections; the clinical syndrome of infectious mononucleosis is practically unknown in undeveloped regions of the world. Among more affluent populations in industrialized countries, infection during childhood is still most common, but approximately one third of cases occur during adolescence and young adulthood. Primary EBV infection in adolescents and adults is manifest in 50% or more of cases by the classic triad of fatigue, pharyngitis, and generalized lymphadenopathy, which constitute the major clinical manifestations of infectious mononucleosis. This syndrome may be seen at all ages but is rarely apparent in children younger than 4 yr, when most EBV infections are asymptomatic, or in adults older than 40 yr, when most individuals have already been infected by EBV. The true incidence of the syndrome of infectious mononucleosis is unknown but is estimated to occur in 20–70 of 100,000 persons per year; in young adults the incidence rises to about 1 in 1,000 persons per year. The prevalence of serologic evidence of past EBV infection increases with age; almost all adults in the United States are seropositive.

 

PATHOGENESIS.

 

After acquisition in the oral cavity, EBV initially infects oral epithelial cells; this may contribute to the symptoms of pharyngitis. After intracellular viral replication and cell lysis with release of new virions, virus spreads to contiguous structures such as the salivary glands with eventual viremia and infection of B lymphocytes in the peripheral blood and the entire lymphoreticular system including the liver and spleen. The atypical lymphocytes that are characteristic of infectious mononucleosis are CD8+{plus} T lymphocytes, which exhibit both suppressor and cytotoxic functions that develop in response to the infected B lymphocytes. This relative as well as absolute increase in CD8+{plus} lymphocytes results in a transient reversal of the normal 2:1 CD4+{plus}/CD8+{plus} (helper-suppressor) T-lymphocyte ratio. Many of the clinical manifestations of infectious mononucleosis may result, at least in part, from the host immune response, which is effective in reducing the number of EBV-infected B lymphocytes to less than one per 106 of circulating B lymphocytes.

 

Epithelial cells of the uterine cervix may become infected by sexual transmission of the virus, although neither local symptoms nor infectious mononucleosis have been described following sexual transmission.

 

EBV, like the other herpesviruses, establishes lifelong latent infection after the primary illness. The latent virus is carried in oropharyngeal epithelial cells and systemic B lymphocytes as multiple episomes in the nucleus. The viral episomes replicate with cell division and are distributed to both daughter cells. Viral integration into the cell genome is not typical. Only a few viral proteins, including the EBV-determined nuclear antigens (EBNA), are produced during latency. These proteins are important in maintaining the viral episome during the latent state. Progression to viral replication begins with production of EBV early antigens (EA), proceeds to viral DNA replication, followed by production of viral capsid antigen (VCA), and culminates in cell death and release of mature virions. Reactivation with viral replication occurs at a low rate in populations of latently infected cells and is responsible for intermittent viral shedding in oropharyngeal secretions of infected individuals. Reactivation is apparently asymptomatic and not recognized to be accompanied by distinctive clinical symptoms.

 

Oncogenesis. EBV was the first human virus to be associated with malignancy and, therefore, was the first virus to be identified as a human tumor virus. EBV infection may result in a spectrum of proliferative disorders ranging from self-limited, usually benign disease such as infectious mononucleosis to aggressive, nonmalignant proliferations such as the virus-associated hemophagocytic syndrome to lymphoid and epithelial cell malignancies. Benign EBV-associated proliferations include oral, hairy leukoplakia, primarily in adults with the acquired immunodeficiency syndrome (AIDS), and lymphoid interstitial pneumonitis, primarily in children with AIDS. Malignant EBV-associated proliferations include nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin disease, and lymphoproliferative disorders and leiomyosarcoma in immunodeficient states including AIDS.

 

Nasopharyngeal carcinoma occurs worldwide but is 10 times more common in persons in southern China, where it is the most common malignant tumor among adult men. It is also common among whites in North Africa and Inuits in North America. All malignant cells of undifferentiated nasopharyngeal carcinoma contain a high copy number of EBV episomes. Undifferentiated and partially differentiated, nonkeratinizing nasopharyngeal carcinomas have diagnostic and prognostic antibodies to EBV antigens. High levels of immunoglobulin (Ig) A antibody to EA and VCA may be detected in asymptomatic individuals and can be used to follow response to tumor therapy (Table 215–1 Table 215–1). Cells of well-differentiated, keratinizing nasopharyngeal carcinoma contain a low or zero copy number of EBV genomes and have EBV serologic patterns similar to those of the general population.

 

Endemic (African) Burkitt lymphoma, often found in the jaw, is the most common childhood cancer in equatorial East Africa and New Guinea. The median age of onset is 5 yr. These regions are holoendemic for Plasmodium falciparum malaria and have a high rate of EBV infection early in life. The constant malarial exposure acts as a B-lymphocyte mitogen that contributes to the polyclonal B-lymphocyte proliferation with EBV infection. It also impairs the T-lymphocyte control of EBV-infected B lymphocytes. Approximately 98% of cases of endemic Burkitt lymphoma contain the EBV genome compared with only 20% of nonendemic (sporadic or American) Burkitt lymphoma cases. Individuals with Burkitt lymphoma have unusually and characteristically high levels of antibody to VCA and EA that correlate with the risk of developing tumor.

 

All cases of Burkitt lymphoma, including those that are EBV negative, are monoclonal and demonstrate chromosomal translocation of the c-myc proto-oncogene to the constant region of the immunoglobulin heavy-chain locus, t(8;14), to the kappa constant light-chain locus, t(2;8), or to the lambda constant light-chain locus, t(8;22). This results in the deregulation and constitutive transcription of the c-myc gene with overproduction of a normal c-myc product that autosuppresses c-myc production on the untranslocated chromosome.

 

The incidence of Hodgkin disease peaks in childhood in developing countries and in young adulthood in developed countries. Levels of EBV antibodies are consistently elevated preceding development of Hodgkin disease; only a small minority of patients are seronegative for EBV. Infection with EBV appears to increase the risk of Hodgkin disease by a factor of two to four. EBV is associated with more than one half of cases of mixed-cellularity Hodgkin disease and approximately one quarter of cases of the nodular sclerosing subtype and is rarely associated with lymphocyte-predominant Hodgkin disease. Immunohistochemical studies have localized EBV to the Reed-Sternberg cells and their variants, the pathognomonic malignant cells of Hodgkin disease.

 

Failure to control EBV infection may result from host immunologic deficits. The prototype is the X-linked lymphoproliferative syndrome (Duncan syndrome), an X chromosome–linked recessive disorder of the immune system associated with severe, persistent, and sometimes fatal EBV infection. Approximately two thirds of these male patients die of disseminated and fulminating lymphoproliferation involving multiple organs at the time of primary EBV infection. Surviving patients acquire hypogammaglobulinemia, B-cell lymphoma, or both. Most patients die by 10 yr.

 

A number of other congenital and acquired immunodeficiency syndromes are associated with an increased incidence of EBV-associated B-lymphocyte lymphoma, particularly central nervous system lymphoma. The incidence of lymphoproliferative syndromes parallels the degree of immunosuppression. A decline in T-cell function evidently permits EBV to escape from immune surveillance. Congenital immunodeficiencies predisposing to EBV-associated lymphoproliferations include the X-linked lymphoproliferative syndrome, common-variable immunodeficiency, ataxia-telangiectasia, Wiskott-Aldrich syndrome, and Ché-iak-Higashi syndrome. Individuals with acquired immunodeficiencies resulting from anticancer chemotherapy, immunosuppression after solid organ or bone marrow transplantation, or HIV infection have a significantly increased risk of EBV-associated lymphoproliferations. The lymphomas may be focal or diffuse, and they are usually histologically polyclonal but may become monoclonal. Their growth is not reversed on cessation of immunosuppression.

 

EBV has been linked with a multitude of other tumors; the strongest association of EBV is to primary central nervous system lymphoma and carcinoma of the salivary glands. Other tumors include T-lymphocyte lymphoma, lethal midline granuloma (a T-cell lymphoma), angioimmunoblastic lymphadenopathy–like lymphoma, thymomas and thymic carcinomas derived from thymic epithelial cells, supraglottic laryngeal carcinomas, lymphoepithelial tumors of the respiratory tract and gastrointestinal tract, leiomyosarcoma, and gastric adenocarcinoma. The precise contribution of EBV to these various malignancies is not well defined.

 

CLINICAL MANIFESTATIONS.

 

The incubation period of infectious mononucleosis in adolescents is 30–50 days. In children it may be shorter. The majority of cases of primary EBV infection in infants and young children are clinically silent. In older patients, the onset of illness is usually insidious and vague. Patients may complain of malaise, fatigue, fever, headache, sore throat, nausea, abdominal pain, and myalgia. This prodromal period may last 1–2 wk. The complaints of sore throat and fever gradually increase until patients seek medical care. Splenic enlargement may be rapid enough to cause left upper quadrant abdominal discomfort and tenderness, which may be the presenting complaint.

 

The physical examination is characterized by generalized lymphadenopathy (90% of cases), splenomegaly (50% of cases), and hepatomegaly (10% of cases). Lymphadenopathy occurs most commonly in the anterior and posterior cervical nodes, and submandibular lymph nodes and less commonly in the axillary and inguinal lymph nodes. Epitrochlear lymphadenopathy is particularly suggestive of infectious mononucleosis. Symptomatic hepatitis or jaundice is uncommon. Splenomegaly to 2–3 cm below the costal margin is typical; massive enlargement is uncommon.

 

The sore throat is often accompanied by moderate to severe pharyngitis with marked tonsillar enlargement, occasionally with exudates.

 

 

Fig. Tonsillitis with membrane formation in infectious mononucleosis.

 

Tonsillitis in infectious mononucleosis

 

chiae at the junction of the hard and soft palate are frequently seen. The pharyngitis resembles that caused by streptococcal infection. Other clinical findings may include rashes and edema of the eyelids. Rashes are usually maculopapular and have been reported in 3–15% of patients. Eighty per cent of patients with infectious mononucleosis will experience a rash if treated with ampicillin or amoxicillin; the reason for this phenomenon is unknown.

 

COMPLICATIONS.

 

Very few patients with infectious mononucleosis experience complications. The most feared complication is splenic rupture, which occurs most frequently during the 2nd week of the disease. A 0.2% rate has been reported in adults; the rate in children is unknown but is probably much lower. Rupture is commonly related to trauma, which often may be mild. Swelling of the tonsils and oropharyngeal lymphoid tissue may be substantial and cause airway impairment manifest by stridor and interference with breathing. Airway impairment may be treated by administration of corticosteroids; respiratory distress with incipient or actual airway occlusion should be managed by maintaining the airway with intubation in an intensive care setting.

 

Many uncommon and unusual conditions have been reported to be associated with EBV infectious mononucleosis. Neurologic involvement may be serious with ataxia and seizures. Perceptual distortions of space and size, referred to as the Alice in Wonderland syndrome, may be a presenting symptom. There may be meningitis with nuchal rigidity and mononuclear cells in the cerebrospinal fluid, facial nerve palsy, transverse myelitis, and encephalitis. Guillain-Barré syndrome or Reye syndrome may follow acute illness. Hemolytic anemia, often with a positive Coombs test and with cold agglutinins specific for red cell antigen i, may occur late in the illness. Aplastic anemia is a rare complication that usually presents 1 mo after the onset of illness. The prognosis for eventual recovery is good, although substantial supportive treatment is necessary during the acute stages. Myocarditis or interstitial pneumonia may occur, both resolving in 3–4 wk. Other rare complications include pancreatitis, parotitis, and orchitis.

 

DIAGNOSIS.

 

The diagnosis of infectious mononucleosis implies primary EBV infection. A presumptive diagnosis may be made by the presence of typical clinical symptoms with atypical lymphocytosis in the peripheral blood. The diagnosis is confirmed by serologic testing.

 

 

Differential Diagnosis.

 

Infectious mononucleosis–like illnesses may be caused by primary infection with cytomegalovirus, T. gondii, adenovirus, viral hepatitis, HIV, or possibly rubella virus. Cytomegalovirus infection is a particularly common cause in adults. Streptococcal pharyngitis may cause sore throat and cervical lymphadenopathy indistinguishable from that of infectious mononucleosis but is not associated with hepatosplenomegaly. Approximately 5% of cases of EBV-associated infectious mononucleosis have positive throat cultures for group A b-hemolytic streptococci; this represents pharyngeal streptococcal carriage. Failure of a patient with streptococcal pharyngitis to improve within 48–72 hr should evoke suspicion of infectious mononucleosis. The most serious problem in the diagnosis of acute illness arises in the occasional patients with low white cell counts, moderate thrombocytopenia, and even hemolytic anemia. In these patients, bone marrow examination and hematologic consultation are warranted to exclude the possibility of leukemia.

 

Routine Laboratory Tests. In more than 90% of cases, there is leukocytosis of 10,000–20,000 cells/mm3, of which at least two thirds are lymphocytes; atypical lymphocytes usually account for 20–40% of the total number. The atypical cells are mature T lymphocytes that have been antigenically activated. Compared with regular lymphocytes microscopically, atypical lymphocytes are larger overall, with larger, eccentrically placed indented and folded nuclei with a lower nuclear-cytoplasm ratio. Although atypical lymphocytosis may be seen with many of the infections usually causing lymphocytosis, the highest degree of atypical lymphocytes is classically seen with EBV infection. Other syndromes associated with atypical lymphocytosis include acquired cytomegalovirus infection (as contrasted to congenital cytomegalovirus infection), toxoplasmosis, viral hepatitis, rubella, roseola, mumps, tuberculosis, typhoid, mycoplasma infection, malaria, as well as some drug reactions. Mild thrombocytopenia to 50,000–200,000 platelets/mm3 occurs in more than 50% of patients, but only rarely are values low enough to cause purpura. Mild elevation of hepatic transaminases occurs in approximately 50% of uncomplicated cases but is usually asymptomatic without jaundice.

 

Heterophile Antibody Test. Heterophile antibodies agglutinate cells from species different from those in the source serum. The transient heterophile antibodies seen in infectious mononucleosis, also known as Paul-Bunnell antibodies, are IgM antibodies detected by the Paul-Bunnell–Davidsohn test for sheep red cell agglutination. The heterophile antibodies of infectious mononucleosis agglutinate sheep or, for greater sensitivity, horse red cells but not guinea pig kidney cells. This adsorption property differentiates this response from the heterophile response found in patients with serum sickness, rheumatic diseases, and some normal individuals. Titers greater than 1:28 or 1:40 (depending on the dilution system used) after absorption with guinea pig cells are considered positive.

 

The sheep red cell agglutination test is likely to be positive for several months after infectious mononucleosis; the horse red cell agglutination test may be positive for as long as 2 yr. The most widely used method is the qualitative, rapid slide test using horse erythrocytes. It detects heterophile antibody in 90% of cases of EBV-associated infectious mononucleosis in older children and adults but in only up to 50% of cases in children younger than 4 yr because they typically develop a lower titer. Approximately 5–10% of cases of infectious mononucleosis are not caused by EBV and are not uniformly associated with a heterophile antibody response. The false-positive rate is less than 10%, usually resulting from erroneous interpretation. If the heterophile test is negative and an EBV infection is suspected, EBV-specific antibody testing is indicated.

 

Specific EBV Antibodies. EBV-specific antibody testing is useful to confirm acute EBV infection, especially in heterophile-negative cases, or to confirm past infection and determine susceptibility to future infection. Several distinct EBV antigen systems have been characterized for diagnostic purposes.

 

 The EBNA, EA, and VCA antigen systems are most useful for diagnostic purposes. The acute phase of infectious mononucleosis is characterized by rapid IgM and IgG antibody responses to VCA in all cases and an IgG response to EA in most cases. The IgM response to VCA is transient but can be detected for at least 4 wk and occasionally up to 3 mo. The laboratory must take steps to remove rheumatoid factor, which may cause a false-positive IgM VCA result. The IgG response to VCA usually peaks late in the acute phase, declines slightly over the next several weeks to months, and then persists at a relatively stable level for life.

 

Anti-EA antibodies are usually detectable for several months but may persist or be detected intermittently at low levels for many years. Antibodies to the diffuse-staining component of EA, EA-D, are found transiently in 80% of patients during the acute phase of infectious mononucleosis and reach high titers in patients with nasopharyngeal carcinoma. Antibodies to the cytoplasmic-restricted component of EA, EA-R, emerge transiently in the convalescence from infectious mononucleosis and often attain high titers in patients with EBV-associated Burkitt lymphoma, which in the terminal stage of the disease may be exceeded by antibodies to EA-D. High levels of antibodies to EA-D or EA-R may be found also in immunocompromised patients with persistent EBV infections and active EBV replication. Anti-EBNA antibodies are the last to develop in infectious mononucleosis and gradually appear 3–4 mo after the onset of illness and remain at low levels for life. Absence of anti-EBNA when other antibodies are present implies recent infection, while the presence of anti-EBNA implies infection occurring more than 3–4 mo previously. The wide range of individual antibody responses and the various laboratory methods used can occasionally make interpretation of an antibody profile difficult. The detection of IgM antibody to VCA is the most valuable and specific serologic test for the diagnosis of acute EBV infection and is generally sufficient to confirm the diagnosis.

 

TREATMENT.

 

There is no specific treatment for infectious mononucleosis. Therapy with high doses of intravenous acyclovir decreases viral replication and oropharyngeal shedding during the period of administration but does not affect the severity of symptoms or the eventual clinical course. Rest and symptomatic therapy are the mainstays of management. Bed rest is necessary only when the patient has debilitating fatigue. As soon as there is definite symptomatic improvement, the patient should be allowed to begin resuming normal activities. Because blunt abdominal trauma may predispose patients to splenic rupture, it is customary and prudent to advise withdrawal from contact sports and strenuous athletic activities during the first 2–3 wk of illness or while splenomegaly is present.

 

Short courses of corticosteroids (less than 2 wk) may be helpful for complications of infectious mononucleosis, but their use has not been evaluated critically. Some appropriate indications include incipient airway obstruction, thrombocytopenia with hemorrhaging, autoimmune hemolytic anemia, and seizures and meningitis. A recommended dosage is prednisone 1 mg/kg/24 hr (maximum 60 mg/24 hr) or equivalent for 7 days and tapered over another 7 days. There are no controlled data to show efficacy of corticosteroids in any of these conditions. In view of the potential and unknown hazards of immunosuppression for a virus infection with oncogenic complications, corticosteroids should not be used in usual cases of infectious mononucleosis.

 

PROGNOSIS. The prognosis for complete recovery is excellent if no complications ensue during the acute illness. The major symptoms typically last 2–4 wk followed by gradual recovery. Second attacks of infectious mononucleosis caused by EBV have not been documented. Fatigue, malaise, and some disability that may wax and wane for several weeks to a few months are common complaints even in otherwise unremarkable cases. Occasional persistence of fatigue for a few years after infectious mononucleosis is well recognized. At present, there is no specific evidence linking EBV infection to chronic fatigue syndrome (see Chapter 661).

 

 

Short statement of the material

 

Infectious mononucleosis is an acute infectious disease that is caused by the Epstein-Barr virus is characterized by the fever, tonsillitis, increase of lymphatic nodes, hepato- and splenomegaly, by presence of atypical mononuclear cells in a peripheral blood and heterophyl antibodies.

 

Etiology: an EBV, belong to Herpes viruses, type IV

 

Epidemiology:

·                       Source of infection are patients with symptomatic and asymptomatic forms, EBV-carriers

·                       Mechanism of transmission is droplet, rarer is contact. The virus is transmitted primarily through saliva during speaking, breathing, coughing, especially during kisses, hand-to-hand contacts.

·                       The transmission of EBV through blood product transfusions has been well documented.

·                       Susceptibility – any age, disease is low contagious, more frequent up to 15 years, in boys

 

Pathogenesis:

1.                    Inoculation of the virus into upper respiratory tract mucous membranes.

2.                    Diffusion by lymph to the lymph nodes, spleen, liver.

3.                    Lymphoprolipherative syndrome.

4.                    Bacterial complications.

5.                    Persistence of the virus (even 16 months or more).

 

Clinical criteria

·            Incubation period is 10-15 days (may be longer-2 month).

·            Beginning is acute from fever, intoxication (headache, myalgia, arthralgias, malaise).

·            Fever usually febrile from 3 days till 3 weeks

·            Tonsilopharyngitis, which may be exudative (follicular, lacunar) in case of secondary bacterial infection (photo), lymphoid follicles hyperplasia (on the back pharyngeal wall).

·            Adenoiditis, posterior rhinitis (appearance of the patient is typical – breathing with open mouth, absence of nasal discharge, usually snore is present).

·            Generalized lymphadenopathy with previous enlargement of cervical and occipital lymph nodes (photo).

·            Hepatosplenomegaly is the sign of lymphoproliferative syndrome (photo).

·            Maculopapular rashes (photo), wich may confluence with erythema development (photo), sometimes hemorrhagic elements with later skin pigmentation (photo) may occur as a sign of hypersensitivity in case of amoxicillin, ampicillin treatment (in 70-80%).  In the young childhood patient in 25% of cases “spontaneous” rashes can develop.

·            Other signs: hepatitis (jaundice form of infectious mononucleosis);

·            toxic myocarditis

·            diarrhea.

 

Tonsilopharyngitis

 

Tonsilopharyngitis

 

Generalized lymphadenopathy with previous enlargement of cervical lymph nodes

 

Generalized lymphadenopathy with previous enlargement of cervical lymph nodes

 

 

Hepatosplenomegaly

 

Maculopapular rashes

 

Maculopapular rashes wich confluence

 

Maculopapular rashes wich confluence

 

Toxic erythema (next day)

 

Pigmentation in few days

 

Classification       

  Form:         – typical                                           

                     – atypical:   – effaced (mild)              

                                       – asymptomatic (subclinical) mild

  – visceral – severe (heart, kidneys, adrenal glands, CNS damage)

  Severity (for typical forms):    – mild

                                       – moderate

                                       – severe

  Duration    –    smooth (uncomplicated)

–             complicated

–             prolonged

 

Infectious mononucleosis Severity Criteria

 

Sign	Mild	Moderate	Severe
Toxic syndrome	absent, mild	Moderate	Expressed
Body t°	Up to 38 °С	38,5-39 °С	More than 40 °С
Lymph nodes damage	mild, cervical predominantly	marked, cervical especially, visible	conglomerates, neck disfiguration, neck subcutaneous tissue swelling
Nasal breathing	Some labored	Labored, “snoring” in sleep	Absent, snoring, opened mouth, puffy face
Throat damage	Catarrhal tonsillitis	tonsils hyperplasia  1st-2nd degree, considerable exudates	tonsils hyperplasia  3rd  degree, large membranous exudates
Hepato–  splenomegaly (outcome from the rib arch)	Up to 2-3 сm	3-4 сm	4-5 сm and more, jaundice
Atypical mononuclear cells number	Up to 30 %	20-50 %	More than 50 %
Cough	Rare	Often	Often
Rashes	Rare	Often	Hemorrhagic in 1/3, nasal bleeding
Dyspepsia	Rare	Present abdominal pain, vomiting	abdominal pain, several vomiting
Heart changes “toxic-infectious heart”	Not typical	Rare	Often

 

Peculiarities of infectious mononucleosis in infants:

·                       often catarrhal syndrome is present (cough, sneezing, corryza);

·                       expressed polyadenia, snore, edematous face from the first day of the disease;

·                       early development of bacterial tonsillitis (on the third day);

·                       rashes are more often;

·                       dyspepsia;

·                       in the peripheral blood – neutrophyllosis with left shift;

·                       favorable duration.

 

Complications, which may occur (rare):  

1.         Respiratory tract – pneumonia, airway obstructions.

2.         Neurological – seizures, meningitis, encephalitis, peripheral facial nerve paralysis, Gillian – Barrette syndrome. 

3.         Hematological – thrombocytopenia, hemolytic anemia.

4.         Infectious – recurrent tonsilopharyngitis.

5.         Renal – glomerulonephritis.

6.         Genital – orchitis.

7.         Spleen rupture (is lethal).

 

Laboratory findings

1.         Blood analyses: leucocytosis, even 15-30,000/mm3, lymphocytosis, monocytosis, appearing of atypical mononuclear cells (virocytes) more than 10%, ESR enlarges to 20-30mm/hour.

2.         Heterophil agglutination test (is positive in 25-95% of preschool children, 53-94 young school children, and nearly 100% of older children).

3.         Immune-enzyme method – VCA Ig M, EA Ig M presence in the blood.

4.         PCR (measuring of EBV nucleinic acid in the blood, saliva, lymphatic tissues).

 

atypical mononuclear cells

 

Diagnosis example:

Infectious mononucleosis, typical form, moderate severity, complicated by the bilateral  bronchopneumonia  

 

Differential diagnosis should be performed with ‘mononucleosis like’ syndrome caused of AIDS. Another disease, which has similar features: diphtheria, adenoviral infection, acute leukemia, lymphogranulomathosis, viral hepatitis etc.

 

 

Differential diagnostic of tonsillitis different etiology

 

 

Treatment

1.         Reduction of activity and bed rest.

2.         special diet (diet N 5),

·                       Exclude heavy fats (like pork), spices, fried foods, “fast food””; avoid stimulators of gastrointestinal secretions, the diet must be rich by metionine, lecithin, and choline to stimulate synthesis of proteins and enzymes in the liver. Diet with normal value of proteins and vitamins, with restriction of fats and carbohydrates is administered, also restrict salt.

·                       Foods boiled, steamed and baked are recommended; food taking 5 times daily

3.         Control of fever and myalgia (when the temperature is more than 38.5-39˚C); in children before 2 mo and in case of perinatal CNS damage, seizures in the history, severe heart diseases – when the temperature is up to 38˚C with acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 times per day) or ibuprophen 10 mg/kg per dose, not often than every 6 hours. Aspirin is contraindicated for children before 12 years.

4.         Antihistamines (in average doses) – pipolphen, suprastin, claritin, cetirizin.

5.         Corticosteroids – in severe cases 1-2 mg/kg/day prednisone for 3-5 days.

6.         In case of secondary bacterial complications macrolides (erythromycin 30-50 mg/kg/day, azythromycin 10 mg/kg/day, clarythromycin) or cefalosporins (cefalexin 50 mg/kg/day, cefuroxim 50 mg/kg/day, cephasolin 100 mg/kg/day), Ampicillin and other semisynthetic penicillins are contraindicated!

The administration of oral acyclovir does not significantly alter the course of clinical illness from placebo.

 

Prophylaxis: is nonspecific, includes disinfecting;

·            Isolation of the patient, hospitalization of children younger 1 year, in case of severe forms.

·            A quarantine is not imposed.

Key words and phrases: infectious mononucleosis, EBV-infection, lymphoprolipherative syndrome, atypical mononuclear cells, heterophyl  agglutination test, and “mononucleosis” syndrome.

 

 

MUMPS (INFECTIOUS PAROTITIS).

 

 Mumps is an acute, generalized viral disease in which painful enlargement of the salivary glands, chiefly the parotids, is the usual presenting sign.

 

ETIOLOGY.

The virus is a member of the paramyxovirus group, which also includes the parainfluenza, measles, and Newcastle disease viruses. Only one serotype is known. Primary cultures of human or monkey kidney cells are used for viral isolation. Cytopathic effect is occasionally observed, but hemadsorption is the most sensitive indicator of infection. Virus has been isolated from saliva, cerebrospinal fluid, blood, urine, brain, and other infected tissues.

 

EPIDEMIOLOGY.

Mumps is endemic in most urban populations; the virus is spread from a human reservoir by direct contact, airborne droplets, fomites contaminated by saliva, and possibly by urine. It is distributed worldwide and affects both sexes equally; 85% of infections occurred in children younger than 15 yr prior to widespread immunization. Now disease often occurs in young adults, producing epidemics in colleges or in the work place. Epidemics appear to be primarily related to lack of immunization rather than to waning of immunity. Epidemics occur at all seasons but are slightly more frequent in late winter and spring. Sources of infection may be difficult to trace because 30–40% of infections are subclinical. There has been a decrease in the incidence since the introduction of mumps vaccine in 1968.

Virus has been isolated from saliva as long as 6 days before and up to 9 days after appearance of salivary gland swelling. Transmission does not seem to occur longer than 24 hr before appearance of the swelling or later than 3 days after it has subsided. Virus has been isolated from urine from the 1st–14th day after the onset of salivary gland swelling.

 

Lifelong immunity usually follows clinical or subclinical infection, although second infections have been documented. Transplacental antibodies seem to be effective in protecting infants during their first 6–8 mo. Infants born to mothers who have mumps in the week prior to delivery may have clinically apparent mumps at birth or experience illness in the neonatal period. Severity ranges from mild parotitis to severe pancreatitis. The serum neutralization test is the most reliable method for determining immunity but is cumbersome and expensive. A complement-fixing antibody test is available (see Diagnosis). The presence of V antibodies alone suggests previous mumps infection.

 

PATHOGENESIS.

 

After entry and initial multiplication in the cells of the respiratory tract, the virus is blood-borne to many tissues, among which the salivary and other glands are the most susceptible.

 

CLINICAL MANIFESTATIONS.

The incubation period ranges from 14–24 days, with a peak at 17–18 days. In children, prodromal manifestations are rare but may be manifest by fever, muscular pain (especially in the neck), headache, and malaise. The onset is usually characterized by pain and swelling in one or both parotid glands. The parotid swells characteristically; it first fills the space between the posterior border of the mandible and the mastoid and then extends in a series of crescents downward and forward, being limited above by the zygoma. Edema of the skin and soft tissues usually extends further and obscures the limit of the glandular swelling, so that the swelling is more readily appreciated by sight than by palpation. Swelling may proceed extremely rapidly, reaching a maximum within a few hours, although it usually peaks in 1–3 days. The swollen tissues push the ear lobe upward and outward, and the angle of the mandible is no longer visible. Swelling slowly subsides within 3–7 days but occasionally lasts longer. One parotid gland usually swells a day or two before the other, but swelling limited to one gland is common. The swollen area is tender and painful, pain being elicited especially by tasting sour liquids such as lemon juice or vinegar. Redness and swelling about the opening of the Stensen duct are common. Edema of the homolateral pharynx and soft palate accompanies the parotid swelling and displaces the tonsil medially; acute edema of the larynx has also been described. Edema over the manubrium and upper chest wall may occur probably because of lymphatic obstruction. The parotid swelling is usually accompanied by moderate fever; normal temperatures are common (20%), but temperatures of 40º C (104º F) or more are rare.

 

Although the parotid glands alone are affected in the majority of patients, swelling of the submandibular glands occurs frequently and usually accompanies or closely follows that of the parotid glands. In 10–15% of patients only the submandibular gland(s) may be swollen. Little pain is associated with the submandibular infection, but the swelling subsides more slowly than that of the parotids. Redness and swelling at the orifice of the Wharton duct frequently accompany swelling of the gland.

 

Least commonly the sublingual glands are infected, usually bilaterally; the swelling is evident in the submental region and in the floor of the mouth.

 

A maculopapular erythematous rash, most prominent on the trunk, occurs infrequently; rarely it is urticarial.

 

OTHER ORGANS DAMAGE

Meningoencephalomyelitis. This is the most frequent complication in childhood. The true incidence is hard to estimate because subclinical infection of the central nervous system, as evidenced by cerebrospinal fluid pleocytosis, has been reported in more than 65% of patients with parotitis. Clinical manifestations occur in over 10% of patients. The incidence of mumps meningoencephalitis is approximately 250/100,000 cases; 10% of these cases occurred in patients older than 20 yr. The mortality rate is about 2%. Males are affected three to five times as frequently as females. Mumps is one of the most common causes of aseptic meningitis

The pathogenesis of mumps meningoencephalitis has been described as (1) a primary infection of neurons and (2) a postinfectious encephalitis with demyelination. In the first type, parotitis frequently appears at the same time or following the onset of encephalitis. In the latter type, encephalitis follows parotitis by an average of 10 days. Parotitis may in some cases be absent. Aqueductal stenosis and hydrocephalus have been associated with mumps infection. Injecting mumps virus into suckling hamsters has produced similar lesions.

Mumps meningoencephalitis is clinically indistinguishable from meningoencephalitis of other origins. Moderate stiffness of the neck is seen, but the remainder of the neurologic examination is usually normal. The cerebrospinal fluid (CSF) usually contains fewer than 500 cells/mm3, although occasionally the count may exceed 2,000. The cells are almost exclusively lymphocytes, in contrast to enteroviral aseptic meningitis, in which polymorphonuclear leukocytes often predominate early in the disease. Mumps virus can be isolated from cerebrospinal fluid early in the illness.

Orchitis, Epididymitis. These complications rarely occur in prepubescent boys but are common (14–35%) in adolescents and adults. The testis is most often infected with or without epididymitis; epididymitis may also occur alone. Rarely, there is a hydrocele. The orchitis usually follows parotitis within 8 days or so; it may also occur without evidence of salivary gland infection. In about 30% of patients both testes are affected. The onset is usually abrupt, with a rise in temperature, chills, headache, nausea, and lower abdominal pain; when the right testis is implicated, appendicitis may be suggested as a diagnostic possibility. The affected testis becomes tender and swollen, and the adjacent skin is edematous and red. The average duration is 4 days. Approximately 30–40% of affected testes atrophy. Impairment of fertility is estimated to be about 13%, but absolute infertility is probably rare.

Oophoritis. Pelvic pain and tenderness are noted in about 7% of postpubertal female patients. There is no evidence of impairment of fertility.

Pancreatitis. Severe involvement of the pancreas is rare, but mild or subclinical infection may be more common than is recognized. It may be unassociated with salivary gland manifestations and be misdiagnosed as gastroenteritis. Epigastric pain and tenderness, which are suggestive, may be accompanied by fever, chills, vomiting, and prostration. An elevated serum amylase value is characteristically present with mumps, with or without clinical manifestations of pancreatitis.

        Nephritis. Viruria has been reported frequently. In one study of adults, abnormal renal function occurred at some time in every patient, and viruria was detected in 75%. The frequency of renal involvement in children is unknown. Fatal nephritis, occurring 10–14 days after parotitis, has been reported.

Thyroiditis. Although uncommon in children, a diffuse, tender swelling of the thyroid may occur about 1 wk after the onset of parotitis with subsequent development of antithyroid antibodies.

Myocarditis. Serious cardiac manifestations are extremely rare, but mild infection of the myocardium may be more common than is recognized. Electrocardiographic tracings revealed changes, mostly depression of the ST segment, in 13% of adults in one series. Such involvement may explain the precordial pain, bradycardia, and fatigue sometimes noted among adolescents and adults with mumps.

Mastitis. This is uncommon in each sex.

 

COMPLICATIONS.

Deafness. Unilateral, rarely bilateral, nerve deafness may occur; although the incidence is low (1:15,000), mumps is a leading cause of unilateral nerve deafness. The hearing loss may be transient or permanent.

 

Ocular Complications. These include dacryoadenitis, painful swelling, usually bilateral, of the lacrimal glands; optic neuritis (papillitis) with symptoms varying from loss of vision to mild blurring with recovery in 10–20 days; uveokeratitis, usually unilateral, with photophobia, tearing, rapid loss of vision, and recovery within 20 days; scleritis; tenonitis, with resultant exophthalmos; and central vein thrombosis.

Arthritis. Arthralgia associated with swelling and redness of the joints is an infrequent complication; complete recovery is the rule.

Thrombocytopenic Purpura. This sign is infrequent.

Mumps Embryopathy. There is no firm evidence that maternal infection is damaging to the fetus; a possible relationship to endocardial fibroelastosis has not been established. Mumps in early pregnancy does increase the chance of abortion.

DIAGNOSIS.

 

The diagnosis of mumps parotitis is usually apparent from the symptoms and physical examination. When the clinical manifestations are limited to those of one of the less common lesions, the diagnosis is not so clear but may be suspected, especially during an epidemic. The routine laboratory tests are nonspecific; there is usually leukopenia with relative lymphocytosis, but complications often result in polymorphonuclear leukocytosis of moderate degree. An elevation of serum amylase is common; the rise tends to parallel the parotid swelling and then to return to normal within 2 wk or so. The etiologic diagnosis depends on isolation of the virus from the saliva, urine, spinal fluid, or blood or the demonstration of a significant rise in circulating complement fixation antibodies during convalescence. Serum antibodies to the S antigen reach their peak early in about 75% of patients and are detectable at the time of the presenting symptoms. They gradually disappear within 6–12 mo; antibodies against the V or viral antigen usually reach a peak titer in about 1 mo, remain stationary for about 6 mo, and then slowly decline during the ensuing 2 yr to a low level, at which they persist. The presence of a high anti-S titer and a low anti-V titer during the acute stage of an otherwise undiagnosed meningoencephalitis, for example, strongly suggests a mumps infection, which would be confirmed if a convalescent serum (taken 14–21 days later) revealed a fourfold rise of anti-V antibodies accompanied by little change in the titer of anti-S antibodies.

 

DIFFERENTIAL DIAGNOSIS.

This includes parotitis of other origin, as in viral infections including human immunodeficiency virus (HIV) infection, influenza, parainfluenza 1 and 3, cytomegalovirus, or the rare instances of coxsackievirus A and lymphocytic choriomeningitis infections. These infections can be distinguished by specific laboratory tests; suppurative parotitis, in which pus can often be expressed from the duct; recurrent parotitis, a condition of unknown origin, but possibly allergic iature, which has frequent recurrences and a characteristic sialogram; salivary calculus, obstructing either a parotid or, more commonly, a submandibular duct, in which the swelling is intermittent; preauricular or anterior cervical lymphadenitis from any cause; lymphosarcoma or other rare tumors of the parotid; orchitis resulting from infections other than mumps, for example, the rare infections by coxsackievirus A or lymphocytic choriomeningitis viruses; and parotitis caused by cytomegalovirus in immunocompromised children.

 

TREATMENT.

Treatment of parotitis is entirely symptomatic. Bed rest should be guided by the patient’s needs, but no statistical evidence indicates that it prevents complications. The diet should be adjusted to the patient’s ability to chew. Orchitis should be treated with local support and bed rest. Mumps arthritis may respond to a 2-wk course of corticosteroids or a nonsteroidal anti-inflammatory agent. Salicylates do not appear to be effective.

 

PROPHYLAXIS

 

Passive. Hyperimmune mumps gamma globulin is not effective in preventing mumps or decreasing complications.

Active. The routine administration of live, attenuated mumps vaccine is discussed in Chapter 247. Vaccinated children usually do not experience fever or other detectable clinical reactions, do not excrete virus, and are not contagious to susceptible contacts. Rarely, parotitis can develop 7–10 days after vaccination. The vaccine induces antibody in about 96% of seronegative recipients and has a protective efficacy of about 97% against natural mumps infection. The protection appears to be long lasting. In one outbreak of mumps, several children who had been immunized with mumps vaccine in the past experienced an illness characterized by fever, malaise, nausea, and a red papular rash involving the trunk and extremities but sparing the palms and soles. The rash lasted about 24 hr. No virus was isolated from these children, but increases in the titer of mumps antibody were demonstrated

 

Short statement of the material

Mumps (parotid infection) is an acute viral disease, that is caused by a virus from Pramyxovirus family, is transmitted by droplet mechanism, is characterized by the predominant damage of salivary glands, rarer – other glandular organs (pancreas, testicles, ovaries, pectoral glands and other), and also nervous system.

Etiology: an RNA virus, myxovirus parotitis, pathogenic only in humans.

Epidemiology:

·        A source is a patient with clinical, effaced, subclinical forms of infection, contagiousness is up to 9 days from the beginning of disease;

·        the mechanism of transmission is droplet, the virus is transmitted primarily through saliva during speaking, breathing (air-droplet way), hand-to-hand (contact way);

·        the morbidity index does not exceed 50%, more frequent children 3-6 years are ill;

·        Immunity is persistent.

Pathogenesis:

1.         Acquired through the mucous membrane of oral cavity, pharynx, respiratory tract, the virus proliferates locally and in regional lymph nodes;

2.         Then occurs a viremia;

3.         Dissemination of the virus to salivary glands,

4.         Reproduction in them

5.         Secretion of the virus by saliva

6.         Secondary viremia

7.         Damage of other organs: pancreas, testes, ovaries, thyroid, breasts and meninges.

8.         Immune response, elimination of the virus.

 

 

 

Classification

Typical forms 

·             glandular (parotitis, submaxillitis, sublinguitis, pancreatitis, orchitis, oophoritis,  mastitis, bartolonitis, prostatitis, tyroiditis);

·             nervous (serous meningitis, meningoencephalitis);

·             combined (parotitis + pancreatitis + serous meningitis).

Atypical forms  

·              effaced;

·              subclinical (without clinical signs).

Severity:    –

·              mild degree;

·              moderate degree;

·              severe degree.

Course:   

·              acute;

·              further asthenic, hypertensive syndrome (in case of encephalitis);

·              complicated;

·              uncomplicated

Severity indexes:

·              degree of glands damage (swelling, tenderness, edema);

·              the CNS damage (meningeal and meningoencephalitis signs severity);

·              degree of toxic syndrome (body temperature, violation of the common state).

 

Clinical presentation

Incubation period range 11-21 days.

Prodromal symptoms are: general malaise, anorexia, and myalgia with a low-grade fewer. They are followed by parotitis; other manifestations may include pancreatitis, oophoritis, orchitis, mastitis, myocarditis, meningoencephalitis and cranial nerve involvement. These symptoms can occur singly, sequentially or concurrently.

·            Parotitis presents as an earache, parotid edema begins with erythema (or usually colorless) and tenderness above the angle of the mandible (during chewing, speaking) within 1-2 days. Edema increases over several days, may cause an upturning of the earlobe (photo). An examination of the buccal mucosa often reveals erytematous and edematous orifices of Wharton`s and Stensens ducts (Positive Moorson sign). Fever may increase to 40 ^oC. Another parotid gland usually inflamed in 1-2 days.

·            Other signs of mumps tend to occur 1 week or more after the onset of parotid edema.

 

Bylateral parotitis

 

Upturing of the earlobe

 

Moorson sign

 

Submaxillitis

·        Acute beginning from fever (temperature 38 – 39°С), toxic syndrome.

·        Pain in the area of the damaged gland.

·        Slight swelling in submandibular area.

·        Hyperemia and infiltration in the place of external duct of salivary gland.

·        Often comes with the damage of parotid glands.

Submaxillitis

 

Orchitis

·        Orchitis: symptoms include testicular edema and tenderness, nausea, vomiting and fever. In 25 % – is bilateral. Mild atrophy of one testis may develop in many cases.

·        Repeated rising of temperature on 7 – 14 day of illness, toxic syndrome.

·        Previous damage of salivary glands.

·        Pain in a groin increases at walking with an irradiation in a testicle.

·        A testicle is enlarged in sizes; thickened, very painful, skin of scrotum above him is red, shining.

·            In future is violation of testicles function, atrophy in 1/3

 

Orchitis

 

Oophoritis is found primarily in post pubertal patients.

Mastitis has been described in 1/3 post pubertal females.

Meningoencephalitis is one of most significant manifestations of mumps. Meningitis symptoms are: fever, general cerebral symptoms as headache, nausea, vomiting and meningeal signs (nuchal rigidity, Brudzinski‘s upper sign, but Kerning’s sign may be absent).

Encephalitis may present with convulsions, focal neurologic signs, movement disorders, or marked changes in sensory. Muscular weakness, loss or reflexes indicate myelin involvement.

·        Develops secondary on 7 – 10 day of illness, it is combined with the of salivary glands defeat.

·        Toxic syndrome, repeated increase of temperature.

·        Total cerebral syndrome: headache, nausea, repeated vomits, languor.

·        Meningeal syndrome.

·        In the cerebro-spinal fluid lymphocytic (95 – 98 %) pleocytosis (hundred, thousand cells in 1 mm3), increased protein (0.99 – 1.98g/l), normal level of sugar, chlorides, increased pressure.

·        Favorable course of the disease.

Pancreatitis manifests with upper abdominal pain and tenderness in the epigastrium.

·            Develops secondary on 5 – 7 day of illness, it is combined with the of salivary glands defeat.

·            Dyspepsia (nausea, vomits, diarrhea).

·            metheorism.

·            Amylase, lipase, trypsin in the blood are increased

·            Amylase in the urine is increased

·            In coprogram – signs op enzymopathy.

·            Myocarditis occurs primarily in adults, presenting with ECG changes.

·            Joint, thyroid, renal and prostate involvement may also occur.

 

Laboratory tests are usually not helpful. Serum amylase increases. Most laboratories are also no equipped to differentiate between parotid and pancreatic amylase. A lumbar puncture is necessary in a patient with “severe” neurological findings (shows serous meningitis).

In the blood – leucopenia (may be leucocytosis in the beginning), relative lymphocytosis, shift to the left, rare – monocytosis, or elevated ESR.

Serology: NR, CBR, DHAR, with paired sera.

Immune-enzyme method (ELISA) – presence of specific antibodies (Ig M) to the mumps virus.

 

Diagnosis example:

·            Mumps, typical isolated glandular form (bilateral parotitis, left side submaxillitis), moderate severity, uncomplicated.

·            Mumps, typical poliglandular form (bilateral parotitis, pancreatitis, bilateral orchitis) severe degree, complicated by the bilateral bronchopneumonia.

·            Mumps, typical combined form (bilateral submaxillitis, sublinguitis, meningitis), severe degree, uncomplicated.

 

Differential diagnose:

The viral agents, parainfluenza types 1 and 3, Coxsackie’s – virus A, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and echovirus, may all cause parotitis.

Purulent parotitis most often caused by staphylococcus, pneumococcus, or gram-negative bacilli.

 

Noninfectious causes of parotid enlargement include obstruction, tumors, congenital or acquired cysts and drugs such as iodides and phenothiazines.

Cervical lymphadenitis, toxic form of diphtheria must be excluded.

 

Submandibular and cervical lymphadenitis

 

Differential diagnose of the Mumps

 

 

Treatment is symptomatic. In mild, moderate cases of isolate salivary glands damage home treatment is indicated.

 

Basic therapy in case of

Isolate salivary glands damage (parotitis, submaxillitis, and sublinguitis):

·        Bed regimen up to 7 days.

·        Mechanically sparing diet (liquid, semi liquid, soft food; exclude uncooked vegetables and fruits, juices, fatty and spicy food)

·        Care for oral cavity (gurgling with 2 % NaHCO₃, 5% boric acid, and other antiseptic solutions).

·        Dry heat on the staggered glands.

 

In case of Pancreatitis additionally:

·        1 – 2 days hunger, diet №5 for 10 – 12 days.

·        Detoxication therapy (orally, IV: crioplasm, albumen, 5% glucose, physiologic sodium chloride solution).

·        Protease inhibitors (contrical 10-20 IU/kg/day)

·        Spasmolytics for the pain syndrome decrease (nospani, papaverini).

·        Enzymic preparations (pancreatin, creon, pangrol, digestin).

 

In case of Orhitis additionally:

·        Bed regimen up to 10 days, suspensorium.

·        Glucocorticoids 2-3 mg/kg (in equivalent to prednisolone) in 3 – 4 receptions 3 – 4 days, gradual diminishment of dose, course 7 – 10 days.

·        Analgesics (analgin, ibuprophen).

Suspensorium

 

In case of Meningitis

Base therapy:

·                       Bed regimen till body temperature normalization, improvement of general condition, and CSF parametres, not less than 7-10 days, besides – semibed regimen during 5-7 days;

·                       A diet (before stable vital functions is due to adequate parenteral infusion therapy),

·                       Brest feeding or bottle feeding by adopted formulas for infants, in the first day 1/2-1/3 of average volume with a next increase to the complete volume during 2-3rd days, in case of impaired swallowing – nasogastric tube feeding.

·                       A milk vegetable diet (№5) is appointed for preschoolers or school children, 5-6 times per day with the next passing to the diet №2 whether №15 (depending the age) in the recovery period;

·                       Oral fluids intake corresponds to age norms (with including the IV fluids);

Pathogenetic therapy:

·                       In case of brain edema – dehydration by 25 % MgSO4 IM, lasix 1-3 mg/kg IV or IM, acethazolamid orally;

·                       Detoxication in moderate case – orally (oral fluids intake corresponds to age norms with including the IV fluids);

·                       Detoxication in severe cases – IV not more than 1/2 of physiologic age norms during the 1st day, total fluids intake (IV and PO) not more than 2/3 of physiologic age norms in case of normal urination and absense of dehydration. From the 2^nd week correct fluids intake (daily amount of urine not less than 2/3 of all fluids intake);

·                       In case of seizures – Anticonvulsant therapy: benzodiasepins (seduxenum, sibasonum) 0.3-0.5 mg/kg IV, if they are ineffective – 1 % hexenalum or thiopenthalum sodii in 3-5 mg/kg IV. Dehydration therapy: lasix 2-3 mg/kg IM or IV.

Etiologic therapy is indicated in severe cases:

• Recombined interpheron for 7-10 days.

• Endogen interpheron inductors.

• Antiviral medicine (innosini pranobex – 50 mg/kg).

 

Prevention

Nonspecific

·        Isolation of contacts (aged to 10 years, not vaccinated, and were not ill before), from 11 till 22 day after the contact: examination, temperature measuring.

·        Ventilation, moist cleaning up.

Specific:

·                       Vaccination by a living mumps vaccine (or combined MMR vaccine together with vaccination against measles, rubella) in 12-15 months. Revaccination – in 6 years, if was not done – in 11 years; in 15 years – monovaccine (boys).

Key words and phrases: mumps infectious parotitis, earlobe, orifices of  Wharton’s and Stensen’s ducts, parotid edema, orchitis, oophoritis, mastitis,  meningoencephalitis, meningitis, encephalitis, pancreatitis, myocarditis, lumbar puncture.

 

Diphtheria is an acute toxic infection caused by toxigenic strains of Corynebacterium diphtheria, characterized by a local lesion consisting of a membrane. The constitutional symptoms are due to circulation exotoxin, which has a special affinity for nerve tissue, heart muscle and kidneys. 

 

Etiology:  Corynebacterium diphtheria

·            Corynebacterium species are aerobic, no encapsulated, non-sporeforming, mostly no motile, gram-positive bacilli.

 

·            Sensitive to high temperature and disinfection

·            Stabile to freezing and dryness

·            Three biotypes –

–               mitis

–               gravis

–               intermedius

 

 

C.diphtheriae colonies

 

Epidemiology:

Transmission is from person-to-person (from a patient or carrier)

·           through direct contact

·           or airborne respiratory droplets

These materials include discharge from the nose, throat, and lesions on the skin, eyes and even the vagina.

Contagious index – 10-15%

Seasonality – autumn-winter

Immunity – instable

 

Pathogenesis: 

1.                    Entrance for the infection: throat, nose, larynx, sex organs, wound.

2.                    Dissemination of the Corynebacterium, production of exotoxin.

3.                    Local toxin effects with membranous inflammation.

4.                    Toxemia.

5.                    Diffuse toxic effects on kidneys, suprarenal glands, cardiovascular system, and peripheral nervous system.

 

Fibrinous inflammation

·            Diphtheritic (on flat multilayer epithelium)

·            Crupose (on cylindrical single layer epithelium)

 

Incubation period is short (from one to seven days)

 

Clinical features: diphtheria may be localized, spread, toxic (with edema of subcutaneous tissue), hypertoxic, hemorrhagic.

 

Classification of Diphtheria

 

Classification of Diphtheria by localization

1. Diphtheria of tonsills

·                       localized (catarrhal, islet-like, membranous)  

·                       spread form     

·                       toxic form:

o         I grade  

o         II grade

o         III grade

o         hypertoxic

·                       hemorrhagic   form

·                       gangrenous form

 

Diphtheria of the pharynx: The clinical onset is generally insidious with low-grade fever, cough, hoarseness, and mild sore throat. Intensity of the body temperature and intoxication increases proportionally to the square of damages (localized, spread, toxic forms). While examining the throat you could see a gray adherent membranous exudates on the tonsils (localized forms), extending to soft palate, cheeks, even tongue (spread form). The exudates bleed when removed. Hyperemia of throat has cyanotic color with edema of mucous membrane.  Regional lymph nodes are enlarged and tenderness appears. In case of toxic forms you could see “bull neck” due to the neck subcutaneous tissue edema which may extend even to the thorax. Hypertoxic form has sudden onset with hard intoxication (nausea, vomiting, seizures, unconsciousness, body temperature is more than 40^o C) which exceeds local symptoms. Hemorrhagic form is characterized by hemorrhages, bleeding, membranous exudates consists blood.

 

   

Tonsillar diphtheria, localized (moderate)

 

 

Tonsillar diphtheria, spread (moderate)

 

 

Tonsillar diphtheria, toxic (severe)

 

  

Tonsillar diphtheria, toxic (“bull neck” sign)

 

2. Diphtheria of the larynx (laryngotracheitis, croup)

·                       Localized croup   

·                       Spread croup

o         laryngotracheitis

o         laryngotracheobronchitis

·                       Stages of croup

o         Catarrhal croup

o         Stenosis

§     Compensated 

§     Subcompensated

§     Decompensated

o         Asphyxia

 

Diphtheria of the upper respiratory tract demonstrates clinical features of croup. It has slow development, intoxication usually is absent because between membranous exudates and mucous membrane of larynx, trachea and bronchi mucous is present. That’s why toxemia is absent. Croup has catarrhal, stenotic stages and asphyxia.

Catarrhal stage: – duration 2-3 days; intoxication is small or moderate; barking cough, voice becomes hoarse; slow development of signs and symptoms/

Stenotic stage: – duration 2 hours – 2-3 days; moderate intoxication; stenotic breathing appears; signs of hypoxia (peripheral, then general cyanosis, tachycardia, anxiety).

Asphyxia: – pallor or grayness of skin; sleepiness; superficial breathing; arrhythmia, hypotonia, hypothermia, other signs of coma, then – death of the patient.

 

3. Diphtheria of the nasopharynx (nasopharyngitis, pharyngitis)

• difficulty of the nasal breathing;

• nasality of voice;

•throat pain with an irradiation in ears;

• nasal dyscharge is bloody-purulent;

• visible inflammation in the nasal cavity is absent;

• during posterior rhinoscopic examination edema and moderate hyperemia of  adenoid tonsill mucus and (or) fibrinous membranes on its surface;

• “spear-shaped” coat which slips down by the back pharyngeal wall;

• regional (posterior cervical) lymphadenitis;

• the signs of general intoxication are moderate or severe (fatigue, pallor, anorexia, increase of temperature).

 

4. Diphtheria of the anterior part of a nose

• Localized:

– Catarrhal,

– Islet-like,

– Membranous.

• Spread;

• Toxic.

 

Diphtheria of the anterior part of a nose also may be localized, spread and toxic. Signs of it: slow development; minimal toxic signs; it is hard to breathe by nose; purulent and bleed discharges from the nose; maceration of the perinasal area; rhinoscopy reveals gray adherent membranous exudates on the mucous membranes  or ulcers; in case of spread form they extend to additional cavities; in case of toxic form – perinasal edema appears, intoxication enlarges.

 

 

Diphtheria of the nose

 

5. Diphtheria of other localization: diphtheria of the eye, ear, sex organs,  umbilical, wounds, lip, and cheek.

 

diphtheria of the lip

 

In case of 2 or more localizations combined diphtheria is diagnosed.

• diphtheria of tonsills and diphtherial pharyngitis are the most frequent combination;

• diphtheria of tonsills and anterior part of nose;

• diphtheria of tonsills and laryngeal diphtheria;

• rapid growth of clinical symptoms and their dynamics;

• toxic syndrome is considerably severe;

• polymorphism of clinical symptoms.

 

Diphtheria severity

mild	localized	Tonsils (islet-form), nose eye ear skin genital tract
moderate	localized       spread	Tonsils (membranous-form) Nasopharyngeal Localized croup   Tonsils, nose eye ear skin genital tract
severe	Spread   Toxic, hypertoxic	Spread croup   Tonsils , nose eye ear skin genital tract

 

The course of disease

·                       With complication

·                       Without complication

 

Complications

·            early:

–                       toxic shock syndrome;

–                      DIC syndrome

–                      suprarenal glands insufficiency;

–                      Kidneys insufficiency

–                      Respiratory insufficiency

–                      Plural organs insufficiency

–                       (in the end of 1^st to 2^nd week) nephritis; myocarditis; peripheral cranial nerves palsies;

·                       Late (on the 3^rd to 7^th week): myocarditis; peripheral spinal nerves palsies.

 

Laboratory tests. Diphtheria can be confirmed with isolation of C.diphtheriae from the pharyngeal membrane, nose (bacterioscopic or bacteriologic method); serologic reactions, fluorescent antibody techniques are available.

·                       Used to confirm infection combine isolation of C diphtheria on cultures with toxigenicity testing.

o         Bacteriologic culturing is essential to confirm the diagnosis of diphtheria.

o         Toxigenicity testing: Perform toxigenicity testing using the Elek test to determine if the C. diphtheriae isolate produces toxin.

·                       Polymerase chain reaction

·                       Serology: PHAR with erythrocyte diagnostic test before the DAT injection to measure the diphtheria toxin level in the blood; AR, PHAR, CBR with specific diagnostic test systems, growth of antibodies title in the dynamics.

·                       Complete blood analysis: leucocytosis, neuthrophylosis with a shift to the left, the increased ESR.

·                       Urinalysis: proteinuria, leucocyturia, erythrocyturia, casts, (infectiously-toxic damage of kidneys).

·                       Biochemical blood test measure of the rest nitrogen, creatinine, urea

·                       ECG in dynamics

·                       Otolaryngologist, cardiologist, neurologist examination in dynamics, posterior rhioscopy in case of nasopharyngeal diphtheria, laryngoscopy in case of laryngeal diphtheria.

 

Diagnosis example:

Diphtheria of the pharynx, local membranous form, moderate degree.

Diphtheria, combined form: pharyngeal, toxic 1^st grade and laryngeal, local: severe degree

 

Differential diagnose

Diphtheria of the pharynx must be differentiated from scarlet fever, acute bacterial tonsillitis, infectious mononucleosis; diphtheria of the upper respiratory tract – with viral croup caused by parainfluenza, measles, chickenpox, and influenza viruses.

 

Differential diagnostic of tonsillitis different etiology

 

 

 

Bacterial follicular tonsillitis

 

Bacterial lacunar tonsillitis

 

 

Necrotizing tonsillitis

 

 

Bacterial membranous tonsillitis

 

  

Candidiasis

 

 

Peritonsillitis, peritonsillar abscess

 

 

Mumps

 

Differential Diagnosis of the Respiratory Tract Diphtheria

 

Normal larynx

 

 Viral laryngitis, treated viral laryngitis

 

 Fungal laryngitis

 

Death may occur from

·                       Toxemia toward the end of the firth week

·                       Cardiac failure from toxic myocarditis (second week of illness)

·                       Respiratory failure due to peripheral neuritis affecting the vagus nerve (third to seventh week)

 

Treatment: all the patients are hospitalized into infectious or resuscitative department (for severe forms and in case of laryngeal diphtheria).

• Absolute bed regime (2-3 wks);

• Diphtheritic antitoxin therapy (etiological) (Doses see in table);

• Antibacterial therapy for 10-14 days

– In moderate or severe cases:

n Semisynthetic penicillines 50-100 mg/kg/day

n or cefalosporins 100 mg/kg/day

– In mild cases:

n Erythromycin 40-50 mg/kg/day or

n Rifampicin 10-15 mg/kg/day

• Antiseptic fluids locally (in spray or for gurgling);

• Disintoxication therapy (50-100 ml/kg/day) with glucose, crystalloid and colloid fluids IV in moderate or severe cases;

• Corticosteroids therapy by prednisolone 2-3 mg/kg/day in moderate form, 10-20 mg/kg/day in severe form.

 

Prompt treatment with diphtheria antitoxin (DAT) from horse serum is mandatory following tests for hypersensitivity.

 

Diphtheria severity	First dose of serum (in thousands of IU)
Mild form of diphtheria	20 000 – 40 000
Moderate form of diphtheria	50 000 – 80 000
Severe form of diphtheria	90 000 – 120 000
Very severe form of diphtheria (TSH syndrom, DIC syndrome)	120 000 – 150 000

 

In the mild case all the dose is given for one time IM.

In case of prolongation of intoxication and exudates or their increasing repeated dose should be given in 24 hours.

In the mild case when diagnosis is disputable serum may be given in 8-24 hours in case of positive bacteriological culture.

In the moderate case the repeated dose in 24 hours is used (as in table).

In the severe case the first dose is 2/3 of the total one. The repeated dose in 12 hours is used, or in 8 hours if all the serum was given IV.

In case of toxic and hypertoxic forms I dose of DAT must be put intravenously with physiologic saline.

 

In case of toxic shock syndrome:

– Immediately intravenous infusion of DAT with prednisone intravenously 30-50 mg before DAT;

– Prednisone 10-20 mg/kg/day in equal doses 2-4 times per day;

– Detoxication, correction of acid-base balance and electrolytes;

– Dopamine, trental, corglicon.

In case of diphtheria of the larynx (except DAT):

– Inhalation of antiedematous drugs (2 % NaHCO3, hydrocortisone, euphyllin, and mucolithics);

– suctioning of membranes and mucus;

– inhalation of oxygen;

– in the III stage of stenosis – intubation;

– In case of spread croup, combined with diphtheria of pharynx – tracheotomy.

 

Treatment of complications

Myocarditis:

• needs bed regimen on 35-50 days;

• cardiomonitoring;

• prednisone 2 mg/kg/ day per os;

• rhiboxin or ATPh,

• per oral potassium (panangin);

• diuretics.

Neuritis:

• proserin;

• galanthamin;

• strychnine nitric;

• vitamins group B (B1, B6, B12), C;

• diuretics.

Discharge of the patient:

• Clinically healthy;

– Mild and moderate in 14-21 days;

– Severe – in 30-60 days.

• With two documented negative pharyngeal and nasal cultures taken 48 hrs apart in 3 days after stopping antibacterial treatment;

• Dispensarizatioot less than 6 months (in uncomplicated cases).

 

Treatment of healthy infected by C. diphtheria person:

– Erythromycin 40-50 mg/kg/day, or

– Roxitromycinum 5-8 mg/kg, or

– Rifampicin 10-15 mg/kg/day;

• Antiseptic fluids locally;

• Vitamins B-group, C;

• Immune modulators in case of chronic site of infection;

• Tonsillectomy, adenotomy in case of chronic carrying.

 

Prophylaxis

Specific:

• by DTP vaccine from 3 months age 3 times with 30 days interval (3, 4, 5 months), revaccination in 18 months (DTaP), 6, 14, 18 years (DT), later – every 10 years.

 

 

 

 

Combined vaccines

 

Nonspecific:

• Close contacts who were previously immunized longer than 5 years before should receive booster dose of diphtheria toxicoid;

• Antibiotic (erythromycin, rifampin) orally for 7 days;

• Revealing, sanation of healthy infected persons;

• Looking after contacts for 10 days;

• Disinfection of epidemic focus.

 

Key words and phrases: diphtheria, localization, gray adherent membranous exudates, hyperemia with cyanotic color, regional lymph nodes enlargement, “bull neck”, croup, catarrhal, stenotic stage, asphyxia, fluorescent antibody technique, ultraviolet radiation.

 

 

 

PERTUSSIS

 

Pertussis is an acute respiratory tract infection that was well described in the 1500s. Current worldwide prevalence is diminished only by active immunization. Sydenham first used the term pertussis (intense cough) in 1670; it is preferable to “whooping cough,” since most infected individuals do not whoop.

 

ETIOLOGY.

 

Bordetella pertussis is the sole cause of epidemic pertussis and the usual cause of sporadic pertussis. B. parapertussis is an occasional cause of pertussis, accounting for fewer than 5% of isolates of Bordetella species in the United States. B. parapertussis contributes significantly to total cases of pertussis in other areas such as Denmark, the Czech Republic, Slovakia, and the Russian Republic. B. pertussis and B. parapertussis are exclusive pathogens of humans (and some primates). B. bronchiseptica is a common animal pathogen; occasional case reports in humans involve any body site and typically occur in immunocompromised patients or young children with unusual exposure to animals. Protracted coughing can be caused by Mycoplasma, parainfluenza or influenza viruses, enteroviruses, respiratory syncytial virus, or adenoviruses. None is an important cause of pertussis.

 

EPIDEMIOLOGY.

 

Worldwide there are 60 million cases of pertussis a year with more than half a million deaths. During the prevaccine era of 1922–1948, pertussis was the leading cause of death from communicable disease among children under 14 yr of age in the United States. Widespread use of pertussis vaccine is responsible for a dramatic decline in cases. The high incidence of disease in developing and developed countries, such as Italy and certain regions of Germany, where vaccine coverage is low, or Nova Scotia, where a less potent vaccine may have been utilized, and the dramatic resurgence of disease when immunization was halted attest to the pivotal role of vaccination. In the United States, lax implementation of policy is partially responsible for the rise in annual pertussis incidence to 1.2 cases/100,000 population from 1980 through 1989 and epidemic pertussis in many states in 1989–1990 and 1993. The more than 4,500 cases reported to the Centers for Disease Control and Prevention in 1993 is the highest incidence since 1967.

 

Pertussis is endemic, with superimposed epidemic cycles every 3–4 yr after accumulation of a sizable susceptible cohort. The majority of cases occur from July through October. Pertussis is extremely contagious, with attack rates as high as 100% in susceptible individuals exposed to aerosol droplets at close range. B. pertussis does not survive for prolonged periods in the environment. Chronic carriage by humans is not documented. Following intense exposure as in households, the rate of subclinical infection is as high as 50% in fully immunized and naturally immune individuals. When carefully sought, a symptomatic source case can be found for most patients.

 

Neither natural disease nor vaccination provide complete or lifelong immunity against reinfection or disease. Protection against typical disease begins to wane 3–5 yr after vaccination and is unmeasurable after 12 yr. Subclinical reinfection undoubtedly contributes significantly to immunity against disease ascribed to both vaccine and prior infection. Adults in the United States have inadequate antibody to B. pertussis. Despite history of disease or complete immunization, outbreaks of pertussis have occurred in the elderly, iursing homes, in residential facilities with limited exposures, in highly immunized suburbia, and in adolescents and adults with lapsing time since immunization. Coughing adolescents and adults (usually not recognized as having pertussis) are the major reservoir for B. pertussis currently and are the usual sources for “index cases” in infants and children.

 

In the prevaccine era and in countries such as Germany, Sweden, and Italy with limited immunization, the peak incidence of pertussis is in children 1–5 yr of age; infants younger than 1 yr account for less than 15% of cases. In contrast, of the almost 5,000 cases of pertussis reported in the United States during 1993, 44% were younger than 1 yr of age, 21% were aged 1–4 yr, 11% were aged 5–9 yr, and 24% were 12 yr of age or older. For those younger than 1 yr, 79% were under 6 mo and could benefit little from immunization. Children with pertussis between 7 mo and 4 yr were underimmunized. The proportion of teenagers and adults with pertussis has risen concurrently, from less than 20% in the prevaccine era to 27% in 1992–1993. Partial control by vaccination has led to the current epidemiology of pertussis in the United States and has caused vulnerability of age groups never previously affected. Without natural reinfection with B. pertussis or repeated booster vaccinations, older children and adults are susceptible to clinical disease if exposed, and mothers provide little if any passive protection to young infants. The latter observation provides correction to an old tenet that there was little transplacental protection against pertussis.

 

PATHOGEN AND PATHOPHYSIOLOGY. Bordetella are tiny gram-negative coccobacilli that grow aerobically on starch blood agar or completely synthetic media with nicotinamide growth factor, amino acids for energy, and charcoal or cyclodextrin resin to absorb noxious substances. Bordetella species share a high degree of DNA homology among virulence genes, and there is controversy whether sufficient diversity exists to warrant classification as distinct species. Only B. pertussis expresses pertussis toxin (PT), the major virulence protein. Serotyping is dependent upon heat-labile K agglutinogens. Of 14 agglutinogens, 6 are specific to B. pertussis. Serotypes vary geographically and over time.

 

B. pertussis produces an array of biologically active substances, many of which are postulated to play a role in disease and immunity. Following aerosol acquisition, filamentous hemagglutinin (FHA), some agglutinogens (especially FIM2 and FIM3), and a 69-kD nonfimbrial surface protein called pertactin (PRN) are important for attachment to ciliated respiratory epithelial cells. Tracheal cytotoxin, adenylate cyclase, and PT appear to inhibit clearance of organisms. Tracheal cytotoxin, dermonecrotic factor, and adenylate cyclase are postulated to be predominantly responsible for the local epithelial damage that produces respiratory symptomatology and facilitates absorption of PT. PT has multiple proven biologic activities (e.g., histamine sensitivity, insulin secretion, leukocyte dysfunction), some of which may account for systemic manifestations of disease. PT causes lymphocytosis immediately in experimental animals by rerouting lymphocytes to remain in the circulating blood pool. PT appears to play a central but not a singular role in pathogenesis.

Bronchiolar plugging ieonate with pertussis pneumonia

 

CLINICAL MANIFESTATIONS.

 

Pertussis is a lengthy disease, divided into catarrhal, paroxysmal, and convalescent stages, each lasting 2 wk. Classically, following an incubation period ranging from 3 to 12 days, nondistinctive catarrhal symptoms of congestion and rhinorrhea occur, variably accompanied by low-grade fever, sneezing, lacrimation, and conjunctival suffusion. As symptoms wane, coughing begins first as a dry, intermittent, irritative hack and evolves into the inexorable paroxysms that are the hallmark of pertussis. Following the most insignificant startle from a draught, light, sound, sucking, or stretching, the well-appearing young infant begins to choke, gasp, and flail extremities, eyes watering and bulging, face reddened. Cough (expiratory grunt) may not be present, prominent, or appreciated at this stage and age. Whoop (forceful inspiratory gasp) infrequently occurs in infants under 3 mo who are exhausted or lack muscular strength to create suddeegative intrathoracic pressure. The well-appearing playful toddler with similarly insignificant provocation suddenly expresses an anxious aura and may clutch a parent or comforting adult before beginning a machine-gun burst of uninterrupted coughs, chin and chest held forward, tongue protruding maximally, eyes bulging and watering, face purple, until at the seeming last moment of consciousness, coughing ceases and a loud whoop follows as inspired air traverses the still partially closed airway. The episode may end with expulsion of a thick plug of inspissated tracheal secretions, denuded cilia, and necrotic epithelium. Adults describe a sudden feeling of strangulation followed by uninterrupted coughs, feeling of suffocation, bursting headache, diminished awareness, and then the chest heaves and air rushes into the lungs, usually without a whoop. Post-tussive emesis is common in pertussis at all ages and is a major clue to the diagnosis in adolescents and adults. Post-tussive exhaustion is universal. The number and severity of paroxysms progress over days to a week (more rapidly in young infants) and remain at that plateau for days to weeks (longer in young infants). At the peak of the paroxysmal stage, patients may have more than one episode hourly. As paroxysmal stage fades into convalescence, the number, severity, and duration of episodes diminish. Paradoxically in infants, with growth and increased strength, cough and whoops may become louder and more classic in convalescence.

   

Children during the cough paroxism

 

  

Children during the cough paroxism

 

 

Apnea

 

Malnutrition in pertussis patient

 

 

Filatov’s sign (ulcer on the tongue frenula)

 

Immunized children have foreshortening of all stages of pertussis. Adults have no distinct stages. In infants under 3 mo the catarrhal phase is usually a few days or not recognized at all when apnea, choking, or gasping cough herald the onset of disease; convalescence includes intermittent paroxysmal coughing throughout the 1st yr of life including “recurrences” with subsequent respiratory illnesses; these are not due to recurrent infection or reactivation of B. pertussis.

 

The physical examination is generally uninformative. Signs of lower respiratory tract disease are not expected. Conjunctival hemorrhages and petechiae on the upper body are common.

 

Conjunctival hemorrhages and bruises on the lower eyelids

 

Conjunctival hemorrhages

 

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS.

 

Pertussis should be suspected in any individual who has pure or predominant complaint of cough, especially if the following are absent: fever, malaise or myalgia, exanthem or enanthem, sore throat, hoarseness, tachypnea, wheezes, and rales. For sporadic cases, a clinical case definition of cough of 14 or more days’ duration with at least one associated symptom of paroxysms, whoop, or post-tussive vomiting has sensitivity of 81% and specificity of 58% for culture confirmation. Approximately 25% of university students studied randomly in California and Australia without known contact with pertussis who had coughing illness for 7 days or more had pertussis. Apnea or cyanosis (before appreciation of cough) is a clue in infants under 3 mo. B. pertussis is an occasional cause of sudden infant death.

 

Adenoviral infections are usually distinguishable by associated features, such as fever, sore throat, and conjunctivitis. Mycoplasma causes protracted episodic coughing, but there is usually a history of fever, headache, and systemic symptoms at the onset of disease as well as frequent finding of rales on auscultation of the chest. Although pertussis is often included in the laboratory evaluation of young infants with “afebrile pneumonia,” B. pertussis is associated uncommonly with staccato cough (breath with every cough), purulent conjunctivitis, tachypnea, rales or wheezes that typify infection due to Chlamydia trachomatis, or predominant lower respiratory tract signs that typify infection due to respiratory syncytial virus. Unless the infant with pertussis has secondary bacterial pneumonia (and is then ill appearing), the examination between paroxysms is entirely normal, including respiratory rate.

 

Leukocytosis (15,000–100,000 cells/mm3) due to absolute lymphocytosis is a characteristic in late catarrhal and paroxysmal stages. Lymphocytes are of T- and B-cell origin and are normal small cells, rather than the large atypical lymphocytes seen with viral infections. Adults and partially immune children have less impressive lymphocytosis. Absolute increase ieutrophils suggests a different diagnosis or secondary bacterial infection. Eosinophilia is not common in pertussis, even in young infants. A severe course and death are correlated with extreme leukocytosis (median peak white cell count fatal vs nonfatal cases, 94 vs 18 ´ 109 cells/L) and thrombocytosis (median peak platelet count fatal vs nonfatal cases, 782 vs 556 ´ 109/L). Mild hyperinsulinemia and reduced glycemic response to epinephrine have been demonstrated; hypoglycemia is only reported occasionally. The chest radiograph is mildly abnormal in the majority of hospitalized infants showing perihilar infiltrate or edema (sometimes with a butterfly appearance) and variable atelectasis. Parenchymal consolidation suggests secondary bacterial infection. Pneumothorax, pneumomediastinum, and air in soft tissues can be seen occasionally.

 

All current methods for confirmation of infection due to B. pertussis have limitations in sensitivity, specificity, or practicality. Isolation of B. pertussis in culture remains the gold standard and is a more sensitive and specific method of diagnosis than direct fluorescent antibody (DFA) testing of nasopharyngeal secretions if careful attention is paid to specimen collection, transport, and isolation technique. Cultures are positive during the catarrhal stage and escalating paroxysmal stage but are less likely to be positive in partially immune individuals and in those who have received amoxicillin or erythromycin. The specimen is obtained by deep nasopharyngeal aspiration or by use of a flexible swab (Dacron or calcium alginate preferred) held in the posterior nasopharynx for 15–30 sec. (or until coughing). A 1.0% casamino acid liquid is acceptable for holding a specimen up to 2 hr; Stainer-Scholte broth or Regan-Lowe semisolid transport media is used for longer periods, up to 4 days. Regan-Lowe charcoal agar with 10% horse blood and 5–40 mg/mL cephalexin or Stainer-Scholte media with cyclodextrin resins are the preferred isolation media. Cultures are incubated at 35–37º F in humid environment (with or without 5% CO2) and examined daily for 7 days for slow-growing, tiny glistening colonies. DFA testing of potential isolates using specific antibody for B. pertussis and B. parapertussis maximizes recovery. Direct testing of nasopharyngeal secretions by DFA is a rapid test, especially helpful in patients who have received antibiotics, but is only reliable in laboratories with continuous experience. Experience with the polymerase chain reaction to test nasopharyngeal specimens is increasing rapidly. Serologic tests for detection of a variety of antibodies to components of the organism in acute and convalescent samples are the most sensitive tests and are useful epidemiologically. They are not generally available, are not helpful during acute illness, and are difficult to interpret in immunized individuals.

 

COMPLICATIONS AND PROGNOSIS. Rates of complications are difficult to establish because severe outcomes are preferentially reported, but infants under 6 mo of age have excessive mortality and morbidity. Those under 2 mo of age have the highest reported rates of pertussis-associated hospitalization (82%), pneumonia (25%), seizures (4%), encephalopathy (1%), and death (1%).

 

The principal complications of pertussis are apnea, secondary infections (such as otitis media and pneumonia), and physical sequelae of forceful coughing. The need for intensive care and artificial ventilation is usually limited to infants under 3 mo of age. Apnea, cyanosis, and secondary bacterial pneumonia are events precipitating intubation and ventilation. Bacterial pneumonia and/or adult respiratory distress syndrome are the usual cause of death at any age; pulmonary hemorrhage has occurred in the neonate. Fever, tachypnea or respiratory distress between paroxysms, and absolute neutrophilia are clues to pneumonia. Expected pathogens include Staphylococcus aureus, S. pneumoniae, and bacteria of mouth flora. Bronchiectasis has been reported rarely following pertussis. Abnormal pulmonary function may persist for 12 mo after uncomplicated pertussis in children under 2 yr.

 

Increased intrathoracic and intra-abdominal pressure during coughing can result in conjunctival and scleral hemorrhages, petechiae on the upper body, epistaxis, hemorrhage in the central nervous system and retina, pneumothorax and subcutaneous emphysema, and umbilical and inguinal hernias. Laceration of the lingual frenulum is not uncommon. Rectal prolapse, once reported as a frequent complication of pertussis, was probably due to pertussis in malnourished children or missed diagnosis of cystic fibrosis. It is distinctly unusual and should elicit evaluation for underlying condition. Especially in infants in developing countries, dehydration and malnutrition following post-tussive vomiting can have a severe impact. Tetany has been associated with profound post-tussive alkalosis.

 

Central nervous system abnormalities occur at a relatively high frequency and are almost always the result of hypoxemia or hemorrhage associated with coughing or apnea in young infants. Apnea or bradycardia or both may occur from apparent laryngospasm or vagal stimulation just before a coughing episode, from obstruction during an episode, or from hypoxemia following an episode. Lack of associated signs in some young infants with apnea raises the possibility of a primary effect of PT on the central nervous system. Seizures are usually the result of hypoxemia, but hyponatremia from inappropriate secretion of antidiuretic hormone during pneumonia can occur. Although hypoglycemia, a direct effect of PT, or secondary infection due to neurotropic virus have been postulated mechanisms for neurologic symptomatology, no animal data support such theories, and the only neuropathology documented in humans is parenchymal hemorrhage and ischemic necrosis.

 

TREATMENT.

 

Assessment and Supportive Care. Goals of therapy are to limit the number of paroxysms, to observe severity of cough to provide assistance wheecessary, and to maximize nutrition, rest and recovery without sequelae. Infants less than 3 mo of age are admitted to hospital almost without exception, at between 3 and 6 mo unless witnessed paroxysms are not severe, and at any age if complications occur or the family is unable to provide supportive care. Prematurely born young infants and children with underlying cardiac, pulmonary, muscular, or neurologic disorders have a high risk for severe disease.

 

The specific, limited goals of hospitalization are to (1) assess progression of disease and likelihood of life-threatening events at peak of disease, (2) prevent or treat complications, and (3) educate parents in the natural history of the disease and in care that will be given at home. For most infants without complications, this is accomplished in 48–72 hr. Heart rate, respiratory rate, and pulse oximetry are continuously monitored, with alarm settings so that every paroxysm is witnessed by health care personnel. Detailed cough records and documentation of feeding, vomiting, and weight change provide data to assess severity. Typical paroxysms that are not life threatening have the following features: duration less than 45 sec; red but not blue color change; tachycardia, bradycardia (not <60 beats/min in infants), or oxygen desaturation that spontaneously resolves at the end of the paroxysm; whooping or strength for self-rescue at the end of the paroxysm; self-expectorated mucus plug; and post-tussive exhaustion but not unresponsiveness. Assessing the need to provide oxygen, stimulation, or suctioning requires skilled personnel who can document an infant’s ability for self-rescue but who will intervene rapidly and expertly wheecessary. Infants whose paroxysms repeatedly lead to life-threatening events despite passive delivery of oxygen require intubation, paralysis, and ventilation. Subsequent management is difficult, with frequent need to suction the airway and intervene when bradycardia or secondary pulmonary processes occur. Mist by tent, specifically avoided by some experts, can be useful in some infants with thick tenacious secretions and excessively irritable airways. The benefit of a quiet, dimly lighted, undisturbed, comforting environment cannot be overestimated or forfeited in a desire to monitor and intervene. Feeding children with pertussis is challenging. The risk of precipitating cough by nipple feeding does not warrant nasogastric, nasojejunal, or parenteral alimentation in most infants. The composition or thickness of formula does not affect the quality of secretions, cough, or retention. Large-volume feedings are avoided.

 

Within 48–72 hr, the direction and severity of disease is usually obvious by analysis of recorded information. Many infants have marked improvement following hospitalization and antibiotic therapy, especially if they are early in the course of disease or have been removed from aggravating environmental smoke, excessive stimulation, or a dry or polluted heat source. Apnea and seizures occur in the incremental phase of illness and in those with complicated disease. Portable oxygen, monitoring, or suction apparatus should not be needed at home.

 

Therapeutic Agents. ANTIMICROBIAL AGENTS. An antimicrobial agent is always given when pertussis is suspected or confirmed for potential clinical benefit and to limit the spread of infection. Erythromycin, 40–50 mg/kg/24 hr, orally in four divided doses (maximum 2 g/d 24 hr) for 14 days is standard treatment. Some experts prefer the estolate preparation, but ethylsuccinate and stearate are also efficacious. Small studies of erythromycin ethylsuccinate given at a dosage of 50 mg/kg/24 hr divided into two doses, at a dosage of 60 mg/kg/24 hr divided into three doses, and erythromycin estolate given at a dosage of 40 mg/kg/24 hr divided into two doses showed elimination of organisms in 98% of children. Ampicillin, rifampin, and trimethoprim-sulfamethoxazole are modestly active but 1st and 2nd generation cephalosporins are not. In clinical studies, erythromycin is superior to amoxicillin for eradication of B. pertussis and is the only agent with proven efficacy.

 

SALBUTAMOL. A handful of small clinical trials and reports suggest a modest reduction of symptoms from the b{beta}2-adrenergic stimulant salbutamol (albuterol). No rigorous clinical trial has demonstrated a beneficial effect; one small study showed no effect. Fussing associated with aerosol treatment triggers paroxysms.

 

CORTICOSTEROIDS. No randomized, blinded clinical trial of sufficient size has been performed to evaluate the usefulness of corticosteroids in the management of pertussis. Studies in animals have shown a salutary effect on disease manifestations that do not have a corollary in respiratory infection in humans. Their clinical use is not warranted.

 

PERTUSSIS IMMUNE GLOBULIN. Hyperimmune serum, derived from adults convalescing from pertussis, was widely prescribed and regarded as beneficial in the 1930s and 1940s; later studies and the only placebo-controlled trial demonstrated little or no value. In a recent double-blind study in Sweden using large intramuscular doses of hyperimmune serum (raised by immunization of adults), whooping (but not cough or vomiting) was significantly reduced in infants treated in the 1st wk of disease compared with patients given placebo. Use of an immunoglobulin preparation of any sort is not warranted unless further study confirms beneficial effect.

 

CONTROL MEASURES.

 

Isolation. The patient is placed in respiratory isolation for at least 5 days after initiation of erythromycin therapy.

 

Care of Household and Other Close Contacts. Erythromycin, 40–50 mg/kg/24 hr, orally in four divided doses (maximum 2 g/24 hr) for 14 days should be given promptly to all household contacts and other close contacts, such as those in day care, regardless of age, history of immunization, or symptomatology. Visitation and movement of coughing family members in the hospital must be assiduously controlled until erythromycin has been taken for 5 days. Close contacts younger than 7 yr who are underimmunized should be given a pertussis-containing vaccine, with further doses to complete recommended series. Children younger than 7 yr who received a 3rd dose 6 mo or more before exposure, or a 4th dose 3 yr or more before exposure, should receive a booster dose. If infection with B. pertussis is documented at any age, the individual is exempted from routine pertussis immunization. Antimicrobial prophylaxis is not routinely recommended for exposed health care workers. Coughing health care workers, with or without known exposure to pertussis, should be tested for pertussis promptly. For major hospital outbreaks, multifaceted control procedures including targeted erythromycin treatment of coughing individuals and subsequent mass erythromycin prophylaxis may contain hospital spread.

 

PREVENTION Universal immunization of children with pertussis vaccine, beginning in infancy, is central to the control of pertussis. Despite enormous effort, the critical mechanism(s) of immunity following disease or vaccination, a serologic correlate of protection, and the cause of vaccine-associated adverse events are not known. The only current standards for vaccine usefulness are clinical efficacy and safety. Current goals of immunization are protection of the individual from a significant coughing illness and control of endemic and epidemic disease.

 

Whole Cell Vaccine. The vaccine currently used for primary immunization series in the United States and recommended by the World Health Organization for use throughout most of the world is a killed whole cell vaccine composed of a suspension of inactivated B. pertussis, combined with diphtheria and tetanus (DT) toxoids and aluminum-containing adjuvants (DTP vaccine). Potency of pertussis vaccine is assayed in the mouse by intracerebral challenge–protection test, a standard shown to correlate with protective efficacy of vaccine in humans. Vaccine potency is translated to opacity units (also a safety standard) or protective units. U.S. preparations contain 4–12 protective units and not more than 16 opacity units per 0.5-mL dose. Efficacy of whole cell vaccine varies by case definition from 64% for mild cough, to 81% for paroxysmal cough, and to 95% for severe clinical illness. Composition of the preparation used, degree of match between agglutinogen types in vaccine and challenge strain, type of exposure, time after immunization, and requirement for culture confirmation of cases all impact on estimates of vaccine efficacy. Individuals over 7 yr of age are not routinely given pertussis-containing vaccine. When used in adults to control a hospital outbreak, whole cell vaccine was found to be less reactogenic than reported in children.

 

A major limitation of whole cell vaccine use has been the associated reactogenicity, reported a decade ago to occur in approximately 75% of vaccinees. Compared to DT, DTP vaccine has significantly more local reactions, such as pain, swelling, erythema, and systemic reactions, such as fever, fretfulness, crying, drowsiness, and vomiting. These manifestations occur within several hours of immunization and subside spontaneously without sequelae. Recent studies report lower rates of common local and systemic reactions, suggesting that modifications of whole cell vaccine have occurred. Severe anaphylaxis or sterile abscess are extremely rare following DTP vaccine. Transient urticaria is uncommon, is probably related to circulating antigen antibody complex, and unless it occurs within minutes of immunization is unlikely to be IgE mediated, serious, or recur on subsequent immunization.

 

Seizures, occurring within 48 hr of approximately 1:1,750 doses administered, are brief, generalized, and self-limited, occurring in febrile children in almost all instances. They occur more commonly in those with a personal or family history of convulsion and do not result in epilepsy or permanent neurologic sequelae. Persistent inconsolable crying or screaming for 3 or more hours reported after 1% of doses administered, usually in very young infants who have local reactions, is not unique to pertussis immunization and appears to be a manifestation of pain in many instances. Collapse or shocklike state (hypotonic-hyporesponsive episode), usually unrelated to fever or local reactions, has been observed after approximately 1:1,750 pertussis vaccinations, usually in young infants. It appears to be uniquely associated with pertussis vaccine and has no permanent neurologic sequelae. Sixty children were carefully evaluated immediately following serious pertussis vaccine-related adverse events, including seizure, persistent inconsolable crying, extremely high fever, and hypotonic-hyporesponsive episode. Ninety per cent of seizures were typical febrile seizures. No metabolic derangement or measurable pertussis toxin was found in the blood. Infants under 1 yr of age tended to have higher than expected insulin values, suggesting a possible individual age-related susceptibility or vaccine-induced alteration in insulin regulation.

 

Very rarely (1:140,000 doses administered) pertussis vaccine may be associated with acute neurologic illness in children who were previously normal. Severe adverse events, such as death, encephalopathy, onset of a seizure disorder, developmental delay, or learning or behavioral problems, have occurred in individuals temporally associated with pertussis immunization or alleged to be causally associated. Five major epidemiologic studies have examined neurologic risks related to pertussis immunization. Sudden infant death (SIDS) and infantile spasm were found to be neither temporally nor causally related. Analysis and reanalysis by seven major committees found information insufficient to accept a causal relationship between DTP and chronic neurologic disorders. Consideration of benefits versus risks of whole cell vaccine has repeatedly concluded in favor of its continued use.

 

Acellular Vaccine. Purified component acellular pertussis (aP) vaccines, originally developed in Japan, are immunogenic and associated with fewer adverse events when compared with DTP. Vaccines provided by six manufacturers have been used exclusively in Japan since 1981, and their use has controlled pertussis. A randomized, placebo-controlled (but not DTP-controlled) efficacy trial of two acellular pertussis vaccines (developed by the Japanese Institute of Health and conducted in Sweden during 1986 and 1987 under sponsorship of the United States) showed slighter lower efficacy of these acellular vaccines compared historically with whole-cell pertussis vaccine used in the United States. Lower reactogenicity of acellular vaccines and good immunogenicity in American toddlers, coupled with evidence of efficacy in household-exposure and population-based studies from Japan, led to U.S. licensure (1991 and 1992) of DTaP for use in children 15 mo of age or older as the 4th and/or 5th doses of the recommended DTP series. These vaccines have been well tolerated, and use is associated with fewer common local reactions and systemic symptoms, fever, and febrile seizures. Whether rare, more serious adverse events associated with DTP will occur less frequently after DTaP is not known.

 

Immunogenicity and low reactogenicity of 13 candidate acellular vaccines, multinationally manufactured, and containing variably PT, FHA, PRN, FIM2, FIM3 have been documented. Efficacy trials for primary immunization are ongoing in several countries. Experience is accumulating with use of acellular vaccines in adults as well. Licensure of one or more DTaPs in the United States for primary immunization awaits results of these trials. In countries where pertussis has been partially controlled, further reduction of cases will require implementation of booster doses of pertussis vaccine throughout life.

 

Short statement of the material

 

Whooping-cough is an acute infectious disease with the droplet mechanism of transmission, is characterized by the cyclic prolonged duration and presence of paroxysmal cough attacks, absence of intoxication.

 

Etiology:  gram negative bacterium Bordetella pertussis

 

Epidemiology:

·                       Humans are the sole reservoir of B. Pertussis (from the last days of the latent period up to 30 days, the disease has begun.

·                       Infection is spread by way of droplets (droplet mechanism, air-droplet way of transmission) produced by the coughing of infected persons.

·                       Pertussis is highly contagious. More than 90 % of susceptible house hold contacts become infected. More often occurs in infants (who were not vaccinated).

 

Pathogenesis        

·                       Entrance gate  is URT mucus membrane;

·                       Due to several surface adhesions B. Pertussis attach to the respiratory epithelium of trachea;

·                       colonization on a cylinder epithelium, toxin production;

·                       local inflammatory processes, necrosis (catarrhal period);

·                       The organism rarely invades tissues but produces the characteristic disease by Pertussis toxin systemic effects at distant sites in CNS (respiratory center, vascular center):

§     violation of breathing rhythm , hypoxemia, hypoxia;

§     vascular disorders + hypoxia = encephalopathy.

·                       formation of stagnant excitation focus in the brain.

·                       prolonged clinical disease.

 

Clinical presentation.

Incubation period typically is 7 to 10 days, but may be as short as 3 days, or as long as 20 days.

 

Catarrhal (prodromal) 7-14 days period: Whooping cough begins as an undifferentiated, typically subfebrile, upper respiratory tract infection with corryza and dry cough, more in the nighttime (with its gradual intensification). Toxic syndrome is absent.

 

Paroxysmal stage (4 -6 weeks) appears during the second week.

·                       Paroxysmal cough should always alert the physical to the diagnosis. These paroxysms occur at variable intervals, and between episodes the patient usually appears comfortable, without signs of severe illness.

·                       In young infants coughing may be accompanied by an inspiratory whoop. In the end of the cough – discharge much of transparent viscous phlegm. Vomiting, cyanosis, face swelling, apnea or respiratory arrest may complicate paroxysms of coughing. After severe paroxysms the patient may perspire profusely and appear exhausted. Subconjunctival hemorrhages, petechia, or epistaxis may result from severe spasmodic coughing.

·                       The severing and frequency of these paroxysms of cough usually peak during the second or third week of the illness, but coughing can persist for 3 months or longer.

·                       Hemorrhages in sclera, nose-bleeds, petechia on face are typical for this period.

·                       Ulcer on the tongue frenula (Filatov’s sign) is Whooping cough characteristic sign.

·                       Changes in other systems and organs: 

o         whooping cough lung (hard breathing, emphysema, intensification of pulmonary picture), bronchitis, bronchiolitis, pneumonia, athelectasis;

o         high blood pressure, tachycardia;

o         encephalopathy (anxiety or apathy, tremor, bad sleeping, seizures);

o         diarrhea (in infants).

Recovery period for 2 – 4 weeks

•                       a cough loses spasmodic character, becomes easier, more rare;

•                       vomiting disappears;

•                       Asthenia for long period.

 

Typical Whooping cough severity

 

Signs		Mild	moderate	Severe
Prodromal period		9 – 14 days	6 – 9 days	3 – 5 days
Paroxysmal		4 – 5 weeks	5-6 weeks	6 – 8 weeks
Coughing number (per day)		Up to 15	16 – 25	> 25
Whoops number		3 – 5	10	> 10
Coughing number (between two woops)		3 – 5	6 – 9	10 – 12
Coughing paroxysm duration		Short	Prolonged	Very long with vomiting, hemorrhages, urination or defecation in the end
Apnea		Absent	Absent	Present
Complications		Absent	May be present	Typical
General condition		satisfactory	disorders of sleep, excitation, irritates	malaise, lowering of appetite, violation of sleep
Vomiting		Rare	Often	Often repeating
Cyanosis	In the rest	perinasal	perinasal	Perinasal, acrocyanosis
	During cough	Increased	Face	Face
Edema		Face, eyelids after the paroxysm	Constantly	Constantly
Hemorrhages		rare	often	Very often
Lungs symptoms		emphysema	Emphysema, single wheezes, rales	Emphysema, pneumonia
CNS symptoms		–	–	encephalopathy

 

Complications:

•           pneumonia (specific, caused by B.pertussis or secondary, caused by other bacteria);

•           encephalopathy;

•           apnea;

•           hemorrhages into sclera, skin, brain, inner organs, nasal bleeding;

•           umbilical or inguinal hernia;

•           prolapsed rectum mucous membrane;

•           pneumomediastinum or pneumothorax;

•           ulcer under the tongue.

 

Peculiarities of the pertussis in young infants:

•           Incubation and catarrhal periods are shorter (few days).

•           Paroxysmal period is longer (60-90 days).

•           Whoops are absent.

•           Apnea occurs often.

•           Paroxysms of sneezing.

•           Often pneumonia, encephalopathy may develop.

 

Laboratory Tests

1.         A culture of nasopharyngeal secretions for B. pertussis may confirm the diagnosis.

2.         Direct fluorescent antibody staining of nasopharyngeal secretions.

3.         Serologic tests (AR, PHAR): antibody to pertussis toxin measured by enzyme-linked immunosorbent assay.

4.         WBC count may be elevated above 15 000/ mm³ with 70 % or more lymphocytes.

5.         PCR positive for B. pertussis from the nasopharyngeal mucus.

 

Diagnosis example:

·                       Whooping cough, typical form, paroxysmal period, severe degree, complicated by apnea and encephalopathy

·                       Whooping cough, typical form, paroxysmal period, moderate degree, complicated by the leftside lobar pneumonia with cardiovascular syndrome, cardiac insufficiency 1^st  degree.

·                       Whooping cough, typical form, catarrhal period

 

Differential diagnosis

Pertussis in catarrhal period may be confused with upper respiratory tract infections.

In paroxysmal period – with pneumonia caused by Chlamydia trachomatis, RS – virus, parapertussis.

In older children – with sinusitis, cystic fibrosis, aspirated foreign body, or tuberculosis.

 

Whooping Cough Differential Diagnosis

 

 

 

Treatment:

If etiotrope therapy is begun in the catarrhal stage – the duration of illness is shortened. Etiotrope therapy is prescribed to all patients, if the disease duration is not longer than 3 wks.

The erythromycin regimen is 40-to-50 mg/kg/day in four divided doses (or another macrolides) for 14 days. If azythromycin is given its’ dose is 10 mg/kg/ for the 1^st day, and 5 mg/kg/day for next days (the course is 5 days).

Alternative medicine (in case of hypersensitivity to macrolides) is trimethoprim/sulfomethoxasolum in average doses or ampicillin (100-200 mg/kg/day) for 14 days.

If the disease course is longer than 3 wks prescription of etiotrope therapy is discussed individually.

 

Pathogenetical therapy:

·            quiet and comfort; often ventilation, in mild and moderate cases – prolonged walks on fresh air

·            diet: usual daily food volume with increased numbers of feeding

·            therapy to decrease the cough center irritation (synecod)

 

In severe cases also:

·            therapy to decrease the cough center irritation (aminazin 1-2.5 mg/kg/day in 2-3 injections before going to sleep) or lytic suspension

o         novocain 0.25% 4 ml, +

o         aminazin 2.5% 1 ml, +

o         pipolphen 2.5% 1 ml (0.1 ml/kg of prepared solution).

·            intubation and ventilator support – in cause of apnea;

·            euphyllin 5-10 mg/ kg/day;

·            bronchial secretolytics (ambroxol, acetylcystein etc.), suctioning of secretions;

·            parenteral detoxication (5% glucose, physiologic sodium chloride solution);

·            Corticosteroids – 1-2 mg/kg/day prednisone or its equivalents for 3-5 days.

 

Prevention:

–  Isolation of the ill person on 30 days from the beginning of the disease.

–  Isolation of the contact persons younger 7 years old on 14 days.

–  Their throat culture (2 times), if negative – may attend preschool, school

–  Specific vaccination by DTP vaccine from 3 months of old 3 times with 30 days interval, revaccination in 18 months by DTaP vaccine

Key words and phrases: pertussis, whooping cough, pertussis toxin, catarrhal period, paroxysmal stage, reprise, spasmodic coughing, “whooping cough lung”, encephalopathy, and apnea.

 

References:

1.   Manual of children’s infectious diseases / O. Ye. Fedortsiv, I. L. Horishna, I. M. Horishniy. – TERNOPІL : UKRMEDKNYHA, 2010. – 382 p. – ISBN 978-966-673-145-9

2.   Manual of Childhood Infections: The Blue Book (Oxford Specialist Handbooks in Paediatrics) by Mike Sharland, Andrew Cant and al. Published by  Oxford University Press Inc., New York, 2011 , p. 881  ISBN: 978-019-957-358-5.

3.   Illustrated Textbook of Paediatrics, 4th Edition.  Published by  Lissauer & Clayden, 2012, p. 552 ISBN: 978-072-343-566-2.

4.    Nelson Textbook of Pediatrics, 19th Edition Kliegman, Behrman. Published by Jenson & Stanton, 2011, 2608.  ISBN: 978-080-892-420-3.

5.   Oxford Textbook of Medicine: Infection by David Warrell, Timothy M. Cox, John Firth and Mili Estee Torok , Published by Wiley-Blackwell, 2012

6.   http://www.merckmanuals.com/professional/index.html