Lesson 3

Lesson 3

Theme 3. Diphtheria. Infectious mononucleosis. Mumps. Whooping-cough

 

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

 

Etiology:  nCorynebacterium diphtheria

·            nCorynebacterium species are aerobic, no encapsulated, nnon-sporeforming, mostly no motile, gram-positive bacilli.

 

·            nSensitive to high temperature and disinfection

·            nStabile to freezing and dryness

·            nThree biotypes –

–               nmitis

–               ngravis

–               nintermedius

 

 

C.diphtheriae colonies

 

Epidemiology:

Transmissiois from person-to-person (from a patient or carrier)

·           nthrough direct contact

·           nor airborne respiratory droplets

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

Contagious index n– 10-15%

Seasonality n– autumn-winter

Immunity – ninstable

 

Pathogenesis: 

1.                    nEntrance for the infection: throat, nose, larynx, sex norgans, wound.

2.                    nDissemination of the Corynebacterium, production of nexotoxin.

3.                    nLocal toxin effects with membranous inflammation.

4.                    nToxemia.

5.                    nDiffuse toxic effects on kidneys, suprarenal glands, ncardiovascular system, and peripheral nervous system.

 

Fibrinous inflammation

·            nDiphtheritic (on flat multilayer epithelium)

·            nCrupose (on cylindrical single layer epithelium)

 

Incubation period is short (from one to sevedays)

 

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

 

Classification of Diphtheria

 

Classification of Diphtheria by localization

1. Diphtheria of tonsills

·                       nlocalized (catarrhal, islet-like, membranous)  

·                       nspread form      n

·                       ntoxic form:

o         nI grade  

o         nII grade

o         nIII grade

o         nhypertoxic

·                       nhemorrhagic   nform

·                       ngangrenous form

 

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

 

   

Tonsillar ndiphtheria, localized (moderate)

 

 

Tonsillar diphtheria, nspread (moderate)

 

 

Tonsillar ndiphtheria, toxic (severe)

 

  

Tonsillar ndiphtheria, toxic (“bull neck” sign)

 

2. Diphtheria of the larynx (laryngotracheitis, croup)

·                       nLocalized croup    n

·                       nSpread croup

o         nlaryngotracheitis

o         nlaryngotracheobronchitis

·                       nStages of croup

o         nCatarrhal croup

o         nStenosis

§     Compensated 

§     Subcompensated

§     Decompensated

o         nAsphyxia

 

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

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

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

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

 

3. nDiphtheria 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 nof  adenoid tonsill mucus and (or) nfibrinous 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, npallor, anorexia, increase of temperature).

 

4. nDiphtheria of the anterior part of a nose

• Localized:

– Catarrhal,

– Islet-like,

– Membranous.

• Spread;

• Toxic.

 

Diphtheria of nthe anterior part of a nose also may be nlocalized, spread and toxic. Signs of it: slow development; minimal toxic nsigns; it is hard to breathe by nose; purulent and bleed discharges from the nnose; maceration of the perinasal area; rhinoscopy reveals gray adherent nmembranous exudates on the mucous membranes  nor ulcers; in case of spread form they extend to additional cavities; icase of toxic form – perinasal edema appears, intoxication enlarges.

 

 

Diphtheria of the nose

 

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

 

diphtheria of nthe lip

 

In case of 2 or nmore localizations combined ndiphtheria is diagnosed.

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

• 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 nseverity

n

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 ndisease

·                       nWith complication

·                       nWithout complication

 

Complications

·            nearly:

–                      n toxic shock nsyndrome;

–                      nDIC syndrome

–                      nsuprarenal glands insufficiency;

–                      nKidneys insufficiency

–                      nRespiratory insufficiency

–                      nPlural organs insufficiency

–                      n (in the end of n1^st to 2^nd week) nephritis; myocarditis; peripheral ncranial nerves palsies;

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

 

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

·                       nUsed to confirm infection combine nisolation of C diphtheria non cultures with toxigenicity testing.

o         nBacteriologic culturing is essential to nconfirm the diagnosis of diphtheria.

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

·                       nPolymerase chain reaction

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

·                       nComplete blood analysis: leucocytosis, nneuthrophylosis with a shift to the left, the increased ESR.

·                       nUrinalysis: proteinuria, nleucocyturia, erythrocyturia, casts, (infectiously-toxic damage of kidneys).

·                       nBiochemical blood test measure nof the rest nitrogen, creatinine, urea

·                       nECG in dynamics

·                       nOtolaryngologist, cardiologist, neurologist examinatioin dynamics, posterior rhioscopy in case of nasopharyngeal diphtheria, nlaryngoscopy in case of laryngeal diphtheria.

 

Diagnosis example:

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

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

 

Differential diagnose

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

 

Differential diagnostic of tonsillitis different netiology

 

 

 

Bacterial follicular ntonsillitis

 

Bacterial lacunar tonsillitis

 

 

Necrotizing ntonsillitis

 

 

Bacterial membranous ntonsillitis

 

  

Candidiasis n

 

 

Peritonsillitis, nperitonsillar abscess

 

 

Mumps

 

Differential Diagnosis of the Respiratory Tract Diphtheria

 

Normal larynx

 

 Viral laryngitis, treated viral laryngitis

 

 Fungal laryngitis

 

Death may occur nfrom

·                       nToxemia toward the end of the nfirth week

·                       nCardiac failure from toxic nmyocarditis (second week of illness)

·                       nRespiratory failure due to nperipheral neuritis affecting the vagus nerve (third to seventh week)

 

Treatment: all the patients are hospitalized into infectious or resuscitative ndepartment (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

– Imoderate or severe cases:

n Semisynthetic npenicillines 50-100 mg/kg/day

n or ncefalosporins 100 mg/kg/day

– In mild ncases:

n Erythromyci40-50 mg/kg/day or

n Rifampici10-15 mg/kg/day

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

• Disintoxication therapy n(50-100 ml/kg/day) with glucose, crystalloid and colloid fluids IV in moderate nor severe cases;

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

 

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

 

n

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 nis given for one time IM.

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

In the mild case whediagnosis is disputable serum may be given in 8-24 hours in case of positive nbacteriological culture.

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

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

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

 

In case of ntoxic shock syndrome:

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

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

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

– Dopamine, trental, ncorglicon.

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

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

– suctioning of membranes and nmucus;

– inhalation of oxygen;

– in the III stage of stenosis n– intubation;

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

 

Treatment of ncomplications

Myocarditis:

• needs bed regimen on 35-50 ndays;

• cardiomonitoring;

• prednisone 2 mg/kg/ day per nos;

• rhiboxin or ATPh,

• per oral potassium n(panangin);

• diuretics.

Neuritis:

• proserin;

• galanthamin;

• strychnine nitric;

• vitamins group B (B1, B6, nB12), C;

• diuretics.

Discharge of nthe patient:

• Clinically healthy;

– Mild and moderate in 14-21 ndays;

– Severe – in 30-60 days.

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

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

 

Treatment of nhealthy 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 nchronic site of infection;

• Tonsillectomy, adenotomy icase of chronic carrying.

 

Prophylaxis

Specific:

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

 

 

 

 

Combined vaccines

 

Nonspecific:

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

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

• Revealing, sanation of nhealthy infected persons;

• Looking after contacts for n10 days;

• Disinfection of epidemic nfocus.

 

Key words nand phrases: diphtheria, localization, gray nadherent membranous exudates, hyperemia with cyanotic color, regional lymph nnodes enlargement, “bull neck”, croup, catarrhal, stenotic stage, asphyxia, fluorescent nantibody technique, ultraviolet radiation.

 

 

INFECTIOUS MONONUCLEOSIS (EPSTAIN – BARR VIRUS

INFECTION)

 

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

 

ETIOLOGY. 

 

 

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

 

EPIDEMIOLOGY.

 

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

 

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

 

Infection with EBV in developing countries and among nsocioeconomically disadvantaged populations of developed countries usually noccurs during infancy and early childhood. In central Africa, nalmost all children are infected by 3 yr of age. Primary infection with EBV nduring childhood is usually inapparent or indistinguishable from other nchildhood infections; the clinical syndrome of infectious mononucleosis is npractically unknown in undeveloped regions of the world. Among more affluent npopulations in industrialized countries, infection during childhood is still nmost common, but approximately one third of cases occur during adolescence and nyoung adulthood. Primary EBV infection in adolescents and adults is manifest i50% or more of cases by the classic triad of fatigue, pharyngitis, and ngeneralized lymphadenopathy, which constitute the major clinical manifestations nof infectious mononucleosis. This syndrome may be seen at all ages but is nrarely apparent in children younger than 4 yr, when most EBV infections are nasymptomatic, or in adults older than 40 yr, when most individuals have already nbeen infected by EBV. The true incidence of the syndrome of infectious nmononucleosis is unknown but is estimated to occur in 20–70 of 100,000 persons nper year; in young adults the incidence rises to about 1 in 1,000 persons per year. nThe prevalence of serologic evidence of past EBV infection increases with age; nalmost all adults in the United States are seropositive.

 

PATHOGENESIS.

 

After acquisition in the oral cavity, EBV initially ninfects oral epithelial cells; this may contribute to the symptoms of npharyngitis. After intracellular viral replication and cell lysis with release nof new virions, virus spreads to contiguous structures such as the salivary nglands with eventual viremia and infection of B lymphocytes in the peripheral nblood and the entire lymphoreticular system including the liver and spleen. The natypical lymphocytes that are characteristic of infectious mononucleosis are nCD8+{plus} T lymphocytes, which exhibit both suppressor and cytotoxic functions nthat develop in response to the infected B lymphocytes. This relative as well nas absolute increase in CD8+{plus} lymphocytes results in a transient reversal nof the normal 2:1 CD4+{plus}/CD8+{plus} (helper-suppressor) T-lymphocyte ratio. nMany of the clinical manifestations of infectious mononucleosis may result, at nleast in part, from the host immune response, which is effective in reducing nthe number of EBV-infected B lymphocytes to less than one per 106 of ncirculating B lymphocytes.

 

Epithelial cells of the uterine cervix may become ninfected by sexual transmission of the virus, although neither local symptoms nnor infectious mononucleosis have been described following sexual transmission.

 

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

 

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

 

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

 

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

 

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

 

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

 

Failure to control EBV infection may result from host nimmunologic deficits. The prototype is the X-linked lymphoproliferative nsyndrome (Duncasyndrome), an X chromosome–linked recessive disorder of the immune system nassociated with severe, persistent, and sometimes fatal EBV infection. nApproximately two thirds of these male patients die of disseminated and nfulminating lymphoproliferation involving multiple organs at the time of nprimary EBV infection. Surviving patients acquire hypogammaglobulinemia, B-cell nlymphoma, or both. Most patients die by 10 yr.

 

A number of other congenital and acquired immunodeficiency nsyndromes are associated with an increased incidence of EBV-associated nB-lymphocyte lymphoma, particularly central nervous system lymphoma. The nincidence of lymphoproliferative syndromes parallels the degree of nimmunosuppression. A decline in T-cell function evidently permits EBV to escape nfrom immune surveillance. Congenital immunodeficiencies predisposing to nEBV-associated lymphoproliferations include the X-linked lymphoproliferative nsyndrome, common-variable immunodeficiency, ataxia-telangiectasia, nWiskott-Aldrich syndrome, and Ché-iak-Higashi syndrome. Individuals with nacquired immunodeficiencies resulting from anticancer chemotherapy, nimmunosuppression after solid organ or bone marrow transplantation, or HIV ninfection have a significantly increased risk of EBV-associated nlymphoproliferations. The lymphomas may be focal or diffuse, and they are nusually histologically polyclonal but may become monoclonal. Their growth is nnot reversed on cessation of immunosuppression.

 

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

 

CLINICAL MANIFESTATIONS.

 

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

 

The physical examination is characterized by ngeneralized lymphadenopathy (90% of cases), splenomegaly (50% of cases), and nhepatomegaly (10% of cases). Lymphadenopathy occurs most commonly in the nanterior and posterior cervical nodes, and submandibular lymph nodes and less ncommonly in the axillary and inguinal lymph nodes. Epitrochlear lymphadenopathy nis particularly suggestive of infectious mononucleosis. Symptomatic hepatitis nor jaundice is uncommon. Splenomegaly to 2–3 cm below the costal margin is ntypical; massive enlargement is uncommon.

 

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

 

 

Fig. Tonsillitis with membrane formation in infectious nmononucleosis.

 

Tonsillitis in infectious mononucleosis

 

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

 

COMPLICATIONS.

 

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

 

Many uncommon and unusual conditions have beereported to be associated with EBV infectious mononucleosis. Neurologic ninvolvement may be serious with ataxia and seizures. Perceptual distortions of nspace and size, referred to as the Alice nin Wonderland syndrome, may be a presenting symptom. There may be meningitis nwith nuchal rigidity and mononuclear cells in the cerebrospinal fluid, facial nnerve palsy, transverse myelitis, and encephalitis. Guillain-Barré nsyndrome or Reye syndrome may follow acute illness. Hemolytic anemia, oftewith a positive Coombs test and with cold agglutinins specific for red cell nantigen i, may occur late in the illness. Aplastic anemia is a rare ncomplication that usually presents 1 mo after the onset of illness. The nprognosis for eventual recovery is good, although substantial supportive ntreatment is necessary during the acute stages. Myocarditis or interstitial npneumonia may occur, both resolving in 3–4 wk. Other rare complications include npancreatitis, parotitis, and orchitis.

 

DIAGNOSIS.

 

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

 

 

Differential Diagnosis.

 

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

 

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

 

Heterophile Antibody Test. Heterophile antibodies nagglutinate cells from species different from those in the source serum. The ntransient heterophile antibodies seen in infectious mononucleosis, also knowas Paul-Bunnell antibodies, are IgM antibodies detected by the nPaul-Bunnell–Davidsohn test for sheep red cell agglutination. The heterophile nantibodies of infectious mononucleosis agglutinate sheep or, for greater nsensitivity, horse red cells but not guinea pig kidney cells. This adsorptioproperty differentiates this response from the heterophile response found ipatients with serum sickness, rheumatic diseases, and some normal individuals. nTiters greater than 1:28 or 1:40 (depending on the dilution system used) after nabsorption with guinea pig cells are considered positive.

 

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

 

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

 

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

 

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

 

TREATMENT.

 

There is no specific treatment for infectious nmononucleosis. Therapy with high doses of intravenous acyclovir decreases viral nreplication and oropharyngeal shedding during the period of administration but does nnot affect the severity of symptoms or the eventual clinical course. Rest and nsymptomatic therapy are the mainstays of management. Bed rest is necessary only nwhen the patient has debilitating fatigue. As soon as there is definite nsymptomatic improvement, the patient should be allowed to begin resuming normal nactivities. Because blunt abdominal trauma may predispose patients to splenic nrupture, it is customary and prudent to advise withdrawal from contact sports nand strenuous athletic activities during the first 2–3 wk of illness or while nsplenomegaly is present.

 

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

 

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

 

 

Short statement of the material

 

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

 

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

 

Epidemiology:

·                       nSource of infection are patients with symptomatic nand asymptomatic forms, EBV-carriers

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

·                       nThe ntransmission of EBV through blood product transfusions has been well ndocumented.

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

 

Pathogenesis:

1.                    nInoculatioof the virus into upper respiratory tract mucous membranes.

2.                    nDiffusioby lymph to the lymph nodes, spleen, liver.

3.                    nLymphoprolipherative nsyndrome.

4.                    nBacterial ncomplications.

5.                    nPersistence nof the virus (even 16 months or more).

 

Clinical criteria

·            nIncubatioperiod is 10-15 days n(may be longer-2 month).

·            nBeginning nis acute from nfever, intoxication (headache, myalgia, arthralgias, malaise).

·            nFever nusually febrile from 3 days till 3 weeks

·            nTonsilopharyngitis, nwhich may be exudative (follicular, lacunar) in case of secondary bacterial ninfection (photo), lymphoid follicles nhyperplasia (on the back pharyngeal wall).

·            nAdenoiditis, nposterior rhinitis (appearance of the patient is typical – breathing with opemouth, absence of nasal discharge, usually snore is present). n

·            nGeneralized nlymphadenopathy with previous enlargement of cervical and occipital lymph nodes n(photo).

·            nHepatosplenomegaly nis the sign of lymphoproliferative syndrome (photo). n

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

·            nOther nsigns: hepatitis (jaundice form of infectious mononucleosis);

·            ntoxic nmyocarditis

·            ndiarrhea.

 

Tonsilopharyngitis

 

Tonsilopharyngitis

 

Generalized nlymphadenopathy with previous enlargement of cervical lymph nodes

 

Generalized nlymphadenopathy with previous enlargement of cervical lymph nodes

 

 

Hepatosplenomegaly

 

Maculopapular nrashes

 

Maculopapular nrashes wich confluence

 

Maculopapular nrashes wich confluence

 

Toxic nerythema (next day)

 

Pigmentatioin few days

 

Classification       

  Form:         – typical                                           

                     – atypical:   – effaced (mild)              

                                       – nasymptomatic (subclinical) mild

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

  Severity (for typical forms):    – mild

                                       – moderate

                                       – severe

  Duration    –    smooth (uncomplicated)

–             ncomplicated

–             nprolonged

 

Infectious mononucleosis Severity Criteria

 

n

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 nmononucleosis in infants:

·                       noftecatarrhal syndrome is present (cough, sneezing, ncorryza);

·                       nexpressed npolyadenia, snore, nedematous face from the first nday of the disease;

·                       nearly ndevelopment of bacterial tonsillitis (on the third day);

·                       nrashes nare more often;

·                       ndyspepsia;

·                       nithe peripheral blood – neutrophyllosis with left shift;

·                       nfavorable nduration.

 

Complications, which nmay occur (rare):  

1.         nRespiratory ntract – pneumonia, nairway obstructions.

2.         nNeurological n– seizures, nmeningitis, encephalitis, peripheral facial nerve paralysis, Gillian – Barrette nsyndrome. 

3.         nHematological – thrombocytopenia, hemolytic anemia.

4.         nInfectious – recurrent tonsilopharyngitis.

5.         nRenal – glomerulonephritis.

6.         nGenital – orchitis.

7.         nSpleerupture (is lethal).

 

Laboratory findings

1.         nBlood nanalyses: leucocytosis, neven 15-30,000/mm3, lymphocytosis, monocytosis, appearing of atypical nmononuclear cells (virocytes) more than 10%, ESR enlarges to 20-30mm/hour.

2.         nHeterophil nagglutination test n(is positive in 25-95% of preschool children, 53-94 young school children, and nnearly 100% of older children).

3.         nImmune-enzyme nmethod – VCA Ig M, EA Ig M presence in the blood.

4.         nPCR n(measuring of EBV nnucleinic acid in the blood, saliva, lymphatic tissues).

 

atypical mononuclear cells

 

Diagnosis nexample:

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

 

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

 

 

Differential diagnostic of tonsillitis different etiology

 

 

Treatment

1.         nReduction of nactivity and bed rest.

2.         nspecial diet (diet N 5),

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

·                       nFoods nboiled, steamed and baked are recommended; food taking 5 times daily

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

4.         nAntihistamines (in average doses) – pipolphen, suprastin, claritin, ncetirizin.

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

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

The administratioof oral acyclovir does not significantly alter the course of clinical illness nfrom placebo.

 

Prophylaxis: is nonspecific, includes disinfecting;

·            nIsolation of the npatient, hospitalization of children younger 1 year, in case of severe forms.

·            nA quarantine is not nimposed.

Key words nand phrases: infectious mononucleosis, nEBV-infection, lymphoprolipherative syndrome, atypical mononuclear cells, nheterophyl  agglutination test, and “mononucleosis” nsyndrome.

 

 

MUMPS (INFECTIOUS PAROTITIS).

 

 Mumps is aacute, generalized viral disease in which painful enlargement of the salivary nglands, chiefly the parotids, is the usual presenting sign.

 

ETIOLOGY.

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

 

EPIDEMIOLOGY.

Mumps is endemic in most urban populations; the virus nis spread from a human reservoir by direct contact, airborne droplets, fomites ncontaminated by saliva, and possibly by urine. It is distributed worldwide and naffects both sexes equally; 85% of infections occurred in children younger tha15 yr prior to widespread immunization. Now disease often occurs in young nadults, producing epidemics in colleges or in the work place. Epidemics appear nto be primarily related to lack of immunization rather than to waning of nimmunity. Epidemics occur at all seasons but are slightly more frequent in late nwinter and spring. Sources of infection may be difficult to trace because n30–40% of infections are subclinical. There has been a decrease in the nincidence since the introduction of mumps vaccine in 1968.

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

 

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

 

PATHOGENESIS.

 

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

 

CLINICAL MANIFESTATIONS.

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

 

Although the parotid glands alone are affected in the nmajority of patients, swelling of the submandibular glands occurs frequently nand usually accompanies or closely follows that of the parotid glands. I10–15% of patients only the submandibular gland(s) may be swollen. Little paiis associated with the submandibular infection, but the swelling subsides more nslowly than that of the parotids. Redness and swelling at the orifice of the nWharton duct frequently accompany swelling of the gland.

 

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

 

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

 

OTHER ORGANS DAMAGE

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

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

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

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

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

Pancreatitis. Severe involvement of the pancreas is rare, but mild nor subclinical infection may be more common than is recognized. It may be nunassociated with salivary gland manifestations and be misdiagnosed as ngastroenteritis. Epigastric pain and tenderness, which are suggestive, may be naccompanied by fever, chills, vomiting, and prostration. An elevated serum namylase value is characteristically present with mumps, with or without nclinical manifestations of pancreatitis.

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

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

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

Mastitis. This is uncommon in each sex.

 

COMPLICATIONS.

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

 

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

Arthritis. Arthralgia associated with swelling and redness of nthe 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 ndamaging to the fetus; a possible relationship to endocardial fibroelastosis nhas not been established. Mumps in early pregnancy does increase the chance of nabortion.

DIAGNOSIS.

 

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

 

DIFFERENTIAL DIAGNOSIS.

This includes parotitis of other origin, as in viral ninfections including human immunodeficiency virus (HIV) infection, influenza, nparainfluenza 1 and 3, cytomegalovirus, or the rare instances of coxsackievirus nA and lymphocytic choriomeningitis infections. These infections can be ndistinguished by specific laboratory tests; suppurative parotitis, in which pus ncan often be expressed from the duct; recurrent parotitis, a condition of nunknown origin, but possibly allergic iature, which has frequent recurrences nand a characteristic sialogram; salivary calculus, obstructing either a parotid nor, more commonly, a submandibular duct, in which the swelling is intermittent; npreauricular or anterior cervical lymphadenitis from any cause; lymphosarcoma nor other rare tumors of the parotid; orchitis resulting from infections other nthan mumps, for example, the rare infections by coxsackievirus A or lymphocytic nchoriomeningitis viruses; and parotitis caused by cytomegalovirus iimmunocompromised children.

 

TREATMENT.

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

 

PROPHYLAXIS

 

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

Active. The routine administration of live, attenuated mumps nvaccine is discussed in Chapter 247. Vaccinated children usually do not nexperience fever or other detectable clinical reactions, do not excrete virus, nand are not contagious to susceptible contacts. Rarely, parotitis can develop n7–10 days after vaccination. The vaccine induces antibody in about 96% of nseronegative recipients and has a protective efficacy of about 97% against nnatural mumps infection. The protection appears to be long lasting. In one noutbreak of mumps, several children who had been immunized with mumps vaccine nin the past experienced an illness characterized by fever, malaise, nausea, and na red papular rash involving the trunk and extremities but sparing the palms nand soles. The rash lasted about 24 hr. No virus was isolated from these nchildren, but increases in the titer of mumps antibody were demonstrated

 

Short statement of the material

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

Etiology: an RNA virus, myxovirus parotitis, pathogenic only ihumans.

Epidemiology:

·        nA source is a patient with clinical, effaced, nsubclinical forms of infection, contagiousness is up to 9 days from the nbeginning of disease;

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

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

·        nImmunity is persistent.

Pathogenesis:

1.         nAcquired through the mucous membrane of oral cavity, npharynx, respiratory tract, the virus proliferates locally and in regional nlymph nodes;

2.         nThen occurs a viremia;

3.         nDissemination of the virus to salivary glands,

4.         nReproduction in them

5.         nSecretion of the virus by saliva

6.         nSecondary viremia

7.         nDamage of other organs: pancreas, testes, ovaries, nthyroid, breasts and meninges.

8.         nImmune response, elimination of the virus.

 

 

 

Classification

Typical forms 

·             nglandular (parotitis, submaxillitis, nsublinguitis, pancreatitis, orchitis, oophoritis,  mastitis, bartolonitis, prostatitis, ntyroiditis);

·             nnervous (serous meningitis, meningoencephalitis);

·             ncombined (parotitis + pancreatitis + nserous meningitis).

Atypical forms  

·              neffaced;

·              nsubclinical (without clinical signs).

Severity:    –

·              nmild degree;

·              nmoderate degree;

·              nsevere degree.

Course:   

·              nacute;

·              nfurther asthenic, hypertensive syndrome (in case of nencephalitis);

·              ncomplicated;

·              nuncomplicated

Severity indexes:

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

·              nthe CNS damage (meningeal and meningoencephalitis nsigns severity);

·              ndegree of toxic syndrome (body temperature, violatioof the common state).

 

Clinical presentation

Incubation period range 11-21 days.

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

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

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

 

Bylateral parotitis

 

Upturing of the earlobe

 

Moorson sign

 

Submaxillitis

·        nAcute beginning from fever (temperature 38 – 39°С), ntoxic syndrome.

·        nPain in the area of the damaged gland.

·        nSlight swelling in submandibular area.

·        nHyperemia and infiltration in the place of external nduct of salivary gland.

·        nOften comes with the damage of parotid glands.

Submaxillitis

 

Orchitis

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

·        nRepeated rising of temperature on 7 – 14 day of illness, ntoxic syndrome.

·        nPrevious damage of salivary glands.

·        nPain in a groin increases at walking with airradiation in a testicle.

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

·            nIn future is violation of testicles function, atrophy nin 1/3

 

Orchitis

 

Oophoritis is found primarily in post npubertal patients.

Mastitis has beedescribed in 1/3 post pubertal females.

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

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

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

·        nToxic syndrome, repeated increase of temperature.

·        nTotal cerebral syndrome: headache, nausea, repeated nvomits, languor.

·        nMeningeal syndrome.

·        nIn the cerebro-spinal fluid lymphocytic (95 – 98 %) npleocytosis (hundred, thousand cells in 1 mm3), increased protein (0.99 – n1.98g/l), normal level of sugar, chlorides, increased pressure.

·        nFavorable course of the disease.

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

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

·            nDyspepsia n(nausea, vomits, diarrhea).

·            nmetheorism.

·            nAmylase, nlipase, trypsin in the blood are increased

·            nAmylase nin the urine is increased

·            nIcoprogram – signs op nenzymopathy.

·            nMyocarditis occurs primarily in adults, npresenting with ECG changes.

·            nJoint, thyroid, renal and prostate involvement may nalso occur.

 

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

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

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

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

 

Diagnosis example:

·            nMumps, typical nisolated glandular form (bilateral parotitis, left side submaxillitis), moderate nseverity, uncomplicated.

·            nMumps, typical npoliglandular form (bilateral parotitis, pancreatitis, bilateral orchitis) nsevere degree, complicated by the bilateral bronchopneumonia.

·            nMumps, typical ncombined form (bilateral submaxillitis, sublinguitis, meningitis), severe degree, uncomplicated.

 

Differential diagnose:

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

Purulent nparotitis most often caused by staphylococcus, pneumococcus, or gram-negative nbacilli.

 

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

Cervical nlymphadenitis, 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 nsalivary glands damage home treatment is indicated.

 

Basic therapy in case of

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

·        nBed regimen up to 7 days.

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

·        nCare for oral cavity (gurgling with 2 % NaHCO₃, n5% boric acid, and other antiseptic solutions).

·        nDry heat on the staggered glands.

 

In case of Pancreatitis additionally:

·        n1 – 2 days hunger, diet №5 for 10 – 12 days.

·        nDetoxication therapy (orally, IV: crioplasm, albumen, n5% glucose, physiologic sodium chloride solution).

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

·        nSpasmolytics for the pain syndrome decrease (nospani, npapaverini).

·        nEnzymic preparations (pancreatin, creon, pangrol, ndigestin).

 

In case of Orhitis additionally:

·        nBed regimen up to 10 days, suspensorium.

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

·        nAnalgesics (analgin, ibuprophen).

Suspensorium n

 

Icase of Meningitis

Base ntherapy:

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

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

·                       nBrest nfeeding or bottle feeding by adopted formulas for infants, in the first day n1/2-1/3 of average volume with a next increase to the complete volume during n2-3rd days, in case of impaired swallowing – nasogastric tube feeding.

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

·                       nOral fluids nintake corresponds to age norms (with including the IV fluids);

Pathogenetic ntherapy:

·                       nIn case of braiedema – dehydration by 25 % MgSO4 IM, lasix 1-3 mg/kg IV or IM, acethazolamid norally;

·                       nDetoxicatioin moderate case – orally (oral fluids intake corresponds to age norms with nincluding the IV fluids);

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

·                       nIn case of nseizures – Anticonvulsant therapy: benzodiasepins (seduxenum, sibasonum) n0.3-0.5 mg/kg IV, if they are ineffective – 1 % hexenalum or thiopenthalum nsodii in 3-5 mg/kg IV. Dehydration therapy: lasix 2-3 mg/kg IM or IV.

Etiologic ntherapy is indicated in severe cases:

• Recombined interpheron for n7-10 days.

• Endogen interpheroinductors.

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

 

Prevention

Nonspecific

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

·        nVentilation, moist cleaning up.

Specific:

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

Key words nand phrases: mumps infectious parotitis, nearlobe, orifices of  Wharton’s and Stensen’s nducts, parotid edema, orchitis, oophoritis, mastitis,  meningoencephalitis, meningitis, nencephalitis, pancreatitis, myocarditis, lumbar puncture.

 

PERTUSSIS

 

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

 

ETIOLOGY.

 

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

 

EPIDEMIOLOGY.

 

Worldwide there are 60 million cases of pertussis a nyear with more than half a million deaths. During the prevaccine era of n1922–1948, pertussis was the leading cause of death from communicable disease namong children under 14 yr of age in the United States. Widespread use of npertussis vaccine is responsible for a dramatic decline in cases. The high nincidence of disease in developing and developed countries, such as Italy and ncertain regions of Germany, where vaccine coverage is low, or Nova Scotia, nwhere a less potent vaccine may have been utilized, and the dramatic resurgence nof disease when immunization was halted attest to the pivotal role of nvaccination. In the United States, lax implementation of policy is npartially responsible for the rise in annual pertussis incidence to 1.2 ncases/100,000 population from 1980 through 1989 and epidemic pertussis in many nstates in 1989–1990 and 1993. The more than 4,500 cases reported to the Centers nfor Disease Control and Prevention in 1993 is the highest incidence since 1967.

 

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

 

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

 

In the prevaccine era and in countries such as Germany, Sweden, nand Italy nwith limited immunization, the peak incidence of pertussis is in children 1–5 nyr of age; infants younger than 1 yr account for less than 15% of cases. Icontrast, of the almost 5,000 cases of pertussis reported in the United States nduring 1993, 44% were younger than 1 yr of age, 21% were aged 1–4 yr, 11% were naged 5–9 yr, and 24% were 12 yr of age or older. For those younger than 1 yr, n79% were under 6 mo and could benefit little from immunization. Children with npertussis between 7 mo and 4 yr were underimmunized. The proportion of teenagers nand adults with pertussis has risen concurrently, from less than 20% in the nprevaccine era to 27% in 1992–1993. Partial control by vaccination has led to nthe current epidemiology of pertussis in the United States and has caused nvulnerability of age groups never previously affected. Without natural nreinfection with B. pertussis or repeated booster vaccinations, older childreand adults are susceptible to clinical disease if exposed, and mothers provide nlittle if any passive protection to young infants. The latter observatioprovides correction to an old tenet that there was little transplacental nprotection against pertussis.

 

PATHOGEN AND PATHOPHYSIOLOGY. Bordetella are tiny gram-negative coccobacilli that ngrow aerobically on starch blood agar or completely synthetic media with nnicotinamide growth factor, amino acids for energy, and charcoal or ncyclodextrin resin to absorb noxious substances. Bordetella species share a nhigh degree of DNA homology among virulence genes, and there is controversy whether nsufficient diversity exists to warrant classification as distinct species. Only nB. pertussis expresses pertussis toxin (PT), the major virulence protein. nSerotyping is dependent upon heat-labile K agglutinogens. Of 14 agglutinogens, n6 are specific to B. pertussis. Serotypes vary geographically and over time.

 

B. pertussis produces an array of biologically active nsubstances, many of which are postulated to play a role in disease and nimmunity. Following aerosol acquisition, filamentous hemagglutinin (FHA), some nagglutinogens (especially FIM2 and FIM3), and a 69-kD nonfimbrial surface nprotein called pertactin (PRN) are important for attachment to ciliated nrespiratory epithelial cells. Tracheal cytotoxin, adenylate cyclase, and PT nappear to inhibit clearance of organisms. Tracheal cytotoxin, dermonecrotic nfactor, and adenylate cyclase are postulated to be predominantly responsible nfor the local epithelial damage that produces respiratory symptomatology and nfacilitates absorption of PT. PT has multiple proven biologic activities (e.g., nhistamine sensitivity, insulin secretion, leukocyte dysfunction), some of which nmay account for systemic manifestations of disease. PT causes lymphocytosis nimmediately in experimental animals by rerouting lymphocytes to remain in the ncirculating blood pool. PT appears to play a central but not a singular role ipathogenesis.

Bronchiolar plugging ieonate with pertussis npneumonia

 

CLINICAL MANIFESTATIONS.

 

Pertussis is a lengthy disease, divided into ncatarrhal, paroxysmal, and convalescent stages, each lasting 2 wk. Classically, nfollowing an incubation period ranging from 3 to 12 days, nondistinctive ncatarrhal symptoms of congestion and rhinorrhea occur, variably accompanied by nlow-grade fever, sneezing, lacrimation, and conjunctival suffusion. As symptoms nwane, coughing begins first as a dry, intermittent, irritative hack and evolves ninto the inexorable paroxysms that are the hallmark of pertussis. Following the nmost insignificant startle from a draught, light, sound, sucking, or nstretching, the well-appearing young infant begins to choke, gasp, and flail nextremities, eyes watering and bulging, face reddened. Cough (expiratory grunt) nmay not be present, prominent, or appreciated at this stage and age. Whoop n(forceful inspiratory gasp) infrequently occurs in infants under 3 mo who are nexhausted or lack muscular strength to create suddeegative intrathoracic npressure. The well-appearing playful toddler with similarly insignificant nprovocation suddenly expresses an anxious aura and may clutch a parent or ncomforting adult before beginning a machine-gun burst of uninterrupted coughs, nchin and chest held forward, tongue protruding maximally, eyes bulging and nwatering, face purple, until at the seeming last moment of consciousness, coughing nceases and a loud whoop follows as inspired air traverses the still partially nclosed airway. The episode may end with expulsion of a thick plug of ninspissated tracheal secretions, denuded cilia, and necrotic epithelium. Adults ndescribe a sudden feeling of strangulation followed by uninterrupted coughs, nfeeling of suffocation, bursting headache, diminished awareness, and then the nchest heaves and air rushes into the lungs, usually without a whoop. nPost-tussive emesis is common in pertussis at all ages and is a major clue to nthe diagnosis in adolescents and adults. Post-tussive exhaustion is universal. nThe number and severity of paroxysms progress over days to a week (more rapidly nin young infants) and remain at that plateau for days to weeks (longer in young ninfants). At the peak of the paroxysmal stage, patients may have more than one nepisode hourly. As paroxysmal stage fades into convalescence, the number, nseverity, and duration of episodes diminish. Paradoxically in infants, with ngrowth and increased strength, cough and whoops may become louder and more nclassic 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 nof pertussis. Adults have no distinct stages. In infants under 3 mo the ncatarrhal phase is usually a few days or not recognized at all when apnea, nchoking, or gasping cough herald the onset of disease; convalescence includes nintermittent paroxysmal coughing throughout the 1st yr of life including n”recurrences” with subsequent respiratory illnesses; these are not ndue to recurrent infection or reactivation of B. pertussis.

 

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

 

Conjunctival hemorrhages and nbruises on the lower eyelids

 

Conjunctival hemorrhages

 

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS.

 

Pertussis should be suspected in any individual who nhas pure or predominant complaint of cough, especially if the following are absent: nfever, malaise or myalgia, exanthem or enanthem, sore throat, hoarseness, ntachypnea, wheezes, and rales. For sporadic cases, a clinical case definitioof cough of 14 or more days’ duration with at least one associated symptom of nparoxysms, whoop, or post-tussive vomiting has sensitivity of 81% and nspecificity of 58% for culture confirmation. Approximately 25% of university nstudents studied randomly in California and Australia nwithout known contact with pertussis who had coughing illness for 7 days or nmore had pertussis. Apnea or cyanosis (before appreciation of cough) is a clue nin infants under 3 mo. B. pertussis is an occasional cause of sudden infant ndeath.

 

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

 

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

 

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

 

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

 

The principal complications of pertussis are apnea, nsecondary infections (such as otitis media and pneumonia), and physical nsequelae of forceful coughing. The need for intensive care and artificial nventilation is usually limited to infants under 3 mo of age. Apnea, cyanosis, nand secondary bacterial pneumonia are events precipitating intubation and nventilation. Bacterial pneumonia and/or adult respiratory distress syndrome are nthe usual cause of death at any age; pulmonary hemorrhage has occurred in the nneonate. Fever, tachypnea or respiratory distress between paroxysms, and nabsolute neutrophilia are clues to pneumonia. Expected pathogens include nStaphylococcus aureus, S. pneumoniae, and bacteria of mouth flora. nBronchiectasis has been reported rarely following pertussis. Abnormal pulmonary nfunction may persist for 12 mo after uncomplicated pertussis in children under n2 yr.

 

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

 

Central nervous system abnormalities occur at a nrelatively high frequency and are almost always the result of hypoxemia or nhemorrhage associated with coughing or apnea in young infants. Apnea or nbradycardia or both may occur from apparent laryngospasm or vagal stimulatiojust before a coughing episode, from obstruction during an episode, or from nhypoxemia following an episode. Lack of associated signs in some young infants nwith apnea raises the possibility of a primary effect of PT on the central nnervous system. Seizures are usually the result of hypoxemia, but hyponatremia nfrom inappropriate secretion of antidiuretic hormone during pneumonia caoccur. Although hypoglycemia, a direct effect of PT, or secondary infection due nto neurotropic virus have been postulated mechanisms for neurologic nsymptomatology, no animal data support such theories, and the only nneuropathology documented in humans is parenchymal hemorrhage and ischemic nnecrosis.

 

TREATMENT.

 

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

 

The specific, limited goals of hospitalization are to n(1) assess progression of disease and likelihood of life-threatening events at npeak of disease, (2) prevent or treat complications, and (3) educate parents ithe natural history of the disease and in care that will be given at home. For nmost infants without complications, this is accomplished in 48–72 hr. Heart nrate, respiratory rate, and pulse oximetry are continuously monitored, with nalarm settings so that every paroxysm is witnessed by health care personnel. nDetailed cough records and documentation of feeding, vomiting, and weight nchange provide data to assess severity. Typical paroxysms that are not life nthreatening have the following features: duration less than 45 sec; red but not nblue color change; tachycardia, bradycardia (not <60 beats/min in infants), nor oxygen desaturation that spontaneously resolves at the end of the paroxysm; nwhooping or strength for self-rescue at the end of the paroxysm; nself-expectorated mucus plug; and post-tussive exhaustion but not nunresponsiveness. Assessing the need to provide oxygen, stimulation, or nsuctioning requires skilled personnel who can document an infant’s ability for nself-rescue but who will intervene rapidly and expertly wheecessary. Infants nwhose paroxysms repeatedly lead to life-threatening events despite passive ndelivery of oxygen require intubation, paralysis, and ventilation. Subsequent nmanagement is difficult, with frequent need to suction the airway and intervene nwhen bradycardia or secondary pulmonary processes occur. Mist by tent, nspecifically avoided by some experts, can be useful in some infants with thick ntenacious secretions and excessively irritable airways. The benefit of a quiet, ndimly lighted, undisturbed, comforting environment cannot be overestimated or nforfeited in a desire to monitor and intervene. Feeding children with pertussis nis challenging. The risk of precipitating cough by nipple feeding does not nwarrant nasogastric, nasojejunal, or parenteral alimentation in most infants. nThe composition or thickness of formula does not affect the quality of nsecretions, cough, or retention. Large-volume feedings are avoided.

 

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

 

Therapeutic Agents. ANTIMICROBIAL nAGENTS. An antimicrobial nagent is always given when pertussis is suspected or confirmed for potential nclinical benefit and to limit the spread of infection. Erythromycin, 40–50 nmg/kg/24 hr, orally in four divided doses (maximum 2 g/d 24 hr) for 14 days is nstandard treatment. Some experts prefer the estolate preparation, but nethylsuccinate and stearate are also efficacious. Small studies of erythromyciethylsuccinate given at a dosage of 50 mg/kg/24 hr divided into two doses, at a ndosage of 60 mg/kg/24 hr divided into three doses, and erythromycin estolate ngiven at a dosage of 40 mg/kg/24 hr divided into two doses showed eliminatioof organisms in 98% of children. Ampicillin, rifampin, and ntrimethoprim-sulfamethoxazole are modestly active but 1st and 2nd generatiocephalosporins are not. In clinical studies, erythromycin is superior to namoxicillin for eradication of B. pertussis and is the only agent with proveefficacy.

 

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

 

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

 

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

 

CONTROL MEASURES.

 

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

 

Care of Household and Other Close nContacts. Erythromycin, n40–50 mg/kg/24 hr, orally in four divided doses (maximum 2 g/24 hr) for 14 days nshould be given promptly to all household contacts and other close contacts, nsuch as those in day care, regardless of age, history of immunization, or nsymptomatology. Visitation and movement of coughing family members in the nhospital must be assiduously controlled until erythromycin has been taken for 5 ndays. Close contacts younger than 7 yr who are underimmunized should be given a npertussis-containing vaccine, with further doses to complete recommended nseries. Children younger than 7 yr who received a 3rd dose 6 mo or more before nexposure, or a 4th dose 3 yr or more before exposure, should receive a booster ndose. If infection with B. pertussis is documented at any age, the individual nis exempted from routine pertussis immunization. Antimicrobial prophylaxis is nnot routinely recommended for exposed health care workers. Coughing health care nworkers, with or without known exposure to pertussis, should be tested for npertussis promptly. For major hospital outbreaks, multifaceted control nprocedures including targeted erythromycin treatment of coughing individuals nand subsequent mass erythromycin prophylaxis may contain hospital spread.

 

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

 

Whole Cell Vaccine. The vaccine currently used for primary immunizatioseries in the United States and recommended by the World Health Organizatiofor use throughout most of the world is a killed whole cell vaccine composed of na suspension of inactivated B. pertussis, combined with diphtheria and tetanus n(DT) toxoids and aluminum-containing adjuvants (DTP vaccine). Potency of npertussis vaccine is assayed in the mouse by intracerebral challenge–protectiotest, a standard shown to correlate with protective efficacy of vaccine ihumans. Vaccine potency is translated to opacity units (also a safety standard) nor protective units. U.S. npreparations contain 4–12 protective units and not more than 16 opacity units nper 0.5-mL dose. Efficacy of whole cell vaccine varies by case definition from n64% for mild cough, to 81% for paroxysmal cough, and to 95% for severe clinical nillness. Composition of the preparation used, degree of match betweeagglutinogen types in vaccine and challenge strain, type of exposure, time nafter immunization, and requirement for culture confirmation of cases all nimpact on estimates of vaccine efficacy. Individuals over 7 yr of age are not nroutinely given pertussis-containing vaccine. When used in adults to control a nhospital outbreak, whole cell vaccine was found to be less reactogenic thareported in children.

 

A major limitation of whole cell vaccine use has beethe associated reactogenicity, reported a decade ago to occur in approximately n75% of vaccinees. Compared to DT, DTP vaccine has significantly more local nreactions, such as pain, swelling, erythema, and systemic reactions, such as nfever, fretfulness, crying, drowsiness, and vomiting. These manifestations noccur within several hours of immunization and subside spontaneously without nsequelae. Recent studies report lower rates of common local and systemic nreactions, suggesting that modifications of whole cell vaccine have occurred. nSevere anaphylaxis or sterile abscess are extremely rare following DTP vaccine. nTransient urticaria is uncommon, is probably related to circulating antigeantibody complex, and unless it occurs within minutes of immunization is nunlikely to be IgE mediated, serious, or recur on subsequent immunization.

 

Seizures, occurring within 48 hr of approximately n1:1,750 doses administered, are brief, generalized, and self-limited, occurring nin febrile children in almost all instances. They occur more commonly in those nwith a personal or family history of convulsion and do not result in epilepsy nor permanent neurologic sequelae. Persistent inconsolable crying or screaming nfor 3 or more hours reported after 1% of doses administered, usually in very nyoung infants who have local reactions, is not unique to pertussis immunizatioand appears to be a manifestation of pain in many instances. Collapse or nshocklike state (hypotonic-hyporesponsive episode), usually unrelated to fever nor local reactions, has been observed after approximately 1:1,750 pertussis nvaccinations, usually in young infants. It appears to be uniquely associated nwith pertussis vaccine and has no permanent neurologic sequelae. Sixty childrewere carefully evaluated immediately following serious pertussis nvaccine-related adverse events, including seizure, persistent inconsolable ncrying, extremely high fever, and hypotonic-hyporesponsive episode. Ninety per ncent of seizures were typical febrile seizures. No metabolic derangement or nmeasurable pertussis toxin was found in the blood. Infants under 1 yr of age ntended to have higher than expected insulin values, suggesting a possible nindividual age-related susceptibility or vaccine-induced alteration in insuliregulation.

 

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

 

Acellular Vaccine. Purified component acellular pertussis (aP) vaccines, noriginally developed in Japan, nare immunogenic and associated with fewer adverse events when compared with nDTP. Vaccines provided by six manufacturers have been used exclusively in Japan since n1981, and their use has controlled pertussis. A randomized, placebo-controlled n(but not DTP-controlled) efficacy trial of two acellular pertussis vaccines n(developed by the Japanese Institute of Health and conducted in Sweden during n1986 and 1987 under sponsorship of the United States) showed slighter lower nefficacy of these acellular vaccines compared historically with whole-cell npertussis vaccine used in the United States. Lower reactogenicity of acellular nvaccines and good immunogenicity in American toddlers, coupled with evidence of nefficacy in household-exposure and population-based studies from Japan, led to nU.S. licensure (1991 and 1992) of DTaP for use in children 15 mo of age or nolder as the 4th and/or 5th doses of the recommended DTP series. These vaccines nhave been well tolerated, and use is associated with fewer common local nreactions and systemic symptoms, fever, and febrile seizures. Whether rare, nmore serious adverse events associated with DTP will occur less frequently nafter DTaP is not known.

 

Immunogenicity and low reactogenicity of 13 candidate acellular nvaccines, multinationally manufactured, and containing variably PT, FHA, PRN, nFIM2, FIM3 have been documented. Efficacy trials for primary immunization are nongoing in several countries. Experience is accumulating with use of acellular nvaccines in adults as well. Licensure of one or more DTaPs in the United States nfor primary immunization awaits results of these trials. In countries where npertussis has been partially controlled, further reduction of cases will nrequire implementation of booster doses of pertussis vaccine throughout life.

 

Short statement of the material

 

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

 

Etiology:  gram negative nbacterium Bordetella pertussis

 

Epidemiology: n

·                       nHumans nare the sole reservoir of B. nPertussis (from the last days of the latent period up to 30 days, the disease nhas begun.

·                       nInfectiois spread by way of droplets (droplet nmechanism, air-droplet way of transmission) produced by the coughing of ninfected persons.

·                       nPertussis nis highly contagious. More than 90 % nof susceptible house hold contacts become infected. More often occurs iinfants (who were not vaccinated).

 

Pathogenesis        

·                       nEntrance gate  is nURT mucus membrane;

·                       nDue nto several surface adhesions B. Pertussis attach to the respiratory epithelium of ntrachea;

·                       ncolonization on a cylinder nepithelium, toxin production;

·                       nlocal inflammatory processes, nnecrosis (catarrhal period);

·                       nThe norganism rarely invades tissues but produces the characteristic disease by nPertussis toxin systemic effects at distant sites iCNS (respiratory center, vascular center):

§     nviolation of breathing nrhythm , hypoxemia, hypoxia;

§     nvascular disorders + hypoxia n= encephalopathy.

·                       nformation of stagnant excitation focus in the brain.

·                       nprolonged clinical disease.

 

Clinical presentation.

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

 

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

 

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

·                       nParoxysmal cough should always nalert the physical to the diagnosis. These paroxysms occur at variable nintervals, and between episodes the patient usually appears comfortable, nwithout signs of severe illness.

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

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

·                       nHemorrhages in sclera, nose-bleeds, petechia oface are typical for this period.

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

·                       nChanges in other systems and organs:  n

o         nwhooping cough lung (hard breathing, nemphysema, intensification of pulmonary npicture), bronchitis, bronchiolitis, pneumonia, nathelectasis;

o         nhigh blood pressure, ntachycardia;

o         nencephalopathy (anxiety or apathy, ntremor, bad sleeping, seizures);

o         ndiarrhea (in infants).

Recovery nperiod for 2 – 4 weeks

•                       na cough loses spasmodic character, becomes neasier, more rare;

•                       nvomiting disappears;

•                       nAsthenia for long period.

 

Typical nWhooping cough severity

 

n

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	I 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:

•           npneumonia (specific, caused by nB.pertussis or secondary, caused by other bacteria);

•           nencephalopathy;

•           napnea;

•           nhemorrhages into sclera, skin, brain, ninner organs, nasal bleeding;

•           numbilical or inguinal hernia;

•           nprolapsed rectum mucous nmembrane;

•           npneumomediastinum or npneumothorax;

•           nulcer under the tongue.

 

Peculiarities of the npertussis in young infants:

•           nIncubation and catarrhal nperiods are shorter (few days).

•           nParoxysmal period is longer n(60-90 days).

•           nWhoops are absent.

•           nApnea occurs often.

•           nParoxysms of sneezing.

•           nOften pneumonia, encephalopathy nmay develop.

 

Laboratory Tests

1.         nA culture of nasopharyngeal nsecretions for B. pertussis may confirm the diagnosis.

2.         nDirect fluorescent antibody nstaining of nasopharyngeal secretions.

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

4.         nWBC count may be elevated above n15 000/ mm³ with 70 % or more lymphocytes.

5.         nPCR positive for B. pertussis nfrom the nasopharyngeal mucus.

 

Diagnosis example:

·                       nWhooping cough, typical form, paroxysmal period, severe degree, ncomplicated by apnea and encephalopathy

·                       nWhooping cough, typical form, paroxysmal period, moderate degree, ncomplicated by the leftside lobar pneumonia with cardiovascular syndrome, ncardiac insufficiency 1^st  ndegree.

·                       nWhooping cough, typical form, catarrhal period

 

Differential diagnosis

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

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

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

 

n

Whooping Cough Differential nDiagnosis

 

 

 

Treatment:

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

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

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

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

 

Pathogenetical therapy:

·            nquiet and comfort; ofteventilation, in mild and moderate cases – prolonged walks on fresh air

·            ndiet: usual daily food volume with nincreased numbers of feeding

·            ntherapy to decrease the cough ncenter irritation (synecod)

 

In severe cases also:

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

o         nnovocai0.25% 4 ml, +

o         naminazi2.5% 1 ml, +

o         npipolphe2.5% 1 ml (0.1 ml/kg of prepared solution).

·            nintubation and ventilator nsupport – in cause of apnea;

·            neuphyllin 5-10 mg/ kg/day;

·            nbronchial secretolytics (ambroxol, nacetylcystein etc.), suctioning of secretions;

·            nparenteral detoxication (5% nglucose, physiologic sodium chloride solution);

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

 

Prevention:

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

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

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

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

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

 

References:

1.   nManual nof 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.   nManual nof Childhood Infections: The Blue Book (Oxford Specialist Handbooks iPaediatrics) by Mike Sharland, Andrew Cant and al. Published by  Oxford University Press Inc., New York, 2011 n, p. 881  ISBN: 978-019-957-358-5.

3.   nIllustrated nTextbook of Paediatrics, 4th Edition.  nPublished by  Lissauer & nClayden, 2012, p. 552 ISBN: 978-072-343-566-2.

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

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

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