TonsillitisTonsillitis а аnd nd DiphtheriaDiphtheria

Prof. L. Shostakovych-KoretskayaDep.Inf.Dis. DMA

Tonsillitis Tonsillitis is is

an inflammation of the an inflammation of the tonsils.tonsils.

DifinitionsDifinitions

ICD-10 provides: streptococcal ICD-10 provides: streptococcal tonsillitis-J02tonsillitis-J02

J03-streptococcal pharyngitis J03-streptococcal pharyngitis streptococcal tonzillopharyngitisstreptococcal tonzillopharyngitis

Types of Inflammation Types of Inflammation

• Catarrhal tonsillitis• Exudative tonsillitis - Due Viral infections - Purulent (bacterial) • Membranous tonsillitis - Diphtheria -EBV-infection - Oropharyngeal candidiasis • Herpetic pharyngitis

Causes of TonsillitisCauses of Tonsillitis

Viral infections:Viral infections: Adenovirus,other ARIAdenovirus,other ARI

Group A streptococcal Group A streptococcal bacteriabacteria..

Epstein-Barr virusEpstein-Barr virus BacteroidesBacteroides and and

FusobacteriumFusobacterium

Non InfectiousNon Infectious

Systemic Lupus Systemic Lupus ErythematosusErythematosus

Syndrome Stevens Syndrome Stevens JohnsonJohnson

LeukemiaLeukemia Radiation Radiation Burns pharyngitisBurns pharyngitis

InfectiousInfectious

Catarrhal tonsillitis Catarrhal tonsillitis (Commonly viral)(Commonly viral) Hyperemia of the pharynx and Hyperemia of the pharynx and

tonsil with follicular tonsil with follicular hyperplasia hyperplasia

Serous exudate Serous exudate Other catarrhal symptoms: Other catarrhal symptoms:

cough, rhinitis, conjunctivitis, cough, rhinitis, conjunctivitis, fever, lymph node fever, lymph node enlargement Duration 5-7 enlargement Duration 5-7 daysdays

Types of exudative Types of exudative tonsillitistonsillitisFollicular tonsillitis

• Membranous tonsillitis

Streptococcal tonsillitis-B-Streptococcal tonsillitis-B-Hemolytic streptococcus Hemolytic streptococcus group Agroup A

Epidemyology GASEpidemyology GAS

Source: sick patients, or carries Source: sick patients, or carries of infectionof infection

Transmission: air-drop , person to Transmission: air-drop , person to person contacts: person contacts:

Season: spring-summerSeason: spring-summer

Clinical PresentationClinical Presentation Rapid onsetRapid onset Fever 39-40° C Fever 39-40° C Cervical lymphadenitisCervical lymphadenitis Intense pain in the throat, Intense pain in the throat,

hyperemia pharynx and tonsilshyperemia pharynx and tonsils Bright, purulent exudate coating Bright, purulent exudate coating

the tonsils or white patches on the tonsils or white patches on mucous of the tonsil,mucous of the tonsil,

Swelling of the soft palate Swelling of the soft palate

Diagnostic GASDiagnostic GAS

Bacteriological method Bacteriological method Rapid tests: Latex-Agglutination, Rapid tests: Latex-Agglutination,

agglutination agglutination ELISA, ELISA, DNA hybridization, polymerase DNA hybridization, polymerase

chain reaction-exposure of DNAchain reaction-exposure of DNA

Treatment GASTreatment GAS

Penicillin (oral, parenteral) Penicillin (oral, parenteral) Cephalosporins 1-2 generation of Cephalosporins 1-2 generation of MacrolidesMacrolides Duration of the therapy – 10 daysDuration of the therapy – 10 days

Diphtheria Diphtheria

Acute anthroponous diseaseAcute anthroponous disease, , caused by Gramcaused by Gram(+) (+) toxigenic toxigenic bacillus bacillus Corynebacterium Corynebacterium diphtheria, diphtheria, characterized by local characterized by local fibrinous-inflammation of the fibrinous-inflammation of the mucus and/or skin, general mucus and/or skin, general intoxication and toxic intoxication and toxic complicationscomplications: : myocarditismyocarditis, , polyneuritispolyneuritis, , nephrosis.nephrosis.

Corynebacterium  diphtheriaeCorynebacterium  diphtheriae cells cells stained by Albert's techniquestained by Albert's technique

HistoryHistory Throughout history, diphtheria was a Throughout history, diphtheria was a

leading cause of death among childrenleading cause of death among children Through the ages, several epidemics Through the ages, several epidemics

struck Europe, and even the American struck Europe, and even the American colonies in the 18th century.colonies in the 18th century.

In 1921, there were 206,000 cases of In 1921, there were 206,000 cases of diphtheria recorded in the U.S., with diphtheria recorded in the U.S., with 15,520 deaths.15,520 deaths.

More recently, in the 1990s, large More recently, in the 1990s, large outbreaks of diphtheria occurred in outbreaks of diphtheria occurred in Russia ,Ukraine and in other the former of Russia ,Ukraine and in other the former of the Soviet Union countriesthe Soviet Union countries

HistoryHistory

The diphtheria bacterium was first The diphtheria bacterium was first identified in the 1880s.identified in the 1880s.

In the 1890s, the antitoxin against In the 1890s, the antitoxin against diphtheria was developed, with the first diphtheria was developed, with the first vaccine being developed in the 1920s. vaccine being developed in the 1920s.

With the development and With the development and administration of the diphtheria administration of the diphtheria vaccine, the incidence of diphtheria vaccine, the incidence of diphtheria has decreased significantlyhas decreased significantly

EpidemiologyEpidemiology

The source of infection is sick person and The source of infection is sick person and carrier carrier

The way of transmission is respiratory The way of transmission is respiratory primarily during close contact.primarily during close contact.

The autumn-winter seasonably is The autumn-winter seasonably is characteristic of diphtheriacharacteristic of diphtheria

Immunity after this disease isn’t strong. Immunity after this disease isn’t strong. Person may be sick repeatedlyPerson may be sick repeatedly

TransmissionTransmission

Diphtheria is primarily transmitted via Diphtheria is primarily transmitted via airborne respiratory droplets or by direct airborne respiratory droplets or by direct contact with nasopharyngeal secretions contact with nasopharyngeal secretions or skin lesions from infected people.or skin lesions from infected people.

Rarely, it can be spread by objects Rarely, it can be spread by objects contaminated by an infected person. contaminated by an infected person.

Overcrowding and poor living conditions Overcrowding and poor living conditions can further contribute to the spread of can further contribute to the spread of diphtheriadiphtheria

What type of bacteria cause What type of bacteria cause diphtheria?diphtheria?

Diphtheria is caused by toxin-producing Diphtheria is caused by toxin-producing strains of the gram-positive bacillus strains of the gram-positive bacillus Corynebacterium diphtheriaeCorynebacterium diphtheriae. There are . There are four biotypes of the bacterium (gravis, four biotypes of the bacterium (gravis, mitis, intermedius, and belfanti), and each mitis, intermedius, and belfanti), and each differs in the severity of disease it differs in the severity of disease it produces.produces.

Nontoxigenic strains are usually Nontoxigenic strains are usually responsible for less severe diphtheria responsible for less severe diphtheria involving the skin (cutaneous diphtheria). involving the skin (cutaneous diphtheria).

PathogenesisPathogenesis

1. In majority cases the Corynebacterium diphtheria is an upper respiratory tract disease.

2. The common sections where the bacterium multiplies is at throat and nasopharynx (common symptom is advance sore throat) the bacterium can also spread around the body by the blood circulation system (lymph nodes).

PathogenesisPathogenesis

Corynebacterium diphtheria is a bacterium which produces toxin. This toxin has effects on the membrane cells, by inhibiting cellular protein synthesis.

It is also responsible for local tissue damage and affects cell membrane structure.

Inflammation reaction to the toxin also has an effect on the cell which results in tissue necrosis.

Corynebacterium diphtheria toxin

The toxin is 62,000-dalton polypeptide composed of two parts which are A and B.

Part A fragment inhibits protein synthesis in eukaryotic cells by catalyzing the NAD+-dependent ADP-ribosylation of elongation factor.

Part B fragment facilitates delivery of fragment A to the cytosol by binding to the cell surface receptors

PathogenesisPathogenesis Corynebacterium diphtheria can also

cause lesions and ulcers which are formed by bacteria, fibrin and inflammatory cells (pseudomembrane).

The lesions and ulcers are caused by the toxin secretion which has an effect on the cell membrane.

The pus which is produced by the bacterium can also effect breathing by blocking passage way with a coated pus which is located at back of the throat

PathogenesisPathogenesis

The toxin produced by Corynebacterium diphtheria is absorbed by the membrane into the bloodstream and distributed to the tissues of the body which cause the symptoms of mild fever and chills.

Also, the infection Corynebacterium diphtheria can cause the lymph glands to enlarge and swell to an abnormal size.

This enlarge lymph will appear on the neck (both sides of the neck) this is because Corynebacterium diphtheria invades the lymph nodes which cause them to inflame and harden

PathogenesisPathogenesis

The toxin is liable for major problems which are inflammation of the heart(myocarditis), heart failure, and neuromyelitis optica (nerve damage, paralysis).

It can also cause low platelet counts (thrombocytopenia) and can also cause the depletion of protein in the urine (proteinuria).

PathogenesisPathogenesis

The toxin secretion can also cause a number of different diseases which include necrosis of kidney tubules, cardiomyopathy, thrombocytopenia and demyelination of nerves .

The disease is caused in undeveloped countries where people have poor health styles and who are also susceptible (weak immunity) and people who have not been vaccinated.

Classification of Classification of DiphtheriaDiphtheriaDiphtheria of tonsils, mild formDiphtheria of tonsils, mild form..2. 2. Diphtheria of tonsils, moderate formDiphtheria of tonsils, moderate form..3. 3. Diphtheria of tonsils, severe form.Diphtheria of tonsils, severe form.4. 4. Hypertoxic form of Diphtheria of tonsilsHypertoxic form of Diphtheria of tonsils..

5. 5. Laryngeal diphtheria Laryngeal diphtheria ((diphtherial diphtherial laryngotracheitis, crouplaryngotracheitis, croup))

6. 6. Nasopharyngeal diphtheria Nasopharyngeal diphtheria ((diphtherial diphtherial nasopharyngitis, pharyngitisnasopharyngitis, pharyngitis) )

7. 7. Diphtheria of anterior parts of the noseDiphtheria of anterior parts of the nose8. 8. Diphtheria other localization (skin, eyes)Diphtheria other localization (skin, eyes)9. 9. Combined diphtheriaCombined diphtheria

SymptomsSymptoms The symptoms of respiratory diphtheria usually The symptoms of respiratory diphtheria usually

begin between two to five days after exposure to begin between two to five days after exposure to the diphtheria bacterium (the incubation period). the diphtheria bacterium (the incubation period). Symptoms of diphtheria of tonsil may include the Symptoms of diphtheria of tonsil may include the following: following:

Sore throatSore throat FeverFever MalaiseMalaise HoarsenessHoarseness Foul smelling nasal dischargeFoul smelling nasal discharge HeadacheHeadache CoughCough Difficulty swallowingDifficulty swallowing Difficulty breathingDifficulty breathing

ClinicClinic With the progression of diphtheria, the infected With the progression of diphtheria, the infected

individual may also develop an adherent gray individual may also develop an adherent gray membrane (pseudomembrane) forming over the membrane (pseudomembrane) forming over the lining tissues of the tonsils and/or nasopharynx. lining tissues of the tonsils and/or nasopharynx.

This pseudomembrane is necrotic (dead) tissue that This pseudomembrane is necrotic (dead) tissue that develops from the effects of the diphtheria toxin. develops from the effects of the diphtheria toxin.

Individuals with severe disease may also develop Individuals with severe disease may also develop neck swelling and enlarged lymph nodes of the neck swelling and enlarged lymph nodes of the neck, leading to a "bull-neck" appearance. neck, leading to a "bull-neck" appearance.

Extension of the pseudomembrane into the larynx Extension of the pseudomembrane into the larynx and trachea can lead to obstruction of the airway and trachea can lead to obstruction of the airway with subsequent suffocation and death.with subsequent suffocation and death.

Local features Local features (pharynx)(pharynx) Local inflammatory changes of the Local inflammatory changes of the

tonsils are followingtonsils are following: :

- - Mild hyperemia with cyanotic colorMild hyperemia with cyanotic color, , - - Edema of the pharynx and/or subcutaneous Edema of the pharynx and/or subcutaneous

neck tissueneck tissue, , - - Covers on the tonsilsCovers on the tonsils. . - - Covers are of grayish-whitish color, hard Covers are of grayish-whitish color, hard

to remove, the mucus bleeds after removalto remove, the mucus bleeds after removal. . - - Regional lymphadenitis – edema and mild Regional lymphadenitis – edema and mild

tenderness of the cervical lymph nodes.tenderness of the cervical lymph nodes.

Diphtheria tonsillDiphtheria tonsill

Bull-NeckBull-Neck

Systemic SymptomsSystemic Symptoms

The dissemination of the diphtheria toxin The dissemination of the diphtheria toxin to the rest of the body can also lead to to the rest of the body can also lead to systemic disease, causing complications :systemic disease, causing complications :

Inflammation of the heart (myocarditis) Inflammation of the heart (myocarditis) neurologic problems such as paralysis of neurologic problems such as paralysis of

the soft palate, vision problems, and the soft palate, vision problems, and muscle weakness. muscle weakness.

NephrosisNephrosis

Cutaneous diphtheriaCutaneous diphtheria

Cutaneous diphtheria is Cutaneous diphtheria is characterized by a nonhealing characterized by a nonhealing skin ulcer covered by a gray-skin ulcer covered by a gray-brown membrane. It is typically a brown membrane. It is typically a localized infection that is rarely localized infection that is rarely associated with systemic associated with systemic complicationscomplications

How is diphtheria How is diphtheria diagnosed?diagnosed?

The diagnosis of diphtheria is confirmed The diagnosis of diphtheria is confirmed by isolation of the bacterium by isolation of the bacterium Corynebacterium diphtheriaeCorynebacterium diphtheriae..

Diagnostic tests to isolate the bacterium Diagnostic tests to isolate the bacterium involve obtaining cultures from the nose involve obtaining cultures from the nose and throat in any individual suspected of and throat in any individual suspected of having diphtheria, as well as their close having diphtheria, as well as their close contacts.contacts.

Determining of toxin Determining of toxin productionproduction

It is also important to determine whether or not the It is also important to determine whether or not the isolate from an infected person is capable of producing isolate from an infected person is capable of producing diphtheria toxin, and this can be accomplished as well diphtheria toxin, and this can be accomplished as well by testing in specialized laboratories.by testing in specialized laboratories.

Finally, determining the patient's antibody levels to Finally, determining the patient's antibody levels to diphtheria toxin can also be helpful for evaluating the diphtheria toxin can also be helpful for evaluating the probability of the diagnosis of diphtheria and the probability of the diagnosis of diphtheria and the potential for severe illness. potential for severe illness.

Other tests, such as ECG, imaging studies, and blood Other tests, such as ECG, imaging studies, and blood work can also help assess the extent of involvement of work can also help assess the extent of involvement of the diseasethe disease

Laboratory Diagnosis of the Laboratory Diagnosis of the Diphtheria Diphtheria

А) А) Reaction of neutralization Reaction of neutralization ((Yensen methodYensen method): ): --Level of antitoxins Level of antitoxins ≤ 0,03 ≤ 0,03 IUIU\\mlml → → probable probable DiphtheriaDiphtheria;; --Level of antitoxins Level of antitoxins 0,05 0,05 toto 0,4 0,4 IUIU\\mlml → → Diphtheria Diphtheria can not be excludedcan not be excluded;; - - Level of antitoxins Level of antitoxins ≥0,5 ≥0,5 IUIU\\mlml ( (in first in first 5 5 days of days of the diseasethe disease) → ) → DiphtheriaDiphtheria is excluded is excluded В) В) Reaction of direct hemagglutination (protective Reaction of direct hemagglutination (protective level level ≥ 1:320 (≥ 1:320 (in first in first 5 5 days of the diseasedays of the disease) – ) – excludes excludes Diphtheria Diphtheria - - Determination of diphtheria antitoxin level in Determination of diphtheria antitoxin level in blood serum blood serum - - Molecular genetic methodsMolecular genetic methods ((PCRPCR)) – – determination of the genetic material of phage determination of the genetic material of phage producing toxin.producing toxin.

ReportReport

Suspected or confirmed cases of Suspected or confirmed cases of respiratory diphtheria should be respiratory diphtheria should be reported to your state health reported to your state health department. department.

If cutaneous diphtheria is If cutaneous diphtheria is suspected, samples from the skin suspected, samples from the skin can be obtained and sent to can be obtained and sent to specialized laboratories. specialized laboratories.

What is the treatment for What is the treatment for diphtheria?diphtheria?

If diphtheria is suspected in a patient, If diphtheria is suspected in a patient, prompt treatment should be undertaken prompt treatment should be undertaken even before confirmatory lab results are even before confirmatory lab results are available. Patients should also be placed available. Patients should also be placed in isolation to prevent further in isolation to prevent further transmission of the disease.transmission of the disease.

AntitoxinAntitoxin Diphtheria antitoxin is the mainstay of Diphtheria antitoxin is the mainstay of

therapy. It neutralizes circulating diphtheria therapy. It neutralizes circulating diphtheria toxin and reduces the progression of the toxin and reduces the progression of the disease.disease.

The effectiveness of diphtheria antitoxin is The effectiveness of diphtheria antitoxin is greatest if it is administered early in the greatest if it is administered early in the course of the disease. course of the disease.

The CDC can assist in obtaining the diphtheria The CDC can assist in obtaining the diphtheria antitoxin. Antitoxin is not recommended for antitoxin. Antitoxin is not recommended for asymptomatic carriers and it is usually of no asymptomatic carriers and it is usually of no value in localized cutaneous diphtheriavalue in localized cutaneous diphtheria

Diphtheria antitoxinDiphtheria antitoxin serum and antibiotics serum and antibiotics must be used immediatelymust be used immediately, , without waiting the without waiting the results of bacterial and serological results of bacterial and serological investigationsinvestigations

Form of DiphtheriaFirst dosage of

serumWay of

investigation

Mild diphtheria of tonsils

40 – 60 thousand IU Intramuscular

Moderate diphtheria of tonsils

80 - 100 thousand IU

Intramuscular

Severe diphtheria of tonsils, hypertoxic or combined forms of diphtheria

120 – 150 thousand IU

50% - Intramuscular, 50% - intravenous

AntibioticsAntibiotics Antibiotics should also be administered as soon Antibiotics should also be administered as soon

as possible to patients with suspected diphtheria. as possible to patients with suspected diphtheria. Antibiotics help eradicate the bacteria, thereby Antibiotics help eradicate the bacteria, thereby stopping toxin production, and they also help to stopping toxin production, and they also help to prevent transmission of diphtheria to close prevent transmission of diphtheria to close contacts.contacts.

Penicillin and erythromycin are the Penicillin and erythromycin are the recommended antibiotics. Asymptomatic carriers, recommended antibiotics. Asymptomatic carriers, as well as all close contacts potentially exposed as well as all close contacts potentially exposed to diphtheria, also require antibiotic treatment.to diphtheria, also require antibiotic treatment.

Affected individuals are usually not contagious Affected individuals are usually not contagious after 48 hours of antibiotic administrationafter 48 hours of antibiotic administration. .

Supportive measuresSupportive measures Supportive measures, such as Supportive measures, such as

inserting a breathing tube inserting a breathing tube (intubation), may be necessary if the (intubation), may be necessary if the patient cannot breathe on their own or patient cannot breathe on their own or if there is the potential for airway if there is the potential for airway obstruction. obstruction.

Potential cardiac and neurologic Potential cardiac and neurologic complications also need to be closely complications also need to be closely followed and addressed in followed and addressed in consultation with the proper specialist.consultation with the proper specialist.

AntibioticsAntibiotics procaine penicillin G at a dosage of 600,000 procaine penicillin G at a dosage of 600,000

units IM every 12 h until the patient can units IM every 12 h until the patient can swallow comfortably, after which oral swallow comfortably, after which oral penicillin V is given at 125–250 mg four times penicillin V is given at 125–250 mg four times daily to complete a 14-day course; daily to complete a 14-day course;

Or erythromycin at a dosage of 500 mg IV Or erythromycin at a dosage of 500 mg IV every 6 h until the patient can swallow every 6 h until the patient can swallow comfortably, after which 500 mg is given PO comfortably, after which 500 mg is given PO four times daily to complete a 14-day course.four times daily to complete a 14-day course.

PreventionPrevention The person with diphtheria is excluded from

school until they have recovered and had two negative throat swabs.

Contacts of the person with diphtheria are given antibiotics and may also need to have a booster vaccination with a diphtheria-toxoid containing vaccine

Contacts who are children are excluded from early childhood education, daycare, school and community activities until throat swabs shown they do not have the disease.

Adults who work with food or children are excluded from their work until throat swabs shown they do not have the disease.

Prophylaxis of Prophylaxis of Diphtheria Diphtheria in close contacts in close contacts

1.1. Determination of subjects of close contactDetermination of subjects of close contact2.2. Medical observation during 7Medical observation during 7 days from the days from the

last contactlast contact3.3. Laboratory investigation: all the contacts are Laboratory investigation: all the contacts are

performed cultures of throat and nose performed cultures of throat and nose independent of their vaccinal statusindependent of their vaccinal status

4.4. All the contacts are evaluated for the All the contacts are evaluated for the presence of skin erosions and if present, presence of skin erosions and if present, cultures must be done from skin erosionscultures must be done from skin erosions

5.5. At first signs of probable diphtheria in these At first signs of probable diphtheria in these patients the antitoxic serum is indicatedpatients the antitoxic serum is indicated

Antibiotic prophylaxis Antibiotic prophylaxis in contactsin contacts

Close contacts must receive Close contacts must receive antibiotic prophylaxis antibiotic prophylaxis

– – prolonged penicillin intramuscular once prolonged penicillin intramuscular once (1,2 (1,2 mlnmln UU););– – erythromycinerythromycin – – during during 7–10 7–10 days days (1 (1 gg//dayday))2. 2. All the carriers of toxigen strains of All the carriers of toxigen strains of C.diphtheriae must receive antibiotic C.diphtheriae must receive antibiotic treatmenttreatment

Immunization after Immunization after contact contact 1.1. All the contacts without complete course of All the contacts without complete course of

vaccination vaccination ((that is, who received less than 3 that is, who received less than 3 doses of anatoxindoses of anatoxin), ), should receive buster should receive buster dosage of vaccine, than should complete the dosage of vaccine, than should complete the vaccination according to the vaccination vaccination according to the vaccination schedule.schedule.

2.2. All the contacts with unknown vaccination All the contacts with unknown vaccination history history should receive buster dosage of should receive buster dosage of vaccine, than should complete the vaccination vaccine, than should complete the vaccination according to the vaccination scheduleaccording to the vaccination schedule..

3.3. All the contacts with complete course of All the contacts with complete course of vaccinationvaccination, , should also receive buster dosage should also receive buster dosage of vaccine, if vaccination was not performed of vaccine, if vaccination was not performed within the last 12 monthswithin the last 12 months. .

Immunization against Immunization against DiphtheriaDiphtheria

95%95% of children under 2 years of age should be of children under 2 years of age should be vaccinated by DPT. vaccinated by DPT.

Children of school age should receive buster Children of school age should receive buster immunization with diphtheria anatoxin; immunization with diphtheria anatoxin; 95%95% should be vaccinatedshould be vaccinated

90% 90% of adult population should be vaccinated with of adult population should be vaccinated with preferentially DT every 10 years.preferentially DT every 10 years.

In case of diphtheria outbreak, all the adult In case of diphtheria outbreak, all the adult population should be vaccinatedpopulation should be vaccinated: :

Clinical forms of diphtheria do not guarantee the Clinical forms of diphtheria do not guarantee the protective immune level protective immune level → all the patients after → all the patients after diphtheria should be vaccinated (Ukraine - after diphtheria should be vaccinated (Ukraine - after 6 months, USA - upon discharge from the 6 months, USA - upon discharge from the hospital)hospital)

FACT: Diphtheria can be prevented with a safe and effective

vaccine. Diphtheria can lead to breathing problems, heart

failure, paralysis, and sometimes death. Nearly one out of every 10 people who get diphtheria

will die from it. Most cases of diphtheria occur among unvaccinated or

inadequately vaccinated people.

Recovery from diphtheria is not always followed by lasting immunity, so even those persons who have survived the disease need to be immunized.