1. UPPER RESPIRATORY TRACT INFECTIONS

2. The classification of upper respiratory tract infections includes: The common cold The common cold Pharyngitis Pharyngitis Epiglotitis Epiglotitis Acute laryngitis Acute laryngitis Acute laryngotracheobronchitis Acute laryngotracheobronchitis Sinusitis Sinusitis Otitis externa, otitis media and mastoiditis Otitis externa, otitis media and mastoiditis

3. 1. The common cold Viruses associated with the common cold are adenoviruses, parainfluenza virus, influenza virus, rhinoviruses and respiratory syncytial virus. Viruses associated with the common cold are adenoviruses, parainfluenza virus, influenza virus, rhinoviruses and respiratory syncytial virus.

4. 2. Pharyngitis Table 1. Etiology of pharyngitis Viral:-Rhinoviruses-Adenoviruses -Herpes simplex virus (type 1 and 2) -Parainfluenza virus -Influenza virus -Coxsackievirus A --Epstein Barr virus -Cytomegalovirus-HIV-1 Bacterial: -Streptococcus pyogenes (Group A and C beta-hemolytic streptococcus) -N. gonorrhoeae -Corynebacterium diphteriae -Yersinia enterocolitica -Treponema Chlamydia pneumoniae Mycoplasma pneumoniae and hominis Mixed anaerobic bacterial infection (Vincent’s angina)

5. Clinical manifestations Streptococcal pharyngitis Streptococcal pharyngitis Streptococcal pharyngitis - is characterized by: Streptococcal pharyngitis - is characterized by: High fever High fever Severe pharyngeal pain Severe pharyngeal pain Odynophagia Odynophagia Headache, chills Headache, chills Edema and hyperemia of the tonsills/uvula Edema and hyperemia of the tonsills/uvula A patchy, grayish-yellow exudate on the tonsils A patchy, grayish-yellow exudate on the tonsils Tender, enlarged cervical lymph nodes. Tender, enlarged cervical lymph nodes.

6. Complications of streptococcal pharyngitis Suppurative complications: Suppurative complications: Nonsuppurative complications: acute rheumatic fever, acute glomerulonephritis. Nonsuppurative complications: acute rheumatic fever, acute glomerulonephritis.

7. Anaerobic pharyngitis (Vincent’s angina) Anaerobic pharyngitis (Vincent’s angina) The etiology is represented by mixture of anaerobic bacteria (Fusobacterium necrophorum) and spirochetes. The etiology is represented by mixture of anaerobic bacteria (Fusobacterium necrophorum) and spirochetes. Pharyngoconjunctival fever Pharyngoconjunctival fever Adenoviruses are involved in etiology and the manifestations include: malaise, myalgia, sore throat, headache, chills, dizziness, conjunctivitis, erythema and inflammatory exudate. Evolution of temperature is usually 5-6 days. Adenoviruses are involved in etiology and the manifestations include: malaise, myalgia, sore throat, headache, chills, dizziness, conjunctivitis, erythema and inflammatory exudate. Evolution of temperature is usually 5-6 days. Herpetic pharyngitis Herpetic pharyngitis It is characterized by the presence of: It is characterized by the presence of: - vesicle and shallow ulcers on the palate - vesicle and shallow ulcers on the palate - inflammation and inflammatory exudate - inflammation and inflammatory exudate -cervical adenopahy. -cervical adenopahy.

8. Herpangina Herpangina Herpangina is primarily seen in children. The etiologic agent are coxsackieviruses. Herpangina is primarily seen in children. The etiologic agent are coxsackieviruses. Clinical features consist of: Clinical features consist of: -marked sore throat, dysphagia, anorexia -marked sore throat, dysphagia, anorexia -small vesicles (1-2 mm) on the soft palate, uvula, and anterior tonsilar pillars; after the rupture of vesicles, small and white ulcers appear. -small vesicles (1-2 mm) on the soft palate, uvula, and anterior tonsilar pillars; after the rupture of vesicles, small and white ulcers appear. Infection with Mycoplasma pneumoniae occurs primarily in collectivities of children and young. Infection with Mycoplasma pneumoniae occurs primarily in collectivities of children and young.

9. Differential diagnosis Infectious pharyngitis must be distinguished from noninfectious conditions: Infectious pharyngitis must be distinguished from noninfectious conditions: Bullous pemphigoid Bullous pemphigoid Systemic lupus erythematous Systemic lupus erythematous Behcet’s disease Behcet’s disease Kawasaki disease Kawasaki disease

10. Laboratory diagnosis Throat culture Throat culture Rapid antigen detection tests in throat swab Rapid antigen detection tests in throat swab Specific serologic tests for infectious mononucleosis Specific serologic tests for infectious mononucleosis Serologic tests for My. pneumoniae, herpes simplex, adenoviruses, etc. Serologic tests for My. pneumoniae, herpes simplex, adenoviruses, etc.

11. Treatment of sterptococcal pharyngitis: 1. The current recommended treatment for this infection is penicillin V 25-50 mg/kg/day divided into a 4-dose-per- day schedule for 10 days. 2. Benzathine penicillin (penicillin G) 50,000 u/kg intramuscular 2. Benzathine penicillin (penicillin G) 50,000 u/kg intramuscular 3. If a patient is penicillin-allergic: erythromycin 30 mg/kg/day or azithromycin (given once daily for 5 days only) or clarithromycin (twice daily for 10 days) First-generation cephalosporins First-generation cephalosporins Second-generation cephalosporins Second-generation cephalosporins

12. 3. Epiglottitis Acute epiglottitis is defined as a cellulitis of the epiglottis and adjacent structures that may produces complete airway obstruction. Acute epiglottitis is defined as a cellulitis of the epiglottis and adjacent structures that may produces complete airway obstruction. The most frequently etiologic pathogen is H. influenza type B, and occasionally pneumococcus, staphylococcus, streptococcus. H. influenzae epiglottitis may be associated in a large proportion of cases with bacteremia and sepsis, with different secondary location of infection. The most frequently etiologic pathogen is H. influenza type B, and occasionally pneumococcus, staphylococcus, streptococcus. H. influenzae epiglottitis may be associated in a large proportion of cases with bacteremia and sepsis, with different secondary location of infection.

13. Clinical manifestations Onset is abrupt, marked by fever, irritability, dysphonia, dysphagia, followed by respiratory distressLaryngoscopy reveals a “cherry-red” epiglottis. Onset is abrupt, marked by fever, irritability, dysphonia, dysphagia, followed by respiratory distressLaryngoscopy reveals a “cherry-red” epiglottis.

14. Laboratory features Leukocytosis with neutrophilia Leukocytosis with neutrophilia Positive cultures of blood and epiglottis Positive cultures of blood and epiglottis Radiograph of the lateral neck shows enlarged Radiograph of the lateral neck shows enlarged Differential diagnosis includes: croup, dyphteria, angioneurotic edema, foreign body aspiration, etc.. Differential diagnosis includes: croup, dyphteria, angioneurotic edema, foreign body aspiration, etc..

15. Therapy: intravenous therapy with antibiotics such as: cefotaxime (100-180mg/kg/day), ceftriaxone (80-100mg/kg/day) or amocicillin-clavulanic acid(200mg of amoxicillin/kg/day) for 7-10 days. intravenous therapy with antibiotics such as: cefotaxime (100-180mg/kg/day), ceftriaxone (80-100mg/kg/day) or amocicillin-clavulanic acid(200mg of amoxicillin/kg/day) for 7-10 days.

16. 4. Acute laryngitis Etiology: Etiology: - viruses - viruses - bacteria - bacteria - fungi - fungi Clinical manifestations: recent onset of hoarsness or episodes of aphonia. Clinical manifestations: recent onset of hoarsness or episodes of aphonia. Examination of larynx reveals hyperemia of vocal folds. Examination of larynx reveals hyperemia of vocal folds. Differential diagnosis: croup, acute epiglottitis, supraglottitis, bacterial tracheitis, voice abuse, gastroesophageal reflux disease, laryngeal malignancy. Differential diagnosis: croup, acute epiglottitis, supraglottitis, bacterial tracheitis, voice abuse, gastroesophageal reflux disease, laryngeal malignancy. Antibiotics are not routinely recommended. Antibiotics are not routinely recommended.

17. 5. Acute laryngotracheobronchitis (croup) Acute laryngotracheobronchitis is a viral infection that consists of inflammation in the subglottic area. Acute laryngotracheobronchitis is a viral infection that consists of inflammation in the subglottic area. Etiology: parainfluenza viruses, influenza A, B viruses, respiratory syncitial virus, adenovirus, rhinovirus, enterovirus, and rarely, Mycoplasma pneumoniae. Etiology: parainfluenza viruses, influenza A, B viruses, respiratory syncitial virus, adenovirus, rhinovirus, enterovirus, and rarely, Mycoplasma pneumoniae. Clinical manifestations Clinical manifestations The croup is preceded by an upper respiratory tract infection. The croup is preceded by an upper respiratory tract infection.. Laboratory findings Laboratory findings Differential diagnosis Differential diagnosis Non infectious causes of stridor: Non infectious causes of stridor: Bacterial epiglottitis Bacterial epiglottitis Complications Complications Therapy: humidification devices of the airway, good supportive care, corticosteroids. Therapy: humidification devices of the airway, good supportive care, corticosteroids.

18. 6. Sinusitis The most common bacteria are: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, and Staphylococcus aureus. Anaerobic bacteria,Fungal sinusitis The most common bacteria are: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, and Staphylococcus aureus. Anaerobic bacteria,Fungal sinusitis Viruses may also cause sinusitis. Viruses may also cause sinusitis. Diagnostic modalities include fiberoptic nasal endoscopy, CT scans, and plain x-rays. Diagnostic modalities include fiberoptic nasal endoscopy, CT scans, and plain x-rays. Amoxicillin-clavulanic acid, trimethoprim/sulfametoxazole, amocillin Amoxicillin-clavulanic acid, trimethoprim/sulfametoxazole, amocillin Azithromycin/Clarithromycin (if penicillin allergy); Azithromycin/Clarithromycin (if penicillin allergy); Levofloxacin/moxifloxacin (when Penicillin-Resistant Pneumococcus is suspected); Levofloxacin/moxifloxacin (when Penicillin-Resistant Pneumococcus is suspected);

19. 7. Otitis Media Etiological agents the most frequently seen are: S. pneumoniae, H. influenzae, M. catarrhalis, viruses (respiratory syncitial virus, rhinoviruses) Etiological agents the most frequently seen are: S. pneumoniae, H. influenzae, M. catarrhalis, viruses (respiratory syncitial virus, rhinoviruses) Diagnosis is suggested by: Diagnosis is suggested by: Hearing loss Hearing loss Ear pain Ear pain Fever Fever Delayed speech development in children Delayed speech development in children Therapy Therapy -Amoxillin or amoxicillin-clavulanic acid -Amoxillin or amoxicillin-clavulanic acid -Cefuroxime, ceftriaxone (50 mg/kg/day) -Cefuroxime, ceftriaxone (50 mg/kg/day) -Clindamycin (if failure of treatment after 3 days). -Clindamycin (if failure of treatment after 3 days).

20. INFLUENZA The Orthomyxoviridae (influenza viruses) Three immunologic types are known: Type A; Type B Type C Etiology The HA protein. The HA protein. The antigenicity of NA, The antigenicity of NA, The standard nomenclature system for influenza virus isolates includes the following information: -type, -host of origin, -geographic origin, -strain number, -year of isolation (example: A/Hong Kong/03/68(H3N2). So far, 14 subtypes of HA (H1-H14) and nine subtypes of NA (N1-N9) in many different combinations have been recovered. So far, 14 subtypes of HA (H1-H14) and nine subtypes of NA (N1-N9) in many different combinations have been recovered. Antigenic drift and antigenic shift Antigenic drift and antigenic shift. Minor antigenic changes are termed antigenic drift; Major antigenic changes in HA or NA, called antigenic shift Influenza virus replication Influenza virus replication

21. Epidemiology The three types of influenza vary in their epidemiologic patterns. Influenza C is least significant: it causes mild, sporadic respiratory disease, but not epidemic. Influenza C is least significant: it causes mild, sporadic respiratory disease, but not epidemic. Influenza B sometimes causes epidemics, Influenza B sometimes causes epidemics, Influenza type A can causes around the world massive epidemics called pandemics Influenza type A can causes around the world massive epidemics called pandemics

22. Pathogenesis Influenza virus spreads from person to person by airborne droplets or by contact with contaminated hands or surfaces. Influenza virus spreads from person to person by airborne droplets or by contact with contaminated hands or surfaces.

23. Clinical findings Clinical findings Uncomplicated Influenza Uncomplicated Influenza Incubation period: 1-4 days. Incubation period: 1-4 days. Symptoms usually appear abruptly and include: Symptoms usually appear abruptly and include: - chills, - chills, - headache, - headache, - dry cough- respiratory symptoms typically last another 3-4 days. The cough and weakness may persist for 1-3 weeks. - dry cough- respiratory symptoms typically last another 3-4 days. The cough and weakness may persist for 1-3 weeks. - high fever- lasts 3 days - high fever- lasts 3 days - generalised muscle aches, - generalised muscle aches, - malaise and anorexia - malaise and anorexia Complications Complications -Pneumonia -Pneumonia

24. Reye’s Syndrome :. Early signs: Early signs: -persistent/continuous vomiting -loss of energy -irritability -fluctuating personality changes -confusion As the encephalopathy becomes more severe, extreme irritability, agitation, delirium, convulsions, and coma may develop. As the encephalopathy becomes more severe, extreme irritability, agitation, delirium, convulsions, and coma may develop.

25. Laboratory findings hyperammoniemia hyperammoniemia elevated levels of alanin aminotransferase and aspartat aminotransferase elevated levels of alanin aminotransferase and aspartat aminotransferase prolonged prothrombin time prolonged prothrombin time hypoglycemia hypoglycemia hyperlactatemia hyperlactatemia acid-base disorders acid-base disorders CSF – with <8cells/mmc, and normal level of protein and glucose CSF – with <8cells/mmc, and normal level of protein and glucose

26. Treatment Glucose administration Glucose administration Antiedematous drugs, diuretics Antiedematous drugs, diuretics Fresh frozen plasma/fresh blood (if bleeding occurs) Fresh frozen plasma/fresh blood (if bleeding occurs) Corticosteroids Corticosteroids The mortality rate is high (10-50%). The mortality rate is high (10-50%).

27. Other complications: sinusites, myocarditis, pericarditis, cardiac failure, renal failure, neurological complications. Other complications: sinusites, myocarditis, pericarditis, cardiac failure, renal failure, neurological complications.

28. Immunity Immunity to influenza is long-lived and subtype-specific. Immunity to influenza is long-lived and subtype-specific.

29. Laboratory Diagnosis Diagnosis of influenza relies on: Diagnosis of influenza relies on: isolation of the virus; isolation of the virus; identification of viral antigen or viral nucleic acid in the patient’s cells, or identification of viral antigen or viral nucleic acid in the patient’s cells, or demonstration of a specific immunologic response. demonstration of a specific immunologic response. Other tests are: ELISA and RIA. Paired acute and convalescent sera are necessary, because normal individuals usually have influenza antibodies. A fourfold or greater increased in titer must occur to indicate influenza infection. Other tests are: ELISA and RIA. Paired acute and convalescent sera are necessary, because normal individuals usually have influenza antibodies. A fourfold or greater increased in titer must occur to indicate influenza infection.

30. Treatment Amantadine and rimantadine, Amantadine and rimantadine, Zanamivir and Oseltamivir Zanamivir and Oseltamivir All people at risk in whom influenza develops All people at risk in whom influenza develops Persons with severe influenza Persons with severe influenza For persons who wish to shorten the duration of illness. For persons who wish to shorten the duration of illness.

31. Prevention Inactivated viral vaccines Inactivated viral vaccines The vaccine is usually a cocktail containing two influenza A subtypes (H1N1, H3N2) and a type B virus of the strains isolated in the previous winter’s outbreaks. The vaccine is usually a cocktail containing two influenza A subtypes (H1N1, H3N2) and a type B virus of the strains isolated in the previous winter’s outbreaks. Annual influenza vaccination is recommended for high-risk groups.: Annual influenza vaccination is recommended for high-risk groups.: Persons >50 years old Persons >50 years old those with either chronic heart or lung disease, those with either chronic heart or lung disease, adult and children with asthma, or metabolic or renal disorders, immunossuppression, hemoglobinopathy adult and children with asthma, or metabolic or renal disorders, immunossuppression, hemoglobinopathy residents of nursing homes; residents of nursing homes; persons who might transmit influenza to high-risk groups : persons who might transmit influenza to high-risk groups : - medical personnel, - medical personnel, - employees in chronic care facilities, - employees in chronic care facilities, - household members. - household members.

32. MUMPS Mumps is an acute viral disease characterized by nonsuppurative swelling and tenderness of the salivary glands. Mumps is an acute viral disease characterized by nonsuppurative swelling and tenderness of the salivary glands.

33. Etiology Etiology Mumps virus belongs to paramyxoviridae family. Epidemiology Epidemiology The virus is spread by infectious saliva or by urine. Neonates are protected by transplacental maternal antibodies.

34. Clinical manifestations Incubation period: 14-25 days. Incubation period: 14-25 days. Prodromal symptoms (3 days): fever, headache, malaise. Prodromal symptoms (3 days): fever, headache, malaise. Glandular involvement: Glandular involvement: The onset of parotitis: The onset of parotitis: Submandibular/sublingual glands involvement (10% of cases) Epididymo-orchitis Oophoritis –

35. Neurologic manifestations 1.CSF pleoocytosis -Meningitis -Meningitis2.Encephalitis 3.Other features in mumps are: -Renal function abnormalities (>60%); -ECG abnormalities (5-15%); -Pancreatitis -Thyroid inflammation:

36. Complications Myocarditis – is very rare Myocarditis – is very rare Arthritis. Arthritis. Hemolytic anemia, trombocytopenia; Hemolytic anemia, trombocytopenia; Deafness with uni, or bilateral involvement; Deafness with uni, or bilateral involvement; In pregnant women (with gestational viral infection): In pregnant women (with gestational viral infection): fetal death is common during the first trimester. fetal death is common during the first trimester. low birth weight low birth weight endocardial fibroelastosis endocardial fibroelastosis juvenile diabetes mellitus. juvenile diabetes mellitus.

37. Laboratory features Laboratory features Diagnosis is based on: history of exposure, parotid swelling and tenderness, constitutional symptoms. Diagnosis is based on: history of exposure, parotid swelling and tenderness, constitutional symptoms. Differential diagnosis Differential diagnosis Parotid swelling must be differentiated by: Parotid swelling must be differentiated by: - Other infectious causes: - Other infectious causes: - Noninfectious causes: - Noninfectious causes: - Extraparotid causes: - Extraparotid causes: Prognosis is generally good, except severe forms of encephalitis, myocarditis, glotic edema. Lethality is approximately 0,01%. Prognosis is generally good, except severe forms of encephalitis, myocarditis, glotic edema. Lethality is approximately 0,01%.

38. Treatment Treatment is entirely symptomatic: analgesics for orchitis or pancreatitis, drugs against vomiting, etc. Patients should avoid acid food, the diet must be light, with a good hydration. Treatment is entirely symptomatic: analgesics for orchitis or pancreatitis, drugs against vomiting, etc. Patients should avoid acid food, the diet must be light, with a good hydration. The vaccine contains a live mumps, virus and may be administrated alone or in combination with measles and rubella vaccines. The vaccine contains a live mumps, virus and may be administrated alone or in combination with measles and rubella vaccines.

39. INFECTIOUS MONONUCLEOSIS Infectious mononucleosis is an acute illness characterized by fever, pharyngitis, lymphadenopathy, and mononuclear leukocytosis with atypical lymphocytes. Infectious mononucleosis is an acute illness characterized by fever, pharyngitis, lymphadenopathy, and mononuclear leukocytosis with atypical lymphocytes.

40. Etiology Etiology The Epstein-Barr virus (EBV) The Epstein-Barr virus (EBV) Pathogenesis Pathogenesis EBV infects B lymphocytes and epithelial cells in the oropharynx and cervix. EBV infects B lymphocytes and epithelial cells in the oropharynx and cervix. During primary infection, EBV-infected B-cells undergo lytic infection with production of virus or express the full complement of latent viral proteins. The latter cells are kept in check by natural killer and cytotoxic T cells, which may appear as “atypical lymphocytes” on the peripheral blood smear. During primary infection, EBV-infected B-cells undergo lytic infection with production of virus or express the full complement of latent viral proteins. The latter cells are kept in check by natural killer and cytotoxic T cells, which may appear as “atypical lymphocytes” on the peripheral blood smear. Some latently infected cells undergo lytic replication in the oropharynx, resulting in production of virus with shedding the virus into the saliva. Some latently infected cells undergo lytic replication in the oropharynx, resulting in production of virus with shedding the virus into the saliva.

41. Clinical manifestations Incubation period: 30-50 days. Incubation period: 30-50 days. Characteristic triad consists of: fever (75% of cases), pharyngitis (84%), and lymphadenopathy (94%). Characteristic triad consists of: fever (75% of cases), pharyngitis (84%), and lymphadenopathy (94%). Other common signs and symptoms are: splenomegaly (50%), hepatomegaly (10%), palatal petechiae (10%), rash (10%), jaundice (10%) associated with sore throat, headache, anorexia, abdominal pain, nausea, chills, myalgia. Other common signs and symptoms are: splenomegaly (50%), hepatomegaly (10%), palatal petechiae (10%), rash (10%), jaundice (10%) associated with sore throat, headache, anorexia, abdominal pain, nausea, chills, myalgia. A morbilliform rash A morbilliform rash As a result of congenital infection an embriopathy may occasionally result: As a result of congenital infection an embriopathy may occasionally result:

42. Complications Neurologic complications. Neurologic complications. Haematologic complication: Haematologic complication: Hepatitis, myocarditis, splenic rupture, genital ulcers. Hepatitis, myocarditis, splenic rupture, genital ulcers.

43. Laboratory tests Laboratory tests a. Hemoleucogram shows a mononucleosis syndrome: -Leukocytosis -Leukocytosis - an absolute increase in the number of peripheral mononuclear cells - an absolute increase in the number of peripheral mononuclear cells -atypical lymphocytes (>10%) which are primary T cells responding to the EBV-infected cells. -atypical lymphocytes (>10%) which are primary T cells responding to the EBV-infected cells. b. Elevated serum aminotransferase levels c. Serological tests. The humoral immune response to EBV infection involves both viral-specific and nonspecific antibodies. The humoral immune response to EBV infection involves both viral-specific and nonspecific antibodies.

44. Nonspecific antibodies: Nonspecific antibodies: Paul-Bunnell-Davidson test – Paul-Bunnell-Davidson test – Three specific antibodies to EBV antigens are diagnostically important, and the antigens are: Three specific antibodies to EBV antigens are diagnostically important, and the antigens are: VCA – viral capsid antigen VCA – viral capsid antigen EA – early antigen EA – early antigen EBNA – EBV nuclear antigen EBNA – EBV nuclear antigen

45. d. Isolation of the pathogen -EBV culture is not a routine method -demonstration of EBV genoma by PCR and of EBV antigen by immunoblot techniques.

46. Other clinical syndromes produced by EBV infection Other clinical syndromes produced by EBV infection Chronic active EBV infection - is a rare disorder Chronic active EBV infection - is a rare disorder X-Linked Lymphoproliferative Disease -. X-Linked Lymphoproliferative Disease -. Cancers associated with EBV Cancers associated with EBV 1.Nasopharyngeal carcinoma – 3.Hodgkin’s disease. 4.Lymphoproliferative disease – 5.Other tumors: Treatment Treatment No specific therapy is indicated for most patients with infectious mononucleosis. No specific therapy is indicated for most patients with infectious mononucleosis. Corticosteroid therapy is recommended for patients with severe complications: Corticosteroid therapy is recommended for patients with severe complications:

47. Treatment No specific therapy is indicated for most patients with infectious mononucleosis. No specific therapy is indicated for most patients with infectious mononucleosis. Corticosteroid therapy is recommended for patients with severe complications: Corticosteroid therapy is recommended for patients with severe complications:

48. DIPHTHERIA Diphtheria is an acute disease manifested by both local infection of the upper respiratory tract and the systemic effects of a toxin, which are most notable in the heart and peripheral nerves. Diphtheria is an acute disease manifested by both local infection of the upper respiratory tract and the systemic effects of a toxin, which are most notable in the heart and peripheral nerves.

49. Etiology The etiologic agent is the principal human pathogen of the Corynebacterium group, C. diphtheriae, an aerobic gram-positive bacillus with irregular shape. The etiologic agent is the principal human pathogen of the Corynebacterium group, C. diphtheriae, an aerobic gram-positive bacillus with irregular shape.

50. Pathology All human tissues may suffer by the toxin because all human cells have receptor sites. All human tissues may suffer by the toxin because all human cells have receptor sites. The diphtheria bacilli within the membrane continue to produce toxin actively. This is absorbed and leads to distant toxic damage, particularly parenchymatous degeneration, fatty infiltration and necrosis in heart muscle, liver, kidneys (tubular necrosis), adrenals, sometimes accompanied by important hemorrhage. The toxin also produces nerve damage (neuronal demyelination), resulting often in paralysis of the soft palate, eye muscles, or extremities. The diphtheria bacilli within the membrane continue to produce toxin actively. This is absorbed and leads to distant toxic damage, particularly parenchymatous degeneration, fatty infiltration and necrosis in heart muscle, liver, kidneys (tubular necrosis), adrenals, sometimes accompanied by important hemorrhage. The toxin also produces nerve damage (neuronal demyelination), resulting often in paralysis of the soft palate, eye muscles, or extremities. There are 2 phases of diphtheria: the initial local presentation as a severe pharyngitis with tough membranes that can cause suffocation and a late systemic phase caused by the effects of the circulating exotoxin on tissues of the host. There are 2 phases of diphtheria: the initial local presentation as a severe pharyngitis with tough membranes that can cause suffocation and a late systemic phase caused by the effects of the circulating exotoxin on tissues of the host. Nondiptheria corynebacteria produce localized or systemic diseases Nondiptheria corynebacteria produce localized or systemic diseases

51. Clinical Findings Incubation period is usually less than 1 week. Incubation period is usually less than 1 week.Pharyngitis. Laryngeal diphtheria. Laryngeal diphtheria. Nasal diphteria Cutaneous infection Cutaneous infection Other organ involvement includes: ears, conjunctiva, cornea. Other organ involvement includes: ears, conjunctiva, cornea.

52. Complications 1. Cardiovascular complications Myocarditis Myocarditis Late myocarditis Late myocarditis 2. Neurologic complications a.Palatal paralysis a.Palatal paralysis b.Oculomotor paralysis b.Oculomotor paralysis c.Peripheral polyneuritis c.Peripheral polyneuritis

53. Laboratory Tests Laboratory Tests 1.Isolation of C. diphteriae 1.Isolation of C. diphteriae 2. Stained smears show beaded rods in typical arrangement. 2. Stained smears show beaded rods in typical arrangement.

54. Diagnosis Differential diagnosis Other pharyngeal diseases: Other pharyngeal diseases: Retropharyngeal and peritonsillar abscesses. Retropharyngeal and peritonsillar abscesses. A foreign body in the larynx, viral laryngitis A foreign body in the larynx, viral laryngitis

55. Treatment Note: specific treatment must never be delayed for laboratory reports if the clinical picture is strongly suggestive of diphtheria. Note: specific treatment must never be delayed for laboratory reports if the clinical picture is strongly suggestive of diphtheria. 1.The imperative in diphtheria treatment is to administer the antitoxin as soon as possible, as it is the only mean to neutralize toxin that has not already bound to cells. The mainstay of therapy is prompt administration of equine diphtheria antitoxin: 20000-100000 IU, i.v. the test for hypersensitivity consists of administration of one drop of antitoxin diluted 1:10 in one eye. as possible, as it is the only mean to neutralize toxin that has not already bound to cells. The mainstay of therapy is prompt administration of equine diphtheria antitoxin: 20000-100000 IU, i.v. the test for hypersensitivity consists of administration of one drop of antitoxin diluted 1:10 in one eye. If the antitoxin is administrated in the first day of illness, the mortality is less than 1%. If the antitoxin is administrated in the first day of illness, the mortality is less than 1%. Antibiotics PENICILLIN or ERYTHROMYCIN Antibiotics PENICILLIN or ERYTHROMYCIN 2. Supportive care and maintenance of an airway 2. Supportive care and maintenance of an airway 3.Strict bed rest during the acute phase of diphteria. 3.Strict bed rest during the acute phase of diphteria.

56. Prevention Diphtheria was the first bacterial disease for which toxic cause was demonstrated and the first to be treated successfully with an antitoxin. In 1913 a vaccine was created, composed of treated diphtheria toxin, called anatoxin, later transformed in diphtheria toxoid. In 1940 a combined vaccine appeared: DTP = Diphtheria toxoid + Tetanus toxoid + Pertussis vaccine. Diphtheria was the first bacterial disease for which toxic cause was demonstrated and the first to be treated successfully with an antitoxin. In 1913 a vaccine was created, composed of treated diphtheria toxin, called anatoxin, later transformed in diphtheria toxoid. In 1940 a combined vaccine appeared: DTP = Diphtheria toxoid + Tetanus toxoid + Pertussis vaccine. Active immunization in childhood with diphtheria toxoid Active immunization in childhood with diphtheria toxoid In the most developing countries, immunization with diphteria and tetanus toxoids and pertussis vaccine was introduced by the late 1970s; in countries with low immunization coverage, diphteria continues to be endemic. In the most developing countries, immunization with diphteria and tetanus toxoids and pertussis vaccine was introduced by the late 1970s; in countries with low immunization coverage, diphteria continues to be endemic.