UPPER RESPIRATORY TRACT INFECTIONS The classification of upper

UPPER RESPIRATORY TRACT INFECTIONS

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

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

2. Pharyngitis Table 1. Etiology of pharyngitis Viral: Bacterial: -Rhinoviruses -Adenoviruses -Herpes simplex virus (type 1 and 2) -Parainfluenza virus -Influenza virus -Coxsackievirus A --Epstein Barr virus -Cytomegalovirus -HIV-1 -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)

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

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

Anaerobic pharyngitis (Vincent’s angina) The etiology is represented by mixture of anaerobic bacteria (Fusobacterium necrophorum) and spirochetes. 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. Herpetic pharyngitis It is characterized by the presence of: - vesicle and shallow ulcers on the palate - inflammation and inflammatory exudate -cervical adenopahy.

Herpangina is primarily seen in children. The etiologic agent are coxsackieviruses. Clinical features consist of: -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. Infection with Mycoplasma pneumoniae occurs primarily in collectivities of children and young.

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

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

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-perday schedule for 10 days. 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 Second-generation cephalosporins

3. Epiglottitis 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.

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

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

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

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

5. Acute laryngotracheobronchitis (croup) 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. Clinical manifestations . The croup is preceded by an upper respiratory tract infection. Laboratory findings Differential diagnosis Non infectious causes of stridor: Bacterial epiglottitis Complications Therapy: humidification devices of the airway, good supportive care, corticosteroids.

6. 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. Diagnostic modalities include fiberoptic nasal endoscopy, CT scans, and plain x-rays. Amoxicillin-clavulanic acid, trimethoprim/sulfametoxazole, amocillin Azithromycin/Clarithromycin (if penicillin allergy); Levofloxacin/moxifloxacin (when Penicillin-Resistant Pneumococcus is suspected);

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

INFLUENZA The Orthomyxoviridae (influenza viruses) Three immunologic types are known: Type A; Type B Type C Etiology The HA protein. 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(H 3 N 2). So far, 14 subtypes of HA (H 1 -H 14) and nine subtypes of NA (N 1 -N 9) in many different combinations have been recovered. 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

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 B sometimes causes epidemics, Influenza type A can causes around the world massive epidemics called pandemics

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

Clinical findings Uncomplicated Influenza Incubation period: 1 -4 days. Symptoms usually appear abruptly and include: - chills, - headache, - 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 - generalised muscle aches, - malaise and anorexia Complications -Pneumonia

Reye’s Syndrome : . 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.

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

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

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

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

Laboratory Diagnosis of influenza relies on: isolation of the virus; identification of viral antigen or viral nucleic acid in the patient’s cells, or 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.

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

Prevention Inactivated viral vaccines The vaccine is usually a cocktail containing two influenza A subtypes (H 1 N 1, H 3 N 2) and a type B virus of the strains isolated in the previous winter’s outbreaks. Annual influenza vaccination is recommended for high-risk groups. : • Persons >50 years old • those with either chronic heart or lung disease, • adult and children with asthma, or metabolic or renal disorders, immunossuppression, hemoglobinopathy • residents of nursing homes; • persons who might transmit influenza to high-risk groups : - medical personnel, - employees in chronic care facilities, - household members.

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

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

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

Neurologic manifestations 1. CSF pleoocytosis -Meningitis 2. Encephalitis 3. Other features in mumps are: -Renal function abnormalities (>60%); -ECG abnormalities (5 -15%); -Pancreatitis -Thyroid inflammation:

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

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

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.

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

Etiology The Epstein-Barr virus (EBV) Pathogenesis 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. Some latently infected cells undergo lytic replication in the oropharynx, resulting in production of virus with shedding the virus into the saliva.

Clinical manifestations Incubation period: 30 -50 days. 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. A morbilliform rash As a result of congenital infection an embriopathy may occasionally result:

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

Laboratory tests a. Hemoleucogram shows a mononucleosis syndrome: -Leukocytosis - an absolute increase in the number of peripheral mononuclear 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.

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

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.

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

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

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.

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

Pathology 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. 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

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

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

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

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

Treatment 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. If the antitoxin is administrated in the first day of illness, the mortality is less than 1%. Antibiotics PENICILLIN or ERYTHROMYCIN 2. Supportive care and maintenance of an airway 3. Strict bed rest during the acute phase of diphteria.

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. 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 1970 s; in countries with low immunization coverage, diphteria continues to be endemic.