Chapter 2

Upper Infections

Tatjana Peroš-Golubičić, Jasna Tekavec-Trkanjec

Abstract Upper respiratory tract infections are the most common infections in the population. The term “upper respiratory tract” covers several mutually connected anatomical structures: nose, , middle ear, , , and proximal part of . Thus, infection in one part usually attacks the adjacent structures and may spread to the tracheobronchial tree and lungs. Most of acute upper respiratory tract infections are caused by viruses. Bacterial pathogens can also be the primary causative agents of acute upper respiratory infections, but more frequently, they cause chronic infections. although most of the upper respiratory infections are self-limiting, some of them may cause severe complications. These includes intracranial spreading of suppurative infection, sudden due to and diphtheria, rheumatic after streptococcal , etc. In this chapter, we will describe clinical settings, diagnostic work-up, and treatment of upper respiratory infections, with special consideration to complications and life-threatening diseases occurring as a result of these infections.

INTRODUCTION Most of these infections are of viral origin, involving more or less all the parts of upper The upper respiratory system includes the nose, nasal and associated structures, such as paranasal sinuses cavity, pharynx, and larynx with subglottic area of and middle ear. Common upper respiratory tract trachea. In the normal circumstances, air enters the infections include (inflammation of the nasal respiratory system through nostrils where it is filtered, mucosa), rhinosinusitis or (inflammation of humidified, and warmed inside the nasal cavity. the nares and paranasal sinuses, including frontal, Conditioned air passes through pharynx, larynx, and ethmoid, maxillary, and sphenoid), nasopharyngitis trachea and then enters in lower respiratory system. (rhinopharyngitis or the —inflammation Dysfunction of any part of upper respiratory tract may of the nares pharynx, hypopharynx, uvula, and ), change quality of inhaled air and consequently, may (inflammation of the pharynx, hypopharynx, impair function of tracheobronchial tree and lung. uvula, and tonsils), epiglottitis (inflammation of the Upper respiratory tract infections are the most common superior portion of the larynx and supraglottic area), infections in the population. They are the leading cause (inflammation of the larynx), laryngotracheitis for people missing work or school and, thus, have (inflammation of the larynx, trachea, and subglottic important social implications. They range from mild, area), and (inflammation of the trachea and self-limiting disease like common cold, syndrome of the subglottic area). nasopharynx to serious, life-threatening illnesses, such In most cases, these diseases are self-limiting and can as epiglottitis. be managed at home. The more severe cases or those

Chapter_2.indd 1 17-01-2014 15:29:40 Chapter_2.indd 2 2 Textbook of Respiratory and Critical Care Infections a simple respiratory upper tract may infection rapidly treatment andfollow-up should advocated, be because cell or organ transplantation. chemotherapy, dialysis, undergoing andthose stem patients infection, cancer, with (HIV) patients receiving human virus with those spleen, immunodeficiency immune like defenses for instance, those a without attention suboptimal isrecommended with inthose tract orprolonged infection course ofdisease. Special increased fordeveloping respiratory risk theupper oracquired),immune function(inherited there isan to engulf anddestroy invaders. In case ofdiminished by means ofnumerous andothermediates cytokines monocytes, neutrophils, coordinate and eosinophils) Inflammatory andimmune cells(macrophages, cellular immunity, actsto reduce thelocal infections. immunoglobulin from there, are they swallowed into thestomach. help transportupto thepharynx; allkinds ofparticles efficient.escalator-like withits Ciliated cells properties filter andtrapsome pathogens and mucus coats are very defenses. Mechanical like hair innose, barrier which physical, mechanical, humoral, andcellular immune all kinds ofinvaders. mechanisms Thedefense include tract, and nasal polyposis. mucosal resistance, anatomic changes of respiratory ‑handsmoking (second smoke which too!), may alter travellers exposure with to numerous individuals, small children whoattend thekindergarten orschool, tract are infections contact close like contact close of viral ofaprimarily infection. dueto superinfection be also cause respiratory ofupper tract butmay infection, they respiratory droplets. Bacterial could infections a be prime touching thesecretions by hand ordirectly by inhaling the cases, spreads theinfection from person-to-person, when andbacteria, which invadeviruses themucosa. In most Most respiratoryupper tract are infections caused by is necessary. cases,most serious care intheintensive care unit(ICU) of cure are R used. also instances ,in some traditional orsome way adrenergic agonists, corticosteroids, decongestants), anticholinergic agents, antihistamines, antitussives, symptomatic therapy issufficient (analgesics, antipyretics, complications medical help.with to seek need In general, The Disea Natural Occurrenc Of H to combatThe equipped well respiratory tract is very R isk factors forthedevelopment respiratory ofupper umoral immunity, by means oflocally secreted A and other immunoglobulins and arely, surgical orin intervention A

dequate antimicrobial clinical features approximately 10%ofadultcases ofpharyngitis. The A pharyngitis, colloquiallyknownasa“strep throat”. Group Throat cultures maybe indicated ofinvestigation as part of or fortheconfirmation ofnegative rapid antigen tests. evaluationthe routine pharyngitis ofadults with primary Throatis satisfactory. cultures are not for recommended it gives results inabout half an hour, anditsspecificity The rapid antigen test forgroup isfast, as AStreptococcus diagnosis isinconclusive, testing further isrecommended. andempirical isgiven. the When necessary • • • • • • Microbiology Microbiology final diagnosis is huge. techniques help inthemanagement patients. ofthese therapy. In instances, some visualization andimaging thecausativeor detect agent and,thus, enable efficient medical Theaimis to attention recognize isnecessary. immunocompromised persons, epidemics, orduring duration, othercircumstances orinsome like in the symptoms are severe, have prolonged unexpected mentioned. is built theclinical upon manifestations, asalready . The classification diseases ofthose cases rests recognition only upon ofthesymptoms and The diagnosis ofupper respiratory tract inmost infections patients. progress to asystemic illness inimmunocompromised is a group cases. insome Mostshould performed be frequent immunocompromised patients. except onseveral occasions like influenzaorin suspected for most viruses, viral testing usually isnotindicated, caused byandasthere viruses are notargeted therapies As mostrespiratory oftheupper tract are infections DIAGNOSI b-hemolytic streptococcus is the etiologic agent in If clinical suspicion is high, testing no further is (winter-spring). highest prevalence with Occurrence intheseason P (common inviral illness) A T Fever atemperature with ofat least 38.3°Cfor24hours E The armamentariumofinvestigations to reach the can treated be diseases ofthese Some at home. If The searchThe of type forthe causative infection bacterial ender anterior cervical lymph nodes ender anterior cervical atient age 5–15 years rythema, swelling,rythema, orexudates on tonsils or pharynx bsence ofcough,bsence , andconjunctivitis A

1 infection, especially with especially with infection, Streptococcal that can raise a suspicion are: 17-01-2014 15:29:41 3 Upper Respiratory Tract Infections T 17-01-2014 15:29:41 3 findings findings T findings, including including T findings, that owing to a very to owing that 4 CT thickening sinuses shows scan of paranasal findings suggestive of chronic sinusitis include include sinusitis chronic of suggestive T findings scanning can be helpful in the diagnosis of acute acute of diagnosis the in behelpful can scanning T levels, air-fluid opacification, sinus of T findings C C C or therapy despite extend of rhinosinusitis If symptoms also be useful in the may ultrasonography Sinus ecently, it has been reported it has ecently, -mode ultrasound may be a useful first-line examination examination be a useful first-line may -mode ultrasound good specificity and negative predictive value, bedside value, predictive good specificity and negative A patients ventilated and mechanically for intubated FIGURE 2 of the left maxillarypredominantly almost diffuse sinus, of ethmoid sinuses (especially leftopacification sinus) with partially thickening of sphenoidal septa. Marginal intracellular resorbed sinuses and thickening of the nasal passage is also detected. and chronic sinusitis, but it cannot distinguish between distinguish it cannot but sinusitis, and chronic C The sinusitis. paranasal chronic and acute features. clinical to with respect be to interpreted have of acute all features are mucosa localized and thickened nonspecific C Many sinusitis. sinus and diffusely thickened turbinates thickened 2). be detected (Figure may mucosa remodeling, bony opacified air cells, thickening, mucosal inflammatory due to of the osteitis thickening and bony occur in severe can erosion Bony walls. cavity sinus polyps or with especially,if associated cases massive mucocele. is suspected, tissue adjacent of disease into if propagation which or symptoms, Signs is indicated. imaging sinus C infection, of request extension intracranial warrent anfirm to the of an intracranial possibility analysis may symptoms Such complications. or other suppurative movements, intraocular impaired proptosis, include status, mental in changes papilledema, vision, decreased findings. or other neurologic be is to avoided. exposure or if radiation care intensive R ), ultrasound, and endoscopic inspection ), ultrasound, T Plain radiograph of sinuses shows polypoid edema of sinuses shows radiograph Plain

2

Common plain radiographic findings of sinus include include sinus of findings radiographic plain Common In most patients with­ suspected bacterial rhino patients most In collected are analysis for microbiology materials The when helpful are agents specificfor tests Diagnostic adiological studies, plain radiographic films, computed computed films, radiographic plain studies, adiological FIGURE 1 predominantly on the left maxillarypredominantly edema of the nasal sinus, and nasal septal deviation. conches, are not indicated in most cases, for instance, in common for instance, cases, in most indicated not are cold. all although thickening, mucosal and levels air-fluid 1). (Figure levels air-fluid not show do patients sinusitis Imaging R (C tomography sinusitis, the search for causative bacteria is not indicated. bacteria is not indicated. for causative the search sinusitis, be performed trained may by aspiration puncture Sinus disease, in a persistent like occasions personnel in rare in immunocompromised and spread, suppurative for The search or in nosocomial infections. patients be necessary may if in rhinosinusitis agent causative or if , duration, extended the disease an has suspected. is In or herpes simplex mononucleosis, of diphtheria the suspicion laryngitis, of occasions rare specifictests. warrants or swabs, wash, nasal swab, procedures: throat several by the aid by or and aspiration, puncture, for sinus aspirates of endoscope. follows infection therapy tract upper respiratory targeted a specific of microbe. the isolation -hemolytic streptococcal disease, disease, streptococcal A b-hemolytic of group outbreaks antibiotic of spread and for monitoring the development as Gonococcus such or when pathogens resistance, are considered. being Chapter_2.indd 3 Chapter_2.indd 4 4 Textbook of Respiratory and Critical Care Infections virus, (R respiratory virus syncytial are caused by corona virus, adenovirus, parainfluenza responsible for50–80%ofallcommoncolds andtherest knownascommoncold.H pharynx respiratory ofanupper the part which involves infection, A Acute Viral (Common Rhinitis Cold) because of blockages inintranasal passages. ofsinusitisassociated episode inapredisposed patient among many ( number ofcauses, andinfectious rhinitis isonly one rhinitis may acute be orchronic. E duration ofsymptoms andchanges ofnasal mucosa, breathing, cases, andinsome thebasis of pruritus. On rhinorrhea, sneezing, ofnasal congestion, obstruction membranes ofthenose, characterized by nose, arunny Rhinitis isaninflammation and swelling ofthe mucous spasms and induce respiratory insufficiency. avoided.be Theinstrumentation can provoke airway medical centers where thepossible complications could epiglottitis great with caution, only inwell-equipped tube problems, andnasal obstruction. forlymphoid hyperplasia,the nasopharynx E obtaining aculture ofpurulent secretions, evaluation of complications orimminent complications ofsinusitis, edema, and inflammation),evaluation of patientswith of polyps, purulent secretions, convalescence ofmucosal smell) , evaluation of medical treatment (e.g., resolution nasal orcongestion, of ordecreased obstruction sense (e.g., mucopurulent drainage, facial pain or pressure, inpatientsof disease sinonasal experiencing symptoms complicationsa suspicion of serious exists. prolonged with those course, severe symptoms, orwhen medical attentionwho seek forthefirst time but only to notapplydoes to most ofthepatients acute diseases with of sinonasal disease. But ithas that underlined to be it Nasal endoscopy has a definite role in theidentification Nasal Endoscopy andL sinusitis.maxillary in intensive care, to especially eliminate suspicion of of common cold per yearof common cold per onan average, while adolescents Children younger than 5 years tend to have 3–8 episodes Rhinitis And cute infectious rhinitis andrhinosinusitis are usually The laryngoscopy is performed in cases of suspected in of suspected cases performed is The laryngoscopy The indications for the procedure are the detection The incidence of the common cold varies by age. T able 1). Rhinosinuiti ach type Eachof rhinitistype may induce aryngoscopy SV), orenterovirus.SV), uman rhinovirus is tiology includes a tiology ustachian 5

Classification andE inflammatory drugs. inflammatory inhibitors; NSAID,ACEI, enzyme angiotensin-converting nonsteroidal anti- middle ear space, and resulting in otitis media. Since congestion ofE rhinitis inyoung children may accompanied be by recovery. reduced,be because rest intheprocess isbeneficial of like fever orcough are present, physical activities should andreduced losses insensible oral intake. Ifsymptoms avoided.be Fluid intake should encouraged be to replace decongestants leads to rebound symptoms and should pyretics, andsaline irrigation.of topical Theuse ororal to symptomatic care, which includes analgesics, anti­ resolve 7–10days. within Therapy shouldbe directed mouth. dry painful. Nasal blockage may cause mouth breathing and act of swallowing could transientlybe disturbed and involvement, Due infection. bacterial to pharyngeal the adults. properties These donotdifferentiate viral from clear to mat, greenish andyellow. Fever isunusual in Duringinfection. 2–3days thenasal discharge turns from symptoms, myalgia, andfatigue are present. also streptococcal or enterovirus), infections gastrointestinal present. Occasionally, headache, rash group (with A a low-grade fever. Facial pain and pressure may be also altered cough, ofsmell,postnasal with sense drip and congestion, clear-to-mucopurulent nasal discharge, an year. and adultsmay have approximately inan 1–4episodes TABLE with eosinophilia rhinitis Gustatory rhinitis Drug-induced rhinitis Hormonal rhinitis Occupational Vasomotor rhinitis rhinitis Infectious Type ofrhinitis Because ofanatomical predisposition, acute viral Viral are infections generally self-limiting and Substantial rhinorrhea isadistinctive feature ofviral P 6 atients typically present nose, runny with sneezing, 1 ustachian tube, reducing airinfluxinthe tiology ofRhinitis tiology Abnormal prostaglandinAbnormal metabolism Various allergens food Hot andspicy estrogen, oral contraceptives penicillamine, inhaled cocaine, NSAID, phentolamine, chlorpromazine, ACEI, Estrogen imbalance irritants Inhaled sympathetic system Disbalance oftheparasympathetic and Viruses, fungi bacteria, Etiology b-blockers, methyldopa, aspirin, 17-01-2014 15:29:41 5 Upper Respiratory Tract Infections

10 17-01-2014 15:29:42 Untreated 11 ndoscopically ndoscopically Bacterial rhinosinusitis ≥10 days Yes Yes Yes Yes , and anaerobes. In In , and anaerobes. able 2). able T For this reason empirical empirical this reason For 12 Viral Viral rhinosinusitis 7–10 days No No No No . Yet, it is clinically explicit in explicit clinically is it Yet, . T The major pathogens of acute bacterial of acute pathogens major The ) has been increasingly recognized as a recognized been increasingly A) has 9 S Staphylococcus aureus acterial Rhinosinusitis: Differential acterialDiagnosis Rhinosinusitis: Differential Sinusitis is common in persons upper with viral Sinusitis provides a detailed view of the paranasal sinuses, but but sinuses, a detailed of the paranasal view T provides lain radiograph of the sinuses may reveal complete sinus sinus complete reveal may of the sinuses radiograph lain ble 2 2 able Features Duration of symptoms and of symptoms Duration with acute compatible signs rhinosinusitis Fever ≥39°C Fever Purulent nasal discharge nasal discharge Purulent 3 or more lasting for days consecutive Facial pain lasting for 3 or pain lasting for Facial days consecutive more New onset of symptoms New onset of symptoms after initial improvment T antimicrobial therapy should be initiated immediately immediately be initiated should therapy antimicrobial of bacterial infection diagnosis is the clinical after first-choice is the Amoxicillin-clavulanate established. is superior which in amoxicillin to agent, antimicrobial sinusitis, and facial tenderness in the projection of frontal of frontal in the projection tenderness and facial sinusitis, and maxillary sinus. the to only it refers infection, but tract respiratory C on changes transitional 2–10% of persons upper respiratory with about only viral infection. tract P thickening. mucosal marked or level, opacity, air-fluid C in evaluation indicated this technique is not routinely While nasopharyngeal sinusitis. of uncomplicated be should cultures microbiological unreliable, is swab E aspiration. sinus direct obtained by be considered may of the middle meatus guided cultures not been has in children their reliability but in adults, of practicality and of precision lack to Due established. of diagnosis the clinical methods, diagnostic current primarily on the is made bacterialacute rhinosinusitis of historybasis ( and symptoms Viral and B Viral Hemophilus Streptococcus and Hemophilus pneumoniae are sinusitis and b-hemolytic a-hemolytic , followed by influenzae streptococci, and methicillin-resistant anginosus S. decade, the past S. aureus (MR and adolescents. in children of bacterial sinusitis cause bacterial rhinosinusitis may cause a number of severe of severe a number cause may bacterial rhinosinusitis cellulitis, orbital complications: bones, of the sinus osteitis nervous system of bacteria the central to and spread or infection of abscess, brain in meningitis, resulting sinus. cavernous intracranial owever, owever, 7,8 yposmia or anosmia is transitional. Usually, Usually, yposmia is transitional. or anosmia acterial Rhinosinusitis

The inspection reveals mucopurulent secretion, edema edema secretion, mucopurulent reveals inspectionThe In patients with acute bacterial rhinosinusitis, nasal nasal with bacterial acute rhinosinusitis, patients In ersistent symptoms of acute rhinosinusitis for longer for longer rhinosinusitis of acute symptoms ersistent FIGURE 3 Bacterial rhinosinusitis and nasal drip (endoscopic nasopharynx the leakage from view). Notice secretion of purulent oropharynxto and larynx. laryngeal Nasal drip induces irritation L, larynx;and cough. nasopharynx; ; Np, secretion. E, s, ). Collection Private PhD. Mladina, MD, Ranko (Courtesy of Professor and erythema of mucosa, causes of nasal obstruction like of nasal causes and erythema of mucosa, periorbitalpolyps or septal in ethmoid deviation, swelling especially in adults, the pain is restricted to diseased sinus. diseased to is restricted the pain sinus. especially in adults, but around, day all is present rhinosinusitis in The cough waking after striking in the morning, it is most usually in the secretions the accumulated to a reaction as up, posteriorpharynx during the night. discharge is purulent and minimal, not responding to to responding not minimal, and purulent is discharge accompanied occasionally, and, medication symptomatic H sneezing. by than 10 days or worsening of symptoms after 5–7 after or worseningsymptoms of days 10 than days, fever grade moderate-to-high and discharge, purulent In 3). secondarya suggest bacterial infection (Figure bacterialof symptoms common most the children, and fever, discharge, nasal cough, are rhinosinusitis breath. malodorous Acute B Acute P 1980s, there was controversy regarding antimicrobial antimicrobial regarding controversy was there 1980s, with observationconfirmed a versus in children therapy upper otitis media acute due to of acute diagnosis origin. H viral of infection, presumably respiratory recent investigations showed that children recovered recovered children showed that investigations recent with amoxicillin- treated when they were quickly more diagnosis. time of the at initiated clavulanate, Chapter_2.indd 5 Chapter_2.indd 6 6 Textbook of Respiratory and Critical Care Infections antibiotics. and forwhich patients should receive which specific which probiotics are thegreatest associated with efficacy was thatconcluded more research to determine, is needed areductionwith inantibiotic-associated diarrhea, but it evidence suggested thatpooled probiotics are associated allergic orimmunologic disorders. environmentor industrial high predisposition with to dominant described. has been inheritance also African- racialwith preference amongst Asians, H young adults, andmiddle-aged females, especially that ofunclear etiology disease predominantly affects atrophicPrimary rhinitis known as ozena)(also is a iatrogenically excessive induced nasal tissue extirpation. dueto Wegener’s orsecondary primary granulomatosis or in amount A andvascularity. squamous epithelium, and the lamina propria is reduced pseudostratified columnar epithelium to stratified bone. The mucous membrane changes from ciliated atrophy andsclerosis ofnasal mucosa andunderlying atrophic rhinitis, which ischaracterized by progressive purulent discharge, andfrequent bleeding. symptoms ofchronic rhinitis are nasal obstruction, tissue, cartilage, (Figure andbone 4).Themost common formation ofgranulomas, resulting ofsoft indestruction leprosy. leishmaniasis, blastomycosis, histoplasmosis, and diseases, such assyphilis, , rhinosporidiosis, inflammation. It mayoccur in chronic also infective may irritants and airborne contribute to prolonged orinfectious viralinflammatory rhinitis.Low humidity Chronic rhinitis isusually aprolongation ofsubacute Chronic Rhinitis associated diarrhea has reported recently. been The advantage of probiotics in preventing the antibiotic- in whom first-line therapy has failed. clindamycin. Fluoroquinolones are forpatients reserved combination of a third-generation oral cephalosporin and I allergy penicillin non-type maywith treated be with an alternative allergy. Children penicillin inadultswith among respiratory upper tract isolates. is Doxycycline coverage ofincreasing b-lactamase-producing pathogens decongestants and antihistamines should avoided.be ofallergic rhinitis.a history Over-the-counter like drugs recommended asanadjunct therapy inindividualswith 10–14 days in children. Intranasal corticosteroids are uncomplicated rhinosinusitis bacterial inadults, and days for duration ofantimicrobial treatment is5–7 special form ofchronic form A special rhinitis ischronic Americans. ll these diseases are diseases All these characterized by the 15 Most ofthepatients are from rural trophic rhinitis may be 16 Familial with etiology 6

R ecommended ecommended ispanics, and 17 P atients 13 The 14 6

topical and systemic antibiotics, vasodilators, estrogens, irrigation, drops liquidparaffin), nose (glucose-glycerin, modalities have in the literature: described been nasal tissues andcartilages (Figure 5).Different treatment epistaxis, anosmia, andsometimes, ofsoft destruction atrophic rhinitis include fetor, crusting, nasal obstruction, chronic andsecondary symptoms primary inboth ozaen.Thecommon Klebsiella species, K. especially have prolonged mainly infection, bacterial caused by septum; CS,cobweb pattern ofsecretion. molds (Fusarium spp.). S,destroyed nostril; LN,left RN,rightnostril; Cobweb secretion isconsistent withcolonization andinvasion of mucosal erosions andalmostcompletely destroyed nasalseptum. Endoscopy nostril). revealsleft chronic withmultiple rhinitis FIGURE 4 (arrow A), andmucosal crustsinthecontralateral (arrow nostril B). Noticeright nostril). theremains ofdestroyed nasalseptum FIGURE 5 Chronic “cobweb” (endoscopic rhinitis viewfrom the Chronic atrophic (endoscopic rhinitis viewfrom the 17-01-2014 15:29:42 7 Upper Respiratory Tract Infections ­ 17-01-2014 15:29:42 ersons with 20 Symptoms include include Symptoms 22 pproximately, 60% of pproximately, A is suggested in adolescents in adolescents is suggested 21 owever, no special precautions or no special precautions owever, HIVinfection (also acute as known BV spreads by a close contact between a close contact by spreads EBV BV requires intimate contact contact intimate requires BV of E Transmission 19 recently infected persons primary develop recently infection acute HIV. to 2–6 weeks exposure after fever, fatigue, myalgia, mucocutaneous ulcerations, ulcerations, mucocutaneous myalgia, fatigue, fever, terized by fever, tonsillar pharyngitis, lymphadenopathy, lymphadenopathy, pharyngitis, tonsillar fever, terized by cells in mononuclear atypical and lymphocytosis, blood.the of majority The shedders. susceptible persons and EBV and inapparent. subclinical primary infections are EBV in 90–95% been demonstrated have EBV to Antibodies symptomatic of incidence The worldwide. adults of adult infection adolescence begins through rise to from years. HIV Infection Acute Primary acute or initial the interval to from refers syndrome) retroviral HIV to is detectable. antibody infection the time that to infectious highly are of infection, patients this stage During in blood load and genital secretion enormousdue to viral indeterminate or negative and copies/mL), (>100,000 results. HIV test antibody Infectious Mononucleosis charac is which mononucleosis, infectious causes EBV infectious mononucleosis may spread the infection for spread may mononucleosis infectious a period H of weeks. the virus since is recommended, are procedures isolation people who carry of healthy also in the saliva found and These people are for life. virus the intermittently spread the primaryusually and for this reason reservoir of virus, prevent. to is impossible the transmission with of an infected person. the saliva The incubation diagnosis clinical The 6 weeks. 4 to from period ranges mononucleosis of infectious throat, sore adults with of fever, the symptoms or young and of liver An enlargement glands. and swollen lymph an include results Laboratory also be present. spleen may percentage an increased blood white cell count, elevated a positive and blood white cells, of certain atypical for strategy Treatment a “monospot” to test. reaction supportive is and symptomatic. mononucleosis infectious reportedto has also been occasionally The usesteroids of and severity of illness, prolongation the overall decrease studies clinical randomized is no available there but P approach. supportto therapeutic such laboratory analyses are not necessary in most of cases, necessary not are of cases, most in analyses laboratory self-limiting mild and is usually herpangina because adequate hydration, includes therapy Supportive illness. and topical limited activity, antipyretics, caloric intake, analgesics.

9 owever, owever, Clinical Clinical IV. HIV. erpangina erpangina 18 nlargement of cervicalnlargement erpangina occurs worldwide, occurs worldwide, erpangina pstein-Barr viruspstein-Barr (EBV), and nteroviral infections may be accompanied be accompanied infections may nteroviral E owever, there is no evidence from randomized randomized evidencefrom no is there owever, , and D sprayed into the nose or taken through through the nose or taken into , and D sprayed H ngitis

y

Similar to other upper respiratory infections, the most the most infections, upper other to respiratory Similar erpangina is a painful pharyngitis caused by various various pharyngitis is a painful by caused erpangina haryngitis is caused by inflammation and swelling and inflammation haryngitisby caused is Phar Herpangina H virus virus A16, Coxsackie Coxsackie like enteroviruses 1, adenovirus, parechovirus 71, echovirus, B, enterovirus H virus. and herpes simplex mainly during summer, and most commonly affects commonly and most during summer, mainly years. aged3–10 children young and infants of pharyngeal mucosa. The main symptom of acute of acute symptom main The of pharyngeal mucosa. include may Other symptoms throat. pharyngitis is a sore rashes, skin aches, and muscle pain joint headache, fever, discloses Inspection nodes in the . and swollen lymph sometimes mucosal pharyngeal erythema, exudates, anterior hypertrophy, tonsillar vesicles, and erosions rash. and skin conjunctivitis, cervicallymphadenopathy, infection pharyngitisof acute is a viral common cause common of common cold or flu. The most in settings A and B. and influenza Some rhinovirus, are pathogens specificsuch other viruses forms cause of pharyngitis, can E as enteroviruses, P controlled trials concerning the long-termbenefitstrialsthe of concerning controlled rhinitis. atrophic modalities for treatment different vitamin A of the size decrease to aims treatment Surgical mouth. of dry lubrication nasal and improves cavities the nasal mucosa. Acute Viral Pharyngitis Viral Acute manifestation includes high fever, , , throat, sore malaise, fever, high includes manifestation emesis, anorexia, headache, swallowing, painful mimic may which pain, abdominal and sometimes, appendicitis. in diameter) 5 mm than (less small by is characterized affect posterior that lesions or ulcerative vesicular and sometimes uvula, soft palate, pharyngeal tonsils, wall, E mucosa. and buccal tongue basedis Diagnosis also be present. nodesmay lymph signs, physical characteristic symptoms, upon clinical appearance. seasonal and data, epidemiological age, is based for diagnosis on standard Microbiological obtained from in cell culture of enterovirus isolation of the nasopharynx.swabs Other specimens stool, include fluid (CSF). H serum, and cerebrospinal urine, by various type of rash, which depends on viral subtype. subtype. depends which on viral type various of rash, by aseptic by be accompanied may herpangina cases rare In H symptoms. and neurological meningitis Chapter_2.indd 7 Chapter_2.indd 8 8 Textbook of Respiratory and Critical Care Infections 4 weeks, except lymphadenopathy4 weeks, that may last longer. transaminase elevations. Symptoms persist forless than findings include leukopenia, thrombocytopenia, andmild folds andarytenoids. of tissue rapidly progresses, andinvolves aryepiglottic invasion, inducing inflammationedema. and Swelling from swallowing during food may predispose to bacterial epithelial trauma by viral ormucosal infection damage aureus, andb-hemolytic streptococci. Microscopic S. microorganisms are H. influenzae, Themost frequent wallcausative ofnasopharynx. posterior microbialsource pathogens. is of bacteria Theprimary from bacteremia, ordirect invasion oftheepitheliumby adjacent tissues. Infection ofepiglottis isaconsequence cellulitis oftheepiglottis, folds, aryepiglottic andother and trachea from aspiration. Infectious epiglottitis is a During theactofswallowing, protects italso larynx wall of the vallecular space below oftongue. the base E macrolides, andclindamycin. are otherb-lactams (e.g., amoxicillin, cephalosporins), tonsillopharyngitis. Alternatives to this“gold” standard isthestandard penicillin with ofcare forstreptococcal rheumatic fever. A10-day course ofantibiotic therapy occurrence ofnonsuppurative complications, such as resolution ofclinical symptoms, andto prevent the Antibiotic therapy isrecommended to hasten the inchildrencases ofpharyngitis andfor10%inadults. ), which isresponsible(S. for15–30%ofall pyogenes common cause isgroup Ab-hemolytic usually thecoldermonths. during occur Themost A Acute B (“mononucleosis-like” illness). lymphadenopathy resembling infectious mononucleosis usually exudative, cervical is accompanied with rash, neurologic andsometimes symptoms. P pharyngitis, anorexia, generalized lymphadenopathy, maintenance P ofairway. Treatment position). (tripod ofepiglottitis onthe isbased neck, andmouth forenhancing open theexchange ofair the child to sit upright, hyperextended with lean forward, dyspnea, tachypnea, and cyanosis. often causesDyspnea , loss ofvoice, inspiratorystridor, fever, anxiety, hours ofonset. Symptoms andsigns include sore throat, threatening obstruction. airway Epigl piglottis is a part of oropharynx, and it forms theback anditforms piglottis oforopharynx, isapart cute bacterial pharyngitis and tonsillopharyngitis andtonsillopharyngitis pharyngitis cute bacterial In children, symptoms afew develop within abruptly ottitis acterial Pharyngitis acterial 25 Thus, epiglottitis may cause life- atients should monitored be 23 Common laboratory S. pneumoniae, Streptococcus Streptococcus haryngitis, 24

, rate a mortality with of around 1% in adults. orcomplicationsof airways like meningitis, empyema, or Classifications andE noninfectious causes listedintable 3.Themost common structures. E isanacute orchronic Laryngitis inflammation of laryngeal as should cover themost likely causative pathogens, such results, empirically administered antimicrobial therapy Before theairway. initiated culturebe after securing arrest occurs. Antibiotic therapy but should isnecessary situation whenrespiratory inanemergency performed intubation cricothyroidotomy orneedle should be SLE, systemic lupuserythematosus. RSV, virus;GERD, respiratorysyncytial gastroesophageal reflux disease; Candida albicansCandida stabilization andventilation. ofairway, care unitby staff that is rapidperform able to resuscitation, continuously department orintensive intheemergency T Lar Viral laryngitis Infectious angioneurotic edema involvement SLE, hypothyroidism, ofrheumatoid arthritis, drugs(crack),smoking, allergy, GERD, vocal abuse, laryngeal dueto inhalation oftoxic laryngitis agents,Irritant alcoholism, laryngitis Noninfectious Fungal Bacterial able 3 S. aureus, group Astreptococci, E piglottitis may fatal be dueto sudden compromise y ngitis tiology includes anumbertiology ofinfectious and • • • • • • • • • • • • • • • • • • • inimmunocompromised patients. Cryptococcus neoformans Cryptococcus Histoplasma capsulatum Blastomyces dermatitidis Candida albicans Syphilis (Treponema pallidum) Tuberculosis (Mycobacterium tuberculosis) ulceransCorynebacterium ) diphtheriae, Diphtheria (Corynebacterium Staphylococcus aureus pneumoniae Klebsiella Streptococcus pneumoniae Moraxella catarrhalis b-hemolytic streptococci B Hemophilus influenzaetype Varicella-zoster Measles RSV Parainfluenza viruses Adenoviruses A, Influenza B, C Rhinovirus tiology ofL tiology aryngitis 27

H. influenzae, and 26 Orotracheal 28

17-01-2014 15:29:43 9 Upper Respiratory Tract Infections 17-01-2014 15:29:43 xtension xtension E 31 hysical examination examination hysical t the beginning patients t the beginning patients ), and hypothyroidism. E), and hypothyroidism. apid antigen detection test is also is detection test antigen apid cute hoarseness is present in hay fever, fever, in hay hoarseness is present cute Diphtheria occurs throughout the year year the throughout occurs Diphtheria 30 Duration of hoarseness is important in differential in differential is important of hoarseness Duration was first identified in 1880. The first C. in 1880. The identified first was diphtheriae obtained for cultures. R obtained for cultures. useful in detection of bacterial of infection. Diagnosis tract respiratory from culture positive requires diphtheria of laryngeal Diagnosis assay. toxin and positive secretion, of extensive a complication is usually that tuberculosis is based acid fast on positive pulmonary tuberculosis and positive swab, or oropharyngeal in sputum bacilli . for Mycobacterium tuberculosis cultures A diagnosis. aspiration fumes and irritants, toxic of inhalation acute and body aspiration, foreign chemicals, of caustic laryngitis. infectious besides acute edema, angioneurotic hoarseness includes chronic of diagnosis Differential cancer lung laryngealas such cancer, diseases, numerous cords, of vocal trauma with involvement, mediastinal disease (GERD), reflux gastroesophageal abuse, vocal syndrome, with sinobronchial rhinosinusitis chronic systemic arthritis, in rheumatoid laryngeal involvement erythematosus (SL lupus Diphtheria is caused by the Gram-positive bacillus bacillus the Gram-positive by is caused Diphtheria Corynebacterium and in some by diphtheriae cases C. ulcerans respiratory develop individuals may . Infected or become asymptomatic disease, cutaneous disease, with close contact by spreads Infection carrier. lesions. skin or from secretions respiratory infectious been has milk cow’s of C. via ulcerans The transmission described. Diphtheria Diphtheria with peak incidence in winter. A with peak incidence in winter. fever. grade low and throat, sore malaise, from suffer and cough, barking hoarseness, to progress Symptoms with severe Individuals also known as . , disease cervicaldevelop node enlargement lymph (“bull-neck”). P swelling and neck reveals hyperemic pharyngeal and laryngeal hyperemic mucosa reveals grey forming the adherent exudates of white with areas bleeds with scraping. that pseudomembrane of the pseudomembrane into larynx and trachea may lead lead larynx may into of the pseudomembrane and trachea airwayto and obstruction with suffocation subsequent of cultures positive requires Definitive diagnosis death. C. cutaneous or secretions respiratory from diphtheriae for cultures Specimens assay. toxin positive and lesions, a including and nose, the throat be obtainedshould from portionof membrane. developed in the 1890s, was diphtheria against antitoxin With the vaccine developedwith in the 1920s. first the of disease the incidence has of vaccine, administration still endemic in it is although significantly, decreased

Laboratory Laboratory 29 hysical examination should should examination hysical P Chronic laryngitis (endoscopic view). The laryngealThe laryngitisChronic view). (endoscopic -hemolytic streptococci, typeH. influenzae B, streptococci, b-hemolytic

cute laryngitis may occur as an isolated infection isolated an occuras laryngitis cute may A

Diagnostic procedure begins with comprehensive begins with comprehensive procedure Diagnostic findings (white blood cell count, C-reactive protein) may may protein) C-reactive blood count, (white cell findings bacterial infection. from viral distinguishing beaid in an cause, on bacterial or fungal is a suspicion If there be should swab laryngealoropharyngeal and exudate or, more commonly, as a part of a generalized viral or viral a part as commonly, of a generalized more or, begins with infection. It tract bacterial upper respiratory painful of voice), loss mild-to-complete hoarseness (from dry and laryngeal or speaking, swallowing cough, edema are and malaise 6). Fever of varying (Figure degrees in 7 days. chronic resolve In usually common. Symptoms that symptom only the usually is hoarseness laryngitis, When the clinical weeks. three than for more persists subtype, lies between and chronic acute presentation as utility classify to be of clinical sometimes it may subacute. of the condition, history chronicity includes of disease that fumes environmental to exposure epidemiologicdata, acute In habits. and smoking medication, and irritants, inflamed, red, laryngoscopy reveals indirect laryngitis, with round cords vocal hemorrhagic and occasionally, edgesexudates. and swelling causative agent of acute laryngitis is the rhinovirus. Others Others laryngitis acute of agent is the rhinovirus. causative parainfluenza influenza A and B,include adenoviruses, viruses, etc. and cervicalalso the oropharynx, include lymph thyroid, laryngitis C. fungal by caused Chronic nodes. albicans mucosa appears hyperemic and swollen, forming inflammatory forming and swollen, appears hyperemic mucosa partpseudotumors in the anterior folds. of both vocal FIGURE 6 that is a common side effect of inhaled steroids, is steroids, effect is a common side of inhaled that patches mucosal chalk-white multiple by characterized and oropharynx. on epiglottis, spreading Chapter_2.indd 9 Chapter_2.indd 10 10

Textbook of Respiratory and Critical Care Infections mucolytics, requiring treatment, only supportive such asanalgesics, isusuallycommon acute self-limiting, viral laryngitis of illness anddegree compromise. ofairway The most laryngotracheobroncho­ 3. Laryngotracheobronchitis, 2. A 1. areillnesses in three divided clinical entities: from particularly infection, feature bacterial isdueto secondary bronchopneumonitis tracheitis, and bacterial the croup rhinovirus. In instances, some such asthelaryngotracheal A influenza virus commonly caused by parainfluenza viruses, following by of age with a peak incidence between 7and36 months. incidencebetween apeak of age with infants affects illnesses and children younger than 6 years bacterial infection issuspected. infection bacterial caffeine intake. Antibiotics are only whena needed important inthepathogenesis. H intheregionobstruction ofthelarynx. degrees ofstridor, barking cough, andhoarsenessdueto of respiratory that illnesses are characterized by varying diphtheria. T In prevaccination era “croup” theterm was asynonym for Croup Illnesses and adults. unvaccinated orinadequately immunized adolescents era, today anincreasing proportion ofcasesin occur young affected primarily children intheprevaccination many Furthermore, oftheworld. parts whilediphtheria should administered be inall patients possible with inflammationstructures. of laryngeal Corticosteroids develop severe even in settings obstruction of slight airway such assubglottic stenosis orvocal cord paralysis, may patients an underlying factor that with risk limits airway, “croup” illnesses, require care. particular In addition, suffering from especially those diphtheria andother antibiotics are required. it isachallenge forthephysician to recognize when ost factors, allergic especially factors, to be seem Treatment onseverity depends ofacute laryngitis is common. toxic infection presentation, bacterial and secondary and barking cough, severe stridor, high fever, typically hoarseness , tracheitis: and bacterial minimal toxic presentation. barking cough, minimal-to-severe stridor, high fever, inflammation, nontoxic presentation. andbarkingstridor cough, fever, without without Spasmodic croup: sudden night of timeonset P atients any degree compromise, with ofairway cute laryngotracheobronchitis: hoarsenessand cute laryngotracheobronchitis: S. aureus. A 32 36

voice rest, increased hydration, andlimited oday, theword “croup” refers to anumber ccording to symptoms andsigns, croup , R SV, measles virus, adenovirus, and 35 Croup are illnesses most 37 H owever, sometimes 33 “That group of 34

is possible. ofcorticosteroidthe dose should reduced be wherever it mouth before to rinse advised andafter inhalation and corticosteroids forasthma control. P regular is often associated with laryngitis usage of inhaled antifungal drugs. In immunocompetent individuals, fungal compromised patients, and treatment on systemic is based prompt diagnosis andadequate treatment are critical. tuberculosis.pulmonary Since it is highly contagious, requires thesame antituberculosis regimen drug as complication tuberculosis ofactive pulmonary and mechanical andtreatment airway inanintensive care unit. such severewith ofcroup form require placement of after cultures have Most obtained. been ofthechildren Moraxella catarrhalis, antibiotics should administered be need forintubation.need haveepinephrine andoften decreased used the been mg/kg). In severe cases, repeated treatments with 0.6 oncorticosteroidsbased (intramuscular dexamethasone frequent causes of tracheitis are of mucopurulent secretion trachea. within Themost to subglottic edema oraccumulationdevelop secondary narrowest of the trachea. part isatsite ofdisease thesubglottic area, which isthe of thesize andanatomic shape The major oftheairway. age, it presents problem aspecial inchildren because Although infectious tracheitis may patients affect ofany the trachea and increase the likelihood of infections. smoke anddense can injureirritants theepitheliumof the trachea however, are orviral bacterial infections; trachea, andbronchi. Most conditionsthat affect Tracheitis process is aninflammatory ofthe larynx, infection due toinfection croup bacterial are illnesses secondary associated with waiting forculture results. should administeredbe as early as possible, without Diphtheria antitoxin step oftreatment, isacrucial and must isolated be to avoid exposing others to theinfection. antitoxin and antibiotic or erythromycin). (penicillin They hospitalized to be andshould given be need diphtheria necessary. breathingown, inserting tube andtracheotomy may be when patientobstruction, cannot breathe on their closely to assess the need for tracheotomy. to assesstheneed closely compromise,airway should monitored be andairways Tracheitis Fungal commonly appears inimmuno­ laryngitis Chronic tuberculous isalmost always laryngitis a Treatment ofcroup otherthan illnesses diphtheria is P atients whoare to have suspected diphtheria, 40

S. aureus, 41 Since the most severe of types S. pneumoniae, 39 In severe cases ofairway A irway obstruction may obstruction irway S. aureus’ group atients should be , or H. influenzae, or 38

17-01-2014 15:29:43 A Upper Respiratory Tract Infections 11 ­ 17-01-2014 15:29:43 47 48

49 SV, bocavirus, and adenovirus in and adenovirus bocavirus, SV, infection will lead to earlier diagnosis, patient patient infection will diagnosis, earlier to lead usion streptococcal A streptococcal of group complications ossible atients with chronic obstructive pulmonary disease with chronic atients for more lasting cough persistent who have atients The bronchial hyperreactivity may be enhanced or enhanced be may hyperreactivity The bronchial Bacterial superinfection of viral infection may occur infectionsuperinfection may Bacterial of viral P and include numerous, of influenza are Complications rupture, splenic are of mononucleosis Complications airway include may of diphtherias The complications P P oncl C . The risk was higher . The higher influenzae was and H. pneumoniae risk S. together. and H. influenzae of bocavirus for the presence otitis media acute differed risk was that The conclusion the with specific and that virusesbacteria and involved reducing efforts methods consider for should preventive R by infections caused otitis media acute bacterialto addition pathogens. Symptom-severity infections. tract respiratory by provoked were exacerbations and the frequency of severe of and susceptibility exacerbations withassociated previous novel to infection, according tract upperto respiratory 7000 patients. than on more research Upper respiratory tract infections are the most common most the infections are tract respiratory Upper with social important population, infections in general infectious cough. In patients who have a cough lasting lasting a cough who have patients In cough. infectious findings, weeks8 to 3 with radiograph chest normal from into be to taken has cough of postinfectious the diagnosis agent a specific etiologic patients, most In consideration. helpful. be may will empiric and therapy benot identified, Bordetella due to for cough of suspicion degree A high pertussis treatment. antibiotic and isolation, adjacent of infection into The propagation occasionally. sequence such of but ensue may organs or distant tissues, rare. is quite events glomerulonephritis, acute fever, rheumatic pharyngitis are syndrome. shock toxic and streptococcal fever, scarlet depletion, bacterial volume superinfection, , encephalitis, rhabdomyolysis, pericarditis, myositis, disseminated and failure, renal myelitis, meningitis, also poses a Influenza of risk coagulation. intravascular as heart such conditions, medical worsening underlying or diabetes. asthma, failure, hemo­ encephalitis, syndrome, Guillain-Barré hepatitis, Burkitt’s and myocarditis, agranulocytosis, anemia, lytic lymphoma. thrombocytopenia, polyneuritis, obstruction, myocarditis, and hearingloss. proteinuria, may also experiencean exacerbation. may symptoms acute got through 3 weeks they after than have post a have infection, may tract upperan respiratory of A S owever, it is owever, H. influenzae bronchoscopy bronchoscopy ­ anti mpirical Children with Children H , 45 43 Clinical presentation presentation Clinical 44 owever, up to 60% of patients patients of 60% to up owever, H arely, bacterial tracheitis may develop develop may bacterial tracheitis arely, R in adjusted models controlling for the models controlling in adjusted 42 46 , and influenza A , and influenza pneumoniae Mycoplasma

Otitis media may be a complication in some 5% of be a complication Otitis media may s s omplication C species, species, Pseudomonas species, type B, Klebsiella anaerobes, virus (H1N1). as a complication of a preceding viral infection or an viral of a preceding as a complication tracheitis Bacterial intubation. endotracheal injury from is uncommon, withincidence of approximately the per year. per0.1 cases 100 000 children includes high fever, toxic appearance, inspiratory appearance, toxic fever, high includes and dysphonia, hoarseness, cough, like bark and stridor, can Diagnosis distress. respiratory of degree variable laryngotracheobronchoscopy, beby direct confirmed in purulent and secretions inflammation shows which reveals which X-ray, neck lateral by or area subglottic the Laryngotracheo ­ narrowing. subglottic under specimens for cultures obtaining enables by also be therapeutic may and visualization, direct includes diagnosis Differential toilet. performing tracheal peritonsillar epiglottitis, diphtheria, croup, angioedema, tuberculosis. and abscess, retropharyngeal abscess, of an adequate is based on maintenance Treatment of in most intubation airway, endotracheal implies which cover should antibiotics Initial and antibiotics. patients, E bacteria. causative common the most cephalosporin a third-generation include biotic regimens penicillin, or clindamycin and a penicillinase-resistant of MR is a suspicion If there intravenously. administered in the community, vancomycin should be started. should Once vancomycin in the community, appropriate made, is diagnosis microbiological definitive 10 days. than for more continue should therapy antibiotic patients airway support and antibiotics, appropriate With within days. 5 improve include that complications one or more develop may adult respiratory shock, toxic , , subglottic (ARDS), post-extubation syndrome distress arrest, cardiorespiratory encephalopathy, anoxic stenosis, or cellulitis. abscess and retropharyngeal presence of key viruses, bacteria, and acute otitis media otitis and acute bacteria, viruses, of key presence mediaotitis riskindependently acute was riskthat factors with syncytialload viral with respiratory associated high colds in children and around 2% in adults. It has recently recently has It 2% in adults. and around colds in children been shown In most cases, respiratory tract infections resolve entirely entirely infections resolve tract respiratory cases, most In arise. may complications of cases, number in a minor but -hemolytic streptococci, M. catarrhalis streptococci, b-hemolytic the condition of high priority, the condition of high the mortality because rate 4–20%. at been estimated has bacterial tracheitis should be admitted in the intensive bethe intensive in admitted should bacterial tracheitis with unit, multidisciplinarysupport. medical care Chapter_2.indd 11 Chapter_2.indd 12 12

Textbook of Respiratory and Critical Care Infections infections. otitis media, pertussis, diphtheria, andchronic bacterial forstreptococcalused pharyngitis, sinusitis bacterial and treatment.specific respiratory are infections self-limiting, requiring no cell ororgan transplantation. Most oftheacute upper chemotherapy, dialysis, undergoing andthose stem splenectomy, infection, HIV cancer, patients receiving disease. Special attention isrecommended with inthose for developing the prolonged or complicated course of mononucleosis. pharyngitis, diphtheria andcroup disease, epigotittis, and circumstances andspecial infection such asstreptococcal inprolonged andchronic performed be course of examination. A onrecognitionup isbased ofsymptoms andphysical viral infections. prolonged and/orchronic to primary adhering infection pathogens are more commonly causative agents of for more than 80%ofallcommoncolds. Bacterial influenza virus, R rhinovirus,especially corona virus, adenovirus, para­ respiratoryupper tract are infections caused by viruses, implications likeworking missed hours. Most ofacute

References 1. 2. t 3. 4. 5. 6. p 9. t 8. 7. H Immunocompromised have persons increased risk In most cases ofacute infections, diagnostic work-

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. Croup hospitalization in Ontario: a 14-year time-series in Ontario: time-series a 14-year hospitalization . Croup F, Ospina E Ospina AF, L,eveiz Cardona World H World http://www.who.int/immunization/topics/diphtheria/ 2011. en/index.html. June Fitzgerald D Fitzgerald 2006;7:73-81. Rev. Respir Pediatr 2007;(2): Rev. Database Cochrane laryngitis Syst in adults. CD004783. Garett CG, Ossoff RH. H CG, Garett 1999;83:115-23. Welliver R Welliver . 1995;6:90-5. Dis Infect Segal A RE analysis. . 2008;358:384-91. J Med N Engl Cherry Croup. JD. Galazka AM, R Galazka in the developing world and the industrializedin the developing world. . 1995;11:107-17. J Epidemiol Eur Farizio KM, Strebel P KM, Strebel Farizio disease Corynebacterium to due respiratory Cochi SL. Fatal for of guidelines and review report : case diphtheriae . Dis Clin Infect and control. investigation, management, 1993;16:59-68. D, Gilbert F R AD, Bostock infection associated with untreated bacterium infection with associated untreated ulcerans milk. Wong KK, P Wong J Otolaryngol setting. Head in the outpatient candidiasis 2009;38:624-7. . Surg Neck Chiou CC,Chiou Seibel NL, Derito F . Concomitant Candida epiglottitis and disseminated and disseminated epiglottitis Candida AH. Concomitant virus zoster infection with associated acute Varicella ­blastic lympho leukemia. 757-9. . 2007;21:449-69. Am ClinDis North

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Chapter_2.indd 13