Basic principles of infectious diseases

1. Basic principles of infectious diseases • The term infectious diseases applies when an interaction with a microbe • causes damage to the host and the associated damage or altered physiology • results in clinical signs and symptoms of disease. • So pathogen is defined as any microrganism that has the capacity to cause • disease. • Not all pathogens have an equal probability of causing disease in the same host • population. • Virulence provides a measure of pathogenicity: for example encapsulated • pneumococci are more virulent than nonencapsulated pneumococci. • Escherichia coli strains expressing Shiga-like toxin are more virulent than those • that do not express these toxins

2. Opportunistic microrganisms • These microrganisms, usually do not cause disease in people with intact host • defence systems, on the contrary, they can cause devasting diseases in many • hospitalized and immunocompromized patients. • Most microrganisms with a capacity to multiply in humans (including members • of the indigenous commensal flora) cause disease more readily in individuals • with underlying chronic diseases or different compromises. • The term opportunist indicates well this category of pathogen. • Opportunistic pathogens a vary emergency in hospital are considered, • they are vehicolated by paramedical staff or assistance staff

3. Interaction of pathogenic microrganisms with host • Adherence indicates the process by which the microrganisms bind to surfaces (initial interaction between pathogenic microrganism and host). • It is the first step of cellular invasion and toxins delivery process by microbial pathogens. • Adhesins are microbial surface molecules binding the organisms to host surfaces. • Capsules are formed by extracellular • polymeric substances. They inhibits • phagocytosis.

4. Interaction of pathogenic microrganisms with host: other factors • Fibrillae are the fine “hairy” structures on bacterial cells. • Fimbriae arenonflagellar filamentous structures on bacterial cells. • Glycocalyx is a superficial polysaccharide-containing structure on cellular • surface. • Lectins are glycoproteins that inhibit specific binding to carbohydrates.

5. Interaction of pathogenic microrganisms with host: receptors • Receptorsare host molecules able to recognize and bind • the microbial adhesins. • A single adhesin may have more than one receptor, and a single • receptor may be recognized by many different adhesins. • The central role of adhesins in microbial colonization and • pathogenesis makes them ideal target for preventive and • therapeutic treatment

6. Examples in which bacterial adherence correlates with bacterial virulence

7. Specific adherence mechanisms and their roles in pathogenesis • Microbial biofilms • Many of the studies of bacterial adherence have been done on free-floating • “planktonic” bacteria growing in culture. • In nature, however many bacteria exist in a complex community-like structure • known as Biofilm. • Biofilms are bacterial populations that are inclosed in a matrix of extracellular • polymeric substances.

8. Microbial biofilms Bacteria form microcolonies with conelike and mushroom-shaped morphologies by adhering to each other and to a surface. Water-filled channels surround the microcolonies and function somewhat like a primitive circulatory system, allowing access to nutrients and interbacterial communication

9. Microbial Biofilms • In the medical area biofilms are seen in native valve endocarditis, otitis media, dental plaque • and they are a problem for cystic fibrosis patients. • Biofilms also form on synthetic medical implants, including, intravascular • catheters, artificial valves, pacemakers, orthopedic devices and contact lenses.

10. Microbial Biofilms One of the characteristics of Biofilms is their increased resistance to antibiotics. Bacterial biofilms have been reported to be up to 500 times more resistant to antibiotics than planktonic cells. There are several properties of biofilms that could contribute to increased resistance to antibiotics. The esopolysaccharide matrix or slime that surrounds the cells may create an exclusion barrier to antimicrobials or inactive them. Bacteria in biofilms grow more slowly and slower growth may lead to decreased uptake of the drugs.

11. Biofilms formation Biofilms are formed in two phases. The first phase is an initial reversible adherence to a surface. Several factors contribute, including surface hydrophobicity, proteic adhesins and capsular polysaccharides. The second phase involves intracellular adhesion, which results in microcolonies formation and complex biofilm architecture

12. Biofilms formation Pili and flagella have been shown to be important in biofilms formations. Strains lacking flagella appear unable to establish initial adherence to a substrate and microcolony formation. Elucidation of molecular mechanisms of biofilms formation should identify new targets for chemotherapy and provide new approaches to controlling biofilms formation.

13. Respiratory tract infections Respiratory tract infections may be devided into: upper and lower tract

14. Upper respiratory tract infections The common cold Is the traditional term used to indicate a vary common syndrome of upper respiratory tract. Common cold is the most common infectious disease in humans (each adult contracts two to four infections a year, children may have six to ten cold a year). The major respiratory viruses causing colds are found in the family of rhinovirus myxovirus, paramyxovirus,adenovirus, piconavirus and coronavirus (the rhinovirus group accounts for more than 50% of cases in adults). In total more than 200 different viral types cause colds. Eyes congestion A small number of colds is complicated by bacterial infections of the paranasal sinuses and the middle ear, and require antimicrobial therapy.

15. The common cold: incidence, signs and symptoms • Respiratory infections have a seasonal incidence (in the colder mounths, in • temperate areas and in rainy seasons they, more frequently, occur). • Signs and symptoms • Symptoms are cough, sore throat, runny nose, nasal congestion accompanied • by headache, fatigue and loss appetite.

16. The common cold: treatment Not many commercial remedies provide a good symptomatic relief. The first-generation antihistamines and the nonsteroidal anti-inflammatory drugs (NSAID) are commonly used. Antihistamines are recommended in control of rinorrhea and nasal mucus. NSAID are used in reducing cough, probably through blocking prostaglandin action, and in control of headaches, malaise and other symptoms. The combination of a first-generation antihistamines with NSAID provides a good relief in common cold The development of a new vaccine is difficult, because many different viruses are implicated in common cold.

17. Pharyngitis Acute pharyngitis is aninflammatory syndrome of the pharynx caused by both viral and bacterial agents. Most cases are of viral etiology and occur as part of common cold and influenzal syndromes. The most important bacterial infections are due to the group A β hemolytic Streptococcus (Streptococcus pyogenes). It is important to differentiate streptococcal from viral pharyngitis because only bacterial forms are sensitive to penicillin. Streptococcal pharyngitis may be complicated by acute rheumatic fever and acute glomerulonephritis. There are other uncommon or rare types of pharyngitis and for some of these, specific treatment is available

18. Etiology: causes of pharyngitis

19. Pathogenesis The pathogenetic mechanisms of pharyngitis are different in according to various etiologic agents. In viral infections caused by adenovirus and coxsackievirus, direct invasion of pharyngeal mucosa occurs. In infections caused by Streptococcus pyogenes, many factors influence colonization and invasion in host tissue (natural and acquired host immunity, interference by other bacteria present in the oropharynx, different M-types). Streptococcus pyogenes elaborates a number of extracellular factors, including pyrogenic exotoxins, hemolysins, streptokinase, deoxyribonuclease, proteinase, hyaluronidase.

20. Streptococcal pharyngitis The severity of infections varies greatly. In severe cases, there is marked pharyngeal pain, odinophagia and a temperature of 39.4 °C. Headache and abdominal pain may occur; the pharyngeal membrane is fiery red, grayish-yellow exudate is presente on the tonsils. Enlarged, cervical nodes and a rise in the number of leukocytes are typical in acute suppurative bacterial infection

21. Streptococcal pharyngitis: complications Complications of acute streptococcal pharyngitis, may include: acute reumathic fever, acute glomerulonephritis and invasive infections (meningitis, endocarditis etc) There is a general association of specific M serotypes with these complications

22. Scarlet fever Infection with strains of Streptococcus pyogenes producing pyrogenic exotoxins causes scarlet fever. The body is covered by a characteristic erythematous rash followed by desquamation. The tongue is red, and the papillae are enlarged (strawberry tongue) • Characteristics of rash: • is fine and blanches upon pressure • appareas 12-48 hours after the fever • generally it starts on the chest

23. Staphylococcal pharyngitis • Staphylococcus aureus causes pharyngitis • expecially in children (1% of cases) • Staphylococcal pharyngitis is • characterized by: • Mucopurulent drainage • Mucosal erythema • Localized pustules

24. Vincent's angina (Henry Vincent) Vincent's angina also called: acute necrotizing ulcerative gingivitis is a mixed bacteria-spirochetal infection usually present in patients with poor dental hygiene and in immunocompromized patients. Inflamed and ulcered gingivae and halitosis may characterize this form. Exudative tonsillitis, pharyngeal pain and dysphagia occurs. Septic emboli to the lung may lead to pulmonary abscesses and empyema. Treatment includes irrigation and removal of necrotic areas, in untreated cases, infection can spread to the bones.

25. Infectious mononucleosis Pharyngitis often exudative occurs in many cases of infectious mononucleosis. The mononucleosis syndrome is caused by EBV or cytomegalovirus. Fever, fatigue, malaise, petechiae are present associated with headache. Posterior and anterior cervical adenopathy is common and inguinal nodes are more frequently enlarged. Low-grade temperature and halitosis serves to differentiate this form from streptococcal pharyngitis.

26. Diphtheria Diphtheria still occurs in members of socio-economically disadvantaged populations. Human infection is caused by Corynebacterium diphtheriae. It colonizes pharyngeal tract forming a characteristic tonsillar or nasopharyngeal pseudomembrane adherent to the tonsils and pharyngeal mucosa, causing bleeding and occlusion. Swollen neck is present. Patients may experience tiredness, pallor and fast heart rate. These symptoms are caused by the toxin released by bacterium. The majordamages include cardiac function with myocarditis and peripheral neutropathy. The less severe forms are restricted to the skin (caracteristic lesions). Patients are treated with repeated course of antitoxin. Antibiotics are used in patients or in asymptomatic carriers to eradicate Corynebacterium diphtheriae, toreduce the numbers of bacteria and to prevent their trasmission.

27. Diagnosis The first objectives in diagnosis of acute pharyngitis are to distinguish cases of common viral etiology, which predominate, and do not require antimicrobial therapy, from those due to S. pyogenes or other unusual organisms for which treatment is available. This distinction is critical because many patients continue to receive unnecessary antimicrobials increasing prescription for expensive broad-spectrum agents. The presence of pharyngeal or tonsillar exudates, adenophaty or skin rash helps in differential diagnosis, but these findings are not specific in most cases Several commercial kits are available for rapid detention of group A streptococcal antigen from throat swabs. Rapid tests are 60-90% sensitive and 98-99%specific when compared to colture methods. The patient's history and epidemiologic factors may help in suggesting a specific etiologic diagnosis in cases in which cultures or rapid antigen tests are negative for group A streptococci

28. Treatment Patients with Streptococcal pharyngitis should receive a 10-day dose of penicillin (or equivalent antibiotic). In allergic patients to penicillin erythromycin is recommended. Antibiotic treatment serve to prevent suppurative complications (peritonsillar abscess, sinusitis, otitis and pneumonia). Vincent's angina: responds to an oral penicillin such as amoxicillin plus metronidazole or amoxicillin-clavulanate. Peritonsillar abscesses can be treated by surgical drainage or incision Diphtheria: the treatment requires both antimicrobials and hyperimmune diphtheria antitoxin Viral pharyngitis: amantidine or rimantidine can reduce symptoms in uncomplicated influenza, also neuroaminidase inhibitors have a similar effect. Acyclovir, valacyclovir and foscarnet are available for the treatment of ulcerative oropharyngeal Herpes simplex virus infection in immunocompromized patients

29. Otitis • Otitis may be defined such as an inflammatory condition of the ear characterized • by pain, fever, abnormalities of hearing and vertigo. • Is devided into: externa and media otitis Ear anatomy

30. Otitis externa Otitis externa: regards the outer ear (auricle pavilion and auditory canal). The esternal auditory canal is long 2.5 cm. The microbial flora is similar to flora of the skin (Staphylococcus epidermidis, S. aureus, Corynebacteria and anaerobic bacteria) • Infections of the external canal may be subdivided into four categories: • Acute localized otitis externa • Acute diffuse otitis externa • Chronic otitis • Invasive otitis externa

31. Acute localized otitis externa Acute localized otitis externa may occurs as a foruncle due to S. aureus Pain is severe Bluish, red hemorrhagic fluid may be frequent on auditory canal or on tympanic membrane, adenopathy is often present. Local treatment or systemic antibiotic treatment are curative Incision or drainage are necessary in case of severe pain

32. Acute diffuse otitis externa Acute diffuse otitis externa (swimmer's ear) occurs in hot, humid wheathers The skin is edematous and red. Gram negative bacilli especially Pseudomonas aeruginosa play an important role in etiology. Irrigation with hypertonic saline solution (3%), or cleansing with mixtures of alcohol and acetic acid may be used initially. A 10-day regiment of a fluorochinolone otic solution or ear drops associated with hydrocortisone serve to reduce local inflammation and to block infection.

33. Chronic otitis externa The most frequent cause of chronic otitis externa is chronic suppurative otitis media with perforated tympanic membrane. Rare causes include: tubercolosis, syphilis and sarcoidosis.

34. Invasive otitis externa Is a severe necrotizing infection that spreads from the ear canal to adjacent areas of soft tissue, cartilage and bone. Frank pain and inflammation are accompanied by the drainage of pus from the canal. Diabetic, immunocompromized and debilitated patients are at particular risk. Pseudomonas aeruginosa is almost always the etiologic agent. Systemic therapy including anti-Pseudomonas drug should be used. Association of ceftazidime, cefepime or piperacillin with an aminoglycoside (gentamicin or tobramycin) should be considered.

35. Otitis media Otitis media is defined by the presence of fluid in the middle ear accompanied by signs or symptoms

36. Otitis media: epidemiology Otitis media is a pediatric disease. The peak incidence occurs in the first 3 years of life. The highest incidence of acute otitis media occurs between 6 and 24 months of age The disease is less common in adolescens and adults Children with acquired immunodeficiency syndrome have a higher incidence of otitis media beginning at 6 months of age Otitis media is infrequent in adults, but the bacteriology and therapy is similar to those in children

37. Otitis media: pathogenesis • The middle ear includes: the nares, nasopharynx and eustachian tube. • Anatomic or functional disfunction of the eustachian tube appears to play an important role • in the development of otitis media. • Eustachian tube has three physiologic functions: • Protection from nasopharyngeal secretions • Drainage of secretions into the nasopharynx • Ventilation of the middle ear to equilibrate air pressure When one or more of these functions are compromised, the result is the development of fluid and infection in the middle ear. Congestion of the mucosa of the eustachian tube may result in obstruction, and if bacterial pathogens are present a suppurative otitis can occur

38. Etiology of otitis media Bacteria Streptococcus pneumoniaeand Haemophilus influenzaeare the most frequent cause in all age groups Streptococcus pneumoniaeis the most important bacterial cause of otitis media (a 7 valent conjugate polysaccharide vaccine serve to prevent this disease) Haemophilus influenzae is a significant cause of otitis media in older children, adolescent and adults Moraxella catarrhalis was isolated from 10% of children with acute otitis media. Before 1970, all strains of M. catarrhalis were sensitive to penicillin Today most strains produce β-lactamase and are resistant to penicillin ampicillin and amoxicillin

39. Etiology of otitis media Bacterial pathogens isolated from middle ear fluid in children with acute otitis media. Total percentages are greater than 100% because of multiple pathogens may be isolated

40. Etiology of otitis media Viruses Many studies identify respiratory viruses or viral antigens in 25% of middle ear fluids of children with acute otitis media. The most important viruses found in middle ear fluids are: Respiratory syncytial viruses Influenza virus Enteroviruses Rhinoviruses

41. Chlamydia and unusual organisms Chlamydia trachomatisis associated with acute respiratory infections in infants younger than 6 mounths, and is a cause of acute infections of the middle ear in this age group Uncommon forms of otitis include: Diphtheritic otitis (bilateral form of otitis media with effusion due to diphtheria bacillus) Tuberculous otitis (accounts for only 0.04% of all cases of chronic suppurative otitis media). Otogenous tetanus (secondary to chronic ear infections) Otitis due to Mycobacterium chelonae (chronic otorrheaand tympanic membrane perforation)

42. Diagnosis and clinical course Acute otitis media is defined by the presence of fluid in the middle ear accompanied by symptoms and acute illness. Ear pain Ear drainage Specific symptoms Fever Lethargy Irritability Nonspecific symptoms Signs and symptoms usually resolve with antimicrobial treatment

43. Antimicrobial treatment There are now 19 antimicrobial agents approved by the Food and Drug Administration for treatment of acute otitis media. Amoxicillin remains the drug of choice for initial treatment. The drug is ineffective against -lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis (H. influenzae and M. catarrhalis are responsible for about 30% and 10% of acute otitis media cases respectively) For patients with known and severe allergy to β-lactam antibiotics, a macrolide (erithromycin, azithromycin,or clarithromycin) is preferred. Decongestants, and corticosteroids administered alone or in combination with an antihistamine are used extensively for the treatment of otitis media with effusion.

44. Sinusitis • Sinusitis is an inflammatory condition of one or more of the paranasal sinuses (frontal, sphenoid, ethmoid, • mascellar sinus) • Most acute cases result from infection, other causes include allergy. • Acute infectious sinusitis can be classified into various categories on the basis of different characteristics including the immune status of patient or its viral, bacterial or fungal etiology. • The knowledge of these categories is important to understand the pathogenesis and to optimize the treatment of this disease. Paranasal sinuses anatomy

45. Sinusitis: classification • Sinusitis can be classified on the basis of symptoms persistence into • acute (symptoms persisting less than four weeks) • subacute (4-8 weeks) • chronic (8 weeks or more) • All three types of sinusitis have similar symptoms and are often difficult to • distinguish. Sphenoid (not visible)

46. Acute sinusitis • Acute sinusitis is often caused by an upper respiratory tract infection generally • of viral origin. • In case of bacterial infection, three are the most common etiological agents: • Streptococcus pneumoniae • Haemophilus influenzae • Moraxella catarrhalis • Until recently Haemophilus influenzae was the most common bacterial agent. • However introduction of the H. influenzae type B vaccine has decreased the • number of cases.

47. Acute sinusitis: other causes • Other sinusitis causing bacterial pathogens include: • Staphylococcus aureus and other streptococci species • Anaerobic bacteria • Less common Gram negative bacteria • Viral sinusitis typically lasts for 7 to 10 days, bacterial sinusitis is more • persistent. • Acute episodes can also result from fungal invasion. These infection are • typically seen in patients with diabetes or other immune deficiencies syndromes

48. Subacute sinusitis • Subacute sinusitis: infection is present for more than four but less than eight weeks. Symptoms may be less severe and include nasal congestion or post-nasal drip.

49. Chronic sinusitis Chronic sinusitis, by definition, lasts more than three months and can be caused by different diseases. Symptoms may include any combination of nasal congestion, facial pain, headache, night-time coughing, general malaise etc. Often chronic sinusitis can reduce sense of smell. In a small number of cases chronic sinusitis is associated with a dental infection

50. Chronic sinusitis: complicated cases Chronic sinusitis cases are subdivided into cases with polyps and cases without polyps. When polyps are present (ethmoid or mascellary sinuses), the condition is more severe. Abnormally narrow sinus and deviated septum blocks the drainage from the sinus cavities contribuiting to infections. A combination of anaerobic and aerobic bacteria including Staphylococcus aureus and coagulase-negative staphylococci can occur. Also fungi play an important role in this disease (fungi can be found in the nasal cavities and sinuses of most patients with sinusitis). Antibiotic treatment provide a reduction of inflammation.