Learning objectives of the module;xxxxxxxx

At the end of the lesson students are expected to be able to;
Describe the normal microbiota of the upper and lower respiratory tracts.
Illustrate the host defense mechanisms of the respiratory tract (RT)
Describe epidemiology of respiratory tract infections.
List out the common microbial etiologies of respiratory tract infections.

1. CNS… No openings allow microbial colonization of the central nervous system; Therefore , the CNS is an axenic environment-it has no normal microbiota . Pathogens may access the CNS through breaks in the bones and meninges, through medical procedures such as spinal taps, or by traveling via axonal transport in peripheral neurons to the CNS. 6/5/2024 1

2. CNS… Microbes carried in the blood or lymph may penetrate the blood-brain barrier by infecting and killing cells of the meninges, causing meningitis. Some pathogens gain access to the CNS when localized inflammation distorts the cells of the blood-brain barrier, changing its permeability; such change is more likely during chronic infection by many pathogens. Circulation of cerebrospinal fluid can carry infective microbes throughout the cranial cavity and spinal column. 6/5/2024 2

3. Bacterial Diseases of the Nervous System Not only can bacteria infect cells of the nervous system, B ut toxins released by bacteria growing elsewhere in the body can also affect neurons. In the following sections, we consider diseases of both types-leprosy , which is a disease of cells of the PNS, botulism tetanus, which involve toxins. However, the most common bacterial infection of the nervous system is bacterial meningitis, which we consider next 6/5/2024 3

4. CNS… Bacterial meningitis involves inflammatory bacterial infection of the meninges, commonly the pia mater and arachnoid mater and more rarely the dura mater. 6/5/2024 4

5. CNS… 1. Neisseria meningitidis Neisseria meningitidis is one of only two species of Gram-negative cocci that regularly causes disease in humans. 13 antigenic strains; strains A, B, C, and W135 cause most cases of disease in humans. The cells of all strains of Neisseria are nonmotile and are typically arranged as diplococci (pairs) with their common sides flattened in a manner reminiscent of coffee beans 6/5/2024 5

6. Neisseria meningitidis The bacterium is known as the meningococcus and its disease as meningococcal meningitis . Pathogenesis and clinical findings Aspiration of infective bacteria Attach to epithelial cells of nasopharyngeal and oropharyngeal mucosa Cross the mucosal barrier & enter the bloodstream May enter the CNS and cause meningitis. Meningococcal LPS is responsible for the toxic effects found in meningococcal disease Also antiphagocytic polysaccharide capsule play a role in the pathogenesis 6/5/2024 6

7. Neisseria meningitidis Manifestations of meningococcal infections Fulminant Meningococcemia ( Purpura Fulminans ) The most severe form of meningococcemia is the life-threatening Waterhouse- Friderichsen Syndrome. Characterized by high fever , shock , wide spread purpura , disseminated intravascular coagulation , and adrenal insufficiency 6/5/2024 7

8. Neisseria meningitidis Meningococci shed LOS which stimulate monocytes, neutrophils, and endothelial cells, release cytokines and other mediators In addition, meningococci invade the vascular endothelium, produces molecules that can be procoagulant as well as adhesive for leukocytes. 6/5/2024 8

9. Neisseria meningitidis Fulminant meningococcemia: Occurs in 5 to 15% of patients begins abruptly with sudden high fever, chills, myalgias , weakness, nausea, vomiting, and headache. typically, no signs of meningitis Pulmonary insufficiency develops within a few hours and patients many die within 24 hours even with appropriate antibiotic therapy and intensive care. 6/5/2024 9

10. Neisseria meningitidis Petechial rash and neck extension characteristic of meningococcal meningitis . 6/5/2024 10

11. Neisseria meningitidis Meningococcal meningitis the meninges are inflamed, with thrombosis of blood vessels after an Ip of 1-3 days, the onset of meningococcal meningitis is sudden with a sore throat, headache, & drowsiness and signs of meningitis which include fever, irritability, stiff neck , photophobia and an increased level of PMNs in spinal fluid 6/5/2024 11

12. Neisseria meningitidis Diagnostic Laboratory Tests Specimens : blood for culture, and CSF for smear and culture Culture : CSF specimens are plated on "chocolate" agar and incubated at 37 °C in an atmosphere of 5% CO2 A modified Thayer-Martin medium with antibiotics ( vancomycin , colistin , amphotericin) oxidase + ve : a key test for identifying Neisseriae Serology : antibodies to polysaccharides can be measured by latex agglutination 6/5/2024 12

13. Epidemiology, Prevention, & Control Humans only natural hosts Person-to-person transmission by aerosolization of respiratory tract secretions in crowded conditions Close contact with infectious person (e.g., family members, day care centers, military barracks, prisons, and other institutional settings) Highest incidence in children younger than 5 years and particularly those younger than 1 year of age 5% to 30% Commonly colonize nasopharynx of healthy individuals Vaccine for groups A, C, Y, and W-135 are the capsular polysaccharides 6/5/2024 13

14. Treatment Penicillin G is the drug of choice Either chloramphenicol or a third-generation cephalosporin is used in persons allergic to penicillins 6/5/2024 14

15. 2. Streptococcus pneumoniae Streptococcus pneumoniae Louis Pasteur discovered Streptococcus pneumoniae “ Diplococcus .” Ninety-two different strains of S. pneumoniae , collectively called pneumococci, are known to infect humans as normal members of the microbiota of the throat that opportunistically grow in the lungs, sinuses, and middle ear and from those locations move into the meninges via the blood. Streptococcus pneumoniae is the leading cause of meningitis in adults. 6/5/2024 15

16. Streptococcus pneumoniae About 40 – 70% of healthy adults are carriers Infections usually arise from normal flora (endogenous) 6/5/2024 16

17. Virulence factors Capsule Major determinant of virulence A nti -phagocytosis by preventing C3b complement deposition on the surface Cell Wall Stimulate leukocytes for production of cytokines Teichoic acid enhances inflammatory activity 6/5/2024 17

18. Pneumococcal surface protein A, PspA (Choline binding protein A, CBpA ) Surface – exposed protein Adherence to host tissue, colonization prevent the deposition of C3b on the cell surface binds to lactoferrin , may be involved in iron acquisition 6/5/2024 18

19. Autolysin . breaks the peptide cross-linking of the cell wall peptidoglycan, leading to lysis of the bacteria. Autolysis enables the release of pneumolysin and large amounts of cell wall fragments. The massive inflammatory response to these peptidoglycan fragments is an important component of the pathogenesis of pneumococcal pneumonia and meningitis . 6/5/2024 19

20. Pneumolysin : Intracellular membrane-damaging toxin released by autolysis. Pneumolysin inhibits: neutrophil chemotaxis phagocytosis lymphocyte proliferation and immunoglobulin synthesis. 6/5/2024 20

21. IgA1 protease: cleaves human IgA1 in the hinge region. Enables these pathogens to evade the protective functions of the principal immunoglobulin isotype of the upper respiratory tract Hyaluronate lyase Surface protein Facilitates tissue invasion by breaking down the extracellular matrix components. 6/5/2024 21

22. One of the three leading causes of bacterial meningitis Signs and symptoms are similar to those produced by other bacteria Acute purulent meningitis may follow pneumococcal pneumonia May also develop after trauma involving the skull Mortality and frequency of sequelae are slightly higher than with other forms of pyogenic meningitis 6/5/2024 22

23. Common causes of sinusitis and otitis media Otitis frequently occurs in children in association with viral infection Chronic infection of the respiratory sinus sometimes extends to the subarachnoid space to cause meningitis May cause endocarditis, arthritis, and peritonitis, usually in association with bacteremia Pneumococci do not cause pharyngitis or tonsillitis 6/5/2024 23

24. Laboratory Diagnosis Detection of the pathogen in appropriate test samples Smear: CSF, Sputum and others Culture: Blood, CSF, Sputum and others Stained Smears Gram-stained film of rusty-red sputum shows typical organisms, many PMNs, and many red cells Capsule Swelling Tests Fresh emulsified sputum mixed with antiserum causes capsule swelling ( quellung reaction) 6/5/2024 24

25. Culture: grows well overnight on blood agar α – hemolytic colonies Colonies are bile soluble Inhibited by optochin ( ethylhydrocupreine ) Detection of capsular Ag in body fluids is possible 6/5/2024 25

26. Immunity antibodies to capsular polysaccharide (type-specific) Treatment Penicillin G is the drug of choice Resistant strains due to modified penicillin-binding proteins reported (not due to penicillinase) Resistance rate ~ 10% Penicillin resistant strains can be treated with: Erythromycin , vancomycin or quinolones High dose of third-generation cephalosporins Pneumococci remain susceptible to vancomycin 6/5/2024 26

27. Vaccination Type-specific polysaccharides Probably provide 90% protection against bacteremic pneumonia Pneumovax vaccin available: Contains 25 mg of the purified capsul polysaccharides of each of the 23 most frequent serovars protection of high-risk individuals older than two years . 80 to 90 % of all isolated pneumococci have antigens contained in this vaccine hepta-valent conjugate vaccine ( PCV7 ): recommended for all children aged six weeks to five years of age , to help prevent ear infections 6/5/2024 27

28. Heterogeneous collection of α -hemolytic and non-hemolytic Have the basic features of streptococci but lack specific Ags; toxins, & virulence factors of the other group O ptochin resistant and bile insoluble 6/5/2024 28

29. Genus Haemophilus Small, pleomorphic, Gm -negative bacilli or coccobacilli Facultative anaerobes or fermentative. Require enriched media, blood or its derivative. X factor (i.e., hemin ) and/or V factor (NAD or NADP). Haemophilus influenzae type b is an important human pathogen other species are NF of mucous membranes and only occasionally cause disease. 6/5/2024 29

30. Haemophilus influenzae grow both aerobically and anaerobically. Its growth requires: hemin (X factor) and NAD (V factor). six major serotypes identified( a–f) based on the capsular polysaccharide antigen. some strains lack capsule and are referred to as nontypable strains. subtype b ( Hib ) cause over 90% of all invasive infections 6/5/2024 30

31. Unencapsulated strains may cause: Sinusitis, otitis media, and bronchitis may also cause pneumonia in children in developing regions or in adults with immune defects. Hib strains cause: meningitis, bacteremia, epiglottitis, septic arthritis, pericarditis, as well as placentitis and peripartum septicemia in mothers . A small proportion of invasive disease is caused by other capsular types, notably, a and f . 6/5/2024 31

32. About 50% of all reported invasive infections caused by Hib are meningitis case-fatality rates may reach 40% in developing countries. complications include: subdural effusions and CNS sequelae occur in 11% to 40% of survivors of Hib meningitis, with deafness being a common finding. 6/5/2024 32

33. EPIDEMIOLOGY H. influenzae is the NF of nasopharynx spreads by airborne or direct contact person to person. Nonencapsulated strains are frequently found in the URT. up to 3/4 of healthy adults Carriage of Hib can occur up to 30% of children in developing countries 6/5/2024 33

34. Diagnostic Laboratory Tests Specimens nasopharyngeal swabs, pus, blood, and spinal fluid for smears and cultures. Direct Identification immunologic detection of H . influenzae antigens in spinal fluid. Culture grown on chocolate agar typically (small, flat, colorless/transparent) colonies appear. differentiated from related gram-negative bacilli by its requirements for X and V factors and no hemolysis on blood agar 6/5/2024 34

35. Immunity maternal antibodies for infants under age 3 months Prevention Polysaccharide polyribose phosphate capsule vaccines Treatment many strains of Hib are susceptible to ampicillin , but up to 25% produce - lactamase all strains are susceptible to the third-generation cephalosporins . 6/5/2024 35

36. Streptococcus agalactiae (group B Streptococci) Gm + ve cocci , short chains & diplococcal pairs Larger colonies β -hemolytic The only species that carries the Lancefield group B antigen Nine different capsular polysaccharide have been identified ( Ia , Ib , and II-VIII). Serotype III most frequently associated with neonatal infections , adult infections are distributed over the different serotypes. Resident in the GIT Members of the NF of 10 to 30% female genital organ 6/5/2024 36

37. May gain access to the amnoitic fluid or colonize the newborn as it passes through the birth canal A major cause of sepsis and meningitis in neonates Risk is much higher when factors are present that: decreased infant’s innate resistance (prematurity) or increased chances of transmission (ruptured amniotic membranes) 6/5/2024 37

38. Immunocompromised individuals : Infections of the skin & connective tissues, Sepsis, UTI, Pneumonia & Peritonitis Virulence factor Capsular polysaccharide Haemolysins C5a peptidase hyaluronidase (not all strains) 6/5/2024 38

39. Clinical diseases defined by the age of the patient at presentation Neonatal infection i) Early-onset neonatal disease Occur within the first week of life , with a median age of 20 hrs at the onset of illness Infection acquired during or shortly before birth from organisms colonizing the maternal genital tract 6/5/2024 39

40. results from ascending spread of Str. agalactiae from the vagina into the amniotic fluid Then aspirated by the infant, and results in septicaemia of infant or mother or both . ~ 50% of infants delivered vaginally by carrier mothers become colonized only 1 to 2% develop clinically evident infection 6/5/2024 40

41. Purulent Meningitis  most common manifestation but septic arthritis, osteomyelitis, conjunctivitis, sinusitis, otitis media, endocarditis and peritonitis also occur Findings : fever, lethargy or irritability, poor feeding, and seizures 6/5/2024 41

42. Laboratory diagnosis Culture : blood, CSF, or other appropriate specimen Definitive identification: reaction to specific antiserum to the group B carbohydrate antigen Biochemical tests (presumptive identification): hydrolysis of sodium hippurate (99% + ve ) hydrolysis of bile esculin agar (99 to 100% - ve ) bacitracin susceptibility (92% resistant ) 6/5/2024 42

43. Immunity Abs to the capsular polysaccharide afford protection Treatment Penicillin is the treatment of choice (less susceptible than GAS) Neonatal infections  often initially treated with combinations of penicillin (or ampicillin) and an aminoglycoside Prophylactic administration of ampicillin or penicillin during delivery reduce the risk of infection 6/5/2024 43

44. Focused on reducing contact of the infant with the organism In colonized women: attempts to eradicate the carrier state  not successful intrapartum antimicrobial prophylaxis with penicillin or ampicillin  reduce transmission and disease in high-risk populations 6/5/2024 44