Mohammad Emaneini, PhD

Transcription

1 Mohammad Emaneini, PhD Professor in Microbiology Department of Microbiology School of Medicine Tehran University of Medical Sciences

2 Bacterial Meningitis 80% of cases of bacterial meningitis in infants older than 2 months of age: Streptococcus pneumoniae and Neisseria meningitides N. meningitidis ranks second to S. pneumoniae as a cause of meningitis but is the most common cause in the ages of 2 and 18 years Meningococci (group A) are most likely to cause epidemics of meningitis

3 Neisseria

4 اهداف اختصاصي پس از پايان اين جلسه انتظار مي رود فراگير: خصوصيات عمومي نايسريا ها را بيان كند. شاخص هاي ويرولانس نايسرياهاي بيماريزا را با هم مقايسه كرده تفاوت و تشابه ا نها را توضيح دهد. بيماري هاي ايجاد شده توسط نايسرياهاي بيماريزا را تقسيم بندي كرده راه انتقال ا نها را بيان كند. روش های پيشگيری از گونوکوک و مننگوکوک را توضيح دهد. مكانيسم ايجاد مقاومت به پني سيلين ها را در جدايه هاي نايسريا بيان كند. در مورد اهميت باليني موراكسلا كاتالاريس و ا يكنلا كوردونس بحث كند.

5 Neisseriaceae Catalase Oxidase N. gonorrhoeae Gonorrhea Disseminated infections + + Neisseria Ophthalmia neonatorum Meningitis N. meningitidis Meningococcemia + + Pneumonia Eikenella E. corrodens Human bite wounds Subacute endocarditis - + Kingella K. Kingae Subacute endocarditis - + Simonsiella Normal human oral biota - +

6 Neisseria Aerobic, Gram-negative diplococci (coffee beans) Oxidase-positive, most catalase positive 29 species Pathogenic Neisseria N. gonorrhoeae (Gonococci) Oxidize glucose Not grow in Blood agar N. meningitidis (Meningococci) Colonize nasopharynx Oxidize glucose & maltose Not grow Nonpathogenic Neisseria Oropharynx & nasopharynx Grow on Blood agar (BA) & Nutrient agar (NA)

7 Virulence Factors Pili (Pilin) Capsule LOS OMPs Outer Membrane proteins Por Opa Rmp Mediates initial attachment to nonciliated epithelial cells in the vagina, fallopian tube, and buccal cavity Interferes with neutrophil killing The major virulence factor in N. meningitidis Lipooligosaccharide, Has endotoxin activity Porin protein, Promotes intracellular survival by preventing phagolysosome fusion in neutrophils Opacity protein, Mediates firm attachment to host cells Reduction-modifiable protein; Protects other surface antigens (Por, LOS) from bactericidal antibodies Siderophores IgA1 protease β-lactamase Transferrin, lactoferrin, hemoglobin-binding proteins Destroys immunoglobulin A1 Mediates resistance to penicillin

8 Pili All strains (type IV pili ) Attachment Attachment to nonciliated epithelial cells Transfer of genetic material Motility (twitching motility) Resistance to killing by neutrophils Major virulence factor of N. gonorrhoeae Phase variation Antigenic variation Model for twitching motility. Proc Natl Acad Sci U S A. 2011;108(31):

9 Phase variation Piliated (P + & P + + ) & onpiliated (P - ) state Pilins; encode by pile genes Not be expressed Not be assembled FEMS Microbiol Rev Sep;36(5):917-48

10 Antigenic variation PilC; encode by pils genes Phosphorylation & glycosylation of the C- terminal of the pilin 1 copy of pile & ~20 copies of pils Trends in Molecular Medicine, Volume 10, Issue 9, 2004,

11 Capsular Polysaccharides N. meningitidis Major virulence factor 13 Serogroupe (Most infections: A, B, C, Y, & W135) 12 Serogroupe: N-acetyl-neuraminic acid (sialic acid) A: α-linked N-acetylmannosamine-1-phosphate Systemic isolates: encapsulated Carriage strains: less capsular or non-encapsulated N. gonorrhoeae Not a true capsule (capsule-like charge)

12 LOS

13 Pathogenesis & Immunity Gonococci Interacting with non-ciliated epithelial cells Attachment & penetration: Pili, PorB, & Opa Receptors of Gonococci:CD46, CD66, integrins LOS stimulates release TNF-α TNF-α: most of the symptoms IgG3: predominant IgG Nat Rev Microbiol. 2009; 7(4):274-86

14 Pathogenesis & Immunity Meningococci Attach by type IV pili to nonciliated columnar cells Multiply, forming large aggregates of bacteria Penetrate into the host cells & release into the airways Disease occurs in patients who lack antibodies against the capsule LOS

15 Clinical Diseases of N. gonorrhoeae Gonorrhea Men: Acute urethritis, Epididymitis, prostatitis, Women: Ascending genital Infections Pelvic inflammatory disease (PID) [Salpingitis, tuboovarian abscesses] Disseminated infections Gonococcemia (septicemia) Purulent arthritis in adults Fitz-Hugh Curtis syndrome (perihepatitis) Pharyngitis Ophthalmia neonatorum (Purulent conjunctivitis)

16 Clinical Diseases of N. meningitidis Meningitis Meningococcemia Thrombosis of small blood vessels Multiorgan involvement Small, petechial skin lesions Waterhouse-Friderichsen syndrome Arthritis Urethritis Pneumonia

17 Gonorrhea in Men Urethritis (Acute urethritis) Incubation period: 2-5 days A purulent urethral discharge & dysuria 95% acute infection, Discharge (Purulent in 75% of cases, Cloudy in 20%, Mucoid in 5%) 2.5%: asymptomatic Most cases resolve spontaneously <10% of cases: Epididymitis, Prostatitis, Periurethral abscess

18 Gonorrhea in Women The primary site: cervix (columnar cells) Incubation period: 8-10 days Symptomatic patients Cervicovaginal discharge, abdominal pain, dysuria Abnormal or intermenstrual bleeding (cervicitis) Aascending infection (10-20%) Acute pelvic inflammatory (PID) Salpingitis (infection of the fallopian tubes) Endometritis Tubo-ovarian abscess

19 Epidemiology of the N. gonorrhoeae Humans are the only natural hosts Carriage can be asymptomatic, particularly in women Transmission is primarily by sexual contact Deficiencies in late components of complement (Disseminated disease) Incidence of disease highest in people aged 15 to 24 years Risk of acquiring the infection in a single exposure Women: 50% Men: 20%

20 Epidemiology of the N. meningitidis Humans: only natural hosts Nasopharyngeal carrier rate is 10-40% Spread by respiratory droplets Highest incidence in Children < 5 years (6-24 months) Institutionalized people Patients with late complement deficiencies Meningitis & meningococcemia: B, C, & Y Pneumonia: Y & W135 Underdeveloped countries: A & W135

21 Meningococcal disease incidence by Serogroup & Age

22 Diagnosis of the N. gonorrhoeae Gram stain of urethral specimens is accurate only for symptomatic males Gram stain of synovial fluid is diagnostic for septic arthritis Culture of genital specimens is sensitive and specific but has been replaced with nucleic acid amplification tests (NAATs) Culture is the test of choice for all other specimens Sexually transmitted infections (STIs) N. gonorrhoeae Chlamydia trachomatis Sterile pyuria Treponema pallidum

23 Diagnosis of the N. meningitidis Gram stain of CSF is sensitive and specific Gram stain is of limited value for blood specimens Culture is definitive Organism is fastidious & dies rapidly when exposed to cold or dry conditions Tests to detect meningococcal antigens are insensitive and nonspecific NAATs are not yet widely used

24 Treatment Typical Disease Gonorrhea, e.g., urethritis, cervicitis Treatment Ceftriaxone + Doxycycline Pelvic inflammatory disease Ceftriaxone + Doxycycline Disseminated gonococcal infection Ceftriaxone Conjunctivitis (ophthalmia neonatorum) Ceftriaxone Penicillinase-producing N. gonorrhoeae (PPNG)

25 Treatment, & Control of Meningococcal Infections Penicillin G; ceftriaxone, & cefotaxime Infants have passive immunity (first 6 months) Chemoprophylaxis: rifampin or ciprofloxacin Vaccine for serogroups A, C, Y, & W135 No effective vaccine is available for serogroup B

26 Meningococcal Vaccines Polysaccharide vaccine Menomune Purified capsular polysaccharides of serogroups A, C, Y, & W135 Poorly immunogenic in children <18 months No long lasting immunity No reduces nasopharyngeal carriage Conjugate vaccines 1- Menactra Conjugated to diphtheria toxoid In persons 9 months to 55 years of age 2- Menveo Conjugated to diphtheria toxin CRM197 In individuals 2 months to 55 years of age Is induced T cell dependent response Reduces asymptomatic carriage 3- MenHibrix Serogroup B 1- Bexsero 2- Trumenba

27 Eikenella corrodens Facultatively anaerobic, Gram negative rod Nonmotile, non-spore-forming Normal resident of human mouth Clinical Disease Human bite wound or fist fight injury Subacute endocarditis in patients with preexisting heart disease Opportunistic infections in immunocompromised patients Pneumonia Lung or brain abscesses Sinusitis

28 Moraxella catarrhalis Gram-negative diplococci Aerobic, & oxidase-positive Normal resident of the human mouth Opportunistic pathogen Bronchitis or bronchopneumonia Sinusitis and otitis Predisposing factors Immunodeficiency Neutropenia

29 امام محمد باقر (ع) هيچ بنده اي عالم نمي شود مگر اينکه نسبت به بالا دست خود حسادت نورزد و زيردست خود را خوار نشمارد