1. Bacterial Infection of Central Nerve System 3 rd Year Medical Students Prof. Dr Asem Shehabi Faculty of Medicine, University of Jordan

2. Meningitis & Encephalitis-1  Infections of the brain and spinal cord can cause dangerous inflammation.. Encephalitis or Meningitis  Meningitis results from infection of meninges.. the membranes that surround the brain and spinal cord.  Encephalitis is inflammation of the brain itself.  Myelitis is infection of the spinal cord alone.  Encephalomyelitis includes inflammation of both the brain and the spinal cord..Common cause viruses  Acute meningitis can be caused by Viruses, Bacteria, Fungi, Viruses.. produce a wide range of symptoms, including fever, headache, neck stiffness, confusion, vomiting, photophobia..Mild non-specific symptoms.

3. Meningitis & Encephalitis-2 Meningitis & Encephalitis-2  Any delay in treatment menigitis may cause brain damage, stroke, seizures, death.  Any CNS inflammation can harm or destroy nerve cells and cause bleeding in the brain.  Acute Meningitis & Encephalitis are mostly caused by viruses (95%), bacteria ( 2-5%), Fungi (1-2%).. Affect all ages.. majority children aged < 5 years.  Most CNS Pathogens acquired through the blood stream.. travel to the spinal cord.. brain.. Following Resp. Tract Infections, sepsis, Brain Surgery or any surgical procedure.  Aseptic meningitis caused mostly by viruses.. Less clinical sings & symptoms. 

4. Common Cause of Acute Bacterial Meningitis  Pneumococcal meningitis / S. pneumoniae.. Gram+ve diplococcus.. Alpha-Hemolytic.. Pneumococci are spread by personal contact, commonly by sneezing, coughing or close personal contact.  Major virulence factor: Capsule (90 Serotypes),IgA-1 protease, cytotoxin pneumolysin. Respiratory Healthy carriers.. Prevalence Up to 70%.. More in winter months.. More children.. Mostly endogenous infection. Common cause of meningitis.. most serious form of all bacterial meningitis.. High fatality.  Pneumococcal meningitis follow acute /sub acute pneumonia, septicemia, ear and sinus infections.

5. S. pneumoniae-  High risk children under age 3-year, elderly, persons with immunodeficiencies, malignancy, diabetes melitlitus, asplenia, ischaemic heart disease, sickle cell anaemia,..  Following severe viral infections.. Measles, Mumps  Late treated pneumococcal meningitis often causes neurological damage..deafness to severe brain damage.  Treatment: Most S. pneumoniae strains are Highly resistance to penicillin.. less to erythromycin and tetracycline.. Highly susceptible to vancomycin & Cefotaxime / ceftriaxone  Prevention: polyvalent polysaccharide vaccine includes 23 polysaccharides serotyptes (pneumovax).. adults.. protective efficacy about 60%–70%.. Each year.  A second Pneumococcal conjugate vaccine (Prevenar), contains 13- selected polysaccharides serotypes bound to a protein.. used in 2-months infants – children.. less than 2-year.. Two-doses.. Protection > 90%

6. S.pneumoniae Lab diagnosis Blood culture-Optochin/ Gram-stain

7. Neisseria meningitides-  Meningococcal meningitis: N. meningitides.. Gram- negative diplococci..Serotypes A, B. C, Y,W-135.. Nasopharynx.. Human only host.. Few% Respiratory Healthy carriers.. common in late winter.. More common in children than adults.. highly contagious disease.. Causing outbreak in schools, military camps.  Endemic in tropics & subtropics countries in Africa and South America.  Major virulence factor: Pili, Capsule, Lipooligo- saccharides, Outer-membrane proteins, IgA Protease.  High-risk groups include infants & children aged of 6 months - 3 year, persons with suppressed immune systems.. travelers to endemic countries in Africa, South America.. Non-pathogenic Neisseria species.. contribute to host protection

8. /2  Acute disease.. Headache, high Fever, Neck stiffness, vomiting, Septicemia-Meningitis.. Thrombosis small blood vessel, Skin hemorrhagic rash, comma within few hours.  Complication: Adrenal hemorrhage.. Water-house Friderichsen syndrome.. Disseminated Intravascular coagulation, circulatory collapse, Death. Between 10 - 15 % of cases are fatal.. another 10-15 % causing brain damage and other serious side effects..  Capsular polysaccharide vaccine > 2 years.. Adult  Treatment: Penicillin-R low, Cefotaxime / ceftriaxone. Rifampicin only for carriers/contact persons

9. N.meningitidis-Pili Gram-stain/intracellular

10. Haemophilus influenzae  H. influenzae b.. normal flora Nasopharynax.. Low % Healthy carriers encapsulated type b.. Virulent & invasive.. capsule.. High-risk children ages 5 months-5 years.. Rare adults.. Other H. influenzae serotypes less virulent..  Acute onset disease: Mild sore throat / pneumonia, chronic brochitis, empyema, sinusitis, otitis media, conjunctivitis..  Lack bactericidal specific antibodies result in septicemia, meningitis in children.  Before 1990.. Use of Hib vaccine.. was the most common form of bacterial meningitis among young children worldwide.  Haemophilus b conjugate vaccine reduced the incidence of meningitis up to 95% & carrier rate.. Immunization children up 2 months.. > 95% protection.  Treatment: Ampicillin-R 25-50%, Third G-Cephalosprin

11. Virulence of Common Pathogens H. Influenzae Type b N.meningitidis S. pneumonia VirulenceFactors + Thin + Large Capsule +++ IgA Protease ++-Pili ++- Endotoxin- outermembrenes proteins

12. H. influenzae/ Coccobacilli-Short filaments - Listeria monocytogenes

13. Less Common bacterial Meningitis  Group B Streptococci (GBS):  Colonize 10-30% adult women vagina/ intestine.. Rectum.. common cause of acute fatal neonatal sepsis & meningitis.  Infection is spread to infants before or during delivery.. membrane rupture before delivery.. swallowing contaminated amniotic fluid during delivery.  New born baby may develop pneumonia, sepsis, acute meningitis.. Mothers developing Endometritis, Septicemia, Puerperal fever/ bedchild fever..  Lab Diagnosis+ Treatment: Blood Culture.. Ampicillin, 2G Cephalosporins.. Cefixime

14. Listeria monocytogenes  Gram-positive intracellular coccobacilli.. Common in animals intestine.. Infection commonly in compromised host.. contaminated milk, dairy products.. Colonize intestine.. enteritis, mesenteric lymphadenitis, Sepsis  Rarely colonize female genital tract.. can cross the placental barrier and cause abortion or sepsis- meningitis in neonatal & adult.. High fatality without treatment.  Lab Diagnosis+ Treatment: Blood Culture..Treatment: Co-trimoxazole, floroquinlones, aminoglycosides.

15. Less Common bacterial Meningitis-2  Enteric Bacteria: Klebsiella, Enterobacter, Pseudomonas aeruginosa.. Gram-ve bacilli.. Following surgical procedure in spinal cord, Sepsis, Burn cases.. Mostly Nosocomial Infection  E. coli : Common cause of sepsis & meningitis in new born baby.. transmitted through the birth canal /intestine..Infant >6 months susceptible to lipopolysaccharides.  Brucellosis: B. melitensis.. Rare B. abortrus.. intracellular Gram-ve coccobacillus.. septicemia.. survive lymphatic tissues.. Abscess/Granulomatous lesions in Liver, spleen.. any body part.. few % chronic meningitis. Diagnosis by serological agglutination test.. rarely positive culture. Treatment: combination.. doxycycline + rifampicin or ciprofloxacin/co- trimoxazole ( children) 6-8 weeks.. Common in Jordan and other Arab countries.

16. Chronic meningitis & Brain Abscess-1  Tuberculosis: M. tuberculosis.. Rare other species.. Acid-fast bacilli.. cause meningitis in young children with malnutrition.. more than adults following miliary tuberculosis.. Less lung tuberculosis.. Mostly in Developing countries.  Syphilis: Treponema pallidum.. Tertiary stage or congenital Syphilis may cause Neurosyphilis.. meningitis due to presence of its antigens).. diagnosed by serological test.. Difficult to be clinically cured.. Treatment Penicillin. fluid culture

17. Chronic meningitis & Brain Abscess-2  Nocardiosis: N. asteroides, Slightly Acid-fast bacilli, Common in soil.. Inhalation, Chronic Lung lesions.. Immuno-suppresed, meningitis, brain abscess  Rapid aerobic culture growth.. one week  Treatment: ciprofloxacin, co-trimoxazole, Rifampicin  Lyme disease: Borrelia burgdorferi.. spirochaete.. animal skin…deer.. Transmitted by Deer Tick bites.. circular skin rash..Erythema Migrans, mild sepsis, flu- like symptoms, Later involve joints, heart, CNS.. Complication Meningitis-Encephalitis, Chronic arthritis.. Common in USA, Canada, North Europe.  Lab Diagnosis: Dark-field microscopy, Special fluid culture, Specific antibodies (IgG, IgM) ELISA, PCR  Macrolides, Doxycyclines, Ceftriaxone

18. Tick-Lyme Skin Lesion-Borrelia

19. Fungal meningitis-1  Cryptococcosis: C.neoformans.. This fungus is found in the environment worldwide, particularly in soil contaminated with bird droppings.  Enters the body most commonly through the lungs.. Infection develop often in immuno-compromised patients.. advanced AIDS.  Cryptococcus can also cause infections of the lungs, skin, prostate gland.. Fatal without treatment.  Cryptococcal meningitis develop very slow, chronic.. CNS vague symptoms.. mild/sever headache, fever.. difficult to diagnose without full investigation.

20. Capsulated Cryptococcus (India ink preparation)

21. Fungal meningitis-2  Candidasis: C.albicans, C.glabrata, Others.. Lung.. blood Infection.. Rare meningitis.. compromised host.  Histplasmosis: H. capsulatum..Lung, Systemic, Skin  Blastomycosis: B. dermatitidis, Lung, Systemic, Skin Both infection may ended in chronic meningitis. Both infection may ended in chronic meningitis.  Lab Diagnosis: Direct CSF exam, Culture Sabouraud Dextrose agar, Blood agar.. Incubation 1-4 weeks.  Serological methods are not useful.  Treatment: Amphotericin B+ Flucytosine, fluconazole are the most common drugs used.  Fungal Vaccines are still not available.

22. Candida growth- Gram stain

23. Laboratory Diagnosis of Bacterial meningitis  CSF specimens should be sent rapidly for the following investigation: WBC count, Level of glucose+ protein  Bacterial menigitis:  Cloudy fluid, glucose level 50 mg/dL ( normal:15-45 ), numerous WBCs /predominance neutrophils 200 > 20000/uL  Fungal meningitis:  Mild/not cloudy fluid, little change in glucose + protein levels.. 100-1000 uL WBCs.. mostly Lymphocytes.  Tuberculosis meningitis: Mild cloudy fluid, little change in glucose + protein levels.. 100-1000 uL WBCs/ Lymphocytes  Late CNS Syphlis: Clear fluid.. Normal Glucose.. slight elevation Protein.. Few WBCs

24. Bacterial Antigen Test  Direct AntigenTests are available to detect bacterial antigens in the CSF for diagnosis of S. pneumoniae, N. meningitidis, H. influenzae type b, group A, B Streptococcus. N. meningitidis, H. influenzae type b, group A, B Streptococcus.  These tests should be confirmed by positive Gram- stain or culture  Therefore, negative results for a specific bacterial antigen do not rule out bacterial meningitis.  Molecular methods (PCR) that amplify bacterial DNA in CSF may have improved sensitivity and specificity.. used mostly in reference laboratories.

25. Bacterial neurotoxins  Tetanus is an acute, sometimes fatal, disease of the central nervous system, caused by the toxin of Cl. tetani, which usually enters the body through an wound. disseminated to blood, lymphatics.. Toxins act on CNS.. Interferes with release of neurotransmitters, blocking inhibitor impulses.. causing difficult in swallowing, muscle rigidity & spasms. Treatment.. Specific antibodies.  Botulism..Cl. botulinum toxin.. Ingestion food, toxin absorbed.. Spread to CNS.. inhibits acetylcholine release on peripheral nerves.. affects motor & autonomic nervous system.. Rapid flaccid paralysis.. Cardiac & Respiratory failure.. Death.. Specific antitoxin treatment can be helpful if available.

26. Cl.tetani-Cl.botulinum