Bacterial Infection of Central Bacterial Infection of Central Nerve SystemNerve System

33rdrd Year Medical Students Year Medical Students

Prof. Dr Asem ShehabiProf. Dr Asem Shehabi

Faculty of Medicine, University of Faculty of Medicine, University of JordanJordan

Meningitis & Encephalitis-1Meningitis & Encephalitis-1

Infections of the Infections of the brain and spinal cordbrain and spinal cord can cause can cause dangerous inflammation.. dangerous inflammation.. Encephalitis or MeningitisEncephalitis or Meningitis

MeningitisMeningitis results from infection of results from infection of meningesmeninges.. the .. the membranes that surround the brain and spinal cord.membranes that surround the brain and spinal cord.

EncephalitisEncephalitis is inflammation of the is inflammation of the brain itselfbrain itself.. MyelitisMyelitis is infection of the spinal cord alone. is infection of the spinal cord alone. EncephalomyelitisEncephalomyelitis includes inflammation of both the includes inflammation of both the

brain and the spinal cord..Common cause viruses brain and the spinal cord..Common cause viruses Acute meningitis can be caused by Acute meningitis can be caused by VirusesViruses, , BacteriaBacteria, ,

Fungi,Fungi, VirusesViruses.. produce a wide range of symptoms, .. produce a wide range of symptoms, including fever, headache, neck stiffness, confusion, including fever, headache, neck stiffness, confusion, vomiting, photophobia..Mild non-specific symptoms. vomiting, photophobia..Mild non-specific symptoms.

Meningitis & Encephalitis-2Meningitis & Encephalitis-2 Any delay in treatmentAny delay in treatment menigitis may cause brain menigitis may cause brain

damage, stroke, seizures, death. damage, stroke, seizures, death. Any CNS inflammation can harm or Any CNS inflammation can harm or destroy nerve destroy nerve

cells and cause bleeding in the brain.cells and cause bleeding in the brain. Acute MeningitisAcute Meningitis & & EncephalitisEncephalitis are mostly caused are mostly caused

by viruses (95%), bacteria ( 2-5%), Fungi (1-2%).. by viruses (95%), bacteria ( 2-5%), Fungi (1-2%).. Affect all ages.. majority children aged < 5 years.Affect all ages.. majority children aged < 5 years.

Most Most CNS Pathogens CNS Pathogens acquired through the acquired through the blood blood streamstream .. travel to the spinal cord.. brain.. Following .. travel to the spinal cord.. brain.. Following Resp. Tract Infections, sepsis, Brain Surgery or any Resp. Tract Infections, sepsis, Brain Surgery or any surgical procedure.surgical procedure.

Aseptic meningitis caused mostly by viruses.. Less Aseptic meningitis caused mostly by viruses.. Less clinical sings & symptoms. clinical sings & symptoms.

Common Cause of Acute Bacterial MeningitisCommon Cause of Acute Bacterial Meningitis Pneumococcal meningitisPneumococcal meningitis / / S. pneumoniae..S. pneumoniae..

Gram+ve diplococcus.. Alpha-Hemolytic.. Gram+ve diplococcus.. Alpha-Hemolytic.. Pneumococci are spread by personal contact, Pneumococci are spread by personal contact, commonly by sneezing, coughing or close personal commonly by sneezing, coughing or close personal contact. contact.

Major virulence factor:Major virulence factor: Capsule Capsule (90 Serotypes),(90 Serotypes),IgA-1 IgA-1 proteaseprotease, cytotoxin , cytotoxin pneumolysinpneumolysin. Respiratory Healthy . Respiratory Healthy carrierscarriers.. .. Prevalence UpPrevalence Up to to 7070%.. %.. More in winter More in winter months.. More children.. Mostly endogenous infection. months.. More children.. Mostly endogenous infection. Common cause of meningitis .. most serious form of Common cause of meningitis .. most serious form of all bacterial meningitis.. High fatality. all bacterial meningitis.. High fatality.

Pneumococcal meningitisPneumococcal meningitis follow acute /sub acute follow acute /sub acute pneumonia, septicemia, ear and sinus infectionspneumonia, septicemia, ear and sinus infections. .

S. pneumoniaeS. pneumoniae-- High risk children under age 3-year, elderly, persons with High risk children under age 3-year, elderly, persons with

immunodeficiencies, malignancy, diabetes melitlitus,immunodeficiencies, malignancy, diabetes melitlitus, asplenia, asplenia, ischaemic heart diseaseischaemic heart disease, , sickle cell anaemiasickle cell anaemia,.. ,..

Following severe viral infections.Following severe viral infections.. . Measles, Mumps Measles, Mumps Late treated pneumococcal meningitisLate treated pneumococcal meningitis often causes often causes

neurological damage..deafness to severe brain damage.neurological damage..deafness to severe brain damage. Treatment:Treatment: Most S. pneumoniae strains are Highly resistance Most S. pneumoniae strains are Highly resistance

to penicillin.. less to erythromycin and tetracycline.. Highly to penicillin.. less to erythromycin and tetracycline.. Highly susceptible to susceptible to vancomycinvancomycin & & Cefotaxime / ceftriaxoneCefotaxime / ceftriaxone

Prevention:Prevention: polyvalent polysaccharide vaccine includes polyvalent polysaccharide vaccine includes 23 23 polysaccharidespolysaccharides serotyptesserotyptes ((pneumovaxpneumovax).. adults).. adults.. .. protective efficacy about 60%–70%.. Each year. protective efficacy about 60%–70%.. Each year.

A second Pneumococcal conjugate vaccine A second Pneumococcal conjugate vaccine (Prevenar)(Prevenar), , contains contains 13- selected polysaccharides serotypes 13- selected polysaccharides serotypes bound to a bound to a protein.. used in 2-months infants – children.. less than 2-year. . protein.. used in 2-months infants – children.. less than 2-year. . Two-doses.. Protection > 90% Two-doses.. Protection > 90%

S.pneumoniae Lab diagnosisS.pneumoniae Lab diagnosisBlood culture-Optochin/ Gram-stainBlood culture-Optochin/ Gram-stain

Neisseria meningitidesNeisseria meningitides-- Meningococcal meningitisMeningococcal meningitis: : N. meningitides.. Gram-N. meningitides.. Gram-

negative diplococci ..Serotypes A, B. C, Y,W-135.. negative diplococci ..Serotypes A, B. C, Y,W-135.. Nasopharynx.. Human only host.. Few% Respiratory Nasopharynx.. Human only host.. Few% Respiratory Healthy carriers.. common in late winter.. More Healthy carriers.. common in late winter.. More common in children than adults.. common in children than adults.. highly contagious highly contagious diseasedisease.. Causing outbreak in schools, military camps. .. Causing outbreak in schools, military camps.

Endemic in tropics & subtropics countries in Africa and Endemic in tropics & subtropics countries in Africa and South America. South America.

Major virulence factor:Major virulence factor: Pili, Capsule, Lipooligo-Pili, Capsule, Lipooligo-saccharides, Outer-membrane proteins, saccharides, Outer-membrane proteins, IgA ProteaseIgA Protease..

High-risk groups include infants & children aged of 6 High-risk groups include infants & children aged of 6 months - 3 year, persons with suppressed immune months - 3 year, persons with suppressed immune systems.. travelers to endemic countries in Africa, systems.. travelers to endemic countries in Africa, South America.. Non-pathogenic South America.. Non-pathogenic NeisseriaNeisseria species.. species.. contribute to host protection contribute to host protection

/2 Acute diseaseAcute disease.. Headache, high Fever, Neck .. Headache, high Fever, Neck

stiffness, vomiting, Septicemia-Meningitis.. stiffness, vomiting, Septicemia-Meningitis.. Thrombosis small blood vessel, Skin hemorrhagic Thrombosis small blood vessel, Skin hemorrhagic rash, comma within few hours. rash, comma within few hours.

ComplicationComplication: Adrenal hemorrhage.. : Adrenal hemorrhage.. Water-house Water-house Friderichsen syndromeFriderichsen syndrome.. Disseminated Intravascular .. Disseminated Intravascular coagulation, circulatory collapse, Death. Between 10 -coagulation, circulatory collapse, Death. Between 10 -15 % of cases are fatal.. another 10-15 % causing 15 % of cases are fatal.. another 10-15 % causing brain damage and other serious side effects.. brain damage and other serious side effects..

Capsular polysaccharide vaccine > 2 years.. AdultCapsular polysaccharide vaccine > 2 years.. Adult Treatment: Penicillin-R low, Cefotaxime / ceftriaxoneTreatment: Penicillin-R low, Cefotaxime / ceftriaxone. .

Rifampicin only for carriers/contact personsRifampicin only for carriers/contact persons

N.meningitidis-PiliN.meningitidis-PiliGram-stain/intracellularGram-stain/intracellular

Haemophilus Haemophilus influenzaeinfluenzae H. influenzae bH. influenzae b.. .. normal flora Nasopharynax.. Low % Healthy normal flora Nasopharynax.. Low % Healthy

carriers carriers encapsulated type encapsulated type b.. Virulent & invasive.. capsule.. b.. Virulent & invasive.. capsule.. High-risk children ages 5 months-5 years.. Rare adults.. Other High-risk children ages 5 months-5 years.. Rare adults.. Other H. influenzae H. influenzae serotypes less virulent..serotypes less virulent..

Acute onset disease: Acute onset disease: Mild sore throat / pneumonia, chronic Mild sore throat / pneumonia, chronic brochitis, empyema, sinusitis, otitis media, conjunctivitis.. brochitis, empyema, sinusitis, otitis media, conjunctivitis..

Lack bactericidal specific antibodies result in septicemia, Lack bactericidal specific antibodies result in septicemia, meningitis in children.meningitis in children.

Before 1990Before 1990 .. Use of .. Use of Hib vaccineHib vaccine.. was the most common .. was the most common form of bacterial meningitis among young children worldwide.form of bacterial meningitis among young children worldwide.

Haemophilus b conjugate vaccineHaemophilus b conjugate vaccine reduced the incidence of reduced the incidence of meningitis up to 95% & carrier rate.. Immunization children up 2 meningitis up to 95% & carrier rate.. Immunization children up 2 months.. > 95% protection. months.. > 95% protection.

Treatment: Ampicillin-R 25-50%, Third G-CephalosprinTreatment: Ampicillin-R 25-50%, Third G-Cephalosprin

Virulence of Common PathogensVirulence of Common PathogensVirulenceVirulence

FactorsFactors

S. pneumoniaS. pneumoniaN.meningitidisN.meningitidisH. InfluenzaeH. Influenzae

Type bType b

CapsuleCapsule + +LargeLarge + +ThinThin + +ThinThin

IgA ProteaseIgA Protease++++++

PiliPili--++++

Endotoxin- Endotoxin- outermembrenes outermembrenes proteinsproteins

--++++

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

Less Common bacterial MeningitisLess Common bacterial Meningitis

Group BGroup B Streptococci Streptococci (GBS)(GBS): : Colonize 10-30% adult women vagina/ intestine.. Colonize 10-30% adult women vagina/ intestine..

Rectum.. common cause of acute fatal Rectum.. common cause of acute fatal neonatal neonatal sepsis & meningitissepsis & meningitis. .

Infection is spread to infants before or during delivery.. Infection is spread to infants before or during delivery.. membrane rupture before delivery.. swallowing membrane rupture before delivery.. swallowing contaminated amniotic fluid during delivery. contaminated amniotic fluid during delivery.

New born baby may develop pneumonia, sepsis, New born baby may develop pneumonia, sepsis, acute meningitis.. Mothers developing acute meningitis.. Mothers developing Endometritis, Endometritis, Septicemia, Puerperal fever/ bedchild feverSepticemia, Puerperal fever/ bedchild fever.. ..

Lab Diagnosis+ Treatment: Lab Diagnosis+ Treatment: Blood Culture.. Ampicillin, Blood Culture.. Ampicillin, 2G Cephalosporins2G Cephalosporins.. Cefixime.. Cefixime

Listeria monocytogenesListeria monocytogenes Gram-positive intracellular coccobacilli.. Gram-positive intracellular coccobacilli..

Common in animals intestine.. Infection Common in animals intestine.. Infection commonly in compromised host.. contaminated commonly in compromised host.. contaminated milk, dairy products.. Colonize intestine.. milk, dairy products.. Colonize intestine.. enteritisenteritis, , mesenteric lymphadenitis, Sepsismesenteric lymphadenitis, Sepsis

Rarely colonize female genital tract.. can cross Rarely colonize female genital tract.. can cross the placental barrier and cause abortion or the placental barrier and cause abortion or sepsis- meningitissepsis- meningitis in neonatal & adult.. High in neonatal & adult.. High fatality without treatment. fatality without treatment.

Lab Diagnosis+ Treatment: Blood Culture..Treatment: Lab Diagnosis+ Treatment: Blood Culture..Treatment: Co-trimoxazole, floroquinlones, aminoglycosides.Co-trimoxazole, floroquinlones, aminoglycosides.

Less Common bacterial Meningitis-2Less Common bacterial Meningitis-2

EntericEnteric Bacteria Bacteria: Klebsiella, Enterobacter, Pseudomonas : Klebsiella, Enterobacter, Pseudomonas aeruginosa.aeruginosa.. Gram-ve bacilli.. Following surgical procedure in . Gram-ve bacilli.. Following surgical procedure in spinal cord, Sepsis, Burn cases.. Mostly Nosocomial Infectionspinal cord, Sepsis, Burn cases.. Mostly Nosocomial Infection

E. coliE. coli :: Common cause of sepsis & meningitis in new born Common cause of sepsis & meningitis in new born baby.. transmitted through the birth canal /intestine ..Infant >6 baby.. transmitted through the birth canal /intestine ..Infant >6 months susceptible to lipopolysaccharides.months susceptible to lipopolysaccharides.

Brucellosis:Brucellosis: B. melitensis.. Rare B. abortrus ..B. melitensis.. Rare B. abortrus .. intracellular intracellular Gram-ve coccobacillus.. septicemia.. survive lymphatic tissues.. Gram-ve coccobacillus.. septicemia.. survive lymphatic tissues.. Abscess/Granulomatous lesions in Liver, spleen.. any body Abscess/Granulomatous lesions in Liver, spleen.. any body part.. few % chronic meningitis. Diagnosis by serological part.. few % chronic meningitis. Diagnosis by serological agglutination test.. rarely positive culture. Treatment: agglutination test.. rarely positive culture. Treatment: combination.. doxycycline + rifampicin or ciprofloxacin/co-combination.. doxycycline + rifampicin or ciprofloxacin/co-trimoxazole ( children) 6-8 weeks.. Common in Jordan and trimoxazole ( children) 6-8 weeks.. Common in Jordan and other Arab countries.other Arab countries.

Chronic meningitis & Brain Abscess-1Chronic meningitis & Brain Abscess-1

Tuberculosis:Tuberculosis: M. M. tuberculosis tuberculosis .. Rare other .. Rare other species.. Acid-fast bacilli.. cause meningitis in species.. Acid-fast bacilli.. cause meningitis in young children with malnutrition.. more than young children with malnutrition.. more than adults following adults following miliarymiliary tuberculosis.. Less lung tuberculosis.. Less lung tuberculosis.. Mostly in Developing countries. tuberculosis.. Mostly in Developing countries.

Syphilis:Syphilis: Treponema pallidum.. Treponema pallidum.. Tertiary stageTertiary stage oror congenital Syphilis may causecongenital Syphilis may cause Neurosyphilis..Neurosyphilis.. meningitis due to presence of its meningitis due to presence of its antigens).. antigens).. diagnosed by serological testdiagnosed by serological test.. .. Difficult to be clinically cured.. Treatment Difficult to be clinically cured.. Treatment Penicillin.Penicillin.

fluid culturefluid culture

Chronic meningitis & Brain Abscess-2Chronic meningitis & Brain Abscess-2 NocardiosisNocardiosis:: N. asteroides, N. asteroides, Slightly Acid-fast bacilli, Slightly Acid-fast bacilli,

Common in soil.. Inhalation, Chronic Lung lesions.. Common in soil.. Inhalation, Chronic Lung lesions.. Immuno-suppresed, meningitis, brain abscessImmuno-suppresed, meningitis, brain abscess

Rapid aerobic culture growth.. one weekRapid aerobic culture growth.. one week Treatment: ciprofloxacin, co-trimoxazole, Rifampicin Treatment: ciprofloxacin, co-trimoxazole, Rifampicin Lyme diseaseLyme disease:: Borrelia burgdorferiBorrelia burgdorferi.. spirochaete.. .. spirochaete..

animal skin…deer.. Transmitted by Deer Tick bites.. animal skin…deer.. Transmitted by Deer Tick bites.. circular skin rash..Erythema Migrans, mild sepsis, flu-circular skin rash..Erythema Migrans, mild sepsis, flu-like symptoms, Later involve joints, heart, CNS.. like symptoms, Later involve joints, heart, CNS.. Complication Complication Meningitis-Encephalitis,Meningitis-Encephalitis, Chronic Chronic arthritis.. Common in USA, Canada, North Europe. arthritis.. Common in USA, Canada, North Europe.

Lab Diagnosis: Lab Diagnosis: Dark-field microscopy, Special fluid Dark-field microscopy, Special fluid culture, Specific antibodies (IgG, IgM) ELISA, PCRculture, Specific antibodies (IgG, IgM) ELISA, PCR

Macrolides, Doxycyclines, CeftriaxoneMacrolides, Doxycyclines, Ceftriaxone

Tick-Lyme Skin Lesion-BorreliaTick-Lyme Skin Lesion-Borrelia

Fungal meningitis-1Fungal meningitis-1 Cryptococcosis: Cryptococcosis: C.neoformansC.neoformans.. This fungus is found .. This fungus is found

in the environment worldwide, particularly in soil in the environment worldwide, particularly in soil contaminated with bird droppings. contaminated with bird droppings.

Enters the body most commonly through the lungs.. Enters the body most commonly through the lungs.. Infection develop often in Infection develop often in immuno-compromised immuno-compromised patients.. advanced AIDS.patients.. advanced AIDS.

Cryptococcus can also cause infections of the Cryptococcus can also cause infections of the lungs, lungs, skin, prostate gland..skin, prostate gland.. Fatal without treatment. Fatal without treatment.

Cryptococcal meningitisCryptococcal meningitis develop very slow, chronic.. develop very slow, chronic.. CNS vague symptoms.. mild/sever headache, fever.. CNS vague symptoms.. mild/sever headache, fever.. difficult to diagnose without full investigation.difficult to diagnose without full investigation.

Capsulated Capsulated CryptococcusCryptococcus(India ink preparation)(India ink preparation)

Fungal meningitis-2Fungal meningitis-2

CandidasisCandidasis: : C.albicans, C.glabrataC.albicans, C.glabrata, Others.. Lung.. , Others.. Lung.. blood Infection.. Rare meningitis.. compromised host.blood Infection.. Rare meningitis.. compromised host.

HistplasmosisHistplasmosis: : H. capsulatumH. capsulatum ..Lung, Systemic, Skin ..Lung, Systemic, Skin BlastomycosisBlastomycosis:: B. dermatitidisB. dermatitidis, Lung, Systemic, Skin, Lung, Systemic, Skin Both infection may ended in chronic meningitis.Both infection may ended in chronic meningitis. Lab DiagnosisLab Diagnosis: Direct CSF exam, Culture Sabouraud : Direct CSF exam, Culture Sabouraud

Dextrose agar, Blood agar.. Incubation 1-4 weeks.Dextrose agar, Blood agar.. Incubation 1-4 weeks. Serological methods are not useful. Serological methods are not useful. Treatment:Treatment: Amphotericin B+ Flucytosine, fluconazole Amphotericin B+ Flucytosine, fluconazole

are the most common drugs used. are the most common drugs used. Fungal VaccinesFungal Vaccines are still not available. are still not available.

Candida growth- Gram stainCandida growth- Gram stain

Laboratory Diagnosis of Bacterial Laboratory Diagnosis of Bacterial meningitismeningitis

CSF specimens CSF specimens should be sent rapidly for the following should be sent rapidly for the following investigation: investigation: WBC countWBC count, Level of , Level of glucose+ proteinglucose+ protein

Bacterial menigitis:Bacterial menigitis: Cloudy fluid, Cloudy fluid, glucose levelglucose level << 40 mg/dL (normal: 45-85), Protein 40 mg/dL (normal: 45-85), Protein

level >50 mg/dL ( normal:15-45 ), numerous WBCs level >50 mg/dL ( normal:15-45 ), numerous WBCs /predominance /predominance neutrophils neutrophils 200 > 20000/uL 200 > 20000/uL

Fungal meningitis:Fungal meningitis: Mild/not cloudy fluid, Mild/not cloudy fluid, little change in glucose + protein levels.. little change in glucose + protein levels..

100-1000 u100-1000 uL WBCs.. mostly Lymphocytes.L WBCs.. mostly Lymphocytes. Tuberculosis meningitis: Tuberculosis meningitis: Mild cloudy fluid, little change in Mild cloudy fluid, little change in

glucose + protein levels.. 100-1000 uL WBCs/ Lymphocytesglucose + protein levels.. 100-1000 uL WBCs/ Lymphocytes Late CNS Syphlis:Late CNS Syphlis: Clear fluid.. Normal Glucose.. slight Clear fluid.. Normal Glucose.. slight

elevation Protein.. Few WBCselevation Protein.. Few WBCs

Bacterial Antigen TestBacterial Antigen Test

Direct AntigenTestsDirect AntigenTests are available to detect bacterial are available to detect bacterial antigens in the CSF for diagnosis of antigens in the CSF for diagnosis of SS. pneumoniae, . pneumoniae,

N. meningitidis, H. influenzaeN. meningitidis, H. influenzae type b, group A, B type b, group A, B StreptococcusStreptococcus. .

These tests should be confirmed by These tests should be confirmed by positive Gram-positive Gram-stain or culturestain or culture

Therefore, negative results for a specific bacterial Therefore, negative results for a specific bacterial antigen do not rule out bacterial meningitis. antigen do not rule out bacterial meningitis.

Molecular methods (PCR)Molecular methods (PCR) that amplify bacterial DNA that amplify bacterial DNA in CSF may have improved sensitivity and specificity .. in CSF may have improved sensitivity and specificity .. used mostly in reference laboratories. used mostly in reference laboratories.

Bacterial neurotoxinsBacterial neurotoxins TetanusTetanus is an acute, sometimes fatal, disease of the is an acute, sometimes fatal, disease of the

central nervous system, caused by the toxin of central nervous system, caused by the toxin of Cl. Cl. tetanitetani, which usually enters the body through an , which usually enters the body through an wound. disseminated to wound. disseminated to blood, lymphaticsblood, lymphatics.. Toxins act .. Toxins act on CNS.. Interferes with release of neurotransmitters, on CNS.. Interferes with release of neurotransmitters, blocking inhibitor impulses.. causing difficult in blocking inhibitor impulses.. causing difficult in swallowing, muscle rigidity & spasms. Treatment.. swallowing, muscle rigidity & spasms. Treatment.. Specific antibodies. Specific antibodies.

BotulismBotulism ....Cl. botulinumCl. botulinum toxin.. Ingestion food, toxin toxin.. Ingestion food, toxin absorbed.. Spread to CNS.. absorbed.. Spread to CNS.. inhibits acetylcholine inhibits acetylcholine release on peripheral nervesrelease on peripheral nerves.. affects motor & .. affects motor & autonomic nervous system.. Rapid flaccid paralysis.. autonomic nervous system.. Rapid flaccid paralysis.. Cardiac & Respiratory failureCardiac & Respiratory failure.. .. Death..Death.. Specific Specific antitoxin treatment can be helpful if available. antitoxin treatment can be helpful if available.

Cl.tetani-Cl.botulinumCl.tetani-Cl.botulinum