Bacterial Meningitis PDF
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Dr. Mohamed Sakr, MD
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This document provides information about bacterial meningitis. It covers topics such as causes, symptoms, and laboratory diagnosis of this condition. The document is useful for medical professionals.
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Bacterial Meningitis Dr. Mohamed Sakr, MD Medical Microbiology and Immunology Causes of bacterial meningitis Streptococcus pneumoniae Neisseria meningitidis (meningococcus) Haemophilus influenzae type b (Hib) was a common cause of meningitis in babies and young children Liste...
Bacterial Meningitis Dr. Mohamed Sakr, MD Medical Microbiology and Immunology Causes of bacterial meningitis Streptococcus pneumoniae Neisseria meningitidis (meningococcus) Haemophilus influenzae type b (Hib) was a common cause of meningitis in babies and young children Listeria monocytogenes (in older people, pregnant women, or those with immune system problems) Tuberculosis Other bacteria as Staph aureus, streptococci, pseudomonas Spirochetes Symptoms of meningitis Headache Fever Vomiting Neck stiffness (nuchal rigidity) and joint pains Drowsiness or confusion Photophobia Neisseria meningitides (Meningiococcus) Case Carrier Epidemic Cerebrospinal meningitis Neisseria meningitidis Morphology: Encapsulated small, gram-negative diplococci, typically arranged in pairs, with the adjacent sides flattened. Second most common cause (behind S. pneumoniae) of community- acquired meningitis in previously healthy adults. Neisseria meningitidis Virulence factors: Pili-mediated, receptor-specific colonization of nasopharynx Antiphagocytic polysaccharide capsule allows systemic spread in absence of specific immunity Lipooligosaccharide IgA proteases Neisseria meningitidis Classification: Meningococci are capsulated, unlike other Neisseria. Based on their capsular polysaccharide antigens, meningococci are classified into at least 13 serogroups, of which Groups A, B and C are most important. Group A is usually associated with epidemics. Serogroups: A, B, C, Y, W135 account for about 90% of all infections. Pathogenesis and clinical picture The nasopharynx is the primary site for Meningococci. Humans only natural hosts. Person-to-person transmission by aerosolization of respiratory tract secretions in crowded conditions. Following dissemination of virulent organisms from the nasopharynx: Meningitis, Septicemia (meningococcemia) with or without meningitis, Meningoencephalitis, Pneumonia, Arthritis and Urethritis may occur. Pathogenesis and clinical picture Onset of the meningitis is usually sudden, after an incubation period of two to three days, with severe headache, fever, neck stiffness, Skin rash and severe malaise. Severe hemorrhagic sepsis sometimes develops. Epidemic Cerebrospinal meningitis and meningococcal septicemia are the two main types of meningococcal disease. Cultural characteristics Meningococci do not grow on ordinary media. Growth occurs on media enriched with blood, serum or ascetic fluid. They are strict aerobes. The optimum temperature for growth is 35-36oC. no growth takes place below 30oC. Optimum pH is 7.4-7.6. Growth is facilitated by 5-10 % CO2. On solid media after incubation for 24 hrs, the colonies are small translucent, round, convex, bluish grey, with a smooth glistering surface and with entire edges. Blood agar, chocolate agar and are the media commonly used for culturing meningococci. Culture Chocolate Agar inside Candle Jar (5-10% CO2) Laboratory diagnosis In meningococcal meningitis, the cocci are present in large numbers in the spinal fluid and, in the early stage in the blood as well. Demonstration of meningococci in the nasopharynx helps in the detection of carriers (nasopharyngeal swab or west swab). (a) Examination of CSF (taken by lumbar puncture). The fluid will be under pressure and turbid, with a large number of pus cells. For bacteriological examination, the CSF is divided into : One portion is centrifuged and Gram- stained smears are prepared from the deposit, Meningococci will be seen mainly inside polymorphs. Direct detection of meningococcal antigens in CSF by latex agglutination testing. Laboratory diagnosis The second portion of the CSF is inoculated in blood agar or chocolate agar or modified Thayer-Martin medium plates and incubated at 35-36 °C under 5-10% CO2. Colonies appear after18-24 hrs which may be identified by morphological and biochemical reactions. Transparent, non-pigmented nonhemolytic colonies. They are catalase and oxidase positive. Acid production from glucose and maltose but not from other sugars. (b) Blood culture: Meningococcemia and in early cases of meningitis, blood culture is often positive. Cultures should be incubated for 4-7 days, with daily subcultures. Laboratory diagnosis (c) Nasopharyngeal swab (west swab): This is useful for the detection of carriers. (d) Petechial lesions: Meningococci may sometimes be demonstrated in petechial lesions by microscopy and culture. (e) Molecular diagnosis: Can be made by detection of meningococcal DNA sequence in CSF or blood by PCR amplifications. Treatment Intravenous penicillin G is the treatment of choice. or third- generation cephalosporins, e.g., cefotaxime or ceftriaxone. Chloramphenicol is also effective. Then shift according to antimicrobial sensitivity testing. Prevention: Chemoprophylaxis of close contacts with rifampin. Immunoprophylaxis: Polyvalent vaccine containing serogroups A, C, Y, and W135 is effective in people older than 2 years of age for immunoprophylaxis as an adjunct to chemoprophylaxis Infection control measures: use of masks for close contacts. Most infections are caused by Streptococcus pneumonia endogenous spread from the colonized nasopharynx or 5-75% of people are oropharynx to distal site (e.g., colonized. lungs, sinuses, ears, blood, meninges). Or Exogenous from patients or carriers by inhalation. Typically a secondary infection (after the flu,...) Young children and the elderly are at greatest risk for meningitis Virulence factors: 1. Polysaccharide Capsule: It is antiphagocytic. 2. Pneumolysin: It is a membrane damaging toxin has cytotoxic and complement activating properties. 3. IgA protease 4. Autolysin: Lysis of pneumococci due to breaking the crosslinking of peptidoglycan leading to massive inflammatory response CLINICAL DISEASES Lobar pneumonia Sinusitis and Otitis Media Meningitis: Due to local spread from mastoid as in case of otitis media or hematogenous spread from bacteremia LABORATORY DIAGNOSIS: Specimens: Sputum, CSF, Blood, Synovial fluid,... Methods of examination: 1. Direct microscopy: Gram stained smears reveals Gram positive lanceolate shaped diplococci with numerous pus cells. 2. Quellung ( capsular swelling ) reaction: On a slide the sputum is mixed with type specific antiserum against capsular antigen & a loopful of methylene blue solution. The capsule becomes swollen & refractile. 3. Antigen detection: Capsular polysaccharide antigen in blood, CSF & urine can detected by Passive latex agglutination or ELISA. LABORATORY DIAGNOSIS: LABORATORY DIAGNOSIS: 4. Culture: Media used: Blood agar 37ºC in 5% CO2. Gram’s smear: Smears are examined from the culture plate and reveals gram positive lanceolate shaped diplococci. Capsular swelling reaction: Positive. Solubility in bile: soluble Optochin sensitivity: Sensitive. Biochemical reactions: ferment Inulin 5. Animal inoculation (pathogenic): From specimens, isolation may be obtained by intraperitoneal inoculation in mice. 6. Serology: Antibodies can be demonstrated by agglutination & precipitation tests. Prophylaxis: Pneumococcal Conjugate Vaccine (PCV13 or Prevnar 13®) for All children in 4 doses (2,4,6,18 months) All adults 65 years or older A dose of PCV13 is also recommended for adults and children 6 years or older with certain medical conditions. Pneumococcal polysaccharide vaccine (PPSV23 or Pneumovax23®) : A polyvalent vaccine containing the capsular antigens of 23 most prevalent serotypes is being used. All adults 65 years or older routinely Adults 19 through 64 years old with certain medical conditions Adults 19 through 64 years old who smoke cigarettes Penicillin, a penicillin derivative, or a 3rd generation cephalosporin for susceptible strains Antibiotic resistance is increasingly common Penicillin-resistant strains are treated with vancomycin Treatment In cases of allergy to penicillin other drugs are used; Cephalosporins Erythromycin Haemophilus influenzae Haemophilus spp. are fastidious Gram-negative coccobacilli that colonize mucosal surfaces. H. influenzae and H. ducreyi are the main pathogenic species. Haemophilus influenzae expresses an antiphagocytic polysaccharide capsule of which there are six types (a–f). It also expresses a lipopolysaccharide (LPS) and an IgA1 protease. Septicemia, meningitis and osteomyelitis are usually associated with type b infection in individuals who have not been vaccinated. Haemophilus influenzae Clinical features Infection occurs in preschool children, causing pyogenic meningitis, acute epiglottitis, septicemia, facial cellulitis or osteomyelitis. Non-capsulate strains are usually commensal in the nasopharynx, but may cause adult otitis media, sinusitis, and chest infection in patients with obstructive airways disease. Haemophilus influenzae Laboratory diagnosis Gram Stain: Gram –ve , pleomorphic coccobacilli Biochemical Reactions: Oxidase + & Catalase + Growth Factor Requirements requires factors V (NAD+) and X (hematin) for growth. Most strains of Haemophilus spp does not grow on 5% Sheep Blood Agar, which contains hemin (factor X) but lacks NAD (factor V). Culture done on Chocolate agar which contain factor V & factor X at 37 C in presence of (5-10% CO2). Staphylococcus aureus produce NAD as a metabolic byproduct when grow in a culture media containing blood. Therefore, Haemophilus spp may grow on sheep blood agar very close to the colonies of Staphylococcus aureus (as it produces NAD-factor V); this phenomenon is known as satellitism. Haemophilus influenzae Laboratory diagnosis Antigen detection provides rapid diagnosis in meningitis. Direct and indirect Immunofluorescence Increasingly, H. influenzae is diagnosed as part of multiplex nucleic acid amplification tests (NAATs). Haemophilus influenzae Treatment and prevention Ampicillin - Chloramphenicol - 3rd generation Cephalosporin (Ceftriaxone or Cefotaxime ) Treatment course is usually 10 days. Many isolates of H. influenza can produce Beta-lactamase. If Beta lactamase positive, Ceftriaxone becomes the drug of choice. Hib conjugate vaccine is recommended for all children younger than 5 years of age. Vaccination can prevent H. influenzae type b (Hib), but not the other types ("strains"). Hib vaccine can prevent meningitis, epiglottitis, and other infections cause by Hib bacteria. Hib vaccine is usually given to infants 2,4,6 months & booster dose at 15-18 months. Chemoprophylaxis: Rifambin to prevent meningitis in close contact Tuberculous meningitis (TBM) TBM is the most common form of central nervous system tuberculosis (TB) and has very high morbidity and mortality. TBM is typically a subacute disease with symptoms that may persist for weeks before diagnosis. Characteristic cerebrospinal fluid (CSF) findings of TBM include predominant lymphocytes, elevated protein, and low glucose. CSF acid-fast smear and culture can aid in diagnosis.Nucleic acid amplification of the CSF by PCR is highly specific Tuberculous meningitis (TBM) Treatment for TBM should be initiated as soon as clinical suspicion is supported by initial CSF studies. Empiric treatment should include at least four first-line drugs, preferably isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol; the role of fluoroquinolones remains to be determined. Adjunctive treatment with corticosteroids has been shown to improve mortality with TBM. CSF in normal or meningitis