Infections of the Central Nervous System PDF

🦠 Infections of the Central Nervous System Module Microbiology Date @October 10, 2024 Lecturer Dr Ryan Kean Week Week 3 Learning Outcomes...

🦠 Infections of the Central Nervous System Module Microbiology Date @October 10, 2024 Lecturer Dr Ryan Kean Week Week 3 Learning Outcomes Overview of the central nervous system Meningitis Clinical symptoms Transmission of infection Analysis of CSF Microbial agents causing meningitis Group B streptococci Neisseria meningitidis Haemophillus influenzae Streptococcus pneumoniae Infections of the Central Nervous System 1  Brain and the Meninges The brain and the spinal cord are contained within a membrane lining known as the meninges. The meninges forms a structural and functional barrier between the brain and the circulation. Blood-Brain Barrier Meningitis Inflammation of the meninges ↑ CSF protein levels ↑ Lymphocyte count Infections of the Central Nervous System 2  ↑ Antibodies levels ↑ Entry of water-soluble drugs ↑ Quantities of brain water ↑ Intracranial pressure Decreased cerebral perfusion from the blood and reduced cerebral blood flow due to the increase in pressure Severe inflammation increases the risk of CSF obstruction SYMPTOMS OF MENINGITIS Symptoms of meningitis vary greatly and do not appear in any specific order and include: Pale / blotchy skin, there is also a characteristic rash which may present in some cases which starts as small red pin prick sized shaped before quickly spreading and turning into purple blotches, the common test is that this rash does not fade if you press a clear glass firmly against the skin. Infections of the Central Nervous System 3  In babies, some symptoms can be related to refusing feeds and general irritation, as well as unresponsiveness and either a stiff or extremely floppy body. TRANSMISSION OF INFECTION Aerosol transmission Other sites of infection Sinuses Middle ear Pneumonia Infected shunts Nasal epithelium Contamination from lumbar puncture Trauma Nosocomial transmission: Infections of the Central Nervous System 4  ANALYSIS OF CSF Infections of the Central Nervous System 5  Lumbar puncture (spinal tap): obtain CSF, needle inserted between 2 lumbar bones. Can measure the opening pressure from the procedure (rate of production/drainage of the fluid. Elevated opening pressure can indicate infection. CSF appearance: Normally colourless, cloudy sign of infection. Xanthrochromia, which is a yellowish colour that can mean that there is presence of bilirubin which is a by product of red blood cell degradation, this can mean that there is bleeding or haemorrhage in the subarachnoid space. Cell count: Performed using a haemocytometer to quantify the number of white blood cells present in the sample. Healthy individual 1-5 x 106 /litre of sample. In bacterial meningitis, the WBC count would generally be greater than 1000 cells, where as a viral infection would be less than 200. Centrifugation, gram stain and culture: The sample is then centrifuged for between 10 and 15 minutes at 1000g to pellet the microbial contents of the sample. From here, a gram stain can be performed to distinguish between gram positive and gram negative. Also, the sample can then be suspended in diluent and plated out for culture on both CHOC and CBA for at least 24hours at 37 degrees. Normal, CO2 and anaerobic. ~ Biochemistry ~ Infections of the Central Nervous System 6  Biochemistry: Distinguish between bacterial/viral meningitis. Can be performed while awaiting organisms to grow. BM, protein levels are generally elevated well above the normal range in a healthy person, these can get to greater than 5g/litre. In viral meningitis, these levels can also be elevated but generally not as much. Finally, glucose levels of the CSF in bacterial meningitis are very low, this is thought to be because bacteria can consume glucose for their own metabolism. In viral meningitis, these levels of glucose would be similar to that of a healthy persons CSF. MICROBIAL ORIGINS OF MENINGITIS Multiple different microbial origins of meningitis Viral Enteroviruses such as Coxsackie or Echovirus Bacterial Can be caused by various genus of bacteria Fungal Cryptococcus neoformans Candida species Amoebic Naegleria fowleri Infections of the Central Nervous System 7  BACTERIAL MENINGITIS Most common bacterial causes Neisseria menigitidis Streptococcus pneumoniae Haemophillus influenza (capsule type B) Neonatal infections Escherichia coli and other coliforms Group B streptococci (Streptococcus agalactiae) Immunocompromised Listeria monocytogenes Mycobacterium tuberculosis Other causes Syphillus – Treponema pallidum Lyme Disease – Borrelia burgdorferi ~ Prognosis ~ Rapid antimicrobial therapy is essential Coma and death in 100% of untreated cases 10% mortality rate in treated cases Can have serious long term effects – sequelae. 1 in 5 survivors will have long term disabilities Loss of limb(s) Deafness Vision Loss Nervous system problems Brain damage Infections of the Central Nervous System 8  Transmission Outbreaks and high risk groups include those who are living in crowded populations in close quarters, these include and are not limited to, university halls of residence, army barracks and individuals which are partaking in religious pilgrimage. Rates of carriage are higher in adolescents and smokers Neisseria 10 species; 8 commensals, 2 pathogens N. meningitidis N. gonorrhoea Aerobic gram-negative diplococci Fastidious, 37°C, CO2 enriched atmosphere for 48h Cultured on blood and chocolate agar Classic culture medium Thayer Martin VCN Vancomycin Colistin Infections of the Central Nervous System 9  Nyastatin NIESSERIA MENINGITIDIS SEROGROUPS Serogroups Determined by the polysaccharide capsule 13 serotypes recognised worldwide Different based upon the capsule chemical composition Varies depending on geographical region Tested by slide agglutination using specific antibodies to meningococcal polysaccharides Target of meningococcal vaccines WORLDWIDE SEROGROUP DISTRIBUTION Invasive meningococcal disease is thought to cause over 1million infections every year, with reports of around 135k deaths. In countries where there are endemics, this places a massive burden and strain on the public health facilitates. Serogroup distribution varies depending on location, with serogroup A predominantly found in Asia and Africa and B,C,Y and W found within Europe. A - occurs in most countries and is associated with epidemics of meningitis. Most prevalent in sub-Saharan Africa, parts of Asia and the Middle East. Traditionally Infections of the Central Nervous System 10  serogroup A accounted for 90% of these infections resulting in large scale epidemics. There was a mass vaccination programme held in 22 of 26 countries, which is known as the African meningococcal belt. This stretches between Senegal to Ethipoa and is thought to have an estimated population of 300 million. Since then these epidemics have been eliminated but presence of other serotypes here are increasing. B - epidemics and outbreaks. Predominant in industrialised countries. C – similar is said for serogroup C, not as common with epidemics but more commonly associated with local outbreaks Y – very few cases W135 – isolated worldwide, but is associated with outbreaks following pilgrimage to Mecca (The Hajj) VACCINATION Two vaccines now routinely offered in Scotland MenB: Offered to babies alongside their other vaccinations (8, 16 and 52 weeks) MenACWY: Offered to teenagers in S3 of highschool (14 years old) MenACWY has replaced the MenC previously given at the same age MenACWY: two components mixed, MenA powder mixed with MenCWY solution Infections of the Central Nervous System 11  In Scotland, two vaccination programs are offered. This include the MenB vaccine which was introduced in about 2015 and is given to babies alongside their other vaccinations. Two courses of the vaccine are given at weeks 8 and 16, with a booster given after 1 year. This vaccine contains various surface proteins of the group B serotypes. In addition, the MenACWY is also given to teenagers in s3 of high school. This vaccine has replaced the previous vaccine which provided protection against serogroup C. This vaccine contains capsular polysaccharides of all 4 serotypes which are all conjugated to carrier proteins. This vaccine is given with two mixed components, a powder containing MenA and a solution with MenCWY. Meningococcal Complications Infections of the Central Nervous System 12  If meningococcal disease is left untreated, then there are a number of life threatening complications. These compilations can be rapid and happen in a number of hours. Purpuric/Petechial rash can appear which can indicate potential sepsis, this rash is due to the release of endotoxin (LPS) from bacteria which causes vascular necrosis , intravascular coagulation and haemorrhage. This is the rash which does not go away when a clear glass is placed on the skin. If sepsis does occur in the patient there is severe consequences with a mortality rate of up to 50%. Meningococcal Meningitis - Treatment Penicillin as soon as possible Third generation cephalosporin: cefotaxime or ceftriaxone Beta-lactam allergy – Chloramphenicol Adjunctive corticosteroids Prophylactic therapy for close contacts: Rifampicin (children); Ciprofloxacin (adults) Other treatments may be required: Breathing support; low blood pressure medicine; surgery Infections by Neisseria meningitides such as meningitis, are one of the few infections where penicillin is still the routinely recommended antimicrobial due to Infections of the Central Nervous System 13  low reports of resistance. Resistant strains have been reported and these would be treated with a third generation cephalosporin such as cefotaxime or ceftriaxone. If a patient is allergic to beta lactams, chloramphenicol may be administered. In addition, adjunctive the Corticosteroids may be given to help reduce inflammation. Prophalytic therapy should be given for close contacts and those living with close proximity and this would be Rifampicin (children); Ciprofloxacin (adults). Other treatments may be required such as breathing support, low blood pressure medicine and surgery. Group B streptococcal Meningitis Streptococcus agalactiae (GBS) is a leading cause of neonatal invasive disease (pneumonia, sepsis and meningitis) Opportunistic pathogenic which inhabits the genitourinary tract of 30% of women in developed countries Transmission between mother and neonates during/preceding birth Up to 50% 1% will develop serious disease No vaccine Currently under development (WHO, 2017) https://www.thelancet.com/journals/laninf/article/PIIS1473- 3099(20)30478-3/fulltext Infections of the Central Nervous System 14  Haemophillus Part of the HACEK group (previous lecture) Multiple pathogens within the genus H. influenzae and H. parainfluenzae most common Aerobic, gram-negative coccobacillus 37°C, CO2 enriched atmosphere Specific growth requirements Cannot grow on unsupplemented blood agar Requires factor X (haemin) Requires factor V (NAD) H. influenzae requires both factors Hib MENINGITIS Affects the very young, slower onset compared to meningococcal meningitis With appropriate antimicrobials – MR 4% High rate of sequelae (up to 50%) Infections of the Central Nervous System 15  Neurological defects Hearing loss Very rare in the UK due to the Hib vaccine Treatment Broad spectrum cephalosporin: ceftriaxone/cefotaxime Corticosteroids Haemophillus influenzae meningitis is predominantly associated with type b serotype based on its polysaccharide capsule. This predominantly affects the very young and it has a slower onset and progression of infection in comparison to meningococcal meningitis. With the adequate administration of antimicrobials such as a broad spectrum cephalosporin like cefataxime and adjunctive corticosteroids for the inflammation. Up to 50% of cases will develop existing side effects such as neurological defects and hearing loss. It is now very rare in the UK due to the HiB vaccine Streptococcus Pneumoniae Infections of the Central Nervous System 16  Gram-positive diplococcus, alpha-haemolysis on blood agar, polysaccharide capsule Does not have Lancefield antigens Carriage rate highest in first two years then declines Infections of the respiratory tract include otitis media, sinusitis, pneumonia Meningitis and bacteraemia Infections of the Central Nervous System 17  In addition to its high rates of causing CAP, SN can also cause other serious infections like meningitis. Meningitis caused by SN, occurs most commonly in the very young and very old. This is a gram positive cocci which appears in pairs. It is an alpha haemolytic strep (green zones surrounding colonies) and is capsulated unlike many other AHS. S. PNEUMONIAE CAPSULE Unencapsulated strains are usually avirulent Of the approx. 90 serotypes – 23 are associated with Pneumonia Prevents mechanical removal from phagocytes Masks PAMP to which complement proteins or antibodies bind Binds to factor H to degrade complement protein C3b Target of vaccines Pneumococcal Conjugate Vaccine: Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F More common in young children Does not provide protection against other serotypes Pneumococcal Polysaccharide Vaccine: All 23 serotypes People over 65 years old or long term medical conditions Not very effective in children younger than 2 Between 50-70% efficacy Infections of the Central Nervous System 18