Microbial Diseases of the Nervous System, PDF

WHAT TO KNOW: What is the CNS? Components, central vs. peripheral, function, etc. What is the blood-brain barrier? What is its purpose? Are there cons to such tight regulation of entry into the CNS? What is bacterial meningitis? Classic signs, bacterial components that lead to symp...

WHAT TO KNOW: What is the CNS? Components, central vs. peripheral, function, etc. What is the blood-brain barrier? What is its purpose? Are there cons to such tight regulation of entry into the CNS? What is bacterial meningitis? Classic signs, bacterial components that lead to symptoms, diagnosis, treatment, etc. Things to know about bacteria discussed: part of normal microbiota? method of transmission? population affected? prevalence/mortality? pathogenicity? is there are vaccine? Bacteria to know: H. influenzae, N. meningitidis, S. pneumoniae, L. monocytogenes What's the difference between botulism and tetanus? Which organisms cause these syndromes? What are some distinctive characteristics of M. leprae infections that allow it to cause the symptoms associated with this infection? Why is the treatment course so long? Things to know about viruses discussed: method of transmission? population affected? prevalence/mortality? pathogenicity? is there are vaccine? Viruses to know: poliovirus, rabies virus, Zika virus LECTURE: CH. 22 Microbial Diseases of the Nervous System Structure and Function of the Nervous System Central nervous system (CNS): brain and spinal cord ○ Brain: controls how we think, learn, move, feel ○ Spinal cord: carries messages from brain to peripheral nerves Peripheral nervous system (PNS): nerves that branch from the CNS Meninges protective membrane that covers the brain and spinal cord ○ Provides tight anchoring of the CNS to surrounding bone; prevents side to side movement and stability ○ Subarachnoid space of the meninges contains cerebrospinal fluid (CSF) Surrounds and protects the brain, provides nutrition, waste removal, temperature regulation The blood-brain barrier The CNS is highly guarded ○ Skull protects the brain; vertebrae protect the spinal cord ○ Blood-brain barrier: semi-permeable membrane that protects the brain from harmful substances; allows nutrients and essential molecules to pass through ○ Crucial immunological feature of the human central nervous system  ○ Structural and functional roadblock to microorganisms that may be circulating in the bloodstream ○ Limits diffusion of certain drugs into CNS tissue → difficult to treat brain infections ○ Limits migration of immune cells into the brain (“immune privilege”) Diseases of the CNS As selective as the blood-brain barrier is, some parasites, bacteria and viruses have developed CNS invasion strategies ○ Remember: immune cells are limited in quantity in a healthy brain Inflammation in the CNS (often due to infection) is categorized based on the tissues involved: ○ Meningitis: inflammation of the meninges ○ Encephalitis: inflammation of the brain ○ Meningoencephalitis: inflammation of both Bacterial Nervous System Diseases Bacterial Meningitis Initial symptoms of fever, headache, and a stiff neck (hallmark but not always present), nausea and vomiting Can progress to convulsions, coma and death VERY QUICKLY! ○ Endotoxin released from cell walls of Gram- bacteria can lead to shock and inflammation Treatment: heavy administration of IV antibiotics Meningitis due to viral infection is much more common and mild ○ Limited treatment options - more so supportive care (reduction of pain, fever, etc.) Bacterial Meningitis Haemophilus influenzae (type B), aka HiB Gram-negative, aerobic, coccobacilli Normal throat microbiota, but can enter the bloodstream and lead to deadly brain infections ○ Accounts for 45% of bacterial meningitis cases ○ 6% mortality Pathogenicity due to capsule antigen type b Transmitted via respiratory droplets, person-person contact Occurs mostly in children (6 months to 4 years) Prevented by the Hib vaccines Bacterial Meningitis Neisseria meningitidis, aka Meningococcal Meningitis Aerobic, gram-negative diplococcus with a capsule 40% of people are healthy nasopharyngeal (nose and throat) carriers Begins as a throat infection, rash, and bacteremia 80% mortality if left untreated Outbreaks common in dorms and military barracks Vaccination protects against serogroups A, C, Y, W and B, but not X Bacterial Meningitis Streptococcus pneumoniae, aka Pneumococcal Meningitis Gram-positive, diplococcus with a capsule 70% of people are healthy nasopharyngeal carriers Common in children and elderly Mortality: 8% in children, 22% in the elderly Preventable via vaccination Bacterial Meningitis Listeria monocytogenes, aka Listeriosis Gram-positive rod Foodborne transmission ○ Commonly associated with deli meats and unpasteurized milk products, soft-serve ice cream ○ This bacteria can survive refrigeration! Usually asymptomatic in healthy individuals ○ More common in people with weakened immune systems and the elderly Very serious infection in pregnant women - crosses the placenta and can lead to stillbirth  Preferentially invades phagocytes, where it replicates and spreads Diagnosis and Treatment of the Most Common Types of Bacterial Meningitis Spinal tap aka lumbar puncture ○ Hollow needle is inserted into the subarachnoid space in the lower back to extract some cerebral spinal fluid (CSF) ○ CSF sample allows for detection of pathogens, bleeding, cancers ○ Presence of high number of immune cells indicates a CNS infection Antibiotic therapy is initiated before confirmed diagnosis ○ Vancomycin + broad-spectrum third-generation cephalosporin, Penicillin G ○ Duration of treatment varies depending on bacteria Tetanus (aka Lock Jaw) Caused by Clostridium tetani bacteria ○ Gram-positive, endospore-forming, obligate anaerobe Grows in deep wounds where conditions are likely anaerobic Tetanus is not from a rusty nail itself! Neurotoxin is released from dead bacteria (perhaps on a rusty nail) ○ Enters CNS ○ Blocks the relaxation pathway in muscles, causing uncontrolled muscle spasms Death occurs from spasms of respiratory muscles, starvation/dehydration Prevented by vaccination with a tetanus toxoid vaccine (multiple forms exist) ○ Stimulates antibodies that neutralize the toxin ○ Booster required every 10 years Epidemiology: fewer than 10 cases per year (due to high vaccination rates) ○ Mortality of 25-50% Treatment with tetanus immune globulin (antibodies against tetanus (natural passive immunity)) Infected tissue removed via debridement Botulism Caused by Clostridium botulinum bacteria ○ Gram-positive, endospore-forming, obligate anaerobe Intoxication comes from ingesting the botulinum exotoxin ○ Toxin is specific for the synaptic end of nerves ○ Blocks release of the neurotransmitter acetylcholine, causing flaccid paralysis (distinct floppiness) Death usually results from respiratory or cardiac failure Infant botulism: C. botulinum grows in the intestines of infants due to a lack of intestinal microbiota ○ Associated with honey ○ Infants