1/22/2024 Review PDF

1/22/2024 Review By Your Lovely Team TA From First Aid 3 MONTHS) NEONATAL MENINGITIS AND ADULT MENINGITIS Strep pneumoniae Neisseria meningitidis Strep agalactiae BOTULISM E. coli Haemophilus...

1/22/2024 Review By Your Lovely Team TA From First Aid 3 MONTHS) NEONATAL MENINGITIS AND ADULT MENINGITIS Strep pneumoniae Neisseria meningitidis Strep agalactiae BOTULISM E. coli Haemophilus Listeria influenzae Type B monocytogenes Listeria monocytogenes (immunocompromised) Clostridium botulinum Bacterial Meningitis Overview Newborns / Children Symptoms Adult Symptoms Constant crying Classic triad: sudden fever, severe headache, stiff Poor feeding neck Sleeping constantly Sensitivity to light Irritability Confusion Classic signs not present because they cannot Nausea communicate Vomiting Flu-like symptoms developing 1-2 days Petechial rashes (for meningococcal meningitis exclusively) Diagnosis Physical exam findings: Kernig’s sign, Brudzinski’s sign Treatment CSF: ↑ polymorphonuclear neutrophils (PMNs), ↑ Empirical treatment: IV Vancomycin + Ceftriaxone protein, ↓ glucose or Cefotaxime  ADULT MENINGITIS Strep pneumoniae Leading cause of CNS meningitis “Pneumococcal meningitis” = caused by Strep pneumo Prevention Distinguishing feature ○ PPV23 vaccine (adults), polysaccharide ○ Prolonged fever before onset of vaccine classic triad (apparent focal infection) ○ PCV13/15 vaccine (children), conjugate vaccine Virulence factors ○ Polysaccharide capsule ○ Autolysin, pneumolysin ○ IgA protease  ADULT MENINGITIS Neisseria meningitidis “Meningococcal meningitis” = caused by Neisseria meningitidis Bacteremia can cause septicemia FOCAL INFECTION IS INAPPARENT Distinguishing feature ○ Petechial rashes Virulence factors ○ Polysaccharide capsule ○ Pili (for adherence in nasopharynx) ○ Lipooligosaccharide ○ IgA protease ○ OpA, OpC (for attachment) Prevention ○ MCV4 (ACWY Vaccine), part of childhood vaccinations ○ Serogroup B Vaccine (“Bexsero”, “Trumenba”)  ADULT MENINGITIS Haemophilus influenzae - type b “Typeable” = has a capsule Prevention Apparent focal infection ○ Hib polyribose phosphate vaccine conjugate Primarily in non-immunized children (1 month to 3 years)  NEONATAL MENINGITIS Strep agalactiae Usually transmitted during birth Prevention ○ Both baby and mother can get meningitis ○ Screening at 35-37 weeks of gestation Virulence factors ○ Intrapartum antimicrobial prophylaxis (such ○ Polysaccharide capsule rich in sialic acid as penicillin) ○ Hemolysin ○ C5a peptidase  NEONATAL MENINGITIS E. coli Ferments lactose on MacConkey agar Virulent factors ○ K antigen (main virulence factor for development of neonatal meningitis) ○ O antigen, H antigen Meningitis caused by E. coli is transmitted at birth with no apparent disease preceding it Treatment ○ Cephalosporins No screening options available  NEONATAL MENINGITIS Listeria monocytogenes A foodborne infection since it can grow at 4°C Transmission is via ingestion or at birth Can present with gastroenteritis Can transfer from cell-to-cell without even Pregnant women get infection in utero having to be extracellular and can then pass bacteria onto fetus Virulence factors Immunity that develops is cell-mediated ○ Internalin (for internalization) immunity ○ Listeriolysin O (lyses host endosomes) ○ ActA (for assembly of actin tail) Tetanus Overview Symptoms Treatment (prompt and 3-fold) RIGID paralysis Supportive: ventilation, muscle relaxants Lockjaw (trismus) Human tetanus immune globulin (HTIG, Back spasm blocks tetanospasmin) Potential respiratory failure due to Antibiotics (such as metronidazole) paralysis of chest muscles Clostridium tetani Virulence factors ○ Tetanospasmin (tetanus toxin that blocks release of inhibitory NTs, Prevention increasing firing rate of motor neurons ○ Tetanus vaccine (immunization with to cause rigid paralysis) tetanus toxoid) Transmission ○ C. tetani spores (such as from a rusty nail) inoculated into puncture wounds Botulism Overview Symptoms Treatment FLACCID paralysis (“Floppy Baby Syndrome”) GI symptoms since it is a foodborne intoxication Supportive: ventilation Symptom onset quicker than Tetanus since Antitoxin (equine trivalent, but carries risk patients directly ingest botulinum toxin (not of serum sickness) waiting for spore germination) Antimicrobials only if wound infection is Due to less acidic GI, infants can have C. involved botulinum spore germination in their stomach Clostridium botulinum Virulence factors ○ Botulinum toxin blocks release of ACh at neuromuscular junctions by binding to SNARE proteins, causing no muscle contraction resulting in flaccid No current vaccine paralysis No natural immunity to botulism CDC class A bioterrorism agent Spores found in soil, surfaces of fruits and vegetables, home canning (such as honey), and other anaerobic environments Leprosy - Mycobacterium Leprae Obligate Aerobe Non-motile, non-spore forming Acid Fast Bacilli (Ziehl-Neelsen stain) Lipid Cell Wall (Mycolic Acid) Transmission via prolonged contact Human reservoir Virulence Factors: ○ PGL-1 - enables invasion into Schwann cells (PNS) ○ Laminin Binding Protein - enables binding to basal lamina of peripheral nerves Leprosy - Lepromatous and Tuberculoid Transmitted via nasal secretions Tuberculoid: Enters via skin lesion or nasal mucosa ○ Cell Mediated Response - Th1 and CD8+ Long Incubation T cells ○ Granuloma formation - little bacilli Affects Peripheral Nervous System ○ Lepromin skin test positive ○ “Glove and Stocking” distribution ○ Large, asymmetric, pale, hairless, flattened macules on face, trunks, limbs Can progress to Lepromatous form ○ Poor Cell Mediated response - many bacilli ○ Multiple symmetric nodules and plaques - diffuse spread Can cause bone resorption and folding of skin ○ Negative Lepromin skin test ○ Dx: Acid Fast Stain of skin  Viral CNS Infections Important Definitions Direct contact – urine feces, blood, saliva ○ includes petting, touching, bites and scratches Indirect contact – where animals live or roam ○ Aquarium tanks, chicken coops, plants, soil Vector-borne – an insect that preys on animals and may also prey on humans ○ Ticks, mosquitoes, fleas Food-borne – ingesting contaminated animal products (meat, milk, eggs) or plants that have been fertilized with contaminated feces Sylvatic – between wild animals, involving some insect intermediates Urban – when infection moves from sylvatic cycle to humans, either through insect intermediates, direct contact or domestic animals How does a virus cross the BBB to infect the CNS? Multiplying in muscles before moving to CNS take advantage of glial cells such as astrocytes and axon transport proteins to bypass BBB and enter CNS Rabies - uses neuronal architecture to enter neurons in spinal cord and brain, enters at terminal bouton and attach to motor proteins that move retrograde towards neuron cell body, where it completes viral replication cycle. neuronal architecture and axonal trafficking (most take advantage of this system) ○ neurotropic viruses – are attracted to nerves ○ start in periphery ○ neuromuscular junctions ○ transsynaptic Immune cells ○ hide leukocytes that cross BBB during immune response ○ can also induce inflammation that increases permeability so it can cross by itself Rabies Negative single-stranded RNA virus ○ Enveloped ○ Glycoprotein surface spikes Attachment and penetration; antigenic Phosphoprotein spikes may interfere with IFN signaling pathways to inhibit immune response Zoonotic with sylvatic and urban cycle - no insect mediator ○ Primary method of contraction in US is wild animal bite All strains are fatal Replication ○ Replicates at a slow rate to avoid apoptosis Rabies (Cont.) Pathogenesis ○ Variable incubation period Anywhere from weeks to years Replicates in skeletal tissue → cross neuromuscular junction → travel up axon to neuron cell body to DRG in CNS ○ Once in brain, replicates but doesn’t kill host cells, only damages axons and dendrites ○ Then travels anterograde out of CNS to organs and tissues (cornea of eye and salivary glands, sensory nerves in skin), hypersalivation allows easy spread ○ Clinical illness encephalitic (furious) rabies (~80%) site feels abnormal at first, general flu like symptoms quickly progresses to: ○ hydrophobia (pharyngeal spasms difficult to swallow liquids), excitability, hypersalivation, aerophobia (hypersensitivity travelling down sensory neurons) , seizures, coma, death (7 days within onset of symptoms cardiorespiratory death) Paralytic rabies (~20%) less common severe muscle weakness, flaccid paralysis, coma, death Both result in death in 99.9% of cases Rabies … again Diagnosis History of exposure, signs and symptoms May not be in blood samples - goes straight to CNS Viral antigens from biopsies from skin on back of neck Post-mortem exam of brain tissues → Negri bodies (where virus is being produced), usually in hippocampus Treatment and Prevention No effective treatment once symptoms appear ○ Milwaukee Protocol Multidrug cocktail - Ribavirin, amantadine, ketamine Partial recovery (2007 follow up) Prophylaxis ○ Pre-exposure - active vaccine ○ Post-exposure - passive (slow progression of virus) and active vaccine (kill virus that is present) Animal vaccination and control → prevention Poliovirus Kind of enterovirus Positive single stranded (non-segmented) RNA virus ○ Non-enveloped Transmitted via fecal oral route Pathogenesis ○ Most people who have polio develop no symptoms at all, few will get poliomyelitis and 1% get major illness Diagnosis ○ Immunization history ○ Lymphocytes in CSF ○ Cultures from CSF, throat and stool Treatment and Prevention ○ No treatment once infected Prevention by oral vaccine → live, attenuated (high effectivity, some reversion) Killed vaccine is used for those who are immunocompromised Arboviruses Fluctuate seasonally → mosquitoes, ticks are most active in summer/spring Enveloped positive sense single stranded RNA virus ○ Glycoprotein that contains hemagglutinin Eastern and Western Equine Encephalitis ○ Transmitted to humans by a “bridge” vector ○ Replication occurs in cytoplasm of cells → lytic, destruction of cells and spread virus ○ Secondary viremia can spread to CNS Inflammation allows for permeability in brain so virus can get to CNS, infiltrating neutrophils cause damage ○ Symptoms Initial symptoms (non-neuronal): abrupt onset of fever, chills, weakness, headache and myalgia Diffuse CNS involvement: fever, headache, irritability, nausea, convulsions,coma and death EEV is more severe than WEEV Flaviviruses Positive enveloped single stranded RNA virus Incubation period for most is ~1 week Spread via “bridge” vector Shares common surface antigen with EEEV, makes it difficult to differentiate these two Flaviviruses in US ○ St. Louis encephalitis ○ West Nile ○ Zika Virus St. Louis Encephalitis West Nile Viral saturation of reticuloendothelial Transmitted by mosquito bites, system → invasion of CNS migrates to lymph nodes → blood Sudden onset of symptoms: fever, stream → organs ○ May progress to spinal cord malaise, headache, dizziness, nausea Usually self-limited with mild Symptoms may intensify: symptoms: fever, malaise, nausea, disorientation, confusion, irritability, anorexia, myalgia, headache, eye pain tremors and convulsions More severe symptoms when invades Palliative care only CNS (~1% of cases) Mortality: 5-30% ○ Severe muscle weakness, flaccid paralysis, stupor, seizures, coma Zika Virus Usually mild, self-limiting flu-like disease spread by mosquito bite Concerning in pregnant women ○ Vertical transmission from mother ○ Causes microcephaly Neuroinvasive forms - Guillain Barre and microcephaly Transmission: ○ Initially a sporadic zoonotic infection, with increasing amounts of urban/suburban transmission ○ Vertical transmission also across placenta ○ Sexual transmission Diagnosis and Treatment ○ Diagnosis with RT-PCR or IgM antibody ○ No vaccine or treatment Palliative care Mosquito control Restrict travel in pregnant women Bunyaviruses Single negative stranded RNA virus LaCrosse virus ○ Causes “California encephalitis” ○ Symptoms and Diagnosis: Secondary viremia in CNS Symptoms more likely in those disseminated CNS disease and cutaneous manifestation Virulence: ○ Polysaccharide capsule (Latex agglutination test +) -> antiphagocytic ○ Phenoloxidase (increased melanin + prevents binding of phagosome to lysosome) Characteristics: ○ India Ink - Halo stain ○ Brain abscesses Treatment: Amphotericin + Flucytosine then treat with fluconazole (and prophylactic dissemination to lungs, skin, bones, CNS Transmission: Southwestern USA, inhalation of spores Characteristics: ○ Spherules of endospores Treatment: ○ Usually self-limited, fluconazole for mild disease, amphotericin B for disseminated Histoplasma capsulatum and Blastomyces dermatitidis other fungal infections ○ Similar primarily pulmonary manifestation which can have widespread dissemination Protozoal Meningitis African Trypanosomiasis: Sleeping sickness T. brucei gambiense (Western Africa) - human reservoir: Chronic (1 yr to death) T. brucei rhodesiense (Eastern Africa) - wild animals: Acute (3-6 weeks) Transmission: Tsetse fly 3 Stages: ○ Chancre ○ Trypomastigotes in blood: recurrent malaise, lymphadenopathy w/ IgM production Varying antigens (surface glycoprotein) ○ Meningitis - headaches, behavior change American Trypanosomiasis: Chagas disease Trypanosoma cruzi: Southern US and Argentina Transmission: contact with reduviid (Kissing) bug feces ○ Bug bites skin, defecates, gets into skin-> illness Virulence: ○ Penetrin - invasion of cells ○ Pore-forming protein ○ Multiply intracellularly and rupture cell Presentation: ○ Acute: Chagoma (inflammation at site), romaña’s sign (inflammation around the eye), heart, brain, liver, spleen inflammation ○ Chronic: Cardiomyopathy/arrhythmia, giant esophagus, toxic megacolon Diagnosis: Motile trypanosomes in bodily fluid Treatment: Nifurtimox, benznidazole Naegleria Fowleri Amoeba free-living in lakes, swimming pools, tap water of Southeastern US Transmission: Penetration of olfactory neuroepithelium (through nose) Presentation: ○ Primary amebic meningoencephalitis - severe headache, vomiting, seizure, coma ○ Death within 10 days Diagnosis: Trophozoites in CSF Acanthamoeba Primarily immunocompromised Transmission: Brackish and saltwater, acquired by swimming or inhalation Spread: blood-> CNS + lungs and sinuses + skin Presentation: ○ Subacute or chronic: headache, altered mental status, skin lesions, corneal ulcerations Diagnosis: Trophozoites in CSF/brain biopsy/skin scraping, monocytes in CSF Treatment: Self-limiting