Lecture Review
Chapter 26 - Bacterial and Viral Infections of the Nervous System
1. [26-01] Bacterial meningitis – Compare pneumococcal, meningococcal and Hib meningitis by describing their etiological agents – Lecture 12, Slide 4 –
Pneumococcal meningitis is caused by Streptococcus pneumoniae that is Gram-positive, aerotolerant, salt-sensitive, catalase-negative diplococci growing in chains. It can produce the following virulence factors: immunogenic capsule, IgA protease, pneumolysin (cholesterol-depended cytolysin), beta-lactamase. It causes infections only if ciliary escalator non-functional.
Meningococcal meningitis is caused by Neisseria meningitidis that is fastidious Gram-negative, obligate aerobic, catalase-positive diplococci. It can produce the following virulence factors: capsule, antigenic variations, endotoxins.
Hib meningitis is caused by Haemophilus influenzae that is fastidious Gram-negative, facultative anaerobe, catalase-positive coccobacilli. It can produce the following virulence factors: capsule, beta-lactamase, endotoxins.
***All three bacteria can be carried asymptomatically in nasal cavities of healthy individuals.
2. [26-02] Bacterial meningitis – Compare pneumococcal, meningococcal and Hib meningitis by describing their pathogenesis – Lecture 12, Slide 5 –
All three pathogens enter the host’s bloodstream via mucous membrane by directed uptake mechanism, which delivers them to the meninges. The presence of microbes in meninges is resulting in inflammation reaction and meningitis leading to fluids accumulating in infected area and brain swelling. Haemophilus influenzae and Neisseria meningitidis are also producing endotoxins. The appearance of endotoxin in blood is resulting in wide-spread vasodilation of blood vessels, blood pressure drop & disseminated intravascular coagulation (blood clotting).
Clots formed in capillaries block local blood flow, leading to gangrene (tissue necrosis).
Proteases produced by Neisseria meningitidis further contribute to tissue damage. Early diagnostics is important as fatality risk rises to 15% within 12 hours of start of Neisseria meningitidis infection. For diagnostics purposes, lumber puncture is performed to collect cerebrospinal fluid that is tested by PCR, Gram stain, bacterial culture and immunological testing in latex agglutination test.
3. [26-03] Bacterial meningitis – Compare pneumococcal, meningococcal and Hib meningitis by describing their epidemiology – Lecture 12, Slide 6 –
All three bacterial meningitis: All bacteria (S. pneumoniae, N. meningitidis, H. influenzae) can be carried asymptomatically in nasal cavities of healthy individuals. All 3 meningitis are notifiable disease transmitted via respiratory route involving respiratory droplets.
Pneumococcal meningitis is communicable disease that makes up to 50% of bacterial meningitis cases reported in the US. Mortality rate is less than 10%.
Meningococcal meningitis is contagious disease that has high incidence in sub-Saharan Africa but very low one in the US. Mortality rate reaches 15% in the first 12 hours and can reach 80% if left untreated.
Hib meningitis is contagious disease that accounted for 45% of all meningitis cases before introduction of vaccine. Now it accounts for 5% of all meningitis cases. Mortality rate is about 6%, if disease treated, and up to 90%, if disease untreated. 30% of children will suffer from lasting neurological damage.
4. [26-04] Bacterial meningitis – Compare pneumococcal, meningococcal and Hib meningitis by describing their prevention and treatment – Lecture 12, Slide 8 Pneumococcal meningitis: It is prevented in children by conjugated vaccines PCV-7 and in adults by conjugated vaccine PCV-13 or by polysaccharide vaccine PPSV.
Disease is treated by penicillin, macrolides (Azithromycin, Clarithromycin), tetracycline or intravenous fluoroquinolones (Ciprofloxacin).
Meningococcal meningitis: It is prevented by conjugated MCV-4 and polysaccharide MPSV-4 vaccines. Exposed are prescribed antibiotics as prophylaxis. Disease is treated by Penicillin G, Cephalosporin. In severe cases, 3rd generation cephalosporins (Cefotaxime, Ceftriaxone) are used.
Hib meningitis: Vaccine is available only against H. influenzae serotype B (Hib vaccine) that is common in the US and Europe. It is on immunization schedule in the US. Disease is treated by antibiotics cocktail that includes ampicillin, cephalosporin, intravenous fluoroquinolones (Ciprofloxacin). In severe cases, 3rd generation cephalosporins (Cefotaxime, Ceftriaxone) are used.
5. [26-05] Botulism – Describe signs and symptoms. Describe etiological agent – Lecture 12, Slide 13 –
Signs & symptoms: Incubation 12-36 hrs after ingestion of toxin.
In Infants: poor feeding, weak cry, constipation → flaccid paralysis (ex: ptosis, expressionless face, and difficulty swallowing), mild lethargy, hypotonia, failure to thrive, respiratory insufficiency → death.
In adults: Dizziness, dry mouth, blurred vision → flaccid paralysis (impaired eye movement, ptosis, problems chewing + swallowing, difficulties talking, loss of facial expression) → muscle weakness of shoulders → muscle weakness of forearms → muscle weakness of feet → IF severe enough respiratory failure, coma, and death.
Etiological agent: Clostridium botulinum – Gram-positive bacteria, anaerobic, spore forming, bacillus of Firmicutes phylum (low GC content in DNA), produces botulinum toxin.
[26-06] Botulism – Describe pathogenesis. Describe epidemiology – Lecture 12, Slide 14 –
Pathogenesis: Toxin produced during germination of endospores of C. botulinum (produced in warm, protein rich anaerobic environment, toxin different serotypes depending on strain) → toxin blocks acetylcholine release within neuron synapses → disrupts signal transduction between neurons → flaccid paralysis
Epidemiology: Non-communicable, reportable disease.
Reservoir – Soil and dust
Transmission – 3 types of botulism:
Food botulism (toxin ingested by food)
Infant botulism (toxin produced in intestines during germination of ingested endospores)
Wound botulism (Botulinum toxin produced during germination of endospores in deep wound).
Number of cases reported – US 100 cases/yr, majority of cases in infants < 6 months.
Mortality rate – Case-fatality rate of hospitalized patients is less than 1%.
6. [26-07] Botulism – Describe prevention and treatment – Lecture 12, Slide 16 –
Prevention:
Infant botulism = NO raw honey for babies < 1yr; NO renovations until child is > 1 year old.
Wound botulism = Prompt wound clearing, seek immediate medical care for infected wound.
Foodborne botulism = High acidity, high sugar content, nitrites prevent bacterial growth in food. Commercially canned food undergo Botulinum cook @ 121ºC at 15psi for 3mins.
Botulinum toxin is heat-sensitive → can be destroyed by thorough cooking.
BUT Clostridium botulinum endospores are not killed in boiling water.
Treatment: 1) Antitoxin treatment – Botulism immune globin intravenous-human (BIG-IV) or BabyBIG given at first suspicion of botulism w/o delay.
2) Antimicrobial treatment – Antibiotics (tetracycline, erythromycin) kill bacteria, not endospores or toxins.
3) Severe cases – It may require putting patient on ventilator and provide intensive medical & nursing care.
7. [26-08] Rabies – Describe signs and symptoms – Lecture 12, Slides 22 –
Signs & Symptoms: Incubation 2-12 weeks after person bitten by infected animal (tingling/twitching felt at site of animal bite) → slight/partial paralysis of muscles of mouth and pharynx (inability to speak or swallow, saliva dripping, hydrophobia) → anxiety, insomnia, confusion, agitation, paranoia → hallucination that progress to delirium → death 2-10 days after symptoms appear.
Etiological agent: Rabies virus – RNA enveloped virus w/ characteristic bullet appearance, neurotrophic = infects nervous system and kills off neurons.
8. [26-09] Rabies – Describe pathogenesis – Lecture 12, Slides 23 –
Pathogenesis: Virus in saliva enters through animal bite and replicates in skeletal muscle in epidermal cells → enters and travels along peripheral nerves to CNS → enters spinal cord → reaches brain causing encephalitis (Once virus has entered neurons, NO longer accessible to immune system) → virus appears in salivary glands & other organs of victim.
9. [26-10] Rabies – Describe epidemiology – Lecture 12, Slide 23-24 –
Epidemiology: Highly Contagious, Notifiable zoonosis
Reservoir: Bats (carry virus asymptomatically), infected wild animals, infected dogs, cats.
Transmission – Bites of infected animal or exposure to saliva.
Number of cases reported – Over 4000 cases in animals/yr; only 1 to 3 cases in humans/yr
Mortality rate – Once symptoms show the patient is dead.
10. [26-11] Rabies – Describe prevention and treatment – Lecture 12, Slide 25 –
Prevention: Vaccine available, BUT only for individuals w/ high exposure risk. IF person bitten by animal → wound washed, animal tested for virus, if NO animal/(+)rabies = immediate post-exposure prophylaxis (vaccine + immune globulin)
Treatment: Once signs & symptoms set in → NO treatment.
Chapter 27.4-6 Bacterial STDs
11. [27-01] Sexually transmitted diseases: scope of the problem – Lecture 12, Slide 27 – The USA has the highest reported incidence of STD among developed countries. About 85% of students have had sexual intercourse. About third of them have had six or more sexual partners. About two third of sexually active students report that they or their partners rarely or never use condoms. Routes of transmission of STD: Sexual contact, Bodily fluid discharges, Fomites (some diseases), Childbirth, Breast feeding.
New cases reported in USA in 2014: Chlamydia – almost 1.5 million cases, Gonorrhea – over 350,000 cases, Primary and secondary syphilis – almost 20,000 cases. New cases reported in state of New York in 2014: Chlamydia – almost 100,000 cases, Gonorrhea – almost 21,000 cases, Primary and secondary syphilis – over 1,700 cases.
12. [27-02] Gonorrhea – Describe signs and symptoms, and etiological agents – Lecture 12, Slides 28 –
Signs & Symptoms: Incubation 2-5 days. Asymptomatic infection possible (60% women, 20% men). Symptomatic: pain on urination (dysuria), pus-containing discharge, ophthalmia neonatorum in newborn (may lead to blindness).
Etiological agent: Neisseria gonorrhoeae –Gram negative, facultative anaerobic, fastidious, diplococci of ß-proteobacteria.
Virulence factor: Type IV pili used for attachment, gliding along surface, DNA exchange. IgA protease. Lipooligosaccharides (LOS) = inhibit phagocytosis (prevents phagolysosome formation) and provides resistance to host antimicrobial peptides and compliment system.
Avoids opsonization – Inhibition of C3 convertase, antibodies avoided (binding host sialic acid, rapid change of surface antigens, prevention of helper T cell activation)
[27-03] Gonorrhea – Describe pathogenesis. Describe epidemiology – Lecture 12, Slides 29, 30 –
Pathogenesis: Bacteria enters host → attaches to non-ciliated mucosal cells (urethra, uterine cervix, mouth, pharynx, rectum, or conjunctiva) → some bacteria colonize surface, others direct host cells to engulf them → Intracellular bacteria grow inside epithelial cells/released on other side of mucosal barrier → continuous contact with bacteria causes inflammation in human tissues that may cause enough damage to result in infertility.
Epidemiology:
Reservoir: Humans only.
Transmission – Intimate sexual contact, 60% of women and 20% of men asymptomatic.
Number of cases reported – US ≤ 700,000 new infections/yr
Mortality rate – 1% for life threatening complications
13. [27-04] Gonorrhea – Describe prevention and treatment – Lecture 12, Slides 30 –
Prevention: Abstinence or monogamous relationship. Use of condoms reduces risk of STD (NOT 100% guarantee). Ophthalmia neonatorum in newborn is preventable by instilling neomycin solution in eyes 1-hour post delivery.
Treatment: Antibiotics (tetracycline or other antibacterials), problem of increasing resistance.
