Microbial Diseases of the Nervous SystemChapter 22

Objectives Learn how microorganism enter the nervous systemDescribe the causes of meningitis, tetanus, botulism, leprosy, poliomyelitis, rabies, Learn some fungal and protozoan diseases of the nervous systemWhat is mad cow disease?

The Nervous SystemBrain and spinal cord protected by three membranes (meninges)Dura mater, Arachnoid mater, & Pia materSubarachnoid space: Fluid filled space between arachnoid & Pia mater- cerebral spinal fluid (CSF)CSF- few macrophages, complement, or antibodies

Figure 22.1

How Microbes Enter the Nervous SystemVia skull or backbone fracturesDuring medical proceduresVia the peripheral nervesVia blood vessels or lymph vessels

Microbial Diseases of the Nervous SystemBacteria can grow in the cerebrospinal fluid in the subarachnoid space of the CNS.The blood-brain barrier (capillaries) prevents passage of some materials (such as antimicrobial drugs) into the CNS.Meningitis: Inflammation of meninges.Encephalitis: Inflammation of the brain. (includes meninges)

Bacterial MeningitisFever, headache, and stiff neckFollowed by nausea and vomitingMay progress to convulsions and comaDeath follows very quickly if untreatedDiagnosisDraw CSF by Spinal tap (lumbar or spinal puncture)Gram stain and/or Latex agglutination of CSFTreated with cephalosporinsTreatment often begins even before positive identification of microbes.

Bacterial MeningitisFigure 22.3Three major causesH. influenzae, S. pneumoniae N. meningitidisNote that All have capsulesBefore Hib vaccine 45% of meningitis in children,

Haemophilus influenzae MeningitisOrganism: H. influenzaeGram-negative aerobic bacteria, Normal throat microbiotaCapsule antigen type bOccurs mostly in children (6 mo to 4 yrs)Prevented by vaccinationVaccination of children highly recommendedWhat type of vaccine? ____________

Neisseria Meningitis (Meningococcal Meningitis)Organism: N. meningitisGram-negative aerobic diplococci, encapsulated10% of people are healthy carriers (nasopharyngeal)Often begins as throat infection or rashVaccine available (Same as last one) Vaccination recommended for college students

Streptococcus pneumoniae Meningitis, (Pneumococcal Meningitis)Organism: S. pneumoniaeGram-positive diplococci, encapsulated70% of people are healthy carriers (nasopharyngeal)Most common in children (1 month to 4 years)Mortality: 30% in children, 80% in elderlyPrevented by vaccination (What type?)Treatment for meningitis: Third-generation cephalosporin + vancomycinStart even before identification of organism

Listeriosis (Listeria monocytogenes)Figure 22.5Organism: L. monocytogenesGram-positive aerobic rodWidely distributed in soil and waterOf major concern in the food industryInfects monocytes (reproduce within)Has become the fourth most common cause of meningitisAlso cause encephalitisTransmitted to fetus in pregnant women.Still births and neurological damage

Tetanus (Clostridium tetani)Gram (+), endospore-forming, obligate anaerobeGrows in deep wounds.Tetanospasmin toxin released from dead cells blocks relaxation pathway in muscles.Muscle in mouth affected first- Lockjaw Toxoid vaccine available (DTP), booster (dT) every 10 yrs.Adults not adequately protected.Treatment with tetanus immunoglobulins.

Advanced cases: spasms of the back muscles cause the head and heels to bow backwards

Botulism (Clostridium botulinum)Gram (+), obligate anaerobe, endospore-forming, Botulinum toxin blocks release of neurotransmitter causing flaccid paralysis.PreventionProper canning (Toxin is heat labile)Nitrites preservatives prevent endospore germination in sausages.Treat with antitoxin (If given in good time)Infant botulism: (honey is the major source of endospores)C. botulinum growing in intestines.Wound botulism: Growth of C. botulinum in wounds.Botulinum toxin has medical and cosmetic uses (Botox)

Microbial Diseases of the Respiratory System Chapter 24

Respiratory TractMost common type of infectious diseases in humans Respiratory tract divided into:Upper Respiratory tract: Nose, pharynx (throat) & middle ear and auditory tubesLower respiratory tract: Larynx, trachea, bronchial tubes and lungs (alveoli)

Common Upper Respiratory DiseasesUpper respiratory tract infection (URTI), include the common cold, pharyngitis, laryngitis, tonsillitis, sinusitis, epiglottitisEtiologyVirusesCause ~ 40-70% of URTIs BacteriaCause ~15% of URTIsChildren ~5 sore throats every yearAdults ~2 sore throats every yearSymptoms of URTI include nasal congestion, cough, runny nose, sore throat, fever, and sneezing

Fig. 24.1

Pathogen Virulence Factor / DescriptionHost Defense / 1st, 2nd, 3rd / DescriptionTreatmentExotoxins, ability to anchor & multiply in mucosal & phagocytic cells;

Pharyngitis, laryngitis, tonsillitis, sinusitis, epiglottitis;Coarse hairs, ciliated mucous membrane,

Lymphoid tissue next to nose and throat, IgA; alveolar macrophages, Many are self-limiting- no treatment

Bacterial infections- antibiotic therapy ; Bacterial and viral-vaccines

Streptococcal Pharyngitis (Strep Throat)CauseStreptococcus pyogenes (GAS)Cellular Characteristics? b-hemolytic and cause many infectionsResistance to phagocytosisStreptokinases lyse clotsStreptolysins are cytotoxic (tissue cells, RBCs & leukocytes)DiagnosisThroat swab and culturing in the past Now used rapid tests i.e. latex indirect agglutination method or enzyme immunoassay (ELISA, based on double Abs sandwich immunoassay)TreatmentsSensitive to penicillin, although some resistance to erythromycin has appeared

Scarlet FeverCaused by: Streptococcus pyogenesErythrogenic (reddening) toxin produced by lysogenized S. pyogenes (by a bacteriophage)Strawberry tongue; red and enlarged as it loses its upper membranesandpaper & pinkish red skin rash; hypersensitivity reaction to the toxinFigure 24.4http://en.wikipedia.org/wiki/Image:Scarlet_fever_1.JPG

DiphtheriaCorynebacterium diphtheriae: Gram-positive, non-endospore-forming rodClub-shaped and stains unevenlyDiphtheria exotoxin (A-B toxin) produced by lysogenized C. diphtheriaeToxin interferes with protein synthesis; 0.01 mg of this exotoxin can be fatal (leading killer of children in the past)Diphtheria membrane Made of fibrin, dead tissue, and bacteriaCan block the air supply of small childrenCutaneous diphtheria: Infected skin; wound leads to slow healing ulcerPrevented by DTaP vaccine Vaccine: Diphtheria toxoid, Tetanus toxoid & acellular Pertusis toxoidTreatment: penicillin and erythromycin can control growth of bacteria but do not neutralize the diphtheria toxin (require conjunction with antitoxin)Figs. 24.4 & 24.5

Otitis Media (Earache)Infection of the middle earCauses:S. pneumoniae (~35%)H. influenzae (20-30%)Moraxella catarrhalis (10-15%)S. pyogenes (8-10%)S. aureus (1-2%)M/os cause the formation of pus and build up pressure against the eardrumAffects 85% of children < 3 yr oldTreated with broad-spectrum antibiotics, i.e. amoxicillinVaccinations can reduce incidence by H. influenza and S. pneumoniaeFigure 24.6

Common Colds>200 viruses cause the common cold Rhinoviruses (30-50%), Coronaviruses (10-15%)Use PCR for diagnostics & make culturing unnecessaryAccumulate immunities against cold viruses during our lifetime; older people get fewer coldsImmunity is based on conc. of IgAs and # of serotypesRhinoviruses thrive at slightly below body tempWhy common colds increase with colder weather in temperate zones?A single rhinovirus deposited on the nasal mucosa is sufficient to cause a coldAntibiotics are of no use in treatment; untreated cold will recovery in 1 week

Microbial Diseases of the Lower Respiratory SystemCaused by bacteria, viruses, or fungiBronchitisSymptoms: Runny nose, wheezing, difficulty breathing and coughing up extra mucus sometimes with bloodPneumoniaLung alveolar inflammation and abnormal alveolar filling with fluidTypical symptoms: include cough, chest pain, fever and difficulty in breathing

Pertussis (Whooping Cough)Bordetella pertussis:Gram-negative coccobacillusEncapsulated (virulent strains)Tracheal cytotoxin (associated with cell wall, damage ciliated cells)Pertussis toxin (associated with systemic symptoms) Symptoms: severe hacking cough followed by intake of breath that sounds like "whoopVaccine: whole-cell, heat killed vaccine was introduced in 1940s (DTP); recently, an acellular vaccine was introduced (Tdap) (safer, decreased dosage and more expensive?)Treatment: Erythromycin or other macrolides; PCR can also be used to test the presence of the pathogenFigure 24.8Cells of B. pertussis can be seen growing on the cilia; they will eventually cause the loss of the ciliated cells

Ciliary action is compromised; mucus accumulates; patients desperately attempt to cough up mucus; coughing may result in broken ribs in small children

TuberculosisMycobacterium tuberculosis: Acid-fast rod (unusual cell wall, mycolic acid, against environmental stresses such as drying, antimicrobials); form filaments or in clumps, moldlike (myco)Grow in macrophages (intracellular growth)Slow growing (> 20 h generation time) or in dormant, difficult to be killed by antibiotics Human to human transmissionM. bovis: Causes

A Third of the Earth's Population is Infected with TB 9 M develop active TB every year>2M deaths annuallyBCG: In 1990, 70% of the worlds children received it and was the mostly widely used vaccineTB is the leading direct cause of death in population affected by HIV

Diagnosis of TuberculosisTuberculin skin test screeningPositive reaction means current or previous infection (a delayed hypersensitivity reaction due to sensitized T cells)Followed by X-ray or CT exam, acid-fast staining of sputum, culturing of bacteria

Pneumococcal PneumoniaStreptococcus pneumoniae: Gram-positive; 2/3 of bacterial pneumonias Encapsulated diplococci (lancet shape)Resistant to phagocytosis, basis of >90 serotypesInfection involved both the bronchi and alveoliWhat other serious infections are caused by this organism?Otitis media, meningitis and sepsisDiagnosis is by culturing bacteria from the throat, sputum & other fluidsSymptoms: high fever, breathing difficulty & chest painTreatment:Penicillin is drug of choiceMacrolides & fluoroquinolones are now replacing itFigure 24.13

Haemophilus Influenzae PneumoniaGram-negative coccobacillusAlcoholism, poor nutrition, cancer, or diabetes are predisposing factorsTreatment by 2nd and 3rd generation cephalosporins

Viral PneumoniaViral pneumonia as a complication of influenza, measles, or chickenpoxViral etiology suspected if no other cause is determined

Influenza (Flu)Chills, fever, headache, and muscle aches (no intestinal symptoms)Recovery normally occurs in a few days and coldlike symptoms appear~30 to 50K Americans die annually1% mortality due to secondary bacterial infectionsTreatment: Tamiflu (inhibitor of neuraminidase, slow replication)Vaccine for high-risk individuals

Influenza (Flu)InfluenzavirusHemagglutinin (HA) spikes used for attachment to host cells (sialic acids); ~500 per virusNeuraminidase (NA) spikes used to release virus from infected cell after intracellular replication; ~100 per virusChanges in H and N spikes allow virus to avoid mucosal IgA antibodiesEight separate RNA segmentsReassortment or recombination in mixing vessels such as pigs can occur Humans, domestic chickens, swine are live in close proximity in AsiaAntigenic shifts: Viral strains are identified by variation in HA & NA; 16 subtypes of HA and 9 of NA; each number change represents a substantial alteration in the make up of spikes

Figure 24.16

Three Major Types of Human Influenza VirusesA types are responsible for the major pandemics; H3N2, H1N1, H2N2B types are responsible for more geographically limited and milder infectionsC types are rare; very mild diseases

Crossing the Species BarrierUN 13.3Pigs can be infected with several influenza A viruses. The viruses could re-assort and produce new viruses.A human virus infecting pigs will re-assort with viruses from birds and pigs (genes from the human virus and new properties from other viruses)New virus may be more virulent in human, spread more efficiently, and may not be recognized by the immune systems of the general public

*cerebrospinal fluid- rich in nutrients*Viruses and protozoans can also cause meningitis

*Note that bacteria such as S. pneumoniae also cause other diseases like pneumonia*What type of vaccine? Acellular type conjugated vaccine, connected to some protein

**Can grow well in refrigerator condition**Mostly aerobic organisms affecting**