MCB 2010 22,24 Diseases of Nervous, Resp System

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Nervous System Infections

Peripheral NS: botulism, tetanus, leprosy, polio, herpes simplex, varicella >>>> Central NS: meningitis, encephalitis, myelitis

C. botulinum

GPR, OA, endospores

C. botulinum toxin

AB exotoxin--neurotoxin. Blocks acetylcholine transmission in synapse

Botulism symptoms

FLACCID paralysis -- muscles do not contract, inhalation stops. Antitoxins from CDC bind the neurotoxin

C. tetani

GPR, OA, endospores, AB exotoxin neurotoxin tetanospasmin

Tetanus symptoms

SPASTIC paralysis, muscles contract and do not relax. Exhalation stops.

Opistho-tonos definition

extreme contraction

Tetanus vaccine contains

antibodies to bind toxin, stimulates formation of antibodies to neutralize any future toxin, booster every 10 yrs. 50% of population no antibodies

Mycobacterium leprae

GPR--acid fast. IDed in 1870

CNS portals of entry

Skull or vertebral fx: staph spp. >>> medical procedures: lumbar puncture, epideral >>> climbs along peripheral nerves: rabies, HSV >>> via cribriform foramina: amoebas >>> via sinuses >>> Hemato-logous spread [MOST COMMON] across blood-brain barrier

CNS infections testing

CT scan for abcesses, tumors, cysts >>> Lumbar puncture LP for cerebral spinal fluid tests

Cerebral Spinal Fluid CSF tests

gram, capsule and acid fast stains, low glucose [suggesting bacteria], neutrophils [suggesting bacteria], lymphocytes [suggesting virus, TB, cryptococcus or HIV]

CSF tests #2

Serology: for syphilis, HIV, Lyme >>> and cultures.

CSF test if immuno-compromised

test for atypical organisms

Bacterial meningitis symptoms

fever, headache, stiff neck [inflamed meninges causes pain so pt will not move neck], nausea >>> rapid progression to convulsions, coma

Acute Meningitis pathogens

Most common. [1] H. influenza [2] S. pnuemoniae [3] N. meningitidis >>> GNR, Listeria spp, and M. tuberculosis

H. influenza

GNR, capsule, aerobic: everyone has as normal nasopharyngeal flora, but if it crosses the blood-brain barrier ---> meningitis. Also otitis media, epiglottitis and pneumonia

HiB vaccine consists of

capsule antigen conjugated with a protein

"Meningococcal meningitis"

N. menigiditis: a GN cocci, aerobic, w/ a capsule. Very rapid endotoxin damage. college/military

S. pneumoniae

GP diplo-cocci capsule. 80% mortality elderly. Vaccination with capsule subunits from 7 strains

Cryptococcus neoformans

Meningitis mortality up to 30%. Systemic fungus with a thick capsule. IDed by CSF india ink stain. Pigeon droppings. Mild lung infection unless hematologous spread. Amphotericin B

Viral meningitis earmarks

Aseptic: meaning no growth in the usual cultures. CSF has elevated lymphocytes.

Non-polio enterovirus meningitis

mild, self-limited

Herpes simplex meningitis

Severe. Hematologous. Along cranial nerves. Treat with Ayclovir.

Arboviral encephaltis varieties

WEE, EEE, St. Louis, Calif., W Nile. All from mosquitos with bird-mammal reservoirs except Calif -- small mammal reservoir.

EEE mortality

> 30%

St. Louis E mortality

>20%

W Nile mortality rate

<20%

Polio is spread how?

fecal-oral route

What percentage of polio infections are enteric only?

99%. Only one percent gets to the CNS.

What route does it take to the CNS

Hemato-logous. Destroys the grey matter spinal cord motor horns.

What kind of paralysis?

FLACCID paralysis with limbs and respiratory muscles affected -- can't inhale.

Last known US wild case of polio?

1979.

Rabies types

"Furious" type: restless, excitable >>> "Paralytic" type: docile

Rabies virus vaccine is

killed virus or inactivated vaccine

How does rabies virus get to encephalitis

virus travels along PNS into the CNS at rate of approx. 1 cm./day. A month to a year until encephalitis. Immune systems are ineffective because the virus is not traveling via the blood or lymph system

Rabies symptoms

"Autonomic system instability" like fever, sweating, foaming. Delirium. Hydrophobia.

Post-exposure prophylaxis rabies

Rabies Immune Globulin RIG + a chick embryo vaccine called Human Diploid Cell Vaccine HDCV

Negri body

What you observe microscopically in brain of autopsied rabies victim

Serology?

Rabies antibodies are found in serum and CSF

Rabies Antigens?

testing by direct fluorescent antibody of cerebellum and brain stem

PCR

RNA in saliva and neck nape skin biopsy of nerve around hair root

Sleeping Sickness

African Trypanosoma Encephalitis

Types of Sleeping Sickness

T. brucei gambiense: milder then brain damage >>> T. brucei rhodesiense: lethal

Sleeping sickness reservoirs

cattle

Medication for Trypanosoma

none. Rapidly evolving protein coat.

Creutzfeldt-Jakob disease

prions. Infectious "pieces of protein"

Prion transmission

ingestion, transplant, inherited

Kuru

Pacific Islanders, eyeball ingestion

related to Italian family how

Familial Fatal Insomnia

Upper respiratory infections

symptoms all look the same whether bacteria or virus. Normal flora is potentially pathogenic. We are talking sinusitis, pharyngitis, tonsillitis, otitis media, epiglottitis

What pathogen causes epiglottitis?

Only one. H. influenzae. Nothing else.

the Common Cold is caused by:

50% Rhinoviruses, 15-20% Coronaviruses, and Mastadenoviruses. Altogether, there are over 200 causative viruses, and each one of those has multiple strains.

Otitis Media bacterial prevalence

S. pneumoniae [35%] >>> H. influenzae [20-30%] >>> M. catarrhalis [10-15%] >>> S. pyogenes [8-10%] >>> S. aureus [1-2%]

Otitis Media treatment

Broad-spectrum antiobiotics

Strep throat agent

Streptococcus pyogenes: GP cocci

GAS

Group A Streptococcus

GAS has extra goodies

Steptokinases: lyse clots to allow spread of infection >>>>> Streptolysins: cytoxins to kill tissue, RBCs and phagocytes

GAS lab tests

Indirect Agglutination tests take 10 minutes, and you need to culture the tissue to determine sensitivity

Untreated GAS

Can lead to rheumatic fever and heart valve destruction. Scarlet fever is another toxin -- an erythrogenic toxin -- that causes skin splotching.

Diphtherial upper respiratory infections

GP rod, non-endospore. Pharyngitis with gray membrane of fibrin, dead tissue and bacteria. Toxins: cardio and neuro

Diphtheria treatment

Antibiotics do not affect the toxin, only CDC approved administration of antitoxins

Cutaneous diptheria

slow healing ulcer

Lower Respiratory infections

Normally sterile environment, no potentially pathologic flora. Larynx, trachea, bronchus, bronchioles, alveoli. Pathogens are inhaled

Whooping cough

Bordetella pertussis: GN coccobacillus with a capsule. Tracheal cytotoxin damages ciliated cells -- Pertussis toxin enters the bloodstream and is assoc. w/ systemic symptoms.

Stages of pertussis

catarrhal stage: 1-2 weeks, like common cold ... violent coughing stage: 2-8 weeks ... convalescence: 1-2 weeks

Pertussis treatment

Erythro- or Azithro-mycin if given early can shorten the duration.

Pertussis vaccine

Acellular, cell fragments in TDP, adult booster with tetanus shot

Community Acquired Pneumonias

VEHICLES MF ... Varicella pneumonia virus, H. influenza GN coccobacillus, Chlamydiphila psittaci: GN intracellular, Legionella pneumophila GN, Strep pneumoniae, GP diplococci, Mycoplasma pneumo: GP pleo, Fungal pneumonias

Community Acquired Pneumonias Diagnosis model

Chest x-ray, culture, serology

"Pneumo-coccal pneumonia"

Streptococcus pneumoniae: otitis media and menigitis along with pneumonia. Bleeding into aveoli, rust-colored sputum, 20% mortality in elderly, vaccination w capsular antigens

S. pneumonia serotypes, how many?

90 capsule types

"Psittacosis pneumonia"

Chlamydophila psittaci: GN obligate intracellular. Bird droppings. Diagnosis via cell culture, Tx: Tetracycline

Fungal Pneumonias

BACH: Blastomyces dermatitidis -- Miss Valley, extensive tissue destruction ... Aspergillus fumigatus: compost ... Coccidio-oido-mycosis immitis: Valley Fever, spores SW dust storms ... Histoplasma capsulatum: bird, bat droppings Miss Valley

Fungal pneumonias treatment

Amphotericin B

TB

Myco-bacterium tuberculosis Acid-Fast Rod. Resistant to drying, sunlight and disinfectants

Incidence in FL

5 to 10/100k ... in 1948, it was 100/100k nationwide

Most ethnic US TB

Asians

TB skin test

PPD, or Purified Protein Derivative [coat of bacterium]. Definitive Diagnosis: chest x-ray and culture.

TB diagnosis

Positive x-ray with positive Acid Fast Bacterium sputum. X-ray looking for cavitating lesion called Ghon complex

TB process

Alveolar macrophages ingest bacilli, which are either destroyed or they start multiplying faster, immune response brings more macrophages. A tubercle with a cavity. Enlarges, invading bronchioles, capillaries

Systemic TB

Attacks bones that have lots of marrow causing Pott's Disease -- a disabling scoliosis. Attacks all the organs causing Miliary TB -- named for millet seed-sized tubercles. Attacks testes. Attacks meniges and causes brain abcesses

Flu

Orthomyxo-virus Influenza A ... spreads from respiratory system to a systemic disease ... 16 subtypes of Hemagglutinin spikes ... 9 subtypes of Neuraminidase spikes or 144 in toto.

H5N1

Asian flu --- not spread person to person

Seasonal flu comes from ...

SE Asia.

Current flu

H2N2, H3N2

Antigenic DRIFT

Influenza variation with gene changes to H or N surface proteins ... subtypes of strains in which virus avoids antibodies. "Expected Routine"

Antigenic SHIFT

Influenza variation with changes to H and N combinations. Not different subtypes of strains, but different strains altogether. "Big Deal"

Major flu strains

1918 H1N1 Spanish evolved in pigs and humans ... 1957 H2N2 Asian replaced H1N1 ... 1968 H3N2 Hong Kong flu replaces H2N2 ... 2009 H1N1 Swine replaces H3N2

Many flu strains infect

humans, birds, and pigs. An animal can be infected with several strains at once -- the viruses can re-assort and maybe produce an entirely new strain

Will a new animal strain infect a human?

Maybe

Will a human with a new strain infect another human?

Maybe

Reassortment can cause

pandemics

What is stomach flu?

No such thing. There are no intestinal symptoms with influenza.

Diagnosis of flu ...

from antibodies.

What percent die from secondary infections?

1%

Who is likely to die with seasonal flu?

ill and elderly

Who is likely to die with pandemic flu?

kids

Antivirals

Za-nami-vir ---> Relenza® inhalation ... Osel-tami-vir --->Tamiflu® for H1N1 not H3N2

"Pneumocystis pneumonia"

Fungus: Pneumocystis joroveci ... affects infants, immuno-suppressed, AIDs.

Treatment

Bactrim® [Trimethoprim-sulfamethoxazole TMP-SMZ] and pen-tam-idine ise-thio-nate

"Pneumoncystis pneumonia" diagnosis

characteristic chest x-ray: alveoli filled with froth

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