Lecture 8: HIV Infection in the Immunocompromised Flashcards
HIV
transmission (4)
dx (3)
T: 1. blood contaminated needles
- unprotected sexual contact
- mother-fetus
- breast milk
dx: 1. ELISA type antibody screening- test for patient’s anti-HIV antibodies
2. Western blot-test for viral proteins in blood
3. RT-PCR to detect virus RNA in blood
PCR vs. RT-PCR
PCR detecs pathogen’s DNA
RT-PCR can detect pathogen RNA by adding a step to convert the RNA to DNA and then doing PCR
**PCR amplifies DNA nor RNA
HIV epidemic
ardor in the late 19th-early 20th century
- social changes and urbanization
- disruption in tribal values that favored cause; sexual practices with multiple partners - vaccination practices assoc. with colonialism
- increased bushmeat hunting
- forced labor (extreme stress depresses immune system)
HIV structure (5)
- family
- virulence
- structure
- member retroviridae
- lipid-enveloped with viral gp120/gp41 envelope glycoprotein with cylindrical psuedoicosahedral capsid
- gp120-attachment to host cell
- gp41-promotes fusion of viral envelope with host plasma membrane - 2 copies single-stranded RNA
- genome packed with several enzymes
- reverse transcriptase copies single-stranded RNS into double stranded DNA
Reverse transcriptase
enzyme capable of making a DNA copy with RNA template
Replication HIV (4)
- attachment and entry
- gp20, gp41 fusion protein
- *typically infected helper T cells - Reverse transcription and integration
- forms provirus which can remain latent - Biosynthesis
- active provirus transcribed into multiple copies now viral RNA - Assembly and release
- new capsid forms around each viral RNA genome and fever transcriptase
- new nucleocapsids bud off plasma membrane taking up viral envelope spikes as each virion is released from the cell
Stage I: Primary HIV infection` (4)
- may be asymptomatic
- can have flu-like illness
- occurs within 1-2 months exposure
- seroconversion occurs
Stage II: Asymptomatic stage HIV (4)
- viral load rises
- as CD4T cells decline
- skin rashes, night sweats
- Diarrhea, fever, weight loss
Stage III: HIV infection/AIDS (4)
- steep rise in viral load
- CD4 count < 200 cells/mm sqared
- opportunistic infection
- death from opportunistic infection
Opportunistic Infections
- As immune system deteriorates due to HIV, opportunistic infections develop
- CD4T cells count falls bellow 200 cells/mm squared
Viral opportunistic diseases in HIV pts. (5)
- HIV encephalopathy
- progressive multifocal leukoencephalopathy
- shingles
- cytomegalovirus
- recurrent HSV
Bacterial opportunistic disease in HIV pts. (4)
- persisten pneumonia
- tuberculosis
- mycobacterium avian complex
- salmonella septicemia
Fungal opportunistic diseases in HIV pt. (5)
- cryptococcus
- candidiasis
- histoplasmosis
- coccidioidmycosis
- pneumocystis pneumonia
Protozoal Opportunistic Diseases HIV pts. (2)
- toxoplasmosis
2. chronic cryptosporidium diarrhea
Cancers in HIV Pts. (2)
- lymphomas of brain, lympatic tissue
2. Kaposi sarcoma
Misc. conditions affected HIV pts. (5)
- persistent dairrhea
- persistent generalized lymphadenopathy
- wasting syndrome
- night sweats
- persistent fever
HIV tx
- antivirals: Azodiothymidine
- interferes with reverse transcriptase
- chain terminator-inhibiting DNA synthesis
HIV resistance
- many variants become resistant to antivirals
- monotherapy= resistant viruses selected
- resistant variant becomes dominant-dishes progression
HAART
Highly Active Antiretroviral Therapy
HAART tx (4)
- fusion inhibitors
- intefere with virus binding CD4 - reverse transcriptase
- inhibits viral RNA conversion to DNA - DNA Polymerase
- inhibits production of a DNA copy of a virus - Integrase
- inhibits integration of viral DNA into host genome
*can keep disease from progressing indefinitely
Long-term Non-Progressives Def.
- indv. infected with HIV many years, w/o therapy maintain CD4 count > 500, and low viral loads
- eventually can get AIDS if they remain untreated
Elite Controllers
HIV infected individuals with even lower viral loads and LTNP pts.
- HLA allele allows CD8 T cells to efficiently recognize HIV infected cells
- immume response to gag unusually strong
Stem cell transplant
transplant using CCR5 homozygous mutant has achieved “cure” of HIV in 2 patients
CCR5
co-receptor for HIV and crucial for infection in some strains
most common causes fungal lung infections (4)
- Histoplasma capsulatum
- Cryptococcus neoformans
- blastomyces dermatitidis
- coccidioides immitis
2 most important rx factors assoc. w acquiring fungal infection in lung
- immunosuppression
* particularly susceptible to poor outcomes from fungal infection - environmental exposure
Endemic Mycoses Causative agents (3)
- Coccidioides Immitis
- coccidioidomycosis - Histoplasma Capsulatum
- histoplasmosis - Blastomyces dermatitidus
- blastomycosis pulmonary (cough, fever, chest pain, SOB)- skin, bone, CNS involvement
Where are fungi found?
air, soil, droppings of birds and bats
Dimorphic Fungi
grow as hype in soil and yeast in vivo
Coccidioidomycosis- fungal lung infection
pathogen (2) found where? transmission sx (3) tx
- coccidioides immitis and c. posadasii
- valley fever: southwest US (az and ca), mexico, central/south america
- typically found in soil growing as hyphae
- spores released when soil turned up
- develop into spherules in diaphragm
- no human-human transmission
- sx: cough, chest pain, fever
- most recover in a few weeks
- if immuncompromised, can become disseminated beyond lungs - tx: amphotericin B for 6 months
Histoplasmosis - fungal lung infection
pathogen
sx
dx
tx
- histoplasmosis capsulate
- found in bat guano, often asymptomatic
- some develop severe pulmonary and/or systemic infections
- sx: flu-like sx, HA, cough, chest pain, shortness breath
- Macrophage can ingest but cannot kill-disseminate to other organs
- dx: culture, antigen detection (EIA), serology
- tx: amphotericin B (severe) or itraconozole
* Ohio river valley/mississippi valley
Aspergillus- fungal lung infection
pathogens
disease
dx
- causes opportunistic mycoses
- Aspergillus fumigateurs, aspergillus niger, others
- common both indoors and outdoors, most people breath in fungal spores everyday
- disease= aspergillosis
- sx: cough, brown mucous, fever, flu-like sx, wheezing, coughing up blood, weight loss, fatigue, disseminated forms to skin, brain, eyes, liver, kidneys-poor prognosis
Cyptococcus Neoformans
found where?
causes what disease?
sx
- opportunistic mycosis
- found in soil, decaying wood, tree hallows, or bird droppings
- causes cryptococcosis
- affects lungs or CNS - sx: shortness of breath, rales, cough, HA, nausea, nuchal rigidity, photophobia
Cyrptococcus Neoformans lifecycle (5)
- spores
- inhalation in lungs
- lodging in alveoli
- dissemination to CNS
- positiv Culture
Pneumocystis Jirovecii
*fungus
- life threatening infection of immunocompromised
- also immunosuppressive medications of conditions (TNS inhibitors, cancers) - acuis= person to person, from people with normal immune systems via aerosols
- sx: HIV= severe respiratory failure, fever, dry cough
non-HIV= mild to moderate pneumonia - dx: id organism in sample, detect DNA via PCR
- beta-D-glucan in serum (presumptive) - tx: TMP-SMX orally or IV for 21 days
Sterilization
destruction ALL living microbes, spore, and viruses
-sterilized objects become contaminated when exposed to air and surroundings
Sanitization
reduced the numbers of pathogens or discourages their growth
Control
limiting exposure to agents
- microorganisms are part of our environment
- microbes can be controlled by either eliminating them or reducing their numbers
-static
remains in place, reduce microbial numbers or inhibit their growth
-bacteriastatic
-cide
kill
-bacteriacidal
Heat
physical control method
- fast, reliable, inexpensive
- temperative about growth range: proteins and nucleic acids are destroyed/denatured
- water is removed
Autoclave Sterilization
- Pressurized stream
- most dependable method sterilization
- blankets, bedding, utensils, instruments, IV solutions, etc
Limitation of autoclave (3)
- plastic ware can melt
- metal ware can become dull in heat
- chemical breakdown can occur in the process
Prevaccum autoclave
- draws air out of sterilizing chamber at the beginning of cycle
- decreases cycle time
- decreases exposure of sensitive materials to steam
Pasteruization
- uses moist heat to reduce bacterial populations in liquid
- destroys mycobacterium tuberculosis
- bacterial spores not affected*
holding/batch method
heats at 63 degrees C for 30 minutes in pasteurization
flash pasteurization
heating at 71.6 degrees celsius for 15sec
-regular milk, only pathogens killed
Ultra high temp method
heating at 140 celsius for 3sec, pastuerization
-only method capable of sterilization liquid if it is performed under aseptic conditions
-organic milk, completely sterile
filtration
- mechanic method used to remove microorganisms suspended in liquids or gases
- as fluid passes through filter, size threshold draped in pores
HEPA
High-Efficiency Particulate Air filter
UV light to control microbial growth
- exposure to UV light causes thymine molecules to link together-disrupts DNA replication
- errors in protein synthesis and impairment of chromosome replication occur
Ionizing radiation to control Microbial growth
x-rays and gamma rays (ionizing radiations) force electrons out of microbial molecules
- ions combine with cellular water and form free radicals, which damage proteins and DNA in cells
- affects cell metabolism and physiology
- often used for preserving food
Radiation to control microbes in food
radiation can control microbes in food, hopeful step for CDC in eradicating foodborne ilness
General principles of chemical control (4)
- medicine chemicals came into widespread use in 1800s
- chemical agents rarely achieve sterilization
- but they do disinfect/destroy pathogens
- disinfection-process of eliminating or reducing pathogens
Antiseptics
used to destroy pathogens on living tissue
-sepsis refers to contamination by microorganisms
disinfectants
for non living surfaces
sanitizing
reducing microbial population to a safe level
Degermins
removing organisms from an object’s surface
Antiseptics/disinfectsns properties (6)
- able to kill or slow growth of microbes
- nontoxic to humans and animals
- soluble in water
- storable
- effective quickly and at low concentration
- important in choosing agent
- pH
- temp
- conctentration of agent
- time-duration disinfection
Soaps
- surface-active agents
2. remove mircobes my emulsifying and solubilizing particle on skin
Detergents
surface-active agents
- can kill some microbes
- cause cytoplasm leakage from microbial membranes
- Quaternary ammonium compounds react with cell membranes and destroy some bacteria and viruses
alcohol based hand sanitizer
- use when soap and water unavailable
2. at least 60% alcohol (ethyl)
H2O2
- damages microbial components
- come microbes have catalase to protect them
- catalyst is in wounded tissue and transforms h202 to oxygen and water
- the oxygen is effective against anaerobic bacteris
- not receomned as antiseptic for open wounds
Alehydes
cause cross-linking that inactivates proteins and nucleic acids
-ex0 hcutaraldehyde-sterilize medical and dental equipment, toxic and strong irritant
ethylene oxide gas
effective microbicidal and sporicidal, but is carcinogenic and explosive
chlorine dioxide gas
non-toxic non-carcinogenic agent
-used to decontaminate anthrax-exposed mail in 2001
gp120
virulence factor HIV
allows attachment to host cell
Gp41
virulence factor HIV
promotes fusion of viral envelope with host plasma membrane
Stages HIV infection (3)
- Primary
- Asymptomatic
- AIDS
