Immunopathology IV: HIV Flashcards
1
Q
HIV infection causes sickness and death largely by
A
damaging the immune system, leading to opportunistic infections and unusual tumors/ odd cel proliferations
2
Q
the fully manifest dz of HIV
A
aquired immunodeficiency syndrome
aids
3
Q
List of dz.’s that define AIDS
A
cryptospridiosis/isosporidiosis pneumocystosis toxoplasmosis candidiasis (esophagus, trachea, lung( cryptococcosis (CNS) coccidioidomycosis (disseminated) histplasmosis (disseminated) mycobacteria (MAC or TB) Nocardiosis Salmonellosis (disseminated) CMV herpes simplex/ herpes zoster progressive multifocal leukencephalopaty Kaposi's sarcoma primary lymphoma of the brain invasive cancer of the uterine cervix
4
Q
Pnemocystis jirovecii
A
is an atypical fungus that will not grow in the lab and is probably a commensal in humans
it grows in the alveoli (PCP, an established acronym now stands for pneumoCystis Pneumonia) and produces the lung infection that led, in combination with Kaposie’s in MSMs to the first identification of AIDS as a new disease
5
Q
PCP pcoduces
A
consolidation of the lung. The alveoli fill with micro-organisms with a limited or absent inflammatory response.
6
Q
Pneumocystis morphology
A
Silver stain: they look like crushed ping pong balls
7
Q
pneumocystis pneumonia morpology
A
the pink frothy looking material in the alveolar spaces contains the pale staining microorganisms
there may be a fair inflammatory response in the interstitial or none at all.
a high resolution CT scan show ground glass opacities, because the alveoli are either packed or empty
8
Q
The PCP fungi anchor to
A
type I pneumocytes. Thus, very little material is coughed up in PCP - the cough is non productive.
9
Q
Pneumocystis has always been most strongly linked to the kind of immune defect seen in
A
AIDS - low CD4 counts. It may affect its immunosupressed from other causes, especially hematologic malignancies
PCP historically seen when CD4 counts dropped below 200
10
Q
pneumocystis as a pathogen was first describes as the cause of
A
a plasma cell rich interstitial pneumonia in malnourished infants in the years after WWI
apart from the abundant plasma cells in the interstitial, the pathology was the same as pcp seen in aids today, with the foamy, organism rich exudate within the alveolar spaces
11
Q
making the diagnosis of PCP can be tough
A
1-beta-d-glucan is produced by pneumocystis and blood levels above 80pg/mL favor PCP
you may need to induce sputum to send to the lab to search for the organisms. Lavage fluid, endotrachial aspirate or lung biopsy are more likely to show as posititve
12
Q
mycobacterial infections include both
A
the familiar TB bug and the atypical mycobacterium (avium, intracellular, etc)
13
Q
many people have been exposed and have confined M tuberculosis with ian
A
Ghon focus of complex.
The caseous necrosis, granuoma formation with giant cells and acid fast bacilli are familiar to you from general pathology
14
Q
The appearance of advanced TB in the lungs (more severe at the apices with cavities) is similar in HIV
A
positive and negative patients.
macrophages can form granulomas even with few CD4’s
15
Q
Miliary TB results form
A
invasion of the blood stream. The name comes from a resemblance to millet seed.
16
Q
Overview of immunopathogenesis of TB
A
perforin and granulysin from the CD8 T cells kill bacteria and ones own cells
17
Q
When you suspect TB (history , physical, imaging) in an HIV positive pt, the lab can help you
A
look for acid fast microbes in sputum
culture the microbe from sputum/ bronchoscopy specimens/ pleural biopsies (2-8 weeks to grow)
see/cultrue the microbe on lymph nod aspirates
search for TB using nucleic acid assays
determine susceptibility to anti TB medicines
18
Q
Mycobacterium avium complex (MAC; includes the species mycobacterium avium and mycobacterium intracellular) is probably the most treacherous of the
A
aids oppotunists
19
Q
MAC microbe can produce
A
a trivial infection in helthy pts and diarrhea in pts who have advancing HIV (GI involvement)
20
Q
MAC - when cd4 counts drop below around 50, patients are at risk for
A
sudden development of a systemic illness with fever, sweats, weight loss, and perhaps lung (pneumonia) GI (diarrhea, malabsorption) and/or marrow problems
The microbe grows from the blood, but it takes 1-2 weeks. If MAC isn’t diagnosed and treated it is rapidly fatal. SOme treatment protocols give prophylaxis for its at risk
21
Q
Mycobacterium avium organisms (like real TB and other non TB mycobacteria) occasionally produce infection of
A
the cervical lymph nodes in health people, especially children
(you may have heard this cervical lymphadenitis called scrofula, superstition had tit that it could be cured by the touch of a king)
curiously this has reappeared in the HAART era, during immune recontitituion MAC can preset as single-site lymphadenitis
22
Q
Cytomegalovirus (herpes 5) is a common virus that infects
A
a majority of humankind. it is generally acquired early in life through kissing (saliva) or less often by blood transfusion
most often transmission produces no symptoms, but in teens and adults, it may produce fever, lymphadenopaty, and/or sore throat, and a blood picture with atypical lymphocytes
23
Q
The diagnosis of acute CMV infection is made clinically by
A
a rise in complement fixing antibodies (4-fold titer over 2-4 weeks) or finding IgM 30% or more of IgG
like the more common and more familiar Epstein Barr infectious mononucleosis, CMV travels by kissing
24
Q
If mom has her first CMV infection while pregnant , it can do
A
major harm to the child, even if she has normal immunity. Hearing loss or extensive brain damage are common.
CMV is one of the dread neonate infections
25
CMV produces enormous cells because
the emerging viruses destroy the cytoskeleton
26
CMV, like all herpes viruses, remains
latent following initial infection.
as immunity disappears in advancing HIV infection or from one other cause, CMV is prone to reactivate
27
When the AIDS epidemic struck, we were already familiar with CMV as an
opportunistic infection in immunosupressed transplant recipients
28
CMV cells are easy to spot by
their huge size, and big, single intranuclear inclusion
29
CMV pneumonia in advanced HIV infection could be
fatal
30
CMV retinitis
was a common, dread illness in full blow aids
| histopathology shows hemorrhage, necrosis, and big CMV cells
31
Glanciclovir implant
used in the eye to control CMV chorioretinitis in the era before effective antiretroviral therapy
32
CMV in the colon was a common problem in
classic AIDS
33
CMV encephalitis is less common than toxoplasmosis as a cause of
focal brain lesions, and less common than eye, GI tract or liver involvement, but devistating
34
Making the diagnosis of CMV
most often it presents as chorioretinitis or colitis. Usually the pt has a CD4 count below 50
in serious CMV p65 (lower matrix protein) antigenemia will usually be detectably by the lab, and PCR may help show the virus to be present
CMV can be grown on fibroblast cultures, or a shell via culture
ask your lab about testing using PCR for resistance genes against the common antivirals. This still takes about a week
35
more extensive oral candidiasis is more worrisome. Before effective treatment, oral candidiasis tended to paper when
the CD4 count dropped below 500 or so
36
______ defines AIDS
candida
37
esophageal candidiasis was well known as a sign that
HIV infection was progressing to the late stage (AIDS)
usually the CD4 count will be below100
38
Candida looks like
balloon animals
39
______ help fight candida, and it is seldom the ______ infection in aids
neutrophils
| fatal
40
Toxoplasmosis is infection with the protozoan ______, which completes its life cycle in_____
toxoplasma gondii
| cats
41
If you avoid eating undercooked meant and change the cat litter box dilly, you are u
unlikely to contract toxoplasmosis.
| only about 10% of folks in th eUS have antibodies
42
Primary infection of toxoplasmosis is usually
asymptomatic or may mimic infectious mononucleosis,
43
if toxoplasmosis mimics mononucleosis, the diagnosis will not be made unless
the physician finds anti-toxoplasmosis IgM without IgG in the serum or the tacyzoites are found on fine nee dal aspiration of the enlarged lymph nodes
44
Toxoplasmosis remains
latent in the body after infection, and HIV patients who have antibodies as well as CD4 counts below 100 are prone to develop opportunistic toxoplasmosis
45
most common and most feared of toxoplasmosis
are areas of necrosis in the brain. These are often multiple and appear as ring-enhanging lesions, often in the basal ganglia.
brain biopsy may be required, unless the presentation is classic
46
Toxoplasmosis involving the retina.
this can happen to healthy people for unknown reasons, but is fairly common in AIDS
more white fluff, less hemorrhage than CMV retinitis, you'll get a consult
47
Cryptococcus
a single narrow based bud, and a capsule
48
cryptococcosis is a deep fungal infection caused by
cryptococcus fungus (usually C. neoformans) found in the environment. A link to pigeons remain anecdotal
49
cyrptococcal meningoencephalitis may occur in
anyone
some people with apparent normal immunity get this infection and mount a fair immune response. In the immunocompromised, there is little or no inflammatory response, and headache, mental changes, and perhaps CN problems (from the increased ICP - the fungus makes CSF gooey and hard to reabsorb)
50
pulmonary cryptococcosis occurs only when
immunity is very poor. The yeasts fill the alveoli with little or no inflammation
51
If cyrptococcosis is suspect, perform
neuroimaging first, and if no other cause of symptoms is found and lumbar puncture is safe, send CSF for culture, antigen assay, and india in prep (you will miss the organisms on frame stain)
52
what defines infection of cryptococcus
growth of cryptococcus on culture
they usually grow by 3 days, at the max, 7. Blood culture may also be positive, but its lower yield.
around 75% of patients will have a positive India ink preparation on the CSF, and the antigen assays are very sensitive and specific (there may be cross-reaction with other deep fungi)
53
Worldwide, there are around ______ cases of cryptococccal meningoencephalitis
a million yearly with around 600,000 deaths. Most are in aids patients
54
cryptococcus in the lung
yeasts with big invisible capsules, and single, narrow based buds
capsular goo separates the yeasts (aids its can drown in the organisms)
55
Progressive multifocal leukoencephalopathy
| CD4 count usually below
200
| JC papovavirus damages the brain
56
PML's anatomic pathology in Aids is similar to
other immune compromised conditions, with loss of myelin in patches of grey and white matter, and the glial changes you learned in Neuro
PML was the major cause of seizures/ status epileptics in AIDS
57
Cryptosporidiosis is infection by ____ or _____ , 3-4 m protozoan that life in _____
C. hominis or C. parvum
| live in the brush border of the small intestine
58
The life cycle of cryptosporidiosis is
complex and completed in a single host. C hominis is generally passed human to human, C parvum infections often follow contact with farm animals, especially cattle
59
Cryptosproidiosis organisms fill the
brush border of the gut. This accounts for much of the diarrhea in developing AIDS
60
How cryptosporidiosis causes illness
remains unknown
probably its mostly due to damage to the microvilli of the brush border
There're no know cytokine activity, little or no inflammation, and no cell necrosis. The microbes may make their way into the bile ducts, but never go systemic
61
Healthy folks with crypto may h ave
diarrhea for up to two weeks, usually without blood or white cells in the stool
62
outbreaks of crypto are generally
water-borne, including swimming pools and ponds, and are more common where there's poor sanitation, and during the rainy season in the tropics.
63
among the immunocompromised, especially those with ______ and _________, cryptosporidium becomes a
HIV and depletion of CD4+ cells,
crhonic illness, and was the cause of the diarrhea that made life miserable for its with AIDS related complex during the years before the life threatening infections began.
64
in advanced HIV immunodeficiency, crypto is blamed for
cholangitis and pancreatitis, by invading the ducts
65
In the lab you can test for cryptosporidium
easisest is examining the stool - cryptosporidia are acid fast and can be seen easily on microcopy
immunoflourescence is more sensitive and specific. You can see the internal structure of the cysts
biopsy may reveal the microbes, or it may miss them because infection can be patch. There are ELISA and PCR tests as well
66
IN HIV patients, crypto can be managed uzing
antiprotozoal drugs, but reconstitution of the immune system using antiretroviral drugs is usually required to eradicate the microbe
67
________ and some of cryptosproridium's other relative can also produce the same anatomic and clinical lesion
isosopora
68
______ is also fairly common in advanced HIV infection, and like cryptosproidiosis is an aids defining illness
salmonella
69
Histoplasma capsulatum, the cause of )______ is a _______ fungus - a mold in the soil, a yeast at 37 degrees.
histplasmosis
| a thermally dimorphic fungus
70
When a healthy person meet the istoplasmosis fungus (by _______), usually the infection is ________
by inhaling the microconidia spores from the environment, they ar plentiful especially in bird and bat droppings, starkly roosts are famous
usually the infection is asymptomatic or subclinical
71
HIstoplasmosis yeasts mulitiply in the
lungs, and probably some travel in the bloodstream. Before they can do any real damage, they are surrounded and either killed or walled off by macrophages
72
HIV patients who have immigrated from other counties and then developed histoplasmosisi usually have the
genetic strains from their former countries, showing that the yeasts live within the body, walled off, probably for a lifetime
73
LIke other fungal diseases ,histoplasmosis is
not contagious. It's estimated that only about 1 in 2000 who meet histoplasmosis in the wild will get seriously sick, but the rid is greater if ter's a big dose (camping in starling territory, cavers getting into bat guano)
74
The severe acute dz with histoplasmosis
may be pneumonia, or a systemic infection with lung involvement (maybe) enlarged liver/spleen (usually) and/or bone marrow replacement (likely)
75
IN KC autopsies, its very common to find a _______ from the person's long ago meeting with _____
Ghon focus or complex
hist.
there's no telling histoplasmosis from TB on 'gross'
76
In a histoplasmosis pneumonia and disseminated histoplasmosis, the infiltrate is composed almost entirely of
macrophages, laden with the yeast forms
if the immune response is good, granulomas form by the influence of g-interferon. This is probably why anti interferon medications such as the anti TNF agents increase the risk from histoplasmosis
77
Chronic pulmonary histoplasmosis closely resembles
TB, with the same caseous necrosis and cavity formation
Sputum culture is likely to be positive,though it takes weeks to grow
78
HIstoplasmosis in bone marrow and in liver. look for
two micron yeasts
79
Unusual presentations of histoplasmosis, in immunocompromised individuals or sometimes health folks include
fibrosing mediastinitis and eyeball invasion (both as bad as they sound)
80
in people with ________, especially where old histoplasmosis is common, _____________ always needs to be a consideration. Two micron yeasts.
advanced HIV
| recurrence of histoplasmosis
81
If you suspect seriou histoplasmosis, your lab can help
draw blood and sputum for culture. yield is low
get tissue for culture and microscopy if you can . usu the pathologist can find the microbes
send blood and urine for antigen assays (galactomannan) these are very sensitive nowadays though thers's cross reactivity with other sep fungi
draw titer for complement fixing antibody. a titer over 1:32 or rising titer suggests active dz. again, cross reactivity with other fungi may be a problem
we can't recommend skin testing, up to 90% in many areas
82
Coccidioides immitis is a fungus that grows in the
US southwest and usually causes a mild lung infection when first encountered. . either or both forms may be seen in tissue during infections (coccidioidomycosis)
83
forms of coccidioides
a sphere flu of yeasts, or hyphae with barrel-shaped spores
84
healthy ppl differ in their ability to handle coccidioides fungi. Rarely a severe
pnemonia and/or skin involvement develops in people who seem immunocompetent
85
Coccidioides can produce a _____ in aids pts
deadly pneumonia or disseminated infection in AIDS patients.
in areas where coccidioides is endemic, HIV positive ppl with low CD4 counts may be given prophylaxis
86
Aspergillosis can produce
the familiar fungus balls, invasive pulmonary dz, or disseminated dz. It's infamous for following pneumocystis pneumonia, which damages the lungs and may requires teroid treatment, making the lungs vulnerable.
87
aspergillus is famillar. mophology
septa, 45 degree branching, fruiting bodies
88
spirochetosis of the colon - another cause of
diarrhea. The cell will be made on biopsy, and the right antibiotics clear it easily
89
spirochetosis iof the colon is easier to see on
silver stain
90
Herpes simplex II in aids. _____ confirms the dx
Tzanch touch prep
91
_____ was another famiiarsign that HIV infection was advancing to the later stages, however it could and did occur at any CD4 count. Today the vaccine can be given if the CD4 count is over _____
Zoster
| 200
92
______ has always been rare in AIDS
herpes iii pneumonia
93
Erythroviruses (parvo B19 and its kindred) usually produce a
mild flu like illness that may be followed with a rash and/or joint pain (fifth dz, erythema infectious)
94
erythrovirus causes episodes of
red cell production failure in folks with hemolytic anemias, or severe anemia before birth "hydrops"
95
Erythrovirus morphology
nucleated red blood cell precursor with parvo inclusions in the nucleus
96
in HIV pts, parvo may cause
a longstanding failure of production of RBCs with severe anemia
These HIV its for some reason fail to make Abs against the virus
97
Bartonella species
bacillary angiomatosis. an unusual bacterial infection due to immune compromise
98
Bacillary angiomatosis morphology
solid masses of bugs
99
NOcardiosis
a filamentous, weakly acid fast bacterium. is a relatively uncommon pathogen in AIDS, it can produce pneumonia, meningitis, or isseminated infection
100
Scabies is
even worse in AIDS patients than in other folks
101
penicillium marneffei is a
fungal opportunistic seen among immune compromised people in southeast asia and in returned travelers.
local or systemic illness.
102
seborrhea is likely to flare up as Cd4 counts drop below
400
| and become severe below 200
103
Hairy leukoplakia
an EBV effect in which the squamous epithelium on the tongue proliferates
104
______ with _____ led to the identification of AIDS and HIV
kaposi's sarcoma with pneumocystis pneumonia.
105
Kaposi's is caused by infection with
```
herpes 8 (KSHV)
has varying presentations
```
106
classi Kaposi's
seen mostly in older men in the developed world. Generally, lesions are confined to the skin and do not shorten life expectancy
107
african kaposis
widespread in the subsaharan areas, even before HIV sometimes aggressive
108
transplant asociated kaposi's
seen especially in people suppressed for renal allografts. Could be aggressive
109
HIV associated
ranges from minor skin lesions to very aggressive dz with sometimes fatal GI/lung involvement
110
Kaposi's sarcoma is actually a
virally induced polyclonal proliferation of blood vessels
111
kapok's famous locations
on the palate and the nose.
112
one of the most troubling features of kapok's
the emotional impact - people knew what it meant
113
kaposis of the small intestine can produce
obstruction or serious bleeding
114
microscopically, kapok's looks like
granulation tissue, because it's an overgrowth of little blood vessels
at high magnification, look for red cells caught in the cracks
115
KSHV exists as an
episome in the host nucleus
116
Several of KSHV proteins (LAMA, vFLIP, and VCyclin) encourage cells to
proliferate - the lesions often, but not always regress partly or completely when antiretroviral therapy is instituted
117
Cancers of the lymphocytes that grow as solid masses.
malignang lymphoma
| much studied, classified and reclassifed, may of them are much more common in HIV patients than in other folks
118
Malignang lymphomas in HIV infected people fall into two categories
those that develop early
| those that develop later
119
Malignant lymphomas in HIV - that develop early
are usually aggressive B cell lymphomas. Probably these are common bc of the greatly increased turnover of B cells during the early years of the infection, providing an opportunity for selection for mutant clones (HIV as cancer promotor)
120
Malignant lymphomas in HIV - that develop later
usually related to EBV (less often KSHV) these are often polyclonal and may regress when immunity is restored
121
B cell lymphomas in aids
early - Burkitt lymphoma, large B cell lymphoma
| later - EBV+ large cell lymphoma, KSHV+ primary effusion lymphoma, EBV+ hodgkin lympoma
122
primary brain lymphomas, usually caused by ____ are___-
EBV
common
tend to center around blood vessels
123
the 'other' target of HIV (after the immune system) is the
nervous system
HIV doesn't infect neurons, astrocytes, or oligodendroglia
we think the damage is done by chemokines and infected microblia. and gp120 may be a neurotoxin
124
HIV in the nervous system
aids encephalopathy /-itis
macrophage "typhus" nodule
giant cell encephalitis
neuronal loss/gliosis
125
The giant cell encephalitis results from
macrophages trying to phagocytose one another, as each has HIV gp120 on its surface
126
AIDS peripheral neuropathy includes
a variety of lesions, but is seldom studied microscopically. More familiar to pathologists is the late, catastrophic spinal cored vacuolar myelopathy
127
Cachexia in aids has been attributed at least in part to
immune mediated apoptosis of skeletal muscle fibers
128
hair loss in advancing HIV infection is
poorly understood
129
Thrombocytopenia=
low platelets
130
Thrombocytopenia occasionally severe enough to came bleeding problems is a common problem in
hiv infection that often precedes damage to the immune and nervous systems.
131
thrombocytopenia
megakaryocytic can express CD4 and either coreceptor and are often abnormal and/or unproductive in numbers in HIV infection. Circulating platelets are often coated with gp120 containing immune complexes and destroyed.
132
once a problem affecting 40% of HIV positive patients at some point in their illness, thrombocytopenia is now uncommon thanks to
antiretroviral therapy. When it still requires focused treatment, Rx intravenous immunoglobulin or and anti-RhD (for Rh+ patients - this keeps the spleen busy destroying red cells rather than platelets)
133
structue of the aids virus
HIV 1/ HIV2
134
no reasonable person questions that the HIV viruses cause
AIDS
135
HIV's interaction with NFkB may help explain
how it reactivates and why transmission is more likely when there's already another infection
136
HIV contains
double stranded RNA, the reverse transcriptase to copi ti to DNA and other enzymes to incorporate it into the host genome.
the mutation rate is 10^6 more than for DNA, with an average of 1-2 mutations per replication cycle, with replication cycles averaging 2.6 days.
hence each HIV infection is a rapidly evolving system, which is why antiretrovirral therapy requires multiple drugs
137
When transmitted, most HIV is ____ binding to the Cd4 receptor and CCR5 coreceptors most abundant on ______ and _____
m-tropic (R5)
| dendritic macrophages and memory T cells
138
Over the course of the infection, the m tropic strains tend to be replaced by
T tropic mutants (X4 binding best to CD4 receptors and CXCR4 co receptors most abundandt on working T helper cells
139
A few percent of folks, mostly of European ancestry have mutant
CCR5 receptors. One mutated coply slows progression of the dz; two mutated copies confers resistance to infection
140
Initial infection is followed, in a marjoiry of cases, in around 3-7 weeks by
an acute febrile illness (my worst case of the flu ever), often with sore throat, muscle aches, and otherwise resembling infectious mononucleosis.
A rash and long duration may be tip-offs that its "acute retroviral syndrome" At theist ime virus levels are very high in the blood, and patients are extremely infectious
"acute retroviral syndrome" resolves in 2-4 weeks.
141
mucosal ulcers, often at the site of inoculation may alert the physician to
acute HIV
142
During the acute infection
there is often a high level of virus in the bloodstream and a low cd4 count. ( a few people's cd4s have dropped well below 100 and they;ve gotten pneumocystis-- recovering when the CD4 clls rebounded)
At the peak of the viremia, seroconversion occurs and the virus level drops
143
After the acute infection
the CD4 count recovers. After this, the virus lives and multiplies primarily in the deep lymphoid tissue. memory T cells are vulnerable to infection, and other CD4 positive cells can become infected when they are activated
eventually, the cd4 cells are depleted, and the immune system otherwise sufficiently damaged to allow one of the AIDS defining opportunistic infections or tumors to appear.
144
Long before the opportunistic infections appear,
the lymph nodes enlarge (big germinal centers, B cell proliferation) and the total blood (immune) globulins increase (polyclonal)
145
In late AIDS, the lymphoid tissues are
largely depleted, especially in the areas where there should be T cells
146
HIV destroys T cells through
cytopathic lysis from massive virus production
147
HIV in macrophages
seldom produces lysis. HIV viruses are sequestered in vacuoles and transported out of the macrophage without damaging it.
148
In additon to lysing CD4 cells and slowing down infected macrophages, HIV has a number of other effects
immune cells may die as a result of prolonged activation, or an abortive infection may cause a cell to self-destruct by activating the inflammasomes "pyroptosis"
follicular dendritic cells in the lymphoid tissue become coated with HIV virus and infect CD4 cells as they pass by. Its likely that this reservoir explains why no one is cured of HIV infection
and for some reason, HIV infection causes polyclonal activation of B cells, accounting for the generalized lymph nod enlargement that is often seen before symptoms of AIDS appear, and the polyclonal gammopathy sen in HIV infection
149
What defines retroviruses
reverse transcriptase
150
HIV is transmitted when
infectious material is injected directly into the bloodstream, or the virus is taken up by dendritic macrophages at the site of inoculation
151
HIV infection was originally recognized in the US as a disease of
MSMs. the explanation is that passive anal intercourse is an especially efficient means of transmission. remains the most common route of transmission in the US
152
The other major risk factor for HIV is
needle sharing, and female partners of infected male needle sharers are also at high risk.
153
the most common means of HIV transmission worldwide
heterosexual transmission
| although a self sustaining HIV epidemic never developed in the straight community in the US
154
transmission of HIV from mother to child may occur
across the placenta or from nursing, but it is most common during or just after the birth process
155
HIV infection is a
zoonosis
HIV-1 was a chimp virus. HIV2 was a sooty mangabey virus. The infections could only become established as epidemics among humans when social changes greatly increased the likelihood of transmission from human to human
156
The old PGL category "persistent generalized lymphadenopathy" reflected the
B cell/germinal center hyperplasia of the lymph nodes throughout the body.
in unRx's HIV this lasts for years
157
There was a massive die off of america's hemophiliacs due to
contaminated factor VIII
158
The antiretroviral drugs bring their own new anatomic pathology
lipodystrophy seen with some protease inhibitors - fat disappears from the face and becomes more abundant on the abdomen. On biopsy, look for fat cells in skeletal muscle itself.
159
IRIS=
immune reconstitution inflammatory syndrom
160
IRIS is seen
in one form or another in around 10% of patients with very low CD4 counts in the weeks/ months after initiation of anti retroviral therapy.
it's an aggressive immune response against opportunists that may have been known to be present already (paradoxical IRIS) or maybe not (unmasking IRIS)
161
infections producing IRIS
cryptococcal meningitis and CMV involving the eye (immune recovery uveitis) are perhaps the most common;
cryptococcal and JC papovaviurs IRIS can be lethal
most other infections producing IRIS (TB, other mycobacteria, pneumocystis, Kaposi's, zoster) may require no treatment or may be managed with prednisone
162
Today's screen for HIV is
an elisa, which is sensitive enough to make a good screen. The average person turns positive around day 25, most by 42 and it is rare to remain negative at 6 mo.
a positive elisa is followed up by a nucleic acid assay, which is replacing the classic western blot
163
Nucleic acid testing for HIV remains important for testing, and most people turn positive by days 13-28. No one is certain about the rate of false negatives after a month, but it is low.
You are likely to order nucleic acid testing
if you suspect acute HIV infection. It turns positive before any other test, but may be negative (eclipse phase) during the illness
in screening for neonatal HIV infection
after an indeterminate ELISA serology
all blood donor units are screened with a qualitative nucleic acid test
so far FDA approved nucleic acid tests only tsp for HIV 1
164
When diagnosis of HIV infection is established
quantitative nucleic acid based assays are used to follow the viral load
genetic studies are performed to test for resistance to current antiretroviral medications. around 20% of new infections are resistant to at least one medication
165
the viral capsid antigen p24, is
relatively inexpensive and as a fourth generation assay may turn positive earlier than the elisa
the cdc recommends a p24 and an elisa for screening; if either is positive, follow by an assay for antibodies against HIV1 and HIV2.
others recommend just an elisa unless there's a suspicion of acute HIV infection, in which case, order nucleic acid testing. The p24 assay tends to turn negative as the person develops antibodies against the protein.
and blood units are of course tested instead using an assay for HIV nucleic acid
166
Seven interventions that work against the spread of AIDS
1. Safe blood/blood components for transfusion
2. antiretroviral prophylaxis before and during childbirth
3. condom distribution and use
4. needle exchange programs for addicts
5. male circumcision
6. formula feeding instead of breast feeding for HIV+ moms
7. early treatment of the infected partner in serodiscordant unions
