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Medical Forum / Diseases and Disorders / AIDS / October 2004

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CAUSES OF FALSE POSITIVES

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PaulKing - 14 Oct 2004 20:53 GMT
Factors Known to Cause
False Positive HIV Antibody Test Results

1.Anti-carbohydrate antibodies 52,19,13
2.Naturally-occurring antibodies 5,19
3.Passive immunization: receipt of gamma globulin or immune (as
prophylaxis against infection which contains antibodies) 18, 26, 60, 4,
22, 42, 43, 13
4.Leprosy 2, 25
5.Tuberculosis 25
6.Mycobacterium avium 25
7.Systemic lupus erythematosus 15, 23
8.Renal (kidney) failure 48, 23, 13
9.Hemodialysis/renal failure 56, 16, 41, 10, 49
10.Alpha interferon therapy in hemodialysis patients 54
11.Flu 36
12.Flu vaccination 30, 11, 3, 20, 13, 43
13.Herpes simplex I 27
14.Herpes simplex II 11
15.Upper respiratory tract infection (cold or flu) 11
16.Recent viral infection or exposure to viral vaccines 11
17.Pregnancy in multiparous women 58, 53, 13, 43, 36
18.Malaria 6, 12
19.High levels of circulating immune complexes 6, 33
20.Hypergammaglobulinemia (high levels of antibodies) 40, 33
21.False positives on other tests, including RPR (rapid plasma
reagent) test for syphilis 17, 48, 33, 10, 49
22.Rheumatoid arthritis 36
23.Hepatitis B vaccination 28, 21, 40, 43
24.Tetanus vaccination 40
25.Organ transplantation 1, 36
26.Renal transplantation 35, 9, 48, 13, 56
27.Anti-lymphocyte antibodies 56, 31
28.Anti-collagen antibodies (found in gay men, haemophiliacs, Africans of
both sexes and people with leprosy) 31
29.Serum-positive for rheumatoid factor, antinuclear antibody (both found
in rheumatoid arthritis and other autoantibodies) 14, 62, 53
30.Autoimmune diseases 44, 29, 1O, 40, 49, 43
31.Systemic lupus erythematosus, scleroderma, connective tissue disease,
dermatomyositis Acute viral infections, DNA viral infections 59,
48, 43, 53, 40, 13
32.Malignant neoplasms (cancers) 40
33.Alcoholic hepatitis/alcoholic liver disease 32, 48, 40, 10, 13, 49, 43,
53
34.Primary sclerosing cholangitis 48, 53
35.Hepatitis 54
36."Sticky" blood (in Africans) 38, 34, 40
37.Antibodies with a high affinity for polystyrene (used in the test kits)
62, 40, 3
38.Blood transfusions, multiple blood transfusions 63, 36, 13, 49, 43, 41

39.Multiple myeloma 10, 43, 53
40.HLA antibodies (to Class I and II leukocyte antigens) 7, 46, 63, 48,
10, 13, 49, 43, 53
41.Anti-smooth muscle antibody 48
42.Anti-parietal cell antibody 48
43.Anti-hepatitis A IgM (antibody) 48
44.Anti-Hbc IgM 48
45.Administration of human immunoglobulin preparations pooled before 1985
10
46.Haemophilia 10, 49
47.Haematologic malignant disorders/lymphoma 43, 53, 9, 48, 13
48.Primary biliary cirrhosis 43, 53, 13, 48
49.Stevens-Johnson syndrome 9, 48, 13
50.Q-fever with associated hepatitis 61
51.Heat-treated specimens 51, 57, 24, 49, 48
52.Lipemic serum (blood with high levels of fat or lipids) 49
53.Haemolyzed serum (blood where haemoglobin is separated from red cells)
49
54.Hyperbilirubinemia 10, 13
55.Globulins produced during polyclonal gammopathies (which are seen in
AIDS risk groups) 10, 13, 48 cross-reactions 10
57.Normal human ribonucleoproteins 48, 13
58.Other retroviruses 8, 55, 14, 48, 13
59.Anti-mitochondrial antibodies 48, 13
60.Anti-nuclear antibodies 48, 13, 53
61.Anti-microsomal antibodies 34
62.T-cell leukocyte antigen antibodies 48, 13
63.Proteins on the filter paper 13
64.Epstein-Barr virus 37
65.Visceral leishmaniasis 45
66.Receptive anal sex 39, 64
Christine Johnson, a researcher and author, compiled this list of
conditions documented in the scientific literature to cause positives on
HIV tests, and provides references for each condition.
Christine notes:
"Just because something is on this list doesn't mean that it will
definitely, or even probably, cause a false-positive. It depends on what
antibodies the individual carries as well as the characteristics of each
particular test kit.
For instance, some, but not all people who have had blood transfusions,
prior pregnancies or an organ transplant will make HLA antibodies. And
some, but not all test kits (both ELISA and Western blot) will be
contaminated with HLA antigens to which these antibodies can react. Only
if these two conditions coincide might you get a false-positive due to HLA
cross-reactivity.
There are conditions that are more likely than others to cause
false-positives. And there are some conditions that we aren't aware of yet
which may be documented in the future to cause false-positives. Some of
the factors on the list have been documented only for ELISA, while some
have been documented for both ELISA and Western blot (WB) tests.
People may be eager to argue that if a factor is only known to cause
false-positives on ELISA, this problem won't be carried over to the WB.
But remember, a WB is positive by virtue of accumulating enough individual
positive bands to add up to the total required by whatever criteria is
used to interpret it 39. So the more exposure a person has had to foreign
antigens, proteins and infectious agents, the more various antibodies he
or she will have in their system, and the more likely it is
that there will be several cross-reacting antibodies, enough to make the
WB positive.
It is to be noted that all AIDS risk groups (and Africans as well), but
not the general US or Western European population, have this problem in
common: they have been exposed to a plethora of foreign antigens and
proteins. This is why people in the AIDS "risk groups" tend to have
positive WBs (i.e., to be considered "HIV-infected") and people in the
population don't. However, even people in low-risk populations have
false-positive Western blots for poorly understood reasons 47.
Since false-positives to every single HIV protein have been documented 36,
how do we know if the positive WB bands represent the various proteins to
HIV, or a collection of false-positive bands reacting to several different
non-HIV antibodies?"
GMCarter - 15 Oct 2004 10:43 GMT
>Factors Known to Cause
>False Positive HIV Antibody Test Results

Well, the list collector also notes:
>Christine Johnson, a researcher and author, compiled this list of
>conditions documented in the scientific literature to cause positives on
[quoted text clipped - 4 lines]
>antibodies the individual carries as well as the characteristics of each
>particular test kit.

All tests have the possibility of causing false positive or false
negative results. For every disease or condition. The measure for
these is known as sensitivity and specificity. As tests goes, triple
ELISA or ELISA with Western Blot follow up has some very high
specificity and sensitivity.

If this is concomitant with CD4 decline and clinical manifestations of
disease, you can be pretty sure that the test was accurate.

        George M. Carter

>For instance, some, but not all people who have had blood transfusions,
>prior pregnancies or an organ transplant will make HLA antibodies. And
[quoted text clipped - 7 lines]
>the factors on the list have been documented only for ELISA, while some
>have been documented for both ELISA and Western blot (WB) tests.
PaulKing - 20 Oct 2004 02:26 GMT
"As tests goes, triple
ELISA or ELISA with Western Blot follow up has some very high
specificity and sensitivity. "

So you think THREE inaccurate tests add up to one accurate one?

Interesting idea.
GMCarter - 20 Oct 2004 10:18 GMT
>"As tests goes, triple
>ELISA or ELISA with Western Blot follow up has some very high
>specificity and sensitivity. "
>
>So you think THREE inaccurate tests add up to one accurate one?
>Interesting idea.

You should consider the concept! Might cause a neuron or two to fire
and connect.

Yes, indeed! Measurements of anything are prone to the messiness of
reality. In construction, they say, "measure twice, cut once." There
IS a reality of a set distance between two points--or an antibody
reaction to an infecting pathogen. But the tools used may not be
completely accurate. So you repeat the test and that will give you
increased confidence that your measurement is accurate.

In the case of HIV testing--compared to other tests--the accuracy
where there is a risk of a false positive or a false negative is in
99+% range. Pretty good confidence.

Of course, tests are not necessary for HIV to cause wasting, dementia,
CD4+ declines and increased risk of opportunistic infections.

        George M. Carter
Baby Peanut - 20 Oct 2004 13:28 GMT
> "As tests goes, triple
> ELISA or ELISA with Western Blot follow up has some very high
[quoted text clipped - 3 lines]
>
> Interesting idea.

Oil Exploration Costs Far Exceed Value of Discoveries

The value of new discoveries by the world's 10 largest oil companies
fell well below the amount they have spent on exploration over the
past three years, according to research by the energy consultants Wood
Mackenzie.  A Financial Times report ('Top oil groups fail to recoup
exploration costs', October 10, 2004) says companies are spending
record levels on developing known fields to keep pace with growing
demand.  But after 2008, according to Robert Plummer, corporate
analyst at Wood Mackenzie, "they will need more discoveries to
maintain growth ... the problem is exploration has not been generating
returns."  Combined expenditure of about $8 billion on exploration
last year — down from $11 billion in 2001 — produced discoveries
valued at less than half that amount.  "These figures will improve as
more of the technical reserves discovered in these years are
commercialised and initial reserve estimates are upgraded," Mr Plummer
said, "but the value added through exploration for 2001-2003 is
running well below the average for 1996-2000."  The FT article said
the findings reflected the fears of some companies that claim they
need greater access to Opec nations to boost reserves. The chief
executive of Total, the French oil group, was reported to have said
recently that oil companies could not discover enough new oil to
ensure supply meets demand in coming years.

[Posted 15 October 2004]
 
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