THIS IS THE EMAIL CORRESPONDENCE BETWEEN PROFESSOR MAKOGBA AND THE PERTH GROUP
DEPARTMENT OF MEDICAL PHYSICS
ROYAL PERTH HOSPITAL
WELLINGTON ST
PERTH WESTERN AUSTRALIA
16/5/00
Dear Professor Makgoba,
You have been reported as saying that scientific problems cannot be solved by consensus (Sunday Independent, 19 March 2000) and that President Mbeki's panel should not address the question as to "whether malnutrition or TB causes AIDS or any of those things that come from the dissidents. We're undertaking a series of projects to try to understand the peculiarities of the disease in SA". (Financial Mail, 12 May 2000).
In a commentary by Michael Cherry, (Nature,
We agree with you that scientific problems cannot be solved
by consensus and that the role of HIV in AIDS cannot be answered by addressing
such questions as "whether malnutrition or TB" or "any of those
things that come from the dissidents", such as "environmental
pollutants and other unspecified chemicals" (Financial Mail,
(1) According
to a Lancet editorial, (Horton R, Lancet 1998;352:122)
the developing world "bears more than 90% of the global burden of HIV
infection" and that "Tuberculosis (TB) is the leading cause of death
worldwide among the people with HIV".
And one of the most eminent experts on HIV/AIDS in Africa, De Cock, and
his associates, state that the prevalent cases of TB in the developing World is
12-16 million; annual incidence of TB is 3.5 - 10.7 million and the annual
deaths 1.14 - 3.96 million. In
sub-Sahara
By the end of the 1980's, long before TB became a "clinical identification" of AIDS, ample evidence existed that the vast majority of TB patients had a positive antibody test. In other words ample evidence already exists for a correlation between a positive antibody test and the clinical identification of AIDS. Why then repeat all these experiments if the answers are already known ?.
(2) In a paper published by researchers from Harvard, including one of the best known retrovirologists, Max Essex, they found that "... leprosy patients and their contacts show an unexpectedly high rate of false positive reactivity of HIV-1 proteins on WB [83.6% patients; 64.1% contacts] and ELISA….sera from 63.6% of leprosy patients and 23% of their contacts were repeatedly positive for HIV-1 by ELISA". They went one step further and proved that the antibodies which reacted with the proteins in the ELISA and WB kits were directed against two major carbohydrate-containing Mycobacterium leprae antigens-phenolic glycolipid I and especially lipoarabinomannan which is also present in Mycobacterium tuberculosis and other mycobacteria. They also suggested that at least some of the antibodies in patient sera reacting with the proteins in the ELISA and WB may be auto-antibodies induced by mycobacterial infections.
They
concluded: "ELISA and WB may not be
sufficient for HIV diagnosis in AIDS-endemic areas of
The questions then are:
(i) How are you going to determine in which, if any, TB patients the positive WB or repeated ELISA prove HIV infection, that is the tests are true positives?
(ii) In which patients the underlying cause of TB and thus of the majority of AIDS cases in the developing world, including SA, is HIV and in which is not?
(3) In regard to the "epidemiological study correlating HIV-positive children with the HIV status of their parents":
(a) As you know antibodies can and do cross the placenta.
(b) A significant proportion of pregnant women in sub-Sahara
They may also suffer from malaria which is also known to be
associated with a false positive HIV antibody test. As far back as 1985, Biggar
and his colleagues found that in
(c) Such a
study cannot be conducted in
How are you going then to know in which, if any, mother-child pair the positive antibody tests is true positive?
If we assume that in all patients a positive antibody test proves HIV infection and that a perfect correlation exists between HIV infection and the "clinical identification" of AIDS, is the virological correlation sufficient to prove causation? Should not one also have immunological data which proves that the decrease in T4 cells in AIDS patients is due to their destruction by HIV?
It is our view that the experiments as reported in the media and some scientific publications are not going to clarify the role of HIV in AIDS. We have been working on the AIDS problem from the very first beginning and conceptualised experiments which in our view may clarify the role of HIV in AIDS. If you are interested, we would very much appreciate your comments and would be delighted to collaborate with you on such experiments.
Yours sincerely,
Eleni Papadopulos-Eleopulos
Email vturner@cyllene.uwa.edu.au
Fax int + 618 92241138
REPLY
From: "Malegapuru William Makgoba" <malegapuru.makgoba@mrc.ac.za>
To: Val F Turner <vturner@cyllene.uwa.edu.au>
Date:
Subject: Re:
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Dear Val,
Thank you very much for your letter. It appears to me that your
understanding of clinical medicine and diagnosis is limited.
First of all I agree entirely with the notioon of false positive results.
However you must agree that in
follows a history, a physical examination, laboratory investigations
and treatment. All these four essential steps are used to come to a
probable diagnosis.
Secondly, I spelt out this morning a cohort of 504 infants of whom
54 were found to be HIV positive by antibody test and by PCR.
Even you would agree that while the antibody crosses the placenta
the finding of positive viral DNA is significant. The mere presence of
a positive antibody test in a neonate is by itself not significant
provided it does not persist over time.
Thirdly I have also mentioned that the highest TB area in South
simply with TB then the reverse would be found. There is no
correlation between TB and a positive antibody test in our setting.
We are the authorities here and not you mind you!!
The point I am trying to get you to undertand is that the diagnosis
of AIDS in
supported by laboratory tests. Clinicians are trained to work in this
manner. The importance of a false positive antibody tests is usually
seen in the light of good clinical and other laboratory tests.
For a practising physician it is not usually difficult to discriminate.
I hope you find this helpful but I resent the notion that what we see
and diagnose is somehow wrong because you continue to confuse
good clinical practice and the accurate interpretation of laboratory
tests in a clinical setting.
yours sincerely,
MW Makgoba DPhil(Oxon);FRCP(Lond); FRS(SAFr)
REPLY
Dear Professor Makgoba:
My colleagues and I are sorry that we apparently confused
you by our
Please find below our comments to your answer as follows:
· "I really look forward to a discussion in which you respect the authority of those that are at the coal face of this epidemic."
We apologise if you thought that we do not respect your authority. In fact, we have written to you because:
* We know that you are the authority there and respect you.
* Your people are said to have the highest incidence of AIDS.
* You care about them.
* We have been working on AIDS since it was first diagnosed and we believe that we may be able to contribute to find a solution.
However, we would also like to point out that if one always respects authorities in science, science would never progress.
Permit me to quote Giordano Bruno's Latin Frankfurt Trilogy, published in 1591:
"He who desires to philosophize must first of all doubt all things. He must not assume a position in a debate before he has listened to the various opinions, and considered and compared the reasons for and against. He must never judge or take up a position on the evidence of what he has heard, on the opinion of the majority, the age, the merits, or prestige of the speaker concerned, but he must proceed according to the persuasion of an organic doctrine which adheres to real things, and to a truth that can be understood by the light of reason".
· "I agree entirely with the notion of false positive results".
We are glad. The question then is how does one know that a positive antibody test, even in a single patient with TB, for example, is due to HIV infection? This is a question you did not answer.
· "In
·
Although I am well aware that clinicians may elect to treat patients "on the balance of probabilities" or because not to treat may lead to disaster (eg meningococcal septicamia), it is scieintifically impossible to use treatment as a criteria for diagnosis. (Otherwise we might have to conclude that heart failure for example is due to deficiency of foxglove). I do not believe that pragmatism has any place in discovering scientific truths.
The use of the other three criteria for the diagnosis of AIDS, is best illustrated by an example:
In a paper published in 1992, researchers from the
(i) AIDS cannot be diagnosed in the absence of an HIV laboratory test,
(ii) The vast
majority of AIDS cases in
· "I spelt out this morning a cohort of 504 infants of whom 54 were found to be HIV positive by antibody test and by PCR. Even you would agree that while the antibody crosses the placenta the finding of positive viral DNA is significant".
Significant of what? With the available data, it is not possible to consider it significant for HIV infection. As we pointed out to Harvey Bialy, in a court of law even the most inept lawyer would have no problem convincing a jury that a PCR or indeed any genomic study does not prove the detection of a retroviral genome much less that of a specific retrovirus HIV, when he presents proof that the RNA (cDNA) used to prove infection originated from material:
(a) which contained no particles "with morphology typical
of retroviruses" (Tahi D. Did Luc Montagnier discover HIV? Text of video interview
with Professor Luc Montagnier at the Pasteur Institute
(b) consisting of "purified microvesicles" (Gluschankof P, Mondor I, Gelderblom HR, Sattentau QJ. Cell membrane vesicles are a major contaminant of gradient-enriched human immunodeficiency virus type-1 preparations. Virol. 1997;230:125-133.)
Apparently HIV experts are either incapable or unwilling to consider that the possession of antibodies which react with a selection of proteins deemed unique to HIV (that is, being HIV seropositive) is not proof of infection although our group do agree it does correlate with a risk of either having or developing the diseases which constitute AIDS. Yet the same clinicians, yourself included, have no problem reconciling the rate with which red blood cells fall through a column of normal saline (the ESR) being predicitive of the presence of or the propensity to develop a variety of diseases more extensive than AIDS.
· "the highest TB area in
a) We never said that a positive "HIV" antibody test in SA is related "simply with TB". There are many diseases, including leprosy and malaria not to mention weight loss (weight loss leads to a positive antibody test and not vice versa (Moore PS, Allen S, Sowell AL, et al. (1993). Role of nutritional status and weight loss in HIV seroconversion among Rwandan women. J. Acquir. Immune Defic. Syndr. 6:611-616) which are also related to a positive test.
It is important to notice that your finding is in contradiction with many papers which report "co-infection" with mycobacteria and "HIV". And if TB is a predominant AIDS defining illness in Africa, and if HIV causes AIDS and the tests specific, then one can only conclude that in your part of the world TB is not an predominant AIDS defining disease. If not then what is?
b) In the "Profile of South African Medicine", Lancet May 24, 1997, in which you are a contributor, in the contribution headed "HIV and Tuberculosis" by Dr Abdool Karim one reads: "Clinically, pulmonary tuberculosis (TB) is the main presenting illness among HIV infected persons. The incidence rate of TB in South Africa is one of the highest in the world at 341 per 100 000 per year. To illustrate the burden in the era of HIV, the incidence rate of TB in one rural district with a population of about 200 000 rose from 154/100 000 in 1991 to 413/100 000 in 1995. At the same time, prevalence of HIV infection among these TB patients rose from 29% to 55%. Drug resistant in TB is closely monitored. Multiple-drug resistant TB has not increased as a fraction of all TB cases over the past two decades".
c) If :
i) The lancet editorial of July 11, 1998, is wrong; that is, in SA unlike anywhere else in the developing world TB is not "the leading cause of death among people with HIV";
ii) In SA, AIDS is a sexually transmitted disease caused by a sexually transmitted virus, whose transmission can be prevented by the use of condoms;
how do you explain the South African Demographic and Health Survey 1998, which shows no relationship between condom use and a positive "HIV" antibody test? (data below)
· "I resent the notion that what we see and diagnose is somehow wrong because you continue to confuse good clinical practice and the accurate interpretation of laboratory tests in a clinical setting".
I assure you I have no confusion about the application of diagnostic tests in clinical medicine. And as I am sure you will agree, the predictive value of such tests is determined by their specificity and the prevalence of the condition for which the tests are used. In this case HIV infection. Let me point out that the clinical syndrome of AIDS cannot be used to define the specificity of an antibody test, no matter how good the clinical practice. For the HIV antibody test this is impossible. You cannot, on the one hand, say that a disease is caused by HIV because the patient has a positive antibody test; and on the other hand, that the antibody test is specific because the patient has the disease. The only way to detemine the specificity of the antibody tests for HIV infection is to measure them against an independent gold standard, HIV isolation. This has never been reported. Why do you think manufactures such as Abbott Laboratories include the following in their packet inserts:
"At present there is no recognized standard for establishing the presence or absence of HIV-1 antibody in human blood". The identical statement is present in their 1988 and 1998 packet inserts.
My colleagues and I have spent nearly twenty years researching AIDS. In this quest we are the only people to question whether HIV has been isolated and for us this in now the only question of relevance. Even you must agree that without HIV there can be no HIV theory of AIDS or of anything. If you find the notion that the phenomena said to prove the existence of HIV are a misinterpration and too hard to bear, then may I ask you to spend some time reading our papers and respond to them point by point. As I have to your letter. If you find the idea that a group of scientists could mistakenly identify a retrovirus then I urge to you to study the papers that relate to the isolation, the antibody tests and the demise of HL23V. This was the "first" human retrovirus, discovered in the mid 1970s by Gallo and now recognised as an embarrassing error. There are uncanny parallels between HIV and HL23V.
Yours sincerely,
REPLY
From: "Malegapuru William Makgoba" <malegapuru.makgoba@mrc.ac.za>
To: Val F Turner <vturner@cyllene.uwa.edu.au>
Date: Fri, 2 Jun 2000 14:21:56 +0200
Subject: Re: Reply to your
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Dear Val,
Thank you for your replies, unfortunately you have got things wrong
and this is not surprising. To say that a response to foxglove in
patient with heart failure implies that the patient is foxglove
deficient is an intepretation that is ridiculous and laughable but that
is how you interpret my statement that a response to treatment
constitutes evidence in causation in medicine when taken into with
the other three criteria.
Secondly patient who are TB positive and are HIV positive would
not have HIV specific cytotoxic T cells if this is due to false positive
results.
In the interest of my own sanity, I hope you understand how my
logic is derived and I am quite confident that you can distinguish
false positives easily if you are well trained and you reason
logically.
Again I want to thank you I wish you well. I do not need any further
replies or responses.
Bye now.
yours sincerely,
MW Makgoba
PLACE |
CONDOM |
|
HIV POSITIVE |
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KwaZulu Natal |
2.5 |
|
32.5 |
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Mpumalanga |
2.2 |
|
30 |
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Free State |
3 |
|
22.8 |
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Gauteng |
2.8 |
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22.5 |
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North West |
1.6 |
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21.3 |
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Eastern Cape |
1.4 |
|
15.9 |
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Northern |
2.1 |
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11.5 |
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Northern Cape |
0.4 |
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9.9 |
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Western Cape |
2.2 |
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5.2 |
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CONDOM = |
percentage of sexually active women
currently using condoms as their method of contraception |
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HIV POSITIVE=women attending antenatal
clinics. Not the same group of women. |
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