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, 11 May 2000) regarding your
proposal to conduct experiments in an effort to "establish conclusively the
link between HIV and AIDS" (Financial Mail, 12 May 2000) one reads:
'According to MRC President Malegapuru Makgoba, the surveys could involve
the clinical identification of a sample of AIDS sufferers , who would be
tested for HIV. Another possibility is an epidemiological study
correlating HIV-positive children with the HIV status of their parents".
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, 12 May 2000). As you say, any
attempt to answer the role of HIV in AIDS must involve HIV. We also agree
that the best way to solve a scientific problem is to conduct experiments.
However, we do have some questions regarding the suggested experiments.
(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 Africa these numbers are 2-3; 0.66 - 1.66 and 0.27
- 0.79 million respectively (De Cock KM, et al. JAMA 1992; 268:1581-7).
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 Central Africa where the prevalence of mycobacterial
diseases is quite high (Kashala O, et al. J Infec Dis. 1994;169:296-304).
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 Africa will
suffer from mycobacterial infections or come in contact with such
individuals. "Tuberculosis may spread via the placenta or the foetus may
acquire it from ingestion of contaminated amniotic fluid. Congenital TB
may affect the liver, spleen lymph nodes and other organs"(Harrison's
Principles of Internal Medicine).
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 Africa a positive HIV antibody test
"correlated strongly with level of antibodies against Plasmodium
falciparum", the microorganism which causes malaria (Biggar RJ. Lancet
1985;2:520-3). One year later, researchers from the USA and Venezuela
reported that 3 out of 12 patients (25%) with Plasmodium vivax at no risk
of AIDS and 5 of 12 (41%) of patients with Plasmodium falciparum, also at
no risk of AIDS, 'were found to be positive for HTLV-III/LAV [HIV]
antibodies by the indirect immunofluorescence, Western blot and
radioimmunoprecipitation tests, … The frequency of antibodies of
HTLV-III/LAV among healthy blood donors in this area was less than 1
percent" (Volsky et al. NEJM 1986;314:647-648). In one study it was found
that Amazonian Indians who have no contact with individuals outside their
tribes and have no AIDS have a 3.3-13.3% HIV WB seropositivity rate
depending on the tribe studied (Rodriquez L, et al. Lancet 1985;2:1098-1100)
(c) Such a study cannot be conducted in Australia because such cases are
extremely rare. In the USA and Europe, the majority of mother-infant pairs
reported to have a positive antibody test originated from Africa or Asia or
belonged to such communities, that is, in countries and communities where
the prevalence of mycobacterial diseases is quite high. For example, in
the Women and Infants Transmission Study from the USA published in 1996,
56% of women were either black or Hispanic (Rodriguez EM, et al. AIDS
1996;10:273-82). In another study from the USA published in 1997, 41% of
the women were black and 42% Hispanic (Turner BJ, et al. 1997;14:327-37).
In the Paediatric AIDS Clinical Trials Group Protocol 185, USA, 51% of the
women were black and 35% Hispanic (Stiehm ER, et al. J Infec Dis
1999;179:567-75). In the French Perinatal Cohort 40% of the women "were
born in sub-Sahara Africa or the Caribean" (Mandelbrot L, et al. JAMA
1998;280:55-60). By April 1996, 276 of the 389 (71%) children with HIV
infection or AIDS reported to the UK combined obstetric and paediatric
national confidential registers were from London, 80% of whom were born in
sub-Saharan Africa (Gibb DM, et al.. Arch Dis Childhood 1997;77:478-82).
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
From: "Malegapuru William Makgoba" <malegapuru.makgoba@mrc.ac.za>
To: Val F Turner <vturner@cyllene.uwa.edu.au>
Date: Tue, 16 May 2000 15:14:18 +0200
Subject: Re: Letter from Eleni Papadopulos-Eleopulos
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 Africa, the diagnosis of AIDS
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
Africa has the lowest HIV antibody positivity. If the correclation was
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 South Africa is based on solid clinical grounds that are
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)
From: Val F Turner <vturner@cyllene.uwa.edu.au>
To: "Malegapuru William Makgoba" <malegapuru.makgoba@mrc.ac.za>
Date: Tue, 2 June 2000 18:11:18 +0800
Subject: Re: Letter from Eleni Papadopulos-Eleopulos
Dear Professor Makgoba:
My colleagues and I are sorry that we apparently confused you by our email
with regards to the sender since your answer was addressed to me instead of
E P-E who "signed" our letter to you. Generally we use my email address as
a central address for all correspondence. Since you may not be aware
who I am, permit me to give some information. I belong to a group which
over the years others have called "The Perth Group" in AIDS research. The
group is led by E P-E who put forward a theory on the cause of AIDS before
the HIV theory was introduced. Since then the group has published
extensively on the questions surrounding the cause of AIDS. The group
includes three medically qualified individuals, namely, a professor of
Pathology, a medical researcher and myself. I've been in Emergency Medicine
since 1979 and am probably the oldest practising Emergency Physician in
Australia. I'm a foundation Fellow of my College and I've taught hundreds
of medical students, interns and residents. I've seen thousands of
patients and even had a few wins. I would never question your clinical
abilities without seeing you in action at the bedside for a long period of
time. How you can pass judgement on mine is impossible to tell.
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 Africa, the diagnosis of AIDS follows a history, a physical
examination and treatment".
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 University of Ghana
collected blood samples from 227 Ghanian patients diagnosed as having AIDS,
without testing for HIV. Of the 227 patients, 59% had neither a positive
or indeterminate result for either HIV-1 or HIV-2. (74% were negative for
HIV-1). This means either:
(i) AIDS cannot be diagnosed in the absence of an HIV laboratory test,
(ii) The vast majority of AIDS cases in Africa are not caused by HIV, and
as the Ghanian researchers urge, one should search for "novel aetiological
agents of the disease". (Hishida et al Lancet 1992; 340:971-72).
"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 July 18th
1997. Continuum 1998;5:30-34) www.virusmyth.com/aids/data/dtinterviewlm.htm);
(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 South Africa has the lowest HIV antibody
positivity. If the correlation was 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!!"
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 an inverse relationship between condom use and a positive "HIV"
antibody test?
"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,
Val Turner
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 email 16/5/00
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
From: Val F Turner <vturner@cyllene.uwa.edu.au>
To: "Malegapuru William Makgoba" <malegapuru.makgoba@mrc.ac.za>
Date: Wed, 14 Jun 2000 07:33:24 +0800
Subject: Re: Reply to your email 16/5/00
Dear Professor Makgoba,
I would greatly appreciate your permission to place our email
correspondence on the Perth group website.
I am very happy to send you exactly what will be posted before it is posted.
Professor Robin Weiss agreed to the same proposal when he and I conduced
email disussions over the isolation of HIV. I believe it important to
present the views of everyone.
Thank you for considering this matter.
Yours sincerely,
Val Turner