Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso, Sam Mhlongo, Todd Miller, Christian Fiala
Send response to journal:
PCP and "HIV"
In his rapid response: "Re: "HIV" and PCP", 18 October, Peter Flegg wrote: "In an attempt to deny the link between Pneumocystis and HIV/AIDS, they [the Perth Group] serve up a paper published in 1991 as evidence that PCP has nothing to do with AIDS".
We have always questioned the link between PCP and "HIV", but never the link between PCP and gay men, haemophiliacs and drug users.
Peter Flegg wrote: "I have stated that PCP is extremely unusual in the absence of HIV, a fact they dispute. They ask me, "Can the diagnosis of PCP in five immunocompetent, "HIV" negative individuals in one hospital, within 3 months, be considered as evidence that PCP is "extremely unusual" in the absence of HIV?".
The answer is "Yes, it can", and not just because I say so, but because the article’s authors say so themselves. They published the case series precisely because PCP is "extremely unusual" in the absence of HIV. Here are some further direct quotes, so there can be doubt:
"Before 1981 [when PCP was first described in AIDS patients] it was a rare condition. Pneumocystis carinii pneumonia was first reported in the United States in 1955, and only 107 cases were reported during the subsequent decade" [interpretative hint to Perth Group - this means "rare"]
"Reports of PCP in non-immunocompromised adults are extremely rare." [Interpretative hint to Perth Group – this means "extremely rare"]
It is true that before 1981 PCP was rarely reported in the medical journals. Jacobs and his colleagues do not mention how often T4, T8 counts were performed in individuals with pneumonia and test for a differential diagnosis of PCP before the AIDS era or why they performed the immunological or PCP tests in their patients with lung disease. Nor do they comment what is the reason that in such a short period they found so many patients with PCP in their hospital.
The fact is that before the AIDS era, the only test used to diagnose PCP was open lung biopsy. Since the test is invasive it was rarely used for the differential diagnosis of lung disease. Peter Flegg admits that "drug users were well recognised as having increased susceptibility" for both non-pneumonia chest infections and pneumonia, "even in the pre-HIV era".[1 2]
This was also the case in haemophiliacs. Would Peter Flegg please tell us how often he was requesting open lung biopsies for the differential diagnosis of lung disease in his drug abusing patients, or any other patient, in "the pre-HIV era" or even today? How often would Peter Flegg or any other physician request open lung biopsies in a haemophiliac in "the pre-HIV" and pre-factor VIII era or even today? If not too often, then how does Peter Flegg, or anybody else, know that in the "HIV" era there is an increase in the frequency of PCP and, if this is the case, the cause of PCP in gay men, haemophiliacs and drug abusers is "HIV"?
Jacob et al wrote: "Fiberoptic bronchoscopy in our institution almost always includes bronchoalveolar lavage, which has a diagnostic sensitivity of 79 to 98 per cent in patients with AIDS who have P. carinii pneumonia". No mention is made of specificity.
As in the patients with AIDS the diagnosis of PCP in the 5 "non-immunocompromised" patients was done using bronchoalveolar lavage. However, "one might expect to find P. carinni in the fluids from bronchoalveolar lavage of about 40% of patients with AIDS who present with symptomatic pneumonia caused by other organisms". That is, the test is not specific.
In this regard it is significant that in the two patients whose lungs were examined they reported the following findings: "In patient 2, after the finding of P.carinii on two occasions in the bronchoalveolar-lavage fluid, an open-lung biopsy performed after 21 days of antipneumocystis therapy showed pathologic changes characteristic of adult respiratory distress syndrome but none characteristic of P. carinii pneumonia; the patient subsequently made a complete recovery".
In patient 3 "Combination therapy with 160mg of trimethoprim and 800mg of sulfamethoxazole intravenously every six hours was added to the regimen; nevertheless, subsequent chest films showed worsening of the bilateral infiltrates. On hospital day 22, hypotension and hypoxia were noted, and the patient died…Postmortem examination of the lung tissue demonstrated acute suppurative broncho-pneumonia with hemorrhage and necrosis. No P. carinii organisms were found".
It is also significant that although Peter Flegg has written repeatedly about PCP in his patients, in no publication does he mention what tests he used for its diagnosis. We found only the following comment: "Differentiating BCIs [bacterial chest infections] from PCP was often difficult…Symptoms of weight loss, fever and breathlessness were more marked in PCP, whereas cough productive of sputum was more characteristic of BCIs".
Peter Flegg wrote: "Of the five cases, all in people over 65, there was one woman with diabetes, CCF and asthma, one man with diabetes and alcohol abuse, one woman with cardiac valve disease, one woman with COPD and CCF, and the only case below the age of 70 was in a healthy male. Immunological studies on three of the five cases showed normal CD4 count in only one, and all three had low CD8 counts and evidence of a "cellular immunodeficiency as demonstrated by the low stimulation indexes in response to mitogen and antigen".
So it would seem that perhaps they were not as immunocompetent as the Perth Group would have us believe, and certainly not as immunocompetent as we would expect 30 year olds to be (who have the highest incidence of HIV-PCP). This is all rather irrelevant, however, because even if they were fully immunocompetent, this in no way detracts from the recognition that PCP in the absence of HIV immunodeficiency is exceedingly rare, a point the Perth group seem to keep trying to disclaim, even though their own citations merely confirm it."
If diabetes, CCF, asthma, alcohol abuse, cardiac valve disease, lower immunocompetence, which in turn predisposes to the development of PCP, then given the fact that these type of patients: (a) have been present in the New York Hospital-Cornell Medical Centre long before the 5 cases were reported, as well as since then, why was PCP reported only in this small period of 3 months; (b) are present in every major hospital around the world, why "PCP in the absence of HIV immunodeficiency is exceedingly rare?" Could it be because patients other than those suspected of having AIDS are not tested? Is it possible that the reported high frequency of PCP in the Jacobs et al study and in many, if not all AIDS patients, is not real but the result of a non specific test?
Would Peter Flegg please tell us why there is such a high frequency of PCP among USA AIDS patients, but is seldom if ever reported in African AIDS patients.
Peter Flegg wrote: "Let us put these 5 cases into perspective. In 1991, the year this series was published, there were over 20 thousand reported cases of PCP in AIDS patients in the USA alone . This huge disparity in cases is precisely why non-HIV cases of PCP continue get written up in journals - it is because they are the exception, and not the rule."
Of the "over 20 thousand" cases of PCP "reported in 1991", in the USA only 13,697 had "Definitive diagnosis", the other 7,189 had "Presumptive diagnosis".
Regarding the method for definite diagnosis of PCP, the CDC definition states: "Pneumocystis carinni pneumonia (on histology or microscopy of a "touch" preparation, bronchial washing or sputum). In fact in the 1987 CDC definition of AIDS there are so many degrees of freedom, that nearly any lung disease can be diagnosed as PCP. (Below there is an abstract of an article published in Continuum with such a case).
In his rapid response: "Re: 'HIV", Factor VIII and CD4s", 19 October, Peter Flegg wrote: "HIV seronegative haemophiliacs or drug users only extremely rarely develop AIDS-defining conditions like Pneumocystis. Since the Perth Group insist that they do, then they should be able to provide us with numerous references showing not just small case series or sporadic cases of this phenomenon, but many thousands of cases (to match the tens of thousands of cases of PCP reported in HIV-infected patients).
Can they please do so?
Can they also explain why PCP occurs in HIV positive recipients of blood products, but not in HIV-negatives?
Can they explain why PCP occurs in HIV positive drug users, but not in HIV-negatives?
Can they explain why PCP occurs in HIV positive heterosexuals, but not in HIV-negatives?
Can they explain why PCP occurs in HIV positive homosexuals, but not in HIV-negatives?"
Would Peter Flegg please give us a major randomised, blind study and a few confirmatory studies with evidence showing that PCP occurs in "HIV" positive recipients of blood products, drug users, heterosexuals and homosexuals but not in "HIV" negative recipients of blood products, drug users, heterosexuals and homosexuals.
In all our publications, and in this debate, we have claimed that a positive "HIV" antibody test is a non-specific indicator, serendipitously discovered in 1983/84, of altered homeostasis connoting a propensity to develop particular diseases including PCP.
Anti-lymphocyte antibodies and ESR[5-8] are equally as good predictors of AIDS, and thus PCP, as is a positive "HIV" antibody test. Would Peter Flegg claim that lymphocytes and the factors (such as rouleaux formation which may result from changes in the negative charge of red cells), which cause and increase ESR are the cause of AIDS and thus PCP?
In 1990 Peter Flegg wrote: "We conclude, therefore, that IgG anti-cardiolipin antibodies are associated with HIV infection per se. Indeed, an unexplained positive anti-cardiolipin antibody result should perhaps be regarded as an indication for testing for antibodies to HIV".
Since antibodies which react with cardiolipins are a predictor for a positive "HIV" antibody test and thus for AIDS and PCP, should one conclude that cardiolipin or Treponema pallidum is the cause of AIDS (PCP)?
The only evidence which the "HIV" experts have in support of their claim that "HIV" is the cause of AIDS, is the positive predictive value of the antibody test.
However, as we stated many times before (something which the "HIV" experts including Peter Flegg chose to ignore) the question is not if a positive "HIV" antibody test is an indicator for present or future development of AIDS, but does it prove infection with "HIV". The absolutely necessary but not sufficient condition for any scientist worth his salt to claim or accept that "HIV" is the cause of AIDS, is evidence that a positive antibody test is proof of infection. In this debate, we have drawn the attention to the "HIV" participants, including Peter Flegg, that according to the test kits manufacturers and, most importantly, to some of the best known experts in "HIV" testing, at present no evidence exists that a positive test means infection. For some unknown reason all of them, including Peter Flegg, have ignored this fact. We asked them to provide evidence that the "HIV" antibody tests are specific. So far no such evidence has been forthcoming.
If Peter Flegg and his colleagues fail to provide such evidence, then we must conclude that their argument for a causal relationship between "HIV" and AIDS (PCP), based on a correlation between a positive antibody test and AIDS, collapses and any further debate is superfluous.
1. Flegg PJ, Willocks LJ, Brettle RP, Bird AG. Investigation of pulmonary disease in HIV infection. Thorax 1990;45:777.
2. Willocks L, Cowan F, Brettle RP, Emmanuel FX, Flegg PJ, Burns S. The spectrum of chest infections in HIV positive patients in Edinburgh. The Journal of Infection 1992;24:37-42.
3. Hughes WT. Pneumocystis carinii pneumonitis. N Engl J Med 1987;317:1021-1023.
4. Anti-lymphocyte antibodies and progression of disease in HIV infected patients. VII International AIDS Conference; 1991; Florence.
5. Arango CA, Midani S, Alvarez A, Kubilis PS, Rathore MH. Usefulness of acute phase reactants in the diagnosis of acute infections in HIV-infected children. Southern Med J 1999;92:209-13.
6. Monsuez JJ, Dufaux J, Vittecoq D, Flaud P, Vicaut E. Hemorheology in asymptomatic HIV-infected patients. Clin Hemorheol Microcirc 2000;23:59-66.
7. Morfeldt-Manson L, Bottiger B, Nilsson B, von Stedingk LV. Clinical signs and laboratory markers in predicting progression to AIDS in HIV-1 infected patients. Scand J Infect Dis 1991;23:443-9.
8. Lefrere JJ, Salmon D, Doinel C, Rouger P, Courouce AM, Lambin P, et al. Sedimentation rate as a predictive marker in HIV infection. AIDS 1988;2:63-4.
9. Maclean C, Flegg PJ, Kilpatrick DC. Anti-cardiolipin antibodies and HIV infection. Clin Exp Immunol 1990;81:263-6.
TB or not TB: John Kennedy's unnecessary death
by TOM ASHFORD
…John first got ill in August when we returned form holiday in Greece. His chest was tight, sore and restricted, so he went to see his GP who told him he was suffering from pollution, prescribed an antihistamine drug and advised him to get out of London. He went straight to Ireland. Three days later he was in hospital fighting for his life.
PCP was diagnosed, without a sputum test, a bronchoscopy or any explanation as to why John's chest was so painful – such pain is not usually associated with PCP. DF118s were prescribed, along with steroids, two antibiotics and oxygen therapy. Well, the X-ray "said" PCP – not TB, not another chest infection, but PCP – well, it's an AIDS-defining illness, this patient has HIV, it's a logical conclusion and we know best.
Radiographically John was clear after three weeks. Literally, he was still very unwell and still had a searing pain in his chest, which the consultant could not explain…So to London, and St Tommy's a week later, where John was told the PCP was back. They did an X-ray and PCP doesn't look like anything else – does it? So, the same antibiotics with no steroids, no oxygen, were administered and, after 11 days at home, I had to wheel John into hospital. He was very ill and, on top of his illness, he had a dreadful reaction to the drugs. Once again, he was admitted with a PCP diagnosis. He was put straight onto Pentamidine to which, after a week, he had still not responded and the doctors told me that he might die.
It was then that they decided to do a bronchoscopy and lo, "abnormal amounts" of CMV were reported, and very abnormal amounts of Ganciclovir were administered, and once where natural blood was flowing there were not outrageous amounts of toxic drugs. John was told by one of the most eminent consultants that they never found PCP but they treated for it anyway. John thanked them for their kind consideration.
Whilst feeling understandably at a very low ebb John contracted pseudomonas from the hospital and was moved to his own room. It was a pleasant room with a sunny disposition and a wonderful view over south London. His neighbour was a lovely girl who spent most of her time in bed. "You look awful," I remember thinking as I passed her room, and she would look out with an expression is her eyes of, "Oh my god! What is wrong with me? Why can't they find out what is wrong with me?" There were times when she obviously felt better because I would see her struggling down the ward with her drip as a walking stick, stopping to cough every now and again. Little did I know that she was coughing and spluttering MDR-TB all over me, John and the whole ward.
After a four week stay at St Tommy's, John went to stay at the London Lighthouse for respite care. He was doing amazingly well and the doctors were astonished that he had bounced back. I was relieved and everything was on the up. We spent Christmas together up north and travelled back a week after New Year. By this time, John's hair was falling out and he had a red rash all over his face. He wasn't feeling too well either, so he revisited St Tommy's. When he came back home that evening, he was crying and he told me that the doctors said that the PCP had come back….For the next ten weeks John's condition slowly deteriorated…His temperature often went up to forty degrees centigrade. He was dizzy, had no appetite and we were on a desperate and futile course of popping pills that did nothing, trying to stay positive in the face of extreme circumstances. The period culminated in yet another admission to St Thomas' where John's treatment was for Mycobacterium avium intracellulare (MAI). It was after 3 weeks of John being in isolation that the microbiologist came up with MDR-TB – the strain matched his neighbour's at St Tommy's from the previous November – and John was moved to Kings College where they had proper isolation rooms…He died three weeks later…I'm disgusted at John's treatment, tired and weary after having fought a long and losing battle, not to mention the loss of my partner – and so unneccessarily too. And I know that if the specialists didn't constantly jump to conclusions, refuse to listen and insist on their "we know best" attitude, then I wouldn't be writing this and you wouldn't be reading it.
Competing interests: None declared