AIDS IN THAILAND
An appraisal of the data professing proof of heterosexual transmission
Eleni Papadopulos-Eleopulos (1) Valendar F.Turner (2) David Causer1 John M. Papadimitriou (3)
(1) Department of Medical Physics, (2) Department of Emergency Medicine, Royal Perth Hospital, Perth, Western Australia; (3) Department of Pathology, University of Western Australia.
Rejected by two journals 1995
The data cited as evidence for widespread HIV infection of Thai men by heterosexual contacts has been critically analysed. It is concluded that these data do not prove that Thai men acquire HIV by sexual contact with prostitutes specifically or by heterosexual contact in general.
Since 1984, it has been generally accepted that HIV and AIDS are bidirectionally, sexually transmitted. This is the main reason for the prediction that AIDS will eventually become an epidemic worse than the pandemic of bubonic plague that afflicted Europe and Asia in the fourteenth century and caused over 50 million deaths. Nonetheless, in the West, AIDS still remains restricted to the original risk groups, that is, gay men, intravenous drug users and haemophiliacs treated with clotting concentrates. Until recently, data obtained from Africa have been presented as evidence supporting the claim for bidirectional sexual transmission of both HIV and AIDS but lately HIV/AIDS researchers claim additional evidence from Thailand (Cohen 1994). In what follows we will analyse the data from Thailand that has been published in scientific publications in the West regarding sexual transmission of HIV. The African data have been examined previously in this journal (Papadopulos-Eleopulos et al. 1995a).
"The epidemic in Thailand"
In a study conducted in June 1989 by researchers from the Ministry of Public Health, Bangkok, 44 out of 100 (44%) prostitutes from 7 brothels tested in the northern Thai province of Chiang Mai were found to be seropositive. In the 13 other provinces surveyed seropositivity ranged from 0% to 5%. In August 1989 researchers tested another 238 prostitutes from 14 brothels in the Chiang Mai province and found the HIV seroprevalence rate to be 36.5%. "Univariate analysis of all 238 subjects showed a significant association between HIV seropositivity and increasing frequency of sexual intercourse, lower charges for sexual service, lower rate of condom use by male clients, and genital cleansing with water alone. Subjects with a history of venereal disease, positive VDRL, low education level, history of drug use, and opiate-negative urine sample were more frequently HIV-positive, but the difference was not statistically significant. No associations with HIV serostatus were found for mean age, duration of prostitution, marital status, contraceptive practice, or other sexual practices" (Siraprapasiri et al. 1991).
In 1993, two papers were published with evidence from Thailand which the authors claimed proved transmission of HIV from women to men. Both studies were cross-sectional, one was conducted by researchers from The John Hopkins University, Baltimore, USA, the Chiang Mai University, Thailand, and the Royal Thai Army (Nelson et al. 1993), and the other by researchers from "The HIV/AIDS Collaboration, Bangkok", of the Thailand Ministry of Public Health and the US Centres for Disease Control and Prevention (Nopkesorn et al. 1993).
The diagnosis of the first AIDS case in Thailand (according to Nopkesorn et al. this took place in 1984 and to Nelson et al. in September 1985) led to the establishment of "semiannual routine serological surveillance for human immunodeficiency virus (HIV) among several risk groups throughout the country, beginning in 1989. The risk groups included "injecting drug users", female "commercial sex workers", (CSW), "male sexually transmitted disease (STD) clinic patients, pregnant women attending antenatal clinics, and blood donors". In addition, in the same year 1989, "the Royal Thai Army established routine serological testing of all potential military conscripts". Because:
(A) Of the total of 642 AIDS cases in Thailand reported through June 1992, "70% (449 out of 642) were heterosexually transmitted; IDU [injection drug users] comprised 10% of all cases (n=64), and homosexual/bisexual men accounted for 6% (n=39)", that is, heterosexual transmission was the major risk factor (Celentano et al. 1993),
(B) "A consistent finding in HIV-1 serosurveys of groups with sexual risk factors for infection has been high infection rates in the northern region" of Thailand;
Nelson et al. evaluated young men in northern Thailand at the time of their entry into the military in May 1991 and November 1991. "In addition to serological screening for antibodies to HIV and syphilis, each recruit underwent a face-to-face interview with a trained interviewer, a Chiang Mai University medical student, who was not connected with the military. This interview included questions on sociodemographic status; lifetime and recent (ie, in the last year) sexual experiences with females and males; frequency of sexual contact with female CSW, girlfriends, or spouses; use of condoms; medical history, including STDs and surgery; use of illicit drugs by injection or other routes; tattoos; alcohol and tobacco use; and blood transfusion and donation". Of 2417 men tested, 289 (12%) "were HIV-seropositive". "Syphilis seroprevalence was 4.0% (96/2417)". "Sociodemographic characteristics associated with HIV infection included a history of 4 years or less of formal education (ie. primary school or less) and a history of employment...Several behavioural variables were significantly associated with HIV prevalence. A history of cigarette smoking and alcohol and marijuana use were significantly associated with prevalent HIV infection on univariate analysis. However, the strongest association was detected with sexual behaviour. In particular, a history of sexual intercourse with a female was the strongest predictor of HIV infection, with an OR of 13.7. Nearly all those who were HIV-seropositive reported having had sexual contact with a female. In contrast, sex with another male was reported by only 3.0% (73/2417) of the subjects and was not associated with HIV prevalence. In addition, injection of illicit drugs was rare and independent of HIV infection in this population...A history of an STD was strongly associated with HIV seroprevalence...History of sex with a female CSW was strongly associated with HIV infection; 96.5% of HIV-seropositive men gave a history of sexual contact with a CSW" [OR=odds ratio].
They concluded : "The quantitative relationship between sexual contact with female CSW and the rate of HIV infection indicates that this behaviour is a dominant risk for HIV infection in this population". Like Nelson et al., Nopkesorn and his associates (1993), including Weniger, in May 1991 tested 1115 young men selected by lottery for conscription in Northern Thailand: "In general, men become eligible for conscription on their 21st birthday and are chosen by a random lottery system based on legal registration address. Middle and upper-class men, a small minority of those eligible, often obtain educational deferments and other exceptions from participation in the lottery". These men, "voluntarily completed a confidential, self-administered, Thai-language questionnaire addressing the following areas: demographics, sexual behaviour, condom use, history of STD, other HIV risk factors and knowledge and attitudes about HIV and AIDS...Participants were predominantly young, unmarried men with < 6 years of education who worked as farmers or labourers...Seventy-seven (6.9%) men were HIV-1 seropositive. Another four (0.4%) were EIA-positive and WB-indeterminate. Sexual intercourse was reported by 90.9% of the men: 79.6% reported sex with women only, 10.9% with men and women and 0.4% with men only. Sex with a female prostitute, ever, was reported by 74.7% of men and was highly associated with HIV-1 infection...Factors not significantly associated with HIV-1 infection included anal sex with men, ever, reported by 126 (11.3%) men: 111 (10.0%) reported insertive and 46 (4.1%) reported receptive anal sex. None of the 46 men who reported receptive anal sex was HIV-1 seropositive, compared with eight (10.0%) of the 80 men who reported only insertive anal sex with a man (P = 0.03)...Risk factors for HIV-1 infection were evaluated in a multiple logistic regression analysis. Birth in a province in the upper north subregion, rural residence, non-married status and self-reported STD (with a very strong trend for increased number of STD syndromes) were associated with HIV-1 infection", Weniger and his associates concluded:
"This study indicates that men are at high risk for HIV-1 infection via a very common behaviour, sex with female prostitutes".
(1) "History of sex with a female CSW was strongly associated with HIV infection; 96.5% of HIV-seropositive men gave a history of sexual contact with a CSW";
(2) "A history of STD symptoms was the factor most strongly associated with HIV-1 infection" (ie, positive WB);
the two groups concluded that the men were infected with HIV and that they were infected by having sex with prostitutes.
Using the data from the 1115 conscripts the CDC workers "estimate that the probability of female-to-male transmission of HIV-1 per sexual contact in the epidemic in northern Thailand was 0.031 [1/33] (95% CL 0.025-0.040). When we allowed for random measurement error in the self-reported frequency of contacts, the estimate was 0.056 [1/18] (95% CL, 0.041-0.075). These estimates are an order of magnitude greater than analogous estimates made in North America of about 0.001 [1/1000] for male-to-female transmission" (Mastro et al. 1994).
In 1994 Jean Carr (Carr et al. 1994) from the Henry M. Jackson Foundation, Maryland, USA and her associates from the Royal Thai Army, Bangkok and the Walter Reed Institute of Research U.S. Army, reported their results on 17,409 seronegative enlistees, "tested for HIV-1 seropositivity prospectively in order to explore their feasibility on a cohort in an HIV-1 preventative vaccine efficacy trial". Cohorts were enlisted in November 1991 and May 1992 from northern Thailand and Bangkok.
The November 1991 cohort was re-tested in August 1992 and again in February 1993. The May 1992 cohort had one follow-up visit, in February 1993. The authors do not give their criteria for defining a positive WB. They only stated that samples which were found twice reactive in ELISA, were re-tested with WB, at the Armed Forces Research Institute of Medical Science, Bangkok. "When the ELISA was positive but the Western blot was indeterminate, the recombigen assay (Cambridge Biotech) was performed, and the result was considered definitive".
Fifty per cent of the enlistees were lost to follow-up. "A higher proportion of the recruits who were lost to follow-up were stationed in Bangkok and the lower north, were from urban areas, were better educated, and were married. The recruits who are included in the following incidence analysis were disproportionately from the upper north, rural, single, and less well educated....... A total of 133 people seroconverted during the period of observation...... In addition to the 133 individuals who seroconverted, 19 individuals seroreverted...... The relative risk of infection was increased almost 20-fold if the recruit was born in the upper north. This finding implies that the most important risk to the recruit is the location of birth rather than the location of the military base".
Carr et al. concluded: "It is clear from both prevalence and incidence studies that the upper north of Thailand is experiencing an intense epidemic of HIV-1 infection. The reason for the geographical concentration of the HIV-1 epidemic to the upper north of Thailand is fundamentally unknown".
The above researchers interpreted clinical/epidemiological and serological data as proof of transmission of HIV from infected female sex workers to uninfected men. These conclusions can be questioned on several grounds.
A. Clinical/epidemiological evidence
1. "nearly 80% of men who were HIV-negative" also "reported having had sex with a female CSW",
2. From such studies, it is impossible to determine if one infectious agent is transmitted from men to women or vice versa. If the men were infected by having sex with the CSW, and if in Thailand IV drug use and homosexuality are not significant in the spread of HIV, how did the CSW become infected? If the first AIDS cases in Thailand were reported in 1984/85 why, by 1989 were more than 30% of non-drug using prostitutes in Thailand infected with HIV when, even in 1990, no non-drug using prostitutes have been found HIV positive in Spain (Pineda et al. 1992), the United Kingdom (Carr et al. 1992), Israel (Modan et al. 1992), and New Mexico (Tabet et al. 1992)?
3. There was no laboratory confirmation of the STD history. Nelson et al. "attempted to elicit accurate history of specific STD diagnosis by description of the clinical symptomatology by the medical student interviewer which included the use of pictures depicting the appearance of the lesions". In the Weniger et al. study, "Study personnel provided pre-test counselling, explained the questionnaire to the participants, supervised its administration and explained questions to men requesting assistance...STD questions used well-known Thai terms for urethritis (nong nai: 'pus comes out'), genital ulcer (plae ab-wai-yawab phed: 'sore on penis'), inguinal mass (phee mamoong: 'mango abscess') and genital warts (ngon ghai: 'cock's comb)". One must question the validity of STD diagnosed retrospectively, without obtaining an isolate or other laboratory confirmation and employing self-diagnosis assisted by pictures and medical students.
When the men had VDRL tests for syphilis, 4.0% were found positive compared to 12% for HIV. This means that:
(a) although the men needed help to recognise STD symptoms and signs, they asked for and promptly received treatment for syphilis before the study began or,
(b) in Thailand, HIV is more efficiently transmitted from women to men than Treponema pallidum or,
(c) there was no relationship between sexual contact and a "positive WB".
The finding that "none of the 46 men who reported receptive anal sex was HIV-1 seropositive, compared with eight (10.0%) of 80 men who reported only insertive anal sex with a man (P = 0.03)", is completely at odds with all the presently available data from the large and well designed prospective studies of gay men in the USA and Europe which have shown that, "the cited reports yield convincing evidence that unprotected anogenital receptive intercourse poses the highest risk for the sexual acquisition of HIV-1 infection...there is mounting epidemiologic evidence for a small risk attached to orogenital receptive sex, biologic plausibility, credible case reports and some studies show a modest risk, detectable only with powerful designs;...no or no consistent risk of the acquisition of HIV-1 infection has been reported regarding insertive intercourse and oroanal sex" (Caceres & van Griensven 1994). Thus, the only sexual act which leads to seropositivity is receptive anal intercourse, (and perhaps receptive oral intercourse).
The only reliable evidence from North America or anywhere else, regarding "female-to-male transmission of HIV", is found in Nancy Padian's prospective study of heterosexual couples where, from a cohort recruited from 1985 to March 1991 involving 72 male partners of HIV infected women, there was "one probable instance" of female-to-male transmission (Padian et al. 1991). This means that either there is something fundamentally wrong with the serological data (or its interpretation), or that not only HIV is unidirectionally transmitted but it is transmitted in one direction in one continent and the opposite in others.
According to Nelson et al.: "It would seem likely that the associations between HIV infection and alcohol and marijuana use in univariate analysis occurred primarily because of the effect these behaviours had on the frequency of sexual contact with a CSW and their role in preventing the effective use of a condom during such contact". However, both groups found a direct relationship between a positive WB and condom use, "increased condom use was associated with an increased risk for HIV-1", "indeed, those who reported ever having used a condom with a CSW had a higher HIV prevalence". This finding also means (if as the authors of the two studies claim a positive WB is proof that the men have been infected with HIV by CSW), that unlike all sexually transmitted agents HIV is more efficiently transmitted with condoms than without them.
B. Serological evidence
In all the studies from Thailand a positive WB is considered synonymous with HIV infection although such a claim is not supported by the presently available data. When the antibody tests were introduced to define HIV infection, Montagnier and his colleagues considered the presence of a p24 band as the only HIV specific band. In contradistinction, Gallo and his colleagues considered only the presence of antibodies to the glycoprotein gp41 specific to HIV. (When the Western blot was initially introduced for diagnostic purposes only the gp41 band could be detected. Later, when the test conditions were modified, the gp120 and gp160 bands could also be detected). Both Montagnier's and Gallo's interpretations are at odds with the knowledge available in the early 1980s. As far back as 1970 one of Montagnier's collaborators, Philippe Vigier from the Institut du Radium (Biologie), Faculté des Sciences, Orsay, wrote: "Whereas antigenicity of the viral envelope may differ between avian tumor viruses, all cells transformed or only infected by these viruses contain a common group-specific (gs) antigen detectable by complement fixation with serum of hamsters bearing RSV-induced sarcomas...Moreover, the origin of the internal gs antigen of avian viruses, and consequently of murine viruses, may not be as obvious as stated. This is suggested by the finding of an apparently identical antigen in chicken cells free of visible virus-like particles" (Vigier 1970). In 1974, Gelderblom and his colleagues wrote: "While the virus envelope antigens are primarily virus-strain specific, the bulk of internal proteins of the virion with molecular weight (mw) between 10,000 d and 30,000 d are group-specific (gs) for viruses originating in a given animal species (gs-spec. antigens). The major protein constituent of mammalian C-type oncornaviruses with a molecular weight in the range of 30,000 d was found to possess, besides gs spec. antigen, an antigenic determinant that is shared by C-type viruses of many mammalian species including monkeys and was thus termed gs interspecies (gs-interspec.) antigen" (Bauer et al. 1974). Thus, even if p24 and antibodies present in human sera which react with it are specific to a human retrovirus, they cannot be considered HIV specific.
In a paper published in 1981 Gallo and his colleagues acknowledged that antibodies which react with the retroviral glycoproteins are not directed against the virus coded polypeptide portion "but against the carbohydrate moieties on the molecule that are introduced by the host cell as a post-transcriptional event, and which are therefore cell-specific and not virus-specific" (Kalyanaraman et al. 1981).
Notwithstanding, while Montagnier's and Gallo's groups advocated different HIV specific bands, the CDC considered the presence of either the p24 or the gp41 bands indicative of HIV infection. However, by 1987 it was realised that antibodies which react with p24 are widespread in human sera. Since then, very few laboratories consider the presence of the p24 band as proof of HIV infection with the possible exception of Montagnier's group, and the authors of the Multicenter AIDS Cohort Study (Detels et al. 1989) who, in 1989, defined a positive Western blot by the following criteria: "0 was assigned for each negative band, 1 for each weakly reactive band, and 3 for each band strongly reactive to p15, p24, p31, p41, p45, p53, p55, p64 or p120 proteins. The scores of all bands were summed...greater than or equal to 3 was defined as positive serum; a score less than 3 was considered negative". However, to date, the specificity of the HIV antibody tests has not been verified by use of viral isolation, the only valid independent gold standard for the antibody tests. Furthermore, considering the many problems associated with HIV isolation this may not even be feasible (Papadopulos-Eleopulos et al. 1993a, b, 1995c). The generally accepted "specificity of roughly 99.9993 percent" has been obtained without use of a gold standard (Weiss & Thier, Burke et al. 1988). An additional problem with the use of "virus isolation" as a gold standard is the fact that HIV cannot be "isolated" from all antibody positive patients. The success rate varies between 17% and 80% (Chiodi et al. 1988, Ehrnst et al. 1988, Learmont et al. 1992). While genetic techniques are employed for the diagnosis of HIV infection they are highly problematic. With the polymerase chain reaction (PCR) "only small regions may be amplified, a gene at best" (Wain-Hobson 1989) and since the majority of HIV "isolates" studied to date are defective, that is, they lack one or several genes, finding a gene is not proof of the existence of the whole genome. Even if the whole genome were present this still is not proof of the presence of a retroviral particle because the genome may not be expressed. Notwithstanding these already considerable difficulties, in a recent study conducted at seven French laboratories "with extensive experience in PCR detection of HIV DNA", the HIV PCR was found to be non-reproducible and the "concordance with serology ranged from 40 to 100%". Furthermore, of 121 blood samples with "unequivocal" positive HIV ELISAs and Western blots obtained from "stage II of the Centers for Disease Control classification of HIV-1 seropositive individuals", 17 (14%) had a negative HIV PCR (Defer et al. 1992).
Even well known HIV/AIDS researchers concede that the specificity of the HIV "antibodies remain imprecise" (Blattner 1989) and "it may be impossible to relate an antibody response specifically to HIV-1 infection" (Mortimer, 1989). Elsewhere, evidence has been presented that the Western blot is non-specific for HIV infection Papadopulos-Eleopulos et al. 1993a), and in that in at least two AIDS risk groups, haemophiliacs and Africans, a positive Western blot cannot be considered proof of HIV infection (Papadopulos-Eleopulos et al, 1995a, b) and that HIV cannot be the cause of AIDS in haemophiliacs (Duesberg 1995, Papadopulos-Eleopulos et al, 1995b) or considered to be the proven cause of AIDS in Africa (Papadopulos-Eleopulos et al, 1995a). Here, some additional supporting evidence as well evidence directly related to Thailand is presented:
(a) "Uninfected persons applying as potential volunteers for the phase 1 studies of candidate vaccines conducted by units of the AIDS Vaccine Clinical Trials Group are frequently noted to have one, or a few, Western blot bands before vaccination [with a gp160 vaccine]...The presence of p24 bands was common" (Belshe et al. 1994);
(b) of a total of 144 canine sera "obtained from the Veterinary Medical Teaching Hospital, University of California, Davis" tested in commercial Western blot assays, "72 sera (50%) reacted with one or more HIV recombinant proteins [gp120--21.5%, gp41--23%, p31--22%, p24--43%]" (Strandstrom et al. 1990);
(c) antibodies present in human sera which react with HIV glycoproteins are non-specific:
(i) "One half of the molecular weight of gp120 is represented by oligomannosidic oligosaccharides...Polyclonal antibodies to mannan from yeast also recognize the carbohydrate structure of gp120 of the AIDS virus" (Muller et al. 1990);
(ii) in a paper published by Tomiyama et al. in 1991 entitled "Recognition of human immunodeficiency virus glycoproteins by natural anti-carbohydrate antibodies in human serum", it was shown that "normal human serum contains antibodies capable of recognizing the carbohydrate moiety of HIV envelope glycoproteins...from 100ml of human serum approximately 200ug of MBIgG was recovered [MBIgG=mannan-binding IgG]...MBIgG bound to HIV envelope glycoproteins gp160, gp120 and gp41".
(d) In a paper published in 1994, Kashala, Essex and their colleagues presented evidence that antibodies to carbohydrate containing antigens such as lipoarabinomannan and phenolic glycolipid that constitute the cell wall of Mycobacteria leprae, a bacterium which "shares several antigenic determinants with other mycobacterial species" cause "significant cross-reactivities with HIV-1 pol and gag proteins". This led the authors to warn that among leprosy patients and their contacts there is a "very high rate of HIV-1 false-positive ELISA and WB results", that "ELISA and WB results should be interpreted with caution when screening individuals infected with M. tuberculosis or other mycobacterial species", and furthermore that "ELISA and WB may not be sufficient for HIV diagnosis in AIDS-endemic areas of Central Africa where the prevalence of mycobaterial diseases is quite high" (Kashala et al. 1994);
(e) AIDS is accompanied by polyclonal immune activation and the B cells of AIDS patients "manifest abnormal activation reflected by increased spontaneous proliferation and immunoglobulin secretion", a state characterised by "hypergammaglobulinaemia and by the presence of circulating immune complexes and autoantibodies (Fauci & Lane, 1994);
(f) Using a panel of synthetic peptides from the amino acid consensus sequences of HIV gp120, gp41 and p24 Vittorio Colizzi and his colleagues in Rome found that:
(i) In the murine model of autoimmunity, sera from 8 month old MRL/lpr mice bound to all HIV peptides;
(ii) "sera from CBA mice immunised either with BALB/c or C57BL/6 allogenic lymphoid cells showed a significant reactivity with all the tested peptides except for the HIV p24/p59 when the CBA anti-BALB/c sera were used";
(iii) similar binding "was observed with sera from BALB/c mice injected with lipopolysaccharides suggesting that the presence of anti-HIV antibodies may be associated with polyclonal activation" (Personal communication, F. Franchi);
(iv) sera from 29 patients with Sjorgen's syndrome (SS) and 25 with systemic lupus erythematosus (SLE) who were positive for antinuclear antibodies were also tested. Three of fourteen (21.4%) SS sera and 2/20 (10%) of SLE sera reacted with gp41;
(v) "Sera from 62 HIV-negative polytransfused patients with Thalassemia receiving at least ten transfusions/year were tested against" a peptide encompassing the gp120 V3-loop. Twenty two, (35%) of these patients reacted.
(g) If the antibodies present in sera are specific for the "HIV particles" then one would expect the sera to react with both the budding, immature particles and the mature, cell-free particles and no other cellular components. However, according to Gelderblom and his colleagues who put forward the well known structural model for HIV, mature particles are "hardly, if at all, labelled" by sera from patients with AIDS or ARC. Immature particles are "highly labelled", but so is the rest of the cell from which they are budding. This, the authors conclude, "might be due to the fact that natural immune sera are indeed polyspecific" (Hausman et al. 1987, Gelderblom et al. 1985, 1987).
Even if there was evidence in other studies that the specificity of the HIV antibody tests was very high, such a finding may not be valid for the studies in Thailand. This is because:
1. In Thailand "HIV-seropositivity" is apparently restricted to the northern provinces of the country and although all groups expressed the view that "The reason for the higher HIV infection rates in northern Thailand than in other parts of the country is unclear", Weniger and his associates added: "the northern region, where Thailand is bordered by Myanmor (Burma) and Laos...is adjacent to the 'Golden Triangle', one of the world's major opium and heroin-producing areas...Questionnaires were self-administered in a non-anonymous manner to men of generally low educational background. It may be expected that stigmatised behaviour, such as illicit drug use and homosexuality would be under reported". In a separate publication Nelson and his colleagues sought to identify behavioural and sociodemographic risk factors for patterns of CSW visits among their 2417 conscripts. Among other factors they "analysed the association of substance use on frequency of CSW visits. We included in these analyses use or non-use of alcohol, marijuana, inhalants, cocaine, heroin/opium, sedatives and hypnotics, and stimulants as well as cigarette smoking". The authors found that "All substances included in our questionnaire (alcohol, marijuana, other illicit drugs and cigarette smoking) were significantly associated with frequent CSW use in bivariate analysis, and were independently predictive of lifetime CSW use" (Celentano et al. 1993).
Before the AIDS era it was known that drug users often had false positive tests, including antibody tests. As far back as 1986 Jaffe and his colleagues wrote, "It is also recognised that asymptomatic parenteral drug abusers often have hypergammaglobulinemia, high titers of immune complexes, a high prevalence of positive tests for rheumatoid, and high rates of false positivity on a number of routine laboratory tests...On the basis of our positive Western blot data, it appears possible that parenteral drug abusers may have been exposed to HTLV-III or a related virus as early as 1971. An alternative but equally viable explanation is that the HTLV-III seropositivity detected in these specimens represents false positive or nonspecific reactions" (Jaffe et al. 1986). The fact that a higher per cent of individuals who use non-IV cocaine than those who use it IV have a positive WB, suggest that the latter may indeed be the case (Sterk 1988).
2. In a 1992 WHO publication one reads: "The global incidence of malaria is estimated to be nearly 120 million clinical cases each year, with nearly 300 million people carrying the parasite. 90% of the total number of cases reported annually to WHO are from only 19 countries. This does not include the WHO African Region where reporting of cases remains fragmentary and irregular despite improvements in recent years. Some 75% of cases are concentrated in 9 countries (in decreasing order): India, Brazil, Afghanistan, Sri Lanka, Thailand, Indonesia, Vietnam, Cambodia and China. Furthermore, within these countries malaria is concentrated in certain areas...1.7 billion people (32%) live in areas where endemic malaria was considerably reduced or even eliminated but transmission was reinstated and the situation is unstable or deteriorating. These latter areas include zones with the most severe malaria problems which developed following major ecological or social changes, such as agricultural or other economic exploitation of jungle areas, sociopolitical unrest, etc" (WHO 1992). One year later, in a study conducted in 3 northern Thai villages, the author wrote: "Data and observation indicate that land-poor families forced into sudden farming have greater contact with the primary vectors in Thailand...In addition to agricultural activities on clearings near forested areas, clandestine forest activities and cross border traffic contributes to the prevalence of malaria in the Thai border villages" (Singhanetra-Renard et al. 1993). Evidence available as far back as 1985 has shown that malaria is associated with false positive HIV antibody tests (Biggar et al. 1985, Rodriquez et al. 1985, Volsky et al. 1986).
3. Like malaria, TB and to a lesser extent leprosy are also common in Thailand. "In 1990 an estimated 8 million people developed tuberculosis worldwide and 2.6 to 2.9 died. The majority of these cases and deaths occurred in Asia" (Sudre et al. 1992). According to registered cases, the prevalence of leprosy cases in Thailand in 1987 was 0.537 per 1,000. "However, the estimated prevalence rate by random survey is approximately twice the number of registered cases" (Montreewasuwat & Peerapakorn 1988). As already mentioned, no lesser an authority on HIV/AIDS than Myron Essex stated that the sera from patients with disease induced by Mycobacteria cause "significant cross-reactivity with HIV-1 pol and gag proteins" and other researchers have shown that antibodies directed against mannans as well as antibodies present in normal human sera cross-react with the env proteins, gp160, gp120 and gp41.
4. Even if there were some studies in which it was shown that the specificity of the WB was 100% as Nelson et al. and Nopkesorn and his colleagues assume, this may not have been the case in the studies from Thailand since different studies use different criteria to define a positive test. Nelson and his colleagues do not give the criteria they used to define a positive WB, they only state that the ELISA assays were "confirmed with Western Blot using commercially licensed reagents". Siraprapasiri et al. also do not say what criteria they used to define a positive WB. However they do say that at least some of the tests were "re-confirmed by WB at the World Health Organisation (WHO) Collaborating Centre for AIDS in Bangkok". The WHO criteria, which apparently are not used by any Western country, consider a serum positive for HIV-1 antibodies if "two envelope glycoprotein bands (with or without) other viral specific bands are present on the strips". For Nopkesorn and his associates, "Samples were considered positive on WB if antibodies were detected to any two of the following three antigens: p24, gp41 or gp120/160". This is the least "stringent" criteria used by any Western laboratory. According to the Consortium for Retrovirus Serology Standardisation, "A positive result will usually be reflected in the presence of typical bands at p24, p31, gp41 and gp120/160, but at a minimum bands should be present at p24 or p31 and gp41 or gp120/160". By the Weniger criteria, like the WHO criteria, a person can be deemed HIV positive by having gp41 and gp120/160 bands. However as far back as 1989, it was shown that in Western blot strips gp160 and gp120 are oligomers of gp41. The same researchers have also shown that the WB pattern obtained is dependent on many factors including temperature and the concentration of sodium dodecyl sulphate used to disrupt the "pure virus", and concluded: "Confusion over the identification of these bands has resulted in incorrect conclusions in experimental studies. Similarly, some clinical specimens may have been identified erroneously as seropositive, on the assumption that these bands reflected specific reactivity against two distinct viral components and fulfilled a criterion for true or probable positivity. The correct identification of these bands will affect the standards to be established for Western Blot positivity: it may necessitate the reinterpretation of published results" (Pinter et al. 1989, Zolla-Pazner et al. 1989). Thus, many HIV positive Thais would not be HIV positive in the West.
In conclusion, unless and until the specificity of the HIV antibody tests in Thailand is determined it cannot be assumed that Thais are infected with HIV. Whatever the cause of "HIV seropositivity", cross-reactivity or other reactivity, its relationship to sexual activity, in particular, men having sexual intercourse with women, it is not discernible by the present data. The serological and epidemiological findings from Thailand are not proof that Thai men acquire HIV from "infected" female sex workers.
We would like to thank all our colleagues and especially Richard Fox, Bruce Hedland-Thomas, Alun Dufty, Gary James, Iris Peter, Peter Henson, Jennie Brooks, Michael Hart, Hiram Caton, Todd Miller, James Whitehead, Fabio Franchi, Harvey Bialy, Charles Thomas, Peter Duesberg, Neville Hodgkinson and the clerical staff of the Department of Medical Physics and the staff of the Royal Perth Hospital Library.
Bauer, H., Daams, J. H., Watson, K. F., Molling, K., Gelderblom, H. & Schafer, W., 1974. Oncornavirus-like particles in HeLa cells. II. Immunological characterization of the virus. International Journal of Cancer 13, 254-261.
Belshe, R., B., Clements, M., L., Keefer, M., C., Graham, B., S., Corey, L., Sposto, R., Wescott, S. & Lawrence, D. 1994 Interpreting HIV serodiagnostic test results in the 1990s: Social risks of HIV vaccine studies in uninfected volunteers. Annals of Internal Medicine 121, 584-589.
Biggar, R.J., Gigase, P.L., Melbye, M. et al. 1985 ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans. Lancet ii, 520-523.
Blattner, W.A. 1989 Retroviruses. in Viral infections of humans, 3rd edn.,
ed. Evans, A.S. pp. 545-592. New York: Plenum Medical Book Company.
Burke, D., Brundage, J. F., Redfield, R. R., Damato, J. J., Schable, C. A., Putman, P., Visintine, R. & Kim, H. I. 1988 Measurment of the false positive rate in a screening program for human immunodeficiency virus infections. New England Journal of Medicine 319, 961-964.
Caceres, C.F. & van Griensven, G.J.P. 1994 Male homosexual transmission of HIV-1. AIDS 8, 1051-1061.
Carr, J.K., Sirisopana, N., Torugsa, K., Jugsudee, A., Supapongse, T., Chuenchitra, C., Nitayaphan, S., Singharaj, P. & McNeil, J.G. 1994 Incidence of HIV-1 Infection Among Young Men in Thailand. Journal of Acquired Immune Deficiency Syndromes 7, 270-1275.
Carr, S.V., Green, S.T., Goldberg, D.J., Cameron, S., Gruer, L., Frischer, M., Mackie, T. & Follett, E. 1992 HIV prevalence among female street prostitutes attending a health-care drop-in centre in Glasgow. AIDS 6, 1553-1554.
Celentano, D.D., Nelson, K.E., Suprasert, S., Wright, N., Matanasarawoot, A., Eiumtrakul, S., Romyen, S., Tulvatana, S., Kuntolbutra, S., Sirisopona, N., Akaraswei, P. & Theetranont, C. 1993 Behavioural and sociodemographic risks for frequent visits to commercial sex workers among Northern Thai men. AIDS 7, 1647-1652.
Chiodi, F., Albert, J., Olausson, E., Norkrans, G., Hagberg, L., Sonnerborg, A., Asjo, B. & Fenyo, E. M. 1988 Isolation Frequency of Human Immunodeficiency Virus from Cerebrospinal Fluid and Blood of Patients with Varying Severity of HIV Infection. AIDS Research and Human Retroviruses 4, 351-358.
Cohen, J. 1994 The Duesberg Phenomenon. Science 266, 1642-1649.
Defer, C., Agut, H., Garbarg-Chenon, A., Moncany, M., Morinet, F., Vignon, D., Mariotti, M. & Lefrere, J. J. 1992 Multicentre quality control of polymerase chain reaction for detection of HIV DNA. AIDS 6, 659-663.
Detels, R., English, P., Visscher, B., R., Jacobson, L., Kingsley, L., A., Chmiel, J., S., Dudley, J., P., Eldred, L., J. & Ginzburg, H. M. 1989 Seroconversion, sexual activity, and condom use among 2915 seronegative men followed for up to 2 years. Journal of the Acquired Immune Deficiency Syndromes 2, 77-83.
Duesberg, P. H. 1995 Foreign-protein-mediated immunodeficiency in hemophiliacs with and without HIV Genetica 95 No. 1-3 51-70.
Ehrnst, A., Sonnerborg, A., Bergdahl, S. & Strammegard, O. 1988 Efficient Isolation of HIV From Plasma During Different Stages of HIV Infection. Journal of Medical Virology 26, 23-32.
Fauci, A. S. & Lane, H. C. 1994 Human Immunodeficiency Virus (HIV) Disease: AIDS and Related Disorders. In Harrison's Principles of Internal Medicine 13th edn., ed. Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S., Kasper, D.L. pp. 1566-1618. New York: McGraw-Hill Inc.
Gelderblom, H.R., Reupke, H. & Pauli, G. 1985 Loss of envelope antigens of HTLV-III/LAV, a factor in AIDS pathogenesis? Lancet ii, 1016-1017.
Gelderblom, H., Reupke, H., Winkel, T., Kunze, R. & Pauli, G. 1987 MHC-Antigens: Constituents of the Envelopes of Human and Simian Immunodeficiency Viruses. Zeitschrift fur Naturforschung 42C, 1328-1334.
Hausmann, E.H.S., Gelderblom, H.R., Clapham, P.R.. Pauli, G. & Weiss, R. A. 1987. Detection of HIV envelope specific antibodies by immunoelectron microscopy and correlation with antibody titer and virus neutralizing activity. Journal of Virological Methods 16, 125-137.
Jacobs, J.L., Libby, D.M., Winters, R.A., Gelmont, D.M., Fried, E.D., Hartman, B.J. & Laurence, J. 1991 A cluster of Pneumocystic Carinni pneumonia in adults without predisposing illnesses. New England Journal of Medicine 324, 246-250.
Jaffe, J.H., Moore, J.D., Cone, E.J. et al. 1986 HTLV-III seropositivity in 1971-1972 parenteral drug abusers - a case of false positives or evidence of viral exposure? New England Journal of Medicine 314, 1387-1388.
Kalyanaraman, V. S., Sarngadharan, M. G., Bunn, P. A. & Gallo, R. C. Antibodies in human sera reactive against an internal structural protein of human T-cell lymphoma virus. Nature 294, 271-273.
Kashala, O. Marlink, R. Ilunga, M. Diese, M. Gormus, B. Xu, K. Mukeba, P. Kasongo, K. & Essex, M. 1994 Infection with human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1 cross-reactivity and antibodies to lipoarabinomannan. Journal of Infectious Diseases 169, 296-304.
Learmont, J., Tindall, B., Evans, L., Cunningham, A., Cunningham, P., Wells, J., Penny, R., Kaldor, J. & Cooper, D. A. 1992 Long-term symptomless HIV-1 infection in recipients of blood products from a single donor. Lancet 340, 863-867.
Mastro, T.D., Satten, G.A., Nopkesorn, T., Sangkharmomya, Longini Jnr, I.M. 1994 Probability of female-to-male transmission of HIV-1 in Thailand. Lancet 343, 204-207.
Modan, B., Reuven Goldschmidt, P.H., Rubinstein, E., Vonsover, A., Zinn, M., Golan, R., Chetrit, A. & Gottlieb-Stematzky, T. 1992 Prevalence of HIV Antibodies in Transsexual and Female Prostitutes. American Journal of Public Health 82, 590-592.
Montreewasuwat, N. & Peerapakorn, S. 1988 Leprosy situation in Thailand. Southeast Asian Journal of Tropical Medicine and Public Health 19(3), 515-517.
Mortimer, P.P. 1989 The AIDS virus and the AIDS test. Medicine Internationale 56, 2334-2339.
Muller, W.E.G. Schroder, H.C. Reuter, P. Maidhof, A. Uhlenbruck, G. & Winkler, I. 1990 Polyclonal antibodies to mannan from yeast also recognize the carbohydrate structure of gp120 of the AIDS virus: an approach to raise neutralizing antibodies to HIV-1 infection in vitro. AIDS 4, 159-162.
Nelson, K.E., Celentano, D.D., Suprasert, S., Wright, N., Eiumtrakul, S. et al. 1993 Risk Factors for HIV Infection Among Young Adult Men in Northern Thailand. Journal of the American Medical Association. 270, 955-960.
Nopkesorn, T., Mastro, T.D., Sangharomya, S., Sweat, M., Singharaj, P., Limpakarnjanarat, K. 1993 HIV-1 infection in young men in northern Thailand. AIDS 7, 1233-1239.
Padian, N.S., Shiboski, S.C. & Jewell, N.P. 1991 Female-to-Male Transmission of Human Immunodeficiency Virus. Journal of the American Medical Association 266, 1664-1667.
Papadopulos-Eleopulos, E., Turner, V.F. & Papadimitriou, J.M. 1993a Is a Positive Western Blot Proof of HIV Infection? Bio/Technology 11, 696-707.
Papadopulos-Eleopulos, E., Turner, V.F. & Papadimitriou, J.M. 1993b Has Gallo proven the role of HIV in AIDS? Emergency Medicine [Australia] 5, 113-123.
Papadopulos-Eleopulos, Turner, V., Papadimitriou, J., Bialy, H. 1995a AIDS in Africa: Distinguishing fact and fiction. World Journal of Microbiology and Biotechnology. 11, 135-143.
Papadopulos-Eleopulos, E., Turner, V.F., Papadimitriou, J. M. & Causer, D. 1995b Factor VIII, HIV and AIDS in haemophiliacs: an analysis of their relationship. Genetica 95 No. 1-3, 25-50.
Papadopulos-Eleopulos, E., Turner, V.F., Papadimitriou, J. M., Causer, D., Hedland-Thomas, B. & Page, B. 1995c A critical analysis of the HIV-T4-Cell-AIDS Hypothesis. Genetica 95 No. 1-3, 2-24.
Pineda, J.A., Aguado, I., Rivero, A., Vergara, A., Hernandez-Quero, H., Luque, F., Pino, S., Abad, M.A., Santos, J., Cruz, E., Rey, C., Leal, M., Marquez, M. & Lissen, E. 1992 HIV-1 infection among non-intravenous drug user female prostitutes in Spain. No evidence of evolution to Pattern II. AIDS 6, 1365-1369.
Pinter, A., Honnen, W.J., Tilley, S.A. et al. 1989 Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. Journal of Virology 63, 2674-2679.
Rodriquez, L., Dewhurst, S., Sinangil, F. et al. 1985 Antibodies to HTLV-III/LAV among aboriginal Amazonian Indians in Venezuela. Lancet ii, 1098-1100.
Singhanetra-Renard, A. 1993 Malaria and mobility in Thailand. Social Science and Medicine 37(9), 1147-1154.
Siraprapasiri, T., Thanprasertsuk, S., Rodklay, A., Srivanichakorn, S., Sawanpanyalert, P. & Temtanarak, J. 1991 Risk factors for HIV among prostitutes in Chaingmai, Thailand. AIDS 5, 579-582.
Sterk, C. 1988 Cocaine and HIV seropositivity. Lancet i, 1052-1053.
Strandstrom, H., V., Higgins, J., R., Mossie, K. & Theilen, G. H. Studies with canine sera that contain antibodies which recognize human immunodeficiency virus structural proteins. Cancer Research 50, 5628s-5630s.
Sudre, P., ten-Dam, G. & Kochi, A. 1992 Tuberculosis: a global overview of the situation today. Bulletin of the World Health Organisation 70(2), 149-159.
Tabet, S.R., Palmer, D.L., Wiese, W.H., Voorhees, R.E. & Pathak, D.R. 1992. Seroprevalence of HIV-1 and Hepatitis B and C in Prostitutes in Albuguerque, New Mexico. American Journal of Public Health 82, 1151-1154.
Tomiyama, T. Lake, D. Masuho, Y. & Hersh, E.M. 1991 Recognition of human immunodeficiency virus glycoproteins by natural anti-carbohydrate antibodies in human serum. Biochemical and Biophysical Research Communications 177, 279-285.
Vigier, P. 1970 RNA oncogenic viruses: Structure, replication, and oncogenicity. Progess in Medicine and Virology 12, 240-283.
Volsky, D.J., Wu, Y.T., Stevenson, M. et al. 1986 Antibodies to HTLV-III/LAV in Venezuelan patients with acute malarial syndromes. New England Journal of Medicine 314, 647.
Wain-Hobson, S. 1989 HIV genome variability. AIDS, 3, S13-S18.
Weiss, R. & Thier, O. S. 1988 HIV testing is the answer--what's the question? New England Journal of Medicine 319, 1010-1012.
WHO 1992 World malaria situation 1990 Division of Control of Tropical Diseases. World Health Statistics Quarterly 45(203), 257-266.
Zolla-Pazner, S., Gorny, M.K. & Honnen, W.J. 1989 Reinterpretation of human immunodeficiency virus Western blot patterns. New England Journal of Medicine 320, 1280-1281.