LETTER TO EDITOR OF THE LANCET (1998)



LETTER TO EDITOR OF THE LANCET (1998)

This file is at under “Papers/letters rejected by the scientific press”

Sir - In your editorial feature (July 11, p122) you pointed out that 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 people with HIV". However:

(1) "Tuberculosis kills more people than any other single disease - almost 3 million in 1990".1 No less an authority on AIDS in Africa than De Cock admits that TB has been present in an epidemic proportion in developing countries long before the AIDS era.2

(2) Neither in the 1982, nor in the 1985, CDC AIDS definitions is TB considered to indicate AIDS. Extrapulmonary TB became an AIDS indicator disease in the 1987 AIDS definition and in the 1993 definition TB, any TB, was defined as an AIDS indicator disease. This was because a limited number of TB patients were tested and a significant proportion (but by no means all) was found positive in an HIV antibody test, the extrapulmonary outnumbering the pulmonary.

(3) Before the AIDS era it was known that: "In TB as well as in lepromatous leprosy, an immunosuppressive state will frequently develop in the host. This state is characterised by T lymphopenia with a decreased number of T helper cells and an inverted T-helper/T-suppressor cell ratio...Immunosuppression induced by the infection with M.tuberculosis can persist for life, even when the TB is not progressive".3 In 1984 Piot wrote: "Tuberculosis, protein calorie malnutrition, and various parasitic diseases can all be associated with depression of cellular immunity".4

According to researchers from the USA and the Indian Council of Medical Research, in India, a "community with pre-existing endemic diseases such as tuberculosis and diarrhoea disease makes the clinical diagnosis of AIDS difficult".5 In 1992 De Cock wrote; "widespread access to HIV testing will be required, as firm diagnosis of HIV-associated tuberculosis without serological testing for HIV is impossible"2 (italics ours).

Even today the WHO AIDS definition which is used in the developing countries does not require immunological (T4 cells) or HIV antibody tests. Patients can be said to have AIDS on the basis of disease or, even in the absence of disease, when such symptoms and signs as weight loss, diarrhoea, cough and fever are present.6 Most importantly:

(a) As far back as 1986 the HIV/AIDS experts were saying that: "reactivity in both ELISA and Western Blot analysis may be non-specific in Africans".7 In 1994, no less an authority on HIV/AIDS than Myron Essex proved that antibodies to mycobacteria cross-react in the HIV antibody test and concluded: "...ELISA and WB may not be sufficient for HIV diagnosis in AIDS-endemic areas of central African where the prevalence of mycobacterial disease is quite high".8

(b) In 1992 De Cock wrote: "In developing countries the majority of adults coinfected with M.tuberculosis and HIV are likely to have been infected with the former before the latter". In 1986 researchers from the USA were saying: "Of great interest to us is the fact that most Haitians who develop AIDS in south Florida have been previously treated for tuberculosis".1 One year later, before TB was defined as an AIDS indicator disease, researchers from Canada, noticing that the vast majority of patients of African or Haitian origin who were developing the then AIDS defining disease, TB was present "prior to infection with HIV or development of overt AIDS". These led them to "hypothesise that infection with M.tuberculosis prior to exposure to HIV (including heterosexual contact) is a common predisposing factor to infection with the AIDS virus and development of AIDS in Africans and Haitians".3 In other words the effect, TB, preceded the cause, HIV.

Given the above facts will you not canvas the HIV/AIDS experts among your readers to answer the following questions?

(1) Where is the proof that between 1987 and 1993 there were two major precipitating causes for TB? One, HIV, for extrapulmonary, and other(s) for pulmonary?

(2) Where is the proof that in 1993, the major precipitating cause(s) of TB which existed before 1993 suddenly disappeared and TB became synonymous with AIDS, a disease caused by nothing else but HIV?

(3) If in the AIDS era there has been an increase in reported cases, where is the proof that it is caused by a new agent and not due to an increase in the old causes, increased population or better diagnosis?

(4) Since not all TB patients test positive and "diagnosis of HIV-associated tuberculosis without serological testing for HIV is impossible", why in the developing countries is TB classified as AIDS solely on clinical grounds6 without either HIV antibody or immunological tests?

(5) Even if such tests were to be performed, given the fact that neither ELISA nor WB are sufficient to diagnose HIV infection in TB patients, where is the proof that "AIDS" patients with TB, "the leading cause of death worldwide among people with HIV", are indeed infected with this retrovirus?

(6) Even if the antibody tests were 100% specific and all TB patients were tested and found positive, where is the proof that since 1993 the major precipitating cause of TB is HIV and not still drug abuse,9 "crowding, poor sanitation, lack of proper hygiene"3 or "malnutrition and general lack of medical services", which according to Essex, contribute to "diarrhoea, tuberculosis and other common African diseases that signify AIDS"?10 Is it possible that the leading cause of death from AIDS worldwide is based on mistakenly identifying M. tuberculosis antibodies for HIV antibodies?

Eleni Papadopulos-Eleopulos (1) Valendar F.Turner (2) John M. Papadimitriou (3) Bruce Hedland-Thomas (1) David Causer (1)

(1) Department of Medical Physics, (2) Department of Emergency Medicine, Royal Perth Hospital, Perth, Western Australia; (3) Department of Pathology, University of Western Australia.

Correspondence EPE

Voice int + 618 92242500

Fax int + 618 92243511

Email vturner@.au

REFERENCES

1. Anonymous. CDC AIDS Weekly 1986:9.

2. De Cock KM, Soro B, Coulibaly IM, Lucas SB. Tuberculosis and HIV infection in sub-Saharan Africa. J Am Med Assoc 1992;268:1581-7.

3. Lamoureux G, Davignon L, Turcotte R, Laverière M, Mankiewicz E, Walker MC. Is Prior Mycobacterium Infection a Common Predisposing Factor to AIDS in Haitians and Africans. Annales de l'Institut Pasteur Immunologie 1987;138:521-529.

4. Piot P, Taelman H, Minlangu KB, Wobin O, Mbendi N, Ndangi K, et al. Acquired immunodeficiency syndrome in a heterosexual population in Zaire. Lancet 1984;ii:65-69.

5. Bollinger RC, Tripathy SP, Quinn TC. The human immunodeficiency virus epidemic in India. Current magnitude and future projections. Medicine (Baltimore) 1995;74:97-106.

6. WHO. Acquired Immunodeficiency Syndrome (AIDS) WHO/CDC case definition for AIDS. Wkly Epidem Rec 1986;61:69-76.

7. Biggar RJ. Possible nonspecific associations between malaria and HTLV-III/LAV. N Engl J Med 1986;315:457.

8. Kashala O, Marlink R, Ilunga M, Diese M, Gormus B, Xu K, et al. 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. J Infect Dis 1994;169:296-304.

9. Firooznia H, Seliger G, Abrams RM, Valensi V, Shamoun J. Disseminated extrapulmonary tuberculosis in association with heroin addiction. Radiology 1973;109:291-6.

10. Anonymous. The confusing case of African AIDS. New Scientist 1988;18th February:27.

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