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HIV Patients Show Positive

Response With Malariotherapy

Dr. Henry J. Heimlich, of the Heimlich Institute, Cincinnati, Ohio, has been invited to present his AIDS treatment study at the XI International Conference of AIDS in Vancouver, July 10, 1996. The study describes promising results from the use of malariotherapy in treating AIDS virus (HIV) infected patients by boosting their immune systems. Co-presenter is Xiao Ping Chen, MD, of the Municipal Health and Anti-Epidemic Station of Guangzhou, China, where the research was conducted.

Dr. Heimlich, world renowned for devising the Heimlich Maneuver, the Heimlich Chest Drain Valve (used throughout the world to save soldiers and civilians with chest wounds), the Heimlich Micro-Trach (to rehabilitate emphysema patients), the Heimlich Esophagus Replacement Operation, as well as many other lifesaving procedures, has directed his attention in recent years to researching a cure for AIDS.

Drs. Heimlich and Chen presented their early malariotherapy study results at the IX International Conference of Immunology, in San Francisco, July 24, 1995. The scientific interest created from this initial presentation has let to subsequent speaking invitations, where they provided further results, the most recent being at the National Institutes of Health (NIH) in Bethesda, Maryland, to the International Conference on Immunology and Aging sponsored by the Institute for Advanced Studies in Immunology and Aging, the NIH, and the World Health Organization.

The study results describe two patients with HIV infections who were inoculated with a curable form of malaria. Three weeks later, the malaria was cured with medication. Thereafter, the patients CD4 (helper T-cells) increased to high levels and have remained elevated for two full years. In the more advanced patient, CD4 cells rose from 269 to 953 and two years later is 650; the other patient went from 889 to 1258 and is 941 two years after malariotherapy. Both patients remain clinically well with no further treatment of any kind.

If studies continue to demonstrate the effectiveness of malariotherapy for HIV infection, treatment of HIV infection would be available for most of the world at little cost.

The significance of this study is noted by Dr. Heimlich who states "No other single course of treatment thus far reported for HIV infection has produced such prolonged results, nor delivered them as safely and inexpensively."

 

MALARIOTHERAPY FOR HIV PATIENTS

HIV-infection weakens patients' immune system by outstripping the ability of the body's immune cells to respond to the virus. This impaired immunity leaves patients susceptible to secondary infections that prove fatal. Restoration and preservation of the immune system are crucial elements in the successful clinical management of HIV infection.1

Drug therapies attempt to restore the immune system by inhibiting viral reproduction, but the virus mutates and becomes resistant to drugs.1,2 In contrast, immuno-based approaches to treating HIV-infection focus on directly strengthening the immune system. Methods designed to enhance immune response in HIV patients include infusion of an exogenous cytokine,1 therapeutic vaccination with inactivated HIV to provoke a specific immune response, 3-6, or, as we will describe, using malariotherapy to stimulate the production of cytokines.

 

MALARIOTHERAPY FOR NEUROSYPHILIS

Malariotherapy is a well-established treatment.7 Drugs or antibiotics could cure generalized syphilis, but were ineffective against neurosyphilis (syphilis of the brain). There appeared to be a "blood-brain barrier," which effectively prevented medications from reaching brain tissue. Spirochetes (spiral-shaped bacteria causing syphilis), therefore, persisted in the brain, causing progressive neurological damage. In 1927, Wagner-Jauregg was awarded the Nobel Prize for having discovered, in 1918, that malariotherapy cures neurosyphilis.

Malariotherapy consists of inoculating patients with a curable form of malaria (P. vivax). After 3 weeks, the malaria is cured. The reason for malariotherapy's success in treating neurosyphilis was unknown, but was attributed to the malarial fevers (hyperthermia). Scientists speculated that an immune reaction was taking place because some patients were cured even when the malaria did not produce high fevers, and production of fever by mechanical means (fever cabinets) did not achieve the same success as malariotherapy. However, modern immunological methods were unavailable at that time. Between 1931 and 1965 the United States Public Health Service administered malariotherapy to tens of thousands of neurosyphilis patients. By 1975, malariotherapy was discontinued because neurosyphilis was essentially wiped out.

Malariotherapy was extremely safe during the more than 50 years it was successfully used to treat neurosyphilis. In a 1984 review, Chernin (Harvard School of Public Health) states that "the contraindications to malariatherapy, and there were some, must have been carefully observed because records of treatment-related deaths or extreme disability are few relative to the thousands of patients treated . . . It is not hard to imagine the almost certain fate of the thousands of paretics (neurosyphilitics) who would have sickened horribly and died but for malariatherapy."7

In addition to treating neurosyphilis by inducing malaria, examples of using one disease to prevent another include cowpox to prevent smallpox and Sabin live polio vaccine.

 

MALARIOTHERAPY FOR HIV-INFECTED PATIENTS

Our interest in malariotherapy as a treatment for HIV infection came about when we found numerous studies showing that malaria causes the patient's immune system to increase production of a variety of immune substances, including interleukins and interferons (IFN-a,8,9 IFN-y, 8-12 IL-6, 12,13 IL-2R, 11,14-19 and sCD8 11,20). This immunostimulative effect logically seemed to have potential benefit for restoring the immune system of HIV patients.

Furthermore, a study of 112 children with AIDS, at the same hospital as the CDC report described below, revealed: "None of the 41 children with malaria and AIDS died, all recovered from their malaria. However, of the remaining 71 children with AIDS without malaria, 25 (35%) died."21

In addition, three independent studies of malarial regions in Venezuela22, Indonesia23 and the Philippines24 showed that people had HIV-type antibodies, but there was no AIDS. AIDS did exist in nearby non-malarial areas. The studies were carried out by researchers from the University of Nebraska and two U.S. Navy Medical Research teams.

NIH researchers later offered confirmation of the beneficial effect of increasing interleukin-2 (IL-2) in HIV patients.1 They showed that, in HIV patients with CD4 cell counts greater than 200 cells/mm3, IV infusions of IL-2, in combination with zidovudine (AZT) was followed by an increase in CD4 cells. There was no consistent change in overall viral loads. CD4 cell counts subsequently diminished, but CD4 production could be stimulated repeatedly with bimonthly infusions of IL-2. Such intravenous infusions of recombinant IL-2 caused severe secondary reactions.

 

Our studies seek to determine:

1) What effect does malariotherapy have on HIV patients' immune status and clinical well-being.

2) What are the biological mechanisms which cause such effects. 3) How long do such effects last; are they permanent?

 

MALARIOTHERAPY IS SAFE FOR HIV PATIENTS

Before treating HIV patients with malariotherapy, we of course had to have strong evidence that it would be safe to induce malaria in an HIV patient whose immune system was impaired. A U.S. Center for Disease Control (CDC) study of 587 children concluded: "No significant differences were found in the incidence, severity, or response to therapy of malaria between children with progressive HIV-1 infection and the seronegative controls . . . No evidence was found to suggest that malaria has any role in accelerating the rate of progression of HIV-1 disease . . . there is no adverse clinical or epidemiological association between these two important public health problems."25 Other studies also confirm that malaria is not an opportunistic disease in HIV patients. 26-29

It is not known whether the immune system can recover when the CD4 count is less than 200 cells/mm3. As a precaution, our protocol requires that the CD4 of HIV patients selected for malariotherapy be greater than 250 cells/mm3. Only after results are evaluated with CD4 counts above this level, will we consider whether treatment should be extended to patients with lower CD4 counts.

 

 

RESULTS OF MALARIOTHERAPY FOR HIV PATIENTS

On the basis of this information, IRB approval was obtained for a preliminary study of malariotherapy for HIV patients. Our initial HIV patients treated with one course of malariotherapy had no complications. One patient's CD4 cells rose from 889 to 1260 and was 941 two years after malariotherapy; the second patient's CD4 cells rose from 269 to 953 and was 650 two years after treatment. These patients have remained well for two years with no further treatment of any kind. Six additional patients have been treated with malariotherapy and also remain clinically well after six months.

HIV infection causes a gradual fall in CD4 cells, eventually leaving patients susceptible to fatal diseases. The increase in CD4 cells following malariotherapy indicates restoration of the patient's immune system. The sustained increase of CD4 cells to normal levels for two years without further treatment, and the fact that both patients remain in good health, suggests that the virus has been controlled. Further tests and followup will determine whether the virus has been eradicated.

HIV rapidly becomes resistant to drugs, enabling the virus to multiply. The immune system is able to adapt to changes in viruses and still eradicate them. Malariotherapy provides a general stimulus to the immune system, thus allowing for the possible elimination of the virus. Another concept relates to the fact that HIV invades the brain, as evidenced by AIDS dementia. The inadequacy of drug treatment may, therefore, also be due to the "blood-brain barrier," recognized in neurosyphilitics, that was overcome by malariotherapy.

 

FUTURE RESEARCH

Having shown that malariotherapy is safe for HIV patients and that the CD4 cell counts increased and remained elevated for two years, our next steps are to continue followup for a longer period and treat additional patients. We will also study changes in viral loading and viral activity caused by malariotherapy, to determine whether the virus has been controlled or eradicated. To further demonstrate the interaction of malaria and HIV, epidemiological studies of patients in countries where HIV and malaria are both prevalent will be carried out. (The U.S. is not a suitable country for malariotherapy studies at this time because malaria is not readily available.) We are also investigating the mechanism by which malaria-induced immunological response regulates HIV infection, how it can be imitated, and application of malariotherapy to the treatment of other diseases.

 

ACKNOWLEDGEMENTS.

Protocol, data management and information retrieval were supplied by the Heimlich Institute. Patient selection and care, and laboratory measurements were provided by the Municipal Health and Anti- Epidemic Station and the Yishou Hospital, both of Guangzhou. We thank the staffs of these institutions for their assistance.


REFERENCES

1) Kovacs JA, Baseler M, Dewar RJ, et al. Increases in CD4 T lymphocytes with intermittent courses in interleukin-2 in aptients with human immunodeficiency virus infection. N Engl J Med 1995;332:567-575.

2) Kinloch-de Loes S. Hirschel BJ, Hoen B, et al. A controlled trial of zidovudine in primary human immunodeficiency virus infection. N Engl J Med 1995;333:408-413.

3) Salk J. Prospects for the control of AIDS by immunizing seropositive individuals. Nature 1987;327:473-476

4) Walker BD. The rationale for immunotherapy in HIV-1 infection. J Acquir Immune Defic Syndr 1994;7(suppl 1):S6-S13.

5) Trauger RJ, Ferre F, Daigle AE, et al. Effect of immunization with inactivated gp120-depleted human immunodeficiency virus type 1 (HIV-1) immunogen on HIV-1 immunity, viral DNA, and percentage of CD4 cells. J Infect Dis 1994;169:1256-64.

6) Moss RB, Ferre' F, Trauger R, et al. Inactivated HIV-1 Immunogen: impact on markers of disease progression. J acquir Immune Defic Syndr 1994;

7(suppl 1):S21-S27. 7) Chernin E. The malariatherapy of neurosyphilis. J Parasitol 1984;70:611-617

8) Rhodes-Feuillette A, Jaureguiberry G, Ballet JJ, et al. The interferon compartment of the immune response in human malaria: I. Interferon inducers in Plasmodium falciparum cultures. J Interferon Res 1985;5:159-168.

9) Rhodes-Feuillette A, Bellosguardo M, Druilhe P, et al. The interferon compartment of the immune response in human malaria: II. Presence of serum-interferon gamma following the acute attack. J Interferon Res 1985;5:169-178.

10) Slade SJ, Langhorne J. Production of interferon-gamma during infection of mice with Plasmodium chabaudi chabaudi. Immunobiology 1989;179:353-365.

11) Harpaz R, Edleman R, Wasserman SS, Levine MM, Davis JR, Sztein MD. Serum cytokine profiles in experimental human malaria. J Clin Invest 1992;90:515-523.

12) Mshana RN, Boulandi J. Mshana NM, Mayombo J. Mendome G. Cytokines in the pathogenesis of malaria: levels of IL-1B, IL-4, IL-6, TNF-a, and IFN-y in plasma of healthy individuals and malaria patients in a holoendemic area. J Clin Lab Immunol 1991;34:131-139.

13) Kern P, Hemmer CJ, van Damme J, Gruss H-J, Dietrich M. Elevated tumor necrosis factor alpha and interleukin-6 serum levels as markers for complicated Plasmodium falciparum malaria. Am J Med 1989;87:139-143.

14) Ringwald P, Peyron F, Vuillez JP, Touze JE, Le Bras J, Deloron P. Levels of cytokines in plasma during Plasmodium falciparum malaria attacks. J Clin Microbiol 1991;29:2076-2078.

15) Kremsner PG, Zotter GM, Feldmeier H, et al. Immune response in patients during and after Plasmodium falciparum infection. J Infect Dis 1990;161:1025-1028.

16) Josimovic-Alasevic O, Feldmeier H, Zwingenberger K, et al. Interleukin 2 receptor in patients with localized and systemic parasitic diseases. Clin Exp Immunol 1988;72:249-254.

17) Deleron P, Lepers JP, Coulanges P. Evolution of the soluble interleukin-2 receptors during Plasmodium falciparum and P. vivax malaria. J Clin Microbiol 1989;27:1887-1889.

18) Nguyen-Dinh P, Greenberg AE. Increased levels of released interleukin-2 receptors in Plasmodium falciparum malaria. J Infect Dis 1988;158:1403-1404.

19) Riley EM, Rowe P, Allen SJ, Greenwood BM. Soluble plasma IL-2 receptors and malaria. Clin Exp Immunol 1993;91:495- 499.

20) Kresmer PG, Bienzle U. Soluble CD8 antigen in Plasmodium falciparum malaria. J Infect Dis 1989;160:357-358.

21) Davachi F, Kabongo L and Nagule K. Decreased mortality from malaria in children with symptomatic HIV infection [abstract W.A. 1291]. Proceedings of the VI International Conference on AIDS, Florence, 1990.

22) Volsky DJ, Wu YT, Stevenson M, Dewhurst S, Sinangil F, Merino F. Rodriguez L. Godoy G. Antibodies to HTLV-III/LAV in Venezuelan patients with acute malarial infections. New Engl J Med 1986;314:647-648.

23) Anthony RL, Jennings GB, Sie A, Ratiwayanto S, Bangs MJ. Prevalance of serum antibodies to human T lymphotropic virus- 1 in an isolated tribe in the highlands of Irian Jaya, Indonesia. Am J Trop Med Hyg 1993;48:230-236.

24) Hayes CG, Burans JP, Oberst, RB. Antibodies to human T lymphotropic virus type I in a population from the Phillipines: evidence for cross-reactivith with Plasmodium falciparum. J Infect Dis 1991;163:257-262.

25) Greenberg AE, Nsa W, Ryder RW, et al. Plasmodium falciparum malaria and perinatally acquired human immunodeficiency virus Type 1 infection in Kinshasa, Zaire: A prospective, longitudinal cohort study of 587 children. New Eng J Med 1991;325:105-109.

26) Muller O, Moser R. The clinical and parasitological presentation of Plasmodium falciparum malaria in Uganda is unaffected by HIV-1 infection. Trans Roy Soc Trop Med Hyg 1990;84:336-338.

27) Morrow RH, Colebunders RL, Chin J. Interactions of HIV infection with endemic tropical diseases. AIDS 1989;3(suppl 1):S79-S87.

28) Fleming AF. Opportunistic infections in AIDS in developed and developing countries. Trans Roy Soc Trop Med Hyg 1990;84 (suppl. 1):1-6.

29) Lucas SB. Missing infections in AIDS. Trans Roy Soc Trop Med Hyg 1990;84 (suppl. 1):34-38


CONTACT: Henry Heimlich, M.D.

Heimlich Institute

2368 Victory Pkwy., #410

Cincinnati, OH 45206

(513) 221-0002


Copyright © 1996. The Light Party.

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