Download Immunostimulation and Immunomodulation

AIDS
Immunostimulation and Immunomodulation
therapy trials with THYMEX-L
in Kinshasa, Zaire in 1984 and 1985
by Prof. Dr. Waclaw Kornaszewski, M.D.
along with Dr. M. Kornaszewska, M.D.
University of Kinshasa
Medical Faculty
Cliniques Universitaires Mont Amba
Kinshasa XI, Republic of Zaire
1986
Table of Contents
Preface – Professor Rácz _______________________________________________ 3
AIDS: A “New” Disease – Professor Isaković _______________________________ 4
AIDS- Immunostimulation and Immunomodulation Therapy Trials with THYMEX-L
in Kinshasa, Zaire in 1984 and 1985 ______________________________________ 7
Summary __________________________________________________________ 26
Literature __________________________________________________________ 27
Pictures____________________________________________________________ 30
2
Preface
In this article Professor Kornaszewski reports on 62 people suffering from AIDS in Zaire.
The observations are of special importance because Professor Kornaszewski, as longtime director of the Hospital for Infectious Diseases in Zaire, was able to study the
dynamics of being infected with LAV/HTLV-III [Lymphadenopathy-associated Virus/
Human T-cell Lymphotrophic Virus type III]. The LAV/HTLV-III infection belongs to the
most dangerous viral infections for humans. Long-term studies showed that about 10 40% of the cases break out into AIDS. The majority of patients with this infection has
been observed the United States. The epidemic is also spreading to Europe, Australia,
Canada, and the Caribbean as well as South America.
The data from the studies, which were conducted in Central African countries, show that
the epidemic has also spread in this area. Seropositive cases have been found in Zaire,
Rwanda, Zambia and Uganda.
It is of great importance to stop the spread of the LAV/HTLV-III infection in Africa. For
this reason, I gladly wrote the preface to this article even though these tests are just the
beginning of a long-term study. Hopefully, Professor Kornaszewski will have further
possibilities in the future so that he can complete his valuable work with methods as are
required in the USA and Europe for scientific research.
Hamburg, March 1986
Prof. Dr. Paul Rácz, M.D.
Head of the Pathology Department
Bernhard-Nocht-Institute Hamburg
3
AIDS: A “New” Disease
Acquired immune deficiency syndrome (AIDS) is characterized by a serious change of
the immune system with opportunistic infections and malignant diseases. In patients with
AIDS, there is a pronounced immune deficiency with a weakening of the cellular and
humoral immunity. The epidemic characteristic of AIDS was thus considered proven
after the disease had been identified as clinical picture in 1981, and an epidemic and
exponential increase of AIDS-patients could be observed.
A retrovirus, known as lymphadenopathy-associated virus (LAV), or AIDS-related virus
(ARV) is highly suspected to be the cause of AIDS.
HTLV III can be detected in blood, semen and saliva. The average incubation is 29
months in adults and 12 months in children, but the virus can stay silent for up to 5 years
before symptoms start. 2 - 15% of infected persons come down with AIDS, in 23 - 25%
an AIDS-related complex occurs, and in 60 – 70% the virus carrier does not have any
ailments. The rate of serum positivity of HTLV III is high in AIDS patients, however, HLV
III-antibodies will be also found in a considerable number of patients in the risk group.
A lymphadenopathy with or without malignant alterations and opportunistic infections is
characteristic for AIDS, mostly caused by pathogens that occur frequently in the
environment. Clinically, pulmonary infections and diseases of the central nervous
system (infections, vascular complications, and lymphomas), chronic diarrhea and
malignant processes, most frequently in forms of Kaposi’s sarcoma, occur with AIDS.
The immunological dysfunctions with AIDS are numerous and include not only
dysfunction of the T- and B-lymphocytes but also of the accessory cells and regulatory
molecules as interleukin 2 (IL-2), gamma-interferon, and thymosin. T-helperlymphocytes (T4) are seriously damaged in AIDS patients. The main indication for the
immunological dysfunction is a significant insufficiency of T4-cells with a low quotient of
T-helper/T-suppressor lymphocytes.
4
In patients with AIDS, there is not only an insufficiency in T4-lymphocytes, but also the
B-lymphocytes are affected. The polyclonal activation of B-cells with hyperglobulinemia,
reduced reaction of B-cells to mitogenes, the existence of antibodies (rheumatism factor
and anti-nuclear antibodies), hyperplasia of the lymph follicles in the lymph nodes, and
the appearance of malignant processes of the B-cell-type are characteristics of the
change in B-cells with AIDS.
Anomalies of the follicular dendritic cells (FD) and other accessory cells within the lymph
follicles are also described. FD-cells mostly occur in connection with virus particles and,
in some cases, exhibit cytolytic changes. In augmented lymph follicles (germinal
centers) a high percentage of activated B-lymphocytes with uncommon differentiation
can be identified.
In spite of all data about the immune deficiency, the triggering mechanism is still
unexplained. Most test results show agreement in that the changes occur mainly in the
T4-lymphocytes. It is strongly suspected that HTLV III acts cytotropic for T4-lymphocytes
and only T4-cell show receptors for HTLV III. Furthermore it has been proven that the
infection of T4-cells with HTLV III can be blocked by a monoclonal antibody which
recognizes the epitope on the T4-antigen. There, it seems, the T4-antigen is an
essential and specific component of the cell membrane receptor of HTLV and that HTLV
III can infect and kill in vivo T4-lymphocytes.
Contrary to this hypothesis it has been speculated that HTLV III can infect and activate
B-lymphocytes, which on their part then change the homeostasis of the immune system
and lead to stimulation of the T-suppressor cells and consecutively to a suppression of
the immune reaction.
Also, when in AIDS patients the B-lymphocytes are changed nearly as much as the Tlymphocytes, there is no clear evidence for a sensitization of these cells against HTLV
III. In histological examinations of the lymph nodes, changes in the follicular dendritic
cells and other antigen-containing cells have been detected; this, thus, is an argument
for increased absorption of antigens with subsequent augmented reaction of B-cells to
5
the infectious agent. Considering all available data it is more probable that the T4lymphocytes and accessory cells are the primary goal for HTLV III, while the Blymphocytes and accessory cells have an important role in the formation of the immune
syndrome.
During the last years, we have learned much about the etiology, epidemiology and
clinical and immunological characteristics of AIDS. Regardless, the causal mechanism
of the immune suppression is still unclear. For effective treatment and immunological
reconstitution in AIDS-patients, however, understanding the pathogenesis plays a major
role. Regarding this aspect, it has to be emphasized that the reconstitution therapy with
regulatory factors that activate the T4-lymphocytes, e.g. IL-2, can aggravate the
infection. Not only is HTVL III tropic for reacting T4-cells but also for activated T4-cells.
Therefore, IL-2 can only be used in the treatment of patients with lacking T4lymphocytes.
New observations made by Professor W. Kornaszewski about the application of an
immunomodulating complex (THYMEX-L) in clinical practice show a new possibility for
the treatment of AIDS patients.
The readers of this article will find much useful information about AIDS and the results of
treatment with THYMEX-L. Furthermore, THYMEX-L has the ability to reconstitute
humoral as well as cell-operated immunity. THYMEX-L causes a differentiation of T3and T4-lymphocytes in vivo and in vitro. Therefore, an improvement of the immunologic
reactivity in AIDS-patients through a long-term treatment with THYMEX-L can be
anticipated.
Prof. Dr. Sci. Katarina Isakovic. M.D.
Immunological Research Center
Belgrade, Yugoslavia
6
AIDS- Immunostimulation and Immunomodulation Therapy Trials with
THYMEX-L in Kinshasa, Zaire in 1984 and 1985
The characteristics of AIDS (Acquired Immune Deficiency Syndrome) are well-known
(7,14). AIDS is an acquired immune deficiency syndrome, which occurs in patients with
parasitic and recurring illnesses, that indicates defects in the cellular immune system for
which there are no known causes for the immune defects (1, 13, 16, 18, 31).
In general, it is scientifically recognized that the immune system plays a role in the onset
and development of various disease patterns (2). The course of this disease shows a
certain reaction coupling of functional defects in the immune system. A decreased
immune threshold can be the cause of many opportunistic infections (3, 21). Since 1980
AIDS has been a puzzle for the medical world, and it has, yet, to be fully solved.
After five years of observation, we know that AIDS is not truly a syndrome; instead, it is
a clearly defined, new, retrovirus disease. It is also known that this new illness is only
the top of the iceberg. The infection with the retrovirus HTLV III/LAV is known as an
illness of the promiscuous and has already been spread world-wide (12, 22).
It began in the USA in 1980 when a series of similar disease patterns were diagnosed.
Starting 1980 in large American cities, previously healthy homosexuals came down with
pneumonia and Kaposi’s sarcomas, and the progress of these diseases was often
deadly. This new, quick spreading disease pattern that has an acquired destruction of
the cellular immunity as its basis is called AIDS.
It is not possible to give an exact date for the start of the disease in Central Africa.
Although, it appears that an increase in the frequency of lymphadenopathy and other
prodromal AIDS symptoms as well as invasive growing Kaposi’s sarcoma in younger
patients can be traced to about 1978. The number of sufferers has increased
continuously since 1977. Cryptococcen meningitis also increased consistently over the
following years. The old, classic Kaposi’s sarcoma has changed in Africa and is today
still considered dependant on an infection with HTLV III/LAV.
7
Since the diagnosis of the first case, an extreme increase in AIDS has been observed in
many countries, especially the USA and later in Europe (4, 8, 20, 39). The number of
AIDS patients has almost doubled yearly. European countries report their AIDS patients
to a special central office in Paris so an overview of the AIDS incidents in Europe is
possible (40). The disease has spread to a large number of countries in the world (20).
Drug addicts, hemophilic patients, heterosexual partners and children from AIDS
patients as well as the inhabitants of Central Africa have been added to the original risk
group of homosexuals who make up approximately 70% (9, 35, 38).
In 1982 and 1983, 38 Africans were treated for AIDS in Belgium. In November 1983,
Peter Piot and a colleague discovered that in the largest hospital in Kinshasa (Mama
Yemo) 2 to 3 new AIDS cases appeared per day, and that worldwide this disease
appears most frequently in Kinshasa. At the same time in the Department for Internal
Medicine in the University Hospital in Kinshasa, a definite increase of new AIDS cases
was registered. In 1984, every two days 3 new AIDS cases were observed, but in the
first months in 1985, there were 3-4 new AIDS cases daily.
The mortality analysis, which was previously conducted by the Department for Internal
Medicine in the University Hospital in Kinshasa for the years 1965-1974, showed that
during this 10-year time span every 4th death was determined to be caused by liver
disease (primary liver cancer, cirrhosis of the liver or jaundice - acute hepatitis- etc.).
Ten years later the mortality cause had completely changed. In 1984 in the same
department every 5th death was caused by AIDS.
The morbidity rate has also changed. For example, the Clinic for Dermatology in
Kinshasa studied 4478 patients from October 1983 to December 1984 and found 126
possible AIDS cases. From these 126 possible AIDS cases, 93 were proven to actually
have AIDS. Of these 93 actual AIDS cases, 66 showed an opportunistic manifestation
and 10 Kaposi’s sarcoma. In 1980 there had been no AIDS cases diagnosed, and there
were no similar symptoms.
8
It was determined that 5 - 10% of the population in Kinshasa is infected with HTLV
III/LAV. It is estimated that in this city, which has about 3 million inhabitants,
approximately 35,000 new AIDS cases will be diagnosed in 1985/86.
Experts in the USA have estimated that in the meantime one million Americans have
come in contact with the AIDS virus. There are already antibodies in their blood. It is not
clear how many of them will become acutely ill from the AIDS virus or a pre-form thereof.
The estimates lay between 4 and more than 30 percent.
According to Gallo and associates (12), Africa is the home of the HTLV III/LAV virus.
Currently, the antibody studies show an accumulation of the virus in Zaire.
In America and Europe AIDS is mostly found in homosexuals, drug addicts and
hemophiliacs. A very different situation presents itself in Africa. It was found that the
transmittance of the disease take place partially from asymptomatic AIDS carriers to the
sexual partner and partially from a mother with AIDS to her children.
It is possible that AIDS occurred sporadically in Central Africa earlier (17), but the
disease first reached epidemic proportions in 1980, parallel to the cases in the USA (6).
Since 1980, for example, the frequency of cryptococcus neformans meningitis has
increased 40-fold. In Zaire there are entire families who have AIDS; some have already
died.
The CDC (Centers for Disease Control) in Atlanta, USA have defined clinical AIDS as a
disease of patients under 60 years of age who were previously healthy where a defect
causes cellular immune-opportunistic infection or Kaposi’s sarcoma (10, 11, 15). The
incubation time for AIDS can be up to 10 years; some researchers even say up to 14
years (12).
Once the diagnosis had been made, with hindsight, suspicious but non-specific
prodromal symptoms are recognized. Often there is a non-explainable, considerable
9
weight loss over several months, increasing tiredness, weakness, low-grade fever or
fever with no explanation, nightly episodes of sweating, indolent and swollen lymph
nodes and partially hepatosplenomegaly. A dry cough without dyspnea can also be a
biological finding by otherwise healthy persons and a first indication of a pneumocystis
carinii pneumonia. At least 60% of the AIDS patients show, in addition to the destruction
of the bodies own defense system, severe damage to the brain and the central nervous
system. The patients show progressive memory loss, reduced ability to speak and to
think, and even signs of mental deterioration(5, 19, 23, 28, 30).
Currently, it is not possible to make any kind of statement as to a cure for AIDS, but
there are many reports about therapy trials (37).
Some advancement can be seen in the somewhat successful trails where
immunostimmulation and immunomodulation have pushed back the outbreak of the
disease or have even stopped it from breaking out.
The treatment showed better results for a portion of the opportunistic infections. In
Africa many medications are used for opportunistic infections, but they are too
expensive, so that the AIDS sufferers in Africa cannot use them and therefore die.
Many trials have been conducted to improve the immune deficiency situation (26). Most
have had negative results. Because the length, dosage and type of application need to
be varied, it is necessary for a more exact observation of the therapy trials to introduce
further immunostimmulation and immunomodulation medications. Thus, it appeared
indicated to us to supplement the palette with the thymus extract THYMEX-L.
Material and Method
From October 30, 1984 to the end of July 1985 in the medical hospital of the University
of Kinshasa, 62 AIDS patients were treated. The admission to the hospital was done by
external doctors or the hospital’s out patient center. The AIDS patients came from
10
different social backgrounds and both sexes. They were divided into two groups. Group
A was treated with THYMEX-L* (30 patients) and group B as a control group contained
32 patients.
Group A
Group B
Age in Years
Men
Women
Men
Women
20 – 29
1
5
1
8
30 – 39
11
5
6
3
40 – 49
1
3
5
5
50 – 59
3
1
2
2
13
14
14
18
TOTAL
The average age of group A was 37 years and group B 39.7 years. Group A had 53.3%
male patients and group B 43.8% male patients.
Both groups received intensive treatment for opportunistic infections. Additionally, group
A received thymus extract/THYMEX-L. The numerous effects of THYMEX-L have been
reported in various publications (24, 25, 26, 29, 32, 33). The characteristics of stimulation of the immune system was the main reason for the application of THYMEX-L.
The AIDS patients suffered from various opportunistic infections. The AIDS diagnosis
was based on several clinical and laboratory tests. The patients in groups A and B
received their medication for opportunistic infections at the same time and at the same
intervals. The state of health of both groups was for the most part similar.
A very detailed sexual anamnesis was conducted (homosexual, bi-sexual, sexual
practices, sexually transmitted diseases, nationality and number of partners per year).
* We would like to thank TYHMOORGAN GmbH & Co.KG in D-3387 Vienenburg for the friendly support of
our project and the supply of THYMEX-L.
11
Of the 62 AIDS patients, 57 were from Kinshasa. The other were spread out over the
entire country of Zaire (Central Africa). One referral was from Matadi (400 km west of
Kinshasa), another from the Kivu region (2000 km east of Kinshasa) and four from
Kisangani (1550 km north of Kinshasa). All AIDS patients were black. Eight of the AIDS
patients had received a blood transfusion within the last two years. The actual state of
health of the blood donors was not known. 48 AIDS patients had received various
injections; the injections were not always administered with disposable syringes because
these are very expensive in Zaire. Of the 62 AIDS patients, one was a doctor who
worked in a small laboratory in Kinshasa. Two people were from the University Hospital
personnel: a nurse in obstetrics (29 years old) and an employee in the laundry (34
years old).
We could not determine that there was contact between the 62 AIDS patients and the
small number of Haitians who live in Kinshasa (3).
At the beginning of the treatment and after the completion (4 weeks later) the following
laboratory test were conducted in addition to exact clinical examinations and x-rays:
- routine diagnostic tests – large blood count
- differential blood count, including platelet count, erythrocyte sedimentation rate,
determination of the transaminase, alkaline phosphate and serum electrophoresis,
quantitative determination of immunoglobulin, determination of the cell mediated
immunity by intracutaneous test with several so-called “recall antigens” like
tuberculosis and tetanus.
The determination of antibodies
was done for toxoplasma, cryptococcus, and
trypanosomiase. Determination of lymphocyte subpopulations from fresh blood was
done to determine the T-helper/suppressor ratio. Since 1985 we have been using the
ELISA-Test on our AIDS patients and their families to determine the antibodies HTLV
III/LAV. We have also conducted ophthalmological tests on the AIDS patients. The
diagnosis for pneumocystis carinii pneumonia was done with radiology. If Kapoi’s
sarcoma was suspected, the node was excised and histology done.
12
Results : First Manifestations in 62 AIDS patients
Symptoms
Fatigue, malaise
Multiple skin symptoms, muco-cutane efflorescence
Long-lasting diarrhea
Weight loss
Fever, long-lasting or intermittent
Loss of appetite
Enlargement of lymph nodes
Night sweat, increased transpiration
Long-lasting cough and thorax pain
Dyspnea
Difficulties in swallowing
Loss of libido
Amenorrhea (in 32 women)
Patients
56
54
50
49
43
32
30
29
28
10
9
9
9
From this table it can be seen that all the patients showed different initial manifestations.
The most common were fatigue and malaise, i.e. that in the first months before the
diagnosis was confirmed they complained about unexplainable tiredness. Muscle and
joint pain was frequently mentioned.
54 AIDS patients had different skin symptoms: non-specific eczema, acne, pruritus,
herpes, manifested skin fungus, pyoderma and skin abscesses in various areas. 4
patients, who later complained about pruritus, mentioned itching and needing to scratch
after drinking alcohol and washing with warm water.
50 patients complained about diarrhea that lasted many days without a definite cause;
the reasons for diarrhea in Africa differ greatly and are frequent. 49 AIDS patients lost 4
to 8 kg in the first 3 months. Many of the patients who lost a lot of weight complained
about the loss of appetite. 43 patients had long-lasting or intermittent fever. Thirty
patients had swollen lymph glands; 28 patients, who later suffered from pneumocystis
carinii pneumonia, listed chest pains and coughing as the first symptoms.
13
Almost all of the patients suffered from night sweats and increased transpiration. As a
result of the symptoms, the majority of these patients had the first tests and treatments
in tuberculosis clinics. Of the 15 patients with candida esophagitis, 9 had problems
swallowing. Nine patients, both male and female, complained about complete loss of
libido and had had no more sexual contact 3 to 20 months before the diagnosis. Nine of
the 32 women suffered from amenorrhea.
The following table shows the different opportunistic infections of the 62 AIDS patients.
Opportunistic infections with all possible pathogens in 62 AIDS patients
AGENT
NUMBER OF PATIENTS
H. Simplex-Anitis 3
Viruses:
Herpes simplex
42 H. Simplex-Proktitis 2
H. Simples scotalis 1
Herpes zoster
Cytomegalovirus (CMV)
36
8
Bacteria:
M. tuberculosis
Salmonella
Staphylococcus
Klebsiella
B. coli
18
8
9
2 (here in 2 Klebsiella pneumonia)
9 (here in 2 multi-abscesses)
Protozoa:
Pneumocystis carinii
Toxoplasma gondii
Cryptoporidium
Isosopora belli
Plasmodium malariae
Trypanosoma
Entamoeba histolytica
25
10
2
14
16
1
9
Fungus:
Candida
Cryptococcus
Histoplasma capsulatum
Aspergillus
48
12
4
2
Worms:
Ascaris lumbricoides
Ancylostoma
42
13
Tumors:
Angiosarcoma Kaposi
8
14
Herpes simplex was observed in various regions, but herpes simplex labialis occurred
more frequently. Most of the AIDS patients had herpes zoster three times. The diagnosis
of CMV pneumonia was based on radiological findings. We observed 4 stages of
changes in the lung area. We did not conduct virological direct determinations on the
patients because of the lack of laboratory equipment.
18 patients were found to have M. tuberculosis, which is relatively common with AIDS
patients. Twice, we found atypical pneumonias with klebsiella; the klebsiella was found
in the sputum. 7 AIDS patients had B. coli pathogens in urinary tract infections, and the
B. coli were responsible for multiple cutaneous abscesses in the AIDS patients. For
protozoa pathogens, we used radioscopy and radiography to clarify pneumonic findings.
With our possibilities, it was determined that the radiological test was more practical than
an aspiration transbronchial puncture, which was not possible with weak and dyspneic
patients. The results of the analysis of the sputum were always negative. We found 10
patients with a severe toxoplasmosis on the basis of a positive serologic test. We did not
have the possibility to conduct cerebral computer tomography, but the degree of
damage to the brain and the central nervous system along with the clinical history of
meningitis indicated a toxoplasmosis.
In the 20 AIDS patients who suffered from severe diarrhea, we were only able to
diagnosis 2 cryptosporidiosis and 14 isosporiasis. These patients had extremely severe,
watery diarrhea (20 to 30 time a day) that caused serious dehydration and electrolyte
changes. Despite intensive infusion administration, the worst was always the
hypokalemia, which was very difficult to correct and required quick intervention.
Typical, tropical illnesses like malaria were found in 16 AIDS patients and only 1 case of
trypanosomiasis that was connected to AIDS. Entamoeba histolytica localized in the
intestine was present in 9 AIDS patients, who also suffered from diarrhea. This diarrhea
was much easier to cure than that with the cryptosporidiosis. The fungal infections were
mostly candida albicans with 48 cases in the lungs, esophagus and genital area. In 12 of
the AIDS patients who were diagnosed with cryptococcus, the pathogen was found with
15
a lumbar puncture in the liquor. These patients suffered the most severe clinical history
of meningoencephalitis.
With worms there were many cases of ascaris lumbricoides (42 cases) and ancylostoma
(18 cases). This finding is not characteristic for AIDS; such intestinal worm infections
are common for Africans (41).
Angio sarcoma was diagnosed in 8 patients. Most of them had been to a dermatology
clinic first where they were treated for many months. The oldest (first) angio sarcoma
Kaposi started 24 months ago with small, atypical, violet areas on the inside ankle.
Later, multiple cutaneous tumors appeared. While in the hospital, many newly
developed tumors were discovered in various organs, e.g. in the mouth, on the mucous
membranes and in the genital area.
Most of the AIDS patients had at least two or three opportunistic illness at on time.
Sometimes the opportunistic illness could be contained with medication, but then
another illness appeared.
Therapy
More than a dozen different medications are being tested in their effectiveness against
AIDS. A breakthrough has not been made. In our hospital in addition to the main
treatment of the opportunistic infections with antibiotics, antifungal medications, etc., we
administered THYMEX-L to 30 AIDS patients. The dosage was 150 mg in 10 ml
physiological sodium chloride solution 0.9%, 3 times per week. For a 4-week-therapy, 10
injections of THYMEX-L were administered. In order to determine the effect of the
THYMEX-L therapy, we established three parameters. In the first parameter, the
subjective information of the disease was determined. For the second parameter we
compiled the clinical results. The third parameter was for all the laboratory and x-ray
findings.
16
Case Histories
1. A 34-year-old, heterosexual woman gave birth to her 6th child in September 1984.
Since then she had suffered from increasing fatigue, weight loss, fever, convulsions,
headaches, and loss of appetite. Shortly before she was admitted to the hospital, she
had multiple skin abscesses in the anal and gluteal regions. The patient was so weak
that she could not stand. She was severely emaciated: 168 cm / 53 kg. There were
massive leukopenia with clearly indicated lymphocytopenia and cutaneous anergy.
The helper/suppressor ratio was 0.66; the erythrocyte sedimentation rate was
90/hour. Amazingly the was no diarrhea in addition to an obvious hypokalemia 2.4 /
2.6 / 1.8 mmol / l. Antibodies, anti-toxoplasma, anti-trypanosome, and anticryptococcus were negative. After a month-long therapy with various antibiotics and
potassium substitution, no improvement was observed. The abscesses had the
tendency to multiply. The patient could not get up out of bed or sit in bed. From time
to time (once or twice a day) she suddenly would have high blood pressure (180 /130
mm Hg) that could last up to an hour.
Since there was no improvement, we started with THYMEX-L injections. After the first
10 injections a small improvement was observed. The patient could sit up in bed; her
appetite returned, and her temperature normalized. There were no more blood
pressure crises. After 3 therapy treatments (30 THYMEX-L injections) the multiple
abscesses were completely gone. The erythrocyte sedimentation rate was at 80 after
one hour. The hypokalemia normalized: 3.8 / 4.2 mmol / l.
The cause of the hypokalemia and hypertension incidents, which normalized after the
treatment the THYMEX-L, needed to be observed further. On February 10, 1985, the
patient was released from the hospital. She continued to received 3 THYMEX-L
injections á 150 mg per week on an out-patient basis. In the meantime she has
gained 2 kg and has become much stronger. She has been able to enter the hospital
under her own power for each check-up. We still cannot determine how long her wellbeing will last, but in comparison to her condition upon being admitted to the hospital,
where she could not walk at all, this is an objective success.
17
2. A 40-year-old women, widowed for 4 years, 5 children, prostitute, was diagnosed
with an angio sarcoma Kaposi in the dermatology department. Her husband was a
soldier who died from an unidentified diarrhea with high fever and skin lesions the
beginning of 1981. The described symptoms of the dead man are very similar to
today’s known AIDS symptoms. In May 1981 his wife discovered progressive lymph
gland swelling on her neck. She complained about increasing tiredness, night sweats,
loss of appetite, and weight loss. At the same time she also noticed a quick-growingnodule on her left calf. Two months later a similar nodule formed on the right thigh.
The biopsy results were typical anatomical – pathological findings for Kaposi’s
sarcoma. Upon admittance to the hospital, the thin patient (159 cm – 50 kg) was in a
general good state of health. Hyperpigmentation spots and epidermomycosis
generalisata were found on the entire surface of the skin; scratch marks were found.
On the right calf she had brown-black skin nodules and slightly rounded nodules on
the ball of the left foot. The lymph nodes were not enlarged. Her hematological results
were normal (leukocytes 8000), but there was a hypereosinophilia (17%) and a
cutaneous anergy. The helper/suppressor ratio was 0.7.
With THYMEX-L therapy (2 treatments with a total of 20 injections) the actual
condition improved. The patient became stronger. The epidermomycosis generalisata
disappeared completely. The erythrocyte sedimentation rate went from 140 mm to 27
mm per hour. The hypereosinophilia normalized, and the helper/suppressor ratio
increased to 0.8. The cutaneous anergy remained negative.
On February 20, 1985, the patient was released from the hospital. She came as an
out-patient three times a week for check-ups and THYMEX-L injections. Of course,
the sarcoma Kaposi was not cured, but the overall well being increased, so that she
could go home and live with her family. How long this improvement will last is hard to
say, but, in any case, we were able to increase her life expectancy.
3. A 20-year-old, single, heterosexual woman who had been living with a partner for 6
months was admitted to the hospital on December 15, 1984, with increasing fatigue,
18
diverse muscle and joint pain, a dry cough and chest pains. The previous year she
had experienced intermittent fevers. When she entered the hospital, the patients was
172 cm and weighed 45 kg in a slightly reduced state of health. The internal tests
showed an enlargement of the lymph nodes in the neck, which the patient had not
known, as well as discrete signs of bronchial pneumonia. The radiological diagnostic
showed a peribronchial infiltrate without enlargement of the hilus. The radiological
picture was the first sign of a pneumocystis carinii pneumonia. The patient refused a
transbronchial biopsy. The erythrocyte sedimentation rate was 120 mm/hour,
fibrinogen 660, and leukocytes 9100; the helper/suppressor ratio was clearly low with
0.45 with T-helpers at 49 and a cutaneous anergy.
With the treatment of THYMEX-L (3 treatments = 30 injections), the peribronchial
infiltrate subsided. The patient was released from the hospital on February 8, 1985.
She came as an out-patient three times a week for check-ups and THYMEX-L
injections. She had no cough or fever, her appetite returned, and she gained 6 kg.
The cutaneous reaction returned. The patient was so strong again that she could
return to her job as clerical assistant.
4. A 34-year-old man, who worked as a photographer in Kinsangani (third largest city in
North Zaire), was admitted to the hospital the end of January 1981, with diarrhea and
not feeling well. In 1980 he had a child (age 2 ½) who suffered from diarrhea,
unexplainable fever and skin efflorescence; after a 6-month-illness the child died
without an exact diagnosis. In 1982 his wife had similar symptoms (diarrhea, fever,
inguinal lymph node swelling and splenomegaly) and passed away from a very
advanced cachexia after being ill for 10 months.
The patient himself had in June 1984, diarrhea that lasted 3 to 4 weeks. Within 6
months he went from weighing 105 kg to 74 kg. Upon admittance to the hospital, he
was in a very poor state of health because of frequent diarrhea ( 8-10 times/day) with
loss of water as well as electrolytes. A week-long therapy with water and electrolyte
administration was given, but no improvement in the condition was observed. On the
7th day THYMEX-L was added to the therapy. The patient’s conditioned had already
19
improved enough after the 6th THYMEX-L injection that he wanted to go home. After
10 injections (1 treatment), the patient was released from the hospital; since then he
comes in for check-ups. He received a total of 3 treatments and has returned to his
job a photographer. He gained 5 kg. His second wife gave birth to a child in June
1985.
5. A 34-year-old male, middle school teacher in Kinshasa came for treatment in the
hospital because of a persistent diarrhea.
The patient’s history showed tiredness since 1983 and malaria with fevers reaching
41°C two to three times per year.
Before he married, he had lots of contact with prostitutes and was treated 3 times for
gonorrhea (1981-1982). In May 1984, he suffered from diarrhea without an obvious
cause for the first time. He was hospitalized three times in 1984. The vegetative
anamnesis revealed no peculiarities but a weight loss since July 1984. The condition
at the time of admission showed the patient in a somewhat reduced general state of
health with signs of significant water loss.
The pathological and laboratory findings showed a strong susceptibility to infections
and immune deficiency, anemia and low potassium values. As typical, a leukopenia
with an absolute granulocytopenia and lymphopenia was found.
During the 4-week illness an improvement was achieved with water and electrolyte
therapy. The continued course showed that the remitting diarrhea and the general
weakness of the patient were therapy resistant.
The beginning of February 1985, THYMEX-L therapy was started. After the first round
of treatment (10 THYMEX-L injections), the diarrhea had already vanished. The
patient was released from the hospital and came in for check-ups and further
THYMEX-L treatments.
20
He received a total of 4 rounds of THYMEX-L treatments. He had no fever, no more
diarrhea, gained 10 kg within 7 months, and could return to his job at the middle
school.
6. A 32-year-old patient, married in 1978 and divorced 4 years ago, mother of 3 children,
unemployed came in on April 10, 1985, because of fatigue and weight loss. The
history showed a discrete efflorescence during a trip to Europe in 1975.
In November 1984, the condition at the time of admission showed the patient was in a
generally good state of health but with weight loss. Since November 1984, her weight
had gone from 55 kg to 49 kg. A minimal enlargement of the inguinal lymph nodes
could be felt on both sides. The clinical and x-rays did not show any pneumonia or
opportunistic infection. There were the typical laboratory/clinical and immunological
signs of AIDS with leukopenia, hypergammaglobulinemia, and cutaneous anergy.
On April 20, 1985, the patient was released from the hospital with the diagnosis of
“pre-AIDS” for further out-patient treatment. In 1985, she received 3 rounds of
THYMEX-L treatments, a total of 30 injections á 150 mg. She gained 7 kg and
became much stronger.
After the treatment with THYMEX-L, the multitest “Merieux” showed positive reactions
for tuberculin, candida and tetanus. he inguinal lymph nodes were much smaller.
Therefore, the patient clinically has no opportunistic infections, but she still suffers
from reduced immunity.
The disturbed cellular immune reaction, which appears to occur with AIDS, could be
positively influenced in this patient with the administration of thymus hormone.
Discussion
Based on our observations, it can be seen that the AIDS patients already showed the
first symptoms in 1980; these are the symptoms that are considered characteristic for
21
the early stages of AIDS. Very often the AIDS patients were first treated in the
Tuberculosis Department because of lung symptoms (coughing etc.) or by dermatologist
because of skin diseases. In our hospital the patients were treated with various
medications against opportunistic infections.
Of the 32 AIDS patients in the control group, who were treated as above, all died (100%
mortality), but of the 30 AIDS patients who received THYMEX-L in addition to the
treatment for opportunistic infections, 24 died (mortality 80%).
22
Table 1: Mortality Of The Aids Patients After 8 Months
All treated against opportunistic infections
Group A: 30 AIDS patients TREATED WITH THYMUS EXTRACT
Mortality 80%
From this group 6 patients are still alive = 20 %
Group B: 32 AIDS patients
Mortality 100%
23
The patients treated with THYMEX-L showed improvement in the various parameters. A
very noticeable improvement in the general state of health was seen in 6 of the 30
examined and treated patients. The previously mentioned improvements showed
themselves in some cases as a feeling of bodily well-being, a strengthening of certain
muscle groups, mostly legs. Increased performance could be traced back to a good
appetite, the return of sexual desire, and the disappearance of itching and night sweats.
Two of the thirty patients who were admitted to the hospital in coma stage 2 were able to
return home after treatment with THYMEX-L. With two of the AIDS patients the
intracutaneous test was positive. 6 patients gained weight after their THYMEX-L
treatment, e.g., one patient had gained 6 kg in 3 months. A total of 6 of the 30 patients
could be released from the clinical after an 8-month-treatment and were still under
observation as out-patients.
Many objective measurement methods are missing in the African health system, which
are necessary to more precisely estimate immune deficiency as a result of this new retro
virus illness. We tried to choose three different parameters. An important parameter is
surely the determination of the capability of the immune system because it has a very
complex and complicated job. In the course of an infection and tropical diseases, the
work of the immune system decreases.
The observation of the AIDS patients showed that in the development of this retro virus
disease the following factors play a large role: primary HTLV-III/LAV infections, which
are lymphotropic and cytopathogic for T-helper lymphocytes, the damage of the T-helper
lymphocytes, and the immune deficiency with secondary opportunistic infections and
cachexia.
The progressive development of these factors can be shown by the most frequent
clinical symptoms of AIDS that are manifested in fatigue, mucocutanceous
efflorescence, long-lasting diarrhea, weight loss, fever, loss of appetite, and enlargement
of the lymph nodes. In the advanced stages, the long-lasting cough and thorax pain are
often signs of pneumocystis carinii and CMV infection. It must be noted that these were
patients who already showed a dyspnea.
24
As the AIDS disease advances, the immunological cellular defense is greatly reduced
and creates a convenient medium for the development of opportunistic infections. In this
case the patient can experience a series of infections and show new symptoms that can
even change their character.
With AIDS victims there is a significant disturbance of the immunological reaction that
can lead to opportunistic infections.
The cellular immune defense is affected in people suffering from AIDS while the
humoral, also from antibodies, is not directly affected by the virus. In general, the body
cannot produce enough effective antibodies against the HTLV III/LAV virus when the
immune system is disturbed by other infections or factors, especially since this virus is
able to change its surface- the antigen characteristics.
The various symptoms, which depend on the various opportunistic infections, showed
that all patients needed different medications. The use of immunotropic preparationsimmune modulators- represents on possibility. The biological thymus extracts belong to
this group of medications (34, 36).
The use as parenteral injections shows no damaging side-effects. It is not toxic or
allergen; allergic reactions were not observed. The injection must be administered
intramuscular and deeply.
Even a limited, temporary improvement of the stabilization of the immune defense with
THYMEX-L is for AIDS patients a therapeutic starting point; this provides hope and is
positive. There has been no reported cure of an AIDS patient. Just being able to extend
the life of an AIDS patient with the use of THYMEX-L means that a small step has been
made in the area of therapy.
Previous experience has shown the possibility of further treatment with THYMEX-L in
the various stages of the AIDS illness.
25
After the positive observations, in 1985 we started to administer THYMEX-L not only
therapeutically but also as preventative immune therapy to AIDS patients and so-called
AIDS risk groups with early symptoms (pre-AIDS) or the prodromal stage of AIDS.
Summary
In 1984 and 1985, the effect of total thymus extract THYMEX-L was tested on 30 AIDS
patients in the University Hospital in Kinshasa. The influence on the immune system was
in the foreground. THYMEX-L was administered in treatment rounds of 10 injections á
150 mg for four weeks. The following parameters were used: subjective information
about the patient, the clinical testing and the laboratory and x-ray findings. THYMEX-L
proved itself as a valuable remedy during the 8 months of clinical observation.
The result of the treatment of the AIDS patients was a substantial improvement of the
symptoms in 6 of the patients. These patients no longer complained of tiredness and
had no more fevers. In the advanced cases, especially with long-lasting illness,
THYMEX-L therapy was administered as a long-term, out-patient therapy. Here, there
was a vast improvement in the picture in the decreased progress of clinical symptoms
and that life expectancy was extended. Six of the thirty patients were released from the
hospital after the 8-month-treatment. They are still under observation as ambulant
patients.
THYMEX-L is a complex of thymus factors whose affect in AIDS patients has only been
partially clarified. In the reported observations, the influence of THYMEX-L, especially on
the immune system of the AIDS patients, should be investigated further.
The treatment of AIDS still remains a problem as viewed therapeutically. Many further
tests are necessary, and every remedy must be objectified in order to determine if an
application for this world epidemic makes sense. THYMEX-L offers hope that the lifeexpectancy for AIDS sufferers can be extended.
26
Literature
(1)
Aleksandrowicz, J.; Skotnicki, A. Rola quasicy; jej czynnikow humoralnych w
immunoterapii aplastycznych i proliferacyjnyh chorob ukldu krwiotworczeqo, Acta
Med. Pol. 1976, 17.1
(2)
Alexander, W.; Good, R. A. Fundamentals of clinical immunology, Philadelphia,
London, Toronto 1977
(3)
Andreani, T.; Modigliani, R.; le Charpentier, Y.; Gilian, A.; Brouet, J. C.; Liance,
M.; Lachance, M.; Lachance J. R.; Messing, B.; Vernisse, B. Acquired immuno
deficiency with intestinal cryptoparidiosis: possible transmission by Haitan whole
blood, Lancet 1983, 1 (8835), 1187-91
(4)
Bartholomew, C.; Raju, C. C.; Jankey, N. The acquired immuno deficiency
syndrome in Trinindad. A report on two cases; West-Indian-Med-J 1983, 32 (3),
177-80
(5)
Blaser, M. J. Acquired immuno deficiency syndrome possible, arthropod-borne.
Ann-Intern-Med 1983, 99 (6), 877
(6)
Centres for Disease Control (CDC). Acquired immuno deficiency syndrome /
AIDS United States, MMWR 1984, 32, 688
(7)
Clumeck, N. Acquired immuno deficiency syndrome: a fatal but preventable
disease. Acta-Clin-Belg 1983, 38 (3), 145-7
(8)
O-Keefe-FöN; Barniville, H.T.; Otridge, B.; Powderly, W.; Alton, B.; Dervan, P.
Acquired immuno deficiency syndrome with Kaposi’s sarcoma in Ireland.
Ir.J.Med.Sci. 1983, 152 (9), 353-6
(9)
Feremans, W.; Menu, R.; Dustin, P.; Clumeck, N.; Marcelis, L.; Hupin, J. Viruslike particles in lymphocytes of seven cases of AIDS in Black Africans (letter).
Lancet 1983, 2 (8340), 52-3
(10)
Friedman-Kien, A.E. u. M. Disseminated Kapsi’s Sarcoma in homosexual men,
Anm. Int. Med. 1982; 96, 693
(11)
Friedman-Kien, A.E. Epidemic Kapsosi’s sarcoma; a manifestation of the
acquired immune deficiency syndrome. J-Dermataol-Surg-Oncol 1983, 9 (8),
637-40
(12)
Gallo, R.C. u. M. Frequent Detection and Isolation of Cytopatic Retroviruses
(HTLV-III) from patients with AIDS and at Risk for AIDS, Sci 1984, 224, 500-503
(13)
Goldstein, A.L. u. M. Thymosin and the immunopathology of aging, Fed. Proc.
Sept. 1974, 33, Nr. 9
27
(14)
Helm, E.; Stille, W. Acquired Immune Deficiency Syndrome, München, 1984, 79
(35), 8-10
(15)
Kaposi, M. Idiopathisches multiples Pigmentsarkom der Haut; Archive für
Dermatologie und Syphilis; 1872, 4, 265
(16)
Kotlarek-Hans, S. Immunotherapie w chorobach, nowotworowych ze
szczeqolnym uwzqldnieniem biolaczek, Pol. Arch., Med. Wewn 1979, 2, 127
(17)
Kornaszewski, W.; Kornaszewka, M. Torulaza choroba endemiczny w Afryce,
Pol. Tyq. Lek, 1981, 36, 31
(18)
Kuratowka, Z. Zespól nabytych niedoborów, immunologicznych AIDS, Pol. Tyq.
Lek. 1984, 39, 1189
(19)
L’Age-Stehr, J. Erworbene Immundefekte – eine neue Infektionskrankheit AIDS,
Bundesgesundheitsblatt 1963, 26, 93-100
(20)
L’Age-Stehr, J.; Kunze, R. und Koch, M.A. AIDS in West-Germany, Lancet,
1963, 1370 – 1371
(21)
Masur, H. u. M. Outbreak of community, Acquired Pneumocysis’carinis
Pnreumonia (PCP), N. Enq. J.Med. 1981, 305, 1431
(22)
Montagnier, L. u. M. Lymphadenopathy associated virus (LAV) as ethiologic
factor in AIDS, Ann. Virol. 1984, 135, 119
(23)
Pearce, R.B. Intestinal protozoal infections in AIDS. Lancet 1983, 2 (8349), 51
(24)
Pesic, M.C. THX – Immuntherapie mit Thymusextrakt nach Dr. Sandberg;
Erfahrungsheilkunde, Heidelberg 1977, 26, 51
(25)
Pesic, M.C. Wasserlöslicher gesamter Thymusextrakt nach Dr. Sandberg bei
Malignomen; Biologische Medizin, 2/1978, S. 51 – 54
(26)
Pesic, M.C. Immunotherapie mit Thymusextrakt (THX). 2. Auflage, Haug-Verlag,
Heidelberg 1984
(27)
Piot, P. u. M. Acquired immunodeficiency syndrome in a heterosexual population
in Zaire, Lancet 1984, 65-69
(28)
Racz-Tenner, K. u. M. Altered follicular dendritic cells and virus-like particles in
AIDS and AIDS related lymphodenopathy, Lancet 1985, 105 – 106
28
(29)
Sandberg, E. Contribution to the physiology of the thymus, Clinical tests with
thymus extract (THX), translated and reprinted from Medl.-Bl. F SV. Vet.Förb/1963, 23
(30)
Sher, J.H. Cerebral toxoplasmosis (letter); Lancet 1983, 1 (8335), 1225
(31)
Skotnicki, A.B. Der Thymus als Immunitätsquelle, 5. Kongress der
Internationalen Gesellschaft für Thymusforschung, Pörtschach, Österreich, Okt.
1981
(32)
Skotnicki, A.B. Podstawy Immunorequlacji w zespolach autoimmunoagresyjnych
Post Hig. Med. Dosw 1983, 37, 345
(33)
Skotnicki, A.B. u. M. Biological properties and clinical use of calf thymus extract
TFX-Polfa, Thymuc hormones and lymphikines; A.L. Goldstein Raven Press, New
York 1984, 545-564
(34)
Slopek, S. u. M. Immunobiological and pharmacological properties of thymus
factor X (TFX), Arch. Immunol. Ther. Exp. 1980, 28, 827
(35)
St. John, R.K. AIDS and African swine fever (letter). Lancet 1 (8337), 1335
(36)
Tovo, P.A. u. M. Thymus extract therapy in immunodepressed patients with
malignautions and herpes virus infections, Thymus 1980, 41
(37)
Vaith, P. u. M. In-vitro- und In-vivo-Studien mit interleukin-2 (IL-2) und
verschiedenen Immunstimulanzien bei der Patientin mit AIDS; immune. Injetkt.
1985, 13, 51
(38)
Vittocoq, D.; Modai, J. AIDS in a black malian AFR, Lancet 1983, 2 (8357), 1023
(39)
Vogt, M. u. M. Erworbenes Immunmangesyndrom in der Region Zürich, Schweiz.
Med. Wschr. 1984, 39, 1314
(40)
WHO Collaboration Centre on AIDS, Paris. Acquired immune deficiency
syndrome (AIDS) – Report on the situation in Europe as at July 1984; Wkly
Epiderm Rec. 1984, 59, 305 – 307
(41)
Zawadowski, J.; Konaszewski, W. A prospros des helminthiases intestinales
observes par le service medical de l’Office National de Transport au Zaire. Afr.
Med. 1979, 18, 687-690
29
First skin signs after itching scratch marks of an AIDS
patient (age 33) – in a good
state of health
30
Minimum changes of the skin
in the early stage of an AIDS
patient
31
Disseminated, pronounced skin
efflorescence of a 40-year-old
AIDS patient
Pustular skin changes on a
26-year-old AIDS patient
32
Skin area changes "mormorese"
skin symptoms of an advanced
cachectic, 36-year-old AIDS
patient
Disseminated skin efflorescence of a
20-year-old AIDS patient with
generalized trypanosomiasis
33
Lymph node swelling on the
necks of 2 AIDS patients
34
Moniliasis of a young AIDS patient
35
Mycosis in the head area of
AIDS patients with cachexia
36
Herpes zoster of a 33-year-old
AIDS patient
Genital herpes in an AIDS patients
37
Herpes scrotal of 29 AIDS patients after Thymex-L treatment
Before treatment
After the first treatment
Rest as vitiligo after second
treatment
38
Abscesses in the genital area of
a 28-year-old AIDS patient
Skin necrosis on the forehead of
a 22-year-old AIDS patient
39
Cachexia of a 28-year-old
AIDS patient
Cachexia of a 24-year-old
AIDS patient
Extreme cachexia of a 23-yearold AIDS patient (32kg/170cm)
40
Kaposi´s sarcoma of a 31-yearold AIDS patient
AIDS patient with wide spread
Kaposi’s sarcoma skin changes
41
The same patient with skin
changes in leg area. Papular
form of Kaposi’s sarcoma
42
20 year old AIDS patient with
recurring cutaneous tuberculin
reaction
24-year-old AIDS
patient before treatment
After the first 10 injections of
Thymex- L treatment
43
After the second treatment
she put on weight ( 3 kg)
Ambulant treatments to continue
the therapy, accompanied by
her husband. He is suffering
from AIDS, too.
44