Today, there are about 5 to 10 million infected persons in the world who could have the disease themselves or could infect others. More than 80% of the suspected patients in the world are in the USA alone. Till 1986 the total number of patients who have died from AIDS in the UK is about 200 and in the USA about 20,000. AIDS kills ruthlessly, deceptively, remorselessly, and surely.
Mortality approaches 100% in four years. On average, most of the infected persons are men, making 92.5%, followed by women, 6.5%, and children 1%. The vast majority of the patients are homosexuals, making about 75% which is today the major cause of death of single men in the USA in the age group of 25 to 44. (Microbiology Viral Diseases of Man Notes Study Material)
In 1981 while working in a hospital near Los Angeles, Dr. Gottlieb was dismayed to treat in a short period of three months as many as four cases of an extremely rare infection of the lungs-pneumocystis pneumonia, an infection that he would have never come across during his life period. It was an “opportunistic infection”-an infection that invades the body when its defense systems collapse. And to his utter surprise, they all turned out to be avowed homosexuals. After the publication of these cases, reports of similarly afflicted young homosexuals started pouring in at the Centre for Disease Control in Atlanta, USA.
Most of the patients were sexually active. It was, however, later found that all the subjects were not homosexuals and a few were intravenous drug abusers who often shared needles or those who had received blood or its products (like factor VIII), where the donor was an AIDS patient. It was shown to occur in hemophiliacs. The female partner of an AIDS patient or infant born to an AIDS mother may also develop the disease. (Microbiology Viral Diseases of Man Notes Study Material)
It could therefore be assumed that this disease was not infectious by casual contact. The infection is not spread by touch or by contamination of food and drinks as in the case of typhoid, cholera, and jaundice nor is it airborne as in lung tuberculosis and respiratory infections. None of the health service staff in the world had contracted AIDS from a patient.
It is now established that AIDS is prevalent amongst male homosexuals. The association of AIDS with lifestyle is conspicuous.
The risk of contracting the disease depends on living in high-risk areas, anal receptive intercourse, multiple sexual partners exposure to men in high-risk areas (high-risk patients are those who remain asymptomatic throughout their lives while carrying the virus; a patient may be suspected to have AIDS if he shows unexplained fever muscle pains, night sweats, and persistent lymph node enlargement), multiple episodes of sexually transmitted diseases like syphilis, gonorrhea, genital herpes, hepatitis B, giardiasis, etc., intravenous drug abuse and use of recreational drugs like cocaine, amphetamine, methaqualone amyl nitrite, etc.
Anal receptive intercourse helps probably through anal deposition of semen and trauma to the rectal mucosa inflicted in the process, allowing systemic access to retrovirus and the semen. Multiple doses of semen are said to be immunosuppressive. Multiple episodes o sexually-transmissible diseases are also immuno-suppressive. The nitrites facilitate the entry of infective agents into the system through rectal mucosa by man vasodilating effect. (BSc Microbiology Viral Diseases of Man Notes Study Material)
AIDS thus spreads through blood in (i) homosexuals, (ii) intravenous drug abusers, (iii) female sexual partners of any of 1 or 2, (iv) through open wound, (v) transfusion of whole blood, plasma, or platelet transfusion, (vi) use of improperly sterilized or unsterilized syringes and needles, (vii) infants get from their infected mothers. (BSc Microbiology Viral Diseases of Man Notes Study Material)
Proteins, GP120, and GP41 together make up the outer skin of the HIV virus. The genetic material is RNA which is enclosed by another group of proteins, P24 that makes up the inner core of the virus. The genetic information contained in the RNA of the virus is reversed by the enzyme reverse transcriptase. The enzyme is used to translate its genetic information into DNA, which is then inserted into the genes of human cells infected by the virus. (Microbiology Viral Diseases of Man Notes Study Material)
Recent studies on blood samples, taken from Madras have shown the presence of antibodies, and researchers at AIIMS, Delhi presume that there may be an Asian strain of HIV. It is likely that HIV exists as several strains in different parts of the world. HIV-1 is supposed to be the American strain i.e. it has typical characteristics found largely in blood samples of patients from the U.S.A., Europe, and Central and Eastern Africa. HIV-2 perhaps occurs largely in blood samples of patients from West Africa. Perhaps the Indian isolate may be an Asian strain of the virus. (BSc Microbiology Viral Diseases of Man Notes Study Material)
Human beings have a disease defense mechanism, an immune system. The invading microbes are generally killed by this system. The important components of this system are a type of blood cell called lymphocytes. There are T and B types of lymphocytes, of which the former initiate and prime the immune response. (Microbiology Viral Diseases of Man Notes Study Material)
The AIDS virus has a liking for T-lymphocytes-T helper (T4) lymphocytes causing a decline in the number of helper T cells and a change in the T4 (helper): T8 (suppressor) lymphocyte ratio. It multiplies inside them, and finally disintegrates them. The liberated virus particles enter fresh lymphocytes to repeat the cycle, till all lymphocytes are killed. Thus the immune system of the patient collapses and passes into a defenseless state. This state is called AIDS. (Microbiology Viral Diseases of Man Notes Study Material)
The AIDS syndrome could be clearly divided into two stages. First, there is an infection that causes immunosuppression. The excess of suppressive activity is thought to be responsible for the resulting immunodeficient state which characterizes AIDS. Second, such immunodeficient people are susceptible to microbial attack and it is the inability to counter infection which leads to death. It should be emphasized that only 5-20% of those infected by HIV become permanently and grossly immunodeficient, thus evidence of HIV infection is not synonymous with AIDS. (Microbiology Viral Diseases of Man Notes Study Material)
AIDS patients suffer from a variety of diseases where pneumonia caused by the protozoan Pneumocystis carinii is common. One form of cancer, Kaposi’s sarcoma is seen more frequently in AIDS than in non-AIDS people, and this cancer is linked to Cytomegalovirus. Whatever the final cause, clinically recognizable AIDS has a 100% fatality rate.
The period from which the patient is exposed to infection to the development of the full-fledged clinical picture is generally between 9 to 300 months. In blood transfusion-related cases, this period is likely between 4 to 14 months.
Persons having AIDS infection can be classified into three categories as follows:
1. Healthy “carriers”. This is the first and the commonest stage. They have no symptoms. They may remain so throughout their lives. They are capable of infecting others. They themselves are living at top of a volcano. No one knows when it will blow up and how many of them will develop the deadly disease. There are about a million carriers in the USA alone; 5 to 10% of these will develop the full-blown disease within 5-7 years. (Microbiology Viral Diseases of Man Notes Study Material)
2. Prodromal phase. This is also called AIDS-related complex (ARC) Lymph node syndrome (LNS) or Lymph adenopathy syndrome (LAS). This group has a milder form of the disease with fever, diarrhea, weight loss, and enlarged lymph glands but they show unequivocal evidence of depression in the immune system. Sometimes the prodrome may be associated with some fungal infections of the skin or inside (mucosa) the mouth, warts, and herpes. This phase may last for 1-30 months (even up to 5 years). It is seen that all cases of the prodromal phase may not progress to a full-fledged disease, but some 20-30% do in the next three years or so.
3. The end stage. This is the full-blown picture of AIDS. The patient dies of fulminant and uncontrollable infections. The immune system completely collapses and never recovers. The patient may survive a year or two but not longer than four years. The presence of HIV may encourage the development of skin tumor Kaposi’s sarcoma caused by Cytomegalovirus.
The picture comprises symptoms of (i) the respiratory system. Lung infection is the commonest presentation of AIDS. This is seen as dry cough, breathlessness on exertion, vague chest pain, and unexplained fever. Fungi and bacteria may also infect the lungs. (ii) digestive system. There are low volume frequent stool, loss of weight, abdominal pain, and discomfort. (iii) neurological system. The symptoms are caused by infection and the patient may suffer from headaches, personality changes and cognitive changes, loss of memory, changes in consciousness level, and convulsions. (Microbiology Viral Diseases of Man Notes Study Material)
(iv) malignancy. The commonest malignancy that may also develop is Kaposi’s sarcoma – a skin malignancy. This is caused by a virus Cytomegalovirus. The advanced stage of AIDS infection acts as a cofactor for the development of this oncogenic virus. This has a tendency to invade the body all over. Other types of malignancy include that of lymph glands (Non-Hodgkins B cell Lymphoma) and carcinoma of the mouth and the rectum. (Microbiology Viral Diseases of Man Notes Study Material)
The laboratory tests help in the diagnosis of AIDS. Blood samples from the patient are put to virological, serological, and immunological tests. HIV could be isolated from blood. Detection of antibodies against HIV in the serum of AIDS–affected and the high-risk patient shows indirect evidence. The immunosuppression state can be shown by the depletion of T-helper lymphocytes and the alteration of T-helper to T-suppressor lymphocytes in circulating blood. (Microbiology Viral Diseases of Man Notes Study Material)
There are no curative methods to control AIDS. The only ways are (i) a prophylactic vaccine against the AIDS virus and (ii) to check the spread by the development of tests. Work going on HIV may result in the near future development of a vaccine. Attempts are being made to use bone marrow grafts and transfusion of immune cells from healthy individuals. One drug, suramin is being tried. Tests are also being made with Ribavirin (broad spectrum antiviral). The drug Azidothymidine is also being tried and also a mineral compound HPA-23.
The spread of the disease can be greatly checked by the development of tests that can identify persons harboring the AIDS virus. Blood donors should be routinely checked and rejected if found positive. Factor VIII-a product of stored blood used in the treatment of hemophiliacs-is now made safe by heating that kills the virus. Mothers with AIDS are advised against pregnancy. An educational campaign to bring about consciousness about the danger of promiscuity, intravenous drug abuse, and homosexuality, should be given priority. Press and other media also may play an important role. (BSc Microbiology Viral Diseases of Man Notes Study Material)
Cat’s Claw, Possible Cure for AIDS
Recently a climbing plant, Uncaria tomentosa (Rubiaceae) has been claimed to be the elusive cure for this deadly scourge. The plant is found in the jungles of the Amazon, South America, and is better known as a cat’s claw by indigenous people as the plant is covered with hairy claw-like spines. This plant is credited with magical powers. Its anti-inflammatory properties are already known and are now being hailed as the new miracle drug that could cure cancer and even AIDS in the 21st century. (BSc Microbiology Viral Diseases of Man Notes Study Material)
Cat’s claw has been used successfully to treat inflammations associated with gastritis and arthritis. It is now known to strengthen the body’s immunological system. A Peruvian, Manual Moreyra claimed to have cured a malignant tumor in his head by the plant preparation. Dr. Roberto Inchastegui, President of the Peruvian Committee for Sexually Transmitted Diseases and AIDS in the Amazon city of Iquitos, claims to have cured seven AIDS patients with a preparation made from cat’s claw and other jungle plants.
Several biologists and consultants at hospitals in Peru accept that this plant has anti-inflammatory effects and is a powerful immunology stimulant. For instance, Dr. Rumberto Muro at the Lima Naval Hospital confirmed that several patients who were seriously ill with full-blown AIDS are now merely carriers of the HIV virus, after undergoing treatment with the plant Dr. Armando Luza of the naval hospital in Peru has successfully treated a patient. According to a neurosurgeon, Fernando Cabieses, an expert on medicinal plants, tests conducted in Europe have shown that cats’ claws contain substances that inhibit the growth of cancerous cells.
Researchers at the Innsbruck University Pharmacological Institute in Austria discovered that the plant contains six alkaloids with powerful therapeutic effects. In some parts of Central Europe, the plant is being used for patients suffering from allergies, cancer, and AIDS. The plant has already become a highly profitable item marketed and exported under 30 different brand names.
Oscar Schuler’s family has been traditionally associated with this wonder drug plant. It is preferred to sell it powdered in capsules. Cat’s claw comes in many shapes and forms (powder packed in small bags for infusions, in drops, tablets, and capsules). It has become a lucrative business in the United States and Europe, and Peru may not even be asked to pay for a license to sell its own Uncaria.
In 1986, the plant’s oxindole alkaloids were patented in the U.S.A. by a group of European scientists. According to some, there may develop Intellectual Property Rights problems and some experts insist that the American patent is only valid in the U.S.A. because it was never registered in Peru or in any other country. It seems that the humble cat’s claw could, in the future, become a source of discord between nations, as well as a beacon of hope for millions of patients around the world. (BSc Viral Diseases of Man Notes Study Material)
The alarming increase in AIDS cases
According to WHO reports there is the possibility of anything between five to thirty lakh new AIDS cases across the world over the next five years. In the year 1987, there was a swift and dramatic rise in the number of AIDS cases. There were 58,235 cases till August 1987 which rose to 73,747 by the end of December 1987, a 27% rise. Till Feb. 1988, this figure soared to 81,433 from 133 countries. According to WHO, there should be roughly 150,000 cases and between five and ten million persons may be currently infected with HIV. The US Public Health Service estimates that by 1991, some 270,000 cases of AIDS will have occurred in the USA.
In Europe, where 27 countries have reported 10,177 AIDS cases, most countries are said to be facing its rising form. WHO estimates between half to one million persons in Europe are infected with HIV. The highest rates per million population are found in Switzerland, France, and Denmark. By the end of 1988, some 25,000 new cases would have occurred in Europe.
In Africa, the number of countries reporting AIDS has arisen over the past year. By February 1988, 41African countries had reported 9,788 cases. In Asia. 19 countries have reported 233 cases of AIDS. Oceania including Australia and New Zealand has reported 826 cases.
Ebola Haemorrhagic Fever
This deadly disease has recently shaken again Central Africa, killing hundreds of lives in Zaire. The mortality rate is 50 to 90% and no prophylactic (vaccine) or therapeutic method of control could be developed so far.
The disease manifests itself as a high fever with a headache. A severely infected person develops muscle pain, weakness, and sore throat followed by vomiting, diarrhea, rashes, kidney and liver afflictions, and internal as well as external bleeding. The incubation period ranges from 2-21 days. After entering the body, the virus attacks almost every organ jamming it with congealed blood and disintegrating. There is uncontrolled bleeding from the nose and gum. Delirium and death follow even during treatment.
The disease spreads through direct contact with an infected person (contagious) or through body fluids and secretions. The killer disease is caused by a virus, which is a worm-shaped filovirus native to rain forests of Central Africa, also home to HIV. Ebola-related filoviruses were first isolated from cynomolgus monkeys, Macaca fascicularis, imported into the U.S.A. from the Philippines in 1989. It is not known how monkeys become infected, from biting insects or from animals or plants.
The Ebola virus has been classified as Level 4 Pattagen which can be studied only in a controlled, protected environment. Even the AIDS virus is classified at Level 3. (Microbiology Viral Diseases of Man Notes Study Material)
The Ebola epidemic in Zaire first broke out in 1976, when 90% of deaths were linked to contaminated syringes and needles. Out of 300 persons infected by the virus, about 275 died in a single village in Zaire. Like AIDS, the Ebola virus may also spread to other parts of the world. (Microbiology Viral Diseases of Man Notes Study Material)
The primary cause of the epidemic is said to be ecological and environmental degradation by man. There are three types of Ebola virus, (i) Ebola Zaire – the most deadly that broke out in 1976, (ii) Ebola Sudan, isolated around the same time, and (iii) Ebola Reston, which appeared in quarantines in the USA. So two epidemics originated in hospitals with poor hygiene. The use of contaminated needles is believed to be the most important factor in the outbreak of this disease. In the latest, 10 April 1995 epidemic a surgical patient became infected by medical personnel. (Microbiology Viral Diseases of Man Notes Study Material)
Control of Viral Infections
Chemicals are most widely used to treat DNA virus infections of the conjunctiva and cornea of the eye. The agents used are pyrimidine analogs that are incorporated into viral DNA and prevent replication and transcription. These compounds (except acyclovir) are incorporated into cellular DNA hence their use is restricted to the poorly vascularised surface of the eye. In practice 0.1% 5’-iodo 2′-deoxyuridine, an analog of thymidine, improved healing in 72% of infections with herpes simplex type 1, vaccinia, and adenoviruses.
In serious infections such as herpes virus type 1 (causing encephalitis) or vaccinia viruses, analogs of cytidine (cytosine arabinoside) or adenosine (adenine arabinoside) may be used. These chemicals are extremely poisonous and can be used only where death is the likely alternative. (Microbiology Viral Diseases of Man Notes Study Material)
Another anti-viral compound is amantadine, used for type A influenza virus infections. The drug was licensed by Food & Drug Administration, the U.S.A. in 1966. Another drug vidarabine has been in use since 1977 for herpes zoster (shingles) and encephalitis (brain disease) due to herpes simplex virus. A recently developed chemical, and licensed in 1985 acyclovir or Zovirax, properly known as 9-(2 hydroxyl-methoxymethyl) guanine has proved the best anti-viral agent.
Like other pyrimidine analogs, it is a topical ointment, effective against acute infection with herpes simplex viruses. In an infected cell, acyclovir requires viral thymidine kinase to attach the phosphate groups necessary for the DNA synthesis of the virus. Thus, the chemical is toxic only to infected cells. (Microbiology Viral Diseases of Man Notes Study Material)
Interferons
Interferon is the most optimistic approach for antiviral therapy. They were first discovered by Isaacs in 1957. Isaacs and his co-worker had incubated the chorioallantoic membrane from embryonated chicken eggs in a suspension of heat-killed influenza virus and then transferred this membrane to buffer. After storage for 24 hr. the membranes were discarded and the buffer was tested for anti-viral activity. This was done by placing a fresh piece of membrane in the buffer and then challenging the membrane with the active influenza virus.
The treated membrane did not support the growth of active virus whereas the untreated one (not incubated in heat-killed viral suspension) did so. It was therefore concluded that an extracellular product had been liberated in response to viral infection and this substance was named interferon. (Microbiology Viral Diseases of Man Notes Study Material)
Interferon is a group of over 20 substances designated as alpha, beta, and gamma interferons. Each group has many members, all proteins. They are produced by body cells in response to infection by the virus. They trigger a reaction that protects against the stimulating virus as well as many other viruses. Human interferon works only in humans. Unlike antibodies, interferons do not react with viruses but with the cell they protect. Thus, they have a broader inhibitory effect. Interferons are produced when the viral genome is introduced into the cell.
The foreign material (perhaps a double-stranded RNA) induces the cell to synthesize and secrete interferons. These bind to specific receptor sites on the surfaces of adjacent cells and trigger the production of several proteins within these cells. The proteins inhibit viral replication whose mechanism is not completely understood. (BSc Microbiology Viral Diseases of Man Notes Study Material)
Many persons believe that at least one protein binds to messenger RNA molecules coded by the virus. In 1980 a breakthrough came in interferon research when Swiss and Japanese scientists deciphered the genetic code for interferon and spliced E. coli plasmids with the DNA code. Experiments showed that interferon from bacterial factories would reduce hepatitis symptoms, diminish the spread of herpes zoster, and shrink certain cancers. (Microbiology Viral Diseases of Man Notes Study Material)
In 1984, a Swiss biotechnology firm received a patent for alpha interferon and began marketing its product using the trade name intron. In 1986, the U.S. Food & Drug Administration approved the sale of alpha interferon for use against a form of leukemia.
Alpha-and Beta-interferons are similar, the former synthesized by lymphoblastoid cells and the latter (discovered by Isaacs) by fibroblastic cells, macrophages, and others. Both are stimulated by replicating or abortively replicating the virus. Gamma-interferon is released by stimulation of T cells by the antigen for which they are specific, i.e. it is a lymphokine. The interferons are present; like other chemical messengers of the body, in very small amounts. They have been purified and shown to be glycoproteins with carbohydrate groups which are essential for their activity. (BSc Microbiology Viral Diseases of Man Notes Study Material)
Through genetic engineering, however, several milligrams of interferon can be produced by expressing cloned interferon genes in eukaryotic cells, usually yeast. The anti-viral activity of interferons can be measured by inhibition of the incorporation of radioactive uridine into viral RNA in cells infected by a togavirus. Activity is expressed in terms of the amount of interferon required to reduce the normal level of viral RNA by 50% and this is arbitrarily defined as one unit. Purified interferon has a high activity of around 10 units per mg of protein, which is of the same order as the hormones. (Microbiology Viral Diseases of Man Notes Study Material)
The sequences of £, Beta, and Gamma interferons have been determined through cloning. This has been shown that £ and Beta interferon have basic similarities (40% homology), and both are different from Gamma interferon. In the human genome, Beta and Gamma interferons are represented by a single sequence, whereas at least 12 Gamma interferons differing in sequence are present. Interferon enhances the activation of natural killer (*NK) cells, inhibits cell division of tumor cells, and is also a macrophage activating factor (MAF).
In addition, interferons can serve both positive and negative regulatory controls in the expression of immune responses. One very important effect is to control the expression of MHC antigens on the cell surface and hence influence the activity of cytotoxic and delayed-type hypersensitivity T cells. (Microbiology Viral Diseases of Man Notes Study Material)
BSc Microbiology Viral Diseases of Man Notes Study Material
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