ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)

by Maj. M. P. Vora

Maharashtra Medical Journal

Volume No- XXXI, Number – 5, Serial Number 365 of August 1984.

Page No. 99 to 102

and

Current Medical Practice

Vol. No. 28, No. 11 of November 1984

ACCORDING TO THE EDITORS OF HARRISON’S PRINCIPLES OF INTERNAL MEDICINE, ‘The syndrome is a group of symptoms and signs of disordered somatic function, related to one another by some anatomic, physiologic or biochemical peculiarity of the organism. Syndrome diagnosis does not always identify precise course of illness but greatly narrows the number of possibilities.

The Centre for Disease Control in Atlanta, Georgia, reported in the second half of 1981, that the cause of series of alarming and unprecedented deaths in USA, was a new disease complex, labelled AIDS. It connotes that the victims of the syndrome did not inherit immuno-deficiency but acquired it in the course of a disease or AIDS, which they, in the state of already weak defence system of the body, happened to catch. It was found that Haitian immigrants formerly employed in Chad and Zaire were the carriers of the disease. Upto July 1983, 1941 cases were reported, of which 644 had died, giving the mortality rate of about 40%. The disease is now spreading fast to other areas. From 17 other countries, 122 cases were reported with overall mortality rate varying from 40 to 70 percent.

The study undertaken by the Centre for Disease Control, Atlanta to identify the population groups prone to acquire the disease, gives valuable information; 76 percent happen to be active homosexual, 16 percent drug addicts taking nitrites by intravenous route, 5 percent Haitian immigrants, 3 percent female sex partners of AIDS victims, or children either of haemophiliacs who had received blood transfusions, or children of affected parents. From this study a few important facts emerge;

• a person, who does not belong to any of the above divisions, has particularly no fear of acquiring AIDS. It is however, risky to suppose that this disease cannot spread by causal contacts,
• AIDS is often confined to the male homosexuals and lesbians are exceptions,
• the average age of the patient varies between 25 to 40 years,
• the more promiscuous the homosexual male, the greater are his chances of catching the disease. The number of sexual partners one has, is a great hazard. More than one thousand sexual partners in the life-time was an average for most of the victims of the disease,
• Haitians, Slovaks, South Africans, Caucasians and East Europeans have greater predilection to the disease,
• the incidence of the disease is related to the use of drugs like nitrites, which are often taken I.V. by homosexuals to enhance sexual performance and enjoyment.

The most common mode of transmission of the infection is by sexual contacts. Repeated anal coitus leads to trauma, abrasions and petechial bleeding in the rectal mucosa, and permits the entry of the infective agent; unsterilised syringes and needles for injections, blood transfusions and infection from the mother to the infant, while it is in the uterus, are other methods of the spread of AIDS. Earlier studies suggested that the Cytomegalovirus (CMV) or T-cell leukemia virus as the causative agent of AIDS. But their role could not be convincingly proved. Similar immunologic abnormalities in CMV, AIDS, haemophiliacs, sex-partners and infants indicated, a different transferable agent. Though there are some common features and correlation between CMV and AIDS, the number of normal homosexuals, not suffering from AIDS, show antibodies against CMV and low immuno-defence. Now, the studies in France have confirmed that the French virus, called LAV (Lymphoadenopathy virus), is the cause of AIDS. It is invariably and potentially associated with AIDS.

In the meanwhile, the dreaded disease has spread to many other countries. Confirmed cases of AIDS have been reported from Czechoslovakia, Poland, East Germany, Denmark, Norway, Spain, France, Belgium, Italy, Mexico, Trinidad, Canada, Argentina etc. The W.H.O. has naturally stressed the need for an international concerted action to meet the global threat. East Germany has alerted the Polish Institute of Hygiene to issue special guidelines to doctors for an early and accurate diagnosis of AIDS and for blood banks, to be extra cautious against receiving blood for transfusion from AIDS victims.

To understand the nature of biochemical changes that are wrought by LAV, one has to recapitulate the knowledge of the human defence or immune system of the body. Normally, the entry of the foreign substance such as bacterium or virus into the body provides two different kinds of responses from the human body, which aim at elimination of the foreign body or substance. One is ‘humoral response’ in which B-lymphocytes release tiny anti-bodies that destroy the offending agent. The other is the ‘cell-mediated immune response’ in which T-lymphocytes of thymic origin, directly attack the invader but get themselves destroyed in the fight. The immunologic response not only constitutes the principle means of man’s defence against pathogenic microbes, but is also capable of mediating adverse clinical reactions, both beneficial and detrimental to the organism.

AIDS may be classified as either primary, (where etiology and pathogenesis of immuno-deficiency are not known and LAV infection with clinical signs and symptoms is present), or secondary, (if an individual with low immuno-suppression state, either inherent or acquired, catches LAV infection and develops clinical signs and symptoms of AIDS). The chronic immuno-suppression is the genesis of AIDS, which is characterised by gross deficiency of the cell-mediated immune response, reduction in the number of T-lymphocytes, increased susceptibility to recurrent infections- bacterial, viral or fungal,- and the development of malignancy. The immune deficiency is so severe, that the body easily succumbs to variety of avirulent organisms, which are normally harmless. Besides these patients suffer from thymic dysfunction, lack of lymphocyte development and proliferation. An average age of the patient is between 25 to 40 years. The initial clinical presentation pattern is not constant and difficult to interprete. The starting symptoms are mild and insidious to escape one’s attention. The patient may complain of malaise, fatigue, weakness, irritability, myalgia, arthralgia, loss of concentration etc. As the duration of infection increases, some semblance of power of consistency in the presentation is noted. Fever, chills, loss of weight, and enlargement of lymph nodes are noticed. Some patients may develop diarrhoea, pneumonia, pneumocystitis, sores in the mouth and on the perineum, due to opportunistic microorganisms that are normally present in or on the body, or malignant tumors like Kaposi’s sarcoma- localized or diffuse,- or lymphoma. The victim becomes gradually and steadily weak, debilitated and is finally struck down virtually by the disease. He dies in the end of multiple simultaneous infections or of malignancy. AIDS is rather larger and more protean condition than a stereotyped description, because of the wide variability of disease itself.

Since the causative agent of AIDS is reliably determined as LAV, the question is frequently asked, why are homosexual males exposed to semen by anal coitus, more prone to immune suppression, and fall easy prey to other infections than women in general. Its answer can be found in the striking difference in the tissue structure of the vagina and that of the rectum. The vagina is lined by the thick stratified layers of squamous epithelium, below which lies the vascular lamina propria, richly supplied with blood and lymphatic vessels. In contrast, the rectum is lined with a single layer of columnar epithelium, below which is no barrier between the columnar epithelium and the underlying blood and lymphatic vessels of the rectal lamina propria. This anomaly between the walls of the vagina and that of the rectum is primarily responsible to make the former more resistant to trauma, erosion or ulceration and easy infiltration of semen into the vascular layer lying below the squamous epithelium than the latter. Besides, the nature of the sexual intercourse- either vaginal or anal- plays an important role in the transmission AIDS. As a rule, women do not often engage in anal sexual intercourse, as frequently as the promiscuous homosexual men. However, some women do happen to acquire AIDS. In this context, one has a reason to suspect that they may have had anal coitus with homosexual or bisexual men with AIDS. The semen of homosexual men is known to have a greater immuno-suppressive potential than that of heterosexual males, due to complex interaction, i.e. induction of auto-immunity and biochemical changes in the soluble components of the semen. It is a known fact, that auto-immune response- humoral or cellular- is capable of producing tissue injury or biochemical changes in the semen. If this assumption is true, women who have anal coitus with bisexual males may be more prone to AIDS than those, who have anal sexual intercourse with heterosexual males. And just this hypothesis has been confirmed by the fact, women who routinely engage in anal sexual intercourse, exhibit immune abnormalities akin to those found in the homosexual males.

The diagnosis of AIDS is based on the investigations of the immunologic system of the body of the patient. T-cell mediated immune deficiency, low concentration or absence of one or several immunoglobulins, absence of natural antibodies, the thymic dysfunction, failure of lymphoid cellular development, and diminished lymphocytic proliferation, predisposition to severe infections or high susceptibility to the development of malignancy and poor response to infections should arouse clinical suspicion and find ready confirmation in the laboratory. Detection, identification, culture, isolation of LAV by electron or fluorescence microscopy, investigations of immune responses, four-fold rise in specific antibodies in the serum, total and differential leucocytic count, R.B.C. count, ESR, urine analysis, R.A. Factor, electrolyte estimation etc. have to be carried out. In short the defence system of the body has to be carefully studied.

Treatment of AIDS has a limited value. The doctor has to watch and witness helplessly unrelenting progression of the disease. The patient needs a special medical care to preserve good health, to maintain nutrition, general supportive measures, and to prevent emotional disturbances, that are common in chronic ill health. Infections are almost uniformly the urgent problem, and the successful management involves, accurate microbiological diagnosis, specific chemotherapy or antibiotic treatment, supportive measures and early recognition of the underlying immunologic deficiency state; if hypogammaglobulinemia is found, immediate and long-term replacement therapy with concentrated human gamma globulin is indicated. Resistance to infection in most patients is adequate, when the concentration of gamma globulin is 150 mg per 100 ml. Monthly administration of 200 mg of gamma globulin per kg body weight will generally maintain the effective level. The patient has to remain under strict medical supervision continuously, for detection of new infections or development of malignancy and providing prompt and suitable remedies. He has to submit frequently to various tests and investigations. Tendency to prescribe at random and often wide-spectrum antibiotics for infections, or cyto-toxic drugs for malignancy, can be dangerous in AIDS patients with already depleted immunity. Fitting constraints on the use of these drugs are necessary. The very high cost of medicare and maintenance of good health is beyond the capacity of an average patient, specially when death is unescapable under the present conditions. With the advance in knowledge, it might be possible to detect the specific defect and to remedy it or to find a new and effective drug to counter the syndrome. A combined defect in antibody synthesis and cellular immunity is often fatal. Immunologic deficiency state associated with impaired cellular immunity is not amenable to treatment, and calls for transfer of immunologically component cells from normal individuals or infants to restore immunity. However, these procedures are still in the experimental stages.

Because of the present difficulties, the need for preventive approach or an early detection and treatment assumes great importance. Any adult person between 25 and 40 years with a history of homosexuality and susceptible to infections needs a careful search for immuno-deficiency state, which gives an early and significant clue of AIDS. At the same time, his or her associates and contacts should be contacted and examined, as a routine, for an evidence of AIDS and treated before the disease is well established with late complications. A clinical suspension must find ready confirmation in the laboratory. AIDS can be prevented or its spread checked to a great extent by strictly avoiding promiscuity, homosexuality, contacts with suspected victims, unsterilised syringes and needles, blood transfusions from high risk groups, careless handling of laboratory specimens. Besides, regular medical check-ups, early detection of cases, attempts to build up immune forces of the body and continued public education to make masses aware of the disease can go a long way to reduce number of cases and to limit the spread of infection.

Only a few days ago, a very good and heartening news from Emeryville, California, has reached. The researches at a small genetic engineering complex have cloned the genes for the LAV, cause of AIDS, and are expected to produce vaccine against the virus within months.