FEVER THERAPY IN VENEREAL DISEASES

by M. P. Vora

Indian Journal of Medical Sciences

Volume No. I, Number. 6 of December 1947

Page No. 320 to 327

It is well-known fact that recovery from infection is aided by a high-temperature and that micro-organisms, even if they are not killed, have their virulence attenuated by the high temperature. Experiments have shown that agglutins and bacteriolytic substances are produced more quickly and abundantly in infected animals kept at high temperature than in similar animals kept at ordinary temperatures for the purpose of control. The rise of temperature produces increased metabolic changes some of which are necessary for the formation of the protective substances. Hence pyrexia, an essential part in the defence of the body against its infection, is regarded as a part of the response to the invasion of micro-organisms and as such as a protective mechanism. Development of immunity is closely connected with the rise in body temperature.

It was observed that the temperature of a patient could be raised and maintained at a level which would either devitalize or kill infective organisms and form protective substances to strengthen body defence, without at the same time causing injury to any of the body tissues and without involving any serious risk to life. This fact was mainly responsible for the introduction of artificial fever therapy in the treatment of venereal diseases. The treatment of G.P.I. by inoculation of substances producing a rise in temperature was probably the first attempt to introduce fever therapy. Since then a great deal of interest has been noticed in this form of treatment and its use has been extended. Nevertheless clinical experience shows that while there are clear-cut indications for such a remedy, there are also well-defined limitations to its application and venereal disease is not a field for the indiscriminate use of fever therapy. A case of acute gonorrhoea responds very well to properly applied chemotherapy with the sulphanilamides or penicillin; and in early syphilis trivalent arsenic and bismuth, if adequately and regularly given, hold out an excellent prospect of complete cure, without involving any appreciable risk or immediate threat to life. The same degree of success and relative absence of immediate danger cannot be claimed for a procedure which rises and maintains for many hours the patient’s temperature. A remedy which is more dangerous than the disease itself is obviously open to question.

Boak 1 and her colleagues carried out investigations to determine the thermal death time of many different strains of gonococci in vitro, and found that 99.9% of the organisms were killed at the temperature of 105.8° F in 4 to 5 hours. The remaining 0.1% showed varying degree of heat resistance. They also found that at the temperature of 102.2°F, the growth of the gonococcus was not appreciably affected. They placed the thermal death point of cultures of Tr. pallida in vitro at 105.9° F for an hour. It is clear from this that the use of non-specific protein shock therapy, which cannot readily and successfully raise and maintain the temperature in all cases to a sufficient level, is bound to have limited success. However, as these methods help to enhance and mobilize the defensive mechanism by inducing leucocytosis or by promoting increased anti-body formation, their place in treatment is not insignificant. Moreover, when this procedure is used in conjunction with chemotherapy i.e. sulphanilamides in cases of gonorrhoea and arsenic compounds or penicillin in cases of syphilis, it has shown synergic action and has proved very useful. Inoculation of malarial parasites to induce rise in temperature in a case of neurosyphilis, which has proved resistant to other forms of treatment, is now recognized as almost an essential part of treatment. The efficiency of combined pyrexial therapy and chemotherapy in the treatment of G.P.I., interstitial keratitis and in complicated and drug-resistant gonorrhoea has been established to some extent. However, while the results cannot be taken at their face value in cases of syphilis where many years must pass before the results can be properly assessed, in the case of gonorrhoea they have been demonstrated beyond any doubt.

The methods of inducing fever are:

• physical,
• inoculation of disease associated with fever and
• injections of vaccines or proteins.

(1) Physical methods: -

• Diathermy- This may be used to produce local heat or general pyrexia. This method of treatment was introduced in 1913. The clinical results in gonorrhoea and its complications have abundantly justified its application. In almost all cases of gonococcal complications results are very encouraging. The principle is to apply a high frequency alternating electric current to the infected area in the genital or the urinary tract and to increase it slowly and steadily till the patient feels a sensation of warmth and after that just to the point of tolerance. Different electrodes to suit different organs are used. This method produces deep-seated heat in the tissues without muscles or nerve stimulation. Cell metabolism is stimulated and the tissue resistance to gonorrhoea is increased. It helps to lessen the acute pain and swelling, relieves urgent symptoms, assists vascularization of the parts and resolution of inflammatory changes. The action is hostile to the invaders and helpful to the invaded. This mode of treatment must be used along with other recognized methods of treatment, local or general or both. It is very useful adjuvant form of treatment but of itself it is not a complete cure of either the infection or the complication there-of. Diathermy often fails to influence the progress of a case of acute anterior or posterior urethritis in the male. In the female it lessens the severity of the infections of the urethra and the cervix, but it does not eradicate the infection any more rapidly than other simpler methods like sulphanilamides or penicillin. In the complications of gonorrhoea especially metastatic, it relieves urgent symptoms and assists in resolving inflammatory changes. Fever therapy produced by diathermy is not very popular for obvious reasons though it exercises a favourable influence on acute complications of gonorrhoea. It requires costly apparatus, demands special experienced men to supervise the treatment while the results are in no way superior to those of other methods.

Therapeutically the best results of local application would be obtained by exposing the infected parts for the longest time to the highest temperature which the tissues could tolerate without harm. But this ideal is not always possible in acute practice. The temperature to which the tissues between the electrodes can be raised is sufficiently high to interfere with the growth of the organisms but it is difficult to raise the temperature of the infected tissues to such a degree as to destroy them.

The factors which determine the degree of heat developed are:

• Strength of the current,
• Size of the electrode,
• Tissues traversed and their resistance i.e., impedence,
• Rate at which heat is produced and lost, and
• Position of electrodes and distribution of heat.

Dose- An average and a safe dose is one ampere. Each treatment lasts

for 20 to 30 minutes. Two sessions are held per week. A course of

treatment consists of 7 to 8 sessions. If appreciable improvement is not noticed, a second course of treatment should be administered. In certain cases, a third course may be necessary.

It is not possible to give precise information in regard to the most effective dose of diathermy. Theoretical considerations are of little help. The measure of current as indicated by the amperemeter is no guide to dosage in the treatment; for it gives no indication of the heat generated in the body. It merely gives an indication of the current produced by the diathermy machine. The degree of the heat developed in the tissues depends on all the factors mentioned above. However, the most accurate measurement of the dose is the thermometer, such as the thermo-couple which can ascertain the temperature attained in the parts, the patient’s sensation of heat, and the clock. The maximum temperature that can be tolerated without pain is 115°F.

Indications for the application of local diathermy are chronic gonorrhoea, subacute gonorrhoea, prostatitis, vesiculitis, epididymorchitis, cervicitis, salpingitis, oophoritis, endocervicitis, arthritis, fibrositis, bursitis and iridocyclitis.

• Air-conditioned fever cabinet. In all the latest work, the necessary high and sustained temperature is achieved by the use of air-conditioned fever cabinets in which the temperature is raised and maintained either by circulating hot moist air, or by hot humid air plus induced electrical current. No doubt, there is an important difference between these two methods. The Inductotherm method is considered to be more suitable. As regards the type of apparatus, expert opinion favours air-conditioned cabinets, having an electrical inductotherm device for raising body temperature by internal heating. Apparatus of the type known as the “Kettering Hypertherm” is commonly used. In this apparatus undesirable effects are reduced to a minimum. Complications such as anoxaemia, jaundice, renal impairment and circulatory collapse which are common in other types of apparatus are very rare in this type.

However, all of them require complete supervision by specially trained men, adequate preliminary examination of the patient to exclude those with some contra-indication (such as tuberculosis, cardiac insufficiency, extremes of age, acute or uncomplicated gonorrhoea in adults) expert nursing, hospitalization and costly equipment. A general examination of the patient is undertaken to see that the required standard of fitness is present and it includes x-ray examination of the chest, renal function tests, blood counts, electrocardiographic tracings, liver function tests, mental and physical condition of the patient.

The Inductotherm Cabinet, which combines the principles of elevation of temperature by short wave high frequency current and maintainance of the temperature by highly saturated air at a temperature not exceeding 110°F, makes possible production of artificial fever therapy. The patient’s temperature is raised to 106°F in 2 to 2 ½ hours and is kept at any desired level thereafter. On an average the use of twelve sessions of fever, each of three hours at 105.8°F is required for the best results in the treatment of neurosyphilis. However, the importance of planning a separate schedule of treatment for each individual patient, having regard to his age, condition, stage of disease etc. cannot be overstressed. The standard aimed at has been to reach as near as 30 hours at a 105°F, in from 8 to 12 sittings. It is generally considered advisable to employ chemotherapy with fever therapy. Either bismuth or both bismuth and tryparsmide as the conditions permit may be started during the course but on days different from the pyrexial sessions, and continued afterwards for 6 to 8 months.

Indications of termination of this type of fever therapy are uncontrolled rise in body temperature, a pulse rate which remains above 150 per min. after administration of fluids by the intravenous route, pulse poor in volume, a systolic blood pressure below 100 millimeters of Hg. and which does not improve after intravenous salines, stupor with incontinence of urine and faeces, persisting vomiting, restlessness, mental confusion with facial pallor and cynosis.

(2) Inoculation of diseases associated with temperature-

Benign tertian malaria is the infection of choice. Preliminary examination of the donor’s blood for the presence of P. vivax and absence of other parasites especially malignant tertian is necessary. Blood is obtained before any anti-malarial drugs are given and transferred directly from patient to patient. Various routes of inoculation, intradermal, subcutaneous, intramuscular, or intravenous may be used. The incubation period varies with the route chosen, being longest with the first and the shortest with the last. The intravenous route is common in practice and takes on an average from 3 to 8 days’ incubation and requires 2 to 3 cc. blood. In an average case from 8 to 10 paroxysms or rises of temperature are allowed provided no untoward reactions develop. Fever is terminated at the end of the course by administering quinine by the intravenous or intramuscular route. Fever therapy carries with it some risk of life hence it must be used very carefully. A general physical examination of the patient to determine his fitness for treatment is essential. Advanced age, marked malnutrition, active pulmonary tuberculosis, nephritis, cardiac decompensation and aortic regurgitation contraindicate therapy. This treatment can only be given in hospitals where careful nursing, close observation under experts will be possible. During the course of the treatment it is essential to take the temperature two hourly, the blood pressure twice a day, and to examine the blood for counts and estimation of haemoglobin and test the urine daily. These procedures are very useful in avoiding undesirable reactions.

Indication for institution of malarial therapy; General paralysis of the Insane, tabes dorsalis and selected cases of neurosyphilis which have proved resistant to other form of treatment. Paresis and taboparesis are imperative indications for the use of malaria for the results here are very much better than with any other form of treatment; hence to postpone malarial therapy in these conditions in favour of a trial of other methods is to invite progressive degeneration.

Dangers: profound anaemia, very low blood pressure, jaundice, and the onset of cardiac failure are some of the indications for the termination of the fever therapy abruptly.

(3) Injections of vaccines and proteins-

Gonococcal vaccines of various types are available. The commonly used are polyvalent vaccine, “sensitized” vaccine, detoxicated or dissolved vaccine, autogenous vaccine, mixed vaccine. They are used according to the various needs and conditions. Polyvalent detoxicated vaccine is very popular. A slight local and general reaction is noticed. Dosage prescribed is as per dosage laid down by the bacteriologist and according to the individual reaction, and successive doses are regulated by close and accurate observation of the effect which the first dose produces the patient. Generally the subcutaneous route is employed. Recently intracutaneous injections of vaccines in place of subcutaneous injections have been used with better results. In fact this mode of superseded other routes of administration. The usual dose advised by this route is about ½ to ⅓ of the subcutaneous dose. It has been shown that the intracutaneous injections produce a greater stimulation of the reticuloendothelial system and a more satisfactory immunity than the subcutaneous, intramuscular or intravenous. Gonococcus exotoxin may be used in this way but the dosage must be small and carefully regulated. Gonococcal vaccines are used in chronic and subacute gonorrhoea and its complications.

Sterile milk: dose 1 to 10 cc. intramuscularly or 0.2 to 0.4cc. intradermally. Indications: Arthritis, keratitis, iritis, buboes, chancroids, chronic gonorrhoea and its complications.

Arthigon, an emulsion of gonococci in urotropin and gono-yatren, an emulsion of gonococci in 3% yatren are occasionally given in chronic gonorrhoea and its complications.

Dmelcos (M.B.) or Special Soft Chancre Vaccine (U.D.C.), dose- ½ to 3 c.c. intravenously. These preparations are very helpful in chancroids, buboes, chronic gonorrhoea, its metastatic complications, etc. They are administered with the object of causing non-specific reaction and their effects are quite satisfactory, especially in chancroids and buboes. It i.e., artificial fever therapy has its dangers and requires skilful nursing and judicious discretion in prescribing bold dosage and vigorous use so as to induce closely followed bouts of fever with only a day or two of remissions are necessary for excellent results.

T.A.B. Vaccine: Dose 25 to 300 millions intravenously. It is used with the object of inducing non-specific reaction. Indications- buboes, chancroids, chronic gonorrhoea and its complications, keratitis, iritis, non-specific chronic urethritis, lymphogranuloma venereum, neurosyphilis, sulphanilamide resistant gonorrhoea.

Sulphonsin, colloidal preparation of sulphur, 2 to 5 c.c. intramuscularly is given in cases of neurosyphilis.

CONCLUSION

Fever therapy is of great value in the treatment of venereal diseases, but has its limitations. Different methods of inducing fever, and their proper indications must be thoroughly understood to reap the best results.

REFERENCES

• Boak, R.A., Carpenter, C.M. Mucci, L.A., and Warren, S.L.: Quoted in Brit. Encycl. Med. Pract 6: 4, 1937.
• Cushing.J.E, Locke, A, et al : Quoted by Wilson, G.S. and Miles, A.A.: Topley and Wilson’s Principles of Bacteriology and Immunity, pp. 1203-1205, Vol.2 (3 rd Edition), London, Edward Arnold & Co., 1946.

TABLE-I

THE COMMON METHODS OF INDUCING FEVER, THEIR INDICATIONS, DOSAGE, ETC.