male hormones for the preven- tion OF RELAPSES IN MALARIA

By S. J. GROSS, m.d. Medical Superintendent, Baer Hospital, Chirala, India

A number of methods and of drugs are

employed in the after-treatment of malaria Wlth the aim to prevent relapses. The known antimalarial drugs are unable to do so; in fact, some of the drugs have also the property to

Precipitate a relapse. I used salvarsan for some time with quite satisfactory result but gave it up when I had a relapse which proved fatal.

Therefore, I was looking for some measure

which would not be provocative and would be value in the prevention of relapses. I could observe in a number of patients who

had frequent relapses that these relapses recurred at regular intervals, so that the next attack could be predicted accurately. A regular interval between the relapses has also been

observed by Noe et al (1946) in chronic

south-west Pacific malaria, and Nocht and

Mayer (1937) described periodical relapses after three weeks. In my cases the interval was

between three to four weeks. rhe regular recurrence made me suspect that

in these cases some cyclical activity of the body might be responsible for the precipitation of the relapses. The interval of about four weeks ?or a multiple thereof?points to the menstrual cycle as the periodical activity eventually responsible for the recurrence. Closer scrutiny of setiological and of clinical features reveals a

number of facts which indicate the participation of female or (estrogenic factors in the mechanism of malaria. The following facts seem signi- ficant :?

1. Malaria is transmitted by the female

anopheles only. 2. It has been observed by many authors

that female gametocytes are more numerous in the blood than male gametocytes; female

gametocytes have been found to predominate in the relation of from 3 to 1, up to 6 to 1.

3. It is stated that in relapses chiefly female forms are seen in thick drop preparations (Nocht and Mayer, 1937).

4. A great incidence of abortions and of premature births in women suffering from malaria has been observed by many authors. In this connection it may be recalled that administration of cestrin during pregnancy may lead to abortion.

5. Malaria is said to cause impotence, sterility and frigidity in a number of cases.

Animal experiments haAre shown that injections of cestrin will lead to change of the sex character- istics, and may eventually cause atrophy of the gonads.

6. It is generally stated that women are

possibly more susceptible than men to malarial infection.

In view of the above facts I concluded that the inhibitory effect of male hormone might help to suppress and to counteract those factors which are responsible for the periodical relapse. Administration of testicular hormone has the

effect that follicle maturation and luteinization

are suppressed, the vaginal changes of oestrus

are absent, and that menstruation (in monkeys) is completely inhibited. For the present investigation only cases of

vivax infection were selected, as these have a

greater tendency for relapses. One week after routine treatment of the attack nine of these

patients were given four injections of perandren (testosterone propionate) on alternate days. The patients have been under observation for a period of 6 to 8 months after the administra- tion of perandren. During this period all of these cases had an inoculation with T.A.B. vaccine which could have provoked a relapse. None was seen after the inoculation. One of the nine patients had a true relapse, while two had

' relapses ' of an unexpected nature during

the period of observation. A short description of some of the cases is given below :?

1. C. A., male, 46 years old, had his first attack of malaria in 1944. Patient had also a

syphilitic infection, and therefore he was

allowed to have a number of fever bouts before treatment was given. In spite of simultaneous arsenic treatment, patient had a number of relapses. After his last relapse on 2nd October, 1945, he was given four injections of testosterone propionate one week after treatment of the

relapse. On the 2nd November, 1945, he returned to hospital with another relapse. On each occasion P. vivax rings were found in the blood.

2. V. C., male, 32 years old, had attacks of malaria in July and August 1945. On each occasion P. vivax rings were found in the blood. On 23rd September, 1945, he had another

relapse. After treatment of the relapse he was given four injections of testosterone propionate. On 24th October, 1945, he returned to hospital complaining of chills. A blood slide was taken which showed P. vivax rings. However, the

66 THE INDIAN MEDICAL GAZETTE [Feb., 1947

chill was not followed by any rigor or fever, and patient left hospital after a few hours. Before leaving hospital he was given another

injection of 10 mg. of perandren. 48 hours after the first chill, patient returned to hospital with chills, and this time it was followed by rigor and fever. Another slide was taken, and it showed now only falciparum rings. Further course was uneventful, and the patient has not had any further relapse since.

3. B. C., male, 39 years old, had a massive and serious vivax infection on 31st August, 1945. After treatment of the attack he was given 40 mg. of male hormone. He returned to

hospital on the 24th December, 1945, complain- ing of chills. Temperature was 98.6?; a smear was taken and showed falciparum rings only. The chill was not followed by any fever, and the patient left hospital without having any further treatment. Subsequently he did not develop any further chills, nor has he had any relapse since.

4. D. E., male, 30 years old, had an attack of vivax malaria on 8th September, 1945. He was readmitted with a relapse on 5th October, 1945. On admission he had a slight temperature, chill, pains in the joints and abdomen. The next day he was given an injection of male hormone in addition to mepacrine tablets. On the 7th afternoon he had a fever paroxysm of 104?. After this attack of fever the patient had no further paroxysm, nor was any provoked by the other injections of perandren which were

given subsequently on alternate days. Patient lias not had any relapse since.

In none of the other five cases was there any relapse after the injections of male hormone nor was there any untoward reaction.

Comment.?Only one out of nine cases of

relapsing malaria which were given perandren injections as after-treatment had a real relapse. Two other cases had chills, but no fever, though parasites were found in the blood smear. It is noteworthy that when male hormone was

given in the preliminary stage, as in cases 2

and 4, this was followed by a fever attack; however, the patient had no paroxysm thereafter. No fever was caused by the- injections of testosterone propionate in those cases which were injected one week after the actual attack.

It has to be mentioned that all patients felt much better after the injections of male hormone, and that they had a speedier recovery from the debilitating effects of the malaria attack. This

may be attributed to the tonic effects of testosterone propionate. Korenchevsky et al. (1941) investigating the effect of testosterone

propionate on liver, kidney and heart found that it possesses hepatotrophic, nephrotrophic and

cardiotropic effects. The number of cases is admittedly too small

to draw any definite conclusions, but the results seem of sufficient interest, so as to warrant further investigations. It is possible that the dosage used in the present series was too small

and that larger doses, e.g. six injections of 25 mg., might be given.

I want to thank Messrs. Ciba (India) Limited for the

supply of perandren.

REFERENCES

Korenchevsky, V., et al. Brit. Med. J., i, 396. (1941).

.

Nocht, B.. and Mayer, Malaria. John Bale Medical M. (1937). Publications, London.

Noe, W. L., Greene, Amer. J. Med. Set., 211, 215. C. C., and Cheney, G. (1946).

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