Girgis, N. I., M. T. Khayyal, E. McConnell, and J. Norton, "Penicillamine as an adjuvant to antimonial therapy, effect on electrocardiographic changes in dogs.", East African medical journal, vol. 47, issue 11, pp. 576-81, 1970 Nov. Abstract

Intravenous injections of tartar emetic at 5 mg/kg body-weight daily for 4 days were given to 55 healthy dogs. Concomitant injections of 11 mg/kg penicillamine were given to 25 of the dogs. 26% of the dogs given tartar emetic alone died during or shortly after treatment, but the mortality of dogs receiving the combined treatment was only 8%. Changes in electrocardiographic pattern were observed in 90% of tartar emetic-treated dogs and in 55% of dogs treated with combined tartar emetic and penicillamine.


ALL schistosomicidal drugs eventually cause a change of location or ‘shift’ of the worms from the mesenteric veins, where they are normally found in infected animals, into the liver. There the parasites ultimately die and are ensheathed and phagocytosed by the protective mechanisms of the host. These worm migrations may be very rapid in onset and short in duration, as occurs with antimonials1; or they may be slow in onset and permanent in duration, as occurs with diphenoxyalkanes2. Various other schistosomicidal drugs produce ‘hepatic shifts’ with intermediate characteristics. The cause of the worm migrations differs with the different drugs, but essentially it results in paralysis of the worms which are thereafter swept back by the blood stream into the liver. Where the course of treatment is inadequate, the parasites regain their muscle control and return to the mesenteric veins.

BUTTLE, G. A., and M. T. Khayyal, "Rapid hepatic shift of worms in mice infected with Schistosoma mansoni after a single injection of tartar emetic.", Nature, vol. 194, pp. 780-1, 1962 May 26. Abstract

MUCH work has already been carried out on the treatment of mice infected with schistosomes. It has been observed that the worms which normally inhabit the mesenteric veins of animals infected with Schistosoma mansoni are forced to migrate to the liver after treatment with active schistosomicidal drugs1–6. This hepatic shift has usually been observed after a full course of treatment, and where the course had been inadequate, relapses were found to occur owing to the re-migration of the worms back to the mesenteric veins. Standen6observed a hepatic shift as early as one day following two oral doses of 42 mgm./ kgm. sodium antimonyl III gluconate, but after 7 days the worms were completely restored to their normal distribution in the hepatic portal system. In the work reported here we followed up the effect of a single dose of tartar emetic on the worm migration to show that the hepatic shift actually occurs much earlier than had been previously expected

Khayyal, M. T., "THE EFFECTS OF ANTIMONY UPTAKE ON THE LOCATION AND PAIRING OF SCHISTOSOMA MANSONI.", British journal of pharmacology and chemotherapy, vol. 22, pp. 342-8, 1964 Apr. Abstract

The rate of uptake and elimination of antimony by both male and female schistosomes has been measured. It has been confirmed that the female schistosome is more susceptible to antimony therapy than the male since she absorbs more drug. The changes in location of the worms and the separation of the sexes following one or more injections of antimony potassium tartrate have been related to the different rates of uptake and elimination of the drug by the two sexes. The suppressive treatment of schistosomiasis is discussed in the light of these observations.

Khayyal, M. T., "The effect of multiple doses of antimonials in Schistosoma mansoni infection.", Bulletin of the World Health Organization, vol. 33, issue 4, pp. 547-51, 1965. Abstract

The treatment of bilharziasis with antimonials has been carried out in the past in a rather arbitrary manner, dosage levels and schedules varying widely and being based on little valid experimental evidence. The author has therefore attempted to determine the optimum dosage intervals with tartar emetic for cure of mice experimentally infected with Schistosoma mansoni.It was already known that schistosomes are swept back into the liver when their level of antimony reaches a certain threshold but that, once that level drops, they re-migrate back to the mesenteric veins. In this work, therefore, the schedule of treatment was arranged so as to relate the intervals between doses to the re-migration of worms to the mesentery. It is shown that there is probably a direct relationship between the number of doses and the total period of time during which the schistosomes can be kept in the liver, so that relatively few doses given at short intervals may be as effective as a larger number of doses at longer intervals.

Khayyal, M. T., "Treatment of intestinal bilharziasis with antimonials: the possible use of dimercaprol as an adjuvant to therapy.", Bulletin of the World Health Organization, vol. 33, issue 4, pp. 589-91, 1965. Abstract
Khayyal, M. T., N. I. Girgis, and E. McConnell, "The use of penicillamine as an adjuvant to tartar emetic in the treatment of experimental schistosomiasis.", Bulletin of the World Health Organization, vol. 37, issue 3, pp. 387-92, 1967. Abstract

One of the principal drawbacks of antimonial therapy in schistosomiasis has been the prevalence of annoying, and sometimes dangerous, side-effects. The adjuvant administration of chelating agents offers a possible solution to this problem, providing this can be achieved without appreciably decreasing the therapeutic effect of the drug.The authors found that the chelating agent penicillamine lowered the toxicity of tartar emetic for mice and hamsters without affecting the tissue uptake of antimony. When administered in a similar manner to hamsters infected with Schistosoma mansoni there was no effect on the uptake of antimony by the parasites, or on the cure rate. This suggests a potential usefulness of penicillamine in antimony therapy.

Khayyal, M. T., N. I. Girgis, and E. McConnell, "The possible inactivation of antimony by schistosomes.", Annals of tropical medicine and parasitology, vol. 62, issue 1, pp. 74-80, 1968 Mar. Abstract
Mikhail, J. W., M. T. Khayyal, and N. I. Girgis, "Activity of antimony dextran glycoside (RL-712) against visceral leishmaniasis in the hamster.", Bulletin of the World Health Organization, vol. 40, issue 2, pp. 327-8, 1969. Abstract
Khayyal, M. T., "Comparison of the chemotherapeutic potencies of 4 antimonial drugs.", Bulletin of the World Health Organization, vol. 40, issue 6, pp. 959-63, 1969. Abstract