This paper describes an investigation of the antifilarial action of hetrazan in experimental animals, with special reference to the mechanism underlying its action. A preliminary communication on the work was given by Hawking, Sewell, and Thurston (1948).Hetrazan is-I -diethylcarbamyl-4-methylpiperazineThe antifilarial action of hetrazan was discovered and described by Hewitt, Kushner, Stewart, White, Wallace, and SubbaRow (1947) working with cotton rats infected with Litomosaides carinii, and its action on human filariasis due to W. bancrofti was shown by Santiago-Stevenson,-Oliver-Gonzalez, and Hewitt (1947). The present experiments were carried out on cotton rats bred at this Institute and infected with Litomosoides by the methods described by Hawking and Sewell (1948). The hetrazan used was the dihydrogen citrate, kindly supplied by American Cyanamid Co., and all doses refer to this salt. Microfilaria counts were made by spreading 5 to 20 cu.mm. of blood on a slide to form a thick film, dehaemoglobinizing in water, fixing in alcohol, and staining with hot haemalum or with Giemsa's stain; the microfilariae were then counted under the microscope.Preliminary experiments in vivo Infected cotton rats were given hetrazan by intraperitoneal injection according to the schedules shown in Table I and daily counts were made of the microfilariae in the blood taken from the tail. The rats were treated about seventy days after infection; during the next month untreated rats usually show a gradual increase in the microfilaria count. According to Harned et al. (1948) the LD50 of hetrazan hydrochloride when given intraperitoneally to rats is 465 mg./kg. In our experiments single intraperitoneal doses of 500 mg. of the citrate per kg. or hourly doses 100 mg./kg. usually caused prostration for 1-1 hour after each injection; repetition of the 500 mg./kg. dose after one day sometimes caused death, but 250 mg./kg. twice daily was well tolerated. The effect on the number of microfilariae in the blood varied considerably in different animals so that precise quantitative results

Some morphological characteristics of Cephalochlamys namaquensis from Xenopus muelleri collected at Kajansi, Kampala, are described.Specimens of cestodes from other localities in Africa are compared with those from Kajansi in order to assess the reliability of the characters of the proposed genus Pseudocephalochlamys Yamaguti, 1959. Reasons are given for rejecting the genus.The embryonated, non-operculate egg capsules hatch at once in water. The ciliated coracidium is eaten by cyclopid copepods and the oncosphere rapidly penetrates through the mid-gut wall into the haemocoel. The procercoid develops a cercomer which moves actively during development and which retains the six hooks of the oncosphere. The procercoid develops the scolex, osmoregulatory canals and calcareous corpuscles typical of the adult while within the copepod. It is enclosed within a membrane. The procercoid is infective to Xenopus toads 20 days after being ingested by the copepod. No other intermediate host has been found.Thermocyclops infrequens Kiefer is the intermediate host at Kajansi, Kampala. The maximum number of C. namaquensis recovered from one toad was 103; usually there are between 1 and 6 per toad. Between 22% and 100% of Xenopus muelleri and X. laevis from different localities are infected with C. namaquensis.I wish to express by thanks to the Fisheries Officers and fishermen of Kajansi Fish Farm who have willingly caught Xenopus for me whenever required, and also to the many other people who have assisted me in getting specimens with which to work.I am also indebted to Mr L. Rugema who prepared most of the histological preparations, to Dr J. Green, Westfield College, London, who kindly identified Thermocyclops infrequens, and to Dr G. Rees, University College of Wales, Aberystwyth, who gave me many useful comments during the course of this work.A research grant from Makerere University College contributed towards the cost of obtaining specimens.

1. Strains of P. berghei resistant to sulphadiazine, pyrimethamine, and methylene blue were produced by treating acute infections with low doses of drug.2. The strain resistant to methylene blue was sensitive to pamaquin, mepacrine, sulphadiazine, proguanil, pyrimethamine, and 2 : 4-diamino-6 : 7-camphano-pteridine.3. The pyrimethamine-resistant strain was cross-resistant to proguanil and its active metabolite CPT, 2 : 4-diamino-6 : 7-camphanopteridine, 2 : 4-diamino-6 : 7-(l′-ethylindolo)-pteridine, and 2 : 4-diamino-5-p-chlorophenylpyrimidine.4. The sulphadiazine-resistant strain was cross-resistant to pyrimethamine, sulphanilamide, proguanil and its active metabolite CPT, 2 : 4-diamino-6 : 7-dinhexylpteridine, and 2 : 4-diamino-6 : 7-diisopropylpteridine. It was as sensitive as the parent strain to quinine, mepacrine, chloroquin, pamaquin, methylene blue, and M 3349.5. The action of sulphadiazine against the sulphadiazine-resistant strain was inhibited by the same doses of p-aminobenzoic acid and folic acid as were required with the parent strain, although the dose of sulphadiazine was increased 30-fold.

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Non-splenectomized mice developed acute infections of Eperythrozoon coccoides after inoculation, but were then immune to re-infection. Splenectomy evoked acute infections that were heavier and longer in duration than the primary infection; during this phase, the parasites doubled in number in about 5 hr. The presence of splenic tissue transplanted subcutaneously did not prevent this evocation by splenectomy.The number of eperythrozoa decreased rapidly after the peak of infection had been reached, but no immune factor was detected in the blood. No immune factor or infection was transmitted from mother to offspring through the milk.Citrated blood remained infective for 11 days at 3° C., for 17 hr. at 16–17·7°C. and for 3 hr. at 37° C. It was not infective after 24 hr. at either 24° C. or 16–17·7°C., or after 5 hr. at 37° C. Parasitized blood was not infective after drying.Citrated blood was infective to mice when given by mouth, but was not infective when applied externally. Urine and faeces were non-infective.Eperythrozoa remained infective when infected blood was diluted with twice its volume of water and left for 24 hr. at 3° C. Phenol, 0·5%, rendered citrated blood non-infective in 1 hr. Neoarsphenamine, 0·1%, reduced the infectivity of citrated blood in 16 hr., and rendered it non-infective in 26 hr.Cortisone did not affect the course of infection of E. coccoides in mice when given subcutaneously, 1·0 mg. per 20 g. mouse, once daily for 6–9 days.Concurrent infection with Plasmodium berghei evoked relapses of E. coccoides during the terminal stages of the P. berghei infection.