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ANOTHER FIELD EXPERIMENT WITH PLASMOQUINE.
1366
ANOTHER FIELD EXPERIMENT WITH
PLASMOQUINE.
dioxide dissolved in the chloroform. A test sug- tocyte rate for P. falciparum from 10.6 per cent. to. gested by Utz, in which chloroform is treated with nil, the spleen rate remaining fairly constant, and benzidine for 24 hours in the dark, yields a slight the haemoglobin showing a small rise from 66 to 70 turbidity with about 5 parts per million, which is per cent. Based on the total number of labourers rather more delicate ; but a general reaction given by and dependents throughout the experimental period mixtures of phenols and aldehydes with condensing the parasite rate fell from 28-2 to 20-2 per cent. On agents was found by Allport to be more delicate the first control estate the parasite rate rose from 22and rapid. The reagents chosen are resorcinol and to 23-8 per cent. during the year, and although the, vanillin. To 15 c.cm. of medicinal chloroform spleen rate remained constant, the average haemo. contained in a dry stoppered bottle of about 25 c.cm. globin fell. On the second control estate, too, the capacity add 20 mg. each of resorcinol and vanillin. parasite rate fell from 17.2 to 13.7 per cent. ; the Replace the stopper and when the reagents have spleen rate also showed a slight fall, but the haemodissolved, set the bottle aside in a dark place for globin remained constant. In view of all the possione hour. Add 5 c.cm. of 1 per cent. aqueous ammonia bilities of extraneous infection the reduction of the solution, shake and allow the mixture to separate.’ parasite rate within a year from 28 to 17 per cent. When there has been prior formation of phosgene or indicates that the plasmoquine was of definite value, in the presence of hydrochloric acid a pink or red though the results fall somewhat short of expectation. colour develops in the aqueous layer, reaching its Only one instance of idiosyncrasy to plasmoquine full value in about 30 seconds, its intensity varies was noted-an elderly male who developed gastric with the quantity of impurity present. The presence symptoms, combined with albuminuria, after the of alcohol is necessary for the development of the first dose. His spleen was greatly enlarged, and his colour, which is given strongly by as little as 1 part haemoglobin percentage was 90. After a period of per million of phosgene, blank tests with pure chloro- treatment he was able to take plasmoquine 0-02 g. form showing no colour at all until after about twice weekly. two minutes when the liquid darkens by reason of the resorcinol present. The presence of even a small INTRAMUSCULAR ADMINISTRATION OF LIVER amount of phosgene in a drug which is used to produce EXTRACT AND THE RETICULOCYTE CRISIS. anaesthesia seems very undesirable and this new test DURING the last few months we have repeatedly should be of value in deciding whether a sample made mention of both the theoretical and practical is suitable for this purpose. administration of liver extracts value of ____
parenteral
ANOTHER
FIELD EXPERIMENT WITH
PLASMOQUINE. THE gametocidal action of plasmoquine has become familiar, partly as the result of experimental work done at the Institute for Medical Research, Kuala Lumpur, F.M.S., of which Dr. A. Neave
Kingsbury is director. This property is especially noticeable in its action upon the gametocytes of Plasmodium falciparum, and to a lesser extent upon those of P. viu:ax and P. malaria. There now seems good reason to believe that malaria, at all events of the subtertian variety, might be eradicated from an isolated population by regular plasmoquine dosage. How this was put to the test under working conditions in an extensive field experiment lasting one year is described by Dr. Kingsbury in a report from the Institute which has just reached us. A malarious rubber estate, having a population of about 330 labourers and dependents, was chosen for the test, and two neighbouring estates with populations of 360 and 400 were selected as controls. Parasite and spleen rates, and haemoglobin percentages were determined on both just before the commencement of the test, and thereafter at quarterly intervals. Plasmoquine 0-04 g. was given to adults twice weekly, and Thursdays, appropriate smaller on Mondays doses to children down to 6 years of age, and to infants an emulsion of the drug from a graduated pipette. Well over 90 per cent. of the population received plasmoquine on practically every treatment day. The experiment was handicapped by the present unfortunate conditions on rubber estates, and the experimental estate was not absolutely isolated, for in the evenings there was some exchange of visits with neighbouring estates, thus making it possible for an occasional gametocyte carrier to infect anophelines in the experimental area. Nevertheless during the year among the original population the parasite rate on the experimental estate fell from 27.2 to 17-4 per cent., and the game-
in pernicious anaemia. M. Ganssten, who was the first to use intramuscular injections extensively, has now summarised his conclusions 2 from a study of 100 successfully treated cases, though unfortunately he provides no details of the blood examinations which lessens the value -of the work. He gives a daily injection of extract made from 5 g. of liver, only rarely finding it necessary to increase the dose to an equivalent of 400 g. of liver, until a normal blood count is reached, usually in five to eight weeks. The injections are then reduced to once a week, with a larger dose once a fortnight. This method has obvious advantages in treating ambulant patients, and he concludes from its success that the body is capable of storing the essential principle. Relapses associated with some intercurrent infection occurred in most of the cases two to four months after cessation of treatment. A few patients were well as long as 12 months without any form of liver, but remissions of this kind were noted before the introduction of liver and cannot therefore be considered as evidence of a storage mechanism. Ganssten has had no failures, and attributes reported liver-resistant cases as due to faulty diagnosis or insufficient dosage ; in this he agrees with other workers who have had an extensive experience of liver treatment. He offers no data to support the claim that intramuscular extracts are of value in secondary anaemias, especially those of gynaecological origin. His attack on the value of the reticulocyte crisis as a measure of the effectiveness of treatment does not appear justified by his own evidence. He found that there might be a rise in the reticulocyte count with no rise in the total red cell count in patients with acholuric jaundice treated with liver extracts by intramuscular injection. Since, however, the reticulocyte count may be as high as 65 per cent. in untreated cases in this condition (Dawson 3), such observations need careful control. He also obtained a reticulocyte response 1 Verhandl. d. Deut. Gesellsch. f. Inn. Med., 1930, 2 Deut. med. Woch., Nov. 13th, p. 1926. 3 Brit. Med. Jour., 1931, i., 921.
xlii., 524.
ANOTHER FIELD EXPERIMENT WITH
PLASMOQUINE.
dioxide dissolved in the chloroform. A test sug- tocyte rate for P. falciparum from 10.6 per cent. to. gested by Utz, in which chloroform is treated with nil, the spleen rate remaining fairly constant, and benzidine for 24 hours in the dark, yields a slight the haemoglobin showing a small rise from 66 to 70 turbidity with about 5 parts per million, which is per cent. Based on the total number of labourers rather more delicate ; but a general reaction given by and dependents throughout the experimental period mixtures of phenols and aldehydes with condensing the parasite rate fell from 28-2 to 20-2 per cent. On agents was found by Allport to be more delicate the first control estate the parasite rate rose from 22and rapid. The reagents chosen are resorcinol and to 23-8 per cent. during the year, and although the, vanillin. To 15 c.cm. of medicinal chloroform spleen rate remained constant, the average haemo. contained in a dry stoppered bottle of about 25 c.cm. globin fell. On the second control estate, too, the capacity add 20 mg. each of resorcinol and vanillin. parasite rate fell from 17.2 to 13.7 per cent. ; the Replace the stopper and when the reagents have spleen rate also showed a slight fall, but the haemodissolved, set the bottle aside in a dark place for globin remained constant. In view of all the possione hour. Add 5 c.cm. of 1 per cent. aqueous ammonia bilities of extraneous infection the reduction of the solution, shake and allow the mixture to separate.’ parasite rate within a year from 28 to 17 per cent. When there has been prior formation of phosgene or indicates that the plasmoquine was of definite value, in the presence of hydrochloric acid a pink or red though the results fall somewhat short of expectation. colour develops in the aqueous layer, reaching its Only one instance of idiosyncrasy to plasmoquine full value in about 30 seconds, its intensity varies was noted-an elderly male who developed gastric with the quantity of impurity present. The presence symptoms, combined with albuminuria, after the of alcohol is necessary for the development of the first dose. His spleen was greatly enlarged, and his colour, which is given strongly by as little as 1 part haemoglobin percentage was 90. After a period of per million of phosgene, blank tests with pure chloro- treatment he was able to take plasmoquine 0-02 g. form showing no colour at all until after about twice weekly. two minutes when the liquid darkens by reason of the resorcinol present. The presence of even a small INTRAMUSCULAR ADMINISTRATION OF LIVER amount of phosgene in a drug which is used to produce EXTRACT AND THE RETICULOCYTE CRISIS. anaesthesia seems very undesirable and this new test DURING the last few months we have repeatedly should be of value in deciding whether a sample made mention of both the theoretical and practical is suitable for this purpose. administration of liver extracts value of ____
parenteral
ANOTHER
FIELD EXPERIMENT WITH
PLASMOQUINE. THE gametocidal action of plasmoquine has become familiar, partly as the result of experimental work done at the Institute for Medical Research, Kuala Lumpur, F.M.S., of which Dr. A. Neave
Kingsbury is director. This property is especially noticeable in its action upon the gametocytes of Plasmodium falciparum, and to a lesser extent upon those of P. viu:ax and P. malaria. There now seems good reason to believe that malaria, at all events of the subtertian variety, might be eradicated from an isolated population by regular plasmoquine dosage. How this was put to the test under working conditions in an extensive field experiment lasting one year is described by Dr. Kingsbury in a report from the Institute which has just reached us. A malarious rubber estate, having a population of about 330 labourers and dependents, was chosen for the test, and two neighbouring estates with populations of 360 and 400 were selected as controls. Parasite and spleen rates, and haemoglobin percentages were determined on both just before the commencement of the test, and thereafter at quarterly intervals. Plasmoquine 0-04 g. was given to adults twice weekly, and Thursdays, appropriate smaller on Mondays doses to children down to 6 years of age, and to infants an emulsion of the drug from a graduated pipette. Well over 90 per cent. of the population received plasmoquine on practically every treatment day. The experiment was handicapped by the present unfortunate conditions on rubber estates, and the experimental estate was not absolutely isolated, for in the evenings there was some exchange of visits with neighbouring estates, thus making it possible for an occasional gametocyte carrier to infect anophelines in the experimental area. Nevertheless during the year among the original population the parasite rate on the experimental estate fell from 27.2 to 17-4 per cent., and the game-
in pernicious anaemia. M. Ganssten, who was the first to use intramuscular injections extensively, has now summarised his conclusions 2 from a study of 100 successfully treated cases, though unfortunately he provides no details of the blood examinations which lessens the value -of the work. He gives a daily injection of extract made from 5 g. of liver, only rarely finding it necessary to increase the dose to an equivalent of 400 g. of liver, until a normal blood count is reached, usually in five to eight weeks. The injections are then reduced to once a week, with a larger dose once a fortnight. This method has obvious advantages in treating ambulant patients, and he concludes from its success that the body is capable of storing the essential principle. Relapses associated with some intercurrent infection occurred in most of the cases two to four months after cessation of treatment. A few patients were well as long as 12 months without any form of liver, but remissions of this kind were noted before the introduction of liver and cannot therefore be considered as evidence of a storage mechanism. Ganssten has had no failures, and attributes reported liver-resistant cases as due to faulty diagnosis or insufficient dosage ; in this he agrees with other workers who have had an extensive experience of liver treatment. He offers no data to support the claim that intramuscular extracts are of value in secondary anaemias, especially those of gynaecological origin. His attack on the value of the reticulocyte crisis as a measure of the effectiveness of treatment does not appear justified by his own evidence. He found that there might be a rise in the reticulocyte count with no rise in the total red cell count in patients with acholuric jaundice treated with liver extracts by intramuscular injection. Since, however, the reticulocyte count may be as high as 65 per cent. in untreated cases in this condition (Dawson 3), such observations need careful control. He also obtained a reticulocyte response 1 Verhandl. d. Deut. Gesellsch. f. Inn. Med., 1930, 2 Deut. med. Woch., Nov. 13th, p. 1926. 3 Brit. Med. Jour., 1931, i., 921.
xlii., 524.