J. Herrero
Clinical Research Department, F. Hoffmann-La Roche & Co.. Basle, Switzerland
ABSTRACT
Review of the early literature as well as more recent results show that sulfonamides possess a distinct antimalarial activity. However, when give alone, their action is less marked and slower than that of the antimalarials commonly used in the treatment of the acute attack. Combinations with pyrimethamine provide better results, even in cases of pyrimethamine and chloroquine resistance. This warrants further investigations in an attempt to develop a therapeutic agent suitable for the treatment of such resistant cases. It may also be possible with an appropriate combination of pyrimethamine with a sulfonamide to achieve a satisfactory method for suppressive treatment both in areas with and without pyrimethamine resistance. Three main points must still be carefully studied: 1) the risk of developing malaria resistance against one or both of the components of the combination. 2) The risk of developing bacterial resistance to sulfonamides if these substances are used on a large scale in too low doses. It seems indeed that antimalarial effect with the combination of sufonamides +- pyrimethamine can be obtained with doses of sulfonamides which are below those usually employed in bacterial diseases. Since the range of the ratios providing potentiation is rather large, only ratios of the combination sulfonamides: pyrimethamine should be chosen in which an antfbacterial sulfonamidemia is guaranteed. 3) It goes without saying that, although both pyrimethamine and modem sulfonamides, when given by themselves, have proved tc possess a large margin of safety, long term administration of their combination should be careful studied from the point of view of possible side effects.
Substantial evidence has already been produced to show that the long acting sulfonamide Fanasil (Ro 4-4393) given once or once weekly possesses marked schizonticidal activity against P. falciparum. Although its action is slower than that of 4-aminoquinolines, it may be useful as a second choice drug in semi-immune subjects for the therapy of falciparum malaria. Preliminary results show that, when combined with pyrimethamine, Fanasil is highly effective in suppressing fever and asexual parasitemia due to P. falciparum. Single doses of 1 g Fanasil together with 50 mg pyrimethamine seem to be adequate for the treatment of acute falciparum malaria in semi-immune patients. The onset of action of the combination is much more rapid than that of the single components. Weekly doses of 500 mg Fanasil and 25 mg pyrimeihamine appear to provide satisfactory suppressive effects against P. falciparum at least in East Africa. This combination is active on strains which do not respond satisfactorily to the standard doses of pyrimethamine and/or chloroquine and seems to have a satisfactory sporontocidal effect.
Preliminary results indicate that Fanasil alone cannot be recommended for use against the other human malaria parasites. The combination with pyrimethamine appears to be much more effective. East African strains of P. malariae seem to respond better to the combination than do Malayan strains of P. vivax but further trials are required before definite assessment can be made.
Fanasil by itself has no gametocytoddal or sporontocidal action but seems to potentiate the effect of pyrimethamine at least on sporogony of P. falciparum.
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REFERENCES
1) AGUIRRE, M. & JIMÉNEZ CASADO, M.: “Expérimentation clinique avec un nouveau sulfamide, le Ro 4-4393” (paper presented at the III Int. Congr. Chemotherapy, Stuttgart, July 1963. Proceedings pp. 672-675. Thieme Verlag, Stuttgart, 1964). [ Links ]
2) ALMEIDA, D.: “Notas sôbre os trabalhos realizados pela campanha de erradicação da malária, independentemente ou sob forma de convênio, a respeito do comportamento anômalo da cêpa de Plasmodium falciparum resistente aos antimaláricos usuais” (presented at the II Congr. of the Brazil. Soc. Trop. Med.. Goiânia. January 1966). [ Links ]
3) BARCLAY, C.A. et al.: “Terapêutica de la lepra con el preparado Ro 4-4393”. La Semana Médica 72: …. 303-309, 1965. [ Links ]
4) BASU, P.C. et al.: “Treatment of human malaria by diaminodiphenyl-sulfone (DDS), singly and in combination with pyrimethamine. A preliminary study of their effects in P. vivax and P. falciparum infections in Rajasthan, India”. Indian J. Malariol. 16: 157, 1962. [ Links ]
5) BASU, P.C. et. al.: “Potentiation of activity of diaphenyl-sulfone and pyrimethamine against P. gallinaceum and. P. cynomolgi bastianelli“. Bull. WHO 31: 699, 1964. [ Links ]
6) BISHOP, A.: “The action ol 2:4-diamino-6, 7-diisopropylpteridine upon Plasmodium gallinaceum and its relation to other compounds which are pteroylglutamic acid antagonists”. Parasitology 44: 450-464, 1954. [ Links ]
7) BISHOP, A.: “Drug resistance in protozoa”. Biol. Rev. 34: 445, 1959. [ Links ]
8) BISHOP, A.: “Resistance to diaminodiphenylsulphone in Plasmodium gallinaceum“. Parasitology 55: 407-414, 1965. [ Links ]
9) BRENER, Z.: Personal communication. [ Links ]
10) CHOPRA, R.N. & DAS GUPTA, B.M.: “A note on the therapeutic efficiency of soluseptazine in simian malara P. knowlesi). Indian med. Gaz. 73: .. 395, 1938. [ Links ]
11) CHOPRA. R.N. & DAS GUPTA, B.M.: “M. & B. 693 (2-sulphanilyl-aminopyridine) in ape inalaria”. Indian med. Gaz. 74: 201, 1939. [ Links ]
12) CHOPRA, R.N. et al.: “Prontosil in Indian strains of malaria”. Indian med. Gaz. 74: 321, 1939. [ Links ]
13) CHOPRA, R.N. et al.: “M. & B. 693 in Indian strains of malaria”. Indian med. Gaz. 74: 658, 1939. [ Links ]
14) CHOPRA, R.N. & BASU, B.C.: “Studies on the effect of antimalarial círugs upon the infectivity of patients to mosquitoee. III. “Prontosu”. J. mal. Inst. India 2: 153, 1939. [ Links ]
15) COATNEY, G.R. & COOPER, W.C.: “The prophylactic effect of sulfadiazine and sulfaguanidine against mosquitoborne Plasmodium gallinaceum infection in the domestic fowl (preliminary report)”. Publ. Hlth Rep., Wash. 59: 1455, 1944. [ Links ]
16) COATNEY, G.R. et al.: “Studies in human malaria. I. The protective action of sulfadiazine and sulfapyrazine against sporozoite-induced falciparum malaria”. Amer. J. Hyg. 46: 84, 1947. [ Links ]
17) COATNEY, G.R. et al.: “Studies in human malaria. II. The suppressive action of sulfadiazine and sulfapyrazine against snorozoite-induced vivax malaria (St. Elizabeth strain)” Amer. J. Hyg. 46: 105, 1947. [ Links ]
18) COGGESHALL, L.T.: “Prophylactic and therapeutic effect of sulphonamide compounds in experimental malaria”. Proc. Soc. exp. Biol., N. Y., 38: 768, 1938. [ Links ]
19) COGGESHAL, L.T.: “The cure of Plasmodium knowlesi malaria in rhesus monkeys with sulphanilamide and their susceptibility to reinfection” Amer. J. trop. Med. 18: 715, 1938. [ Links ]
20) COGGESHALL, L.T.: “The selective action of sulfanilamide on the parasites of experimental malaria in mon. keys in vivo and in vitro”. J. exp Med. 71: 13, 1940. [ Links ]
21) COGGESHALL, L.T.: “Infection of Anopheles quadrimaculatus with Plasmodium cynomolgi, a monkey malaria parasite, and with Plasmodium lophurae, an avian malaria parasite”. Amer. J. trop. Med. 21: 525, 1941. [ Links ]
22) COGGESHALL, L.T. & MAIER, J.: “Determination of the activity of various drugs against the malaria parasite”. J. infect. Dis. 69: 108, 1941. [ Links ]
23) COGGESHALL, L.T. et al.: “The effectiveness of two new types of chemotherapeutic agents in malaria, sodium p, p’-diaminodiphenylsulfone N,N’-didextrosesulfonate (promin) and 2-sulfanilamida pyrimidine (sulfadiazine)”. J. Amer. med. Ass. 117: 1077. 1941. [ Links ]
24) COGGESHALL, L.T. et al, : “Prophylactic and curative effects of certain sulfonamide compounds on exoerythrocytic stages in Plasmodium gallinaceum malaria”. Proc. Soc. exp. Biol. N.Y., 57: 286, 1944. [ Links ]
25) COTTIER, P. & HALDEMANN, G.: “De l’emploi d’un sulfamidé (Ro 4-4393) à durée d’action prolonegée dans le traitement de la pyélonéphrite chronique”. Rev. méd. Suisse Romande 84, N.° 4, 1964. [ Links ]
26) COXON, R.V. êz HAYES, W.: “Investigation into efficacy of sulphadiazine in treatment of malaria” Trans. Roy. Soc. trop. Med. Hyg. 39: 196, 1945. 1945) . [ Links ]
27) CURD, F.H.S.: “The activity of drug in the malaria of man, monkeys and birds”. Ann. trop. Med. Parasit. 37: 115 1943 [ Links ]
28) DAVEY. D.G.: “The use of avian malaria for the discovery of drugs effective in the treatment and prevention of human malaria. I. Drugs for clinical treatment and clinical prophylaxis”. Ann. Trop. Med. Parasit. 40: 52-73, 1946. [ Links ]
29) DAVEY, D.G.: “Chemotherapy of malaria. Part 1: Biological basis of testine: methods”, in: Schnitzer, R.J. & Hawking, F.: “Experimental chemotherapy”, vol .1. Academic Press, New York & London. 19R3; [ Links ]
30) DeGOWIN, R.L. & POWELL, R.C.: “Drug-resistant falciparum malaria” J. Lab. & Clin. Med. 64: 851, 1964. [ Links ]
31) DÍAZ DE LEÓN. A.: “Primeiros casos de paludismo tratados por un derivado de la sulfanilamida”. Bol.,, Ofic. sanit. panamer. 16: 1039, 1937. [ Links ]
32) DÍAZ DE LEÓN, A.: “Las sulfanilamidas en el tratamiento dei paludismo” Medicina Méx. 18: 89, 1938. [ Links ]
33) DÍAZ DE LEÓN, A.: “El paludismo y su tratamiento intravenoso pór las sulfanilamidas”. Medicina Méx. 20: 551, 1940. [ Links ]
34) EYLES, D.E. & COLEMAN, N.: “Synergistic effect of sulfadiazine and Daraprim against experimental toxoplasmosis in the mouse”. Antibiotics & Chemother. 8: 483, 1953. [ Links ]
35) FAGET, G.H. et al.: “Unsuccessful treatment of malaria with sulfonamide compounds”. Publ. Health Rep., Wash. 53: 1364, 1938. [ Links ]
36) FAIRLEY, N.H. et al.: “Chemotherapeutic suppression and prophylaxis in malaria”. Trans. Roy. Soc. trop. Med. Hyg. 38: 311, 1945. [ Links ]
37) FARINAUD, E. & RAGIOT, C.: “Recherches sur l’emploi des dérivés de la sulfamide dan,s le traitement du paludisme”. Bull. Soc. Path. exot. 31: 907, 1938. [ Links ]
38) FARINAUD, E. & ELICHE, J.: “Nouvelles observations sur le traitement du paludisme par les dérivés de la sul. famíde”. Bull. Soc. Path. exot. 32: du paludisme par les dérivés de la su- 674, 1939. [ Links ]
39) FAUCON, R. et al.: “Etude de l’activité ‘in vitro’ sur Neisserla intracellularis et ‘in vivo’ dans la méningite cérébrospinale de la sulfanilamido-4-diméthoxy-5, 6-pyrimidine”. Médecine Troo. 24, numéro spécial, 1964. [ Links ]
40) FERRARIS DE GASPARE, P.F. & PENNA CAROPPI, M.: “Considérations sur l’emploi d’un nouveau sulfamide retard dans le traitement du tra. chome dans des régions hyperendémiques”. Rev. Int. Trachome 43: 132-136, 1966. [ Links ]
41) FINDLAY, G.M. et al.: “Investigations in the chemotherapy of malaria in West Africa. V. Sulphonamide compounds”. Ann. trop. Med. Parasit. 40: 358, 1946. [ Links ]
42) FINDLAY, G.M.: “Recent advances in chemotherapy”, vol. II. J. & A. London Churchill Ldt., 1951. [ Links ]
43) FREIRE AMERICANO, S. & PARAENSE, W.L.: “The prophylactic and curative action of sulfadiazine (2-sulfanilamide-pyrimidine), sulfapyridine (2-sulfanilamide-pyridine) and sulfanilamide (p-aminobenzo-sulfonamide) on erythro and exoerythrocytic cycles of ‘Plasmodium gallinaecum‘L Therapeutic and parasitological aspects) ” Rev. Bras. Biol. 4: 27, 1944. [ Links ]
44) FRENKEL, J.K. & JACOBS, L.: “Ocular toxoplasmosis”. A.M.A. Arch. Ophth. 69: 260-279, 1958. [ Links ]
45) GARDNER, W.A. & DEXTER, L.: “A case of quartan malaria following transfusion and treated with sulfanilamide”. J. Amer. med. Ass. 111: .. 2473, 1938. [ Links ]
46) GOODWIN, L.G. & ROLLQ, I.M.: In “Biochemistry and Physiology of Protozoa” (S.H. Hutner and A. Lwoff, eds. vol. II, pp. 225-276. Academic Press, New York, 1955. [ Links ]
47) GREENBERG, J.: “The potentiation of the antimalarial activity of chlorguanide by p-aminobenzoic acid competitors”. J. Pharmacol. 97: 238-242. 1949. [ Links ]
48) GREENBERG, J.: “The antimalarial activity of 2, 4-diamino-6, 7-diphenylpterin; its potentiation by sulphadiazine and inhibition by pteroylglutamic acid’. J. Pharmacol. 97: 484-491, 1949. [ Links ]
49) GREENBERG, J.: “The effect of analogues of folic acid on the activity of sulphadiazine against Plasmodium gallinaceum“. Exptl. Parasitol. 3: 351-357, 1954. [ Links ]
50) GREENBERG, J. & RICHESON, E.M.: “Potentiation of the antimalarial activity of sulphadiazine by 2, 4-diamino 5-aryloxypyrimidines”. J.’ Pharmacol. 99: 444-4449, 1950. [ Links ]
51) HALL, W.E.B.; “The sulphanilamides in tertian malaria”. J. Pharmacol. 63: 353, 1938. [ Links ]
52) HARINASUTA, T. & VIRAVAN, C.: “Sulphormethoxine (Fanasil) and combinations of sulphormethoxine (Fanasil) and chloroquine or pyrimethamine (Daraprim) in the treatment of chloroquine-resistant falcinarum malaria in Thailand” (presented at the llth Pacific Science Congress, Tokyo, August 1966). [ Links ]
53) HAWKING, F. & THURSTON, J.P.: “Chemotherapeutic and other studies on the pre-erythrocytic forms of simian malaria Plasmodium cynomolgi“. Trans. Roy. Soc. Trop. Med. Hyg. 46: 293-300, 1952. [ Links ]
54) HAWKING, F.: Quoted by Goodwin. L.G. and Rollo, I.M. in: “The chemotherapy of malaria, piroplasmosis. trypanosomiasis, and leishmaniasis” Biochemistry and physiology of protozoa, vol. II, Academic Press, New York, 1955. [ Links ]
55) HAWKING, F.: “Chloroquine resistance in Plasmodium berghei“. Amer. J. Trop. Med. Hyg. 15: 287-293, 1966. [ Links ]
56) HILL, R.A. & GOODWIN, H.M., Jr.: “‘Prontosil’ in treatment of malaria: report of 100 cases”. Sth. med. J.. Nashville, 30: 1170, 1937. [ Links ]
57) HILL, J.: “The schizonticidal effect of some antimalarials against Plasmodium berghei“. Ann. Trop. Med. Parasitol. 44: 291-297, 1950. [ Links ]
58) HILL, J.: “Chemotherapy of malaria. Part 2: The antimalarial drugs”, in: Schnitzer, R.J. & Hawking, F.: “Experimental chemotherapy”, vol. I Academic Press, New York & London, 1963. [ Links ]
59) HITCHNINGS, G.H.: “The use of an antmietabolite in the chemotherapy of malaria and other indications” Clin. Pharmacol. Therap. 1: 570, 1960. [ Links ]
60) HITCHINGS, G.H.: “The utilization of biochemical differences between host and parasite as a basis for chemotherapy’ in: “Drugs, Parasites and Hosts” (L.G. Goodwin & R.H. Nimmo-Smith, eds.), p. 241. J. & A. Churchill Ltd., London, 1962. [ Links ]
61) HOLZ, J.: (Personal communication). [ Links ]
62) HURLY, M.G.D.: “Potentiation of pyrimethamine by sulphadiazine in human malaria”. Trans. Roy. Soc. Trop. Med. Hyg. 53: 412, 1959. [ Links ]
63) JACOBS, R.L.: “Selection of strains of Plasmodium berghei resistant to quinine. chloroquine and pyrimethamine”. J. Parasitol. 51: 481-482, 1965. [ Links ]
64) KAMINSKY, A. et al.: “Clinical experience with the long-acting sulfona. mide Ro 4-4393 in dermatology”. Paper presented at the III Int. Congr. Chemotherapy, Stuttgart, July 1963. Proceedings pp. 676-80, Thieme Verlag. Stuttgart, 1964. [ Links ]
65) KRISHNASWAMI, A.K. et al.: “Studies on Plasmodium berghei Vincke & Lips, 1948. XV. Acquired resistance to sulühadiazine”. Indian J. Malariol. 8 : 9-18, 1954. [ Links ]
66) LAING, A.B.G.: “Preliminary observations on drug-resistance to malaria in northern Tanzania”. Ann. Rep. East Afr. Inst. Malaria & Vector-Borne Diseases, 1963-64. [ Links ] .
67) LAING, A.B.G.: “Antimalarial effect of sulphorthodimethoxine (Fanasil) ” Brit. Med. J. 1964, 2, 1439-1440. [ Links ]
68) LAING, A.B.G.: “Treatment of acute falciparum malaria with sulphorthodimethoxine (Fanasil)”. Brit. med. J. 1965, 1, 905-907. [ Links ]
69) LAING, A.B.G.: “Treatment of acute falciparum malaria with diaphenylsulfone in North-East Tanzania”. J. Trop. Med. Hyg. 68: 251-253, 1965. [ Links ]
70) LAING, A.B.G.: “Sporogony in Plasmodium falcivarum apparently unaffected by sulforthomidine (Fanasil)” Trans. Roy. Soc. Trop. Mep. Hyg. 59: 357-8, 1965. [ Links ]
71) LAING, A.B.G.: “The treatment of acute malaria with sulforthomidine and a combination of sulforthomidine and primethamine”. Bull. WHO 34: 308-311, 1966. [ Links ]
72) LAING, A.B.G.: Personal communication. [ Links ]
73) LAING, A.B.G.: Personal communication. [ Links ]
74) LOPES, FERREIRA C. et. al.: “Tratamento de micetoma por ‘Nocardia brasiliensis‘ com uma nova sulfamida administrada uma vez por semana” Rev. Assoc. Med Brasil. 11: 135-139. 1965. [ Links ]
75) LOPES, P.F.A. & RODRIGUES DA SILVA, J.: ‘Resistência do Plasmodium falciparum aos quimioterápicos” Presented at the II Congr. of the Brazil. Soc. Trop. Med., Goiânia, January 1966. [ Links ]
76) MAIER, J. & RILEY, E.: “Inhibition of anitmalarial action of sulfonamides by p-aminobenzoic acid”. Proc. Soc. Exptl. Biol. Med. 50: 152-154, 1942. [ Links ]
77) MANWELL R.D. et al.: “Effect of sulfanilamide and sulfapyridine on the avian malarias”. Proc. Soc. exp. Biol. N.Y., 46: 523. 1941. [ Links ]
78) MARSHALL, P.B. “The absorption of sulphonamides in the chick and the canary, and its relationship to antimalarial activity”. J. Pharmacol. 84: 1. 1945 [ Links ]
79) MARSHALL, E.K., Jr., et. al.: “The antimalarial action in ducks of certain sulfanilamide derivatives”. J. Pharmacol. 86: 273 1946. [ Links ]
80) McGREGOR, J .A. etal.: “Pyrimethamine and sulphadiazine in treatment of malaria”. Brit. Med. J. 1963, 2, 728. [ Links ]
81) MENK, W. & MOHR, W.: “Zur Frage der Wirksamkeit des Prontosils bei akuter Malaria”. Arch. Schiffs u. Tropenhyg. 43: 117, 1939. [ Links ]
82) MUDROW-REICHENOW, L.: “Ueber die chemotherapeutische Beinflussbarkeit des Plasmodium berghei Vincke und. Lips”. Z. Tropenmed. u. Parasitol. 2: 471-485, 1951. [ Links ]
83) NIVEN, J.C.: “Sulphanilamide in the treatment of malaria”. Trans. Roy. Soc. trop. Med. Hyg. 32: 413, 1938. [ Links ]
84) PETERS, W.: “Drug resistance in Plasmodium berghei Vincke and Lips. 1948. I. Chloroquine resistance”. Explt. Parasitol. 17: 80-89, 1965. [ Links ]
85) PETERS, W.: “Drug resistance in Plasmodium berghei Vincke and Lips, 1948. II. Triazne resistance”. Exptl. Parasitol. 17: 90-96, 1965. [ Links ]
86) PETERS, W.: “Drug resistance in Plasmodium berghei Vincke and Lips. 1948. III. Multiple drug resistance” Exptl. Parasitol. 17: 97-102, 1965. [ Links ]
87) PETERS, W.: “Drug responses of mepracine- and primaquine- resistant strains of Plasmodium berghei Vincke and Lips 1948″. Ann. Trop. Med. Parasitol. 60: 25-30, 1966. [ Links ]
88) PETERS, W.: “Drgu resistance and cross-resistance in Plasmodium berghei ” (presented at the III Int. Pharrnarological Congr., July 1966, São Paulo). [ Links ]
89) PRINGLE, G. & LANE, F.C.T.: “Notes on the clearance of malaria parasitaemias among children undergoing a comparative trial of repository antimalarial agents, by the sulphonamide sulphorthomidine (Fanasil, Ro 4-4393), and by diaphenylsulfone (DDS)” (presented at the Symposium [ Links ]
90) RAMAKRISHNAN, S.P. et al.: “Stutious Dis., Munich, April 1966) . on Fanasil; IV Int. Congr. for Infecdies on the toxicity and action of diaminodiphenyl-sulfone (DDS) in avian and simian malaria”. Bull. WHO 27: 213-221, 1962. [ Links ]
91) RAMAKRISHNAN, S.P. et. al.: “A study on the joint action of diaminodiphenyl-sulphone (DDS) and pyrimethamine in the sporogony cycle of Plasmodium gallmaceum: Potentiation of the sporontocidal acitvity of pyrimethamine by DDS”. Indian J. Malariol. 17: 141-148, 1963. [ Links ]
92) RAY, A.P. & NAIR, C.P.: “Studies on Nuri strain of P. knowlesi. Part IX. Susceptibility to sulphonamide substituted dihydrotriazine, sulpha-diazine and mepracine”. Indian J. Malariol. 9: 196-202, 1955. [ Links ]
93) READ, H. & PINO, J.O.: “Versuche mit den Sulfonamid-Praparaten bei der Malariabehandlung”. Arch. Schiffsu. Tropenhyg. 42: 132, 1938. [ Links ]
94) RICHARDS, W.H.G.: Personal communication (in press). [ Links ]
95) RICHARDSON, A.P. et al.: “Chemotherapy of Plasmodium knowlesi infections in Macaca mulatta monkeys” J. Pharmacol. 87: 203, 1946. [ Links ]
96) RIEDER, J. & BOEHNI, E.: “Vergleichende Untersuchungen über die chemotherapeutisch wirksamen Plasmaspiegel langrwirkender Sulfanilamide bei künstlich infizierten Versuchstieren”. Presented at the III Int. Congr. Chemotherapy, Stuttgart, July 1963. Proceedings pp. 622-626, Thieme Verlag, Stuttgart, 1964. [ Links ]
97) ROBERTSON, G.I. et al.: “Cross-resistance between Daraprim and Proguanil”. Brit. Med. J. 1952, 2 1255-1256; correspondence. [ Links ]
98) ROLLO, I.M.: “A 2: 4-diamino-pyrimidine in the treatment of proguanil- resistant laboratory malaria strains” ature 168: 332-233, 1951. [ Links ]
99) ROLLO, I.M.: “Daraprim resistance in experimental malarial infections” Nature 170: 415, 1952. [ Links ]
100) ROLLO, I.M.: “Daraprim – experimental chemotherapy”. Trans. Roy. Soc. Trop. Med. Hyg. 46: 474-484, 1952. [ Links ]
101) ROLLO, I.M.: “The mode of action of sulphonamides, proguanil and pyrimethamine on Plasmodium gallinaceum” Brit. J. Pharmacol. 10: 208-214, …. 1955. [ Links ]
102) ROLLO, I.M.: “The chemotherapy of malaria”, in: “BioehemMry and Physiology of Protozoa” (S.H. Hutner, ed.), vol. III. Academic Press, New York & London, 1964. [ Links ]
103) ROSSAN, R.N.: “The effect of antimalarial drugs on the exoerythrocytic and erythrocytic stages of blood- induced infections of Plasmodium fallax in the turkey”. Explt. Parasitol. 6: 163-188 1957. [ Links ]
104) SCHMIDT, L.H. et al.: “Development of resistance to chlorguanide (paludrine) during treatment of infections with Plasmodium cynomolgi“. J. Pharmacol. 95: 382-398, 1949. [ Links ]
105) SCHMIDT, L.H. & GENTHER, C.S.: “The antimalarial properties of 2, 4- diamino-5-p-chlorophenyl-6-ethylpyrimidine (Daraprim)”. J. Pharmacol. Exptl. Therap. 107: 61-91, 1953. [ Links ]
106) SCHNEIDER, J. & CARUANA, M.: “Essais de traitement curatif du paludisme par la sulfaméthyldiazine (sumédine”. Bull. Soc. Path. exot. 41: 478, 1948. [ Links ]
107) SCHNITZER, R.J. & GRUNBERG, E.: “Drug-resistance of micro-organisms” Academic Press, New York, 1957. [ Links ]
108) SCHNITZER, R.J. “Drug resistance in protozoa”. Inter. Rev. Trop. Med. 2: 239-266, 1962. [ Links ]
109) SCHNITZER, R.J.: “Drug resistance of pathogenic protozoa” . Presented at the N.Y. Acad. Sei., April, 22, 1966. [ Links ]
110) SHUTE, G.T. & DOWLING, M.A.C.’ “Effect of sulphorthodimethoxine on parasites of Plasmodium falciparum and Plasmodium malariae on semi- immune schoolchildren in the Western region of Nigéria”. Unpublished WHO document WHO/Mal/66.544. [ Links ]
111) RODRIGUES DA SILVA, J.: Personal communication. [ Links ]
112) SINGH, J. et al.: “Screening of antimalarials against P. gailinaceum in chicks. Part I. Preliminary studies” Indian J. Malariol. 6: 145-158 1952. [ Links ]
113) SINGH, J. et. al.: “Acquired resistance to proguanil in Plasmodium knowlesi“. Transe. Roy. Soc. Trop. Mep. Hyg. 46: 639-649, 1952). [ Links ]
114) SINGH, J. et al.: “Development of resistance to pyrimethamine in P. cynomolgi“. Indian J. Malariol. 7: 357-369, 1953. [ Links ]
115) SINGH, J. et. al.: Studies on Nuri straín of Plasmodium knowlesi. V. Acquired resistance to pyrimethamine”. Indian J. Malariol. 8: 187-195, 1954. [ Links ]
116) STNGH. J. et. al.: “Therapeutic effect of sulphadiazine and dihydrotriazines against blod-induced. P. cynomolgi infection”. Indian J. Malariol. 10: 131-135, 1956. [ Links ]
117) SINTON, J.A. et al “Some sucessful trials of proseptasine as a true causai prophylactic against infection with Plasmodium falciparum“. Ann. trop. Med. Parasit. 33: 37, 1939. [ Links ]
118) SORLEY, E.R. & CURRIE, J.G.: “Notes on the experimental use of prontosil album in the treatment of malaria”. J.R. nav. med. Serv. 24: 322, 1938. [ Links ]
TAYLOR, D.J. & GREENBERG, J.: “Hyperactivity of metachloridine against Plasmodium gallinaceum in chicks maintained on a purified diet” Proc. Soc. Exptl. Biol. Med. 90: .. 551-554, 1955. [ Links ]
120) THOMPSON, P.E. et al.: “Quinine- resistant Plasmodium berghei in mice”. Science 148: 1240-1241, 1965. [ Links ]
121) THOMPSON, P.E. et. al.: “Studies on a dihydrotriazine and a sulfone alone and in combination against Plasmodium berghei in mice”. Amer. J. Trop. Med. Hyg. 14: 198-206, 1965. [ Links ]
122) THOMPSON, P.E.: Drug resistance in malaria and criteria in the selection of new agents for trial against drug- resistant strains”. Presented at the III Int. Pharmacol. Congr., São Paulo, July 1966. [ Links ]
123) THOMPSON, P.E.: Personal communication. [ Links ]
124) THURSTON, J.P.: “The action of antimalarial drugs in mice infected with Plasmodium berghei“. Brit. J. Pharmacol. 5: 409-416, 1956. [ Links ]
125) THURSTON, J.P.: “The action of dyes, antibiotics, and some miscellaneous compounds against Plasmodium berghei“!. Brit. J. Pharmacol. 8: … 162-165. 1953. [ Links ]
126) THURSTON, J.P. “The chemotherapy of Plasmodium berghei. I. Resistance to drugs”. Parasitology 43 : 246-252, .. 1953. [ Links ]
127) THURSTON, J.P.: “The chemotherapy of Plasmodium berghei. II. Antagonism of the action of drugs”. Parasitology 44: 99-110, 1954. [ Links ]
128) TSCHUDI-MADSEN, S.: “Serum concentration and antibacterial activity of 4-sulfanilamido-5, 6-dimethoxypyrimidine”. Amer. J. Mel. Sei. 247: 127, 1964. [ Links ]
129) VAN DER WIELEN, Y.: “Prontosil en malaria quartana”. Ned. Tijdschr. Geneesk, 81: 2905, 1937. [ Links ]
130) VASINA, S.G.: “Testing of chemotherapeutic agents against tissue forms of Plasmodium gallinaceum in chick embryos” (Med. Parasitol. Parasitic Diseases, U.S.S.R., 25: 327-330. 1956. Seen in Top. Dis. Bull. 54: 537-538, 1957. [ Links ]
131) WILLIAMSON, J. & LOÚRIE, E.M.: ‘Acquired paludrine-resistance in Plasmodium gallinaceum. I. Development of resistance to paludrine and failure to develop resistance to certain other antimalarials”. Ann. Trop. Med. Parasitol. 41: 278-291, 1947. [ Links ]
132) WISELOGLE, F.Y.: “A survey of antimalarial drugs, 1941-45”. 2 vols. J. W. Edwards, Ann Arbor, Michigan, .. 1946. [ Links ]
Paper presented at the Kound Table Conference on Malaria (Belo Horizonte, August 2, 1966) which followed the III International Pharmacological Congress in São Paulo (July 24-30, 1966)
