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Chloroquine and Chlorguanide as Suppressants of Malaria in Guatemala¹

To find the most suitable location for an antimalarial drug evaluation project, 160 places in 14 states of the Republic of Guatemala were surveyed in 1948 and 1949. Malaria parasites were found in 3,106, or 13.27 per cent of 23,390 blood films taken during the surveys, and splenomegaly was found in 1,474 or 19.41 per cent of 7,694 examinations. The parasite incidence ranged from zero in the highlands to as high as 60 per cent in the lowlands. Correspondingly high spleen indices were also found in the lowlands. The percentages of the species of parasites found were: Plasmodium vivax 51.5 per cent, P. falciparum 45.9 per cent, P. malariae 2.6 per cent, species undetermined 16.8 per cent, and multiple infections 2.0 per cent. The parasite indices were highest in children and women and lowest in men and infants. The spleen indices were highest in the older children. The principal vector of malaria in the regions surveyed was Anopheles albimanus.

The trials of suppression by chloroquine and chlorguanide were conducted in six areas on the Pacific coastal plain in southern Guatemala. In each area part of the population was treated with chloroquine, part with chlorguanide, and the remainder served as the control. Four population groups received weekly treatments, and two groups received treatment every two weeks. The experimental populations consisted of 2,087 people. The individuals on the weekly regimens of chloroquine, chlorguanide and placebo totaled 538, 683, and 337, respectively. In the biweekly treatment groups, 229 received chloroquine, 73 chlorguanide, and 227 served as the control. Mass movements of the population occurring during treatment periods accounted for the uneven numbers available for study in some groups.

With weekly chloroquine treatments, the incidence of malaria was reduced from 23.1 per cent to 5.3 per cent, and increased to 9.0 per cent in the follow-up period. The parasite index in the chlorguanide-treated groups dropped from 25.9 per cent before treatment to 14.6 per cent during treatment, and was 14.5 per cent after treatment was discontinued. In the control group, parasite indices increased from 18.2 per cent at the base-line to 27.4 per cent during treatment, and dropped to a low dry-season level of 16.9 per cent in the follow-up period. Chloroquine treatments appeared to reduce the spleen index and the size of the average enlarged spleen. Chlorguanide did not appear to affect the spleen index, but seemed to cause a slight reduction in the average enlarged spleen. Treatments were about equally effective in all ages.

Chloroquine more effectively suppressed both P. vivax and P. falciparum than chlorguanide. The gametocyte rate of P. falciparum rose from 55.7 per cent in the pre-treatment period to 77.6 per cent during treatment; a corresponding increase was noted in the controls, in which the gametocyte rate was 54.7 per cent in the pre-treatment period, 63.8 per cent in the treatment period, and 77.7 per cent in the post-treatment period. About 50 per cent of the blood films with falciparum gametocytes also showed ring forms.

Even in individuals taking treatment irregularly, there was a decrease in parasitemias with the increase in the number of treatments taken. Thus, most of the positives, found in the 151 persons given chlorguanide, and in the 31 persons given chloroquine, were reported in individuals who had received but few treatments. Even a small number of doses of chloroquine rapidly and effectively cleared both vivax and falciparum parasitemias. On the other hand, with falciparum at least four doses of chlorguanide were required to obtain results comparable to one treatment with chloroquine.

Biweekly treatments with either drug were not as effective as weekly treatments.

¹ These investigations were conducted with the support of the Laboratory of Tropical Diseases, National Microbiological Institute, National Institutes of Health, under the sponsorship of the Pan American Sanitary Bureau, through a grant from the Division of Research Grants, National Institutes of Health.