Chloroquine Base Research Articles

Spontaneous Rupture of the Spleen inP. VivaxMalaria

Case Report A previously fit airman aged 22 years reported to his sick quarters on 13th June, 1966, with fever. He had just returned from a visit to the East coast of Malaya and claimed that he had taken paludrine regularly. No clinical abnormality was noted apart froni fever and he was better within a few days. On 21st June h~ was well in the morning but developed further fever that evening and was admitted to hospital. The only clinical findings were that he had a fever of 102°F and that the tip of his splean was palpable. A blood film contained P. vivax trophozoites in large numbers. He received chloroquine (base) 600 mg at 10 p.m~

Surveys on chloroquine resistant P. Falciparum in Thailand

Surveys for the prevalence of chloroquine resistant P. falciparum were carried out in north, central and south Thailand. The frequency of unsatisfactory response to 1500 mg. of chloroquine base ranged from a high of 85% to a low of 6% in different areas. In a series of hospital patients 37·5% had a poor clinical response and 25% an inadequate parasitological response.

Chloroquine-resistant falciparum malaria.

During 1967 more than 300,000 American troops are expected to return to the United States from South Vietnam. Those who have engaged in combat in the central highland jungle have probably been exposed to virulent strains of Plasmodium falciparum malaria. These troops have been taking a tablet containing 300 mg chloroquine (base) and 45 mg primaquine (base) once weekly as chemoprophylaxis. Some are receiving a daily dosage of 25 mg of dapsone (diaminodiphenylsulfone) as a third chemosuppressive agent. On being rotated from Vietnam, each individual is issued a supply of the chloroquine-primaquine tablets with instructions to take one each week for eight weeks. He is warned not to use these combined tablets for the therapy of any clinical illness because of the potential hemolytic action of large doses of primaquine. Those troops participating in the field trial of dapsone are given a supply of the tablets and instructed to take

A trial of chloroquine-medicated salt for malaria suppression in Uganda.

SummaryThe distribution of chloroquine-medicated salt has been proposed as an alternative method of malaria eradication where insecticidal attack is not fully effective. The small trial described here was conducted in Uganda during 1964–66 to test the use of medicated salt among a changing population at two sugar estates. Salt containing 0.38% by weight chloroquine base was issued free, and the populations' experience compared with those not receiving medicated salt.Methods for the preparation and distribution of medicated salt are described. Satisfactory distribution led to significant reductions in crude parasite rates and reduction of morbidity to about one-third the level in nonrecipient workers, and to lower levels in women and children. Failure to achieve complete protection was attributed to administrative shortcomings, individual non-co-operation, or inadequate intake. The possibility of chloroquine resistance was excluded by use of a standard test procedure. The results of the trial were not encouraging for wider adoption, but could be justified for the situation in which it was tried.

SULPHORMETHOXINE IN CHLOROQUINE-RESISTANT FALCIPARUM MALARIA IN THAILAND

The long-acting sulphonamide, sulphormethoxine, has proved very effective in patients acutely ill with chloroquine-resistant falciparum malaria in Thailand. In a single dose of 1000 or 1500 mg., sulphormethoxine alone radically cured eleven out of eighteen patients (61%). A lower dose (250 mg.) of sulphormethoxine combined with a single dose of 12·5 or 25 mg. pyrimethamine cured eleven out of fifteen patients (73%). But the clinical response in these two groups was slow. A combination of 1000 mg. sulphormethoxine and 1500 mg. chloroquine base cured eleven of thirteen patients (85%). A single dose of 1000 mg. sulphormethoxine with 50 mg. pyrimethamine cured seventeen of nineteen patients (90%) and the response was rapid. Toxic effects were notably absent. Although these drugs have proved effective in chloroquine-resistant falciparum malaria, the risk of extending drug resistance should prompt caution in adopting such combinations for mass control therapy.

Prevalence of malaria exhibiting reduced sensitivity to chloroquine in Southern Thailand

A study to determine the approximate prevalence of malaria parasites exhibiting reduced sensitivity to 4 mg. of chloroquine base per lb. body weight was undertaken in the Self-Help Land Settlements of Satul, Yala and Narathivas Provinces, Southern Thailand. A further study to determine the approximate prevalence of malaria parasites exhibiting reduced sensitivity to a therapeutic course of 10 mg. per lb. of base was conducted in the Self-Help Land Settlements of Yala and Narathivas Provinces. The data indicate that in approximately 79% of the 307 cases with P. falciparum infections the parasites showed reduced sensitivity to 4 mg. per lb. of the drug, and in approximately 53% of the 111 school children with P. falciparum the parasites exhibited reduced sensitivity to 10 mg. per lb. The 4 cases of simple P. vivax infection appeared to be highly sensitive to chloroquine. The 3 mixed ( P. falciparum and P. vivax) infections reverted to simple infections with P. falciparum. A recommendation to evaluate the usefulness of chloroquine in all malaria eradication and control programmes is proposed.

CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM FROM PORTO VELHO, BRAZIL.

Summary Two cases of Plasmodium falciparum infections, apparently originating in Porto Velho, Brazil, which were not eliminated by the usual curative doses of chloroquine are documented. One patient received a total of 6.675 grams chloroquine base, including four regimens varying from 0.9 to 2.1 grams each, without eradicating the parasites. She was cured subsequently by a 10-day quinine treatment. The second patient received a total of 3.675 grams chloroquine base, including two courses of 1.5 grams each, without eradicating the infection. He was cured by a 5-day treatment totaling 3.1 grams of chloroquine. This study confirms the presence of chloroquine-resistant P. falciparum in Porto Velho, Brazil, the second area in South America where chloroquine-resistant strains have been reported.

Chloroquine treatment for malaria in semi-immune patients.

The research objective was to determine the smallest oral doses of chloroquine that would be effective in the treatment and suppression of malaria among semi-immune natives of East Africa. The chloroquine trials were carried out in holoendemic malarious districts of Tanganyika principally in the vicinity of Muheza. For the clinical trials semi-immune patients complaining of fever and found to have signs consistent with a diagnosis of malaria were treated with chloroquine phosphate. Small children received the drug in a granular preparation each granule containing 1 mg base chloroquine coated in hard sugar. The diagnosis of malaria was based on the presence of signs together with a parasite count raised above the level expected of asymptomatic carriers in the area of holoendemicity. For the suppressive trials semi-immune carriers of malaria were treated with sufficient chloroquine to clear parasitemia and were then given varying doses in order to determine the smallest quantity required to keep the blood clear. It was found in the earlier trials that single doses of 75 mg chloroquine base were almost always sufficient to clear asexual parasitemia among semi-immune children. The only objective indication of lack of tolerance to chloroquine on which reliance could be placed was vomiting occurring within 3 hours after drug ingestion. The incidence of vomiting was low. The treatments were generally given during the morning when most Africans had as yet eaten little. The results indicate that the greater the dosage of the drug the more likely was vomiting. In this investigation temperature readings taken every 8 or 12 hours revealed that fever attributable only to malaria and not to an underlying pulmonary or other condition was relieved in most cases within 24 hours by any dosage capable of clearing parasitemia. In sum the following single doses of chloroquine phosphate were effective in the treatment of malaria caused by any species of parasite and appeared to achieve radical cure of subtertian malaria: age 0-1 years 19 mg; 1-2 years 37 mg; 3-5 years 75 mg; and 6 years and older 120 mg. For suppression the respective dosages were 19 mg 37 mg 75 mg and 75 mg.

Experiments with antimalarial drugs in man: VII. The suppressive effect of 50 mg. of chloroquine base daily in British troops exposed to infection with Plasmodium falciparum

Experiments with antimalarial drugs in man: VII. The suppressive effect of 50 mg. of chloroquine base daily in British troops exposed to infection with Plasmodium falciparum

Chloroquine in treatment of lichen planus and other dermatoses.

Chloroquine phosphate, primarily an antimalarial and amebacidal drug, has been used with considerable success in the treatment of chronic discoid lupus erythematosus1and in actinic dermatitis.2Because of its efficacy in these dermatoses, it was almost inevitable that it would be used in other dermatoses on an empirical basis. We first became interested in trying it in other dermatoses after using it with considerable benefit in a case of lichen planus. This, of course, led us to try it first in other cases of lichen planus as they became available and subsequently in a variety of unrelated dermatoses that had been treatment problems. METHOD AND RESULTS Chloroquine (Aralen) phosphate (tablets 250 mg., containing 150 mg. of chloroquine base) was prescribed to be taken orally, usually twice daily for one week, then once daily. In a few cases, the twice daily dose was continued beyond one week or was

A comparison of the antimalarial effects of suppressive doses of chloroquine, amodiaquin, and pyrimethamine.

Summary and ConclusionsThe antimalarial effects of chloroquine (Aralen), amodiaquin (Camoquin) and pyrimethamine (Daraprim) were tested respectively in three groups of African school children; a fourth group served as control. A total of 148 children were studied over a period of 12 weeks. All drugs were administered at weekly intervals in the following dosages: Chloroquine (base) 0.15 gm., amodiaquin 0.2 gm., pyrimethamine 12.5 mgm.; children in the control group received placebos. Blood smears for parasite rate studies were examined prior to and at weekly intervals during the course of the experiment. Spleen surveys were made before and at 4-weekly intervals during the course of the experiment. At no time was there evidence of drug intolerance.The results of parasite rate studies clearly indicate that in the dosages used all three drugs are highly efficient in clearing the blood of asexual malaria parasites. Chloroquine showed the most rapid action, and although pyrimethamine took somewhat longer to exert its effect it was equally effective in eliminating parasites from the blood. Amodiaquin did not prove to be quite as effective and in several children a temporary “break-through” did occur.The gametocyte rate showed an early transient rise only in children receiving pyrimethamine, an observation also made by Foy and Kondi (1952). However, there was a definite decrease in the gametocyte rate in all three groups receiving antimalarials after several weeks of drug administration.By the end of the 12-week treatment period the children in the three groups receiving the antimalarials showed an equally marked regression in both the spleen rates and the average enlarged spleen. The initial spleen reduction appeared to be somewhat more rapid in children receiving amodiaquin.