Course Of Chloroquine Research Articles

Efficacy of chloroquine plus chlorpheniramine in chloroquine-resistant falciparum malaria during pregnancy in Nigerian women: a preliminary study

The efficacy of chloroquine plus chlorpheniramine, a histamine H receptor antagonist, which reverses chloroquine 1 insensitivity in Plasmodium falciparum in vitro and in vivo , was evaluated in 30 pregnant women with recrudescent chloroquine-resistant Plasmodium falciparum malaria. All patients had at least one or more treatment failures with one or more courses of chloroquine or pyrimethamine-sulphadoxine. There was a prompt response to treatment with parasitaemia and fever clearing in all patients within 48 and 96 hours respectively of commencement of therapy with the combination. The cure rate on day 14 was 77%. Parasitaemia recurred in seven patients after day 14 and was successfully treated with oral mefloquine. The combination was well tolerated; pruritus and drowsiness were the only noticeable adverse effects. The progress of pregnancy and its outcome were not adversely affected by treatment with the combination. When fully developed, the combination of chloroquine plus chlorpheniramine may be an alternative in the treatment of chloroquine-resistant malaria during pregnancy in Nigerian women.

Chloroquine resistance of Plasmodium falciparum malaria in Ethiopia and Eritrea.

We report on the first 2 years of operation of a new strategy for treatment for P. falciparum malaria patients who were not cured by a standard course of chloroquine. Any such patient who returned to a malaria treatment and detection post within 2 weeks was treated daily under supervision with chloroquine. Patients whose parasitaemia had not decreased below 25% of the initial level by day 3 or cleared completely by day 7 were given sulphadoxine/pyrimethamine (Fansidar). Of 39824 patients treated initially with chloroquine, 4% returned to the malaria post within 2 weeks of treatment; 87% of these were chloroquine resistant and treated with Fansidar and 28% of the returning patients were RIII resistant. Resistance was associated with geographical area, initial parasite density and age. Earlier studies had shown resistance to be confined to border areas, but we found that it was highest in the centre of the region, notably in the lowlands of the Shewa and Arsi provinces, and lowest in the west. Although imported cases have been held responsible for the development of resistance in border areas, other factors are likely to be important in the middle of the region. The implications of these findings for a treatment policy of P. falciparum malaria in the region are discussed.

Clinical response and susceptibility in vitro of Plasmodium vivax to the standard regimen of chloroquine in Thailand

The clinical effectiveness of the standard regimen of chloroquine (CQ) (a total dose of 1500 mg, given over 48 h at 0, 6, 24 and 48 h) for the treatment of Plasmodium vivax malaria in Thailand was investigated in 57 patients in an endemic area of Thailand (Chantaburi Province, eastern Thailand). For radical treatment, an additional course of a tissue schizontocidal agent, primaquine, was given following the complete course of CQ. With this regimen, satisfactory whole blood concentration-time profiles of CQ and its major metabolite desethylchloroquine (DECQ) were achieved. Mean whole blood levels of CQ and DECQ always much exceeded the reported therapeutic level of CQ (90 ng/mL) during the first 7 d of treatment. All patients responded well to the treatment; in most cases, complete and rapid clearance of parasitaemia was observed within the first 48 h. No reappearance of the parasitaemia was detected in peripheral blood films of any patient within 14 d of the evaluation period. In 6 patients, however, reappearance of P. vivax parasitaemia was observed after 30 d; 2 of them had not completed the course of primaquine. There was no difference in whole blood concentrations of CQ and DECQ, admission parasitaemia, susceptibility of the isolates to chloroquine in vitro, and parasite clearance time between patients with or without reappearance of parasitaemia. A prominent trend of deteriorating sensitivity of the parasite to the drug was, however, suggested.

Malaria treatment in Queensland, 1992. The use of malaria treatment guidelines.

To investigate treatment patterns for malaria and the use of Australian guidelines which were then current for the treatment of malaria in Queensland in 1992. A review of patient treatment and demographic details, obtained from the treating doctor by questionnaire, for all cases of malaria in Queensland in 1992 which were reported to Queensland Health (316 people treated for 341 episodes of malaria). Plasmodium falciparum infections were treated according to the recommendations in the guidelines in 20% of cases. Thirty-five per cent of infections were treated with chloroquine, even though most of these were acquired in countries where chloroquine or chloroquine/antifolate-resistant P. falciparum malaria existed. Plasmodium vivax infections were treated with the recommended course of chloroquine in 58% of cases. Fifty per cent of patients with P. vivax infection were treated with primaquine, but only 57% of these received the dose recommended in the guidelines for the eradication of hypnozoites. Patterns of malaria treatment were basically similar in the malaria-receptive zone and elsewhere in Queensland, although P. falciparum infections in the receptive zone were treated according to the guidelines at a higher rate (32%) than in the rest of Queensland (13%). In 1992, many cases of malaria in Queensland were not treated according to the recommendations in the Australian malaria treatment guidelines. We suggest that improved distribution of simple but comprehensive guidelines for malaria treatment may assist medical practitioners in the provision of prompt, effective treatment, and help prevent the reestablishment of endemic malaria in Australia.

Pharmacokinetics of primaquine in G6PD deficient and G6PD normal patients with vivax malaria

The pharmacokinetics of primaquine have been studied in 13 G6PD normal and 13 G6PD deficient Thai male patients with Plasmodium vivax malaria who were given daily doses of 15 mg of primaquine over 14 d, following a full course of chloroquine. After the first dose (15 mg), primaquine underwent rapid absorption. Mean values (SD in parentheses) of maximum plasma concentration of 57.7 (7.7) vs. 55.7 (7.4) ng/mL were reached at 2.2 (0.6) vs. 2.2 (0.6) h, for the G6PD deficient and G6PD normal groups, respectively. Thereafter, drug levels declined rapidly and monoexponentially with a t1 2γ of 6.4(1.9) vs. 6.3 (2.7) h. The respective mean values (SD in parentheses) for MRT, AUC 0–∞, Cl f , and V z f were 6.8 (0.4) vs. 6.8 (0.5) h, 0.547 (0.070) vs. 0.521 (0.090) μg/h/mL, 8.54 (0.37) vs. 8.97 (1.46) mL/min/kg and 4.8 (1.7) vs. 5.1 (1.2) L/kg. There was no difference in the plasma concentrations or pharmacokinetics of primaquine between patients with normal G6PD and G6PD deficiency. In the G6PD deficient group, no relationship between the severity of haemolysis (<20% or >20% haemolysis) and the concentrations/pharmacokinetics of primaquine was observed.

Vivax malaria resistant to treatment and prophylaxis with chloroquine

Chloroquine has been the treatment of choice for vivax malaria for more than 40 years. Lately, several case-reports have suggested the emergence of resistance to chloroquine in Plasmodium vivax in Papua New Guinea and Indonesia. We undertook prospective treatment and prophylaxis trials of chloroquine in children and adults with vivax malaria living in Irian Jaya (Indonesian New Guinea). 46 villagers with P vivax parasitaemia were treated with chloroquine by mouth (25 mg base/kg body weight divided over 3 days) and followed up for 14 days. Parasitaemia cleared initially but recurred within 14 days in 10 (22%) subjects. All recurrences were in children younger than 11 years, 7 of whom were younger than 4 years; the failure rate among children under 4 was 70%. 7 of the patients with recurrences were given a second course of chloroquine. In all, the infections initially cleared but recurrent parasitaemia developed in 5 (71%) within 14 days. Whole-blood chloroquine concentrations were consistently above those previously shown to cure P vivax blood infections (90 μg/L whole blood). Subjects whose initial infections cleared and who had no parasitaemia on day 14 received weekly prophylaxis with chloroquine. Despite the presence of expected blood chloroquine concentrations, P vivax parasitaemia developed in 9 of 17 subjects receiving prophylaxis during 8 weeks of follow-up (median time to parasitaemia 5·3 weeks). Chloroquine can no longer be relied upon for effective treatment or chemoprophylaxis of P vivaxblood infections acquired in this part of New Guinea. Lancet 1993; 341: 96-100.

Norfloxacin Is Inferior to Chloroquine for Falciparum Malaria in Northwestern Zambia: A Comparative Clinical Trial

Fluoroquinolones are active against Plasmodium falciparum in vitro. In a prospective, randomized, comparative trial, norfloxacin, 400 mg twice a day for 3 days, was compared with a standard course of chloroquine in semiimmune adults with symptomatic falciparum malaria in northwestern Zambia, where chloroquine resistance is uncommon. Patients were followed for 28 days. The trial was terminated after 38 patients were studied because chloroquine was markedly more effective, curing all 18 patients (100%) compared with only 8 (40%) of 20 who received norfloxacin (P less than .001). Of the 12 norfloxacin failures, 6 had clearing of trophozoites but recurrence during the study period (RI), 4 had incomplete clearance of trophozoites with later recurrence (RII), and 2 had no improvement (RIII). The mean parasite clearance time was significantly shorter with chloroquine (30.4 vs. 52.7 h; P = .02). The mean defervescence time was also shorter with chloroquine (16.9 vs. 24.5 h; not significant). In contrast to its inferior efficacy, norfloxacin caused fewer adverse effects than did chloroquine (33% vs. 0; P less than .001).

Use of illiterate volunteer workers for malaria case detection and treatment

We evaluated the use of illiterate community volunteers for malaria case detection and treatment in Guatemala. Volunteer workers, known as Volunteer Medicators, were selected by members of their communities and were trained and supervised by National Malaria Service (NMS) staff. Their responsibilities included recording basic demographic data and administering a three-day course of chloroquine (25 mg kg-1) to all febrile patients who visited their homes. Patient information was recorded on a special form which consisted of stick-figure drawings. During a one-year evaluation period, no differences were noted between literate and illiterate Volunteer Medicators with respect to the length of time required for their training or supervision, the average number of patients they treated per month, the frequency of errors in recording data or administering medication, or their acceptance by the community residents.

The Seroepidemiology of Malaria in Middle America

Serologic assessment was carried out in a sample of the population living in an area endemic for malaria in which control measures were being applied. The study area was in El Salvador, Central America, and antimalarial activities consisted of the residual application of the pesticide, propoxur, and drug distribution through a combination of active and passive case detection. Indirect fluorescent antibody (IFA) responses to Plasmodium vivax and P. falciparum antigens were determined on four occasions, at approximately 6-month intervals. The study population consisted of one resident from each of 268 widely distributed houses. Each person was treated with a curative course of chloroquine and primaquine at the beginning of the investigation. An increase in the proportion of positive IFA responses (greater than or equal to 1:20) and an increasing number of serologic conversions (i.e., from negative to positive or a 2-fold increase in titer) during the course of the 18-month study confirmed continued transmission of malaria. The presence of parasites in some individuals without associated serologic changes is discussed.

A Refractory Case of Hepatic Amoebiasis

A 39-year-old man had three separate episodes of hepatic amoebiasis despite one course of emetine and chloroquine, two courses of metronidazole, and one prolonged course of chloroquine. Asymptomatic intestinal amoebiasis was first detected after his third episode of hepatic disease, and his eventual cure followed an intensive regimen designed primarily to treat the intestinal infection. It seems likely that the intestinal amoebiasis had been present undetected since the onset of hepatic disease and had served as the source for reinfection of the liver.

The treatment of malaria.

At least four doses of quinine followed by a single dose of mefloquine or by a single dose of sulfadoxine-pyrimethamine are two highly effective regimens for chloroquine-resistant falciparum malaria. Mefloquine alone is valuable in ambulant patients. Chloroquine-sensitive falciparum malaria can be treated with a course of chloroquine. Vivax and all other types of malaria should be treated with sequential chloroquine and primaquine. Quinine, by intravenous infusion, is the most effective drug for severe falciparum malaria. The optimum intravenous dose varies between 5 mg/kg and 10 mg/kg administered over four hours. Intravenous or oral quinine should be administered about every 12 hours and the total daily dose of quinine should rarely exceed 20 mg/kg. Intravenous fluid input should be controlled in falciparum malaria to prevent pulmonary oedema. Established renal failure is best treated by dialysis. The value of adrenocortical steroids for falciparum coma has not been established. Fresh blood transfusion may be helpful in small doses for severe anaemia and to replace clotting factors. Anticoagulants, such as heparin, should not be used in falciparum malaria.

Tetracycline Treatment of Chloroquine-Resistant Falciparum Malaria in Thailand

Tetracycline hydrochloride was evaluated in asymptomatic and acutely ill subjects naturally infected with chloroquine resistant strains of<i>Plasmodium falciparum</i>. Sixteen asymptomatic subjects of whom eight had recently experienced chloroquine treatment failures received 250 mg of tetracycline hydrochloride, four times daily for ten days. A presumptive radical cure was demonstrated in 12. In the other four, treatment was discontinued within 72 hours because of symptomatic development. Acutely ill subjects were assigned to one of two treatment groups. One group received 640 mg of quinine sulfate, three times daily for three days, followed by 250 mg of tetracycline hydrochloride, four times daily for ten days. The other group received a similar course of quinine followed by a conventional course of chloroquine. A presumptive radical cure was demonstrated in 29 of 30 treated with the quinine-tetracycline regimen, and in 15 of 36 treated with the quinine-chloroquine regimen.

Experimental treatment with chloroquine.

Today I shall present evidence suggesting that chloroquine is an effective therapeutic agent for sarcoidosis. Before presenting this evidence, I think I might tell you how we came to administer chloroquine to sarcoid patients. Several years ago it was noted that 15 to 20 per cent of serum specimens from our sarcoidosis service gave positive latex-fixation tests. This finding led us to speculate about the possible relationships between sarcoidosis and rheumatoid arthritis. One result of this speculation was the decision to give chloroquine to a few patients with sarcoidosis. Somewhat to our surprise, distinct improvement seemed to result from treatment with chloroquine. The difficulty of assessing the results of therapy in a disease so prone to spontaneous remission as sarcoidosis need not be emphasized to this group. With this in mind, we have set up two separate clinical investigations of the effect of chloroquine in sarcoidosis. All subacute cases, that is, those of less than two years' duration, are included in a controlled blind study, the results of which will not be available for some time yet. Selected chronic cases of the type not likely to improve spontaneously have been given a six-month course of chloroquine, 250 mg. twice a day. The results of therapy in this chronic group form the basis for this presentation. A summary of the results is shown in table 16. In all instances, the nature of the disease was confirmed by tissue biopsy and/or a positive Kveim test. Duration of disease ranged from three to eighteen years. Most of the patients presented skin lesions, and in each there was marked improvement or dearing of the dermal sarcoidosis following chloroquine therapy. Response of skin lesions was usually apparent after two to three months of treatment, maximal response often requiring six months or more. Characteristically, the lupoid skin papules were replaced by areas of increased pigmentation as they resorbed. Peripheral lymphadenopathy was present in only 3 patients; hmvever, in each of these instances the nodes diminished markedly in size or disappeared following administration of

Observations on two Plasmodium falciparum infections with an abnormal response to chloroquine.

Summary The first of two patients with Plasmodium falciparum infections which failed to respond to chloroquine therapy administered in Colombia, South America, received three further courses of 1.5 g of chloroquine and experienced clinical and parasitic relapses 12 and 8 days, respectively, after the first two courses. Upon the completion of the third course the drug was continued for 14 more days at a dosage of 0.3 g daily. Blood smears remained positive during this period. A 3-day course of quinine sulphate (90 grains) produced negative blood smears, but a parasitic relapse occurred after 17 days. An apparent cure was effected by a 10-day course of quinine. The second patient experienced a clinical and parasitic relapse approximately 20 days after a first course of chloroquine; and after a second course (2.1 g) followed by a 14-day course of primaquine, a recurrence of parasitemia accompanied by minor symptoms approximately 21 days after the completion of the chloroquine therapy was observed. A 10-day course of quinine produced an apparent cure.