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Objectives: To analyze the relapse pattern of Plasmodium vivax in the city of Mumbai., Methods: 283 cases of smear positive vivax malaria were treated with full dose (25 mg/kg) chloroquine and were asked to follow up for at least one year. None of the patients received primaquine., Results: Of the 150 cases who followed up for at least one year, 19 relapsed, 17/19 relapsed within the first 6 months; indicating that the relapse pattern in the city is predominantly of the tropical or Chesson strain type., Conclusions: Vivax malaria patients should be monitored for at least six months. Those who do relapse should receive treatment with full dose chloroquine and 14 days of primaquine treatment.

A major problem in the control of malaria is the development of resistance, of the parasites to the existing drugs and of the vectors to insecticides. With few new drugs in the pipeline, in an era of declining resources, it is imperative to make judicious use of the existing antimalarials. In the city of Mumbai, resistance exists to chloroquine (CQ) and to sulfadoxine-pyrimethamine (SP). Use of a combination of CQ with SP would theoretically slow down the development of resistance to each of the drugs and increase their useful lives. The effectiveness of this combination in the treatment of adults from Mumbai, who had acute, uncomplicated Plasmodium falciparum malaria, was compared with that of CQ alone. The combination was found to be significantly more effective, in terms of 28- or 42-day cure rates, and to be more cost-effective.

In India, treatment of acute, uncomplicated Plasmodium falciparum malaria is becoming increasingly difficult due to resistance to chloroquine, thus there is a need for new antimalarial drugs. CGP 56697 (co-artemether), a new drug, is a combination of artemether and lumefantrine in a single oral formulation (one tablet = 20 mg of artemether plus 120 mg of lumefantrine). In a double-blind study, 179 patients with acute uncomplicated P. falciparum malaria were randomly assigned to receive either CGP (n = 89) given as a short course of 4 x 4 tablets over a 48-hr period or chloroquine (n = 90) given as four tablets (one tablet = 150 mg of chloroquine base) initially, followed by two tablets each at 6-8, 24, and 48 hr. Due to a death in the chloroquine group and a decrease in the chloroquine cure rate to < 50% (based on the blinded overall cure rate at that time), recruitment was terminated prematurely. CGP 56697 showed a superior 28-day cure rate (95.4% versus 19.7%; P < 0.001), time to parasite clearance (median = 36 versus 60 hr; P < 0.001), and resolution of fever (median = 18 versus 27 hr; P = 0.0456). This drug provides a safe, effective, and rapid therapy for the treatment of acute uncomplicated P. falciparum malaria.

In the city of Mumbai (formerly Bombay), chloroquine (CQ) continues to be recommended as the drug of first choice for the treatment of Plasmodium vivax and P. falciparum infections, even though > 50% of local isolates of P. falciparum are resistant to it. Primaquine, an 8-aminoquinoline is also given to patients with falciparum malaria, in a single, 45-mg dose, to kill the gametocytes and so reduce transmission. The gametocytocidal activity of supervised primaquine (45 mg given on day 8) was investigated in 90 patients who had been treated with CQ. Of these, 15 were found to be CQ-sensitive patients, 61 were resistant (49, eight and four considered RI, RII and RIII, respectively) and 14 were lost before completion of the follow-up. The mean (S.D.) baseline gametocytaemias in the CQ-sensitive and RI-resistant cases were 665.1 (411.3) and 1537.4 (1045.5)/microliter, respectively. Despite supervised primaquine treatment, four of the 15 CQ-sensitive patients and 32 of the 49 patients found to be RI-resistant had gametocytes on day 29. There therefore appears to be a need to review the current, gametocytocidal, primaquine-dosage schedule and to re-treat patients who remain gametocytaemic with higher doses of primaquine, as an important, transmission-blocking strategy.

Objectives: Given the steep increase in the incidence of malaria in the city of Mumbai in the nineties, we decided to study the causes for the same as well as analyse the resistance pattern of P. falciparum in the city., Methods: Smear positive cases of acute uncomplicated P. falciparum malaria who presented to us in 1994, 1995 and 1996 were analysed for their response to full dose chloroquine (25 mg/kg over 3 days). Samples of those patients who satisfied criteria for in vitro resistance testing to chloroquine and other antimalarials, were also studied. Chloroquine level in all patients was studied on Day 3 by HPLC. In vivo response to chloroquine was studied in 30, 71 and 78 patients while in vitro response was studied in 17, 35 and 30 patients respectively in the above years., Results: We found in vivo chloroquine resistance figures of 36.78%, 45% and 53.8% in the years '94, '95 and '96 and the in vitro resistance figures of 41.17%, 54.28% and 66.6% in the same years., Conclusions: Our previous studies documenting 15% chloroquine resistance in 1993 and the increasing incidence in subsequent years suggests resistance to chloroquine as one of the causes of resurgence and maintenance of malaria in the city. If patients of uncomplicated P. falciparum malaria are to be treated with chloroquine, rigorous monitoring for nonresponse and timely rescue medication is necessary. Alternative antimalarial drugs such as mefloquine, artemisinin derivatives and sulfadoxine-pyrimethamine should be used in patients where this is not possible.

Several reports have confirmed the existence of chloroquine resistant Plasmodium falciparum malaria in Bombay. In the management of these cases, of the therapeutic options available, sulfadoxine-pyrimethamine (SP) (administered as a single dose) is preferred, since quinine has to be administered over a period of 7 days while mefloquine is yet to be marketed in India. With increasing reports of falciparum malaria resistant to SP from Thailand and Africa, the present study was conducted to determine the efficacy of SP in the treatment of chloroquine resistant falciparum malaria cases in Bombay. 17 uncomplicated falciparum malaria patients documented to be resistant to chloroquine (10 RI, 5 RII and 2 RIII) by the WHO (1973) in-vivo extended field test criteria and by estimation of plasma chloroquine levels by High Performance Liquid Chromatography were included in the study. These adult patients were then treated with a supervised single dose of 3 tablets of SP and peripheral blood smears were then repeated on days 3, 4, 5, 7, 14, 21, 28, 35 and 42 after treatment. 14 patients responded and were sensitive while 3 patients showed RII grade resistance to SP. These 3 patients then responded to a 7 day course of quinine (30 mg/kg/day)+doxycycline (100 mg/day). These results thus document that SP can be used as an effective second-line antimalarial drug. However one should monitor the patient for plasmodial resistance to sulfadoxine-pyrimethamine.

Nilima A Kshirsagar,1 Nithya J Gogtay,1 Diego Moran,2 Gregory Utz,3 Ashok Sethia,4 Shirsendu Sarkar,5 Pol Vandenbroucke6 1Seth G S Medical College and KEM Hospital, Mumbai, India; 2Hospital San Andrés de Tumaco, Narino, Colombia; 3US Naval Medical Research Unit 6, Lima, Peru; 4Gita Bhawan Hospital and Research Centre, Indore, 5Pfizer, Mumbai, India; 6Pfizer, New York, NY, USA Background: To explore the use of azithromycin–chloroquine (AZCQ) for the treatment of malaria, we conducted double-blind, randomized, non-inferiority studies in India, Colombia, and Suriname comparing the combination of azithromycin 1 g and chloroquine (CQ) 600 mg base once daily (QD) for 3 days versus atovaquone–proguanil (AP) or chloroquine plus sulfadoxine–pyrimethamine (SPCQ) in adults with acute uncomplicated Plasmodium falciparum malaria.Methods: Patients were hospitalized until three documented negative blood smears and followed through Day 42. The primary end point was parasitologic cure at Day 28.Results: In India, parasite clearance rates were 84% and 94% for AZCQ and SPCQ, respectively (95% confidence interval [CI] for the difference: –22.6, 0.8). In Colombia and Suriname, parasite clearance rates were 57% and 99% for AZCQ and AP, respectively (95% CI: –52, –32). A subsequent open-label, non-comparative third study using a 2 g dose of azithromycin and 600 mg of CQ in India and Colombia resulted in an overall efficacy rate of 97%.Conclusion: In India, Colombia, and Suriname, 1 g azithromycin with CQ QD for 3 days was inferior to established comparator agents. An improved response rate was observed when the dose of azithromycin was increased to 2 g. Keywords: acute, uncomplicated malaria, antimalarial, azithromycin, chloroquine, malaria, parasitologic cure rate, plasmodium

The article presents information on the drug resistance found in the parasite species of malaria. Mainly four kind of species including P. falciparum, P. vivax and P. malariae are accountable for the most human malaria infections across the world. According to the researches, drug resistance has been found in P. vivax and P. falciparum. The cases that reveal resistance to the first-line drug chloroquine has been reported mainly from Papua New Guinea and Irian Jaya, Indonesia.