A randomized, parallel study of the safety and efficacy of 45 mg primaquine versus 75 mg bulaquine as gametocytocidal agents in adults with blood schizonticide-responsive uncomplicated falciparum malaria [ISCRTN50134587].

BACKGROUND: The WHO recommends that adults with uncomplicated P. falciparum successfully treated with a blood schizonticide receive a single dose of primaquine (PQ) 45 mg as a gametocytocidal agent. An earlier pilot study suggested that 75 mg of bulaquine (BQ), of which PQ is a major metabolite, may be a useful alternate to PQ. METHODS: In a randomized, partial blind study, 90 hospitalized adults with Plasmodium falciparum malaria that was blood schizonticide-responsive and a gametocytemia of > 55/microl within 3 days of diagnosis were randomized to receive single doses of either PQ 45 mg or BQ 75 mg on day 4. We assessed gametocytemia on days 8, 15, 22 and 29 and gametocyte viability as determined by exflagellation (2 degrees end point) on day 8. RESULTS: On day 8, 20/31 (65%) primaquine recipients versus 19/59 (32%) bulaquine recipients showed persistence of gametocytes (P = 0.002). At day 15 and beyond, all patients were gametocyte free. On day 8, 16/31 PQ and 7/59 BQ volunteers showed gametocyte viability (p = 0.000065). CONCLUSION: BQ is a safe, useful alternate to PQ as a Plasmodium falciparum gametocytocidal agent and may clear gametocytemia faster than PQ.

A prospective study evaluating the efficacy of a single, 45-mg dose of primaquine, as a gametocytocidal agent, in patients with Plasmodium falciparum malaria in Mumbai, India.

The efficacy of a single dose of 45 mg primaquine, as a gametocytocidal agent, was assessed in Mumbai, India, among adults with uncomplicated or severe Plasmodium falciparum malaria. All the patients investigated had been found gametocytaemic, with at least 56 gametocytes/microl blood, within the first 72 h of their illness. Those with uncomplicated malaria, like those with severe malaria, were randomized to receive or not receive primaquine. All the patients were followed up for 29 days post-admission, for gametocytaemia and gametocyte viability (as determined by exflagellation). Among those with uncomplicated malaria, six (27.3%) of the 22 who did not receive primaquine but only one (4.2%) of the 24 who did receive the drug, on day 4, remained gametocytaemic on day 29 (P < 0.05). Similarly, seven (31.8%) of the 22 severe cases who did not receive primaquine but only two (9.5%) of the 21 severe cases who received the drug, on day 8, were found gametocytaemic on day 15 (P < 0.05). While the single, 45-mg dose of primaquine recommended by the World Health Organization was effective in clearing gametocytes from the blood of > 90% of the present cases of malaria, > 4% of the patients with uncomplicated malaria and > 9% of those with the severe disease continued to harbour gametocytes in their peripheral blood 29 and 15 days after taking the primaquine, respectively.

Efficacy of a 14-day primaquine regimen in preventing relapses in patients with Plasmodium vivax malaria in Mumbai, India.

We studied the antirelapse efficacy of a supervised 14-d 15 mg/d regimen of primaquine therapy (n = 131) compared with no antirelapse therapy (n = 142) in 273 patients with confirmed Plasmodium vivax malaria in Mumbai, India, between July 1998 and April 2000. There were 6/131 (4.6%) recurrences in patients given primaquine compared with 13/142 (9.2%) in those not given antirelapse therapy. In the 14-d primaquine group, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) genotyping analysis of pre- and post-treatment blood samples was done for the 6 patients who had a recurrence of parasitaemia and the results gave a true relapse rate of 2.29% (3/131), 2 samples were classified as reinfections and 1 sample did not amplify. Our results indicate probable resistance to the 14-d regimen of primaquine for the first time in India and illustrate the need to (i) monitor patients given this regimen and (ii) carry out comparative studies between primaquine and new drugs such as tafenoquine and bulaquine for preventing relapses.

A cost-effectiveness analysis of three antimalarial treatments for acute, uncomplicated Plasmodium falciparum malaria in Mumbai, India.

BACKGROUND: Malaria is a major public health problem representing 2.3% of the overall global disease burden. The cost of treatment of malaria continues to rise as older drugs and insecticides become less effective and are replaced by more effective, but also more expensive products. METHODS: A post-hoc pharmacoeconomic analysis (direct and indirect costs only) of three antimalarials, chloroquine, mefloquine and co-artemether, was carried out to address the problem of switch to a more expensive first-line antimalarial in the face of growing chloroquine resistance. RESULTS: From the perspective of a large public hospital, it was seen that in an area of high grade chloroquine resistance, the total expenditure on patients who fail chloroquine would exceed the excess expenditure on mefloquine when the RII + RIII resistance exceeded 9%. CONCLUSIONS: Switch to a more expensive drug like mefloquine as a first-line option would be cost-effective when the moderate-severe chloroquine resistance exceeded 9%.

A randomized, parallel-group study in Mumbai (Bombay), comparing chloroquine with chloroquine plus sulfadoxine-pyrimethamine in the treatment of adults with acute, uncomplicated, Plasmodium falciparum malaria.

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.

Relapse pattern of Plasmodium vivax in Mumbai: a study of 283 cases of vivax malaria.

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.

Efficacies of 5- and 14-day primaquine regimens in the prevention of relapses in Plasmodium vivax infections.

Vivax malaria accounts for 80% of malaria cases in Mumbai (Bombay) and has high morbidity. In India, the standard treatment to prevent relapses of vivax malaria is a 5-day regimen of primaquine. However, between 1977 and 1997, the efficacy of this treatment declined from approximately 99% to 87%. The efficacy of the 5-day regimen was therefore compared with that of the 14-day regimen currently recommended by the World Health Organization, in Mumbai. The relapse rates observed, over a 6-month period of follow-up, were 0% with the 14-day regimen, 26.7% with the 5-day, and 11.7% when no primaquine treatment was given. The expenditure incurred on the door-to-door dispensing of the 5-day regimen appears to be without benefit. There is an urgent need to review the present strategy for controlling relapses in vivax malaria, at least for the city of Mumbai, and similar studies need to be carried out in other parts of India, to make all anti-relapse strategies more appropriate.