Impact of pre-packaging antimalarial drugs and counselling on compliance with malaria treatment at Port Moresby General Hospital Adult Outpatient Department.

We investigated the impact of pre-packaging antimalarial drugs and counselling on compliance with treatment of malaria at the Adult Outpatient Department of Port Moresby General Hospital. Adult patients who were prescribed standard antimalarial drugs following clinical and microscopic diagnosis of malaria were randomly assigned to one of three groups: an intervention group, where pre-packaging and counselling instructions were applied; control group A, with counselling but no pre-packaging; and control group B, with neither counselling nor pre-packaging. Patients were interviewed on two occasions, day 1 of treatment and day 4 post treatment. Of a total of 436 patients, 322 patients (179 males and 143 females) completed the study. Our data indicate an increase of 18% in compliance with treatment in the intervention group and 16% in control group A, when compared with control group B. While compliance with treatment was gender independent, the language spoken and used for giving instructions and counselling may have influenced patients' behaviour on prescribed medication. The results of our study indicate that a simple pre-packaging system and proper counselling could improve compliance with antimalarial drug treatment. As an additional beneficial observation, pre-packaging is likely to eliminate errors and possible contamination of the products during dispensing.

The disposition of oral amodiaquine in Papua New Guinean children with falciparum malaria.

AIMS: We assessed the disposition of oral amodiaquine (AQ) and CYP2C8 polymorphism in 20 children with falciparum malaria. METHODS: AQ and DEAQ concentrations were determined with SPE-HPLC method. CYP2C8 genotypes were assessed by PCR-RFLP method. RESULTS: AQ was not detectable beyond day 3 postdose. Cmax for DEAQ was reached in 3.0 days. The mean values for t1/2, MRT, and AUCtotal were 10.1 days, 15.5 days and 4512.6 microg l(-1) day, respectively. All the children were CYP2C8* homozygous. CONCLUSION: Our data are consistent with those previously reported, and the AQ regimen seems pharmacokinetically adequate in the absence of CYP2C8 polymorphism.

Halofantrine in the treatment of uncomplicated falciparum malaria with a three-dose regimen in Papua New Guinea: a preliminary report.

We evaluated the efficacy and safety of halofantrine in 19 patients with acute uncomplicated falciparum malaria. Each patient received oral halofantrine hydrochloride 500 mg every 6 hours for 3 doses (total 1.5 g). In almost all the patients clinical symptoms of malaria and parasitaemia disappeared within 2 and 3 days, respectively, of starting treatment. We observed no recurrence of parasitaemia during 14 days of follow-up. Tolerance to halofantrine was good except for minor and self-limiting gastrointestinal side-effects. Haematological and biochemical indices were not seriously affected. Halofantrine-induced prolongation of Q-T/Q-Tc intervals was the consistent cardiac manifestation in 84% of patients. The Q-T/Q-Tc interval prolongation increased with each dose; it reached a maximum between 18 and 24 hours and thereafter returned to baseline. These preliminary data indicate that, apart from the cardiac side-effects, halofantrine is an effective and safe drug, well tolerated by most of the patients in the study.

PIP: The authors evaluated the efficacy and safety of halofantrine in 19 patients with acute uncomplicated falciparum malaria. Each patient received oral halofantrine hydrochloride 500 mg every 6 hours, for a total of 3 doses (total 1.5 g). In almost all the patients clinical symptoms of malaria and parasitemia disappeared within 2 and 3 days, respectively, of starting treatment. They observed no recurrence of parasitemia during 14 days of follow-up. Tolerance to halofantrine was good except for minor and self-limiting gastrointestinal side effects. Hematological and biochemical indices were not seriously affected. Halofantrine-induced prolongation of Q-T/Q-Tc intervals was the consistent cardiac manifestation in 84% of patients. The Q-T/Q-Tc interval prolongation increased with each dose; it reached a maximum between 18 and 24 hours and thereafter returned to baseline. These preliminary data indicate that, apart from the cardiac side effects, halofantrine is an effective and safe drug, well tolerated by most of the patients in the study.

In vitro susceptibility of Plasmodium falciparum isolates to halofantrine in the Central Province of Papua New Guinea.

Halofantrine is a newer antimalarial drug which has not been approved for clinical use in Papua New Guinea. We assessed 21 Central Province isolates of Plasmodium falciparum for their in vitro susceptibility to halofantrine. The concentration required to inhibit 50% of parasite growth (IC50) ranged from 0.05 to 7.0 nM with a mean of 1.90 nM and a median of 1.50 nM. The minimum inhibitory concentration (MIC) values ranged from 2.5 to 50 nM with a median of 5.0 nM. All but one isolate had an MIC of 10 nM or less. These results indicate that halofantrine would be a suitable alternative for the treatment of P. falciparum malaria in the region in the future, if and when the need arises, provided that its use was carefully monitored.

PIP: Halofantrine is a newer antimalarial drug which has not been approved for clinical use in Papua New Guinea. The authors assessed 21 Central Province isolates of Plasmodium falciparum for their in vitro susceptibility to halofantrine. The concentration required to inhibit 50% of parasite growth (IC50) ranged from 0.05 to 7.0 nmol with a mean of 1.90 nmol and a median of 1.50 nmol. The minimum inhibitory concentration (MIC) values ranged from 2.5 to 50 nmol with a median of 5.0 nmol. All but one isolate had an MIC of 10 nmol or less. These results indicate that halofantrine would be a suitable alternative for the treatment of P. falciparum malaria in the region in the future, if and when the need arises, provided that its use was carefully monitored.

In vitro susceptibility of Plasmodium falciparum to four antimalarial drugs in the Central Province of Papua New Guinea.

The susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine and halofantrine was investigated in the Central Province of Papua New Guinea between March 1995 and September 1996, when chloroquine resistance was widely present in the country. The standard World Health Organization in vitro microtest methodology was used in the study. Of the 30 isolates tested for chloroquine susceptibility all were resistant to chloroquine with median IC50 of 1.15 mumol/l (range 0.54 to 4.24), indicating a high prevalence and degree of resistance. Three isolates each for quinine (3/31) and halofantrine (3/28) showed resistance at concentrations of 51.2 mumol/l and 10 nM respectively, while all 31 isolates tested for mefloquine were fully susceptible. The comparative analysis of median IC50 values between isolates resistant and susceptible to chloroquine showed chloroquine-resistant isolates to be less susceptible to quinine and halofantrine while fully susceptible to mefloquine. It seems that the evolution of chloroquine resistance together with increased use of quinine treatment of P. falciparum malaria may increase the risk of emergence of quinine resistance and possibly of halofantrine resistance as well. The development of mefloquine resistance, however, is independent of chloroquine resistance.

Plasmodium ovale species in Papua New Guinea--lest we forget.

The microscopical diagnosis of Plasmodium ovale infection is reviewed and its similarity to Plasmodium vivax emphasized. Its presence in Papua New Guinea has been recognized for many years, from a time not long after Stephens first described the species in 1922, but it is rarely reported. There is no doubt of its presence in Papua New Guinea, together with P. falciparum, P. vivax and P. malariae, but its exact prevalence and distribution has not been determined.

Halofantrine versus quinine-Fansidar combination in the treatment of post-chloroquine falciparum parasitaemia.

The standard first-line treatment for malaria in adults in Papua New Guinea is chloroquine; for severe and treatment-failure malaria standard therapy is a combination of quinine and Fansidar (sulphadoxine-pyrimethamine). These standard treatments are currently under revision. The present study evaluated the effect of halofantrine in treatment-failure falciparum malaria in adults in Port Moresby compared to standard therapy. In the halofantrine group all parasites were cleared by day 5 after starting therapy, in the quinine-Fansidar group by day 7. There was no evidence of recurrence of parasitaemia during the 21-day follow-up in either group. Nausea was associated with halofantrine use in 68% of patients. In the quinine-Fansidar group 79% had muffled deafness, 32% tinnitus and 26% dizziness; 32% of patients withdrew from treatment on day 2 because of intolerance to quinine. Halofantrine in this study population provided an efficacy against treatment-failure falciparum malaria similar to that of quinine-Fansidar, with a more favourable profile of adverse effects.

Parasitological response of Plasmodium falciparum infection to chloroquine treatment in malaria patients in Port Moresby.

A 7-day in vivo test system was applied to assess the parasitological response to chloroquine treatment in patients with falciparum malaria in the Central Province and National Capital District of Papua New Guinea. 30 patients were investigated but only 23 took a full course of chloroquine and were completely followed up. Of the 23 patients, 13 (57%) were negative for malaria parasites on day 2, 4 (17%) had significantly reduced parasitaemia by day 2 and cleared parasites by day 7, and 1 (4%) showed a partial response (R2). In 5 (22%) of the patients resistance at the R3 level was observed. The indication from this study is that chloroquine should continue to be the first-line drug for the treatment of uncomplicated falciparum malaria. However, judicious use of chloroquine in uncomplicated falciparum malaria is required to halt the spread of chloroquine-resistant strains of Plasmodium falciparum.