Safety and efficacy of sofosbuvir-based direct-acting antiviral regimens for hepatitis C virus genotypes 1-4 and 6 in Myanmar: Real-world experience.

This open-label, clinical experience investigated the safety and efficacy of direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy in Myanmar; 344 patients completed treatment between June 2015 and May 2016. Patients with HCV genotypes 1-4 and 6 received one of four treatments: (i) Peg-interferon (PEG-IFN)+sofosbuvir (SOF)+ribavirin (RBV) for 12 weeks, (ii) SOF+RBV for 24 weeks, (iii) ledipasvir (LDV)+SOF for 12 weeks or (iv) daclatasvir (DCV)+SOF+RBV for 12 or 24 weeks. Genotype 3 was most common (n=133, 38.7%), followed by genotype 6 (n=122, 35.5%) and genotype 1 (n=86, 25%). Overall, 91% of patients achieved sustained virologic response (SVR); 99% in group 1, (n=148/149), 90% in group 2 (n=95/106), 78% in group 3 (n=65/83) and 100% in group 4 (n=6/6). In group 3, SVR rates were 96.8% in genotype 1 (n=30/31) and 64.1% in genotype 6 (n=25/39). Multivariable regression analysis identified advanced fibrosis (F3-4) (OR=.16 CI: 0.05-0.57, P=.005), genotype 6 (OR=.35, CI: 0.16-0.79, P=.012) and diabetes (OR=.29, CI: 0.12-0.71, P=.007) as negative independent predictors of response. Adverse events were mild with all-oral therapy. CONCLUSION: DAA therapy ±PEG-IFN achieved high SVR rates. Genotype 6 patients had a low SVR to 12 weeks of LDV and SOF raising the need for other regimens, RBV or longer treatment duration in this population.

Single-dose treatment of falciparum malaria with mefloquine: field studies with different doses in semi-immune adults and children in Burma.

Different doses of mefloquine (20 and 30 mg/kg of body weight in children, and 750 and 1000 mg in adults) were tested in controlled clinical trials in 89 children and 60 adults who were semi-immune carriers of Plasmodium falciparum. There was no significant difference in the efficacy of the two doses, either in the children or in the adults. An RI-type resistance was found in 1 adult, when recrudescence occurred on day 7, and in 4 children, who showed recrudescence on day 14. In all 5 patients, spontaneous disappearance of parasites was observed at further parasitological checks, thus indicating that mefloquine has a prolonged action. One patient who vomited after taking the drug was successfully retreated with mefloquine on day 14.Nausea, giddiness, and vomiting are the three symptoms most frequently attributed to mefloquine. The incidence of nausea and giddiness was similar in both dosage groups, but the adults in the higher dosage group had a significantly higher frequency of vomiting than those in the low-dose group.In view of the rapid and reliable action of a single dose, mefloquine seems to be the drug of choice for treatment of cases of falciparum malaria that are resistant to 4-aminoquinolines and to sulfonamide-pyrimethamine combinations. A dose of 20 mg per kg of body weight for children and 750 mg for adults is sufficient for treatment of semi-immune persons.

Falciparum malaria treated with a fixed combination of mefloquine, sulfadoxine and pyrimethamine: a field study in adults in Burma.

In a field study conducted in Burma, 54 semi-immune adults suffering from falciparum malaria (mean parasite count, 15 328/mm(3) before treatment) were given a single dose of a fixed combination of 750 mg mefloquine base, 1500 mg sulfadoxine, and 75 mg pyrimethamine (3 tablets of Fansimef). All these patients were cleared of asexual parasites by day 7, giving a cure rate of 100%; the mean clearance time was 2.6 days. Reappearance of parasitaemia occurred in 10 patients on or before day 7 and persisted for one day in 8 of them and for two days in 2 patients. It eventually disappeared without further treatment. No recrudescence occurred during the follow-up time of four weeks despite the fact that there was active transmission of Plasmodium falciparum in the area throughout the whole of the study period. The drug was generally well tolerated, though mild to moderate giddiness was reported by 49 patients (90.7%) and severe giddiness by 3 patients (5.5%). Nausea occurred in 25 patients (46.3%) and vomiting in 17 (31.5%).

Chloroquine-resistant malaria in Burma.

Two field trials to detect chloroquine-resistant malaria were conducted according to WHO recommendations in a malaria free area near Rangoon. Peripheral blood smears were examined for asexual forms of P. falciparum on day one through to day seven, on day 14, 21, and 28 after a standard dose of 1500 mg. of chloroquine base. Haskins test to detect chloroquine in urine was done on all cases and plasma chloroquine levels were measured in some. Out of 105 patients tested RI resistance was detected in 66, RII in 19 and RIII in three. Subsequent trials with other anti-malarial drugs indicated that the chloroquine-resistant P. falciparum were also resistant to one day therapy with pyrimethamine 50 mg. or sulphamethoxypyridazine 1 G given singly; and resistant to one day therapy with combinations of pyrimethamine 50 mg. plus sulphamethoxy pyridazine 1 G, pyrimethamine 13 mg. plus dapsone 100 mg., and trimethoprim 320 mg. plus sulphamethoxazole 1600 mg. All those tested were sensitive to quinine sulphate, 0-6 G given three times a day for 10 days, and were also sensitive to one day therapy with combinations of trimethoprim 500 mg. plus sulphalene 1 G, and pyrimethamine 50 mg. plus sulphamethoxine 1 G. Pyrimethamine 12-5 mg. plus dapsone 100 mg. in weekly doses was shown to be an effective chemoprophylaxis. Quinine was tested on 38 subjects while other drug schedule were tested on six to eight subjects.