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S Looareesuwan

Publications and source records attributed to S Looareesuwan.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacokinetics of dihydroartemisinin following oral artesunate treatment of pregnant women with acute uncomplicated falciparum malaria.

OBJECTIVE: To determine the pharmacokinetic properties of dihydroartemisinin (DHA) following oral artesunate treatment in women with recrudescent multi-drug resistant falciparum malaria, in the second and third trimesters of pregnancy. METHODS: Serial plasma concentrations of artesunate and DHA were measured in 24 women after the final dose of a 3 day treatment with artesunate (4 mg kg(-1) day(-1)) and atovaquone (20 mg kg(-1) day(-1)) plus proguanil (8 mg kg(-1) day(-1)), daily. Conventional non-compartmental modelling and a population one-compartment pharmacokinetic model were applied to the data. RESULTS: Artesunate was very rapidly eliminated. For DHA the median [90% range] estimate of oral clearance (CI/F) was 4.0 [0.8-20.7] l hour(-1) kg(-1), total apparent volume of distribution (Vd/f) was 3.4 [0.9-60.7] l/kg, and terminal elimination half-life was 1.0 [0.6-2.4] h. CONCLUSION: The kinetics of DHA are modified by pregnancy. The plasma levels of the active antimalarial metabolite DHA are lower than reported previously in non-pregnant adults. Dose-optimisation studies in pregnant women are needed.

Acute Disease↗
PubMed2005

Curdlan sulphate in human severe/cerebral Plasmodium falciparum malaria.

Preclinical studies have shown that curdlan sulphate (CRDS), a sulphated 1-->3-beta-D glucan, inhibits Plasmodium falciparum in vitro and down-modulates the immune response. A direct, non-specific effect on cytoadherence and rosetting may be predicted, as has been described with other sulphated polysaccharides, e.g. heparin. The anticoagulant effect of CRDS is 10-fold lower than heparin. Curdlan sulphate has, therefore, emerged as a candidate for adjunct medication in the treatment of severe/cerebral malaria. Two clinical studies were conducted using CRDS as adjunct medication to conventional therapy (artesunate) in patients with severe and severe/cerebral malaria. Both studies were double-blind and placebo-controlled to evaluate the efficacy and safety of the combination. Curdlan sulphate appeared to reduce the severity of the disease process, e.g. fever clearance time was shortened. Due to the small number of patients, there was no difference in mortality. The two treatment arms in both studies showed similar results for all laboratory parameters. The only adverse event recorded during CRDS treatment was an increase in activated partial thromboplastin time. This can be monitored easily. It seems that the patients who may benefit most are severe/cerebral cases with no organ damage on admission.

Adolescent↗
PubMed2005

Microculture for the isolation of Leishmania parasites from cutaneous lesions -- Sri Lankan experience.

Novy, McNeal and Nicolle (NNN) medium and Evans' modified Tobie's medium are two conventional media for the isolation of Leishmania parasites in in-vitro cultures. Both are biphasic, with a solid layer of blood agar, and are normally prepared in glass test-tubes. In Sri Lanka at least, a monophasic microcapillary culture, based solely on RPMI 1640 medium supplemented with foetal calf serum, has been found simpler, more economical and more sensitive, for the isolation of L. donovani from skin lesions, than the use of Evans' modified Tobie's medium.

Animals↗
PubMed2005

The use of the multi-organ-dysfunction score to discriminate different levels of severity in severe and complicated Plasmodium falciparum malaria.

Clinical presentation of Plasmodium falciparum malaria reflects a continuum from asymptomatic to multi-organ manifestation and death. Severe malaria is defined by the World Health Organization as a qualitative variable. We used the multi-organ dysfunction score (MODS) as a quantitative approach for severity in 29 patients with severe and complicated P. falciparum malaria to test its usefulness in discriminating different severity levels. The MODS on admission was highly correlated with the duration of symptoms after admission (r = 0.73, P < 0.001) and the serum level of tumor necrosis factor alpha (r = 0.41, P = 0.03). In addition, the simplified MODS, based mainly on clinical findings, was also correlated with liver and renal dysfunction during hospitalization (alanine transaminase, r = 0.42, P = 0.02; blood urea nitrogen, r = 0.45, P = 0.015). A score >or= 16 was associated with significantly longer disease duration (P = 0.018). Thus, this score might provide a predictive value for morbidity in P. falciparum malaria.

Adolescent↗
PubMed2005

An open, randomized trial of three-day treatment with artesunate combined with a standard dose of mefloquine divided over either two or three days, for acute, uncomplicated falciparum malaria.

The combination of artesunate and mefloquine is currently one of the most effective treatments for multidrug-resistant Plasmodium falciparum malaria. Simultaneous, rather than sequential treatment with the two drugs, would allow better patient compliance. We therefore evaluated three-day treatment with artesunate combined with either 2 or 3 days of mefloquine co-administered once a day with artesunate. The study was an open, randomized trial for acute, uncomplicated falciparum malaria and was conducted at the Bangkok Hospital for Tropical Diseases. One hundred and twenty adult patients were randomized to two treatment groups. Group 1 patients received 4 mg/kg/day of artesunate for 3 days and 3 daily doses of 8.0 mg/kg/day mefloquine given with artesunate. Group 2 patients received the same dose of artesunate and the same total dose of mefloquine (25 mg/kg). However, the mefloquine was given as 15 mg/kg on the first day and 10 mg/kg/ on the second day, again with artesunate. The baseline demographic and clinical characteristics of the patients in the two groups were similar. The cure rates for the 3-day and 2-day mefloquine regimens were 100% and 99%, respectively. There were no significant differences in either median fever clearance times (group 1=32 hours; group 2=33 hours) or mean parasite clearance times (group 1=42.3 hours; group 2=43.3 hours). Both regimens were well tolerated and there were no significant differences in the incidence of adverse effects. Nausea or vomiting occurred in 3.8% of patients in both groups and transient dizziness occurred in 4% of group 1 and 9% of group 2 patients. These results suggest that a 3-day regimen of mefloquine administered with artesunate is effective and well tolerated. This practical regimen could improve patient compliance.

Adolescent↗
PubMed2005

An open randomized clinical trial of Artekin vs artesunate-mefloquine in the treatment of acute uncomplicated falciparum malaria.

Malaria remains a major cause of morbidity and mortality in tropical countries and subtropical regions in the world. Southeast Asia has the most resistant malaria parasites in the world, which has limited treatment options in this region. In response to this situation, short-course artemisinin-based combination therapies (ACTs) have been developed. The combination of dihydroartemisinin (DHA) and piperaquine (PQP) in the form of Artekin has been developed as an alternative to established combinations, such as artesunate-mefloquine, primarily to reduce treatment costs and toxicity. We conducted a study comparing a standard treatment for acute uncomplicated falciparum malaria (artesunate 4 mg/kg/day together with mefloquine 8 mg/kg/day oral route once a day for 3 days) (Group A) and a combination of dihydroartemisinin 40 mg and piperaquine 320 mg in the form of Artekin given once a day for 3 days (Group B) to determine safety, efficacy, and tolerability. One hundred and eighty patients were randomly enrolled at the ratio of 1:2 into groups A:B. All patients had rapid initial clinical and parasitological responses. There were no significant differences in fever clearance time or parasite clearance time between both groups. The 28-day cure rates were high, at 100% and 99%, in groups A and B, respectively. We conclude that Artekin was as effective and well-tolerated as artesunate-mefloquine, and can be used alternatively as the current treatment for multidrug-resistant P. falciparum malaria.

Acute Disease↗
PubMed2004

Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials.

OBJECTIVE: To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia. DESIGN: Cross-sectional survey. SETTING: Pharmacies and shops selling antimalarial drugs in Myanmar (Burma), Lao PDR, Vietnam, Cambodia and Thailand. MAIN OUTCOME MEASURES: Proportion of artemisinin derivatives or mefloquine containing drugs of substandard quality. RESULTS: Of the 188 tablet packs purchased which were labelled as 'artesunate' 53% did not contain any artesunate. All counterfeit artesunate tablets were labelled as manufactured by 'Guilin Pharma', and refinements of the fake blisterpacks made them often hard to distinguish from their genuine counterparts. No other artemisinin derivatives were found to be counterfeited. Of the 44 mefloquine samples, 9% contained <10% of the expected amount of active ingredient. CONCLUSIONS: An alarmingly high proportion of antimalarial drugs bought in pharmacies and shops in mainland SE Asia are counterfeit, and the problem has increased significantly compared with our previous survey in 1999-2000. This is a serious threat to public health in the region.

Antimalarials↗
PubMed2004

Seasonal fluctuations in the carriage of Plasmodium vivax gametocytes in Thailand.

To study the influence of season on Plasmodium vivax gametocyte carriage, the relationship between monthly rainfall and the proportion of P. vivax patients with detectable gametocytaemia was analysed. Most of the data used came from 6807 aggregated observations collected, in a refugee camp on the Thai-Burmese border, between January 2000 and December 2002. There was a positive correlation between rainfall and the incidence of P. vivax infection (Spearman's rho=+0.42; P =0.01) but the prevalence of gametocyte carriage among those with P. vivax infection was negatively correlated with rainfall (Spearman's rho=-0.58; P <0.001). The latter, negative correlation remained significant after controlling for the proportion of visitors relative to camp residents (P =0.003). Migrations, changes in transmission patterns, seasonal haematological changes, and ultraviolet immunosuppression are discussed as potential explanations for these observations.

Adolescent↗
PubMed2004

Therapeutic efficacy of artesunate in Plasmodium vivax malaria in Thailand.

Our previous study showed that in vitro susceptibility of Plasmodium vivax to chloroquine has significantly decreased in Thailand within the past two decades. Thus, the evaluation of alternative antimalarials for treatment of vivax malaria is needed. The aim of this study was to examine parasitological and clinical efficacy of an artemisinin derivative (artesunate) for the treatment of vivax malaria in patients who were admitted to the Bangkok Hospital for Tropical Diseases. We randomly allocated patients aged 12-56 years to receive 3.3mg/kg (adult dose 200 mg) on the first day, and for the next four days each patient was given 1.65 mg/kg orally (adult dose 100 mg), total dose = 600 mg. After the five-day course of artesunate, primaquine was given: a single oral dose of 15mg for 14 days. A total number of 42 patients received treatment. All participants were followed up for 28 days. In all the cases, both parasitemia and fever were resolved rapidly; the mean fever clearance time and parasite clearance time, 14.6 and 36.7 hours, respectively, showed that therapeutic response to artesunate was better than that of chloroquine. The 14-day cure rate was 100%, but reappearance of parasitemia was seen in two patients on days 21 and 25 following treatment, respectively. These two cases of failure rate should be considered as true relapse rather than recrudescence, since the relapse interval in Southeast Asian vivax malaria according to recent findings seems to be 3 weeks after start of treatment, if primaquine is not given or an inadequate amount is given. In conclusion, artesunate might be useful in treatment of vivax malaria, causing a good blood schizontocidal effect. However, to prevent emerging resistance it should never be used alone.

Adolescent↗
PubMed2004

The pharmacokinetics of oral dihydroartemisinin and artesunate in healthy Thai volunteers.

The pharmacokinetics of oral dihydroartemisinin (DHA) following the dose of 2 and 4 mg/ kg body weight dihydroartemisinin (Twisinin, T-2 Program, Thailand) and 4 mg/kg body weight oral artesunate (AS; Guilin Pharmaceutical Works, Guangxi, China) were investigated in 20 healthy Thai volunteers (10 males, 10 females). All formulations were generally well tolerated. Oral DHA was rapidly absorbed from gastrointestinal tract with marked inter-individual variation. The pharmacokinetics of DHA following the two dose levels were similar and linearity in its kinetics was observed. Based on the model-independent pharmacokinetic analysis, median (95% CI) values for Cmax of 181 (120-306) and 360 (181-658) ng/ml were achieved at 1.5 hours following 2 and 4 mg/kg body weight dose, respectively. The corresponding values for AUC0-infinity, t1/2z, CL/f and Vz/f were 377 (199-1,128) vs 907 (324-2,289) ng.h/ml, 0.96 (0.70-1.81) vs 1.2 (0.75-1.44) hours, 7.7 (4.3-12.3) vs 6.6 (3.1-10.1) l/kg, and 90.5 (28.6-178.2) vs 6.6 (3.1-10.1) ml/min/kg, respectively (2 vs 4 mg/kg dose). Oral AS was rapidly biotransformed to DHA, which was detectable in plasma as early as 15 minutes of AS dosing. Following 4 mg/kg dose, median (95% CI) value for Cmax of 519 (236-284) ng/ml was achieved at 0.7 (0.25-1.5) hours. AUC0-infinity, and t1/2z were 657 (362-2,079) ng.h/ml, 0.74 (0.34-1.42) hours, respectively. Cmax of DHA following oral AS were significantly higher, but total systemic exposure was greater following oral DHA at the same dose level (4 mg/kg body weight). There was no significant sex difference in pharmacokinetics of DHA.

Administration, Oral↗
PubMed2003

Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil.

OBJECTIVE: To determine the effects of late pregnancy and also oestrogen supplementation on the CYP2C19-mediated biotransformation of proguanil (PG) to its active antifol triazine metabolite cycloguanil (CG). METHODS: Case control study conducted on the NW border of Thailand; a single dose of PG (4 mg/kg) was administered to Karen women in late pregnancy and a single blood and urine sample taken 6 h later. Women were studied in late pregnancy (>36 weeks) and restudied 2 months after delivery. A separate cohort of Karen women newly attending a birth-control clinic were studied before and 3 weeks into their first course of oral contraceptives (OCP: levonorgestrel 0.15 mg and ethinyloestradiol 0.03 mg). Forty-five pregnant women and forty-two healthy OCP users were studied. RESULTS: The results were similar in both groups; pregnancy and OCP use were both associated with reduced formation of cycloguanil (CG). Impaired PG biotransformation was seen in women with the "extensive metaboliser" phenotype (urine PG/CG ratio <10). CG levels, adjusted for dose, were a median (range) 73% (-59 to 420%) higher following the pregnancy than during the pregnancy in women characterised as extensive metabolisers ( P<0.001). CG levels in women characterised as extensive metabolisers were 34% (-54 to 323%) higher before than while taking the OCP ( P<0.01). CONCLUSION: Late pregnancy and OCP use impair biotransformation of the active antimalarial metabolite CG from the parent PG. This may be mediated by oestrogen inhibition of CYP2C19 activity. The dose of PG should be increased by 50% in these groups.

Antimalarials↗
PubMed2003

The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria.

OBJECTIVE: To determine the pharmacokinetic properties of atovaquone, proguanil, and the triazine metabolite cycloguanil in women with recrudescent multi-drug resistant falciparum malaria during the second and third trimesters of pregnancy treated by artesunate-atovaquone-proguanil. METHODS: Serial plasma concentrations of atovaquone, proguanil and cycloguanil were measured in 24 women at baseline and after the final dose of the 3-day treatment with atovaquone (20 mg/kg/day) plus proguanil (8 mg/kg/day) plus artesunate (4 mg/kg/day) daily. RESULTS: The triple combination was well tolerated and highly effective. The outcomes of pregnancy were all normal. Population mean (+/- SEM) oral clearance (Cl/F) estimates were 313+/-33 ml/h/kg and 1109+/-43 ml/h/kg, total apparent volume of distribution (Vd/F) 13.0+/-1.3 l/kg and 22.9+/-1.4 l/kg, and terminal elimination half-life; 29.1 h and 14.3 h, for atovaquone and proguanil, respectively. Using conventional and population pharmacokinetic analyses, Cl/F and Vd/F estimates for both drugs were approximately twice, and plasma concentrations less than half those reported previously in healthy subjects and patients with acute malaria. CONCLUSION: Artesunate-atovaquone-proguanil is a promising treatment for multi-drug resistant falciparum malaria during pregnancy, but the dose of atovaquone-proguanil may need to be increased.

Acute Disease↗
PubMed2003

A single-nucleotide substitution from C to T at position -1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand.

We examined a possible association of single-nucleotide polymorphisms (SNPs) in the promoters of IL-3, IL-4, and IL-13 genes on the 5q31-33, IL-3 -16T>C, IL-4 -590T>C, and IL-13 -1055C>T, with severity of malaria in 361 adult malaria patients in Thailand. The IL-13 -1055T allele showed a significant association with protection from severe malaria (OR 0.51, 95% CI 0.32-0.80; P=0.0032 by the chi(2) test), while allele frequencies of IL-3 -16T>C and IL-4 -590T>C were not statistically different between mild and severe malaria patients. An IL-13 -1055C>T has been reported to alter the regulation of IL-13 production. Thus, IL-13 -1055T may show resistance to severe malaria through the alteration of IL-13 production.

Adolescent↗
PubMed2003

Quinine pharmacokinetic-pharmacodynamic relationships in uncomplicated falciparum malaria.

The relationships between the pharmacokinetic properties of quinine during a 7-day treatment course and the therapeutic response were studied in 30 adult patients with uncomplicated falciparum malaria monitored for > or = 28 days. All patients received a 7-day oral quinine regimen either alone (n = 22) or in combination with rifampin (n = 8). The median fever clearance time was 58.5 h, and the mean +/- standard deviation parasite clearance time was 73 +/- 24 h. After recovery, six patients had recrudescences of Plasmodium falciparum malaria and seven had delayed appearances of P. vivax infection between days 16 and 23. Between the patients with and without recrudescences, there were no significant differences either in fever clearance time or parasite clearance time or in the overall pharmacokinetics of quinine and 3-hydroxyquinine. Patients for whom the area under the concentration-time curve from 3 to 7 days for quinine in plasma was <20 microg.day/ml had a relative risk of 5.3 (95% confidence interval = 1.6 to 17.7) of having a subsequent recrudescence of infection (P = 0.016). Modeling of these data suggested an average minimum parasiticidal concentration of quinine in plasma of 3.4 microg/ml and an MIC of 0.7 microg/ml for uncomplicated falciparum malaria in Thailand. To ensure a cure, the minimum parasiticidal concentration must be exceeded during four asexual cycles (>6 days).

Adult↗
PubMed2003

Adverse effect of rifampin on quinine efficacy in uncomplicated falciparum malaria.

The effects of adding rifampin to quinine were assessed in adults with uncomplicated falciparum malaria. Patients were randomized to receive oral quinine either alone (n = 30) or in combination with rifampin (n = 29). Although parasite clearance times were shorter in the quinine-rifampin-treated patients (mean +/- standard deviation, 70 +/- 21 versus 82 +/- 18 h; P = 0.023), recrudescence rates were five times higher (n = 15 of 23; 65%) than those obtained with quinine alone (n = 3 of 25; 12%), P < 0.001. Patients receiving rifampin had significantly greater conversion of quinine to 3-hydroxyquinine and consequently considerably lower concentrations of quinine in their plasma after the second day of treatment (median area under the plasma drug concentration-time curve from day zero to day 7 = 11.7 versus 47.5 micro g/ml. day, P < 0.001). Rifampin significantly increases the metabolic clearance of quinine and thereby reduces cure rates. Rifampin should not be combined with quinine for the treatment of malaria, and the doses of quinine should probably be increased in patients who are already receiving rifampin treatment.

Adult↗
PubMed2003

Paroxysm serum from a case of Plasmodium vivax malaria inhibits the maturation of P. falciparum schizonts in vitro.

In concurrent infections in vivo, the blood stages of Plasmodium vivax suppress those of Plasmodium falciparum. To see if the paroxysm (i.e. the periodic febrile episode) of P. vivax infection contributes to this suppression, sera from a P. vivax-infected volunteer were added to cultures of whole blood taken from cases of P. falciparum malaria. The crude 'rate' of schizont generation from the ring forms, measured as the percentage of all asexual parasites that were schizonts after incubation for 24 h, was similar whether the cultures contained serum samples collected during paroxysms or those collected, from the same volunteer, at other times (19.1% v. 18.9%; P=0.842). After a random-effect linear regression was used to adjust for disparities between the P. falciparum isolates, however, the degree of schizont maturation, measured as the mean number of nuclei per schizont, was significantly lower for the cultures with 'paroxysm serum' than for those with 'non-paroxysm serum' (4.8 v. 5.3; P=0.002). The proportion of schizonts considered mature was also significantly lower when 'paroxysm serum' was used (3.7% v. 6.3%: P=0.03). This appears to be the first in-vitro study in which sera collected during a paroxysm of P. vivax have been shown to inhibit the maturation of P. falciparum schizonts. The role of this mechanism in intra- and inter-specific competition is discussed.

Adolescent↗