PubMed Health⌕ Search

Biomedical subjects

D Bunnag

Publications and source records attributed to D Bunnag.

At least 19 recordsLinked to original sources

Antigenic diversity of Plasmodium vivax and their geographic distribution in Thailand.

Fifty-eight monoclonal antibodies (MAbs) raised against the erythrocytic stages of Plasmodium vivax were selected for typing of 501 P. vivax isolates from different geographic locations throughout Thailand. Based on their reactivities in the indirect fluorescent antibody test, these MAbs were classified into five groups: group I MAbs showing generalized staining of all blood stages; group II MAbs reacting with merozoites and their organelles; group III MAbs reacting with the surface membrane of merozoites; Group V MAbs reacting with the surface membrane of trophozoites and schizonts; and group VII MAbs reacting with internal components of the parasites. Sixteen MAbs reacted with more than 95% of the isolates; the epitopes recognized by these MAbs were considered as being invariant. The remaining MAbs reacted with 30-90% of the isolates, and the epitopes recognized by these MAbs were regarded as being variable. The variant epitopes were associated with > 200-, 135-, and 100-kilodalton (kDa) molecules of all blood stages, the 95-kDa molecule on merozoite organelles, the 200-kDa molecule on the surface of trophozoites and schizonts, and the 85-kDa molecule of the parasite internal components. Antigenic diversity occurred among the P. vivax population in the endemic areas of Thailand and was shown to vary from place to place and was highest in the area with the highest rate of transmission along the Myanmar border in western Thailand and along the Cambodian border in eastern Thailand, including Trat (48.4%), Tak (41.7%), Chantaburi (36.5%), and Mae Hong Son (36.4%). Demonstration of antigenic diversity of P. vivax parasites signals a note of caution in the development of vaccines for vivax malaria. The vaccines should be directed against protective, conserved and not against variant epitopes.

Animals↗

Antigenic disparity of Plasmodium vivax causing initial symptoms and causing relapse.

Relapse infections are an important obstacle to the successful treatment and control of Plasmodium vivax malaria, but little is known about the nature of the relapse. To provide insight into the antigenic disparity of the parasites causing initial clinical symptoms and causing relapse, a panel of 58 monoclonal antibodies (MAbs) against erythrocytic stages of Plasmodium vivax was tested by indirect fluorescent antibody test in five relapse cases. The initial and relapse strains from three patients (R3, R4, and R5) exhibited similar IFA reactivity with all MAbs tested, whereas the isolates from two relapse cases (R1 and R2) showed different patterns of reactivity and were seen only with 15 MAbs In case R1, different IFA reactivities were observed with 12 MAbs, nine of which reacted with the initial (RPV261) but not the relapse (RPV393) isolates, whereas the other three MAbs reacted only with the relapse isolates. With regards to the second relapse case (R2) in whom two relapses occurred, different IFA reactivities were demonstrated with seven MAbs that reacted only with the initial isolate (RPV 182) and with the isolate from the first relapse (RPV 240) but not with the isolate from the second relapse (RPV 300). The antibody responses from patients who developed primary clinical symptoms and relapse were detected by Western immunoblotting. In cases R3, R4 and R5, there was no difference in the spectrum of antigens from initial and relapse sera recognized by the antibodies. In contrast, in cases R1 and R2, the molecules recognized by antibodies in initial and relapse sera were markedly altered. In case R1, the series of molecules of P. vivax antigens recognized by initial (RPV 261) and relapse (RPV 393) sera were 21, 25, 31, 39, 42, 61, 95, 115, 200, > 200 kDa and 21, 24, 31, 35, 57, 75, 200, > 200 kDa, respectively. In case R2, the initial serum (RPV 182) recognized P. vivax antigens with molecular weights of 23, 30, 52, 57, 68, 75, 85, 95, 115, and 195 kDa while the first relapse (RPV 240) and the second relapse sera recognized P. vivax antigens with molecular weights of 23, 30, 52, 85, 95,115 kDa and 30, 57, 68, 75, 85,195 kDa, respectively.

Animals↗

Treatment of Opisthorchis viverrini and intestinal fluke infections with Praziquantel.

The study was carried out from September to November 1997 in Phrae Province of northern Thailand. A total of 95 adult patients with Opisthorchis-like ova in their stools were randomly treated with two different manufactured Praziquantels. Group 1, consisting of 49 patients, received a single dose of 40 mg per kg Praziquantel manufactured by the Thai Government Pharmaceutical Organization. Group 2 (46 patients) received Biltricide at the same dosage. Haplorchis taichui, H. yokogawai, Echinostome spp., O. viverrini, Taenia saginata and Enterobius vermicularis were expelled in the stools after treatment. Minute intestinal flukes were detected in 64% of patients. O. viverrini was found in lower proportion of 17%. By formalin-ether concentration examination one stool specimen from each patient, the cure rate in both groups on the 30th day of treatment was 100%. The side effects of the two different Praziquantel treatments were mild with no significant difference. Praziquantel, regardless of its manufacture, proved effective against O. viverrini and other minute intestinal flukes (H. taichui, H. yokogawai and Echinostome spp).

Adolescent↗

Opisthorchis viverrini infection in Thailand: studies on the morbidity of the infection and resolution following praziquantel treatment.

A community study on opisthorchiasis was conducted in Prachinburi Province in eastern Thailand during 1990-1992. The morbidity from opisthorchiasis in the community and reversibility of biliary pathology following treatment with praziquantel at a single dose of 40 mg/kg were assessed by longitudinal investigations of clinical, laboratory, and ultrasonographic changes. A total of 913 voluntary subjects infected with Opisthorchis viverrini were randomly selected for longitudinal study, and 579 subjects without liver fluke infection were recruited as controls. The majority of the study group suffered from mild and moderate infections that were associated with nonspecific gastrointestinal symptoms. Grade I and II ultrasonographic changes, which indicated chronic inflammation of the biliary tract and gallbladder, were detected in 32% of the infected individuals. Clinical symptoms and ultrasonographic changes were common in subjects 21-40 years of age and older. Satisfactory resolution of morbidity was observed during two years follow-up on days 0, 60, 180, 360, and 720, as shown by significant clinical improvement, normalization of laboratory parameters, and downgrading of ultrasonographic abnormalities. Portable ultrasonography has proved to be a reliable noninvasive technique in the evaluation of the morbidity due to opisthorchiasis in rural areas.

Adolescent↗

Effect of artemether on electrocardiogram in severe falciparum malaria.

The effect of intramuscular artemether (intramuscular loading dose of 160 mg, followed by 80 mg daily for another 6 doses), in comparison with that of quinine (intravenous infusion of loading dose of 20 mg/kg, followed by 10 mg/kg q 8 hourly for 7 days), on the electrocardiograph of severe falciparum malaria patients were investigated in 102 Thai patients (92 males, 10 females) admitted to Pra Pokklao Hospital, Chantaburi, southeast of Thailand. Fifty patients (19 with quinine and 31 with artemether) were eligible for ECG analysis. Hypotension was found significantly more common in the quinine group (13 vs 2 cases). Thirteen, 5 and 1 patients with quinine treatment, respectively, had tachycardia, non-specific T-wave change and QTc prolongation. No significant dysrhythmia was found despite high plasma quinine concentrations. Five patients died; their ECGs were not significantly different from those who survived. In the group with intramuscular artemether, 17 cases had tachycardia prior to artemether treatment. QTc prolongation and non-specific T-wave change were found in 2 and 6 cases. One patient had RBBB and second degree AV-block on Day 1, but returned to normal on Day 2. No other dysrhythmia or other significant changes in ECG tracing which would suggest any effect of artemether on cardiovascular system were observed.

Adolescent↗

Two doses of artemether/mefloquine or artesunate/mefloquine combination for multidrug resistant falciparum Malaria.

Plasmodium falciparum in Southeast Asia is highly resistant to chloroquine, sulfadoxine/ pyrimethamine, quinine and even mefloquine. The use of two doses of short course artemether/mefloquine combination has been shown to be effective in a recent study. In the present study, we have assessed the efficacy of short course treatment with artesunate/mefloquine, in comparison with artemether/mefloquine in patients with multidrug resistant falciparum malaria. Ninety-nine Thai male patients who sought consultation at Makham Malaria Clinic, Chantaburi (eastern part of Thailand), were randomized to receive either the combination of artemether (150 and 100 mg; group A) or artesunate (150 and 100 mg; group B) with mefloquine (750 and 500 mg) at 24 hours apart. The follow-up was on days 1, 2, 7, 14, 21, 28, 35 and 42. Patients in both groups showed a rapid initial response to treatment; fever and parasite were cleared within 48 hours in 100 and 100% vs 91.8 and 96%, for group A vs B, respectively. All patients in group A had completed the 42 day-follow up; however, two patients in group B did not finish the 42-day follow-up. The cure rate was 100% in either group. No serious adverse effects were found. Artemether or artesunate with mefloquine given two doses at 24 hours apart can be used as effective alternative treatment regimens for multidrug resistant falciparum malaria.

Acute Disease↗

Plasma quinine concentrations in falciparum malaria with acute renal failure.

Plasma quinine (Qn) monitoring was performed in 32 patients with severe falciparum malaria (10 with acute renal failure (ARF) and 22 with other severe manifestations) who were treated with the standard regimen of 10 mg/kg body weight Qn dihydrochloride, with a loading dose of 20 mg/kg body weight. Median plasma Qn concentrations prior to the first dose on each day were approximately 10-30% higher in ARF patients than in non-ARF patients during acute infection. Seven patients underwent haemodialysis; 2 died after 2 cycles. There were no significant changes in plasma Qn concentrations in patients with ARF during haemodialysis. No Qn was detectable in haemodialysate fluids. This suggests that dosage adjustment of Qn during haemodialysis is unnecessary. Cardiotoxity of Qn must be of concern in malaria patients with ARF after 3 days of Qn therapy, and ECG monitoring during Qn infusion is recommended in all severe malaria patients with persistent ARF. If there is any arrhythmia, the infusion should be discontinued. However, in some hospitals where ECG facilities are not available, reduction in Qn dosage in persistent ARF patients should be considered after the third day of therapy. The appropriate dosage reduction should be further studied. Monitoring of total plasma Qn concentrations (which has been used routinely) is of no value for predicting the cardiotoxicity in ARF patients; monitoring of free Qn would be more appropriate. However, ECG seems to be the practical procedure to monitor cardiotoxicity of Qn. It may be possible to use the QTc interval to estimate the Qn concentration in severe malaria patients without ARF, but not in patients with persistent ARF.

Acute Kidney Injury↗

Quinine-tetracycline for multidrug resistant falciparum malaria.

Plasmodium falciparum in Southeast Asia is highly resistant to chloroquine and sulfadoxine/ pyrimethamine. Quinine-tetracycline has been used as a second line treatment for uncomplicated falciparum malaria, but duration of treatment varies from place to place. The 7-days course of this combination has been shown to be very effective. However, due to the cinchonism adverse effects, the patient compliance has not been satisfactory. We have evaluated the efficacy of a 7-days course of tetracycline in combination with either 5 or 7-days course of quinine. Ninety male Thai patients who were admitted to the Bangkok Hospital for Tropical Diseases were randomized to receive tetracycline 250 mg qid for 7 days in combination with either quinine 600 mg tid for 5 days (Q5T7; group A) or quinine 600 mg tid for 7 days (Q7T7; group B). The patients were hospitalized for 28 days. Patients in both groups had a comparable initial response to treatment, with the clearance of fever and parasites within 4 days. There were 46 and 40 patients in group A and B, respectively, who completed the 28 day of follow-up. The cure rates were 87 and 100%, respectively for group A and B. No serious adverse effects were found in either group; transient nausea, vomiting and tinnitus were common findings. The incidence of adverse effects was not different between the two groups. The results from the present study suggest that a short course treatment of quinine (Q5T7) had significantly decreased the cure rate. In areas with quinine resistant falciparum malaria, a full course of 7-days quinine, in combination with 7-days course of tetracycline is recommended for hospital treatment. However, an alternative shorter course of antimalarials is suggested for home treatment.

Adolescent↗

Serum antibody responses in opisthorchiasis.

We evaluated an enzyme-linked immunosorbent assay using crude parasite homogenates as a diagnostic test for Opisthorchis viverrini infection in humans. Serum antibody (Ab) responses to O. viverrini adult worm homogenate (AWH) and metacercaria homogenate (MH) were studied in 83 infected residents of an opisthorchiasis-endemic area in Thailand. Elevated levels of Ab persisted for over 1 year following curative treatment with praziquantel, and cross-reactivity to O. viverrini AWH and MH antigens was observed in sera from individuals with other parasitic infections. Serum Ab to crude AWH and MH are therefore unsuitable for immunodiagnosis since they may be non-specific and would not differentiate between ongoing and past infection.

Animals↗

Integration of control measures for malaria vectors in endemic areas of Thailand.

Various vector control measures were applied in different endemic areas in two provinces, Saraburi and Chanthaburi, with comparison among different control measures. Application of IGR (insect growth regurator, pyriproxyfen) was introduced at Wat Tam Pra Pothisat, Tab-Kwang District, Saraburi Province. Some integration measures were performed at villages 6 and 8, Patavee, Makham District, Chanthaburi Province. In Tab-Kwang District with low malaria endemicity at the study site predators were not able to be released due to rapid velocity of running water. IGR could effectively control malaria compared to the basin released predators. Another endemic areas villagers 6 and 8, Patavee, Makham, Chanthaburi Province was chosen. Highly endemic multidrug resistant malaria has been prevalent for many years in this area. Integration of Kanda's trapping system, application of IGR, use of both residual spraying and impregnated bed-net methods with etofenprox successfully interrupted malaria infection. The application of these methods as an integrated control system could be adjusted to environmental conditions. The results of this study suggest rapid effective vector control.

Animals↗

Mefloquine prophylaxis prevents malaria during pregnancy: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled study of mefloquine antimalarial prophylaxis in pregnancy (> 20 weeks of gestation) was conducted in 339 Karen women living in an area of multidrug-resistant malaria transmission on the Thai-Burmese border. Mefloquine gave > or = 86% (95% confidence interval [CI], 59%-94%) protection against Plasmodium falciparum and complete protection against Plasmodium vivax infections. Mefloquine prophylaxis was well tolerated; use of an initial loading dose (10 mg/kg) was associated with transient dizziness, but there were no other significant adverse effects on the mother, the pregnancy, or infant survival or development (followed for 2 years). Falciparum malaria was associated with maternal anemia and a mean reduction in birth weight in gravidae I, II, and III of 225 g (95% CI, 26-423). Maternal anemia at delivery (hematocrit < 30%) was associated with increased infant mortality: 26% versus 15% (relative risk, 1.9; 95% CI, 1.1-3.2). Mefloquine is safe and effective for antimalarial prophylaxis in the second half of pregnancy.

Adult↗

Possible protective immunity in human opisthorchiasis.

Chronic infections with the liver flukes Opisthorchis viverrini and Clonorchis sinensis affect over 30 million people in southeastern Asia. With ongoing exposure, reinfection readily occurs following curative treatment and cumulative infections result in significant morbidity and a predisposition to cholangiocarcinoma. Though protective immunity has never been described in human opisthorchiasis, heterogeneity in worm burden occurs and a small number of exposed residents of endemic areas remain apparently uninfected. To explore the nature of this heterogeneity, we compared levels of serum antibody (Ab) to O. viverrini measured by an enzyme-linked immunosorbent assay in 83 stool egg-positive and 49 stool egg-negative residents of an O. viverrini-endemic area in Thailand. Compared to the egg-positive residents, the egg-negative group had significantly higher levels of immunoglobulin (Ig)G, IgA and IgM to adult worm homogenate (AWH) and total Ab to metacercaria homogenate (MH). Furthermore, immunoblot analyses revealed that a significantly higher proportion of sera from the egg-negative residents had IgA reactivity against a 38-kDa AWH antigen and IgM reactivity against carbohydrate epitopes of a 42-kDa AWH glycoprotein antigen. These findings support a hypothesis that the egg-negative group includes individuals who may be immunologically resistant to this usually chronic infection.

Adolescent↗

Pharmacokinetics of mefloquine alone or in combination with artesunate.

A randomized comparative trial of the pharmacokinetics and pharmacodynamics of oral doses of mefloquine and of mefloquine in combination with artesunate was carried out on 20 Thai male patients with acute, uncomplicated falciparum malaria. The patients were randomized to receive either mefloquine alone (8 patients; 1250 mg of mefloquine--initial dose, 750 mg; followed 6 hours later by 500 mg), or in combination with oral artesunate (12 patients--initial dose, 200 mg of artesunate; followed by 750 mg and 500 mg of mefloquine 6 hours and 12 hours later, respectively). The patients who received mefloquine alone all showed initially good responses to the treatment, with mean +/- SD values for the fever clearance time (FCT) and parasite clearance time (PCT) of 44.7 +/- 43.1 hours and 82.3 +/- 52.3 hours, respectively. Two patients had recrudescences on day 20 and day 31 (RI response). The cure rate was 75%, and one patient had Plasmodium vivax in his peripheral blood on day 52. The patients who received the combination treatment were clinically markedly improved, with a relatively shorter FCT (31.2 +/- 12.4 hours) and significantly shorter PCT (47.5 +/- 19.6 hours). Four had recrudescences on days 12, 18, 26 and 33; the cure rate was 66%. Artesunate caused three significant changes in mefloquine pharmacokinetics: a decrease in the maximum concentration (Cmax: 1623 ng.ml-1 versus 2212 ng.ml-1); an increase in the clearance rate (Cl/f:2.9 ml.min-1.kg-1 versus 1.1 ml.min-1.kg-1); and an expansion of the volume of distribution (Vdz/f: 31.8 l.kg-1 versus 25.0 l.kg-1).

Adolescent↗

Comparison of oral artesunate and quinine plus tetracycline in acute uncomplicated falciparum malaria.

In Thailand Plasmodium falciparum malaria is highly resistant to available antimalarials. Investigations on the efficacy of existing antimalarials and of alternative drugs are urgently needed. Artesunate has been shown to be effective against falciparum malaria, but is associated with a high recrudescence rate. We have carried out a comparative clinical trial of the standard regimen of quinine + tetracycline versus oral artesunate at a 700-mg total dose given over 5 days to patients with acute uncomplicated falciparum malaria. The 64 male patients who took part in the study were randomized to receive either quinine-tetracycline (33 patients) or oral artesunate (31 patients). All the patients were admitted to the Bangkok Hospital for Tropical Diseases for 28 days. Oral artesunate had faster parasite and fever clearance times than the combination quinine-tetracycline, but the cure rate was not significantly different for the two regimens. However, the occurrence of adverse effects, such as tinnitus, was significantly higher in the quinine-tetracycline group. Surprisingly nausea and dizziness were rather common with artesunate. The possibility of neurological adverse effects for artesunate should also be borne in mind. Oral artesunate (700 mg given over 5 days) is effective and better tolerated than the combination quinine-tetracycline. The cure rate we obtained is higher than that reported in previous studies with 600 mg of oral artesunate given over 5 days. Oral artesunate can be considered as an alternative drug for multiple-drug-resistant falciparum malaria; however, adverse effects, particularly neurotoxicity, should be closely monitored before its widespread use can be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Pharmacokinetics of praziquantel in patients with opisthorchiasis.

The pharmacokinetics of praziquantel was investigated in 9 Thai male patients with asymptomatic opisthorchiasis (stool positive) and 9 patients (6 males, 3 females) with moderately advanced infection (hepatomegaly). The geometric means of the pretreatment Opisthorchis viverrini egg count in these patients were 2,950 vs 4,468 eggs per gram of stool. The results indicate the impairment of metabolism of praziquantel in the moderately advanced stage opisthorchiasis. The pharmacokinetics of the drug in these patients during the acute infection was markedly altered when compared with that after recovery and in patients with early stage of the infection. The clearance rate (Cl/f) was significantly reduced [medians and ranges of 106 (43-242) vs 192 (112-692) and 171 (133-427) ml/min/kg] and the t1/2z and MRT were prolonged [t1/2z: 3.8 (2.0-6.2) vs 2.7 (1.7-4.3) and 2.3 (1.7-2.8) hours; MRT: 6.2 (3.2-11.0) vs 4.6 (2.7-6.2) and 4.5 (2.9-5.1) hours]. In addition, AUCo-alpha was significantly greater [6.0 (2.5-15.6) vs 3.5 (0.6-6.0) and 3.9 (1.6-5.0) micrograms hour/ml].

Adult↗