Browsing by Author "Looareesuwan, Sornchai"
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Item Application of real-time polymerase chain reaction (PCR) analysis for detection and discrimination of malaria parasite species in Thai patients.(2004-01-24) Katakai, Yuko; Chiabchalard, Rachatawan; Komaki-Yasuda, Kanako; Kawazu, Shin-ichiro; Singhasivanon, Pratap; Krudsood, Srivicha; Looareesuwan, Sornchai; Kano, ShigeyukiA TaqMan real-time PCR system was used to detect and discriminate the 4 species of human malaria parasites in clinical blood samples. A 150-base pair (bp) region of the small subunit ribosomal RNA (SSU rRNA) gene of each malaria parasite, including species-specific sequences to be detected by TaqMan probe, was used as a target for PCR analysis. The PCR method used universal primers and species-specific TaqMan probes for Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. The detection threshold for the method, as determined with serial dilution of cultured P. falciparum-infected erythrocytes, was 5 parasite-infected erythrocytes per reaction. Fifty blood samples of falciparum malaria and a second set of 50 samples of vivax malaria, diagnosed by microscopic examination at the Hospital for Tropical Diseases, Mahidol University, Thailand, were analyzed by real-time PCR. In the 50 samples of microscopically-diagnosed falciparum malaria, 40 were regarded as P. falciparum single infection, 7 were P. falciparum and P. vivax mixed infections, and 3 were P. vivax single infection by real-time PCR. In the second set of 50 samples of microscopically diagnosed vivax malaria, all were considered P. vivax single infection by PCR. Neither P. ovale nor P. malariae infection was identified in the 100 blood samples. Real-time PCR analysis was shown to be more sensitive and accurate than routine diagnostic methods. Application and extension of the PCR method reported here will provide a powerful tool for further studies of malaria.Item The Asian center of international parasite control (ACIPAC): five years of achievement. I. Introduction.(2005-01-14) Kojima, Somei; Looareesuwan, Sornchai; Singhasivanon, Pratap; Takeuchi, TsutomuACIPAC has made an effort to promote the concept of the school-based approach to malaria and STH control, mainly through human resource development, which could be eventually extended to any other health promotion program. Implementation of SSPP resulted in the establishment of national policies on parasite control and/or school health in some partner countries. It also provides a good opportunity for the formulation of partnerships among health and education sectors and international partners, although it did cause some problems concerning the enrollment of persons of authority from partner countries, and the staff of JICA resident offices as well. As described in the Joint Evaluation Report, ACIPAC is expected to further contribute to human resource development and to strengthening human resource and information networking at regional and global levels.Item Association of intestinal helminths with decreased liver size and sCD23 concentration during falciparum malaria.(2004-03-27) Nacher, Mathieu; Treeprasertsuk, Sombat; Singhasivanon, Pratap; Popakdee, Nuntaporn; Silachamroon, Udomsak; Bussaratid, Valai; Phumratanaprapin, Weerapong; Looareesuwan, Sornchai; Wilairatana, PolratTo determine if intestinal helminths and the CD23/nitric oxide pathway had an influence on liver size, we conducted a cross-sectional study on 438 patients with confirmed P. falciparum malaria admitted at the Hospital for Tropical Diseases in Bangkok. For all patients the liver size was measured as number of centimeters below the rib cage, a stool examination was conducted, and CD23 and reactive nitrogen intermediates were measured. The median liver size was smaller in helminth-infected patients than in helminth-free patients (chi2 for trend = 9.1, p = 0.003). Liver size significantly increased with the concentration of sCD23 (p < 0.0001). The median sCD23 concentration (OD) was significantly lower in helminth-infected patients than in helminth-free patients, respectively 0.33 (quartiles 0.24-0.57) and 0.45 (quartiles 0.27-0.59), (p = 0.01). There was a negative correlation between sCD23 concentrations and RNI (Spearman's rho = -0.40, p < 0.0001). All the above results remained significant after controlling for potential confounders. These results are compatible with a CD23/NO-mediated decrease in liver size in helminth-infected patients.Item Clinical experience with intravenous quinine, intramuscular artemether and intravenous artesunate for the treatment of severe malaria in Thailand.(2003-03-16) Krudsood, Srivicha; Wilairatana, Polrat; Vannaphan, Suparp; Treeprasertsuk, Sombat; Silachamroon, Udomsak; Phomrattanaprapin, Weerapong; Gourdeuk, Victor R; Brittenham, Gary M; Looareesuwan, SornchaiWe prospectively studied 803 Thai patients admitted to the Bangkok Hospital for Tropical Diseases to assess the safety, tolerability and effectiveness of treatments for strictly defined P. falciparum malaria. Patients were assigned to one of five treatment groups: (i) a 5-day course of intravenous artesunate in a total dose of 600 mg, Group Aiv; (ii) intravenous artesunate as in Group Aiv followed by mefloquine, 25 mg/kg, Group Aiv+M; (iii) a 3-day course of intramuscular artemether in a total dose of 480 mg, Group Aim; (iv) intramuscular artemether as in Group Aim followed by mefloquine, 25 mg/kg, Group Aim+M, and (v) intravenous quinine, 200 mg/kg given in divided doses over seven days followed by oral tetracylcine, 10 mg/kg, for 7 days. When patients could take oral medications, the parenteral antimalarials were administered as oral agents. There were no major adverse effects observed with any of the five treatment regimens. With all regimens, 95 to 100% of the patients survived. Mean parasite clearance times were more rapid with the artemisinin regimens (53 to 62 hours) than with quinine (92 hours). The mean fever clearance times with intravenous artesunate (80 to 82 hours) were about a day shorter than those with intramuscular artemether (108 hours) or intravenous quinine (107 hours). Mefloquine reduced the recrudescence rate from 24 to 5% with intravenous artesunate but from 45 to 20% with intramuscular artemether; recrudescence was 4% with quinine and tetracycline. A dose and duration of therapy greater than those in this study are needed for optimal therapy with intramuscular artemether. Effective therapy for severe falciparum malaria can be provided by either intravenous artesunate followed by mefloquine or by intravenous quinine followed by tetracycline.Item Defective erythropoietin production and reticulocyte response in acute Plasmodium falciparum malaria-associated anemia.(2008-07-09) Leowattana, Wattana; Krudsood, Srivicha; Tangpukdee, Noppadon; Brittenham, Gary; Looareesuwan, SornchaiTo elucidate the relationship between falciparum malaria-associated anemia and serum erythropoietin (Epo) levels and reticulocyte response during acute malaria infection, 87 adults aged 18-65 years presenting with acute, uncomplicated malaria were examined on enrollment and for 28 days of follow-up. The 87 patients were divided into 2 groups: those with anemia (n = 45) and those without (n = 42). Serum samples were taken on admission (Day 0), then on Days 7, 21, and 28, to measure the reticulocyte count, absolute reticulocyte count, reticulocyte hemoglobin content, and erythropoietin level (Epo). The absolute reticulocyte counts for the anemic patients were significantly higher than for those without anemia on Days 0, 7, 21, and 28. The serum Epo levels for the anemic patients were significantly higher than the non-anemic group only on Day 0 (44.39 +/- 4.06 vs 25.91 +/- 4.86 mlU/ml, p < 0.001). Inadequate Epo production was found in 31.03% (27/87) of patients on Day 0, 37.93% (33/87) on Day 7, 43.67% (38/87) on Day 21, and 39.08% (34/87) on Day 28. These results indicate defective Epo production and reticulocyte response in adult patients suffering from acute P. falciparum malaria, which differs from pediatric patients. Our findings may provide the basis for further study into the choice of therapeutic strategies to treat acute P. falciparum malaria-associated anemia with recombinant human Epo to correct refractory anemia due to malaria.Item Dose ranging studies of new artemisinin-piperaquine fixed combinations compared to standard regimens of artemisisnin combination therapies for acute uncomplicated falciparum malaria.(2007-11-11) Krudsood, Srivicha; Tangpukdee, Noppadon; Thanchatwet, Vipa; Wilairatana, Polrat; Srivilairit, Siripan; Pothipak, Nantaporn; Jianping, Song; Guoqiao, Li; Brittenham, Gary M; Looareesuwan, SornchaiTo determine the optimum dose of artemisinin-piperaquine combination therapies for acute uncomplicated Plasmodium falciparum malaria, we examined 7 candidate regimens in 411 patients admitted to the Bangkok Hospital for Tropical Diseases. The studies were performed from May 2005 to October 2005 and November 2005 to June 2006. We compared 3-day courses of artesunate-mefloquine, artemether-lumefantrine (Coartem) and of dihydroartemisinin-piperaquine (Artekin) as reference antimalarial treatments, with candidate regimens using 2-3 day courses of artemisinin-piperaquine, Artequick. Initially, patients receiving each of the regimens had a rapid clinical and parasitological response. All treatments were well tolerated and no serious adverse effects occurred. The 28-day cure rates were < 80% for the 2-day treatments with artemisinin-piperaquine at 2.4 mg/kg and 14.4 mg/kg, respectively, in the first study period and artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg, respectively, but > 98% for the 3-day regimens. These results suggest that a 3-day course of artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg, respectively, deserve further evaluation as an alternative treatment for multidrug-resistant P. falciparum malaria.Item Efficacy of Artequick versus artesunate-mefloquine in the treatment of acute uncomplicated falciparum malaria in Thailand.(2008-01-24) Tangpukdee, Noppadon; Krudsood, Srivicha; Thanachartwet, Vipa; Pengruksa, Chaweewan; Phophak, Nanthaporn; Kano, Shigeyuki; Li, Guoqiao; Brittenham, Gary M; Looareesuwan, Sornchai; Wilairatana, PolratTo determine the efficacy, safety and tolerability of an alternative short-course, artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum malaria, we compared Artequick--a fixed-dosed combination of artemisinin (80 mg), piperaquine (400 mg), and primaquine (4 mg), per tablet--with a standard regimen of artesunate-mefloquine. A total of 130 patients were randomly assigned to treatment with an orally administered, once-daily, 3-day regimen of either Artequick (Group A: 3.2 mg/Kg/day of artemisinin, 16 mg/Kg/day of piperaquine, and 0.16 mg/Kg/day of primaquine) or artesunate-mefloquine (Group B: artesunate, 4 mg/Kg/day, with mefloquine, 8 mg/Kg/day). Patients receiving each regimen had a rapid clinical and parasitological response. All treatments were well tolerated, and no serious adverse effects occurred. No significant differences were found in fever- and parasite-clearance times between the two study groups. The 28-day cure rates were similarly high, at 98.5% and 100%, in groups A and B, respectively. We conclude that Artequick was as effective and well tolerated as artesunate-mefloquine and could be used as an alternative treatment for multidrug-resistant Plasmodium falciparum malaria in Southeast Asia.Item Efficacy of ivermectin treatment of cutaneous gnathostomiasis evaluated by placebo-controlled trial.(2006-05-24) Bussaratid, Valai; Desakorn, Varunee; Krudsood, Srivicha; Silachamroon, Udomsak; Looareesuwan, SornchaiPrevious studies have revealed that ivermectin treatment for gnathostomiasis can reduce parasitic loads in animals and make recurrent subcutaneous swelling subside in 76% of patients. Our study aimed to evaluate the efficacy of ivermectin for cutaneous gnathostomiasis treatment in a placebo-controlled trial. This study was a prospective randomized placebo-controlled study performed at The Bangkok Hospital for Tropical Diseases, Mahidol University, Thailand. Thirty patients with a serologically confirmed diagnosis of cutaneous gnathostomiasis were enrolled. Seventeen patients in the ivermectin treated group received a single dose of 12 mg ivermectin (200 microg/kg bodyweight), while 13 patients in the control group received a single dose of 40 mg of vitamin B1. The follow-up period was 1 year. Of the 17 patients, 7 (41.2%) responded to ivermectin, while no patient responded to placebo. The mean (95% Cl) time to the first recurrence of subcutaneous swelling with ivermectin and in the placebo groups were 257 (184-331) and 146 (42-250) days, respectively, (p=0.102). Although this study revealed no significant difference in the mean time to first recurrence of swelling between the ivermectin and placebo groups, there was a trend towards ivermectin efficacy against gnathostomiasis in previous animal and human studies. Further studies with different doses of ivermectin and larger sample sizes, and close monitoring for ivermectin tolerability and treatment response are necessary to confirm an efficacy of ivermectin.Item The epidemiology of patients with severe malaria who died at the Hospital for Tropical Diseases, 1991-2004.(2005-03-27) Vannaphan, Suparp; Saengnetswang, Tosaporn; Suwanakut, Plengsakoon; Kllangbuakong, Auraiwon; Klinnak, Warin; Rungmatcha, Piyathida; Yeamput, Chaweewan; Tanachartwet, Wipa; Krudsood, Srivicha; Looareesuwan, SornchaiThis study is a retrospective case series of the causes of death among patients with severe malaria. Data from the medical records of patients who were admitted to the Intensive Care Unit (ICU) of the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand between 1991 and 2004 were analyzed. The overall hospital mortality rate was 0.2% and the ICU mortality rate was 1.8% for patients with malaria. Thirty-five patients died of malaria in the ICU during the study period, while a total of 1,866 patients were treated for malaria in the ICU during the study period. The most common complication of malaria was cerebral malaria (77.1%). The socioeconomic and demographic characteristics of those who died are examined here, as well as the cost of their treatment.Item Evaluation of the KAT-Quick Malaria Rapid Test for rapid diagnosis of falciparum malaria in Thailand.(2004-03-27) Buchachart, Kasinee; Krudsood, Srivicha; Nacher, Mathieu; Chindanond, Duangrudee; Rungmatcha, Piyathida; Kano, Shigeyuki; Looareesuwan, SornchaiIn recent years, several rapid diagnostic tests for falciparum malaria have been developed. KAT test results were compared with microscopy on 90 consecutive patients hospitalized at the Hospital for Tropical Diseases, Bangkok, Thailand. Fifty-one patients had P. falciparum infections while 49 had malaria due to other plasmodium species. For a geometric mean +/-SD (Min;Max;range) parasitemia of 11,481 +/- 5.0 (88;713,838;713,750), the sensitivity of the KAT test was 96% (95% CI = 86-99.5), the specificity was 92% (95% CI = 80-99), the accuracy was 94% and the reliability was 85%. These findings suggest that the KAT test is of potential interest in the diagnosis of falciparum malaria in Thailand.Item Genetic variants of beta-globin gene in Thai malaria patients.(2003-09-24) Naka, Izumi; Ohashi, Jun; Patarapotikul, Jintana; Hananantachai, Hathairad; Looareesuwan, Sornchai; Tokunaga, KatsushiHemoglobin E (E26K variant of beta-globin gene) causing hemoglobinopathy is commonly observed in parts of Thailand, regardless of the hematologic disadvantage of the homozygotes. In order to detect further variants of the beta-globin gene, we performed variation screening for exon 1 of the beta-globin gene in 64 adult patients with P. falciparum malaria, living in northwest Thailand. We identified E26K and two novel variants, 59C>T and IVS+1G>T. IVS+1G>T lies on the splice donor site, and a substitution of A for G at the same site (IVS+1G>A) is known to be linked to beta-thalassemia. Thus, the biological significance of IVS+1G>T and its association with malarial infection should be clarified in future studies.Item Hematopoietic features and apoptosis in the bone marrow of severe Plasmodium falciparum-infected patients: preliminary study.(2005-05-30) Anantrakulsil, Suwaporn; Maneerat, Yaowapa; Wilairatana, Polrat; Krudsood, Srivicha; Arunsuriyasak, Chaiyong; Atichartakarn, Vichai; Kumsiri, Ratchanok; Pattanapanyasat, Kovit; Looareesuwan, Sornchai; Udomsangpetch, RatchaneeThe mechanism of anemia in severe falciparum malaria is still not completely understood. The purpose of this study was to determine whether apoptosis in the erythroid lineage causes anemia in falciparum malaria. Bone marrow aspirated from 8 severe falciparum malaria patients, 3 normal volunteers and 5 retrospective normal bone marrow smears were investigated. By light microscopic study, 5 of 8 hyperparasitemic patients had hypocellular bone marrows and erythroid hypoplasia, whereas the other 3 patients had normal cellularity. The mean myeloid : erythroid ratio of these 5 patients was significantly (p < or = 0.05) higher than normal. Apoptosis of bone marrow nucleated cells (BMNC) could be determined from the exposure of phosphatidylserine (PS) on the cell membrane but not DNA fragmentation (180-250 bp) or ultrastructural morphology. The percentages of apoptotic BMNC and apoptotic erythroid cells in bone marrow from each patient and controls varied from low to high, and were not associated with parasitemia. This study suggests that destruction of erythroid lineage, particularly through apoptosis regulation, cannot solely account for anemia in falciparum malaria.Item Identification of human malaria parasites and detection of mixed infection in Thai patients by nested PCR.(2004-01-24) Siribal, Saranya; Nakasiri, Souwanit; Looareesuwan, Sornchai; Chavalitshewinkoon-Petmitr, PorntipThe species-specific nested PCR previously described by Snounou and others, for detecting the four species of human malaria parasites, is evaluated in the current study testing 40 blood samples from malaria patients admitted during July-September, 2003, at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand. Parasite DNA of each blood sample was extracted and purified by QIAamp. DNA mini kit. Nested PCR was performed using genus-specific primers for the first PCR cycle and species-specific primer for the second cycle. Thin and thick smears were also made, stained with Giemsa, and examined by expert microscopists. Only one of 40 samples (2.5%) was identified as Plasmodium malariae infection by both microscopy and nested PCR. Twenty blood samples (50%) were identified as Plasmodium falciparum infections by both methods. However, 19 blood samples (47.5%) were reported as Plasmodium vivax infections by microscopic methods, whereas nested PCR could detect a mixed infection of Plasmodium vivax and Plasmodium falciparum in one sample taken from a young girl with 8 ameboid trophozoites of P. vivax per 200 white blood cells. These results demonstrated that the nested PCR assay surpasses microscopy and also offers a clear advantage in the detection of mixed infections, which is important not only for successful medical treatment, but also for the study of malaria epidemiology.Item IgG antibody profile to c-terminal region of Plasmodium vivax merozoite surface protein-1 in Thai individuals exposed to malaria.(2007-01-02) Pitabut, Nada; Panichakorn, Jarinee; Mahakunkijcharoen, Yuvadee; Hirunpetcharat, Chakrit; Looareesuwan, Sornchai; Khusmith, SrisinNaturally acquired immune response to C-terminal region of Plasmodium vivax merozoite surface protein1 (PvMSP1) in 200 individuals with recent clinical episodes of malaria from malaria endemic areas along Thai-Myanmar border in the west and Thai-Cambodia border in the east of Thailand was evaluated by enzyme-linked immunosorbent assay (ELISA). The anti-PvMSP1-IgG antibody was observed in 110 individuals (55%). Among IgG responders, IgG1 coexpressed with IgG3 were the predominant subclasses. The levels of anti-PvMSP1 total IgG, IgG1 and IgG3 antibody response seem to be increased with age although no detectable significant correlation was found (r = 0.004, p = 0.484 for total IgG; r = 0.035, p = 0.386 for IgG1; r = -0.600, p = 0.142 for IgG2; r = 0.077, p = 0.227 for IgG3; r = 0.664, p = 0.051 for IgG4). However, the mean level of specific total IgG was highest in the age group of >40 years. These levels of either specific total IgG or each IgG isotype did not vary among individuals with different malaria episodes. A higher level of specific total IgG, IgG1 and IgG3 antibody response related with the lower of parasitemia density was observed although no significant correlation was found. Our data indicate that individuals exposed to vivax malaria in Thailand developed antibodies to the potential candidate vaccine antigen, PvMSP1 (C-terminal).Item In vitro susceptibility and genetic variations for chloroquine and mefloquine in Plasmodium falciparum isolates from Thai-Myanmar border.(2005-11-28) Hatabu, Toshimitsu; Kawazu, Shin-ichiro; Kojima, Somei; Sato, Kumiko; Singhasivanon, Pratap; Looareesuwan, Sornchai; Kano, ShigeyukiIn vitro drug susceptibility to chloroquine (CQ) and mefloquine (MF) were assessed in 39 P. falciparum isolates from the Thai-Myanmar border area. To further characterize CQ- and MF-resistance profiles in this area, we also analyzed pfcrt K76T mutation that is critical for CQ resistance, and pfmdr1 polymorphism that has an association with MF resistance. Eighteen isolates were successfully examined by in vitro tests for CQ, and 17 of them had resistance to the drug. Geometric mean concentration of CQ that inhibited the growth of parasites at 50% (IC50) was 371 +/- 227 nM (105-971 nM). Sixteen isolates were successfully examined by in vitro tests for MF, and 8 of them were resistant to the drug. Geometric mean of IC50 for MF was 41 +/- 31 nM (4-125 nM). Genotypes of drug resistance, such as pfcrt and pfmdr1 mutations, were also analyzed. All the 39 isolates had the same haplotype (CVIET) for PfCRT at its 72-76th amino acids. A pfmdr1 Y86 mutation was found in 95% of isolates. A pfmdr1 D1042 mutation was also present in 7 isolates, while no pfmdr1 Y1246 mutation was observed. These results indicated a correlation between CQ resistance and the pfcrt T76 and pfmdr1 Y86 mutations.Item Lack of association between interleukin-10 gene promoter polymorphism, -1082G/A, and severe malaria in Thailand.(2002-03-16) Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Looareesuwan, Sornchai; Tokunaga, KatsushiInterleukin-10 (IL-10) is an important cytokine in the down-regulation of inflammatory responses, and it has been reported that a low plasma concentration of IL-10 is associated with severe anemia and cerebral malaria in Plasmodium falciparum infections. The IL-10 gene is located on chromosome 1q31-32, and a promoter polymorphism (-1082G/A) is known to affect IL-10 protein production. In order to examine the possible association of the -1082G/A polymorphism with the severity of malaria, we studied 203 mild malaria, 164 non-cerebral severe malaria, and 109 cerebral malaria patients living in northwest Thailand. The genotyping was performed by a fluorescence resonance energy transfer (FRET) method. The frequencies of a major allele -1082A in mild malaria, in non-cerebral severe malaria, and in cerebral malaria patients were 92.6%, 92.1%, and 92.7% respectively. Our results showed no significant association of the -1082G/A polymorphism with the severity of malaria.Item Medical treatment of malaria in Thailand.(2005-10) Wilairatana, Polrat; Krudsood, Srivicha; Pothipak, Nanthaporn; Srivilairit, Siripan; Vijaykadga, Saowanit; Rojanawatsirivej, Chaiporn; Looareesuwan, SornchaiItem Mekong malaria. II. Update of malaria, multi-drug resistance and economic development in the Mekong region of Southeast Asia.(2003-03-24) Socheat, Doung; Denis, Mey Bouth; Fandeur, Thierry; Zhang, Zaixing; Yang, Henglin; Xu, Jianwei; Zhou, Xingwu; Phompida, Samlane; Phetsouvanh, Rattanaxay; Lwin, Saw; Lin, Khin; Win, Than; Than, Soe Win; Htut, Ye; Prajakwong, Somsak; Rojanawatsirivet, Chaiporn; Tipmontree, Rungrawee; Vijaykadga, Saowanit; Konchom, Supawadee; Cong, Le Dinh; Thien, Nong Thi; Thuan, Le Khanh; Ringwald, Pascal; Schapira, Allan; Christophel, Eva; Palmer, Kevin; Arbani, P R; Prasittisuk, Chusak; Rastogi, R; Monti, Feliciano; Urbani, Carlo; Tsuyuoka, Reiko; Hoyer, Stefan; Otega, Leonard; Thimasarn, Krongthong; Songcharoen, Sakda; Meert, Jean-Pierre; Gay, Frederick; Crissman, Lawrence; Cho-Min-Naing,; Chansuda, Wongsrichanalai; Darasri, Dowreang; Indaratna, Kaemthong; Singhasivanon, Pratap; Chuprapawan, Sirichai; Looareesuwan, Sornchai; Supavej, Suvanee; Kidson, Chev; Baimai, Visut; Yimsamran, Surapon; Buchachart, KasineeIn an expansion of the first Mekong Malaria monograph published in 1999, this second monograph updates the malaria database in the countries comprising the Mekong region of Southeast Asia. The update adds another 3 years' information to cover cumulative data from the 6 Mekong countries (Cambodia, China/Yunnan, Lao PDR, Myanmar, Thailand, Viet Nam) for the six-year period 1999-2001. The objective is to generate a more comprehensive regional perspective in what is a global epicenter of drug resistant falciparum malaria, in order to improve malaria control on a regional basis in the context of social and economic change. The further application of geographical information systems (GIS) to the analysis has underscored the overall asymmetry of disease patterns in the region, with increased emphasis on population mobility in disease spread. Of great importance is the continuing expansion of resistance of P. falciparum to antimalarial drugs in common use and the increasing employment of differing drug combinations as a result. The variation in drug policy among the 6 countries still represents a major obstacle to the institution of region-wide restrictions on drug misuse. An important step forward has been the establishment of 36 sentinel sites throughout the 6 countries, with the objective of standardizing the drug monitoring process; while not all sentinel sites are fully operational yet, the initial implementation has already given encouraging results in relation to disease monitoring. Some decreases in malaria mortality have been recorded. The disease patterns delineated by GIS are particularly instructive when focused on inter-country distribution, which is where more local collaborative effort can be made to rationalize resource utilization and policy development. Placing disease data in the context of socio-economic trends within and between countries serves to further identify the needs and the potential for placing emphasis on resource rationalization on a regional basis. Despite the difficulties, the 6-year time frame represented in this monograph gives confidence that the now well established collaboration is becoming a major factor in improving malaria control on a regional basis and hopefully redressing to a substantial degree the key problem of spread of drug resistance regionally and eventually globally.Item N-acetylcysteine in severe falciparum malaria in Thailand.(2003-03-16) Treeprasertsuk, Sombat; Krudsood, Srivicha; Tosukhowong, Thanawat; Maek-A-Nantawat, Wirach; Vannaphan, Suparp; Saengnetswang, Tosaporn; Looareesuwan, Sornchai; Kuhn, Walter F; Brittenham, Gary; Carroll, JamesOne hundred and eight patients with severe falciparum malaria underwent a placebo controlled trial with the antioxidant, N-acetylcysteine (NAC), as an adjunctive therapy along with standard intravenous artesunate therapy. Three NAC dosage regimens were used: an intravenous loading dose of 140 mg/kg followed by 70 mg/kg every four hours intravenously for up to 18 doses (Group 1); a single intravenous loading dose followed by oral NAC in the same amount as for Group 1 (Group 2); a regimen identical to Group 1 except that oral NAC was administered after the first 24 hours (Group 3). Fifty-four patients received placebo plus artesunate. Two critically ill patients died in Group 1. No patient sustained an adverse reaction to the NAC other than vomiting, and the deaths were attributed to severe disease with multiple organ involvement. The excellent results with NAC, the lack of adverse effects, and the rationale for NAC benefit supports the need for a large, double blind trial of NAC as an adjunctive therapy for severe malaria.Item Polymorphisms of CD36 in Thai malaria patients.(2002-03-16) Omi, Kazuya; Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Looareesuwan, Sornchai; Tokunaga, KatsushiThe human protein CD36 is a major endothelial receptor for Plasmodium falciparum parasitized erythrocytes. Several polymorphisms causing CD36 deficiency have been identified to date: T1264G in Kenyan and Gambian patients, and C478T, 539delAC, and 1159insA in Japanese patients. The T1264G polymorphism is reportedly associated with protection from severe malaria in Kenyans, although there is a contradictory report suggesting the susceptibility of T1264G to severe malaria. The polymorphism of CD36 has not been thoroughly studied in Asian malaria patients. In this study, nucleotide sequence variations in exons 4, 5, 6, and 10 of CD36 were investigated in mild and cerebral malaria patients living in northwest Thailand. A novel synonymous substitution T1168C was detected in exon 10, whereas no variation was found in exons 4 and 6. The 539delAC allele in exon 5 was detected in Thai malaria patients, while T1264G, C478T, and 1159insA were not found. The 539delAC allele was observed in three cerebral malaria patients (3/107), but not in mild malaria patients (0/203). The frequency of 539delAC was significantly higher in cerebral malaria patients than in mild malaria patients (p = 0.040, Fisher's exact test). Although independent studies should be performed in order to confirm our findings, the 539delAC allele might be a high-risk variant for cerebral malaria in Thai.