The Association between Hepcidin and Iron Status in Children and Adolescents with Obesity.

INTRODUCTION: Iron deficiency (ID) is the most common nutritional deficiency found in pediatric practice. A higher prevalence of ID may be found in children with obesity. Obesity is a chronic low-grade inflammatory condition. It is postulated that inflammation increases hepcidin, a regulator of iron homeostasis. The aim of this study was to investigate the associations between iron status, hepcidin, and BMI-standard deviation score (BMI-SDS) in children with and without obesity. METHODS: A cross-sectional study of Thai children with obesity (5 to 15 years old) versus age- and sex-matched, nonobese controls was conducted. A total of 63 children with obesity and 27 controls were enrolled. Complete blood count, serum iron, ferritin, transferrin saturation, and total iron binding capacity were analyzed. Serum hepcidin-25 was assayed using a hepcidin ELISA Kit (Human Hepc25). RESULTS: There were 63 children with obesity, the median age (IQR) being 10 (9-13) years, and 27 controls. The median (IQR) BMI-SDS of the obese group was 2.3 (2.0-2.6) vs. -0.5 ((-1.3)-0.4) of the control group. ID was diagnosed in 27 children in the obese group (42.9%); 4 of the children with obesity and ID had anemia. Serum hepcidin-25 levels of the children with ID vs. without ID in the obese group were not significantly different (median (IQR) 25 (12.9-49.2) and 26.4 (12.6-43.6), respectively) but both of them were significantly higher than controls (19.7 (8.3-25.5) ng/ml, p = 0.04). BMI-SDS was positively correlated with hepcidin-25 (r = 0.28, p = 0.001). CONCLUSION: Prevalence of iron deficiency in Thai children with obesity and serum hepcidin-25 was higher than controls. Further study in a larger population, preferably with interventions such as weight loss program, is warranted to clarify this association.

Molecular characterization of G6PD mutations reveals the high frequency of G6PD Aures in the Lao Theung population.

BACKGROUND: The prevalence and genotypes of G6PD deficiency vary worldwide, with higher prevalence in malaria endemic areas. The first-time assessment of G6PD deficiency prevalence and molecular characterization of G6PD mutations in the Lao Theung population were performed in this study. METHODS: A total of 252 unrelated Lao Theung participants residing in the Lao People's Democratic Republic (PDR) were recruited. All participant samples were tested for G6PD enzyme activity and G6PD gene mutations. The amplification refractory mutation system (ARMS)-PCR for detecting G6PD Aures was developed. RESULTS: The G6PD mutations were detected in 11.51% (29/252) of the participants. Eight G6PD mutations were detected. The G6PD Aures was the most common mutation identified in this cohort, which represented 58.62% (17/29) of all mutation. The mutation pattern was homogenous, predominantly involving the G6PD Aures mutation (6.75%), followed by 1.19% G6PD Union and 0.79% each G6PD Jammu, G6PD Mahidol and G6PD Kaiping. One subject (0.4%) each carried G6PD Viangchan and G6PD Canton. Interestingly, one case of coinheritance of G6PD Aures and Quing Yan was detected in this cohort. Based on levels of G6PD enzyme activity, the prevalence of G6PD deficiency in the Lao Theung population was 9.13% (23/252). The prevalence of G6PD deficient males and females (activity < 30%) in the Lao Theung population was 6.41% (5/78) and 1.72% (3/174), respectively, and the prevalence of G6PD intermediate (activity 30-70%) was 5.95% (15/252). CONCLUSIONS: The G6PD Aures mutation is highly prevalent in the Lao Theung ethnic group. The common G6PD variants in continental Southeast Asian populations, G6PD Viangchan, Canton, Kaiping, Union and Mahidol, were not prevalent in this ethnic group. The technical simplicity of the developed ARMS-PCR will facilitate the final diagnosis of the G6PD Aures.

Evaluating the performance of automated UV enzymatic assay for screening of glucose 6-phosphate dehydrogenase deficiency.

INTRODUCTION: A precise and reliable screening assay for glucose 6-phosphate dehydrogenase (G6PD) deficiency would greatly help avoiding unwanted outcomes due to bilirubin neurotoxicity in neonatal jaundice and antimalarial-induced haemolytic anaemia in malaria patients. Currently, available assays are laborious and require sophisticated laboratory expertise. This study aimed to evaluate the performance of a recently introduced automated screening assay for G6PD deficiency by comparing with a routine spectrophotometric assay. METHODS: An automated UV-based enzymatic (Mindray, PRC) and spectrophotometric assays were performed simultaneously in parallel to determine G6PD activity in 251 blood samples from the subjects. RESULTS: The median G6PD activity value from spectrophotometric assay was significantly lower than that of from the automated assay. The mean difference was -2.0 U/g haemoglobin (-7.3 to 3.2; P < 0.0001). The mean activity values of both assays were strongly correlated with Pearson's correlation coefficient of r = 0.8. Cohen's kappa statistics between assays was 0.77 (0.70-0.83). The sensitivity, specificity, positive and negative predictive values of the automated assay were 85.7%, 99.2%, 85.7%, 99.2%, respectively. The sensitivity and positive predictive values of the automated assay for identifying intermediate G6PD activity levels were 40.0% and 25.0%, respectively. Genotyping was performed to confirm G6PD deficient and intermediate samples. The turnaround time for 40 samples was 60 minutes for the automated assay and 300 minutes for spectrophotometric assay. CONCLUSION: The automated assay for the detection of G6PD deficiency is comparable to a routine spectrophotometric assay and help reducing sample handling time. However, the assay shows limitation in identifying individuals with G6PD intermediate.

An Observational Study of the Effect of Hemoglobinopathy, Alpha Thalassemia and Hemoglobin E on P. Vivax Parasitemia.

BACKGROUND: The protective effect of α-thalassemia, a common hematological disorder in Southeast Asia, against Plasmodium falciparum malaria has been well established. However, there is much less understanding of the effect of α-thalassemia against P. vivax. Here, we aimed to investigate the proportion of α-thalassemia including the impact of α-thalassemia and HbE on the parasitemia of P. vivax in Southeast Asian malaria patients in Thailand. METHODS: A total of 210 malaria patients, admitted to the Hospital for Tropical Diseases, Thailand during 2011-2012, consisting of 159 Myanmeses, 13 Karens, 26 Thais, 3 Mons, 3 Laotians, and 6 Cambodians were recruited. Plasmodium spp. and parasite densities were determined. Group of deletion mutation (--SEA, -α3.7, -α4.2deletion) and substitution mutation (HbCS and HbE) were genotyped using multiplex gap-PCR and PCR-RFLP, respectively. RESULTS: In our malaria patients, 17/210 homozygous and 74/210 heterozygous -α3.7 deletion were found. Only 3/210 heterozygous -α4.2 and 2/210 heterozygous--SEA deletion were detected. HbE is frequently found with 6/210 homozygotes and 35/210 heterozygotes. The most common thalassemia allele frequencies in Myanmar population were -α3.7 deletion (0.282), followed by HbE (0.101), HbCS (0.013), -α4.2 deletion (0.009), and --SEA deletion (0.003). Only density of P. vivax in α-thalassemia trait patients (-α3.7/-α3.7, --SEA/αα, -α3.7/-α4.2) but not in silent α-thalassemia (-α3.7/αα, -α4.2/αα, ααCS/αα) were significantly higher compared with non-α-thalassemia patients (p=0.027). HbE did not affect P. vivax parasitemia. The density of P. falciparum significantly increased in heterozygous HbE patients (p=0.046). CONCLUSIONS: Alpha-thalassemia trait is associated with high levels of P. vivax parasitemia in malaria patients in Southeast Asia.

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests.

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as "radical cure"), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide.Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient's G6PD status is known before deciding to administer an 8-aminoquinoline-based drug.In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure.

Deferiprone (GPO-L-ONE(®) ) monotherapy reduces iron overload in transfusion-dependent thalassemias: 1-year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO-L-ONE; A001) from Thailand.

Accessibility to iron chelators including deferoxamine and deferasirox remains obscured in many developing countries. To provide an alternative, the government pharmaceutical organization of Thailand (GPO) manufactured deferiprone which has similar bioequivalent to the standard product. Seventy-three pediatric patients with severe ß thalassemias, age range 3.2-19 years, were recruited to a 1-year multicenter prospective, single arm, open label, dose escalating Phase III study of deferiprone to determine its clinical efficacy and safety. Sixty-four patients (87.6%) completed the study with good compliance (>94%). Average deferiprone dose was 79.1±4.3 mg/kg/day. Overall, mean serum ferritin (SF) levels at 1 year were not significantly changed from baseline. However, 45% of patients (response group) had SF reduced >15% from baseline at 1 year with a median reduction of 1,065 ng ml(-1) . Baseline SF was the major factor that predicts clinical efficacy; patients with baseline SF>3,500 ng ml(-1) had the most significant fall of SF at 1 year. A subgroup analysis by MRI-T2* confirmed that the response group had higher baseline liver iron and deferiprone could significantly reduce liver iron overload and normalize levels of ALT at 1 year. Although, gastrointestinal irritation (20.5%) was the most common drug-related adverse events (AEs) followed by transaminitis (16.4%) and neutropenia (6.8%), all patients were well tolerated. There was no mortality and agranulocytosis found in this trial. Monotherapy of deferiprone with appropriate dose adjustment and monitoring for adverse events appeared to be an effective chelation therapy in some patients with good compliance and acceptable safety profiles.

Obstructive sleep apnea among children with severe beta-thalassemia.

The aim of this study was to determine the prevalence and associated factors for obstructive sleep apnea (OSA) among children with severe beta-thalassemia. Children with severe beta-thalassemia without a history of bone marrow transplantation were studied. Polysomnography (PSG) was performed in those who habitually snored to identify OSA. One hundred twenty children (aged 9.3 +/- 3.7 years; 42% male) were studied. Nineteen patients (15.8%) habitually snored. Sixteen had PSG performed. OSA was demonstrated in 10 patients. Six had moderate-to-severe OSA. The estimated prevalence of OSA was 8.3%. All OSA patients had adenoid hypertrophy and 80% had associated tonsil enlargement. The OSA group had a higher serum ferritin level compared to the non-OSA group (3,785 +/- 1,780 vs 1,885 +/- 677 ng/ml; p = 0.03). Six of 10 patients who had OSA underwent adenotonsillectomy. Reactive lymphoid hyperplasia was demonstrated in all cases. The estimated prevalence of OSA in children with severe beta-thalassemia was high (8.3%) and some had severe OSA. Adenotonsillar lymphoid hyperplasia was common among those who had OSA. A high serum ferritin level was associated with the occurrence of OSA. A history of snoring and OSA symptoms should be periodically assessed in children with severe beta-thalassemia.

Gas exchange abnormality during sleep in non-snoring severe thalassemia children.

OBJECTIVE: To study the prevalence and associated factors of gas exchange abnormality during sleep in non-snoring severe thalassemia children. MATERIAL AND METHOD: Non-snoring severe thalassemia children aged 6 to 15 years who had been followed up at King Chulalongkorn Memorial Hospital between June 2009 and March 2010 were studied. Overnight pulse oximetry and end-tidal carbon dioxide tension (P(ET)CO2) monitoring as well as pulmonary function tests were evaluated. RESULTS: Fifty-eight non-snoring severe thalassemia children (aged 10.5 +/- 2.6 years, 43% male) were studied. 67.2% showed abnormal gas exchange during sleep. All of them had nocturnal desaturation (nadir SpO2 87 +/- 6.9%; range 65 to 94%). 33.3% of those who had nocturnal desaturation had associated lung function abnormality. Abnormal lung function was found in 32.8% of the present study patients. Of these, 68.4% had associated nocturnal desaturation. Age, gender nutritional status, size of liver and spleen, history of splenectomy, hemoglobin and serum ferritin level, and lung function were not associated with abnormal gas exchange during sleep. CONCLUSION: Nocturnal desaturation was demonstrated in more than a half of non-snoring severe thalassemia children. Normal lung function did not guarantee normal gas exchange during sleep. However, more than a half of those who had lung function abnormality had associated nocturnal desaturation. Evaluation of gas exchange during sleep would be merited in this group of patients.

Natural course of low risk neuroblastoma.

BACKGROUND: Neuroblastoma is characterized by heterogeneity of histology, biology, and clinical behavior. Most epidemiology studies are based on Western and Japanese populations; there are very few studies on neuroblastoma from Southeast Asia. PROCEDURE: Cases of Thai children with neuroblastoma were retrospectively reviewed to determine if the epidemiology of the disease differs from Western populations. Sixty-two cases were assembled from two pathology centers in Bangkok. Histologic prognostic category and MYCN copy number were determined. RESULTS: The median age at diagnosis was 2.9 years. Only 11% of cases presented at less than 1 year of age and 12% cases had low stage disease (1, 2, and 4S). The majority of tumors had unfavorable histology (48/62); this was at least partly due to the higher age at diagnosis for most patients. MYCN amplification was detected in 18/52 (35%) tumors, all in stage 3 or 4 tumors. We assigned patients to high, intermediate and low risk categories using the Children's Oncology Group risk stratification criteria. In contrast to Western studies, the majority of cases (50/59 or 85%) in our series had high risk disease. CONCLUSIONS: Since there is no evidence to date that the biology of neuroblastoma varies by geographic region, the paucity of low risk cases in our study may reflect spontaneous resolution/differentiation of tumors that are not clinically detected. Moreover, a delay in diagnosis of intermediate risk cases could result in higher tumor burden at the time of diagnosis, increasing the proportion of high risk cases observed.

Phylogenetic analysis of serine proteases from Russell's viper (Daboia russelli siamensis) and Agkistrodon piscivorus leucostoma venom.

Serine proteases are widely found in snake venoms. They have variety of functions including contributions to hemostasis. In this study, five serine proteases were cloned and characterized from two different cDNA libraries: factor V activator (RVV-V), alpha fibrinogenase (RVAF) and beta fibrinogenase (RVBF) from Russell's viper (Daboia russelli siamensis), and plasminogen activator (APL-PA) and protein C activator (APL-C) from Agkistrodon piscivorus leucostoma. The snake venom serine proteases were clustered in phylogenetic tree according to their functions. K(A)/K(S) values suggested that accelerated evolution has occurred in the mature protein coding regions in cDNAs of snake venom serine proteases.

Effect of purified Russell's viper venom-factor X activator (RVV-X) on renal hemodynamics, renal functions, and coagulopathy in rats.

Acute renal failure (ARF) is the most frequent and a serious complication in victims of Russell's viper snakebites. Russell's viper venom-factor X activator (RVV-X) has been identified as a main procoagulant enzyme involving coagulopathy, which might be responsible for changes in renal hemodynamics and renal functions. Here, we purified RVV-X from crude Russell's viper venom to study renal hemodynamics, renal functions, intravascular clot, and histopathological changes in Sprague-Dawley rats. Changes in renal hemodynamics and renal functions were evaluated by measuring the mean arterial pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), effective renal blood flow (ERBF), renal vascular resistance (RVR), and fractional excretion of electrolytes. After 10 min, rats receiving both crude venom and purified RVV-X decreased GFR, ERPF, and ERBF and increased RVR. These changes correlated to renal lesions. Along with the determination of intravascular clot, rats injected with purified RVV-X increased the average D-dimer level and reached a peak at 10 min, declined temporarily, and then reached another peak at 30 min. The temporal association between clots and renal dysfunction was observed in rats within 10 min after the injection of purified RVV-X. These findings suggested RVV-X as a major cause of renal failure through intravascular clotting in the renal microcirculation.

Outcome of medulloblastoma in children treated with reduced-dose radiation therapy plus adjuvant chemotherapy.

Medulloblastoma is the most common malignant brain tumor in children. Post-surgical craniospinal irradiation (CSI; 30-36 Gy) plus local boost radiation therapy (RT; 54-56 Gy) is a standard treatment for children with medulloblastoma who are over 3 years old, resulting in a 5-year overall survival (OS) rate of 46% to 65% in average-risk patients and 50% in high-risk patients. The addition of chemotherapy has the benefit of reducing complications from radiation and improving the OS rate. Using this approach, the estimated 5-year OS rates for patients with average- and high-risk medulloblastomas treated with different protocols are 65% to 85% and 16% to 70%, respectively. In this study, we determined the outcome of patients with average- and high-risk medulloblastomas treated with reduced dosage CSI and chemotherapy with an oral etoposide-based regimen. The study included 49 patients, with a mean age of 7.7 ± 3.4 years. Twenty-six patients (53%) were classified as average-risk and 23 patients (47%) as high-risk. In the average-risk group, the 5-year progression free survival (PFS) rate was 62.9% ± 10% and the 5-year OS rate was 70.4% ± 9.5%. In the high-risk group the 5-year PFS rate was 48.9% ± 13% and the 5-year OS rate was 49.7% ± 13%. In the average-risk group, patients who received CSI of either 24 Gy (n=20) or 36 Gy (n=9) showed no difference in their 5-year PFS and OS rates. We found that patients who were ≤ 10 years old and patients who were female had a significantly better 5-year PFS rate.

Childhood cancer incidence and survival 2003-2005, Thailand: study from the Thai Pediatric Oncology Group.

BACKGROUND: Previous population-based incidences of childhood cancer in Thailand were achieved by extrapolating from data limited to a small number of cancer registries, not from the whole country. In addition, survival of childhood cancer patients is often described in specialized hospitals and/or institutions, but not in the general population. METHODS: All children aged 0-15 years who were newly diagnosed as having cancer were registered from 18 treatment centers during 2003-5 and classified into 12 diagnostic groups according to the International Classification of Childhood Cancer. Incidences were calculated by a standard method and survival was investigated using the ThaiPOG (Thai Pediatric Oncology Group) population-based registration data. Overall survival was calculated by the Kaplan Meier method. RESULTS: In the study period (2003-5) 2,792 newly diagnosed cases of childhood cancer were registered, with mean and median ages of 6.5 (SD=0.13) and 5.0 (0-14) years, respectively. The age-peak was between 1 and 4 years and the age-standardized rate (ASR) was 74.9 per million. Leukemia was the most common cancer (N=1421, ASR 38.1) followed by lymphoma (N=266, ASR 6.4) and neoplasms of the central nervous system (CNS, N=246, ASR 6.3). The follow-up duration totaled 101,250 months. The death rate was 1.11 per 100 person-months (95%CI: 1.02 -1.20). The 5-year overall survival was 54.9% (95%CI: 53.0%-56.9%) for all cancers. The respective, 5-year overall survival for (1) acute lymphoblastic leukemia (ALL), (2) acute non-lymphoblastic leukemia (ANLL), (3) lymphoma, (4) retinoblastoma, (5) renal tumors, (6) liver tumors, (7) germ cell tumors, (8) CNS tumors, (9) neuroblastoma, (10) soft tissue tumors and (11) bone tumors were (1) 64.5%, (2) 35.1%, (3) 59.5%, (4) 73.1%, (5) 70.4%, (6) 44.5%, (7) 70.6%, (8) 41.7%, (9) 33.6%, (10) 50.1%, and (11) 33.7%. CONCLUSIONS: The incidence of childhood cancer is lower than in western countries. Respective overall survival for ALL, lymphoma, renal tumors, liver tumors, retinoblastoma, soft tissue tumors is lower than those reported in developed countries while for CNS tumors, neuroblastoma and germ cell tumors the figures are comparable.

Comparative study of anticoagulant and procoagulant properties of 28 snake venoms from families Elapidae, Viperidae, and purified Russell's viper venom-factor X activator (RVV-X).

Snake venoms consist of numerous molecules with diverse biological functions used for capturing prey. Each component of venom has a specific target, and alters the biological function of its target. Once these molecules are identified, characterized, and cloned; they could have medical applications. The activated clotting time (ACT) and clot rate were used for screening procoagulant and anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri from Wrightwood, CA, had procoagulant activity. These venoms induced a significant shortening of the ACT and showed a significant increase in the clot rate when compared to the negative control. Factor X activator activity was also measured in 28 venoms, and D. r. siamensis venom was 5-6 times higher than those of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom, and then procoagulant activity was evaluated by the ACT and clot rate. Other venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A significant increase in the ACT and a significant decrease in the clot rate were observed after the addition of these venoms; therefore, the venoms were considered to have anticoagulant activity. Venoms from the same species did not always have the same ACT and clot rate profiles, but the profiles were an excellent way to identify procoagulant and anticoagulant activities in snake venoms.

Heritability of the human infectious reservoir of malaria parasites.

BACKGROUND: Studies on human genetic factors associated with malaria have hitherto concentrated on their role in susceptibility to and protection from disease. In contrast, virtually no attention has been paid to the role of human genetics in eliciting the production of parasite transmission stages, the gametocytes, and thus enhancing the spread of disease. METHODS AND FINDINGS: We analysed four longitudinal family-based cohort studies from Senegal and Thailand followed for 2-8 years and evaluated the relative impact of the human genetic and non-genetic factors on gametocyte production in infections of Plasmodium falciparum or P. vivax. Prevalence and density of gametocyte carriage were evaluated in asymptomatic and symptomatic infections by examination of Giemsa-stained blood smears and/or RT-PCR (for falciparum in one site). A significant human genetic contribution was found to be associated with gametocyte prevalence in asymptomatic P. falciparum infections. By contrast, there was no heritability associated with the production of gametocytes for P. falciparum or P. vivax symptomatic infections. Sickle cell mutation, HbS, was associated with increased gametocyte prevalence but its contribution was small. CONCLUSIONS: The existence of a significant human genetic contribution to gametocyte prevalence in asymptomatic infections suggests that candidate gene and genome wide association approaches may be usefully applied to explore the underlying human genetics. Prospective epidemiological studies will provide an opportunity to generate novel and perhaps more epidemiologically pertinent gametocyte data with which similar analyses can be performed and the role of human genetics in parasite transmission ascertained.

Factors affecting health-related quality of life in Thai children with thalassemia.

BACKGROUND: Knowledge of the factors associated with health-related quality of life (HRQOL) among patients with thalassemia is essential in developing more suitable clinical, counseling, and social support programs to improve treatment outcomes of these patients. In light of the limited research in this area, this study aims to examine factors associated with HRQOL among children and adolescents with thalassemia in Thailand. METHODS: A cross-sectional survey was conducted in three selected hospitals in Thailand during June to November 2006. PedsQL 4.0 Generic Core Scale (Thai version) was used to assess HRQOL in 315 thalassemia patients between 5 and 18 years of age. Other related clinical characteristics of the patients were collected via medical record review. RESULTS: The mean (SD) of the total summary score was 76.67 (11.40), while the means (SD) for the Physical Health Summary score and Psychosocial Health Summary score were 78.24 (14.77) and 75.54 (12.76), respectively. The school functioning subscale scored the lowest, with a mean of 67.89 (SD = 15.92). The following factors significantly affected the HRQOL of the patients: age; age at onset of anemia and age at first transfusion; pre-transfusion hemoglobin (Hb) level; receiving a blood transfusion during the previous three months; and disease severity. In addition, iron chelation therapy had a significant negative effect on HRQOL in the school functioning subscale. In contrast, serum ferritin level, frequency of blood transfusions per year, and gender were not significantly related to HRQOL among these patients. The results from multivariate analysis also confirmed these findings. CONCLUSIONS: To improve HRQOL of thalassemia patients, suitable programs aimed at providing psychosocial support and a link between the patient, school officials, the family and the physician are important, especially in terms of improving the school functioning score. The findings also confirmed the importance of maintaining a pre-transfusion Hb level of at least 9-10.5 g/dL. In addition, special care and attention should be given to patients with a severe condition, and those who are receiving subcutaneous iron chelation therapy.

Economic burden of beta-thalassemia/Hb E and beta-thalassemia major in Thai children.

BACKGROUND: Hemoglobin E beta-thalassemia (beta-thalassemia/Hb E) has a variable severity, and the cost of treatment has not been well studied. The aim of this study was to analyze the societal cost of caring for children with beta-thalassemias in Thailand. The study was designed as a prevalence-based cost-of-illness analysis in a societal perspective. Medical records from three public hospitals of children aged 2-18 years with beta-thalassemia/Hb E and homozygous beta-thalassemia were reviewed for direct medical cost determination. For direct non-medical cost and indirect cost, a family member was interviewed. FINDINGS: It was found that 201 patients with beta-thalassemia/Hb E (91%) and homozygous beta-thalassemia (9%) were recruited for this study. Ninety-two (46%) were severe thalassemia and 109 (54%) were mild to moderate severity. The annual average cost of treatment was US$950; 59% was direct medical cost, 17% direct non-medical cost, and 24% indirect cost. The costs were differentiated by some potential predictors. Significant predictor variables were: hospital, health insurance scheme, blood transfusion pattern, and iron chelation drug use. CONCLUSIONS: The average annual cost per patient was calculated, and the cost model was estimated. These would be applied for national planning, economic evaluation of treatment and prevention interventions, and budget impact analysis.

Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency--the most common known enzymopathy--is associated with neonatal jaundice and hemolytic anemia usually after exposure to certain infections, foods, or medications. Although G6PD-deficient alleles appear to confer a protective effect against malaria, the link with clinical protection from Plasmodium infection remains unclear. We investigated the effect of a common G6PD deficiency variant in Southeast Asia--the G6PD-Mahidol(487A) variant--on human survival related to vivax and falciparum malaria. Our results show that strong and recent positive selection has targeted the Mahidol variant over the past 1500 years. We found that the G6PD-Mahidol(487A) variant reduces vivax, but not falciparum, parasite density in humans, which indicates that Plasmodium vivax has been a driving force behind the strong selective advantage conferred by this mutation.

Phospholipase A2 genes and their expressions in Thai Russell's viper venom glands.

Phospholipase A2 (PLA2) is a multi-functional enzyme found in many snake venoms and exists in several isoforms. PLA2 causes a variety of pathological effects including anticoagulant, edema, and platelet aggregation inhibition. Here, we reported the cDNA and gene sequences of PLA2 and their expressions in Thai Russell's viper (RV) Daboia russellii siamensis venom glands. We identified 3 PLA2 genes in the RV genome, 2 of which are actively transcribed in the venom gland. The deduced amino acids of these 2 PLA2 isoforms share 80% identity and are the same as PLA2s from Taiwan Russell's viper, Daboia russellii formosensis. A third PLA2 gene has no corresponding mRNA transcript from the venom gland suggesting a very low level of expression in the venom glands.

Folate pathway genetic polymorphisms and susceptibility of central nervous system tumors in Thai children.

BACKGROUND: Folate is an important micronutrient molecule participating in DNA synthesis, methylation and repair mechanisms. Genetic polymorphisms in folate pathway related enzymes including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, thymidylate synthase (TS) 28-bp tandem repeat, and reduced folate carrier (RFC) G80A have been shown to be associated with increased susceptibility for several cancers. The aim of the present study was to evaluate whether single nucleotide polymorphisms in the genes encoding enzymes of the folate pathway predispose to any CNS tumors in Thai children. METHODS: In the present case-control study, we investigated these polymorphisms in genomic DNA from peripheral blood mononuclear cells in 73 Thai children with various types of central nervous system tumors and in 205 age and sex matched controls. RESULTS: Thirty-one out of 73 patients were diagnosed with glial tumors (astrocytoma, oigodendroglioma and ependymoma), 28 with embryonal CNS tumors (medulloblastoma, pinealoblastoma and primitive neuroectodermal tumor), 13 with germ cell tumors and 1 with meningioma. We found that the homozygous CC allele of MTHFR A1298C conferred an increased risk of embryonal CNS tumors (OR: 3.9; 95% CI: 1.3-11.4, p=0.02). CONCLUSION: Our findings thus suggest that folate metabolism may play a role in the pathogenesis of certain specific subtypes of pediatric brain tumor in Thai children, especially embryonal CNS tumors.