Risk of chikungunya virus transmission associated with European travelers returning from southern Thailand (2008-2015).

BACKGROUND: The impact of the spread of chikungunya virus (CHIKV) by autochthonous transmission and blood transfusion in nonendemic areas via travelers returning from CHIKV-affected locations is a concern. METHODS: We analyzed the risks of potential CHIKV importation and transfusion transmission from Thailand to Europe via travelers visiting southern Thailand from 2008 through 2015, using the web-based European Up-front Risk Assessment Tool. RESULTS: The risk of CHIKV importation by European travelers returning from Thailand from 2008 through 2015 varied depending on the year of travel, tourist destination, duration of stay, and time since last possible exposure. Specifically, the risks of acquiring CHIKV among travelers visiting Songkhla and Krabi for 1, 5, or 10-30 days during the highest epidemic activity in 2009 were estimated to be 74.40, 371.99, and 706.77 (Songkhla) and 1.82, 9.08, and 17.25 (Krabi) per 100,000 travelers, respectively. In contrast, such risks were estimated to be fewer than 0.099 per 100,000 travelers in nonepidemic years. The 2009 yearly average rates of expected incidence among 4,059,988 European travelers who stayed for 1 or 10-30 days in all six outbreak activity destinations were calculated to be, respectively, 4.01 × 10-6 or 1.20 × 10-4 cases per day, corresponding to the estimated rates of viremia and transfusion-transmitted CHIKV via traveling blood donations of 3.21 × 10-5 and 0.61, and 9.62 × 10-4 and 3.34, respectively. Additionally, it is probable that 18 (0.0004%) Europeans acquired CHIKV in Thailand, representing a maximum attack rate of 0.0023%. CONCLUSION: The extent of the expected risks and attack rates of CHIKV infection might reflect the travel preferences for popular destinations rather than the true risks of CHIKV transmission in travelers' home nonendemic countries. Nevertheless, preventive and blood-safety intervention measures may be applied to returning travelers at risk for infection to reduce CHIKV transfusion threats in their home countries.

Risk of transfusion-transmitted chikungunya infection and efficacy of blood safety implementation measures: experience from the 2009 epidemic in Songkhla Province, Thailand.

BACKGROUND: To date, neither is there a standard guideline for maintaining a safe blood supply during a chikungunya fever (CHIKF) outbreak nor has a study been performed on actual transfusion-transmitted CHIKF to recipients. This study estimated the potential incidence of transfusion-transmitted CHIKF and compared the efficacies of various blood safety intervention strategies to mitigate the transfusion-transmitted CHIKF risk. STUDY DESIGN AND METHODS: A Web-based tool named the European Up-Front Risk Assessment Tool (EUFRAT) was used to estimate the risk of transfusion-transmitted CHIKF using data inputs from the 2009 Songkhla epidemic in Thailand. RESULTS: The mean and maximal risks of viremic donations during the entire epidemic period were estimated to be 0.9 (95% confidence interval [CI], 0.0-2.7) and 4.8 (95% CI, 0.5-9.1), respectively. This meant that the potential risk of transfusion-transmitted CHIKF to recipients receiving all infective end products in the absence of blood safety measures was from 10.9 (95% CI, 1.8-20.4) to 57.6 (95% CI, 36.4-79.5). Based on experience from the 2009 Thai epidemic, the proportion of 10% asymptomatic cases, for instance, with predonation screening for CHIKF-related symptoms and follow-up observation in donors at risk was estimated to be 88.4% (95% CI, 69.9%-100.0%) to 99.1% (95% CI, 79.6%-100.0%) effective in reducing this transfusion risk compared to 83.7% (95% CI, 65.8%-100.0%) to 90.7% (95% CI, 72.1%-100.0%) by predonation screening for donors at risk of chikungunya virus infection alone. CONCLUSION: This study suggests that prompt blood screening measures can reduce the risk of transfusion-transmitted CHIKF and maintain a safe blood supply during an outbreak.

Full-length nucleotide sequence of ERMAP alleles encoding Scianna (SC) antigens.

BACKGROUND: Scianna (SC) blood group system comprises two antithetical antigens, Sc1 and Sc2, and five additional antigens. The antigens reside on a glycoprotein encoded by the erythroblast membrane-associated protein (ERMAP) gene. For the common ERMAP alleles, we determined the full-length nucleotide sequence that encodes the Scianna glycoprotein. STUDY DESIGN AND METHODS: Blood donor samples from five populations were analyzed including 20 African Americans, 10 Caucasians, 10 Thai, five Asians, and five Hispanics for a total of 100 chromosomes. An assay was devised to determine the genomic sequence of the ERMAP gene in one amplicon, spanning 21.4 kb and covering Exons 2 to 12 and the intervening sequence (IVS). All alleles (confirmed haplotypes) were resolved without ambiguity. RESULTS: Among 50 blood donors, we found 80 single-nucleotide polymorphisms (SNPs), including six novel SNPs, in 21,308 nucleotides covering the coding sequence of the ERMAP gene and including the introns. The noncoding sequences harbored 75 SNPs (68 in the introns and seven in the 3'-UTR). No SNP indicative of a nonfunctional allele was detected. The nucleotide sequences for 48 ERMAP alleles (confirmed haplotypes) were determined by allele-specific polymerase chain reaction and sequencing in 100 chromosomes. CONCLUSIONS: We documented 48 ERMAP alleles of 21,308 nucleotides each. The two nucleotide sequences available in GenBank for ERMAP alleles of similar length have not been found in our 100 chromosomes. Alleles determined without ambiguity can be used as templates to analyze next generation sequencing data, which will enhance the reliability in clinical diagnostics.

The risk of blood transfusion-associated Chikungunya fever during the 2009 epidemic in Songkhla Province, Thailand.

BACKGROUND: Asymptomatic Chikungunya fever (CHIKF)-viremic blood donors could be a potential threat of spreading the disease unwittingly through contaminated blood transfusions. The relatively low prevalence of Chikungunya virus antibodies in the population and the records of more than 9000 suspected CHIKF cases raised concern about the potential transfusion-associated CHIKF during the 2009 epidemic. This study assessed the potential transfusion risk for CHIKF and the implementation of blood safety measures to mitigate this risk. STUDY DESIGN AND METHODS: A probabilistic model using key variables obtained from local information was used to estimate the weekly risk of transfusion-associated CHIKF during the 2009 epidemic. In addition, other blood safety measure-based strategies involving screening for donors at risk, donor tracing, and a 7-day quarantine of blood components at risk were implemented at the time of the epidemic. RESULTS: The risk of viremic donations per 100,000 ranged from 38.2 (95% confidence interval [CI], 36.5-39.8) to 52.3 (95% CI, 50.4-54.2). The potential risk of transfusion-associated CHIKF per 100,000 was estimated to be 1 in 2429 (0.04%; 95% CI, 1 in 6681 [0.02%]-1 in 1572 [0.06%]) to 1 in 1781 (0.06%; 95% CI, 1 in 3817 [0.03%]-1 in 1214 (0.08%]) donations. Among 26,722 donations, 11 (95% CI, 4-17) to 15 (95% CI, 7-22) donations were predicted to associate with transfusion risk. The implementation of blood safety measure-based strategies for this epidemic period suggested to deter 11 blood donations of transfusion risk. CONCLUSION: The interventions for blood safety measures applied in this study had mitigated the potential transfusion-associated CHIKF during the 2009 epidemic.

Prognostic significance of serum proangiogenic molecules in patients with de novo non-Hodgkin lymphomas.

This study was aimed to assess the clinical significances of the serum VEGF and bFGF in Thai patients with de novo NHL. Serum VEGF and bFGF concentrations were measured from 79 adult patients with newly diagnosed stage 2-4 non-Hodgkin lymphomas by quantitative sandwich enzyme immunoassay. At the time of diagnosis, the serum VEGF concentrations from 79 patients ranged from 72.0 to 2919.4 pg/mL, with a mean of 668.0 pg/dL. The serum bFGF concentrations ranged from undetectable to 2919.4 pg/mL, with a mean of 12.15 pg/dL. Multivariate analysis identified higher than the mean of serum VEGF, B symptoms, bulky diseases, anemia, and treatment with CHOP or R-CHOP as independent variables influencing the complete remission rate. From a Cox proportional hazards model, variables independently associated with overall survival were bone marrow involvement, more extranodal involvement, poor performance status, anemia, and higher than the mean of serum bFGF.

The Potential Impact of Chikungunya Virus Outbreaks on Blood Transfusion.

Chikungunya virus (CHIKV) is responsible for large periodic epidemics in both endemic and nonendemic areas where competent mosquitoes are present. Transmission of CHIKV by transfusion during explosive outbreaks has never been documented, and the true impact of CHIKV infection on blood transfusion during an outbreak is unknown. Considerations include not only transfusions in the active outbreak areas but also returning travelers to nonendemic areas. Because there are no documented cases of transfusion-transmitted CHIKV, there are no standard guidelines regarding transfusion policies during a chikungunya fever outbreak. We review current information from studies during outbreaks with the goal of estimating the potential effect of different blood safety interventions (eg, querying donors for possible CHIKV exposure, chikungunya fever-related symptoms, screening for CHIKV RNA).

A suspected new species of Leishmania, the causative agent of visceral leishmaniasis in a Thai patient.

A suspected new species of Leishmania is described as the causative agent of the third reported case of autochthonous visceral leishmaniasis in a Thai man living in Southern Thailand. The results of PCR-restriction fragment length polymorphism and sequence analysis of the internal transcribed spacer 1 of ssrRNA and the mini-exon genes were different from those of previously reported Leishmania species. A direct agglutination test (DAT) revealed that antibody against Leishmania infection was detected in nine domestic cats. No potential vectors could be identified. A large-scale epidemiological survey of leishmaniasis should be urgently conducted since visceral leishmaniasis is considered an emerging disease of public health concern in Thailand.

Incidence and radiographic findings of primary central nervous system lymphoma in immunocompetent patients in southern Thailand.

AIMS AND BACKGROUND: In the last two decades there have been conflicting reports concerning a rising incidence of primary central nervous system lymphoma (PCNSL) in immunocompetent patients. This study is being conducted to review the incidence and radiographic findings of PCNSL in a large tertiary care institution in southern Thailand. PATIENTS: A review was carried out in Songklanagarind University Hospital of the clinical records, CT and MRI images of immunocompetent patients who had histologically proven PCNSL diagnosed between January 1993 and December 2004. RESULTS: A total of 25 PCNSL patients were diagnosed over a 12-year period. The incidence trend was rising but not to a statistically significant extent. The median age at diagnosis was 57.4 years. Based on the Working Formulation classification, diffuse large cell was the most common subtype. All of the 20 patients with available immunohistochemical results had B-cell lymphomas. The radiographic findings in our series show that the majority of patients had a single lesion (60%) at a supratentorial location (50%). Most of the lesions were well circumscribed. Based on the density of the lesions before administration of a contrast medium, 56% of the lesions on CT images appeared hyperdense. On T1-weighted MRI images, the lesions of our patients were most frequently hypointense (67%) while the T2-weighted images were more commonly hyperintense (60%) and contrast enhancement was found in all lesions. There were 21 patients who received whole brain radiotherapy with doses ranging between 4.2 and 6.0 Gy. The median survival time was 14.4 months. CONCLUSIONS: This study indicates that there has been no significant increase in PCNSL cases over the last 12 years. The recognition of characteristic imaging features of PCNSL may facilitate a stereotactic procedure before steroid administration. In addition, we provide evidence that radiotherapy alone is insufficient in PCNSL.

A unique case of transient spontaneous regression complicated with tumor lysis syndrome of T-cell lymphoblastic lymphoma in HIV-infected patient without antiretroviral therapy.

Spontaneous regression in high-grade non-Hodgkin lymphoma is rare. Herein, the authors report the case of a 26-year-old asymptomatic HIV-infected patient presenting with bleeding per gum after a dental extraction. Initially, a complete blood count showed lymphoblasts and thrombocytopenia. Laboratory investigations were compatible with acute tumor lysis syndrome. Without any steroid or chemotherapy, both clinical and laboratory abnormalities were spontaneously returned to normal limits. However, three weeks later he developed generalized lymphadenopathy. A submandibular gland biopsy revealed to be T-cell lymphoblastic lymphoma. This was followed by the second episode of spontaneous tumor lysis syndrome and spontaneous regression of lymphadenopathy again. At this time, he was treated with cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) with whole brain irradiation. During seven months of chemotherapy, the physical examination and blood chemistry were normal. Unfortunately, after seven courses of CHOP, the disease rapidly progressed and ultimately lead to his death.

Physicochemical properties and responses in microcirculation of native tapioca starch-based plasma expander.

Plasma expanders (PEs) such as hydroxyethyl strach are widely used for volume replacement. The plantation and production of tapioca in Thailand is abundant which may provide a new source for PEs starch with novel properties. This work investigated the properties and circulatory effects of native tapioca starch-based PE (TPE). Various formulations of mixture between native tapioca starch and 0.9% sodium chloride solution were prepared and characterized in order to obtain the proper physicochemical and rheological properties. About 1% concentration by weight per volume of TPE was compared with 6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride (HES130/0.4) using an acute hemodilution by 40% of blood volume in an animal protocol. TPE had higher turbidity and viscosity but lower colloid osmotic pressure compared with HES 130/0.4. The in vivo study demonstrated that Golden Syrian hamsters hemodiluted with TPE maintained a mean arterial blood pressure and no significant difference compared to HES 130/0.4. The arterial vasodilation and functional capillary density in the animals hemodiluted with TPE had higher values than in the animals hemodiluted with HES 130/0.4. Although the in vivo study reported positive results using this native tapioca starch-based PE, the product needs work to improve some of its physiochemical properties.

Association of ABO Blood Group Phenotype and Allele Frequency with Chikungunya Fever.

Background. The objective of this study was to investigate the association of the ABO blood group phenotype and allele frequency with CHIK fever. Methods. A rural community survey in Southern Thailand was conducted in August and September 2010. A total of 506 villagers were enrolled. Cases were defined as individuals having anti-CHIK IgG by hemagglutination ≥1 : 10. Results. There were 314 cases (62.1%) with CHIK seropositivity. Females were less likely to have positive anti-CHIK IgG with odds ratio (OR) (95% CI) of 0.63 (0.43, 0.93). All samples tested were Rh positive. Distribution of CHIK seropositivity versus seronegativity (P value) in A, B, AB, and O blood groups was 80 versus 46 (0.003), 80 versus 48 (0.005), 24 versus 20 (0.55), and 130 versus 78 (<0.001), respectively. However, chi-square test between ABO and CHIK infection showed no statistical significance (P = 0.76). Comparison of the ABO blood group allele frequency between CHIK seropositivity and seronegativity was not statistically significant. Conclusion. This finding demonstrated no association of the ABO blood group phenotypes and allele frequencies with CHIK infection.

Genotypic distribution of hepatitis C virus in Thailand and Southeast Asia.

The majority of hepatitis C virus (HCV) infection results in chronic infection, which can lead to liver cirrhosis and hepatocellular carcinoma. Global burden of hepatitis C virus (HCV) is estimated at 150 million individuals, or 3% of the world's population. The distribution of the seven major genotypes of HCV varies with geographical regions. Since Asia has a high incidence of HCV, we assessed the distribution of HCV genotypes in Thailand and Southeast Asia. From 588 HCV-positive samples obtained throughout Thailand, we characterized the HCV 5' untranslated region, Core, and NS5B regions by nested PCR. Nucleotide sequences obtained from both the Core and NS5B of these isolates were subjected to phylogenetic analysis, and genotypes were assigned using published reference genotypes. Results were compared to the epidemiological data of HCV genotypes identified within Southeast Asian. Among the HCV subtypes characterized in the Thai samples, subtype 3a was the most predominant (36.4%), followed by 1a (19.9%), 1b (12.6%), 3b (9.7%) and 2a (0.5%). While genotype 1 was prevalent throughout Thailand (27-36%), genotype 3 was more common in the south. Genotype 6 (20.9%) constituted subtype 6f (7.8%), 6n (7.7%), 6i (3.4%), 6j and 6m (0.7% each), 6c (0.3%), 6v and 6xa (0.2% each) and its prevalence was significantly lower in southern Thailand compared to the north and northeast (p = 0.027 and p = 0.030, respectively). Within Southeast Asia, high prevalence of genotype 6 occurred in northern countries such as Myanmar, Laos, and Vietnam, while genotype 3 was prevalent in Thailand and Malaysia. Island nations of Singapore, Indonesia and Philippines demonstrated prevalence of genotype 1. This study further provides regional HCV genotype information that may be useful in fostering sound public health policy and tracking future patterns of HCV spread.

Applying molecular immunohaematology to regularly transfused thalassaemic patients in Thailand.

BACKGROUND: Red blood cell transfusion is the principal therapy in patients with severe thalassaemias and haemoglobinopathies, which are prevalent in Thailand. Serological red blood cell typing is confounded by chronic transfusion, because of circulating donor red blood cells. We evaluated the concordance of serological phenotypes between a routine and a reference laboratory and with red cell genotyping. MATERIALS AND METHODS: Ten consecutive Thai patients with ß-thalassemia major who received regular transfusions were enrolled in Thailand. Phenotypes were tested serologically at Songklanagarind Hospital and at the National Institutes of Health. Red blood cell genotyping was performed with commercially available kits and a platform. RESULTS: In only three patients was the red cell genotyping concordant with the serological phenotypes for five antithetical antigen pairs in four blood group systems at the two institutions. At the National Institutes of Health, 32 of the 100 serological tests yielded invalid or discrepant results. The positive predictive value of serology did not reach 1 for any blood group system at either of the two institutions in this set of ten patients. DISCUSSION: Within this small study, numerous discrepancies were observed between serological phenotypes at the two institutes; red cell genotyping enabled determination of the blood group when serology failed due to transfused red blood cells. We question the utility of serological tests in regularly transfused paediatric patients and propose relying solely on red cell genotyping, which requires training for laboratory personnel and physicians. Red cell genotyping outperformed red cell serology by an order of magnitude in regularly transfused patients.

Prediction score for effective bleeding control using recombinant activated factor VII in perioperative nonhemophilic patients.

BACKGROUND: Although there has been growing evidence from off-label use of recombinant activated factor VII (rFVIIa) in surgical bleeding, there is limited information on prediction scores. METHODS: A retrospective study was conducted from 2004 to 2009. The primary outcome was efficacy of bleeding control. Multivariate logistic regression was performed to develop a new prediction score for success of rFVIIa. RESULTS: A total of 320 bleeding episodes from 243 nonhemophilic patients who underwent surgery were analyzed. Effective bleeding control was demonstrated in 153 patients. The overall in-hospital mortality rate was 40%. Multivariate analysis identified 4 independent predictors for effective bleeding control: timing of rFVIIa administration, intraoperative blood loss, postoperative international normalization ratio values, and total units of platelets transfused. A rFVIIa success prediction score was developed. CONCLUSIONS: The use of this new prediction score may support decision making by identifying patients with a high probability of obtaining effective bleeding control from rFVIIa therapy.

Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability.

The impact of health insurance with inequitable rituximab coverage on the survival of patients with diffuse large B-cell lymphoma (DLBCL) has never been reported. We conducted a nationwide multicenter analysis on the outcome of 553 adult patients consecutively diagnosed with DLBCL between July 2003 and June 2006, in whom treatment cost was reimbursed under the Civil Servant Medical Benefit Scheme (CSMBS) (n =201) or the Universal Coverage Scheme (UCS) (n =352). The international prognostic index was comparable between the two payment groups. Rituximab-based therapy was administered in 45.3% and 3.1% of CSMBS and UCS patients, respectively (p <0.001). With a median follow-up of 24.6 months, the 6-year progression-free survival (PFS) was superior for CSMBS patients (34.2 vs. 23.2%, p =0.005). "Not treated with rituximab-based therapy" was the strongest adverse prognostic feature indicating a short PFS (hazard ratio 2.1, p <0.001). It is concluded that lack of access to rituximab is the principal factor accounting for the inferior PFS observed in Thai patients with DLBCL who are treated under the UCS.

Incidence, etiology and bone marrow characteristics of non-chemotherapy-induced agranulocytosis.

OBJECTIVE: Agranulocytosis is a rare but fatal condition. The majority of cases are associated with drugs. However, in-patient incidences and the relationship between clinical outcomes and bone marrow characteristics have not been established. METHODS: We conducted a retrospective study in a university hospital. A total of 38 in-patients diagnosed with agranulocytosis were analyzed. RESULTS: The average incidence of agranulocytosis in Songklanagarind Hospital between 1993 and 2007 was 0·98 cases per 10 000 admissions per year. Antimicrobial agents were the most common etiology (63% of patients) and antithyroid agents were the second most common (13·6%). Two patterns of bone marrow were noted: type I was characterized by a left-shifted granulopoiesis and type II was recognized as having hypocellular bone marrow with markedly reduced granulocyte precursors. A significantly higher mortality was associated with type II. CONCLUSION: Antimicrobial agents are the most common cause and the rare granulocyte precursors in bone marrow are associated with higher mortality rates.

No Prognostic Impact of p53 and P-Glycoprotein Expression in Patients with Diffuse Large B-Cell Lymphoma.

The aim of this study was to determine the clinical significances of p53 and p-glycoprotein (P-gp) expression on outcome predictors for patients with DLBC. We assessed the immunohistochemical expression of p53 and P-gp using formalin-fixed, paraffin-embedded specimens in 108 patients diagnosed with de novo DLBC. A high expression of p53 was found in 53.7% of the patients. No expression of P-gp was demonstrated in any of the specimens. There were no significant differences in the complete remission (CR) rate (P = 0.79), overall survival (OS) (P = 0.73), or disease-free survival (DFS) (P = 31) between the p53-positive and p53-negative groups. The final model from multivariate analysis that revealed poor performance status was significantly associated with CR (P < 0.001) and OS (P < 0.001). Moreover, the advanced stage was a significant predictor of DFS (P = 0.03). This study demonstrated no impact of the expression of p53 on either response or survival rates.