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Phayao, Thailand

Nakayama T.,Osaka University | Zhao J.,Harbin Medical University | Takeuchi D.,Osaka University | Kerdsin A.,National Institute of Health | And 6 more authors.
Biosensors and Bioelectronics

A rapid diagnosis kit that detects Streptococcus suis (S. suis) antigens from urine with an immunochromatographic stripe (ICS) test was developed in this study. The ICS test was produced using colloidal gold coated with polyclonal antibodies (pAbs) against S. suis. The pAbs were developed from rabbits immunised with S. suis serotype 2 capsular polysaccharides (CPS). Development of the pAbs was investigated to establish their binding to CPS and to determine the maximum sensitivity of two combination antibodies for the ICS test. The results of the ICS optimisation revealed that the combinations of pAb C-N1 and pAb C-N2 had the highest sensitivity to CPS. The minimum limitation of ICS sensitivity indicated 1.0×104 colony forming units (CFU) and a CPS concentration of 0.05μg. The assay time for detection of S. suis antigens is less than 15min, which is suitable for rapid detection. A cross-reactive test was also conducted, and it detected no other bacteria (Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae). The cross-reactivity of other serotypes in S. suis was also investigated, and tests for serotypes of 1, 1/2, 3, 4, 5, 6, 7, 8, 9, 14, and 16 were positive. This study presents the first report of a development of an ICS that enables the quantitative detection of streptococcal antigens. The S. suis ICS provides several advantages over other methods, including the speed and simplicity of use. © 2014 Elsevier B.V. Source

Cressey T.R.,Chiang Mai University | Cressey T.R.,Harvard University | Cressey T.R.,Institute Of Recherche Pour Le Developpement Ird | Urien S.,University of Paris Descartes | And 12 more authors.
Therapeutic Drug Monitoring

Indinavir boosted with ritonavir (IDV/r) dosing with 400/100 mg, twice daily, is preferred in Thai adults, but this dose can lead to concentrations close to the boundaries of its therapeutic window. The objectives of this analysis were to validate a population pharmacokinetic model to describe IDV/r concentrations in HIV-infected Thai patients and to investigate the impact of patient characteristics on achieving adequate IDV concentrations. IDV/r concentration data from 513 plasma samples were available. Population means and variances of pharmacokinetic parameters were estimated using a nonlinear mixed effects regression model (NONMEM Version VI). Monte Carlo simulations were performed to estimate the probability of achieving IDV concentrations within its therapeutic window. IDV/r pharmacokinetics were best described by a one-compartment model coupled with a single transit compartment absorption model. Body weight influenced indinavir apparent oral clearance and volume of distribution and allometric scaling significantly reduced the interindividual variability. Final population estimates (interindividual variability in percentage) of indinavir apparent oral clearance and volume of distribution were 21.3 L/h/70 kg (30%) and 90.7 L/70 kg (22%), respectively. Based on model simulations, the probability of achieving an IDV trough concentration greater than 0.1 mg/L was greater than 99% for 600/100 mg and greater than 98% for 400/100 mg, twice daily, in patients weighing 40 to 80 kg. However, the probability of achieving IDV concentrations associated with an increased risk of drug toxicity (greater than 10.0 mg/L) increased from 1% to 10% with 600/100 mg compared with less than 1% with 400/100 mg when body weight decreased from 80 to 40 kg. The validated model developed predicts that 400/100 mg of IDV/r, twice daily, provides indinavir concentrations within the recommended therapeutic window for the majority of patients. The risk of toxic drug concentrations increases rapidly with IDV/r dose of 600/100 mg for patients less than 50 kg and therapeutic drug monitoring of IDV concentrations would help to reduce the risk of IDV-induced nephrotoxicity. Copyright © 2011 by Lippincott Williams & Wilkins. Source

Suaysod R.,Chiang Mai University | Ngo-Giang-Huong N.,Chiang Mai University | Ngo-Giang-Huong N.,Harvard University | Salvadori N.,Chiang Mai University | And 17 more authors.
Clinical Infectious Diseases

Background: Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. Methods: HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. Results: A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P =. 03), age >13 years (aHR, 2.9; P <. 001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P =. 03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P <. 001). Conclusions: Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored. © 2015 The Author 2015. Source

Takeuchi D.,Osaka University | Kerdsin A.,National Institute of Health | Pienpringam A.,Chiang Kham General Hospital | Loetthong P.,Phayao Provincial Hospital | And 16 more authors.

Background: Streptococcus suis infection in humans has received increasing worldwide recognition. Methods and Findings: A prospective study of S. suis infection in humans was conducted in Phayao Province in northern Thailand to determine the incidence and the risk behaviors of the disease in this region in 2010. Thirty-one cases were confirmed. The case fatality rate was 16.1%, and the estimated incidence rate was 6.2 per 100,000 in the general population. The peak incidence occurred in May. The median age of the patients was 53 years and 64.5% were men. Consumption of raw pork products was confirmed in 22 cases and the median incubation period (range) was 2 days (0-11) after consumption of raw pork products. Isolates from 31 patients were confirmed as serotype 2 in 23 patients (74.2%) and serotype 14 in eight patients (25.8%). The major sequence types (STs) were ST1 (n = 20) for serotype 2 and ST105 (n = 8) for serotype 14. The epidemiological analysis suggested three possible clusters, which included 17 cases. In the largest possible cluster of 10 cases in Chiang Kham and its neighboring districts in May, the source of infection in four cases was identified as a raw pork dish served at the same restaurant in this district. Microbiological analysis confirmed that three of four cases associated with consumption of raw pork at this restaurant were attributable to an identical strain of serotype 2 with ST1 and pulsotype A2. Conclusions: Our data suggest a high incidence rate of S. suis infection in the general population in Phayao Province in 2010 and confirm a cluster of three cases in 31 human cases. Food safety control should be strengthened especially for raw pork products in northern Thailand. © 2012 Takeuchi et al. Source

Collins I.J.,University of Paris Descartes | Collins I.J.,Harvard University | Collins I.J.,Chiang Mai University | Collins I.J.,London School of Hygiene and Tropical Medicine | And 20 more authors.
Clinical Infectious Diseases

Background. There are scarce data on the long-termsurvival of human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) in lower-middle income countries beyond 2 years of follow-up. Methods. Previously untreated children who initiated ART on meeting immunological and/or clinical criteria were followed in a prospective cohort in Thailand. The probability of survival up to 5 years from initiation was estimated using Kaplan-Meier methods, and factors associated with mortality were assessed using Cox regression analyses. Results. Five hundred seventy-eight children received ART; of these, 111 (19.2%) were followed since birth. At start of ART (baseline), the median age was 6.7 years, 128 children (22%) were aged <2 years, and the median CD4 cell percentage was 7%. Median duration of follow-up was 53 months; 42 children (7%) died, and 38 (7%) were lost to follow-up. Age <12 months, low CD4 cell percentage, and low weight-for-height z score at ART initiation were independently associated with mortality (P < .001). The probability of survival among infants aged <12 months at baseline was 84.3% at 1 year and 76.7% at 5 years of ART, compared with 95.7% and 94.8%, respectively, among children aged ≥1 year. Low CD4 cell percentage and wasting at baseline had a strong association with mortality among older children but weak or no association among infants. Conclusions. Children who initiated ART as infants after meeting immunological and/or clinical criteria had a high risk of mortality which persisted beyond the first year of therapy. Among older children, those with severe wasting or low CD4 cell percentage at treatment initiation were at high risk of mortality during the first 6 months of therapy. These findings support the scale-up of early HIV diagnosis and immediate treatment in infants, before advanced disease progression in older children. © 2010 by the Infectious Diseases Society of America. All rights reserved. Source

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