Browsing by Author "Tawee Chotpitayasunondh"

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    Antiretroviral resistance patterns and HIV-1 subtype in mother-infant pairs after the administration of combination short-course zidovudine plus single-dose nevirapine for the prevention of mother-to-child transmission of HIV.
    (2009-07-15) Amphan Chalermchockcharoenkit; Mary Culnane; Tawee Chotpitayasunondh; Nirun Vanprapa; Wanna Leelawiwat; Philip A. Mock; Suvanna Asavapiriyanont; Achara Teeraratkul; Michelle S. McConnell; Janet M. McNicholl; Jordan W. Tappero; Mahidol University
    BACKGROUND: World Health Organization guidelines for prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) recommend administration of zidovudine and single-dose nevirapine (NVP) for HIV-1-infected women who are not receiving treatment for their own health or if complex regimens are not available. This study assessed antiretroviral resistance patterns among HIV-infected women and infants receiving single-dose NVP in Thailand, where the predominant circulating HIV-1 strains are CRF01_AE recombinants and where the minority are subtype B. METHODS: Venous blood samples were obtained from (1) HIV-infected women who received zidovudine from 34 weeks' gestation and single-dose NVP plus oral zidovudine during labor and (2) HIV-infected infants who received single-dose NVP after birth plus zidovudine for 4 weeks after delivery. HIV-1 drug resistance testing was performed using the TruGene assay (Bayer HealthCare). RESULTS: Most mothers and infants were infected with CRF01_AE. NVP resistance was detected in 34 (18%) of 190 women and 2 (20%) of 10 infants. There was a significantly higher proportion of NVP mutations in women with delivery viral loads of >50,000 copies/mL (adjusted odds ratio, 8.5; 95% confidence interval, 2.2-32.8, [Formula: see text] for linear trend) and in those with subtype B rather than CRF01_AE infections (38% vs. 16%; adjusted odds ratio, 3.6; 95% confidence interval, 1.1-11.8; P = .038). CONCLUSIONS: The lower frequency of NVP mutations among mothers infected with subtype CRF01_AE, compared with mothers infected with subtype B, suggests that individuals infected with subtype CRF01_AE may be less susceptible to the induction of NVP resistance than are individuals infected with subtype B.
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    Assessment of bacille Calmette-Guérin vaccine reaction in HIV-exposed Thai infants
    (2007-10-22) Kulkanya Chokephaibulkit; Tawee Chotpitayasunondh; Nirun Vanprapar; Naris Waranawat; Philip A. Mock; Michelle S. McConnell; Bongkoch Jetswang; Kanchana Neeyapun; Jordan W. Tappero; Mary Culnane; Mahidol University; Queen Sirikit National Institute of Child Health; Centers for Disease Control (CDC), Thailand Field Station; Centers for Disease Control and Prevention
    We evaluated local reactions at 1, 2, and 4 months of age to bacille Calmette-Guérin vaccine given at birth to 1058 infants who were exposed to human immunodeficiency virus (HIV). No scar was discernible in 12 (12.4%) of 97 HIV-infected infants and 20 (2.1%) of 961 uninfected infants (relative risk, 5.9; 95% confidence interval, 3.0-11.8). This difference may reflect poorer immunogenicity in HIV-infected infants. © 2007 by the Infectious Diseases Society of America. All rights reserved.
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    Catch-up vaccination against Haemophilus influenzae type b in human immunodeficiency virus-infected Thai children older than 2 years old
    (2004-05-07) Kulkanya Chokephaibulkit; Wanatpreeya Phongsamart; Nirun Vanprapar; Tawee Chotpitayasunondh; Sanay Chearskul; Mahidol University; Queen Sirikit National Institute of Child Health
    Although most of Thai children older than 2 years are immune against Haemophilus influenzae type b (Hib) without prior vaccination, it may not be the case in HIV-infected children. Of 44 HIV-infected children tested before vaccination at the mean age of 36 months (range 24-84 months), 32 (73%) were susceptible (anti-PRP <0.15 μg/ml). At 6 months after a single dose of tetanus-conjugated Hib vaccination, 67% developed anti-PRP ≥0.15 μg/ml, however, only 33% developed titer of ≥1 μg/ml. Four of seven (57%) with anti-PRP 0.15-0.99 μg/ml at baseline were boosted to the titer of ≥1 μg/ml after vaccination. Seroconversion rate and geometric mean titer (GMT) level in response to the vaccination did not correlate with HIV stage, but did correlate with viral load level of 100,000 copies/ml. HIV-infected children older than 2 years would benefit from Hib vaccination, although, one dose catch-up schedule is not sufficient in a third of these children. A second dose is needed in these children especially those with viral load of level of >100,000 copies/ml. © 2003 Elsevier Ltd. All rights reserved.
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    A chewable pediatric fixed-dose combination tablet of stavudine, lamivudine, and nevirapine: Pharmacokinetics and safety compared with the individual liquid formulations in human immunodeficiency virus-infected children in Thailand
    (2010-01-01) Nirun Vanprapar; Tim R. Cressey; Kulkanya Chokephaibulkit; Petronella Muresan; Nottasorn Plipat; Virat Sirisanthana; Wasana Prasitsuebsai; Suchat Hongsiriwan; Tawee Chotpitayasunondh; Achara Eksaengsri; Maripat Toye; Mary Elizabeth Smith; Kenneth McIntosh; Edmund Capparelli; Ram Yogev; Mahidol University; Chiang Mai University; Harvard School of Public Health; University of Michigan School of Public Health; Chonburi Regional Hospital; Queen Sirikit National Institute of Child Health; Thailand Government Pharmaceutical Organization; Baystate Medical Center; National Institute of Allergy and Infectious Diseases; Children's Hospital Boston; University of California, San Diego; Ann & Robert H. Lurie Children's Hospital of Chicago
    Background: Pediatric fixed-dose combinations (FDCs) are needed to facilitate antiretroviral therapy in children. We evaluated the relative bioavailability, safety, and therapeutic adequacy of a novel chewable pediatric FDC tablet of stavudine (7 mg), lamivudine (30 mg), and nevirapine (50 mg), referred to as GPO-VIR S7, and compared it with the individual original brand-name liquid formulations in human immunodeficiency virus-infected Thai children. Methods: The International Maternal Pediatric Adolescent AIDS Clinical Trials group (IMPAACT) P1056 study was a phase I/II, 2-arm, randomized, open-label, multidose pharmacokinetic cross-over study. Children ≥6 to ≤30 kg receiving nevirapine-based HAART for at least 4 weeks were randomized to receive GPO-VIR S7 chewable tablets or the equivalent liquid formulations. Children were stratified by weight and dosing was weight-based. Intensive 12-hour blood sampling was performed on day 28, and subjects then crossed-over to the alternate formulation at equal doses with identical 12-hour sampling on day 56. Pharmacokinetic indices were determined by noncompartmental analysis. Results: Thirty-four children completed the study. While taking Government Pharmaceutical Organization (GPO)-VIR S7 the geometric mean (90% CI) area under the curve was 1.54 μg•hr/mL (1.42-1.67) for stavudine, 6.39 (5.82-7.00) for lamivudine, and 74.06 (65.62-83.60) for nevirapine. Nevirapine drug exposure for GPO-VIR S7 was therapeutically adequate. Geometric mean area under the curve ratios (90% CI) of GPO-VIR S7/liquid formulation for stavudine, lamivudine, and nevirapine were 0.97 (0.92-1.02), 1.41 (1.30-1.53), and 1.08 (1.04-1.13), respectively. No serious drug-related toxicity was reported. Conclusions: The chewable FDC was safe and provided therapeutically adequate plasma drug exposures in human immunodeficiency virus-infected children. Substituting the FDC for liquid formulations can simplify antiretroviral therapy. © 2010 by Lippincott Williams & Wilkins.
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    Chlamydial and gonococcal cervicitis in HIV-seropositive and HIV- seronegative pregnant women in Bangkok: Prevalence, risk factors, and relation to perinatal HIV transmission
    (1997-10-01) Pongsakdi Chaisilwattana; Rutt Chuachoowong; Wimol Siriwasin; Chaiporn Bhadrakom; Yunyong Mangclaviraj; Nancy L. Young; Sanay Chearskul; Tawee Chotpitayasunondh; Timothy D. Mastro; Nathan Shaffer; Mahidol University; HIV/AIDS Collaboration; Rajavithi Hospital; Bangkok Children's Hospital; National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Thailand Ministry of Public Health
    Objectives: To determine the prevalence and risk factors associated with cervicitis caused by Chlamydia trachomatis and Neisseria gonorrhoeae in human immunodeficiency virus (HIV) type 1-seropositive and HIV-seronegative pregnant women in Bangkok, and the relation to perinatal HIV transmission. Methods: As part of a multicenter perinatal HIV transmission study in an antenatal population with 2% HIV seroprevalence, endocervical swabs obtained at mid-pregnancy from a consecutive sample of 222 HIV-seropositive and 219 HIV-seronegative pregnant women at two large hospitals in Bangkok were tested for the presence of C. trachomatis and N. gonorrhoeae by DNA hybridization probe (Gen-Probe). Clinical risk factors and DNA probe results were analyzed in relation to the women's and newborns' HIV infection status. Results: The prevalence of C. trachomatis was 16.2% in HIV-seropositive pregnant women and 9.1% in HIV-seronegative pregnant women (P = 0.03). The prevalence of N. gonorrhoeae was 2.7% in HIV-seropositive pregnant women and 1.4% in HIV- seronegative pregnant women (P = 0.5). The overall population prevalence estimate was 9.2% for C. trachomatis and 1.4% for N. gonorrhoeae. Women with gonococcal infection were more likely to be positive for C. trachomatis (RRMH = 5.2, P < 0.01). Young age (<21 years) and primigravid status were associated with C. trachomatis infection among HIV-seropositive women; history of multiple sex partners (>1) were associated with C. trachomatis infection among HIV-seronegative women. For HIV-seropositive women, primigravida status also was associated with C. trachomatis infection. The perinatal HIV transmission rates were similar for those with and without C. trachomatis (24.1% and 23.2%, P = 0.9) and among those with and without N. gonorrhoeae (20% and 23.5%, P = 1.0). Conclusions: Among pregnant women in Bangkok, C. trachomatis infection was considerably more common than N. gonorrhoeae infection and was associated with HIV infection, young age and first pregnancy (HIV-seropositive women), and multiple partners (HIV- seronegative women). Our data do not suggest an association between perinatal HIV transmission and maternal C. trachomatis or N. gonorrhoeae infection identified and treated during pregnancy. The high prevalence of C. trachomatis found using a test not readily available in Thailand emphasizes the need for improved, inexpensive ways to screen for and diagnose these sexually transmitted infections in developing countries.
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    Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: A phase 3, randomised, observer-masked, placebo-controlled trial
    (2014-01-01) Maria Rosario Capeding; Ngoc Huu Tran; Sri Rezeki S. Hadinegoro; Hussain Imam Hj Muhammad Ismail; Tawee Chotpitayasunondh; Mary Noreen Chua; Chan Quang Luong; Kusnandi Rusmil; Dewa Nyoman Wirawan; Revathy Nallusamy; Punnee Pitisuttithum; Usa Thisyakorn; In Kyu Yoon; Diane Van Der Vliet; Edith Langevin; Thelma Laot; Yanee Hutagalung; Carina Frago; Mark Boaz; T. Anh Wartel; Nadia G. Tornieporth; Melanie Saville; Alain Bouckenooghe; Gokila; Pasteur Institute in Ho Chi Minh City; University of Indonesia, RSUPN Dr. Cipto Mangunkusumo; Kuala Lumpur Hospital; Queen Sirikit National Institute of Child Health; Chong Hua Hospital; Universitas Padjadjaran; Universitas Udayana; Penang Hospital; Mahidol University; Armed Forces Research Institute of Medical Sciences, Thailand; Sanofi Pasteur; Sanofi Pasteur; Sanofi Pasteur; Sanofi Pasteur; Sanofi Pasteur SA
    © © 2014 Elsevier Ltd. Background An estimated 100 million people have symptomatic dengue infection every year. This is the fi rst report of a phase 3 vaccine effi cacy trial of a candidate dengue vaccine. We aimed to assess the effi cacy of the CYD dengue vaccine against symptomatic, virologically confi rmed dengue in children.Methods We did an observer-masked, randomised controlled, multicentre, phase 3 trial in fi ve countries in the Asia- Pacifi c region. Between June 3, and Dec 1, 2011, healthy children aged 214 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratifi ed by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective effi cacy against symptomatic, virologically confi rmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine effi cacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281.Findings We randomly assigned 10 275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confi rmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 565% (95% CI 438664) effi cacy. We recorded 647 serious adverse events (402 [62%] in the vaccine group and 245 [38%] in the control group). 54 (1%) children in the vaccine group and 33 (1%) of those in the control group had serious adverse events that happened within 28 days of vaccination. Serious adverse events were consistent with medical disorders in this age group and were mainly infections and injuries.Interpretation Our fi ndings show that dengue vaccine is effi cacious when given as three injections at months 0, 6, and 12 to children aged 214 years in endemic areas in Asia, and has a good safety profi le. Vaccination could reduce the incidence of symptomatic infection and hospital admission and has the potential to provide an important public health benefi t.Funding Sanofi Pasteur.
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    Comparing interferon-gamma release assays to tuberculin skin test in thai children with tuberculosis exposure
    (2014-08-14) Hong Van Tieu; Piyarat Suntarattiwong; Thanyawee Puthanakit; Tawee Chotpitayasunondh; Kulkanya Chokephaibulkit; Sunee Sirivichayakul; Supranee Buranapraditkun; Patcharawee Rungrojrat; Nitiya Chomchey; Simon Tsiouris; Scott Hammer; Vijay Nandi; Jintanat Ananworanich; New York Blood Center; Columbia University Medical Center; Queen Sirikit National Institute of Child Health; Chulalongkorn University; The HIV Netherlands Australia Thailand Research Collaboration; Mahidol University; Faculty of Medicine, Thammasat University; SEARCH; Walter Reed Army Institute of Research
    Background: Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure. Methods: This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT. Results: 158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42-46% for TST≥10 mm and 62-67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB. Conclusions: Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings. © 2014 Tieu et al.
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    Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes
    (2000-08-15) Nancy L. Young; Nathan Shaffer; Thongpoon Chaowanachan; Tawee Chotpitayasunondh; Nirun Vanparapar; Philip A. Mock; Naris Waranawat; Kulkanya Chokephaibulkit; Rutt Chuachoowong; Punneeporn Wasinrapee; Timothy D. Mastro; R. J. Simonds; HIV/AIDS Collaboration; Centers for Disease Control and Prevention; Thailand Ministry of Public Health; Mahidol University
    Objectives: To evaluate the sensitivity and specificity of RNA and DNA polymerase chain reaction (PCR) for early diagnosis of perinatal HIV-1 infection and to investigate early viral dynamics in infected infants Design: A cohort study of 395 non-breastfed infants born to HIV-infected mothers in a randomized clinical trial of short-course antenatal zidovudine. Methods: Infant venous blood specimens collected at birth. 2 months, and 6 months of age were tested by qualitative DNA and quantitative RNA PCR (Roche Amplicor). To determine sensitivity and specificity of DNA and RNA PCR, results were compared with later DNA PCR results and to antibody results at 18 months. The HIV-1 subtype of the mother's infection was determined by peptide serotyping. Results: In the study, 92% of mothers were infected with subtype E. DNA PCR sensitivity was 38% (20 of 53) at birth, and 100.% at 2 months (53 of 53) and 6 months (47 of 47). RNA PCR sensitivity was 47% (25 of 53) at birth and 100% (53 of 53) at 2 months. All samples that tested DNA-positive tested RNA-positive. Specificity was 100% for both DNA and RNA testing at all timepoints. For infected infants, the median viral load of RNA-positive specimens was 407,000 copies/ml (5.6 log10) at birth, 3,700,000 copies/ml (6.6 log10) at 2 months, and 1,700,000 copies/ml (6.2 log10) at 6 months. Infant RNA levels at 2 and 6 months did not differ by maternal zidovudine exposure, or RNA level at birth. Conclusion: This RNA PCR assay performed well for diagnosing perinatal HIV subtype E infection, detecting nearly half of infected infants birth, and 100% at 2 and 6 months, with 100% specificity. Infected infant viral RNA-levels were very high at 2 and 6 months, and were unaffected by maternal zidovudine treatment.
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    Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: Double blind randomised controlled trial
    (2013-06-08) Endang Rahayu Sedyaningsih; Moh Suhud Malik; Vivi Setiawaty; Trihono Trihono; Erlina Burhan; Tjandra Yoga Aditama; Prijanti Z. Soepandi; Lia G. Partakusuma; Agung P. Sutiyoso; Ika Priatni; Hadi Jusuf; Emmy Hermiyanti Pranggono; Arto Yuwono Soeroto; Djatnika Setiabudi; Dadang Hudaya Somasetia; Sri Sudarwati; Tini T. Maskoen; Yovita Hartantri; Ida Parwati; Sardikin Giriputro; Dewi Murniati; Sondang Maryutka Sirait; Tony Soetanto; Sri Sulastri; Rismali Agus; Adria Rusli; Sila Wiweka; Steve Wignall; Kevin Baird; Iko Safika; Chariya Sangsajja; Weerawat Manosuthi; Patama Sutha; Chareon Chuchottaworn; Piamlarp Sansayunh; Kittima Bangpattanasiri; Walter R.J. Taylor; Kasia Stepniewska; Caroline Fukuda; Niklas Lindegardh; Nicholas White; Nick Day; Tawee Chotpitayasunondh; Piyarat Suntarattiwong; Umaporn Chantbuddhiwet; Supichaya Netsawang; Kulkanya Chokephaibulkit; Nirun Vanprapar; Wasana Prasitsuebsai; Orasri Wittawatmongkol; Thanomsak Anekthananon; Winai Ratanasuwan; Yong Rongrungruang; Pilaipan Puthavathana; Paul A. Tambyah; Yee Sin Leo; Dale Fisher; Louis Chai; Lawrence Lee; Raymond Lin; Ngo Ngoc Quang Minh; Truong Huu Khanh; Le Phan Kim Thoa; Le Anh Tuan; Tran Thi My Dung; Lam Thi Thuy Ha; Le Minh Qui; Le Quoc Thinh; Nguyen Ngoc Tu Anh; Tran Anh Tuan; Trinh Hong Nhien; Bui Pham Phuong; Phan Tu Qui; Tieu Chau Thy; Bui Xuan Vu; Le Binh Bao Tinh; Dang Thi Thanh; Vo Phuong Khanh; Do Chau Viet; Tran Thi Thuy; Vo Quoc Bao; Le Nguyen Nhat Trung; Ho Thi Kim Thoa; Tran Thi Ngoc Anh; Tran Thi Thu Loan; Tran Quynh Huong; Nguyen Thi Hanh Le; Ho Lu Viet; Ha Manh Tuan; Nguyen Thi Thanh Ha; Nguyen Van Vinh Chau; Nguyen Thanh Truong; Le Thi Thu Thao; Nguyen Thanh Phong; Pham Tran Dieu Hien; Pham Thi Hai Men; Cao Thi Tam; Tran Vinh Diet; Nguyen Van Hao; Badan Penelitian Dan Pengembangan Kesehatan, Kementerian Kesehatan Republik Indonesia; Persahabatan Hospital; Rumah Sakit Hasan Sadikan Bandung; Sulianto Saroso Hospital Jakarta; Eijkman Oxford Clinical Research Unit; Bamrasnaradura Infectious Disease Institute; Chest Disease Institute Nonthaburi; Mahidol Oxford Research Unit Bangkok; Queen Sirikit National Institute of Child Health; Mahidol University; National University Hospital, Singapore; Children's Hospital 1; Children's Hospital 2; UCL; National Hospital for Tropical Diseases
    Objective: To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design: Double blind randomised trial. Setting: Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants: Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions: Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure: Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results: Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (-5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found. Conclusions: There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital. Registration: Clinical Trials NCT00298233.
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    Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study
    (2014-01-01) Gareth Tudor-Williams; Pedro Cahn; Kulkanya Chokephaibulkit; Jan Fourie; Chris Karatzios; S. Dincq; M. Opsomer; T. N. Kakuda; S. Nijs; L. Tambuyzer; F. L. Tomaka; Rosa Bologna; Esaú João; José Henrique Pilotto; Marisa Mussi-Pinhata; Jorge Pinto; Normand Lapointe; Albert Faye; Kamila Kebaili; Steven Welch; Stefania Bernardi; Luisa Galli; Carlo Giaquinto; Nicola Principi; Gian Vincenzo Zuccotti; Henriette J. Scherpbier; Laura Marques; Isabel Soares; Margarida Tavares; Midnela Acevedo; Dan Duiculescu; Sorin Rugina; Gulam H. Latiff; Claudia Fortuny; Juan Antonio Leon Leal; Marissa Navarro; Jose T. Ramos; Tawee Chotpitayasunondh; Pope Kosalaraksa; Kiat Ruxrungtham; Jacobo Abadi; Tess Barton; William Borkowsy; Janet Chen; Joseph Church; Patricia Flynn; Sohail Rana; Richard Rutstein; Leonard Weiner; Imperial College London; Fundacion Huesped; Mahidol University; Dr Jan Fourie Medical Practice; Centre universitaire de sante McGill; Janssen Infectious Diseases BVBA; Janssen
    © 2014 British HIV Association 15 9 October 2014 10.1111/hiv.12141 Original research Original research. © 2014 British HIV Association. Objectives: PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213; NCT00665847) assessed the safety/tolerability, antiviral activity and pharmacokinetics of etravirine plus an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected children (≥6 to <12 years) and adolescents (≥12 to <18 years) over 48 weeks. Methods: In a phase II, open-label, single-arm study, 101 treatment-experienced patients (41 children; 60 adolescents) with screening viral load (VL) ≥500 HIV-1 RNA copies/mL received etravirine 5.2mg/kg (maximum dose 200mg) twice a day (bid) plus OBR. Results: Sixty-seven per cent of patients had previously used efavirenz or nevirapine. At week 48, the most common treatment-related grade ≥2 adverse event (AE) was rash (13%); 12% experienced grade 3 AEs. Only two grade 4 AEs occurred (both thrombocytopaenia, not etravirine related). At week 48, 56% of patients (68% children; 48% adolescents) achieved a virological response (VL<50copies/mL; intent-to-treat, noncompleter=failure). Factors predictive of response were adherence >95%, male sex, low baseline etravirine weighted genotypic score and high etravirine trough concentration (C0h). Seventy-six patients (75%) completed the trial; most discontinuations occurred because of protocol noncompliance or AEs (8% each). Sixty-five per cent of patients were >95% adherent by questionnaire and 39% by pill count. Forty-one patients experienced virological failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29 nonresponders; 12 rebounders). Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine area under the plasma concentration-time curve over 12h (AUC0-12h; 5216ng h/mL) and C0h (346ng/mL) were comparable to adult target values. Conclusions: Results with etravirine 5.2mg/kg bid (with OBR) in this treatment-experienced paediatric population and etravirine 200mg bid in treatment-experienced adults were comparable. Etravirine is an NNRTI option for treatment-experienced paediatric patients. Copyright.
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    Evaluating a new strategy for prophylaxis to prevent Pneumocystis carinii pneumonia in HIV-exposed infants in Thailand
    (2000-09-23) Kulkanya Chokephaibulkit; Rutt Chuachoowong; Tawee Chotpitayasunondh; Sanay Chearskul; Nirun Vanprapar; Naris Waranawat; Philip Mock; Nathan Shaffer; R. J. Simonds; Mahidol University; HIV/AIDS Collaboration; Thailand Ministry of Public Health; National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Faculty of Medicine, Siriraj Hospital, Mahidol University
    Objective: To evaluate a strategy for prophylaxis against Pneumocystis carinii pneumonia (PCP) for infants in Thailand. Methods: HIV-infected women were offered trimethoprim-sulfamethoxazole for PCP prophylaxis for their children at 1-2 months of age. When the children reached 6 months of age, investigators simulated a decision to continue or stop prophylaxis on the basis of clinical criteria, and compared their decisions with results of polymerase chain reaction (PCR) testing for HIV. We calculated the proportions of children who received and completed prophylaxis, and compared the rates of pneumonia and death from pneumonia with rates from an earlier prospective cohort. Results: Of 395 eligible infants, 383 (97%) started prophylaxis. By 6 months of age, 10 (2.6%) were lost to follow-up, three (0.8%) were non-adherent, seven (2%) had stopped because of adverse events, four (1%) had died, and 359 (94%) still received prophylaxis. At 6 months of age, 30 (70%) of 43 HIV-infected children and 16 (5%) of 316 uninfected children met the clinical criteria to continue prophylaxis. The incidence of pneumonia at 1 to 6 months of age was 22% (15/68) in the earlier cohort, and 13% (6/46) in the recent cohort [relative risk (RR) 0.6, 95% confidence interval (Cl) 0.3-1.4; P = 0.22]; mortality rates were 9% and 4%, respectively (RR 0.5; 95% Cl 0.1-2.3; P= 0.47). Conclusion: This PCP prophylaxis strategy appeared to be acceptable and safe, may have reduced morbidity and mortality from pneumonia, and should be considered in developing countries where early laboratory diagnosis of perinatal HIV infection is unavailable. (C) 2000 Lippincott Williams and Wilkins.
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    Evaluating programs to prevent mother-to-child HIV transmission in two large Bangkok hospitals, 1999-2001
    (2005-02-01) Achara Teeraratkul; R. J. Simonds; Suvanna Asavapiriyanont; Amphan Chalermchokcharoenkit; Nirun Vanprapa; Tawee Chotpitayasunondh; Philip A. Mock; Natapakwa Skunodum; Kanchana Neeyapun; Bongkoch Jetsawang; Mary Culnane; Jordan Tappero; Thailand Ministry of Public Health; National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Rajavithi Hospital; Mahidol University
    The 2 largest maternity hospitals in Bangkok implemented comprehensive programs to prevent mother-to-child HIV transmission in 1998. We conducted a cross-sectional survey of postpartum HIV-infected women in 1999 through 2001 to evaluate these programs. Women were given structured interviews at 0 to 3 days, 1 month, and 2 months postpartum. Medical records of women and their newborns were reviewed. Of 488 enrolled women, 443 (91%) had antenatal care: 391 (88%) at study hospitals and 52 (12%) elsewhere. The HIV diagnosis was first known before pregnancy for 61 (13%) women, during pregnancy for 357 (73%) women, during labor for 22 (5%) women, and shortly after delivery for 48 (10%) women. Antenatal zidovudine (ZDV) was used by 347 (71%) women, and intrapartum ZDV was used by 372 (76%) women. Twelve (55%) of the 22 women who first learned of their HIV infection during labor took intrapartum ZDV. All 495 newborn infants started prophylactic ZDV; the first dose was given within 12 hours for 491 (99%) children. Ten (2%) children were breast-fed at least once by their mother, and 10 (2%) were breast-fed at least once by someone else. Although uptake of services was high, inconsistent antenatal care, fear of stigmatization, and difficulty in disclosing HIV status prevented some women from using services.
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    HIV prevalence, risk, and partner serodiscordance among pregnant women in Bangkok
    (1998-07-01) Wimol Siriwasin; Nathan Shaffer; Anuvat Roongpisuthipong; Prapas Bhiraleus; Pratharn Chinayon; Chantapong Wasi; Sunee Singhanati; Tawee Chotpitayasunondh; Sanay Chearskul; Waranee Pokapanichwong; Philip Mock; Bruce G. Weniger; Timothy D. Mastro; Rajavithi Hospital; HIV/AIDS Collaboration; Centers for Disease Control and Prevention; Mahidol University; Bangkok Children's Hospital; Thailand Ministry of Public Health
    Context. - Most prior studies of the human immunodeficiency virus (HIV) epidemic in Thailand have focused on commercial sex encounters; however, because the epidemic increasingly concerns stable heterosexual relationships, determining risk factors for this form of transmission is warranted. Objectives. - To determine temporal trends in HIV prevalence, risk factors for HIV seropositivity, and rates of partner serodiscordance for pregnant women in Bangkok, Thailand. Design. - Retrospective review of hospital antenatal clinic HIV test results from 1991 through 1996. Baseline demographic and behavioral risk factors for HIV were assessed for subjects enrolled from November 1992 through March 1994. Setting. - Two Bangkok hospitals with routine antenatal clinic HIV counseling and testing. Participants. - The HIV-positive pregnant women enrolled in a perinatal HIV transmission study and their partners and HIV-negative pregnant controls. Results. - From 1991 through 1996, antenatal clinic HIV seroprevalence increased from 1.0% to 2.3%. On multivariate analysis of data from 342 HIV- positive and 344 HIV-negative pregnant women, more than 1 lifetime sex partner, history of a sexually transmitted disease, and a high-risk sex partner were the most important factors for seropositivity (all P <.001). Twenty-six percent of partners of HIV-positive women were HIV negative. Women reporting more than 1 lifetime sex partner were more likely to have an HIV- negative partner than women reporting only 1 (45% vs 8%; relative risk, 5.5; 95% confidence interval, 3.2-9.5; P < .001); women reporting no high-risk behaviors were less likely to have an HIV-negative partner (10% vs 44%; relative risk, 0.2; 95% confidence interval, 0.1-0.4; P < .001). Conclusions. - Prevalence of HIV in pregnant women has increased steadily in Bangkok from 1991 through 1996. Sex with current partners was the only identified risk exposure for about half (52%) of the HIV-positive women. Although few HIV- positive pregnant women reported high-risk behaviors, more than 1 lifetime partner and a partner with high-risk behavior were strong risk factors for seropositivity. Together with the unexpected finding that one fourth of partners of seropositive pregnant women were seronegative, these data emphasize that women in the general population are at risk for HIV because of the risk behavior of both current and previous partners.
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    Infection with hepatitis C virus among HIV-infected pregnant women in Thailand
    (2008-12-01) Denise J. Jamieson; Natapakwa Skunodom; Thanyanan Chaowanachan; Anuvat Roongpisuthipong; William A. Bower; Tawee Chotpitayasunondh; Wendy Bhanich Supapol; Wendi L. Kuhnert; Wimol Siriwasin; Jeffrey Wiener; Sanay Chearskul; Michelle S. McConnell; Nathan Shaffer; National Center for Chronic Disease Prevention and Health Promotion; Thailand Ministry of Public Health; Mahidol University; Centers for Disease Control and Prevention; University of Toronto Faculty of Medicine; Rajavithi Hospital
    Objective. The purpose of this study was to describe the epidemiology of coinfection with hepatitis C virus (HCV) and HIV among a cohort of pregnant Thai women. Methods. Samples from 1771 pregnant women enrolled in three vertical transmission of HIV studies in Bangkok, Thailand, were tested for HCV. Results. Among HIV-infected pregnant women, HCV seroprevelance was 3.8% and the active HCV infection rate was 3.0%. Among HIV-uninfected pregnant women, 0.3% were HCV-infected. Intravenous drug use by the woman was the factor most strongly associated with HCV seropositivity. Among 48 infants tested for HCV who were born to HIV/HCV coinfected women, two infants were HCV infected for an HCV transmission rate of 4.2% (95% 0.51-14.25%). Conclusions. HCV seroprevalence and perinatal transmission rates were low among this Thai cohort of HIV-infected pregnant women. Copyright © 2008 Denise J. Jamieson et al.
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    Initiation of antiretroviral treatment with dual nucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected infants with less advanced disease in a resource-limited setting: A Multi-Center Study in Thailand 1998-2000
    (2005-08-01) Kulkanya Chokephaibulkit; Nirun Vanprapar; Ruengpung Sutthent; Wanatpreeya Phongsamart; Tawee Chotpitayasunondh; Piyaporn Bowornkitikajorn; Rudeevilai Samkoset; Uraiwan Tarunothai; Sanay Chearskul; Mahidol University; Queen Sirikit National Institute of Child Health; Charoenkrung-Pracharuk Hospital; Phramongkutklo Hospital; Vachira-Bhayabarn Hospital; Faculty of Medicine, Siriraj Hospital, Mahidol University
    Objectives: To evaluate the feasibility, duration of efficacy, and outcome of therapy with dual nucleoside reverse transcriptase inhibitors (NTRI) initiated in HIV-infected infants with mild to moderate disease. Material and Method: During 1998-2000, a multi-center prospective open-labeled operational study was conducted. Antiretroviral naôve HIV-infected infants were enrolled in seven hospitals to receive either zidovudine (AZT) plus lamivudine (3TC) or AZT plus didanosine (ddI). Infants who were in CDC stage "C3" were excluded from the study. Results: Of the 88 infants, the mean age of treatment initiation was 6.8 months, and the mean initial CD4 was 1538 cells/mm 3 (21.4%). The z-scores for weight and height increased after 4-8 months of treatment, and by the 24 th month, were +0.89 and +0.69 higher than at enrollment. The CD4% peak increased at 8 months of treatment, by a mean increment of 4.19%, but decreased to the level of 1.08% above baseline by the 24 th month of treatment. Three (3.4%) infants died, 11 (12%) had disease progression, 7 (8%) was prematurely discontinued from the study protocol due to poor compliance, and 37 (42%) were lost to follow-up. At the end of 24 months, all remaining 30 children were in stable condition with a chance of clinical and immunological stability of 34% and 68% by intention-to-treat and on-treatment analysis, respectively. Conclusion: Clinical and immunological benefit from dual NRTI was limited. Treatment of HIV-infected infant with mild to moderate disease in a resource-limited setting may have limited feasibility due to the high drop-out rate.
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    Maternal herpes simplex virus type 2 coinfection increases the risk of perinatal HIV transmission: Possibility to further decrease transmission?
    (2008-06-19) Liesbeth J M Bollen; Sara J. Whitehead; Philip A. Mock; Wanna Leelawiwat; Suvanna Asavapiriyanont; Amphan Chalermchockchareonkit; Nirun Vanprapar; Tawee Chotpitayasunondh; Janet M. McNicholl; Jordan W. Tappero; Nathan Shaffer; Rutt Chuachoowong; Thailand Ministry of Public Health; Centers for Disease Control and Prevention; Rajavithi Hospital; Mahidol University
    Objectives:: To evaluate the association between maternal herpes simplex virus type 2 seropositivity and genital herpes simplex virus type 2 shedding with perinatal HIV transmission. Study design:: Evaluation of women who participated in a 1996-1997 perinatal HIV transmission prevention trial in Thailand. Methods:: In this nonbreastfeeding population, women were randomized to zidovudine or placebo from 36 weeks gestation through delivery; maternal plasma and cervicovaginal HIV viral load and infant HIV status were determined for the original study. Stored maternal plasma and cervicovaginal samples were tested for herpes simplex virus type 2 antibodies by enzyme-linked immunoassay and for herpes simplex virus type 2 DNA by real-time PCR, respectively. Results:: Among 307 HIV-positive women with available samples, 228 (74.3%) were herpes simplex virus type 2 seropositive and 24 (7.8%) were shedding herpes simplex virus type 2. Herpes simplex virus type 2 seropositivity was associated with overall perinatal HIV transmission [adjusted odds ratio, 2.6; 95% confidence interval, 1.0-6.7)], and herpes simplex virus type 2 shedding was associated with intrapartum transmission (adjusted odds ratio, 2.9; 95% confidence interval, 1.0-8.5) independent of plasma and cervicovaginal HIV viral load, and zidovudine treatment. Median plasma HIV viral load was higher among herpes simplex virus type 2 shedders (4.2 vs. 4.1 log10copies/ml; P = 0.05), and more shedders had quantifiable levels of HIV in cervicovaginal samples, compared with women not shedding herpes simplex virus type 2 (62.5 vs. 34.3%; P = 0.005). Conclusion:: We found an increased risk of perinatal HIV transmission among herpes simplex virus type 2 seropositive women and an increased risk of intrapartum HIV transmission among women shedding herpes simplex virus type 2. These novel findings suggest that interventions to control herpes simplex virus type 2 infection could further reduce perinatal HIV transmission. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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    Maternal viral load and timing of mother-to-child HIV transmission, Bangkok, Thailand
    (1999-03-03) Philip A. Mock; Nathan Shaffer; Chaiporn Bhadrakom; Wimol Siriwasin; Tawee Chotpitayasunondh; Sanay Chearskul; Nancy L. Young; Anuvat Roongpisuthipong; Pratharn Chinayon; Marcia L. Kalish; Bharat Parekh; Timothy D. Mastro; HIV/AIDS Collaboration; Centers for Disease Control and Prevention; Mahidol University; Rajavithi Hospital; Bangkok Children's Hospital
    Objectives: To determine the proportion of HIV-1-infected infants infected in utero and intrapartum, the relationship between transmission risk factors and time of transmission, and the population-attributable fractions for maternal viral load. Design: Prospective cohort study of 218 formula-fed infants of HIV-1-infected untreated mothers with known infection outcome and a birth HIV-1-positive DNA PCR test result. Methods: Transmission in utero was presumed to have occurred if the birth sample (within 72 h of birth) was HIV-1-positive by PCR; intrapartum transmission was presumed if the birth sample tested negative and a later sample was HIV-1-positive. Two comparisons were carried out for selected risk factors for mother-to-child transmission: infants infected in utero versus all infants with a HIV-1-negative birth PCR test result, and infants infected intrapartum versus uninfected infants. Results: Of 49 infected infants with an HIV-1 birth PCR result, 12 (24.5%) [95% confidence interval (CI), 14-38] were presumed to have been infected in utero and 37 (75.5%) were presumed to have been infected intrapartum. The estimated absolute overall transmission rate was 22.5%; this comprised 5.5% (95% CI, 3-9) in utero transmission and 18% (95% CI, 13-24) intrapartum transmission. Intrapartum transmission accounted for 75.5% of infections. High maternal HIV-1 viral load (> median) was a strong risk factor fur both in utero [adjusted odds ratio (AOR) 5.8 (95% CI, 1.4-38.8] and intrapartum transmission (AOR, 4.4; 95% CI, 1.9-11.2). Low birth-weight was associated with in utero transmission, whereas low maternal natural killer cell and CD4+ T-lymphocyte percentages were associated with intrapartum transmission. The population-attributable fraction for intrapartum transmission associated with viral load > 10 000 copies/ml was 69%. Conclusions: Our results provide further evidence that most perinatal HIV-1 transmission occurs during labor and delivery, and that risk factors may differ according to time of transmission. Interventions to reduce maternal viral load should be effective in reducing both in utero and intrapartum transmission.
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    Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand
    (1999-12-01) Nathan Shaffer; Anuvat Roongpisuthipong; Wimol Siriwasin; Tawee Chotpitayasunondh; Sanay Chearskul; Nancy L. Young; Bharat Parekh; Philip A. Mock; Chaiporn Bhadrakom; Pratharn Chinayon; Marcia L. Kalish; Susan K. Phillips; Timothy C. Granade; Shambavi Subbarao; Bruce G. Weniger; Timothy D. Mastro; Mahidol University; Centers for Disease Control and Prevention
    To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P < .001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load >10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.
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    Patient-based transcriptome-wide analysis identify interferon and ubiquination pathways as potential predictors of influenza a disease severity
    (2014-11-03) Long Truong Hoang; Thomas Tolfvenstam; Eng Eong Ooi; Chiea Chuen Khor; Ahmand Nazri; Mohamed Naim; Eliza Xin Pei Ho; Swee Hoe Ong; Heiman F. Wertheim; Annette Fox; Chau Van Vinh Nguyen; Ngoc My Nghiem; Tuan Manh Ha; Anh Thi Ngoc Tran; Paul Tambayah; Raymond Lin; Chariya Sangsajja; Weerawat Manosuthi; Chareon Chuchottaworn; Piamlarp Sansayunh; Tawee Chotpitayasunondh; Piyarat Suntarattiwong; Kulkanya Chokephaibulkit; Pilaipan Puthavathana; Menno D. De Jong; Jeremy Farrar; H. Rogier Van Doorn; Martin Lloyd Hibberd; Genome Institute of Singapore; UCL; Nuffield Department of Clinical Medicine; Academic Medical Centre, University of Amsterdam; Oxford University Clinical Research Unit; Children's Hospital 2; National University Hospital, Singapore; Bamrasnaradura Infectious Disease Institute; Chest Disease Institute; Queen Sirikit National Institute of Child Health; Mahidol University; Karolinska Institutet
    Background: The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500, 000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged ≥ 65 years, infants, pregnant women, and individuals of any age with underlying health conditions.Methodology/Principal Findings: Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis.Conclusion/Significances: The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.
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    Post-licensure, phase IV, safety study of a live attenuated Japanese encephalitis recombinant vaccine in children in Thailand
    (2017-01-05) Tawee Chotpitayasunondh; Pornpimol Pruekprasert; Thanyawee Puthanakit; Chitsanu Pancharoen; Auchara Tangsathapornpong; Peninnah Oberdorfer; Pope Kosalaraksa; Olarn Prommalikit; Suwimon Tangkittithaworn; Phirangkul Kerdpanich; Chonnamet Techasaensiri; Joanna Korejwo; Sunate Chuenkitmongkol; Guy Houillon; Queen Sirikit National Institute of Child Health; Prince of Songkla University; Chulalongkorn University; Faculty of Medicine, Thammasat University; Chiang Mai University; Srinagarind hospital; Srinakharinwirot University; Phramongkutklao College of Medicine; Mahidol University; Sanofi Pasteur SA; Sanofi Pasteur
    © 2016 The Authors Background Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children. Methods This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9 months to <5 years in Thailand as a primary (Group 1) or booster (Group 2) vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60 days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30 min after JE-CV administration were also described. Results The median age of participants was 1.1 years in Group 1 and 3.8 years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (<0.1%) in Group 2. There were no cases of Japanese encephalitis reported. No Grade 3 immediate systemic AEs were reported after any JE-CV vaccination. Conclusions Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052).