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Biomedical subjects

Kulkanya Chokephaibulkit

Publications and source records attributed to Kulkanya Chokephaibulkit.

At least 19 recordsLinked to original sources

Efficacy and plasma concentrations of indinavir when boosted with ritonavir in human immunodeficiency virus-infected Thai children.

We evaluated 19 children using 220-300 mg/m of indinavir (IDV) boosted with 100 mg ritonavir (RTV) (n = 12) or full-dose RTV (n = 7). Geometric mean (GM) (90% confidence interval, CI) of IDV Ctrough in children who took IDV with 100 mg RTV (n = 12) was 0.17 (0.06-0.50) mg/L. For children who took IDV with full-dosage RTV, GM (90% CI) was 0.40 (0.10-1.61) mg/L. C2hours were less than 10 mg/L in all subjects. Eighteen children had good virologic response. This report demonstrates that smaller IDV dosages given with RTV provide efficacious plasma concentrations and can be safely used.

Antiretroviral Therapy, Highly Active↗

Serotype distribution and antimicrobial susceptibility of S. pneumoniae causing invasive disease in Thai children younger than 5 years old, 2000-2005.

In order to predict the potential benefit of pneumococcal conjugate vaccines (PCV), we evaluated the serotype coverage of the 7-, 9-, 11- and 13-valent PCV over the isolates causing invasive pneumococcal disease (IPD) in Thai children. One hundred and fifteen Streptococcus pneumoniae isolates from sterile sites in children younger than 5 years old between 2000 and 2005 were serotyped. The coverages of 7-, 9-, 11-, and 13-valent PCV were 69%, 73.8%, 73.8% and 85.7% in children younger than 2 years, and 73.9%, 77.4%, 77.4% and 87.8% in children younger than 5 years of age, respectively. 69.6% and 22.6% of the isolates were non-susceptible to penicillin and cefotaxime. 7-valent PCV covered 89% and 100% of penicillin and cefotaxime non-susceptible isolates.

Cefotaxime↗

Pharmacokinetics of nevirapine in HIV-infected children receiving an adult fixed-dose combination of stavudine, lamivudine and nevirapine.

OBJECTIVE: To evaluate the steady state pharmacokinetics of nevirapine (NVP) in HIV-infected children receiving a fixed-dose combination of stavudine, lamivudine and NVP. METHODS: This cross-sectional study enrolled 34 children (18 girls) who had received GPO-VIR S30 (30 mg stavudine, 150 mg lamivudine and 200 mg NVP) for at least 8 weeks. Tablets were divided into quarter fractions (1/4, 1/2, 3/4 or 1 tablet) to attain the NVP dosages of 120-200 mg/m every 12 h. Plasma NVP levels were measured at predose, and at 2 and 6 h after drug administration. RESULTS: The median age was 8.4 years (range, 3-15). Median CD4 lymphocyte count and percentage at study entry was 576 x 10 cells/l and 20.25%, respectively. The median pharmacokinetics parameters were area under the curve at 12 h, 78.4 h x mug/ml; minimum plasma drug concentration, 5.98 microg/ml; plasma half-life, 25.5 h; apparent oral clearance, 0.079 l/kg per h; and volume of distribution, 2.95 l/kg. Only one child had a minimum plasma drug concentration < 3.4 microg/ml (2.57 microg/ml). Of the 13 children who received GPO-VIR as their first-line regimen, 12 had plasma HIV-1 RNA < 400 copies/ml at 6-18 months, with a median CD4 lymphocyte increase of 216 and 433 x 10 cells/l at 6 and 12 months of treatment, respectively. CONCLUSIONS: The administration of GPO-VIR S30 fixed-dose combination tablets in fractions or as a whole tablet to children resulted in appropriate NVP exposure and satisfactory virological and immunological benefit. This finding confirms the effectiveness of using a fixed-dose combination as a "transitional option" while waiting for a paediatric fixed-dose combination drug formulation.

Adolescent↗

Lack of resistant mutation development after receiving short-course zidovudine plus lamivudine to prevent mother-to-child transmission.

A short-course regimen of zidovudine plus lamivudine starting from 34 weeks' gestation in pregnant women to prevent mother-to-child HIV infection, and discontinued after delivery, was evaluated for the development of resistance at 6 weeks postpartum. No resistant mutation was found in 32 women. One of the three infected infants carried the M184V and K219Q mutations.

Anti-HIV Agents↗

A variant in the CD209 promoter is associated with severity of dengue disease.

Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells. Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 x 10(-7)) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 x 10(-6)). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies.

Cell Adhesion Molecules↗

A child with avian influenza A (H5N1) infection.

Human infections with avian influenza viruses can be severe and may be harbingers of the evolution of a pandemic strain. We present a patient in Thailand who was infected with influenza A (H5N1) virus. Prominent features included the progression from fever and dyspnea to the acute respiratory distress syndrome in a short period, lymphopenia and thrombocytopenia. Establishing the diagnosis for this patient increased public awareness of the virus and was soon followed by a halting of poultry-to-human transmission. On the basis of available data, any child with suspected avian influenza infection should be treated with oseltamivir.

Child↗

Hospital-based epidemiologic survey of malignancies in children infected with human immunodeficiency virus in Thailand.

To determine the incidence and spectrum of malignancies in human immunodeficiency virus-infected children, we surveyed 48 hospitals in Thailand between 1996 and 2000. There were 23 children (14 boys and 9 girls; average age at diagnosis of malignancy, 4.2 years), and the incidence rate was 0.6 per 1000 person-years. The most common malignancy was lymphoma (87.0%). The prognosis was poor.

AIDS-Related Opportunistic Infections↗

Influenza A H5N1 replication sites in humans.

Tissue tropism and pathogenesis of influenza A virus subtype H5N1 disease in humans is not well defined. In mammalian experimental models, H5N1 influenza is a disseminated disease. However, limited previous data from human autopsies have not shown evidence of virus dissemination beyond the lung. We investigated a patient with fatal H5N1 influenza. Viral RNA was detected by reverse transcription-polymerase chain reaction in lung, intestine, and spleen tissues, but positive-stranded viral RNA indicating virus replication was confined to the lung and intestine. Viral antigen was detected in pneumocytes by immunohistochemical tests. Tumor necrosis factor-? mRNA was seen in lung tissue. In contrast to disseminated infection documented in other mammals and birds, H5N1 viral replication in humans may be restricted to the lung and intestine, and the major site of H5N1 viral replication in the lung is the pneumocyte.

Child↗

Salmonella meningitis and antimicrobial susceptibilities.

Meningitis caused by Salmonella species is not uncommon in many developing countries. Patients suspected of bacterial meningitis who were admitted to Siriraj Hospital were enrolled in this study during 1986-2001. There were only 19 cases of Salmonella meningitis. Salmonella serogroup D ranked first, followed by serogroup C, serogroup B and then serogroup H. Most patients were children under 1 year of age. The antimicrobial susceptibility pattern for Salmonella meningitis may provide a guideline for the selection of appropriate drug treatment.

Adolescent↗

Bacteremia and antimicrobial susceptibilities in HIV-infected patients at Siriraj Hospital.

Bacterial infections in human immunodeficiency virus (HIV) infected patients may frequently develop into septicemia. Our study evaluated the bacterial pathogens isolated from hemocultures of HIV-infected patients at Siriraj Hospital and their antimicrobial susceptibility tests. The percentages of positive hemocultures were 24.64, 21.38, 23.88, and 28.46% in 1996, 1997, 1998, and 1999, respectively. Salmonella spp was the most pathogen isolated, followed by Escherichia coil (10.93%), Staphylococcus aureus (8.2%), coagulase-negative staphylococci (6.56%), nonfermentative gram-negative rods (6.01%), Pseudomonas aeruginosa (5.46%), Klebsiella pneumoniae (4.37%), and Enterobacter spp (4.37%). Salmonella, serogroup C was the most frequently isolated serogroup. It was sensitive to amoxicillin/clavulanate in 100%, ampicillin/sulbactam in 89%, cefazolin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, imipenem, gentamicin, amikacin, netilmycin, ofloxacin, and ciprofloxacin in 100%. The changing spectrum of bacteria and antimicrobial susceptibility patterns in HIV-1 infected patients may provide a guideline for the selection of appropriate drugs for treatment.

AIDS-Related Opportunistic Infections↗

Pneumococci: drug susceptibilities and preliminary epidemiological studies by penicillin binding protein genotyping.

A collection of 307 pneumococcal isolates form 84 children and 223 adults admitted to Siriraj Hospital were separated into two groups, penicillin-susceptible (PSSP) and penicillin-nonsusceptible (PNSP). Each group was tested for susceptibilities to 12 drugs (cefuroxime, amoxicillin, chloramphenicol, tetracycline, cefotaxime, ceftriaxone, imipenem, meropenem, ciprofloxacin, ofloxacin, erythromycin and co-trimoxazole). PSSP were susceptible to cefuroxime (87.5%), amoxicillin (100%), chloramphenicol (84.7%), tetracycline (45.8%), cefotaxime (99%), ceftriaxone (99%), imipenem (99%), meropenem (100%), ciprofloxacin (76%), ofloxacin (99%), erythromycin (94.8%) and co-trimoxazole (61.5%). PNSP were resistant to most drugs, except for amoxicillin (99%), ofloxacin (99%) and ciprofloxacin (86.3%). Twenty-two pneumococcal isolates belonging to the three most common serotypes (6, 19, 23) were randomly selected for studies of the pbp2b gene with RFLP. There were 7 distinct pbp2b RFLP patterns. RFLP pattern 1 was the most predominant resistant pattern. The RFLP pattern 2 was found only in PSSP.

Adolescent↗

Dyslipidemia and lipodystrophy in HIV-infected Thai children on highly active antiretroviral therapy (HAART).

BACKGROUND: Previous cross sectional studies revealed that dyslipidemia occurs in 50-70% of children receiving highly active antiretroviral therapy (HAART). However, there is no information in children in developing countries where children may have a different nutritional status. OBJECTIVE: To evaluate the incidence and associated risk factors of dyslipidemia following HAART in HIV-infected Thai children. The occurrence of clinical lipodystrophy among these children was also evaluated. MATERIAL AND METHOD: Twenty-three HIV-infected children who initiated HAART from "Access to Care Program" sponsored by MOPH around October 2001. Non-fasting blood tests for lipid profile were performed at enrollment and every 6 months. Triglyceride level was not analysed due to a non-fasting condition. The assessment of clinical lipodystrophy was done every 1-2 months. RESULTS. As of October 2003, 19 (83%) children experienced dyslipidemia. There were 10, 13, 5, and 8 children who had dyslipidemia at 6, 12, 18, and 24 months of HAART The mean total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL) tended to increase over time while the children were on HAART: There was a correlation of elevated total cholesterol and CD4 percentage gain particularly at 18-24 months of treatment (r = 0.596, p = 0.007). Two children developed peripheral lipoatrophy. There were no dyslipidemia-associated risk factors identified. Most of the children had transient abnormal lipid profile. There were only 3 children that had persistent abnormality throughout the 24 months of HAART CONCLUSION: Dyslipidemia was found from 6-12 months of HAART and were mostly transient over time. Peripheral lipoatrophy were found in 2 children. Further follow-up will elucidate the long-term incidence, the association factors, and clinical consequences.

Antiretroviral Therapy, Highly Active↗

Effect of antiretroviral therapy in human immunodeficiency virus-infected children.

BACKGROUND: The appropriate timing of antiretroviral (ARV) therapy initiation in children with human immunodeficiency virus (HIV) infection has been uncertain. There was evidence of poorer outcome in adults who initiated treatment at lower baseline CD4 cell count. However, early initiation may not be possible in resource-limited setting and would increased risk of long term side effects and non-adherence. OBJECTIVE: To elucidate the outcome of HIV-infected children who ARV treatment was initiated at different disease stages. MATERIAL AND METHOD: Data from medical records of HIV-infected children who had been followed at Infectious Disease Division, Department of Pediatric Siriraj Hospital were retrospectively reviewed. Clinical response and outcome data were analyzed. RESULTS: From September 1996 to March 2004, there were 200 patients with a median age at treatment initiation of 38 (2-175) months. The median duration of follow up period was 26 (1-91) months. The median baseline CD4 cell count was 545 (2-5016) cells/mm3. The median baseline CD4 percentage was 14.25 (0.11-60). Monotherapy or dual nucleoside reverse transcriptase inhibitor (NRTI) regimens were initiated in 134 (67%), and HAARTwas initiated in 66 (33%) patients. The survival rate in patients who initiated with HAART tended to be better than those initiated with dual NRTI regimens but salvaged appropriately (p=0.2377). The survival rate in those initiated treatment at baseline CD4 > or = 15% was better than those initiated at baseline CD4 < 15% (p=0.0471). CONCLUSION: Initiation of ARV treatment at CD4 more than 15% resulted in a better survival rate than at CD4 below 15%. Initiation with HAART regimen tended to improve survival and resulted in higher CD4 gain especially in cases with baseline CD4< 15%.

Adolescent↗

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.

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/mm3 (21.4%). The z-scores for weight and height increased after 4-8 months of treatment, and by the 24th 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 24th 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.

Developing Countries↗

Diagnosis disclosure in HIV-infected Thai children.

BACKGROUND: Increasing number of children with perinatally acquired HIV-infection are now surviving into school age and adolescence. Disclosure of diagnosis to these children has become an important clinical issue. Clinical reports and studies from other countries suggest that a significant number of these children have not been told of their HIV status. The objective of this study was to assess diagnosis disclosure status of perinatally acquired HIV-infected Thai children. MATERIAL AND METHOD: Primary caregivers of 96 HIV-infected children aged 5 years and older were interviewed to assess the child disclosure status and the caregivers reasons to disclose or not to disclose the diagnosis to the child. The disclosed children were also interviewed to assess perception of their illness. RESULTS: Nineteen of 96 children (19.8%) had been told of their HIV diagnosis by their caregivers. The mean age of the disclosed children was 9.6 years. Eighty-four percent of the disclosed children reported perception of their illness as having HIV infection or AIDS. Common reasons for non-disclosing were concerns that the child was too young, that the child might be psychologically harmed, and that the child could not keep the secret. Of 77 non-disclosing caregivers, 54 reported that they plan to disclose HIV status to the children in the future. CONCLUSION: This study demonstrates that diagnosis disclosure was made in only 1/5 of HIV-infected children, and that most of the caregivers were reluctant in disclosing serostatus to the child. Development of an appropriate guideline for assisting the caregivers and the children to deal with the difficult disclosure process is needed.

Adolescent↗

Evaluation of guideline for treatment of febrile neutropenia in pediatric cancer at Siriraj Hospital.

BACKGROUND: Febrile neutropenia (FN) is a common and important clinical problem in pediatric cancer. Our Institution has developed a clinical practice guideline (CPG) for treatment of FN to assist the clinicians taking care of these patients. OBJECTIVE: To evaluate characteristics of FN, sources and causative agents of infection, applicability and effectiveness of the CPG, and factors that associated with response to treatment. MATERIALS AND METHODS: The medical records of patients with FN that had completed data from September, 2003 to May, 2005 were reviewed and analysed. RESULTS: A total of 148 FN episodes in 90 patients were analysed. The predominant underlying malignancy was acute leukemia. About 50% had absolute neutrophil count (ANC) less than 100 cells/mm3 at the beginning and at reassesment on day 3 of treatment. The causes of infection with microbiological confirmation was 25%. Urinary tract infection was the predominant source of infection and gram negative bacteria was the predominant causative agent. Sixty-two percents responded to initial treatment without changing of antibiotics. Of all episodes, 91.2% were able to complete treatment according to the CPG. The mortality rate was 1.4%. ANC of less than 100 cell/mm3 on day 3 of treatment was the significant risk factor for prolonged duration of fever and unresponsiveness to low risk regimen of antibiotics. ANC of less than 100 cell/mm3 on day 3, having hematologic malignancies, and recurrent fever were associated risks for the need for antifungal agent or referral to infectious diseases specialist or death. The pretreatment ANC more than 100 cells/mm3 was a significant predictor for the responsiveness to low risk regimen without recurrent fever. CONCLUSION: Our CPG could practically be applied in FN patients and resulted in low mortality rate.

Child↗

Catch-up vaccination against Haemophilus influenzae type b in human immunodeficiency virus-infected Thai children older than 2 years old.

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 microg/ml). At 6 months after a single dose of tetanus-conjugated Hib vaccination, 67% developed anti-PRP >/=0.15 microg/ml, however, only 33% developed titer of >/=1 microg/ml. Four of seven (57%) with anti-PRP 0.15-0.99 microg/ml at baseline were boosted to the titer of >/=1 microg/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.

Antibodies, Bacterial↗

Avian influenza virus infection of children in Vietnam and Thailand.

Influenza viruses from chickens (H5N1) have caused outbreaks in children from both Vietnam and Thailand in 2004. All infected patients presented with fever and cough. Striking laboratory findings included leukopenia and thrombocytopenia. All children who developed progressive pneumonia with acute respiratory distress syndrome died. However, very few children received antiviral therapy.

Adolescent↗