First case report of brucellosis in a child in Thailand.

Brucellosis is uncommon in children. In Thailand, there have been only seven adult cases reported, all with Brucella melitensis. We describe here the first reported pediatric case of brucellosis in Thailand. A 12-year old boy presented with prolonged fever for one month, pancytopenia, pneumonia and peritonitis. The blood culture grew out Brucella melitensis. He responded well to combination therapy consisting of doxycycline and gentamicin. He recovered fully without relapse during the 6 month follow-up.

Development of a diagnosis disclosure model for perinatally HIV-infected children in Thailand.

While disclosure of HIV status to perinatally HIV-infected children has become an increasingly important clinical issue, specific disclosure guidelines are lacking. We developed a pediatric HIV diagnosis disclosure model to support caretakers. All HIV-infected children greater than 7-years-old at two participating hospitals in Bangkok, Thailand, and their caretakers, were offered disclosure according to the 4-step protocol: (1) screening; (2) readiness assessment; (3) disclosure; and (4) follow-up. Disclosure occurred after agreement of both providers and caretakers. Among 438 children who were screened, 398 (89%) were eligible. Readiness assessment was completed for 353 (91%) of eligible children and 216 (61%) were determined ready. Disclosure was done for 186 children. The mean age at eligibility screening was 10.5 years (range: 6.8-15.8 years); the mean age at disclosure was 11.7 years (range: 7.6-17.7 years). The mean duration between eligibility screening and disclosure was 15.2 months. There were no significant negative behavioral or emotional outcomes reported in children following disclosure. This HIV diagnosis disclosure model was feasible to implement and had no negative outcomes. As the time for preparation process was over 1 year for most cases, the disclosure process can be initiated as early as age 7 to allow enough time for disclosure to be completed by the age of adolescence.

Once- versus twice-daily lopinavir/ritonavir tablets in virologically suppressed, HIV-infected, treatment-experienced children: comparative pharmacokinetics and virological outcome after switching to once-daily lopinavir/ritonavir.

OBJECTIVES: Data on lopinavir/ritonavir tablets administered once daily in children are limited. We compared the pharmacokinetics (PK) of lopinavir/ritonavir twice daily versus once daily in virologically suppressed, HIV-infected children, and assessed the virological outcome, at 48 weeks, in children receiving the regimen of lopinavir/ritonavir once daily. PATIENTS AND METHODS: HIV-infected children receiving a twice-daily lopinavir/ritonavir-based regimen and with an HIV-1 RNA viral load (VL) <40 copies/mL for at least 3 months were enrolled. Intensive steady-state 12 h blood sampling for PK assessment was performed at enrolment. Immediately afterwards, the lopinavir/ritonavir dose was changed to once daily with the equivalent daily dose, and intensive steady-state 24 h blood sampling was repeated 2 weeks later. If the lopinavir C(trough) was <1.0 µg/mL, the lopinavir/ritonavir dose was increased by 20%-30% and C(trough) measurement repeated. CD4 cell counts and VL were determined at baseline and at 12, 24 and 48 weeks. RESULTS: Twelve children were enrolled. The median age was 13.1 years. Lopinavir AUC(0-24) following twice-daily and once-daily dosing was 169.7 (124.0-200.8) and 167.1 (95.1-228.1) µg · h/mL, respectively. Seven children, including all six concomitantly receiving efavirenz, had a C(trough) <1.0 µg/mL with once-daily lopinavir/ritonavir dosing, and four of seven children had a C(trough) <1.0 µg/mL after dose adjustment. All children maintained virological suppression throughout the 48 week period. CONCLUSIONS: Lopinavir/ritonavir-based once-daily regimens could simplify therapy in children/adolescents with virological control, but a lower lopinavir C(trough) was evident. Further efficacy studies of lopinavir/ritonavir once daily in children are necessary before routinely recommending this dosing strategy.

The clinical features, risk of prolonged hospitalization and household infections of hospitalized children for pandemic 2009 influenza A (H1N1) virus infection in Thailand.

OBJECTIVE: To evaluate the clinical features, risk of prolonged hospitalization, and household infection in Thai children hospitalized with 2009 pandemic influenza A/H1N1 virus (pH1N1). MATERIAL AND METHOD: The authors conducted a retrospective chart review of children hospitalized in four Thai tertiary care hospitals between June 1 and September 30, 2009, with reverse-transcriptase-polymerase-chain-reaction confirmed pH1N1. Household contact data were obtained by telephone. RESULTS: Pediatric admissions numbered 115, 58 were females (50.4%). Median age was 5.2 (range 0.5 to 15) years. Fifty-one (44.4%) children had underlying diseases, most commonly asthma 17 (14.8%). Median preadmission illness duration was two days (range 1 to 10). Sixty-one (53.0%) children had lymphopenia. Chest X-ray infiltration was detected in 89 (77.4%) children. Oseltamivir was prescribed in 104 (90.4%) children; 47(45.2%) within 48 hours of illness. 70 (60.9%) children received antibiotics. The median hospitalization was three days (range 1 to 94). Independent (multivariate analysis) factors associated with prolonged hospitalization (> or = 7 days) were aged five to nine years (OR 7.4; 95% CI 1.1-48.9, p = 0.037) and having an underlying disease (OR 5.9; 95% CI 1.5-23.3, p = 0.01). Five (4.3%) children required mechanical ventilation; two (1.7%) children died. Household data showed that 63 of 109 (57.8%) patients had contact with a suspected or confirmed pH1N1 case. There were 39 (15.7%) of 249 household contacts who were probable secondary cases: 23 suspected and 16 confirmed pH1N1 of whom 25 (64.1%) were aged < or = 18 years. CONCLUSION: Most pH1N1 infected hospitalized children had pneumonia, an uneventful short hospitalization, and a low in hospital mortality. Half of the patients were household acquired. Secondary household cases affected mostly children.

Immunogenicity of a human rotavirus vaccine (RIX4414) after storage at 37 °C for seven days.

AIM: The lyophilized formulation of the human rotavirus vaccine, RIX4414 (RotarixTM), is recommended to be stored at 2°C-8°C for optimal immunogenicity. In some settings with inadequate infrastructure for vaccine storage, unforeseen circumstances may cause cold chain breakage, resulting in the vaccine to be left at ambient temperatures. This study evaluated the heat stability of lyophilized RIX4414 vaccine in terms of immunogenicity when stored at tropical room temperature (37 °C) for 7 days before reconstitution. RESULTS: There was no statistically significant difference detected between RIX4414 vaccine stored at 2 °C-8 °C (Group RIX4414_control, n = 171) and that stored at 37 °C for 7 days (Group RIX4414_37 °C, n = 47) in terms of seroconversion rate and vaccine take. The anti-rotavirus IgA seroconversion rate 2 months post-Dose 2 was 84.7% (95% CI: 78.1%-90%) and 87.8% (95% CI: 73.8%-95.9%) in Groups RIX4414_control and RIX4414_37 °C, respectively. None of the 25 infants in placebo group seroconverted. The vaccine take in the respective vaccine groups were 88% (95% CI: 82.1%-92.5%) and 93.5% (95% CI: 82.1%-98.6%) and Geometric Mean Concentrations (GMCs) were 134.4 U/mL (95% CI: 104.5-172.9) and 163.7 U/mL (95% CI: 98.9-271.1). METHODS: Healthy infants aged 6-12 weeks, received two oral doses of either the RIX4414 vaccine stored at 2 °C-8 °C, RIX4414 vaccine stored at 37 °C for 7 days or placebo, according to a 0, 2 month schedule. Seroconversion rates in terms of anti-rotavirus IgA antibody levels (cut off: ≥ 20 U/mL by ELISA), anti-rotavirus IgA antibody GMCs and vaccine take were calculated 2 months post-Dose 2. CONCLUSION: Lyophilized RIX4414 vaccine stored at 37°C for 7 days before reconstitution has similar immunogenicity as the vaccine stored at 2 °C-8 °C. These results supported the use of RIX4414 in settings where the vaccine might be exposed to higher than the recommended storage temperatures.

Boosted p24 antigen assay for early diagnosis of perinatal HIV infection.

OBJECTIVE: The authors evaluated the accuracy of in-house boosted-p24 antigen assay for diagnosis of perinatal HIV infection. MATERIAL AND METHOD: The author has retrospectively reviewed the medical records of infants born to HIV-positive mothers. The infants were tested for boosted-p24 antigen assay at the age of 1-2 months and 4-6 months. HIV infection was defined as positive anti-HIV at the age 18 months or older, or had positive HIV-PCR with clinical signs and symptoms compatible with HIV/AIDS. RESULTS: There were 168 infants included in this review and six were HIV-infected. The boosted-p24 antigen assay had the sensitivity, specificity, positive predictive value, and negative predictive value of 33.33%, 98.27%, 50%, and 95.8%, respectively at 1-2 month-old, and 100%, 98.27%, 71.43%, and 100%, respectively at 4-6 month-old. CONCLUSION: Boosted-p24 antigen assay could be a cheaper alternative test to help diagnosis of perinatal HIV infection in infants. The test was very accurate when performed at 4-6 months.

Treatment of cytomegalovirus (CMV) retinitis with intravitreous ganciclovir in HIV-infected children.

OBJECTIVES: To evaluate the efficacy, visual outcomes, and complications of intravitreous ganciclovir treatment in cytomegalovirus (CMV) retinitis in HIV-infected children. MATERIAL AND METHOD: The medical records of HIV-infected children who were screened for CMV retinitis from February 2002 to February 2005 were reviewed. The children with CD4+ < 15%, or with clinical category C would have complete ophthalmic examination every 3 months. Ganciclovir (4 mg/0.04 ml) was administered intravitreously to the eye with CMV retinitis every 2 weeks under general anaesthesia. After injection, fundi were examined immediately, 1 day, 14 days and every 2 weeks until the lesions were stable. RESULTS: Six (9 eyes) out of 45 children (13%) aged 2-12 years were found to have CMV retinitis. All CMV retinitis lesions were "cheese and ketchup like" (retinal hemorrhage and exudate) lesions and presented in the posterior pole. Bilateral CMV retinitis were found in 3 children. Intravitreous ganciclovir was injected in 4 children (5 eyes). The average number of intravitreous injections for each patient was 5.6 (3-7) times. All of the children received antiretroviral therapy and 3 children also received intravenous ganciclovir CMV retinitis lesions were improved in every eye. The visual acuity (VA) remained stable in 4 eyes, but endophthalmitis developed in one eye a few days after injection. The average duration of follow-up was 13.5 months (3-23 months). CONCLUSION: CMV retinitis was not uncommon. The authors found that intravitreous ganciclovir was effective but may cause complications. This treatment should be considered in a resource-limited setting.

Assessment of bacille Calmette-Guérin vaccine reaction in HIV-exposed Thai infants.

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.

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.

Evaluation of a practical method to assess antiretroviral adherence in HIV-infected Thai children.

The objective of this study was to evaluate a practical method to assess adherence to antiretroviral therapy by observing virological and immunological responses. We conducted a 12-month longitudinal cohort study of 162 HIV-infected Thai children. Adherence was assessed using 5 methods (self reporting calendar, records of missed doses, pill counts, physician assessment, and an interview questionnaire). CD4 count, percentage and viral load were performed at baseline and at 12 months. Mean adherence rates at 2, 6, and 12 months were 98, 100, and 99% by the calendar method; 98, 100, and 100% by recording missed doses; 96, 96, and 92% by pill count; and 90, 94, and 97% by physician assessment. Poor agreement (kappa < or = 0.1) was found among the methods. There was a statistically significant difference (p = 0.05) in virological response between participants with > or = 95% adherence (0.8 log10) and those with < 95% adherence (0.2 log10) when pill counts were used to assess adherence. In conclusion, despite poor agreement among these tools, a pill count appeared to be the only practical, validated method to differentiate the virological outcome between those who were fully and partially adhere to the treatment regimen.

Recurrent Campylobacter lari bacteremia in X-linked agammaglobulinemia: a case report and review.

X-linked agammaglobulinemia (XLA) is a primary immune deficiency disease with a B-cell defect. We present the first XLA patient who had recurrent Campylobacter lari bacteremia. High dose intravenous immunoglobulin combined with azithromycin once per week, and a complete avoidance of bacterial reservoirs may be helpful for the prevention of C. lari bacteremia.

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.

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.

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.

A randomized study of 3 umbilical cord care regimens at home in thai neonates: comparison of time to umbilical cord separation, parental satisfaction and bacterial colonization.

OBJECTIVE: To compare time to cord separation, parental satisfaction and bacterial colonization, among 3 regimens of cord care at home. STUDY DESIGN: Randomized controlled trial. MATERIAL AND METHOD: Term infants were randomly assigned based on cord care regimens at home: 1) triple dye, 2) alcohol, and 3) no antiseptic agent. Timing of cord separation, and parental satisfaction were evaluated during the first month of age. RESULTS: 185 infants were recruited. Time to cord separation in infants of group I was significantly longer than in group 2 (p = 0.036) and group 3 (p = 0.003). The satisfaction scores of group I were significantly lower than those of group 2 and group 3. 180 culture specimens were performed and positive in all but none had omphalitis. CONCLUSION: Triple dye delayed time to cord separation and was less satisfactory. The authors conclude that using alcohol or dry clean could be alternative ways of umbilical cord care at home.

Developmental screening by the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) in HIV- infected children.

Bayley Scales of Infant Development (BSID) is considered to be a standard test for child development. The test requires experienced evaluator and is time consuming; therefore, it is not easy to apply in busy clinic. The Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) is an easy assessment method that has been demonstrated to correlate with BSID in many studies among normal and developmental delayed children, including in HIV-infected infants. We created a pilot system of CAT/CLAMS assessment applied to 16 HIV-infected infants ages 12-34 months. They were all in the normal range score of developmental quotient (DQ). However, longitudinal follow-up by CAT/CLAMS assessment is needed in these HIV-infected children. When DQ score is below 70 (assuming to be delayed development), the child should be evaluated by BSID. In this way delayed development can be screened easily and early developmental stimulation program can be implemented appropriately.

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%.

The first pediatric case of Staphylococcus aureus with heterogenous resistant to vancomycin endocarditis in Thailand.

Staphylococcus aureus with reduced susceptibility to vancomycin has been reports worldwide. Here we report the first pediatric case of heterogeneous vancomycin intermediate resistance Staphylacoccus aureus (hVISA) causing endocarditis in Thailand. A 4 months old girl with truncus arteriosus type IV and ventricular septal defect developed methicillin-resistant S. aureus (MRSA) bacteremia and endocarditis after total repair operation. The patient did not respond to combination antimicrobial treatment including vancomycin. The strain was susceptible to trimethoprim-sulfamethoxazole and vancomycin by conventional antimicrobial susceptibily test. The vancomycin minimal inhibitory concentration by E-test was 2 microg/ml. The strain was judged to be possible heteroresistant when screening was done by one-point population analysis. The subsequent population analysis and testing for the emergence of mutants with reduced susceptible to vancomycin confirmed that this strain was hVISA. Despite the treatment with vancomycin, amikacin, rifampicin and cotrimoxazole, the patient died. hVISA should be suspected in MRSA infections that were refractory to vancomycin therapy could be due to. The emergence hVISA underscored the importance of the prudent use of antibiotics, the laboratory capacity to identify MRSA and hVISA and proper communication with treating clinicians, and the meticulous infection-control measures to prevent transmission.

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.

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.