Pagakrong Lumbiganon

Clinical manifestations of melioidosis in children.

Fifty-five children with culture-proved melioidosis treated at Srinagarind Hospital from 1979 to 1993 were retrospectively reviewed. Twenty patients had septicemia and 35 patients had localized infection. Eleven patients (55%) in the septicemic group had underlying diseases but none in the localized infection group. In the septicemic patients the most common organ involvement was the lung (75%). Shock was present in 45% and the case fatality rate was very high (60%). In localized melioidosis suppurative parotitis was the most common manifestation (40%). Other common infections included skin and subcutaneous abscesses and lymphadenitis. There was no shock or death in this group.

Outcomes of antiretroviral therapy in children in Asia and Africa: a comparative analysis of the IeDEA pediatric multiregional collaboration.

Background:We investigated 18-month incidence and determinants of death and loss to follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. Methods:HIV-infected children (positive polymerase chain reaction <18 months or positive serology ≥18 months) from International Epidemiologic Databases to Evaluate AIDS cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of 2 failure types: death and loss to follow-up (>6 months). Findings:Data on 13,611 children, from Asia (N = 1454), East Africa (N = 3114), Southern Africa (N = 6212), and West Africa (N = 2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East Africa, 5.4% in Asia, 5.7% in Southern Africa, and 7.4% in West Africa (P = 0.01). Age < 24 months, World Health Organization stage 4, CD4 < 10%, attending a private sector clinic, larger cohort size, and living in West Africa were independently associated with poorer survival. The adjusted risk of loss to follow-up was 4.1% in Asia, 9.0% in Southern Africa, 14.0% in East Africa, and 21.8% in West Africa (P < 0.01). Age < 12 months, nonnucleoside reverse transcriptase inhibitor I–based ART regimen, World Health Organization stage 4 at ART start, ART initiation after 2005, attending a public sector or a nonurban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East Africa or West Africa were significantly associated with higher loss to follow-up. Conclusions:Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at the program level.

Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks.

Objectives: To assess the 48-week efficacy, safety, pharmacokinetics, and resistance of double boosted protease inhibitors (PI), saquinavir (SQV), and lopinavir/ritonavir (LPV/r), in children who have failed nucleoside reverse transcription inhibitors /non-nucleoside reverse transcription inhibitors-based regimens. Methods: Fifty children at 2 sites in Thailand were treated with standard dosing of SQV and LPV/r. CD4, HIV-RNA viral load (VL), plasma drug concentrations and safety laboratory evaluations were monitored. Virologic failure was defined as having 2 consecutive VL >400 copies/mL after week 12 of therapy. Intention to treat analysis was performed. Results: Baseline data were a median age of 9.3 years (interquartile range [IQR]: 7.1–11.2), Center for Disease Control and Prevention (CDC) classification N:A:B:C 4%:14%:68%:14%, VL 4.8 log10 (IQR: 4.5–5.1), CD4 7% (IQR: 3–9.5). At 48 weeks, 3 had died of bacterial infection but no cases had progressed CDC classification. Median CD4% rise was 9 (IQR: 5–16) and median HIV RNA reduction was −2.8 log10 (IQR: −3.2 to −1.4), both P < 0.001. Thirty-nine (78%) and 32 (64%) children had VL <400 and <50 with significant differences between the 2 sites. Five children (10%) had VL failure as a result of poor adherence to the drug regimen but no one had major PI mutations. Median serum cholesterol and triglyceride increased significantly (+35 mg/dL, +37 mg/dL, respectively, both P < 0.001). Mean minimum plasma concentrations (Cmin) of LPV and SQV were 4.6 and 1.24 mg/L, respectively. Conclusions: Double boosted SQV/LPV/r resulted in significant CD4 rise and VL decline at 48 weeks. Hyperlipidemia was common. Cmin of both PIs exceeded therapeutic concentrations. Poor adherence caused failure in 10%. No major PI mutations were found.

Survival of HIV-Infected Children: A Cohort Study From the Asia-Pacific Region

Background:Combination antiretroviral therapy (ART) has been used for HIV-infected children in many Asian countries since 2002. This study describes survival outcomes among HIV-infected children in a multicenter regional cohort in Asia. Patients and Methods:Retrospective and prospective data collected through March 2009 from children in 5 countries enrolled in TREAT Asias Pediatric HIV Observational Database were analysed. Multivariate Cox proportional hazard models were used to assess factors associated with mortality in children who received ART. Results:Among 2280 children, 1752 (77%) had received ART. During a median follow-up of 3.1 years after ART, 115 (6.6%) deaths occurred, giving a crude mortality rate of 1.9 per 100 child-years [95% confidence interval (CI): 1.6 to 2.4]. The mortality rate was highest in the first 3 months of ART (10.2 per 100 child-years; 95% CI: 7.5 to 13.7) and declined after 12 months (0.9 per 100 child-years; 95% CI: 0.7 to 1.3). Those with a low recent CD4 percentage, who started ART with lower baseline weight-for-age Z score, or with WHO clinical stage 4 had an increased risk of death. Of 528 (23%) children who never received ART, 36 (6.8%) died after presenting to care, giving a crude mortality rate of 4.1 per 100 child-years (95% CI: 3.0 to 5.7), with a lost-to-program rate of 31.5 per 100 child-years (95% CI: 28.0 to 35.5). Conclusions:The high mortality during the first 3 months of ART and in those with low CD4 percentage support the implementation of early diagnosis and ART initiation.

Cohort profile: the TREAT Asia pediatric HIV observational database.

This cohort profile focuses on the Therapeutic Research Education and AIDS Training (TREAT) Asia Pediatric HIV Observational Database (TApHOD) a collaborative cohort of HIV-infected children in the Asia-Pacific region. It describes many aspects of this cohort including: how it was established the objectives the sample characteristics of participating sites patient characteristics measurements findings attrition strengths and weaknesses and funding information.

Immunologic and virologic failure after first-line NNRTI-based antiretroviral therapy in Thai HIV- infected children

BackgroundThere are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined the incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART.MethodsAntiretroviral (ART)-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%≥25%. IF was defined as persistent decline of ≥5% in CD4% in children with CD4%<15% at baseline or decrease in CD4 count ≥30% from baseline. VF was defined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF.Results107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. Baseline data were median (IQR) age 6.2 (4.2-8.9) years, CD4% 7 (3-15), HIV-RNA 5.0 (4.9-5.5) log10copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively.At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and CD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of children had immune recovery (CD4%≥25%) and 75% of children had HIV-RNA <1.7log10copies/ml.Thirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in the first 24 and 48 weeks respectively.Only 1 (0.9%) child experienced IF within 96 weeks and the sensitivity (95%CI) of IF to VF was 4 (0.1-20.4)% and specificity was 100 (93.9-100)%.ConclusionImmunologic failure, as defined here, had low sensitivity compared to VF and should not be recommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to detect early treatment failure.Trial RegistrationClinicaltrials.gov identification numberNCT00476606

Antiretroviral therapy outcomes of HIV-infected children in the TREAT Asia pediatric HIV observational database.

Introduction:We report responses to combination antiretroviral therapy (cART) in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database. Methods:Children included were those who had received cART (ie, ≥3 antiretrovirals) at <18 years. The analysis was intention-to-treat by the first cART regimen. Median values are provided with interquartile ranges; hazard ratios (HRs) with 95% confidence intervals. Results:Of the 1655 children included, 50.4% were male, with a median age at cART of 7.0 (3.9-9.8) years and CD4 of 8% (2.0%-15%); 92.5% were started on an NNRTI; median duration of follow-up was 2.9 (1.4-4.6) years. Loss-to-follow-up and death rates were 4.2 (3.7-4.8) and 2.1 (1.7-2.5) per 100 person-years, respectively. At 36 months, median CD4 was 26% (21%-31%); 81% of those with viral load (n = 302) were <400 copies per milliliter. Children who reached CD4 ≥25% within 5 years were more likely to be females (HR: 1.4; 1.2-1.7), start before 18 months old (HR: 3.8; 2.4-6.2), lack a history of monotherapy/dual therapy (HR: 1.7; 1.4-2.5), and have a higher baseline CD4 (per 10% increase: HR: 2; 1.9-2.2). Conclusions:These data underscore the need for early diagnosis and cART initiation to preserve immune function.

Neonatal melioidosis: a report of 5 cases

Melioidosis, caused by Pseudomonas pseudomallei, occurs in tropical areas and is diagnosed mostly in adults. In Khon Kaen, a province of northeast Thailand, five cases of infantile melioidosis were managed at Srinagarind Hospital. The patients specimens were submitted to microbiologic and serologic examination for P. pseudomallei demonstrated by indirect hemagglutination. Possible modes of transmission such as environment, perinatal exposure and venereal transmission were investigated.

Serological response to trivalent inactive influenza vaccine in HIV-infected children with different immunologic status

Influenza vaccination is usually recommended for HIV-infected children. One hundred and twenty seven HIV-infected and twenty-one HIV-uninfected children aged ≥6 months to <18 years, all of whom were naïve to influenza vaccine, were enrolled to receive an influenza Trivalent Inactivated Vaccine (TIV). In the HIV group, the post-vaccination immune response (geometric mean titer, seroconversion and seroprotection rates) correlated with their immunological status before vaccination. The HIV-infected children with no immunosuppression had comparable serological response to HIV-uninfected children. For moderately and severely immunosuppressed HIV groups, two doses of TIV resulted in greater serological responses and should be recommended in these groups.

Localized Melioidosis in Children in Thailand: Treatment and Long-term Outcome

Melioidosis, an infection caused by Burkholderia pseudomallei, can present as severe septicemia or localized infection. Data on optimum antibiotic treatment regimen for localized melioidosis in children is limited. This is a report on localized melioidosis in children, regarding clinical presentation, treatment and the long-term outcomes. We reviewed 37 cases of localized melioidosis in children treated between 1994 and 2006 and followed up them prospectively until 1 October 2007. The two most common presentations were skin/soft tissue infections and suppurative parotitis. Oral eradication antibiotics after initial parenteral therapy included trimetroprim-sulfamethoxazole (10 patients) and trimetroprim-sulfamethoxazole in combination with doxycycline (four patients). Patients who did not get any parenteral antibiotics for B. pseudomallei were treated with oral trimetroprim-sulfamethoxazole (10 patients) and trimetroprim-sulfamethoxazole in combination with doxycycline (one patient). No adverse effects were reported. We were able to follow-up 32 patients, all recovered except one patient reported a history of possible relapse.