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  1. Fong SM, Wong KJ, Fukushima M, Yeo TW
    Clin. Infect. Dis., 2015 Jun 15;60(12):1802-7.
    PMID: 25767257 DOI: 10.1093/cid/civ189
    Melioidosis is an important cause of community-acquired infection in Southeast Asia and northern Australia. Studies from endemic countries have demonstrated differences in the epidemiology and clinical features among children diagnosed with melioidosis. This suggests that local data are needed to determine the risk factors and outcome in specific areas.
  2. Grimwood K, Fong SM, Ooi MH, Nathan AM, Chang AB
    PMID: 28702286 DOI: 10.1186/s41479-016-0006-x
    Improved access to healthcare, vaccines and treatment with antibiotics has reduced global mortality from childhood community-acquired pneumonia. However, as respiratory viruses are responsible for most episodes of pneumonia, important questions remain over who should receive these agents and the length of each treatment course. Worldwide concerns with increasing antibiotic resistance in respiratory pathogens and appeals for more prudent antibiotic prescribing provide further urgency to these clinical questions. Unfortunately, guidelines for treatment duration in particular are based upon limited (and often weak) evidence, resulting in national and international guidelines recommending treatment courses for uncomplicated pneumonia ranging from 3 to 10 days. The advantages of short-course therapy include a lower risk of developing antibiotic resistance, improved adherence, fewer adverse drug effects, and reduced costs. The risks include treatment failure, leading to increased short- or long-term morbidity, or even death. The initial challenge is how to distinguish between bacterial and non-bacterial causes of pneumonia and then to undertake adequately powered randomised-controlled trials of varying antibiotic treatment durations in children who are most likely to have bacterial pneumonia. Meanwhile, healthcare workers should recognise the limitations of current pneumonia treatment guidelines and remember that antibiotic course duration is also determined by the child's response to therapy.
  3. Arrivé E, Ayaya S, Davies MA, Chimbetete C, Edmonds A, Lelo P, et al.
    J Int AIDS Soc, 2018 07;21(7):e25157.
    PMID: 29972632 DOI: 10.1002/jia2.25157
    INTRODUCTION: Disclosure of HIV status to HIV-infected children and adolescents is a major care challenge. We describe current site characteristics related to disclosure of HIV status in resource-limited paediatric HIV care settings within the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

    METHODS: An online site assessment survey was conducted across the paediatric HIV care sites within six global regions of IeDEA. A standardized questionnaire was administered to the sites through the REDCap platform.

    RESULTS: From June 2014 to March 2015, all 180 sites of the IeDEA consortium in 31 countries completed the online survey: 57% were urban, 43% were health centres and 86% were integrated clinics (serving both adults and children). Almost all the sites (98%) reported offering disclosure counselling services. Disclosure counselling was most often provided by counsellors (87% of sites), but also by nurses (77%), physicians (74%), social workers (68%), or other clinicians (65%). It was offered to both caregivers and children in 92% of 177 sites with disclosure counselling. Disclosure resources and procedures varied across geographical regions. Most sites in each region reported performing staff members' training on disclosure (72% to 96% of sites per region), routinely collecting HIV disclosure status (50% to 91%) and involving caregivers in the disclosure process (71% to 100%). A disclosure protocol was available in 14% to 71% of sites. Among the 143 sites (79%) routinely collecting disclosure status process, the main collection method was by asking the caregiver or child (85%) about the child's knowledge of his/her HIV status. Frequency of disclosure status assessment was every three months in 63% of the sites, and 71% stored disclosure status data electronically.

    CONCLUSION: The majority of the sites reported offering disclosure counselling services, but educational and social support resources and capacities for data collection varied across regions. Paediatric HIV care sites worldwide still need specific staff members' training on disclosure, development and implementation of guidelines for HIV disclosure, and standardized data collection on this key issue to ensure the long-term health and wellbeing of HIV-infected youth.

  4. Kosalaraksa P, Boettiger DC, Bunupuradah T, Hansudewechakul R, Saramony S, Do VC, et al.
    J Pediatric Infect Dis Soc, 2017 Jun 01;6(2):173-177.
    PMID: 27295973 DOI: 10.1093/jpids/piw031
    Background.: Regular CD4 count testing is often used to monitor antiretroviral therapy efficacy. However, this practice may be redundant in children with a suppressed human immunodeficiency virus (HIV) viral load.

    Methods: Study end points were as follows: (1) a CD4 count <200 cells/mm3 followed by a CD4 count ≥200 cells/mm3 (transient CD4 <200); (2) CD4 count <200 cells/mm3 confirmed within 6 months (confirmed CD4 <200); and (3) a new or recurrent World Health Organization (WHO) stage 3 or 4 illness (clinical failure). Kaplan-Meier curves and Cox regression were used to evaluate rates and predictors of transient CD4 <200, confirmed CD4 <200, and clinical failure among virally suppressed children aged 5-15 years who were enrolled in the TREAT Asia Pediatric HIV Observational Database.

    Results: Data from 967 children were included in the analysis. At the time of confirmed viral suppression, median age was 10.2 years, 50.4% of children were female, and 95.4% were perinatally infected with HIV. Median CD4 cell count was 837 cells/mm3, and 54.8% of children were classified as having WHO stage 3 or 4 disease. In total, 18 transient CD4 <200 events, 2 confirmed CD4 <200 events, and10 clinical failures occurred at rates of 0.73 (95% confidence interval [95% CI], 0.46-1.16), 0.08 (95% CI, 0.02-0.32), and 0.40 (95% CI, 0.22-0.75) events per 100 patient-years, respectively. CD4 <500 cells/mm3 at the time of viral suppression confirmation was associated with higher rates of both CD4 outcomes.

    Conclusions: Regular CD4 testing may be unnecessary for virally suppressed children aged 5-15 years with CD4 ≥500 cells/mm3.

  5. Chokephaibulkit K, Kariminia A, Oberdorfer P, Nallusamy R, Bunupuradah T, Hansudewechakul R, et al.
    Pediatr. Infect. Dis. J., 2014 Mar;33(3):291-4.
    PMID: 23942457 DOI: 10.1097/INF.0b013e3182a18223
    More perinatally HIV-infected children in Asia are reaching adolescence.
  6. Boettiger DC, Sudjaritruk T, Nallusamy R, Lumbiganon P, Rungmaitree S, Hansudewechakul R, et al.
    J Adolesc Health, 2016 Apr;58(4):451-459.
    PMID: 26803201 DOI: 10.1016/j.jadohealth.2015.11.006
    PURPOSE: About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population.

    METHODS: Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL.

    RESULTS: Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count ≤200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure.

    CONCLUSIONS: Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.

  7. Boettiger DC, Aurpibul L, Hudaya DM, Fong SM, Lumbiganon P, Saphonn V, et al.
    Pediatr. Infect. Dis. J., 2016 May;35(5):e144-51.
    PMID: 26835972 DOI: 10.1097/INF.0000000000001074
    BACKGROUND: Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population.

    METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.

    RESULTS: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.

    CONCLUSION: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.

  8. Aurpibul L, Bunupuradah T, Sophan S, Boettiger D, Wati DK, Nguyen LV, et al.
    Pediatr. Infect. Dis. J., 2015 Jun;34(6):e153-8.
    PMID: 25970117 DOI: 10.1097/INF.0000000000000693
    We determined the prevalence and incidence of liver dysfunction before and after initiation of combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database.
  9. Chang AB, Fong SM, Yeo TW, Ware RS, McCallum GB, Nathan AM, et al.
    BMJ Open, 2019 Apr 24;9(4):e026411.
    PMID: 31023759 DOI: 10.1136/bmjopen-2018-026411
    INTRODUCTION: Early childhood pneumonia is a common problem globally with long-term complications that include bronchiectasis and chronic obstructive pulmonary disease. It is biologically plausible that these long-term effects may be minimised in young children at increased risk of such sequelae if any residual lower airway infection and inflammation in their developing lungs can be treated successfully by longer antibiotic courses. In contrast, shortened antibiotic treatments are being promoted because of concerns over inducing antimicrobial resistance. Nevertheless, the optimal treatment duration remains unknown. Outcomes from randomised controlled trials (RCTs) on paediatric pneumonia have focused on short-term (usually <2 weeks) results. Indeed, no long-term RCT-generated outcome data are available currently. We hypothesise that a longer antibiotic course, compared with the standard treatment course, reduces the risk of chronic respiratory symptoms/signs or bronchiectasis 24 months after the original pneumonia episode.

    METHODS AND ANALYSIS: This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are 'clinical cure' at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.

    ETHICS AND DISSEMINATION: The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children's and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.

    TRIAL REGISTRATION: ACTRN12616000046404.

  10. Iversen OE, Miranda MJ, Ulied A, Soerdal T, Lazarus E, Chokephaibulkit K, et al.
    JAMA, 2016 12 13;316(22):2411-2421.
    PMID: 27893068 DOI: 10.1001/jama.2016.17615
    Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts.
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