Explore the vast range of titles available.

ObjectiveAs children hospitalised with community-acquired pneumonia (CAP) are at risk of persistent chest radiograph (CXR) abnormalities and respiratory sequelae, we investigated factors associated with incomplete CXR resolution at 4 weeks and 12 months post-discharge in children from populations at high-risk of chronic lung disease.DesignSecondary analysis−multicentre, placebo-controlled, randomised controlled trial.Settings and patients324 children aged 3 months to ≤5 years hospitalised with radiographic-confirmed CAP were enrolled from seven hospitals in Australia, New Zealand and Malaysia. After 1–3 days of intravenous antibiotics, then 3 days of oral amoxicillin–clavulanate, they were randomised to extended (13–14 days) or standard (5–6 days) courses of antibiotics.InterventionCXRs were performed at admission, 4 weeks, and 12 months post-discharge and reviewed in a blinded manner.Main outcome measuresRadiographic changes of pneumonia at 4 weeks and 12 months post-discharge compared with admission CXRs.ResultsAmong children with interpretable CXRs, incomplete resolution was seen in 42/253 (17%) at 4 weeks, and 29/212 (14%) at 12 months. Characteristics at admission associated with incomplete CXR resolution at 4 weeks were previous pneumonia hospitalisation (adjusted odds ratio [ORadj])=6.46, 95% confidence interval [CI] 2.21 to 18.85) and increasing age (ORadj=0.60 per-year, 95% CI 0.38 to 0.94). Continuing respiratory symptoms/signs at 4 weeks post-discharge was also associated with incomplete resolution (OR=5.63, 95% CI 2.38 to 13.32). At 12 months, previous pneumonia hospitalisation was associated with persistent incomplete CXR resolution (OR=4.03, 95 % CI 1.25 to 13.02).ConclusionIn high-risk settings, younger age, those with previous pneumonia hospitalisation, or ongoing respiratory symptoms/signs 4 weeks post-discharge from hospitalised CAP may be associated with incomplete CXR resolution. Consequently, follow-up imaging and monitoring may be warranted in these children.

Letter to the Editor Infection

Despite anti-tuberculous treatment (ATT), central nervous system tuberculosis (CNS-TB) still causes permanent neurological deficits and death. To identify prognostic factors, we profiled a prospective cohort of pediatric HIV-negative tuberculous meningitis (TBM) and non-TBM patients. We found significantly increased cerebrospinal fluid (CSF) matrix metalloproteinases (MMPs) and neutrophil extracellular traps (NETs) in TBM patients with neuroradiological abnormalities and poor outcomes. To dissect mechanisms, we used our existing CNS-TB murine model, which shows neutrophil-rich necrotizing pyogranulomas with MMP-9 and NETs colocalizing, as observed in human CNS-TB pathology. Spatial transcriptomic analysis of both human and murine CNS-TB demonstrates a highly-inflamed and neutrophil-rich microenvironment of inflammatory immune responses, extracellular matrix degradation and angiogenesis within CNS-TB granulomas. Murine CNS-TB treated with ATT and MMP inhibitors SB-3CT or doxycycline show significantly suppressed NETs with improved survival. MMP inhibition arms show attenuated inflammation and well-formed blood vessels within granulomas. Adjunctive doxycycline is highly promising to improve CNS-TB outcomes and survival. Graphical abstract

Despite improvements in HIV testing and earlier antiretroviral therapy (ART) initiation in children living with HIV through the years, a considerable proportion start treatment with advanced disease. We studied characteristics of children and adolescents living with HIV and their level of immunodeficiency at ART initiation using data from a multi-country Asian cohort. We included children and adolescents who were ART-naïve and <18 years of age at ART initiation from 2011 to 2020 at 17 HIV clinics in six countries. Incidence rates of opportunistic infections (OIs) in the first two years of triple-drug ART (≥3 antiretrovirals) was also reported. Competing risk regression analysis was performed to identify factors associated with first occurrence of OI. In 2,027 children and adolescents (54% males), median age at ART initiation increased from 4.5 years in 2011–2013 to 6.7 in 2017–2020, median CD4 count doubled from 237 cells/μl to 466 cells/μl, and proportion of children who initiated ART as severely immunodeficient decreased from 70% to 45%. During follow-up, 275 (14%) children who received triple-drug ART as first treatment and had at least one clinic visit, developed at least one OI in the first two years of treatment (9.40 per 100 person-years). The incidence rate of any first OI declined from 12.52 to 7.58 per 100 person-years during 2011–2013 and 2017–2020. Lower hazard of OIs were found in those with age at first ART 2–14 years, current CD4 ≥200 cells/μl, and receiving ART between 2017 and 2020. The analysis demonstrated increasing number of children and adolescents starting ART with high CD4 count at ART start. The rate of first OI markedly decreased in children who started ART in more recent years. There remains a clear need for improvement in HIV control strategies in children, by promoting earlier diagnosis and timely treatment.

Background: With the increasing cases of multi-resistant organism infection, Antimicrobial Stewardship Programs (ASP) is an important tool in combating this rising challenges. The objective of this study is to review whether the approach of the reduction in usage of second and third generation cephalosporin group antibiotics reduces the incidence of ESBL E.coli and ESBL Klebsiella pneumoniae (KP) cases in Sabah Women and Children Hospital (SWACH) from 2021 until 2023. Methods: After discussion with the head of clinical services, the preferred empirical antibiotic of respective unit was switched to ampicilin-sulbactam or amoxicillin clavulanic acid instead of second or third generation cephalosporin. ASP team actively surveillant and monitored the above mentioned antibiotic, cephalosporin usage would be prescribed only to pre-determined indications, while others will be actively switched to ampicilin-sulbactam and amoxicilin- clavulanic acid. This study summarized the usage of Injection second and third generation of cephalosporin group antibiotics from year 2021 to year 2023 and compare with the incidence of ESBL cases per 100 patients admission during the same period. Usage of pediatric antibiotic described in number of vials over total number of admission, while adult antibiotic usage described in Defined daily dose (DDD). Occurrence of ESBL cases described in total number of cases/100 patient admission. The trend will then compared to the baseline ESBL E coli and KP in SWACH in the year prior this intervention. Results: For pediatric and adult O&G populations, we observed that the usage of overall cephalosporin group antibiotics showed a decreasing trend since year 2021 till year 2023 and a slight reduction in ESBL E coli and KP was observed at the same period. However, in adult oncology group, despite overall reduction in usage of cephalosporin group antibiotic except injection cefepime, the rate of ESBL E coli showed a slight increase. Conclusion: Coordinated efforts between stewardship programs and infection control are essential for reversing conditions that favor the emergence and dissemination of multidrug resistant gram negative bacteria within hospital.

Objective: To describe a collaboration effort between gynae-oncology and infection control unit in a sustainable surgical side infection prevention program Methods: In January 2023, gynae-oncologist noted a surge in surgical side infection (SSI) in gynae-oncology unit in Sabah Women and Children’s Hospital (SWACH), Kota Kinabalu, Sabah, Malaysia. The increasing trend of SSI was further confirmed by active surveillance started in January and February 2023. The SSI rate was found to be up to 46.2% (6 out of 13) in the elective gynae-oncology cases and 5 out of 15ases (31.2%) in February 2023. Outbreak interventions taken place. A combined continuous medical education of the latest SSI guidelines was carried out in the gynae-oncology unit including clinical nurses, clinicians and infection control team (ICT). Ward clinical nurses and infection control nurses developed SSI prevention program based on the latest SSI guideline and started ward clinical nurse education. An active SSI surveillance team was formed consisting ward sister and one clinical nurse, chief clinicians and infection control nurse to collect SSI cases. Results: SSI rate had reduced and maintained since March 2023. The SSI rate was maintained at zero except June and August with one superficial SSI respectively. Since September until December 2023 there was no SSI detected in active surveillance. Conclusions: Collaborative effort and understanding between clinical services and infection control unit are important in creating an effective and sustainable infection prevention program. Effective infection prevention program is not necessarily expensive. In fact, a highly motivated team, simple and practical approach can have amazing results.

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.

Introduction In 2016, the World Health Organization recommended differentiated service delivery (DSD) as a client‐centred approach to simplify HIV care in frequency and intensity, thus reducing the clinic visit burden on individuals and HIV programmes. We describe the scale of DSD implementation among HIV facilities in low‐ and middle‐income countries (LMICs) in Latin America, Africa and the Asia‐Pacific before the COVID‐19 pandemic. Methods We analysed facility‐level survey data from HIV care facilities participating in the International epidemiology Databases to Evaluate AIDS consortium in 2019. We used descriptive statistics to summarise the availability of DSD, multi‐month dispensing (MMD) and DSD for HIV treatment models. We explored factors associated with DSD implementation using multivariable models. Results We included 175 facilities in the Asia‐Pacific (n = 30), Latin America (n = 8), Central Africa (n = 21), East Africa (n = 74), Southern Africa (n = 28) and West Africa (n = 14). Overall, 133 facilities (76%) reported implementing DSD. Of these, 91% offered DSD for HIV treatment, 61% for HIV testing and 59% for antiretroviral therapy (ART) initiation. The most common duration of ART refills for clinically stable clients was 3MMD, (70%), followed by monthly (14%) and 6MMD (10%). Facility‐based individual models were the most frequently available DSD for the HIV treatment model (82%), followed by client‐managed group models (60%). Out‐of‐facility individual models were available at 48% of facilities. Facility‐based individual models were particularly common among facilities in East (92%) and Southern Africa (96%). Facilities in medium and high HIV prevalence countries, and those with 3MMD, were more likely to implement DSD. Conclusions In 2019, DSD was available in most HIV care facilities globally but was not evenly implemented across regions and HIV services. Most offered facility‐based DSD for HIV treatment models and 3MMD for clinically stable clients. Efforts to expand DSD for HIV testing and ART initiation and to offer longer MMD can improve long‐term retention in care of people living with HIV in LMICs, while further alleviating the operational burden on healthcare services. These findings from the pre‐COVID‐19 era underline the need for strengthening DSD in HIV care, which remains at the centre of current efforts towards client‐centred care.

IntroductionEarly 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 analysisThis 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 disseminationThe 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 registrationACTRN12616000046404.

The background incidence of viscerotropic- (VLD) and neurotropic-like disease (NLD) unrelated to immunization in dengue-endemic countries is currently unknown. This retrospective population-based analysis estimated crude and standardized incidences of VLD and NLD in twelve hospitals in Brazil (n = 3), Mexico (n = 3), and Malaysia (n = 6) over a 1-year period before the introduction of the tetravalent dengue vaccine. Catchment areas were estimated using publicly available population census information and administrative data. The denominator population for incidence rates was calculated, and sensitivity analyses assessed the impact of important assumptions. Total cases adjudicated as definite VLD were 5, 57, and 56 in Brazil, Mexico, and Malaysia, respectively. Total cases adjudicated as definite NLD were 103, 29, and 26 in Brazil, Mexico, and Malaysia, respectively. Crude incidence rates of cases adjudicated as definite VLD in Brazil, Mexico, and Malaysia were 1.17, 2.60, and 1.48 per 100,000 person-years, respectively. Crude incidence rates of cases adjudicated as definite NLD in Brazil, Mexico, and Malaysia were 4.45, 1.32, and 0.69 per 100,000 person-years, respectively. Background incidence estimates of VLD and NLD obtained in Mexico, Brazil, and Malaysia could provide context for cases occurring after the introduction of the tetravalent dengue vaccine.