A Clinically Oriented antimicrobial Resistance surveillance Network (ACORN): pilot implementation in three countries in Southeast Asia, 2019-2020.

Background: Case-based surveillance of antimicrobial resistance (AMR) provides more actionable data than isolate- or sample-based surveillance. We developed A Clinically Oriented antimicrobial Resistance surveillance Network (ACORN) as a lightweight but comprehensive platform, in which we combine clinical data collection with diagnostic stewardship, microbiological data collection and visualisation of the linked clinical-microbiology dataset. Data are compatible with WHO GLASS surveillance and can be stratified by syndrome and other metadata. Summary metrics can be visualised and fed back directly for clinical decision-making and to inform local treatment guidelines and national policy. Methods: An ACORN pilot was implemented in three hospitals in Southeast Asia (1 paediatric, 2 general) to collect clinical and microbiological data from patients with community- or hospital-acquired pneumonia, sepsis, or meningitis. The implementation package included tools to capture site and laboratory capacity information, guidelines on diagnostic stewardship, and a web-based data visualisation and analysis platform. Results: Between December 2019 and October 2020, 2294 patients were enrolled with 2464 discrete infection episodes (1786 community-acquired, 518 healthcare-associated and 160 hospital-acquired). Overall, 28-day mortality was 8.7%. Third generation cephalosporin resistance was identified in 54.2% (39/72) of E. coli and 38.7% (12/31) of K. pneumoniae isolates . Almost a quarter of S. aureus isolates were methicillin resistant (23.0%, 14/61). 290/2464 episodes could be linked to a pathogen, highlighting the level of enrolment required to achieve an acceptable volume of isolate data. However, the combination with clinical metadata allowed for more nuanced interpretation and immediate feedback of results. Conclusions: ACORN was technically feasible to implement and acceptable at site level. With minor changes from lessons learned during the pilot ACORN is now being scaled up and implemented in 15 hospitals in 9 low- and middle-income countries to generate sufficient case-based data to determine incidence, outcomes, and susceptibility of target pathogens among patients with infectious syndromes.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Colonization and Invasive Disease in Cambodian Children.

BACKGROUND: Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years. METHODS: There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012-December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE). RESULTS: Comparing 2014 with 2016-2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6-21.8) for all pneumococci and 39.2% (95% CI 26.7-46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7-33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4-35.8) by 2018, with a decrease of 36.3% (95% CI 23.8-46.9) for VT IPD and an increase of 101.4% (95% CI 62.0-145.4) for non-VT IPD. CONCLUSIONS: Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates.

Cambodian Developmental Milestone Assessment Tool (cDMAT): Performance reference charts and reliability check of a tool to assess early childhood development in Cambodian children.

BACKGROUND: Childhood development milestones are essential skills that define how children participate in their environment socially, physically, and intellectually. A culturally-sensible and environmentally-appropriate tool is needed to assess their performance and detect disabilities at an early stage. METHOD: This observational study aimed to create reference charts of performances among healthy rural and semi-rural Cambodian children aged 0-83 months for each milestone using the Denver II-based Cambodian Development Milestone Assessment Tool (cDMAT). Inter-observer reliability testing yielded Kappa scores. RESULTS AND CONCLUSION: 1330 children included in the analyses represented an average population sample with similar gender balance, expected poverty distribution and the illiteracy rate among their mothers (81% with no or attended <7th-grade education). While gender, poverty and the mother's education level were not found to be confounding factors, the child's school enrolment status was (p < 0.005). The performance reference charts document the PASS ratios from which age onwards <25%, 25-75%, 75-90%, 90-99% and 99-100% of the children in each monthly cohort can perform a particular milestone. The mean inter-observer reliability ranged from substantial (Kappa 0.61 for delay) to excellent (Kappa 0.84 for immediate) in all domains. The performance reference charts of a culturally-sensible and environmentally-appropriate cDMAT can be used in Cambodia with special attention given to the child's school enrolment as it was found to be a confounding factor affecting child development. Creating a small-scale pilot program linking the cDMAT to early intervention would help raise awareness and create local expertise on early childhood development.

Prospective surveillance of healthcare associated infections in a Cambodian pediatric hospital.

BACKGROUND: Healthcare associated infections (HAI) are the most common preventable adverse events following admission to healthcare facilities. Data from low-income countries are scarce. We sought to prospectively define HAI incidence at Angkor Hospital for Children (AHC), a Cambodian pediatric referral hospital. METHODS: Prospective HAI surveillance was introduced for medical admissions to AHC. Cases were identified on daily ward rounds and confirmed using locally adapted Centers for Disease Control and Prevention (CDC) definitions. During the surveillance period, established infection prevention and control (IPC) activities continued, including hand hygiene surveillance. In addition, antimicrobial stewardship practices such as the creation of an antimicrobial guideline smartphone app were introduced. RESULTS: Between 1st January and 31st December 2015 there were 3,263 medical admissions and 102 HAI cases. The incidence of HAI was 4.6/1,000 patient-days (95% confidence interval 3.8-5.6) and rates were highest amongst neonates. Median length of stay was significantly longer in HAI cases: 25 days versus 5 days for non-HAI cases (p < 0.0001). All-cause in-hospital mortality increased from 2.0 to 16.1% with HAI (p < 0.0001). Respiratory infections were the most common HAI (54/102; 52.9%). Amongst culture positive infections, Gram-negative organisms predominated (13/16; 81.3%). Resistance to third generation cephalosporins was common, supporting the use of more expensive carbapenem drugs empirically in HAI cases. The total cost of treatment for all 102 HCAI cases combined, based on additional inpatient days, was estimated to be $299,608. CONCLUSIONS: Prospective HAI surveillance can form part of routine practice in low-income healthcare settings. HAI incidence at AHC was relatively low, but human and financial costs remained high due to increased carbapenem use, prolonged admissions and higher mortality rates.

Creating a Cambodia-specific developmental milestone screening tool - a pilot study.

BACKGROUND: Approximately 600 million people are living with various types of disabilities throughout the world and over 200 million children under age of 5 years old not reach their developmental potential. These adverse outcomes can be prevented through early detection and treatment. To accurately assess the development of children, a culturally appropriate screening tool must be used. Cambodia lacks such tool and other studies have shown that western tools are not valid in other cultures. AIMS: This study aimed at creating a culturally appropriate screening tool - called the Angkor Hospital for Children Developmental Milestone Assessment Tool (AHC DMAT) - for screening neurodevelopmental disability in Cambodian children. STUDY DESIGN, SUBJECT, OUTCOME MEASURES: Western milestones from the DDST II were used with cultural modifications. Children of both genders and aged from 1 month to 6 years assumed to have normal development were included in two pilot screenings (N=100 and N=63) with further modifications to the AHC DMAT made as necessary after each screening. RESULTS: The final AHC DMAT consists of 140 milestones (49% directly from DDST II, 17% modified DDST II, 34% added through expert opinion). CONCLUSION: Extensive revision of the DDST II was needed in order to create a more valid Cambodian screening tool. This study was the first step to create a Cambodian-specific screening tool but further large-scale testing of the AHC DMAT is needed to strengthen the tool's validity and to identify the age-range percentiles of each milestone before it can be used for neurodevelopment screening.