Get the Basics Right: A Description of the Key Priorities for Establishing a Neonatal Service in a Resource-Limited Setting in Cambodia.

BACKGROUND: Worldwide, reduction in under-five mortality has not sufficiently included neonates, who represent 45% of deaths in children of age under five years. The least progress has been observed in resource-limited settings. METHODS: This mixed methods study conducted at a Cambodian non-governmental paediatric hospital described the key priorities of the ongoing neonatal service. Routinely collected data from the hospital and microbiology databases included the number of admissions, discharges and deaths and the number of cases of bacteraemias (2011-2016). Semi-structured interviews with the management staff explored the essential features of the service. RESULTS: There were 2127 neonatal admissions and 247 deaths. The incidence of facility-based neonatal mortality decreased by 81%. Bacteraemic healthcare-associated infections decreased by 68%. A dedicated area for neonatal care was perceived as crucial, allowing better infection control and delivery of staff training. CONCLUSIONS: In this hospital, the neonatal service prioritized basic measures, particularly, having a dedicated neonatal area. Facility-based mortality and bacteraemic healthcare-associated infections decreased.

Beliefs and practices during pregnancy, post-partum and in the first days of an infant's life in rural Cambodia.

BACKGROUND: The aim of this study was to record the beliefs, practices during pregnancy, post-partum and in the first few days of an infant's life, held by a cross section of the community in rural Cambodia to determine beneficial community interventions to improve early neonatal health. METHODS: Qualitative study design with data generated from semi structured interviews (SSI) and focus group discussions (FGD). Data were analysed by thematic content analysis, with an a priori coding structure developed using available relevant literature. Further reading of the transcripts permitted additional coding to be performed in vivo. This study was conducted in two locations, firstly the Angkor Hospital for Children and secondarily in five villages in Sotnikum, Siem Reap Province, Cambodia. RESULTS: A total of 20 participants underwent a SSIs (15 in hospital and five in the community) and six (three in hospital and three in the community; a total of 58 participants) FGDs were conducted. Harmful practices that occurred in the past (for example: discarding colostrum and putting mud on the umbilical stump) were not described as being practiced. Village elders did not enforce traditional views. Parents could describe signs of illness and felt responsible to seek care for their child even if other family members disagreed, however participants were unaware of the signs or danger of neonatal jaundice. Cost of transportation was the major barrier to healthcare that was identified. CONCLUSIONS: In the population examined, traditional practices in late pregnancy and the post-partum period were no longer commonly performed. However, jaundice, a potentially serious neonatal condition, was not recognised. Community neonatal interventions should be tailored to the populations existing practice and knowledge.

Detection of maternal transmission of resistant Gram-negative bacteria in a Cambodian hospital setting.

Infection with Extended-spectrum beta-lactamase -producing Enterobacterales (ESBL-E) is common in infants and leads to increased intensive care unit admission and mortality, but the role of maternal transmission in colonization of infants is unclear. Using paired isolates from 50 pairs of mothers and neonates admitted to a Cambodian hospital, we investigated antimicrobial resistance in Escherichia coli and Klebsiella pneumoniae using whole genome sequencing. We detected a wide variety of ESBL-E genes present in this population along with high levels of multidrug resistance. From 21 pairs where the same organism was present in both mother and neonate, we identified eight pairs with identical or near-identical isolates from both individuals suggestive of transmission at or around birth, including a pair with transmission of multiple strains. We found no evidence for transmission of plasmids only from mother to infant. This suggests vertical transmission outside hospitals as a common cause of ESBL-E colonization in neonates.

Barriers to neonatal care in developing countries: parents' and providers' perceptions.

AIM: Hospital care and advanced medical technologies for sick neonates are increasingly available, but not always readily accessible, in many countries. We characterised parents' and providers' perceptions of barriers to neonatal care in developing countries. METHODS: We interviewed parents whose infant was hospitalised within the first month of life in Cambodia, Malaysia, Laos and Vietnam, asking about perceived barriers to obtaining newborn care. We also surveyed health-care providers about perceived barriers to providing care. RESULTS: We interviewed 198 parents and 212 newborn care providers (physicians, nurses, midwives, paediatric and nursing trainees). Most families paid all costs of newborn care, which they reported as a hardship. Although newborn care is accessible, 39% reported that hospitals are too distant; almost 20% did not know where to obtain care. Parents cited lack of cleanliness (46%), poor availability of medications (42%) or services (36%), staff friendliness (42%), poor infant outcome (45%), poor communications with staff (44%) and costs of care (34%) as significant problems during prior newborn care. Providers cited lack of equipment (74%), lack of staff training (61%) and poor infrastructure (51%) as barriers to providing neonatal care. Providers identified distance to hospital, lack of transportation, care costs and low parental education as barriers for families. CONCLUSIONS: Improving cleanliness, staff friendliness and communication with parents may diminish some barriers to neonatal care in developing countries. Costs of newborn care, hospital infrastructure, distance to hospital, staffing shortages, limited staff training and limited access to medications pose more difficult barriers to remedy.

A Treatment-Decision Score for HIV-Infected Children With Suspected Tuberculosis.

BACKGROUND: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis. METHODS: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony. RESULTS: A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis. CONCLUSIONS: Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits.

If you come from a well-known organisation, I will trust you: Exploring and understanding the community's attitudes towards healthcare research in Cambodia.

OBJECTIVE: To explore Cambodian community members' understanding of and attitudes towards healthcare research. DESIGN: This qualitative study generated data from semi-structured interviews and focus group discussions. This study was conducted at a non-governmental paediatric hospital and in nearby villages in Siem Reap province, Cambodia. A total of ten semi-structured interviews and four focus group discussions were conducted, involving 27 participants. Iterative data collection and analysis were performed concurrently. Data were analysed by thematic content analysis and the coding structure was developed using relevant literature. RESULTS: Participants did not have a clear understanding of what activities related to research compared with those for routine healthcare. Key attitudes towards research were responsibility and trust: personal (trust of the researcher directly) and institutional (trust of the institution as a whole). Villagers believe the village headman holds responsibility for community activities, while the village headman believes that this responsibility should be shared across all levels of the government system. CONCLUSIONS: It is essential for researchers to understand the structure and relationship within the community they wish to work with in order to develop trust among community participants. This aids effective communication and understanding among all parties, enabling high quality ethical research to be conducted.

Transmission Dynamics of Hyper-Endemic Multi-Drug Resistant Klebsiella pneumoniae in a Southeast Asian Neonatal Unit: A Longitudinal Study With Whole Genome Sequencing.

Background:Klebsiella pneumoniae is an important and increasing cause of life-threatening disease in hospitalized neonates. Third generation cephalosporin resistance (3GC-R) is frequently a marker of multi-drug resistance, and can complicate management of infections. 3GC-R K. pneumoniae is hyper-endemic in many developing country settings, but its epidemiology is poorly understood and prospective studies of endemic transmission are lacking. We aimed to determine the transmission dynamics of 3GC-R K. pneumoniae in a newly opened neonatal unit (NU) in Cambodia and to address the following questions: what is the diversity of 3GC-R K. pneumoniae both within- and between-host; to what extent is high carriage prevalence driven by ward-based transmission; and to what extent can environmental contamination explain patterns of patient acquisition. Methods: We performed a prospective longitudinal study between September and November 2013. Rectal swabs from consented patients were collected upon NU admission and every 3 days thereafter. Morphologically different colonies from swabs growing cefpodoxime-resistant K. pneumoniae were selected for whole-genome sequencing (WGS). Results: One hundred and fifty-eight samples from 37 patients and 7 environmental sites were collected. 32/37 (86%) patients screened positive for 3GC-R K. pneumoniae and 93 colonies from 119 swabs were successfully sequenced. Isolates were resistant to a median of six (range 3-9) antimicrobials. WGS revealed high diversity; pairwise distances between isolates from the same patient were either 0-1 SNV or >1,000 SNVs; 19/32 colonized patients harbored K. pneumoniae colonies differing by >1000 SNVs. Diverse lineages accounted for 18 probable importations to the NU and nine probable transmission clusters involving 19/37 (51%) of screened patients. Median cluster size was five patients (range 3-9). Seven out of 46 environmental swabs (15%) were positive for 3GC-R K. pneumoniae. Environmental sources were plausible sources for acquisitions in 2/9 transmission clusters, though in both cases other patients were also plausible sources. Conclusion: The epidemiology of 3GC-R K. pneumoniae was characterized by multiple introductions, high within- and between host diversity and a dense network of cross-infection, with half of screened neonates part of a transmission cluster. We found no evidence to suggest that environmental contamination was playing a dominant role in transmission.

Mortality and its determinants in antiretroviral treatment-naive HIV-infected children with suspected tuberculosis: an observational cohort study.

BACKGROUND: Tuberculosis is a major cause of morbidity and mortality in HIV-infected children, but is difficult to diagnose. We studied mortality and its determinants in antiretroviral treatment (ART)-naive HIV-infected children presenting with suspected tuberculosis. METHODS: In this observational cohort study, HIV-infected children aged 13 years or younger with suspected tuberculosis were followed up for 6 months as part of the ANRS 12229 PAANTHER 01 cohort in eight hospitals in four countries (Burkina Faso, Cambodia, Cameroon, and Vietnam). Children started ART and antituberculosis treatment at the clinician's discretion and were retrospectively classified into one of three groups by tuberculosis documentation: confirmed by culture or Xpert MTB/RIF, unconfirmed, and unlikely. We assessed mortality and associated factors using Kaplan-Meier methods and Cox proportional hazard models. The ANRS 12229 PAANTHER 01 study is registered at ClinicalTrials.gov, number NCT01331811. FINDINGS: 266 (61%) of 438 children enrolled in the study between April 27, 2011, and May 31, 2014, were ART-naive and included in the analysis (40 had confirmed tuberculosis, 119 unconfirmed tuberculosis, and 107 unlikely tuberculosis). 112·5 person-years of follow-up were available. 154 children (58%) started antituberculosis treatment and 212 (80%) started ART. 50 children (19%) died. Mortality by 6 months was higher in children with confirmed tuberculosis (14 deaths; 2 month survival probability 65·0% [95% CI 50·2-79·8]) compared with unconfirmed tuberculosis (19 deaths; 83·5% [76·8-90·3]) and unlikely tuberculosis (17 deaths; 83·5% [76·3-90·7]; log-rank p=0·0141) and was lower in children with confirmed or unconfirmed tuberculosis who started antituberculosis treatment (p<0·0001 for both). In a multivariate analysis, ART started during the first month of follow-up (hazard ratio 0·08; 95% CI 0·01-0·67), confirmed tuberculosis (6·33; 2·15-18·64), young age (5·90; 2·02-17·19), CD4 less than 10% (2·63; 1·25-5·53), miliary features (4·08; 1·56-10·66), and elevated serum transaminases (4·40; 1·82-10·65) were all independently associated with mortality. INTERPRETATION: In our cohort, mortality was high in the first 6 months after suspicion of tuberculosis in ART-naive children. ART should be started early, particularly in children with factors associated with high mortality. Documented or empirical tuberculosis treatment decision should be accelerated to reduce mortality and allow early ART initiation. FUNDING: ANRS and Fondation Total.

High Prevalence of Antimicrobial-resistant Gram-negative Colonization in Hospitalized Cambodian Infants.

BACKGROUND: Antimicrobial-resistant Gram-negative infections are a significant cause of mortality in young infants. We aimed to determine characteristics of, and risk factors for, colonization and invasive infection caused by 3rd generation cephalosporin (3GC) or carbapenem-resistant organisms in outborn infants admitted to a neonatal unit (NU) in Cambodia. METHODS: During the first year of operation, patients admitted to the Angkor Hospital for Children NU, Siem Reap, Cambodia, underwent rectal swabbing on admission and twice weekly until discharge. Swabs were taken also from 7 environmental sites. Swabs were cultured to identify 3GC or carbapenem-resistant Acinetobacter sp., Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. RESULTS: The study included 333 infants with a median age at NU admission of 10 days (range, 0-43). Colonization by ≥1 3GC-resistant organism was detected in 85.9% (286/333). Admission swabs were collected in 289 infants: 61.9% were colonized by a 3GC-resistant organism at the time of admission, and a further 23.2% were colonized during hospitalization, at a median of 4 days [95% confidence interval: 3-5]. Probiotic treatment (hazard ratio: 0.58; 95% confidence interval: 0.35-0.98) was associated with delayed colonization. Colonization by a carbapenem-resistant organism occurred in 25 (7.5%) infants. Six infants had NU-associated K. pneumoniae bacteremia; phenotypically identical colonizing strains were found in 3 infants. Environmental colonization occurred early. CONCLUSIONS: Colonization by antimicrobial-resistant Gram-negative organisms occurred early in hospitalized Cambodian infants and was associated with subsequent invasive infection. Trials of potential interventions such as probiotics are needed.