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Background Capacity and demand for paediatric critical care are growing in many resource-constrained contexts. However, tools to support resource stewardship and promote sustainability of critical care services are lacking. Methods This study assessed the ability of nine severity scores to risk stratify children admitted to a paediatric intensive care unit (PICU) in Siem Reap, northern Cambodia. It then developed a bespoke clinical prediction model to enable risk stratification in resource-constrained PICU contexts. The primary outcome was death during PICU admission. Results 1,550 consecutive PICU admissions were included, of which 97 (6.3%) died. Most existing severity scores achieved comparable discrimination (area under the receiver operating characteristic curves [AUCs] 0.71-0.76) but only three scores demonstrated moderate diagnostic utility for triaging admissions into high- and low-risk groups (positive likelihood ratios 2.65-2.97 and negative likelihood ratios 0.40-0.46). The newly derived model outperformed all existing severity scores (AUC 0.84, 95% CI 0.80-0.88; p < 0.001). Using one particular threshold, the model classified 13.0% of admissions as high-risk, amongst which probability of mortality was almost ten-fold greater than admissions triaged as low-risk (PLR 5.75; 95% CI 4.57-7.23 and NLR 0.47; 95% CI 0.37-0.59). Decision curve analyses indicated that the model would be superior to all existing severity scores and could provide utility across the range of clinically plausible decision thresholds. Conclusions Existing paediatric severity scores have limited potential as risk stratification tools in resource-constrained PICUs. If validated, the prediction model developed herein would provide a readily implementable mechanism to support triage of critically ill children on admission to PICU and could be tailored to suit a variety of contexts where resource prioritisation is important.

Objectives Partnerships between low- to middle-income countries (LMICs) and high-income countries (HICs) is one strategy to mitigate observed health disparities. Cambodia’s Angkor Hospital for Children (AHC), an LMIC institution, faces shortages in health care resources, including pathology services. A partnership was created with Children’s Wisconsin (CW), an HIC hospital, including provision of pathology services. We describe our established pathology workflow, examine cases seen in AHC patients, and evaluate the impact of CW’s interpretations. Methods AHC provides clinical history and impression and ships samples to CW, which processes the samples, and pathologists provide interpretations, sending reports electronically to AHC. For analysis, final diagnoses were considered “concordant,” “refined,” or “discordant” based on agreement with the clinical impression. Cases were also classified as “did not change management” or “changed management” based on how CW interpretation affected clinical management. Results We included 347 specimens (177 malignant, 146 benign, 24 insufficient for diagnosis). Of these cases, 31% were discordant and 44% of cases with clinical follow-up had a change in management with CW interpretation. Conclusions Inclusion of pathology services in LMIC-HIC partnerships is crucial for resolving health disparities between the institutions involved. The described partnership and established pathology workflow can be adapted to the needs and resources of many institutions.

Leishmaniasis is considered a neglected tropical disease that is commonly found in Asia, Africa, South America, and Mediterranean countries. Visceral leishmaniasis (VL) is the most severe form of the disease and is almost universally fatal if left untreated. The symptoms of VL overlap with many infectious diseases, malignancies, and other blood disorders. The most common findings include fever, cytopenias, and splenomegaly. Given the nonspecific symptoms, the diagnosis requires detailed laboratory investigations, including bone marrow examination, that can be challenging in low- and middle-income countries. Diagnostic limitations likely lead to the underdiagnosis or delay in diagnosis of VL. We describe, to our knowledge, the first case report of VL in Cambodia in a child presenting with fever, anemia, and thrombocytopenia. The diagnosis required a liver biopsy and multiple bone marrow biopsies to visualize intracellular Leishmania spp. Our case illustrates the diagnostic challenges and the importance of timely diagnosis. This case also highlights the need for heightened awareness of the diagnostic findings of VL and improved reporting of tropical diseases.

Background Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4–6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1–3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI). Method We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI. Results In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4–61.2 mg/L) (uncomplicated dengue, 28.6 (10.5–58.9); severe or intermediate dengue, 34.0 (17.4–71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07–1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14–1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76–0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir. Conclusions In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses.

Partnerships between low- to middle-income countries (LMICs) and high-income countries (HICs) is one strategy to mitigate observed health disparities. Cambodia's Angkor Hospital for Children (AHC), an LMIC institution, faces shortages in health care resources, including pathology services. A partnership was created with Children's Wisconsin (CW), an HIC hospital, including provision of pathology services. We describe our established pathology workflow, examine cases seen in AHC patients, and evaluate the impact of CW's interpretations.AHC provides clinical history and impression and ships samples to CW, which processes the samples, and pathologists provide interpretations, sending reports electronically to AHC. For analysis, final diagnoses were considered "concordant," "refined," or "discordant" based on agreement with the clinical impression. Cases were also classified as "did not change management" or "changed management" based on how CW interpretation affected clinical management.We included 347 specimens (177 malignant, 146 benign, 24 insufficient for diagnosis). Of these cases, 31% were discordant and 44% of cases with clinical follow-up had a change in management with CW interpretation.Inclusion of pathology services in LMIC-HIC partnerships is crucial for resolving health disparities between the institutions involved. The described partnership and established pathology workflow can be adapted to the needs and resources of many institutions.

Background:Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).Methods:We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.Results:On days 1–3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.Conclusions:Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.Funding:This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.

BackgroundEarly identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).MethodsWe performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.ResultsOn days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.ConclusionsOur findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.Summary of the main pointHigher levels of any of VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, and CRP on illness days 1-3 increased the risk of developing severe/moderate dengue. The relationships differed between children and adults and some changed when assessed together.

Additional file 5. Association between CRP level and clinical outcomes in subgroups of age

Infections with Salmonella enterica serovar Typhi isolates that are multidrug resistant (MDR: resistant to chloramphenicol, ampicillin, trimethoprim–sulphamethoxazole) with intermediate ciprofloxacin susceptibility are widespread in Asia but there is little information from Cambodia. We studied invasive salmonellosis in children at a paediatric hospital in Siem Reap, Cambodia. Between 2007 and 2011 Salmonella was isolated from a blood culture in 162 children. There were 151 children with enteric fever, including 148 serovar Typhi and three serovar Paratyphi A infections, and 11 children with a non-typhoidal Salmonella infection. Of the 148 serovar Typhi isolates 126 (85%) were MDR and 133 (90%) had intermediate ciprofloxacin susceptibility. Inpatient antimicrobial treatment was ceftriaxone alone or initial ceftriaxone followed by a step-down to oral ciprofloxacin or azithromycin. Complications developed in 37/128 (29%) children admitted with enteric fever and two (1.6%) died. There was one confirmed relapse. In a sample of 102 serovar Typhi strains genotyped by investigation of a subset of single nucleotide polymorphisms, 98 (96%) were the H58 haplotype, the majority of which had the common serine to phenylalanine substitution at codon 83 in the DNA gyrase. We conclude that antimicrobial-resistant enteric fever is common in Cambodian children and therapeutic options are limited.

BACKGROUND: There are limited data on the epidemiology of paediatric healthcare-associated infection (HCAI) and infection control in low-income countries. We describe the value of intermittent point-prevalence surveys for monitoring HCAI and evaluating infection control interventions in a Cambodian paediatric hospital. METHODS: Hospital-wide, point-prevalence surveys were performed monthly in 2011. Infection control interventions introduced during this period included a hand hygiene programme and a ventilator-associated pneumonia (VAP) care bundle. RESULTS: Overall HCAI prevalence was 13.8/100 patients at-risk, with a significant decline over time. The highest HCAI rates (50%) were observed in critical care; the majority of HCAIs were respiratory (61%). Klebsiella pneumoniae was most commonly isolated and antimicrobial resistance was widespread. Hand hygiene compliance doubled to 51.6%, and total VAP cases/1000 patient-ventilator days fell from 30 to 10. CONCLUSION: Rates of HCAI were substantial in our institution, and antimicrobial resistance a major concern. Point-prevalence surveys are effective for HCAI surveillance, and in monitoring trends in response to infection control interventions.

BACKGROUND: The incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection is rising in the developed world but appears to be rare in developing countries. One explanation for this difference is that resource poor countries lack the diagnostic microbiology facilities necessary to detect the presence of CA-MRSA carriage and infection. METHODOLOGY AND PRINCIPAL FINDINGS: We developed diagnostic microbiology capabilities at the Angkor Hospital for Children, Siem Reap, western Cambodia in January 2006 and in the same month identified a child with severe community-acquired impetigo caused by CA-MRSA. A study was undertaken to identify and describe additional cases presenting between January 2006 and December 2007. Bacterial isolates underwent molecular characterization using multilocus sequence typing, staphylococcal cassette chromosome mec (SCCmec) typing, and PCR for the presence of the genes encoding Panton-Valentine Leukocidin (PVL). Seventeen children were identified with CA-MRSA infection, of which 11 had skin and soft tissue infection and 6 had invasive disease. The majority of cases were unrelated in time or place. Molecular characterization identified two independent MRSA clones; fifteen isolates were sequence type (ST) 834, SCCmec type IV, PVL gene-negative, and two isolates were ST 121, SCCmec type V, PVL gene-positive. CONCLUSIONS: This represents the first ever report of MRSA in Cambodia, spread of which would pose a significant threat to public health. The finding that cases were mostly unrelated in time or place suggests that these were sporadic infections in persons who were CA-MRSA carriers or contacts of carriers, rather than arising in the context of an outbreak.

Typhoid fever was confirmed by positive blood culture in 5 (3.7%) of 134 febrile children hospitalized in Cambodia. Typhoid was suspected in an additional 25 (18.7 %) blood culture-negative children based on: a positive immunoglobulin M lateral flow assay (IgMFA) (16); a positive polymerase chain reaction (PCR) for Salmonella typhi (2); or clinical assessment (7). The specificity of the IgMFA and PCR assays requires further study.

Chromobacterium violaceum infection is rarely described in Southeast Asian children, which may be due partly to the lack of access to adequate microbiology facilities in many areas. This case report describes the first documented case to occur in a Cambodian child. An awareness of the disease and its manifestations is important as treatment can be difficult and may require prolonged courses of antimicrobials and surgery.

The Series paper on emerging infectious diseases in southeast Asia by Richard Coker and colleagues (Feb 12, p 599) focuses attention on high-profi le and undoubtedly signifi cant disorders such as infl uenza, zoonoses, and vector-borne diseases. Other common, important, but less newsworthy infectious diseases including those less conventionally “tropical”, are of at least equal weight locally and also have global relevance. Bacteria resistant to antimicrobial agents are now commonplace in southeast Asia. Such organisms include meticillin-resistant Staphylo coccus aureus, penicillin-resistant pneumococci, multidrug-resistant Salmonella typhi, and extended-spectrum β-lactamase-producing Gram-negative bacteria including Shigella spp, Escherichia coli, and Klebsiella pneumoniae. In Angkor Hospital for Children, a provincial children’s hospital in northwest Cambodia, all of these pathogens are regularly isolated from children in hospital and also, alarmingly, from the community. These infections cause morbidity and mortality in children in a region where access to appropriate treatment with expensive anti microbials for resistant microorganisms is limited. Unfortunately, without intervention, this burden is likely to increase. Many of the factors discussed by Coker and colleagues that encourage the emergence of other infectious diseases also lead to increased antimicrobial resistance. The widespread use of empiric anti microbials based on the clinical syndrome in health3 Bawaskar HS, Bawaskar PH. Endemic fl uorosis in an isolated village in Western Maharashtra, India. Trop Doct 2006; 36: 221–23. 4 Abraham R, Murugan VS, Pukazhvanthen P, Sen SK. Thyroid disorders in women of Puducherry. Indian J Clin Biochem 2009; 24: 52–59. 5 Samu K. Agriculture: farmers’ suicide—2010. New Delhi: Indian Social Institute, 2010. care settings (owing to scarce diagnostic facilities) is likely to be one contributing factor. The use of injected extended-spectrum cephalosporins and other antimicrobials in the community often at subtherapeutic doses is also a concern. The key issue for this region, and indeed many other developing areas, is the scarcity of surveillance infrastructure and diagnostic microbiology facilities, without which coherent assessment, ongoing monitoring, and ultimately clinical management are extremely limited.

An 8-month old girl presented to the Angkor Hospital for Children in Siem Riep, Cambodia with fevers, bilateral eye discharge and an extensive body rash. The rash consisted of large, fluid-filled bullae and significant desquamation. The patient was admitted to the hospital and given intravenous cloxacillin for presumed bullous impetigo. Despite treatment with antibiotics, the skin lesions did not improve and the fevers continued. Telemedicine consultations were initiated by email between Angkor Hospital for Children and paediatric specialists in the USA. Several diagnoses were entertained throughout the subsequent collaborative dialogue. Ultimately, teleconsultation led to a diagnosis of chronic bullous dermatosis of childhood (CBDC), a rare sub-epidermal blistering disease. The child was started on appropriate medications. Within 24 hours, the lesions showed significant improvement and fevers resolved. By enabling advice from distant providers on diagnosis and treatment of paediatric patients, telemedicine may improve health care in developing countries.

Objectives To describe childhood nephrotic syndrome (NS) in Cambodia and to evaluate whether initial presentation or relapse is associated with gastrointestinal parasitic infection. Study design We reviewed the records of 112 children with NS. A retrospective cross-sectional study compared 99 stool exams from 63 children with NS with 12 365 stool exams from 9495 controls. Results The male-to-female ratio was 1.7; the mean age of presentation was 8.95 years--44% were hypertensive, 44% had microscopic hematuria, 40% had eosinophilia, and 41% had acute renal failure; 92.7% were steroid sensitive, 12.7% were steroid dependent, and 8.9% were frequent relapsers. Peritonitis and death were rare outcomes. Giardia lamblia (OR, 3.62; 95% CI, 2.0 to 6.1), Strongyloides stercoralis (OR, 3.59; 95% CI, 1.3 to 8.2), and Hookworm species (OR, 2.57; 95% CI, 1.0 to 5.5) were more likely to be isolated from the children with NS than the controls. Conclusions The clinical course of childhood NS in Cambodia is similar to the developed world. Differences at presentation included older age and increased prevalence of microscopic hematuria, hypertension, eosinophilia, and acute renal failure. This study demonstrates an association between G lamblia, S stercoralis, and possibly Hookworm species and the onset of NS.

Additional file 1. Clinical endpoint definition.

Additional file 11. Correlation between CRP and other biomarkers.

Additional file 3. Summary of clinically diagnosis of bacterial infection.

Additional file 7: Figure S3. Association between CRP level and fever clearance time among dengue patients.

Additional file 4: Figure S1. Association between CRP level and patients diagnosed with dengue or OFI.

Additional file 2. Number of adults/children by sites.

Additional file 1. Clinical endpoint definition.

Additional file 8: Figure S4. Association between CRP level and hospitalization among dengue patients.

Additional file 3. Summary of clinically diagnosis of bacterial infection.

Additional file 9. Association between CRP level and clinical outcomes: sensitivity analysis including 9 cases with CRP values above the upper range of the assay.

Additional file 2. Number of adults/children by sites.

Additional file 6: Figure S2. Association between CRP level and severe or intermediate dengue among dengue patients.

Additional file 8: Figure S4. Association between CRP level and hospitalization among dengue patients.

Additional file 10: Figure S5. Association between CRP and other laboratory tests result.

Additional file 4: Figure S1. Association between CRP level and patients diagnosed with dengue or OFI.

Additional file 6: Figure S2. Association between CRP level and severe or intermediate dengue among dengue patients.