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      Causes and Outcomes of Sepsis in Southeast Asia: A Multinational Multicentre Cross-sectional Study

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      The Lancet. Global health

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          Abstract

          Background

          A better understanding of pathogens causing sepsis is important for management and antimicrobial selection. Here, we explored the causative pathogens of sepsis in Southeast Asia (SEA).

          Methods

          We prospectively recruited children (age≥30 days and <18 years) and adults (age≥18 years) at 13 public hospitals in Indonesia (n=3), Thailand (n=4) and Viet Nam (n=6). Hospitalised patients with suspected or documented community-acquired infection, with ≥3 diagnostic criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within 24 hours of admission were enrolled. Blood from every patient, and nasopharyngeal swab, urine, stool and cerebrospinal fluid, if indicated, were collected for reference diagnostic tests. This study was registered with ClinicalTrials.gov, number NCT02157259.

          Findings

          From December 2013 to December 2015, 1,578 patients (763 children and 815 adults) were enrolled. Dengue viruses (n=122, 8%), Leptospira spp. (n=95, 6%), rickettsial pathogens (n=96, 6%), Escherichia coli (n=76, 5%) and influenza viruses (n=65, 4%) were commonly identified in both age groups, while Plasmodium spp. (n=12, 1%) and Salmonella enterica serovar Typhi (n=3, 0.2%) were rarely observed. Emerging pathogens identified included hantaviruses (n=28, 2%), non-typhoidal Salmonella spp (n=21, 1%), Streptococcus suis (n=18, 1%), Acinetobacter spp. (n=12, 1%), and Burkholderia pseudomallei (n=5, 0.3%). 28-day mortality was 2% in children (14/731) and 13% in adults (108/804). Severe sepsis was identified on enrolment in 27% of children (204/763) and 68% of adults (550/815), and was associated with increased mortality (adjusted odds ratio 5.3, 95% confidence interval 2.7–10.4, p<0.001).

          Interpretation

          Sepsis in SEA is caused by a wide range of known and emerging pathogens, and is associated with substantial mortality.

          Funding

          National Cancer Institute (HHSN261200800001E) and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Wellcome Trust (106680/B/14/Z and 106698/B/14/Z).

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          Most cited references20

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          Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study.

          The adult patients who, between July 2001 and June 2002, presented at any of five hospitals in Thailand with acute febrile illness in the absence of an obvious focus of infection were prospectively investigated. Blood samples were taken from all of the patients and checked for aerobic bacteria and leptospires by culture. In addition, at least two samples of serum were collected at different times (on admission and 2-4 weeks post-discharge) from each patient and tested, in serological tests, for evidence of leptospirosis, rickettsioses, dengue and influenza. The 845 patients investigated, of whom 661 were male, had a median age of 38 years and a median duration of fever, on presentation, of 3.5 days. Most (76.5%) were agricultural workers and most (68.3%) had the cause of their fever identified, as leptospirosis (36.9%), scrub typhus (19.9%), dengue infection or influenza (10.7%), murine typhus (2.8%), Rickettsia helvetica infection (1.3%), Q fever (1%), or other bacterial infection (1.2%). The serological results indicated that 103 (12.2%) and nine (1%) of the patients may have had double and triple infections, respectively. Leptospirosis and rickettsioses, especially scrub typhus, were thus found to be major causes of acute, undifferentiated fever in Thai agricultural workers.
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            A Prospective Study of the Causes of Febrile Illness Requiring Hospitalization in Children in Cambodia

            Background Febrile illnesses are pre-eminent contributors to morbidity and mortality among children in South-East Asia but the causes are poorly understood. We determined the causes of fever in children hospitalised in Siem Reap province, Cambodia. Methods and Findings A one-year prospective study of febrile children admitted to Angkor Hospital for Children, Siem Reap. Demographic, clinical, laboratory and outcome data were comprehensively analysed. Between October 12th 2009 and October 12th 2010 there were 1225 episodes of febrile illness in 1180 children. Median (IQR) age was 2.0 (0.8–6.4) years, with 850 (69%) episodes in children <5 years. Common microbiological diagnoses were dengue virus (16.2%), scrub typhus (7.8%), and Japanese encephalitis virus (5.8%). 76 (6.3%) episodes had culture-proven bloodstream infection, including Salmonella enterica serovar Typhi (22 isolates, 1.8%), Streptococcus pneumoniae (13, 1.1%), Escherichia coli (8, 0.7%), Haemophilus influenzae (7, 0.6%), Staphylococcus aureus (6, 0.5%) and Burkholderia pseudomallei (6, 0.5%). There were 69 deaths (5.6%), including those due to clinically diagnosed pneumonia (19), dengue virus (5), and melioidosis (4). 10 of 69 (14.5%) deaths were associated with culture-proven bloodstream infection in logistic regression analyses (odds ratio for mortality 3.4, 95% CI 1.6–6.9). Antimicrobial resistance was prevalent, particularly in S. enterica Typhi, (where 90% of isolates were resistant to ciprofloxacin, and 86% were multi-drug resistant). Comorbid undernutrition was present in 44% of episodes and a major risk factor for acute mortality (OR 2.1, 95% CI 1.1–4.2), as were HIV infection and cardiac disease. Conclusion We identified a microbiological cause of fever in almost 50% of episodes in this large study of community-acquired febrile illness in hospitalized children in Cambodia. The range of pathogens, antimicrobial susceptibility, and co-morbidities associated with mortality described will be of use in the development of rational guidelines for infectious disease treatment and control in Cambodia and South-East Asia.
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              No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever.

              To evaluate whether cosmetically relevant dental effects occurred among children who had received doxycycline for treatment of suspected Rocky Mountain spotted fever (RMSF).
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                Author and article information

                Contributors
                Role: Asst. Prof.
                Journal
                101613665
                42402
                Lancet Glob Health
                Lancet Glob Health
                The Lancet. Global health
                2214-109X
                3 February 2017
                February 2017
                01 February 2018
                : 5
                : 2
                : e157-e167
                Author notes
                Corresponding author: Asst. Prof. Direk Limmathurotsakul, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand. Tel: +66 2 203 6333, Fax: +66 2 354 9169, direk@ 123456tropmedres.ac
                Article
                NIHMS845702
                10.1016/S2214-109X(17)30007-4
                5332551
                28104185
                7a3d6dab-d244-486b-9087-44fff8fa8289

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

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