Causes and outcomes of sepsis in southeast Asia: a multinational multicentre cross-sectional study

Southeast Asia Infectious Disease Clinical Research Network, Southeast Asia Infectious Disease Clinical Research Network

Abstract

Background: Improved understanding of pathogens that cause sepsis would aid management and antimicrobial selection. In this study, we aimed to identify the causative pathogens of sepsis in southeast Asia.

Methods: In this multinational multicentre cross-sectional study of community-acquired sepsis and severe sepsis, 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 Vietnam (n=6). Hospitalised patients with suspected or documented community-acquired infection, with at least three diagnostic criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within 24 h of admission were enrolled. Blood from every patient, and nasopharyngeal swab, urine, stool, and cerebrospinal fluid, if indicated, were collected for reference diagnostic tests to identify causative pathogens. We report causative pathogens of sepsis and 28-day mortality. We also estimate mortality associated with enrolment with severe sepsis. This study was registered with ClinicalTrials.gov, number NCT02157259.

Findings: From Dec 16, 2013, to Dec 14, 2015, 4736 patients were screened and 1578 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; whereas 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 [<1%]). 28-day mortality occurred in 14 (2%) of 731 children with known statuses and 108 (13%) of 804 adults. Severe sepsis was identified on enrolment in 194 (28%) of 731 children and 546 (68%) of 804 adults, and was associated with increased mortality (adjusted odds ratio 5·3, 95% CI 2·7-10·4; p<0·001).

Interpretation: Sepsis in southeast Asia is caused by a wide range of known and emerging pathogens, and is associated with substantial mortality.

Funding: National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA, and Wellcome Trust, UK.

Conflict of interest statement

Conflict of interest

We declare that we have no conflicts of interest.

Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1. Study Flow Diagram
Figure 1. Study Flow Diagram
Figure 2. Distribution of clinical presentations and…
Figure 2. Distribution of clinical presentations and pathogens identified among 763 paediatric patients
Numbers are numbers of patients with each clinical presentation and of each pathogen identified. In some patients, there was more than one clinical presentation or more than one pathogen identified.
Figure 3. Distribution of clinical presentations and…
Figure 3. Distribution of clinical presentations and pathogens identified among 815 adult patients
Numbers are numbers of patients with each clinical presentation and of each pathogen identified. In some patients, there was more than one clinical presentation or more than one pathogen identified.
Figure 4. Overlap among pathogens identified in…
Figure 4. Overlap among pathogens identified in (A) 763 paediatric patients and (B) 815 adult patients
Figure 4. Overlap among pathogens identified in…
Figure 4. Overlap among pathogens identified in (A) 763 paediatric patients and (B) 815 adult patients

References

    1. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004;30(4):536–555.
    1. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296–327.
    1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.
    1. D’Acremont V, Kilowoko M, Kyungu E, et al. Beyond malaria--causes of fever in outpatient Tanzanian children. N Engl J Med. 2014;370(9):809–817.
    1. Farrar J, Hotez P, Junghanss T, Kang G, Lalloo DG, White N. Manson’s Tropical Infectious Diseases. 2014;23
    1. Mayxay M, Sengvilaipaseuth O, Chanthongthip A, et al. Causes of Fever in Rural Southern Laos. Am J Trop Med Hyg. 2015;93(3):517–520.
    1. Mayxay M, Castonguay-Vanier J, Chansamouth V, et al. Causes of non-malarial fever in Laos: a prospective study. Lancet Glob Health. 2013;1(1):e46–e54.
    1. Chheng K, Carter MJ, Emary K, et al. A prospective study of the causes of febrile illness requiring hospitalization in children in Cambodia. PloS One. 2013;8(4):e60634.
    1. McGready R, Ashley EA, Wuthiekanun V, et al. Arthropod borne disease: the leading cause of fever in pregnancy on the Thai-Burmese border. PLoS Negl Trop Dis. 2010;4(11):e888.
    1. Suttinont C, Losuwanaluk K, Niwatayakul K, et al. Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study. Ann Trop Med Parasitol. 2006;100(4):363–370.
    1. Deen J, von Seidlein L, Andersen F, Elle N, White NJ, Lubell Y. Community-acquired bacterial bloodstream infections in developing countries in south and southeast Asia: a systematic review. The Lancet Infect Dis. 2012;12(6):480–487.
    1. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis organ failure guidelines for the use of innovative therapies in sepsis The ACCP/SCCM Consensus Conference Committee American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–1655.
    1. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250–1256.
    1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA. 2016;315(8):801–810.
    1. World health Organization. IMAI District Clinician Manual: Hospital Care for Adolescents and Adults. Guidelines for the Management of Illnesses with Limited Resources. Geneva: [Accessed 1 Aug 16]. (URL:
    1. Goldstein B, Giroir B, Randolph A. International Consensus Conference on Pediatric S. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric Crit Care Med. 2005;6(1):2–8.
    1. Shahunja KM, Leung DT, Ahmed T, et al. Factors Associated with Non-typhoidal Salmonella Bacteremia versus Typhoidal Salmonella Bacteremia in Patients Presenting for Care in an Urban Diarrheal Disease Hospital in Bangladesh. PLoS Negl Trop Dis. 2015;9(9):e0004066.
    1. Thompson CN, Phan VT, Le TP, et al. Epidemiological features and risk factors of Salmonella gastroenteritis in children resident in Ho Chi Minh City, Vietnam. Epidemiol Infect. 2013;141(8):1604–1613.
    1. Ong CW, Lye DC, Khoo KL, et al. Severe community-acquired Acinetobacter baumannii pneumonia: an emerging highly lethal infectious disease in the Asia-Pacific. Respirology. 2009;14(8):1200–1205.
    1. Kanoksil M, Jatapai A, Peacock SJ, Limmathurotsakul D. Epidemiology, microbiology and mortality associated with community-acquired bacteremia in northeast Thailand: a multicenter surveillance study. PloS One. 2013;8(1):e54714.
    1. Limmathurosakul D, Golding N, Dance D, et al. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol. 2016;1:15008.
    1. Suharti C, van Gorp EC, Dolmans WM, et al. Hanta virus infection during dengue virus infection outbreak in Indonesia. Acta Med Indones. 2009;41(2):75–80.
    1. Pattamadilok S, Lee BH, Kumperasart S, et al. Geographical distribution of hantaviruses in Thailand and potential human health significance of Thailand virus. Am J Trop Med Hyg. 2006;75(5):994–1002.
    1. Nutravong T, Angkititrakul S, Jiwakanon N, Wongchanthong W, Dejsirilerts S, Nawa Y. Identification of major Streptococcus suis serotypes 2, 7, 8 and 9 isolated from pigs and humans in upper northeastern Thailand. Southeast Asian J Trop Med Public Health. 2014;45(5):1173–1181.
    1. Huong VT, Hoa NT, Horby P, et al. Raw pig blood consumption and potential risk for Streptococcus suis infection, Vietnam. Emerg Infect Dis. 2014;20(11):1895–1898.
    1. Dittrich S, Rattanavong S, Lee SJ, et al. Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective study. Lancet Glob Health. 2015;3(2):e104–e112.
    1. Araujo F, Nogueira R, Araujo Mde S, et al. Dengue in patients with central nervous system manifestations, Brazil. Emerg Infect Dis. 2012;18(4):677–679.
    1. He S, Ge L, Jin Y, Huang A. [Clinical analysis of scrub typhus-associated hemophagocytic syndrome] Zhonghua Er Ke Za Zhi. 2014;52(9):683–687.
    1. Ono Y, Ikegami Y, Tasaki K, Abe M, Tase C. Case of scrub typhus complicated by severe disseminated intravascular coagulation and death. Emerg Med Australas. 2012;24(5):577–580.
    1. Todd SR, Dahlgren FS, Traeger MS, et al. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. J Pediatr. 2015;166(5):1246–1251.
    1. Limmathurotsakul D, Turner EL, Wuthiekanun V, et al. Fool’s gold: Why imperfect reference tests are undermining the evaluation of novel diagnostics: a reevaluation of 5 diagnostic tests for leptospirosis. Clin Infect Dis. 2012;55(3):322–331.
    1. Zhang X, Wang H, Ding S, et al. Prevalence of enteroviruses in children with and without hand, foot, and mouth disease in China. BMC Infect Dis. 2013;13:606.

Source: PubMed

3
Abonner