Skip to main content
Top
Published in: Critical Care 1/2019

Open Access 01-12-2019 | Tuberculosis | Research

Aetiology and outcomes of sepsis in adults in sub-Saharan Africa: a systematic review and meta-analysis

Authors: Joseph M. Lewis, Nicholas A. Feasey, Jamie Rylance

Published in: Critical Care | Issue 1/2019

Login to get access

Abstract

Background

Aetiology and outcomes of sepsis in sub-Saharan Africa (sSA) are poorly described; we performed a systematic review and meta-analysis to summarise the available data.

Methods

Systematic searches of PubMed and Scopus were undertaken to identify prospective studies recruiting adults (> 13 years) with community-acquired sepsis in sSA post-2000. Random effects meta-analysis of in-hospital and 30-day mortality was undertaken and available aetiology data also summarised by random effects meta-analysis.

Results

Fifteen studies of 2800 participants were identified. Inclusion criteria were heterogeneous. The majority of patients were HIV-infected, and Mycobacterium tuberculosis was the most common cause of blood stream infection where sought. Pooled in-hospital mortality for Sepsis-2-defined sepsis and severe sepsis was 19% (95% CI 12–29%) and 39% (95% CI 30–47%) respectively, and sepsis mortality was associated with the proportion of HIV-infected participants. Mortality and morbidity data beyond 30 days were absent.

Conclusions

Sepsis in sSA is dominated by HIV and tuberculosis, with poor outcomes. Optimal antimicrobial strategies, including the role of tuberculosis treatment, are unclear. Long-term outcome data are lacking. Standardised sepsis diagnostic criteria that are easily applied in low-resource settings are needed to establish an evidence base for sepsis management in sSA.
Appendix
Available only for authorised users
Literature
1.
go back to reference Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801.CrossRef Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801.CrossRef
2.
go back to reference Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259–72.CrossRef Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259–72.CrossRef
3.
go back to reference Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States*. Crit Care Med. 2013;41:1167–74.CrossRef Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States*. Crit Care Med. 2013;41:1167–74.CrossRef
4.
go back to reference Kaukonen K-M, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014;311:1308–16.CrossRef Kaukonen K-M, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014;311:1308–16.CrossRef
5.
go back to reference Jacob ST, Moore CC, Banura P, Pinkerton R, Meya D, Opendi P, et al. Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population. PLoS One. 2009;4:e7782.CrossRef Jacob ST, Moore CC, Banura P, Pinkerton R, Meya D, Opendi P, et al. Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population. PLoS One. 2009;4:e7782.CrossRef
6.
go back to reference Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011;364:2483–95.CrossRef Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011;364:2483–95.CrossRef
7.
go back to reference Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension. JAMA. 2017;318:1233.CrossRef Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension. JAMA. 2017;318:1233.CrossRef
8.
go back to reference Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis. JAMA. 2016;315:762.CrossRef Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis. JAMA. 2016;315:762.CrossRef
9.
go back to reference Rudd KE, Seymour CW, Aluisio AR, Augustin ME, Bagenda DS, Beane A, et al. Association of the quick sequential (sepsis-related) organ failure assessment (qSOFA) score with excess hospital mortality in adults with suspected infection in low- and middle-income countries. JAMA. 2018;319:2202.CrossRef Rudd KE, Seymour CW, Aluisio AR, Augustin ME, Bagenda DS, Beane A, et al. Association of the quick sequential (sepsis-related) organ failure assessment (qSOFA) score with excess hospital mortality in adults with suspected infection in low- and middle-income countries. JAMA. 2018;319:2202.CrossRef
10.
go back to reference Adhikari NKJ, Rubenfeld GD. qSOFA score for patients with Sepsis in low- and middle-income countries. JAMA. 2018;319:2175.CrossRef Adhikari NKJ, Rubenfeld GD. qSOFA score for patients with Sepsis in low- and middle-income countries. JAMA. 2018;319:2175.CrossRef
11.
go back to reference Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2003;31:1250–6.CrossRef Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2003;31:1250–6.CrossRef
12.
go back to reference Kaukonen K-M, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015;372:1629–38.CrossRef Kaukonen K-M, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015;372:1629–38.CrossRef
13.
go back to reference Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–96.CrossRef Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–96.CrossRef
14.
go back to reference Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376:2235–44.CrossRef Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376:2235–44.CrossRef
15.
go back to reference Muchemwa L, Shabir L, Andrews B, Bwalya M. High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV-infected patients with severe sepsis in Lusaka, Zambia. Int J STD AIDS. 2017;28:584–93.CrossRef Muchemwa L, Shabir L, Andrews B, Bwalya M. High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV-infected patients with severe sepsis in Lusaka, Zambia. Int J STD AIDS. 2017;28:584–93.CrossRef
16.
go back to reference Jacob ST, Pavlinac PB, Nakiyingi L, Banura P, Baeten JM, Morgan K, et al. Mycobacterium tuberculosis bacteremia in a cohort of hiv-infected patients hospitalized with severe sepsis in Uganda-high frequency, low clinical suspicion [corrected] and derivation of a clinical prediction score. PLoS One 2013/08/14. 2013;8:e70305.CrossRef Jacob ST, Pavlinac PB, Nakiyingi L, Banura P, Baeten JM, Morgan K, et al. Mycobacterium tuberculosis bacteremia in a cohort of hiv-infected patients hospitalized with severe sepsis in Uganda-high frequency, low clinical suspicion [corrected] and derivation of a clinical prediction score. PLoS One 2013/08/14. 2013;8:e70305.CrossRef
17.
go back to reference Crump JA, Ramadhani HO, Morrissey AB, Saganda W, Mwako MS, Yang LY, et al. Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania. Clin Infect Dis. 2011;52:341–8.CrossRef Crump JA, Ramadhani HO, Morrissey AB, Saganda W, Mwako MS, Yang LY, et al. Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania. Clin Infect Dis. 2011;52:341–8.CrossRef
18.
go back to reference Crump JA, Morrissey AB, Nicholson WL, Massung RF, Stoddard RA, Galloway RL, et al. Etiology of severe non-malaria febrile illness in northern Tanzania: a prospective cohort study. PLoS Negl Trop Dis. 2013;7:e2324.CrossRef Crump JA, Morrissey AB, Nicholson WL, Massung RF, Stoddard RA, Galloway RL, et al. Etiology of severe non-malaria febrile illness in northern Tanzania: a prospective cohort study. PLoS Negl Trop Dis. 2013;7:e2324.CrossRef
19.
go back to reference Rubach MP, Maro VP, Bartlett JA, Crump JA. Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy. Am J Trop Med Hyg. 2015;92:454–62.CrossRef Rubach MP, Maro VP, Bartlett JA, Crump JA. Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy. Am J Trop Med Hyg. 2015;92:454–62.CrossRef
20.
go back to reference Huson MAM, Kalkman R, Stolp SM, Janssen S, Alabi AS, Beyeme JO, et al. The impact of HIV on presentation and outcome of bacterial sepsis and other causes of acute febrile illness in Gabon. Infection. 2015;43:443–51.CrossRef Huson MAM, Kalkman R, Stolp SM, Janssen S, Alabi AS, Beyeme JO, et al. The impact of HIV on presentation and outcome of bacterial sepsis and other causes of acute febrile illness in Gabon. Infection. 2015;43:443–51.CrossRef
21.
go back to reference Chimese SM, Andrews B, Lakhi S. The etiology and outcome of adult patients presenting with sepsis to the University Teaching Hospital, Lusaka, Zambia. Med J Zambia. 2012;39:19–22.PubMedPubMedCentral Chimese SM, Andrews B, Lakhi S. The etiology and outcome of adult patients presenting with sepsis to the University Teaching Hospital, Lusaka, Zambia. Med J Zambia. 2012;39:19–22.PubMedPubMedCentral
22.
go back to reference Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE. Long-term mortality and quality of life in sepsis: a systematic review*. Crit Care Med. 2010;38:1276–83.CrossRef Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE. Long-term mortality and quality of life in sepsis: a systematic review*. Crit Care Med. 2010;38:1276–83.CrossRef
23.
go back to reference Moore CC, Jacob ST, Banura P, Zhang J, Stroup S, Boulware DR, et al. Etiology of sepsis in Uganda using a quantitative PCR-based TaqMan array card. Clin Infect Dis. 2019;68:266–72.CrossRef Moore CC, Jacob ST, Banura P, Zhang J, Stroup S, Boulware DR, et al. Etiology of sepsis in Uganda using a quantitative PCR-based TaqMan array card. Clin Infect Dis. 2019;68:266–72.CrossRef
24.
go back to reference Amir A, Saulters KJ, Olum S, Pitts K, Parsons A, Churchill C, et al. Outcomes of patients with severe sepsis after the first 6 hours of resuscitation at a regional referral hospital in Uganda. J Crit Care. 2016;33:78–83.CrossRef Amir A, Saulters KJ, Olum S, Pitts K, Parsons A, Churchill C, et al. Outcomes of patients with severe sepsis after the first 6 hours of resuscitation at a regional referral hospital in Uganda. J Crit Care. 2016;33:78–83.CrossRef
25.
go back to reference Nadjm B, Mtove G, Amos B, Walker NF, Diefendal H, Reyburn H, et al. Severe febrile illness in adult hospital admissions in Tanzania: a prospective study in an area of high malaria transmission. Trans R Soc Trop Med Hyg. 2012;106:688–95.CrossRef Nadjm B, Mtove G, Amos B, Walker NF, Diefendal H, Reyburn H, et al. Severe febrile illness in adult hospital admissions in Tanzania: a prospective study in an area of high malaria transmission. Trans R Soc Trop Med Hyg. 2012;106:688–95.CrossRef
26.
go back to reference Waitt PI, Mukaka M, Goodson P, SimuKonda FD, Waitt CJ, Feasey N, et al. Sepsis carries a high mortality among hospitalised adults in Malawi in the era of antiretroviral therapy scale-up: a longitudinal cohort study. J Inf Secur. 2015;70:11–9. Waitt PI, Mukaka M, Goodson P, SimuKonda FD, Waitt CJ, Feasey N, et al. Sepsis carries a high mortality among hospitalised adults in Malawi in the era of antiretroviral therapy scale-up: a longitudinal cohort study. J Inf Secur. 2015;70:11–9.
27.
go back to reference Ssekitoleko R, Jacob ST, Banura P, Pinkerton R, Meya DB, Reynolds SJ, et al. Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis. Crit Care Med. 2011;39:2271–6.CrossRef Ssekitoleko R, Jacob ST, Banura P, Pinkerton R, Meya DB, Reynolds SJ, et al. Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis. Crit Care Med. 2011;39:2271–6.CrossRef
28.
go back to reference Ssekitoleko R, Pinkerton R, Muhindo R, Bhagani S, Moore CC. Aggregate evaluable organ dysfunction predicts in-hospital mortality from sepsis in Uganda. Am J Trop Med Hyg. 2011;85:697–702.CrossRef Ssekitoleko R, Pinkerton R, Muhindo R, Bhagani S, Moore CC. Aggregate evaluable organ dysfunction predicts in-hospital mortality from sepsis in Uganda. Am J Trop Med Hyg. 2011;85:697–702.CrossRef
29.
go back to reference Auma MA, Siedner MJ, Nyehangane D, Nalusaji A, Nakaye M, Mwanga-Amumpaire J, et al. Malaria is an uncommon cause of adult sepsis in South-Western Uganda. Malar J. 2013;12:146.CrossRef Auma MA, Siedner MJ, Nyehangane D, Nalusaji A, Nakaye M, Mwanga-Amumpaire J, et al. Malaria is an uncommon cause of adult sepsis in South-Western Uganda. Malar J. 2013;12:146.CrossRef
30.
go back to reference Seboxa T, Amogne W, Abebe W, Tsegaye T, Azazh A, Hailu W, et al. High mortality from blood stream infection in Addis Ababa, Ethiopia, is due to antimicrobial resistance. PLoS One. 2015;10:e0144944.CrossRef Seboxa T, Amogne W, Abebe W, Tsegaye T, Azazh A, Hailu W, et al. High mortality from blood stream infection in Addis Ababa, Ethiopia, is due to antimicrobial resistance. PLoS One. 2015;10:e0144944.CrossRef
31.
go back to reference Rudd KE, Tutaryebwa LK, West TE. Presentation, management, and outcomes of sepsis in adults and children admitted to a rural Ugandan hospital: a prospective observational cohort study. PLoS One. 2017;12:e0171422.CrossRef Rudd KE, Tutaryebwa LK, West TE. Presentation, management, and outcomes of sepsis in adults and children admitted to a rural Ugandan hospital: a prospective observational cohort study. PLoS One. 2017;12:e0171422.CrossRef
32.
go back to reference Andrews B, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, Bernard GR. Simplified severe sepsis protocol: a randomized controlled trial of modified early goal-directed therapy in Zambia. Crit Care Med. 2014;42:2315–24.CrossRef Andrews B, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, Bernard GR. Simplified severe sepsis protocol: a randomized controlled trial of modified early goal-directed therapy in Zambia. Crit Care Med. 2014;42:2315–24.CrossRef
33.
go back to reference Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. Jama. 2017;318:1233–40.CrossRef Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. Jama. 2017;318:1233–40.CrossRef
34.
go back to reference Jacob ST, Banura P, Baeten JM, Moore CC, Meya D, Nakiyingi L, et al. The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study*. Crit Care Med. 2012;40:2050–8.CrossRef Jacob ST, Banura P, Baeten JM, Moore CC, Meya D, Nakiyingi L, et al. The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study*. Crit Care Med. 2012;40:2050–8.CrossRef
35.
go back to reference Andrews B, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, Bernard GR. Simplified severe sepsis protocol. Crit Care Med. 2014;42:2315–24.CrossRef Andrews B, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, Bernard GR. Simplified severe sepsis protocol. Crit Care Med. 2014;42:2315–24.CrossRef
36.
go back to reference Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA. Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet. 2012;379:2489–99.CrossRef Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA. Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet. 2012;379:2489–99.CrossRef
37.
go back to reference French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, et al. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010;362:812–22.CrossRef French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, et al. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010;362:812–22.CrossRef
38.
go back to reference Musicha P, Cornick JE, Bar-Zeev N, French N, Masesa C, Denis B, et al. Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study. Lancet Infect Dis. 2017;17:1042–52.CrossRef Musicha P, Cornick JE, Bar-Zeev N, French N, Masesa C, Denis B, et al. Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study. Lancet Infect Dis. 2017;17:1042–52.CrossRef
39.
go back to reference Osawa R, Singh N. Cytomegalovirus infection in critically ill patients: a systematic review. Crit Care. 2009;13:R68.CrossRef Osawa R, Singh N. Cytomegalovirus infection in critically ill patients: a systematic review. Crit Care. 2009;13:R68.CrossRef
40.
go back to reference Lai PS, Bebell LM, Meney C, Valeri L, White MC. Epidemiology of antibiotic-resistant wound infections from six countries in Africa. BMJ Glob Health. 2018;2:e000475.CrossRef Lai PS, Bebell LM, Meney C, Valeri L, White MC. Epidemiology of antibiotic-resistant wound infections from six countries in Africa. BMJ Glob Health. 2018;2:e000475.CrossRef
41.
go back to reference Ntirenganya C, Manzi O, Muvunyi CM, Ogbuagu O. High prevalence of antimicrobial resistance among common bacterial isolates in a tertiary healthcare facility in Rwanda. Am J Trop Med Hyg. 2015;92:865–70.CrossRef Ntirenganya C, Manzi O, Muvunyi CM, Ogbuagu O. High prevalence of antimicrobial resistance among common bacterial isolates in a tertiary healthcare facility in Rwanda. Am J Trop Med Hyg. 2015;92:865–70.CrossRef
42.
go back to reference Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.CrossRef Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.CrossRef
43.
go back to reference Hartling L, Milne A, Hamm MP, Vandermeer B, Ansari M, Tsertsvadze A, et al. Testing the Newcastle Ottawa scale showed low reliability between individual reviewers. J Clin Epidemiol. 2013;66:982–93.CrossRef Hartling L, Milne A, Hamm MP, Vandermeer B, Ansari M, Tsertsvadze A, et al. Testing the Newcastle Ottawa scale showed low reliability between individual reviewers. J Clin Epidemiol. 2013;66:982–93.CrossRef
Metadata
Title
Aetiology and outcomes of sepsis in adults in sub-Saharan Africa: a systematic review and meta-analysis
Authors
Joseph M. Lewis
Nicholas A. Feasey
Jamie Rylance
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2501-y

Other articles of this Issue 1/2019

Critical Care 1/2019 Go to the issue