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Lancet Infect Dis. 2018 Jun;18(6):684-695. doi: 10.1016/S1473-3099(18)30121-X. Epub 2018 Mar 6.

Clinical and laboratory predictors of Lassa fever outcome in a dedicated treatment facility in Nigeria: a retrospective, observational cohort study.

Author information

1
Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria; Institute of Lassa fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria; Department of Medicine, Faculty of Clinical Sciences, Ambrose Alli University, Ekpoma, Edo, Nigeria. Electronic address: okokherep@gmail.com.
2
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Maryland, MD, USA. Electronic address: andres@broadinstitute.org.
3
Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
4
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
5
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; University of California, Los Angeles, CA, USA; Department of Bioinformatics, Los Angeles, CA, USA.
6
Massachusetts Institute of Technology, Cambridge, MA, USA.
7
Institute of Lassa fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
8
Lassa fever Ward, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
9
Department of Obstetrics and Gynaecology, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
10
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; German Centre for Infection Research, Partner site, Hamburg, Germany.
11
Fathom Information Design, Boston, MA, USA.
12
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard School of Public Health, Boston, MA, USA.
13
Department of Biological Sciences and African Center of Excellence for Genomics of Infectious Diseases, Redeemer's University, Edo, Nigeria.
14
Department of Paediatrics, Irrua Specialist Teaching Hospital, Irrua, Nigeria; Department of Paediatrics, Faculty of Clinical Sciences, Ambrose Alli University, Ekpoma, Edo, Nigeria.
15
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Maryland, MD, USA; Harvard School of Public Health, Boston, MA, USA.

Erratum in

Abstract

BACKGROUND:

Lassa fever is a viral haemorrhagic disease endemic to west Africa. No large-scale studies exist from Nigeria, where the Lassa virus (LASV) is most diverse. LASV diversity, coupled with host genetic and environmental factors, might cause differences in disease pathophysiology. Small-scale studies in Nigeria suggest that acute kidney injury is an important clinical feature and might be a determinant of survival. We aimed to establish the demographic, clinical, and laboratory factors associated with mortality in Nigerian patients with Lassa fever, and hypothesised that LASV was the direct cause of intrinsic renal damage for a subset of the patients with Lassa fever.

METHODS:

We did a retrospective, observational cohort study of consecutive patients in Nigeria with Lassa fever, who tested positive for LASV with RT-PCR, and were treated in Irrua Specialist Teaching Hospital. We did univariate and multivariate statistical analyses, including logistic regression, of all demographic, clinical, and laboratory variables available at presentation to identify the factors associated with patient mortality.

FINDINGS:

Of 291 patients treated in Irrua Specialist Teaching Hospital between Jan 3, 2011, and Dec 11, 2015, 284 (98%) had known outcomes (died or survived) and seven (2%) were discharged against medical advice. Overall case-fatality rate was 24% (68 of 284 patients), with a 1·4 times increase in mortality risk for each 10 years of age (p=0·00017), reaching 39% (22 of 57) for patients older than 50 years. Of 284 patients, 81 (28%) had acute kidney injury and 104 (37%) had CNS manifestations and thus both were considered important complications of acute Lassa fever in Nigeria. Acute kidney injury was strongly associated with poor outcome (case-fatality rate of 60% [49 of 81 patients]; odds ratio [OR] 15, p<0·00001). Compared with patients without acute kidney injury, those with acute kidney injury had higher incidence of proteinuria (32 [82%] of 39 patients) and haematuria (29 [76%] of 38) and higher mean serum potassium (4·63 [SD 1·04] mmol/L) and lower blood urea nitrogen to creatinine ratio (8·6 for patients without clinical history of fluid loss), suggesting intrinsic renal damage. Normalisation of creatinine concentration was associated with recovery. Elevated serum creatinine (OR 1·3; p=0·046), aspartate aminotransferase (OR 1·5; p=0·075), and potassium (OR 3·6; p=0·0024) were independent predictors of death.

INTERPRETATION:

Our study presents detailed clinical and laboratory data for Nigerian patients with Lassa fever and provides strong evidence for intrinsic renal dysfunction in acute Lassa fever. Early recognition and treatment of acute kidney injury might significantly reduce mortality.

FUNDING:

German Research Foundation, German Center for Infection Research, Howard Hughes Medical Institute, US National Institutes of Health, and World Bank.

PMID:
29523497
PMCID:
PMC5984133
[Available on 2019-06-01]
DOI:
10.1016/S1473-3099(18)30121-X

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