Association of clinical signs and symptoms of Ebola viral disease with case fatality: a systematic review and meta-analysis

Figures & data

Fig. 1 Flow chart with selection criterion.

Table 1 General characteristics of studies in this meta-analysis

Study/source	Outbreak – the study was conducted on this particular outbreak	Ebola subtype virus	Cases (confirmed+probable)	Deaths	Case fatality (%)
WHO Ebola Response Team (2)	West Africa 2014	Zaire	4,010	2,839	71
Schieffelin et al. (8)	Sierra Leone 2014	Zaire	106	78	74
Rollin et al. (9)	Uganda 2000	Sudan	123	55	45
Bah et al. (20)	Guinea 2014	Zaire	37	16	43
WHO Weekly record June (21)	Gabon and Congo 2001	Ebola	122	96	78
Okware et al. (22)	Uganda 2000	Sudan	425	224	53
Georges et al. (23)	Gabson 1994	Ebola	52	31	60
Khan et al. (24)	Congo 1995	Ebola	315	250	81
WHO report (3)	Sudan 1976	Sudan	284	151	53
WHO report (4)	Zaire (Congo) 1976	Ebola	318	280	88

Fig. 2 Forest plot: pooled proportion (random effects) of EBV patients with bleeding events.

Fig. 3 Forest plot: pooled proportion (random effects) of EBV patients with fever.

Fig. 4 Funnel plot: bias assessment for EBV patients with bleeding events.

Table 2 Overall association of clinical symptoms and signs with EVD

Symptom/sign	% of pooled proportion of patients with this symptom/sign
Fever	92.9 (95% CI=87.3–96.9)
Headache	73.4 (95% CI=52.9–89.7)
Diarrhea	73.3 (95% CI=66.4–79.7)
Fatigue	68.6 (95% CI=58.6–77.8)
Myalgia/arthralgia	65.7 (95% CI=37.9–88.7)
Vomiting	61.3 (95% CI=53.9–68.4)
Abdominal pain	44.1 (95% CI=29.3–59.4)
Bleeding events^a	42.5 (95% CI=26.9–58.9)
Sore throat	40.3 (95% CI=18.6–64.2)
Conjunctivitis	38.8 (95% CI=19.9–60.1)
Cough	33.3 (95% CI=24.4–42.8)

^aBleeding events include melena, bright red bleed per rectum, epistaxis, hemoptysis, hematemesis, petechiae, conjunctival hemorrhage, gingival hemorrhage, unexplained bleeding, bleeding per vagina, hematuria, and bleeding under skin.

Table 3 Association of clinical signs and symptoms of EVD patients with fatal outcome versus survivors

Symptom/sign	% of pooled proportion of dead patients with this symptom/sign	% of pooled proportion of EVD survivors with this symptom/sign
Diarrhea	69.9 (95% CI=60.7–78.4)	37.8 (95% CI=13.8–65.6)
Bleeding events	64.5 (95% CI=14.8–99.0)	25.1 (95% CI=5.3–53.4)
Vomiting	60.8 (95% CI=49.9–71.2)	31.7 (95% CI=3.8–70.8)
Abdominal pain	58.3 (95% CI=30.8–83.3)	37.5 (95% CI=20.7–55.9)
Sore throat	47.7 (95% CI=11.6–85.3)	19.8 (95% CI=11.4–29.7)
Conjunctivitis	39.3 (95% CI=16.1–65.4)	20.3 (95% CI=10.2–32.7)
Cough	31.6 (95% CI=26.1–37.4)	22.3 (95% CI=20.4–25.1)

Table 4 Heterogeneity data and risk of bias associated with individual symptoms in pooled patient population

Symptom/sign	I^2 (inconsistency)	Harbord bias
Fever	99.2% (95% CI=99–99.4)	2.33 (92.5% CI=−0.85–5.51), P=0.17
Headache	99.1% (95% CI=99–99.2)	6.46 (92.5% CI=−1.69–14.6), P=0.14
Diarrhea	92.4% (95% CI=87.9–94.7)	2.02 (92.5% CI=−1.66–5.69), P=0.28
Fatigue	99% (95% CI=99–99.1)	−2.37 (92.5% CI=−7.91–3.17), P=0.37
Myalgia/arthralgia	99.5% (95% CI=99.4–99.5)	9.99 (92.5% CI=−3.05–23.03), P=0.14
Vomiting	92.1% (95% CI=87.3–94.5)	−2.40 (92.5% CI=−6.29–1.49), P=0.23
Abdominal pain	97.6% (95% CI=96.7–98.2)	1.59 (92.5% CI=−11.04–14.23), P=0.76
Bleeding events	98.8% (95% CI=98.5–99)	10.50 (92.5% CI=2.36–18.63), P=0.03
Sore throat	99% (95% CI=98.8–99.2)	9.43 (92.5% CI=−8.01–26.87), P=0.24
Conjunctivitis	98.2% (95% CI=97.4–98.6)	8.09 (92.5% CI=−7.89–24.07), P=0.22
Cough	93.2% (95% CI=86.1–95.9)	2.06 (92.5% CI=−10.18–14.29), P=0.62

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