Clinical Infectious Diseases Advance Access published April 2, 2015
BRIEF REPORT
Clinical Predictors of Mortality in Patients With Ebola Virus Disease Moumié Barry,1 Abdoulaye Touré,2 Fodé Amara Traoré,1,3 Fodé-Bangaly Sako,1 Djibril Sylla,4 Dimai Ouo Kpamy,1 Elhadj Ibrahima Bah,1 M’Mah Bangoura,1 Marc Poncin,5 Sakoba Keita,6 Thierno Mamadou Tounkara,2 Mohamed Cisse,2 and Philippe Vanhems7 1
MATERIALS AND METHODS Study Setting and Population
In an observational cohort study including 89 Ebola patients, predictive factors of death were analyzed. The crude mortality rate was 43.8%. Myalgia (adjusted odds ratio [OR], 4.04; P = .02), hemorrrhage (adjusted OR, 3.5; P = .02), and difficulty breathing (adjusted OR, 5.75; P = .01) were independently associated with death. Keywords.
Ebola virus disease; hemorrhagic fever; mortality.
Ebola virus disease (EVD) is often fatal, with a mortality rate of approximately 65% in African countries [1]. No vaccine or other treatment is currently available. A total of 25 outbreaks, believed to have been caused by zoonotic transmission from wild mammals, have occurred since the first observed cases in humans in 1976 [2]. Outbreaks caused by the genera Ebolavirus and Marburgvirus represent a major public health issue in sub-Saharan Africa. Humans infected with Ebolavirus commonly initially present with symptoms such as fever, vomiting, and severe diarrhea, with visible hemorrhaging occurring in less than half the cases [3, 4]. On 21 March 2014, the World Health Organization was notified of a rapidly evolving outbreak of EVD in the forested regions of southeastern Guinea that subsequently spread to the
Received 12 October 2014; accepted 1 February 2015. Correspondence: Abdoulaye Touré, PharmD, PhD, Faculté de Médecine, Pharmacie OdontoStomatologie, Université de Conakry, Conakry, Guinée ([email protected]). Clinical Infectious Diseases® © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/civ202
This prospective observational study was performed at a center for EVD treatment. This center was implemented by the infectious and tropical diseases department of Donka National Hospital and Médecins Sans Frontières (Doctors Without Borders) at Conakry. The center has been the reference center for Ebola clinical management in Conakry since the beginning of the outbreak. All patients with EVD diagnosed between March and August 2014 were included. Inclusion criteria were a diagnosis of Ebola infection and hospitalization at the Donka center for Ebola treatment. Individuals with suspected Ebolavirus infection were not included in this study. Standardized surveillance was performed in all patients. Patients were followed up from the date of admission in the center until discharge or death. The following data were collected on standardized case-report forms: age, sex, comorbidities, nutritional status, and Ebola symptoms including fever, headache, fatigue, asthenia, myalgia, arthralgia, hiccup, anorexia, nausea, vomiting, stomachache, diarrhea, difficulty breathing, back pain, and hemorrhage. We also recorded time from the beginning of the first symptom to date of hospitalization, and evolution of infection (death or survival). Patient outcomes were analyzed until inpatient death or last point of hospital contact. During their hospitalization in the Ebola treatment center, patients received treatment including rehydration (oral rehydration solution, Ringer lactate), vitamin therapy, antibiotic prophylaxis for the prevention of bacterial infections (ceftriaxone, cefixime, metronidazole), and acetaminophen according to their symptoms. Diagnosis of EVD
All cases of EVD included in this study were confirmed by the diagnostic gold standard, reverse transcription polymerase
BRIEF REPORT
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Downloaded from http://cid.oxfordjournals.org/ at USDSM Wegner Health Science Info. Cntr. on April 9, 2015
Service des Maladies Infectieuses et Tropicales, Hôpital National Donka, 2Chaire de Santé Publique, Département de Pharmacie, 3Chaire de Dermatologie et Maladies Infectieuses, and 4Chaire de Médecine Interne, Université de Conakry, CHU Conakry, 5Médecins Sans Frontières-Belgique, and 6Division Prévention et lutte contre la Maladie, Ministère de la Santé Publique, Guinée; and 7Service d’Hygiène Hospitalière, Epidémiologie et Prévention, Hôpital Edouard Herriot, Hospices Civils de Lyon, et Université Claude Bernard, Université Lyon 1, France
capital city, Conakry, marking the world’s first EVD outbreak in a major metropolitan area [5]. The first results showed that mortality was 71% on the basis of clinical suspicion in areas of Guéckédou, Macenta, and Kissidougou [6, 7]. To the best of our knowledge, the factors associated with death in the current Ebola outbreak were not documented. We undertook a single-center cohort investigation to analyze the factors linked to Ebola symptoms and death in Ebola patients hospitalized in Guinea.
Table 1. Predictors of Mortality in Patients With Ebola Virus Disease Treated Between March and August 2014 at Donka National Hospital Univariate Analysis
Multivariate Analysis
Characteristic
OR
95% CI
P Value
Age, ya Female sex
1.02 1.84
.99–1.05 .75–4.51
.30 .18
Healthcare workerb
0.77
.27–2.23
.64
Malaria Symptoms on admission
0.56
.22–1.45
.23
Fever
1.24
.49–3.18
.65
Headache Fatigue and asthenia
0.67 1.14
.29–1.56 .39–3.34
.36 .81
95% CI
P Value
4.04
1.27–12.88
.01
Myalgia
2.63
.96–7.72
.06
Arthralgia Hiccup
1.97 7.21
.57–6.73 .81–64.46
.28 .08
Anorexia
0.88
.38–2.03
.76
Nausea and vomiting Stomachache
1.07 0.98
.45–2.52 .38–2.56
.88 .97
Diarrhea
2.20
.90–5.38
.08
2.65
.96–7.37
.06
Difficulty breathing Back pain
3.45 2.65
.97–12.22 .23–30.33
.05 .43
5.75
1.42–23.17
.01
Hemorrhage
3.28
.02
3.52
1.20–10.36
.02
1.21–8.87
Abbreviations: CI, confidence interval; OR, odds ratio. a
Age was included as a continuous variable.
b
Medical doctor (n = 11), nurse (n = 5), ambulance worker (n = 1).
chain reaction (RT-PCR), which is able to detect the virus both in patients with primo infection and advanced disease. The diagnosis was performed by highly qualified personnel from France Institute Pasteur and Dakar Institute Pasteur. Diagnostic testing was repeated during the course of the disease in patients. A negative RT-PCR was required to confirm cure and allow patients to be discharged. RT-PCR was performed every 48 hours in clinically recovered patients before they could leave the Ebola treatment center.
factors associated with death. All potential risk factors significant at the 0.2 level in univariate analysis were entered into the model. The goodness-of-fit of the models was assessed by the Hosmer-Lemeshow test. For all tests performed, 2-tailed P values 95% of malaria infections. Paracheck (Orchid Biomedical Systems, Goa, India), which detects a P. falciparum–specific histidine-rich protein (PfHRP-2), was used for each patient for malaria testing. This test requires approximately 5 µL of blood and is readable after 15 minutes. Statistical Analysis
Categorical variables were compared by the χ2 test or Fisher exact test. Continuous variables, expressed as median and interquartile range (IQR), were compared by the Mann–Whitney U-test. A multivariate logistic regression model identified
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RESULTS
Downloaded from http://cid.oxfordjournals.org/ at USDSM Wegner Health Science Info. Cntr. on April 9, 2015
Adjusted OR
death was hypovolemic shock and multiorgan failure in the 39 who died. The results of univariate and multivariate analyses are shown in Table 1. The independent predictive factors of death were hemorrhage (adjusted odds ratio [OR], 3.52; 95% confidence interval [CI], 1.20–10.36), myalgia (adjusted OR, 4.04; 95% CI, 1.27–12.88), and difficulty breathing (adjusted OR, 5.75; 95% CI, 1.42–23.17). DISCUSSION
Notes Acknowledgments. The authors thank Médecins Sans Frontières, the Guinea Red Cross, the World Health Organization in Guinea, and all of the organizations, institutions, professionals, healthcare workers, and political and civic leaders who have made efforts to support the patients. Potential conflicts of interest. All authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References 1. Lefebvre A, Fiet C, Belpois-Duchamp C, Tiv M, Astruc K, Aho Glélé LS. Case fatality rates of Ebola virus diseases: a meta-analysis of World Health Organization data. Med Mal Infect 2014; 44:412–6. 2. House T. Epidemiological dynamics of Ebola outbreaks. eLife 2014; doi:10.7554/eLife.03908. 3. Feldmann H. Ebola—a growing threat? N Engl J Med 2014; doi:10. 1056/NEJMp1405314.. 4. MacNeil A, Farnon EC, Wamala J, et al. Proportion of deaths and clinical features in Bundibugyo Ebola virus infection, Uganda. Emerg Infect Dis 2010; 16:1969–72. 5. Fowler RA, Fletcher T, Fischer WA, et al. Caring for critically ill patients with Ebola virus disease: perspectives from West Africa. Am J Respir Crit Care Med 2014; 190:733–7.
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Downloaded from http://cid.oxfordjournals.org/ at USDSM Wegner Health Science Info. Cntr. on April 9, 2015
Since Ebolavirus was first identified in 1976, no previous Ebola outbreak has been as large or persistent as the current epidemic, and none has spread beyond East and Central Africa. It is known that EVD is associated with a high mortality rate. In this study, we aimed to analyze the clinical predictive factors of mortality in patients with EVD treated at Conakry center. Data showed that the overall mortality rate was 43.8%. This finding is consistent with results obtained from other studies [2, 8–13]. However, in Guinea, our finding is lower than previous data reported from Gueckedou, Macenta, and Kissidougou, the outbreak epicenter [6]. This could be explained by the fact that, in this country, the first cases of Ebola were reported in these prefectures and that, at that time, Guinean physicians did not have any experience in the management of this disease. This could also be due to the fact that in the prefectures, people are not compliant with the Ebola campaign. Therefore, these patients could have had delayed access to care compared with patients who were admitted to the Conakry center for Ebola treatment. The early symptoms of Ebola include fever, extreme asthenia, diarrhea, nausea and vomiting, anorexia, abdominal pain, headaches, arthralgia, myalgia, and back pain [5, 14]. In our study, univariate analyses showed that the occurrence of these symptoms was not statistically different between the fatal and nonfatal cases. However, the results of the multivariate models showed that myalgia was an independent factor associated with death. This finding could be explained by the fact that Ebola is a very severe disease, and patients tend to have more severe clinical features such as body temperature >39°C. A previous study showed that almost two-thirds of the survivors continued to suffer from myalgia 21 months after their acute illness, and many described their myalgia and arthralgia as major health problems [14]. Moreover, the factors associated with myalgia in EVD patients are not well known. Hemorrhage is one of the main clinical manifestations of EVD, usually in the form of gastrointestinal bleeding. In this study, hemorrhage occurred in 23 patients, corresponding to 38.5% of those who died and 16.0% of those who survived (P = .04). This figure was 30% in Uganda in 2002. Our finding showed that this symptom was independently associated with death (adjusted OR, 3.52; P = .02). This sign usually appeared in the hours preceding death [15]. The occurrence of bleeding
signs indicated a poor prognosis in Ebola patients, except for melena, which was sometimes noted early in the disease and occurred in survivors and nonsurvivors. Difficulty breathing on admission was independently associated with death. Owing to vomiting and diarrhea, which lead to intravascular volume depletion and complications including profound electrolyte disorders, hypoperfusion, and shock, management of Ebola patients includes systematic parenteral rehydration. This could improve the overall prognosis, but could also lead to edema in patients with respiratory disease. Ebolavirus infections are characterized by immunosuppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock [16]. In the current study, in the 39 patients who died, the causes were hypovolemic shock and multiorgan failure. This study has some limitations. First, we did not take into account the length of stay at the center for treatment because the date of discharge was not recorded. This could be useful for survival analysis. Second, the duration of each symptom was not recorded. Finally, treatments such as hydration were administered to patients, but specific data were not recorded. However, to the best of our knowledge, this is the first study that reports the clinical predictors of death in patients with EVD. These results, particularly myalgia, need to be confirmed and complete with biological data or other features related to death.
6. Baize S, Pannetier D, Oestereich L, et al. Emergence of Zaire Ebola virus disease in guinea—preliminary report. N Engl J Med 2014; 371:1418–25. 7. Aylward B, Barboza P, Bawo L, et al. Ebola virus disease in West Africa —the first 9 months of the epidemic and forward projections. N Engl J Med 2014; 371:1481–95. 8. Onyango CO, Opoka ML, Ksiazek TG, et al. Laboratory diagnosis of Ebola virus disease during an outbreak in Yambio, Sudan, 2004. J Infect Dis 2007; 196:S193–8. 9. Bonnet MJ, Akamituna P, Mazaya A. Unrecognized Ebola virus disease at Mosango Hospital during the 1995 epidemic in Kikwit, Democratic Republic of the Congo. Emerg Infect Dis 1998; 4:508–10. 10. Muyembe-Tamfum JJ, Kipasa M, Kiyungu C, Colebunders R. Ebola outbreak in Kikwit, Democratic Republic of the Congo: discovery and control measures. J Infect Dis 1999; 179:S259–62.
11. Mason C. The strains of Ebola. CMAJ 2008; 178:1266–7. 12. Nkoghe D, Kone ML, Yada A, Leroy E. A limited outbreak of Ebola haemorrhagic fever in Etoumbi, Republic of Congo, 2005. Trans R Soc Trop Med Hyg 2011; 105:466–72. 13. Okware SI, Omaswa FG, Zaramba S, et al. An outbreak of Ebola in Uganda. Trop Med Int Health 2002; 7:1068–75. 14. Bwaka MA, Bonnet MJ, Calain P, et al. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis 1999; 179:S1–7. 15. Rowe AK, Bertolli J, Khan AS, et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola virus disease patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis 1999; 179:S28–35. 16. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet 2011; 377:849–62.
Downloaded from http://cid.oxfordjournals.org/ at USDSM Wegner Health Science Info. Cntr. on April 9, 2015
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BRIEF REPORT
BRIEF REPORT
Clinical Predictors of Mortality in Patients With Ebola Virus Disease Moumié Barry,1 Abdoulaye Touré,2 Fodé Amara Traoré,1,3 Fodé-Bangaly Sako,1 Djibril Sylla,4 Dimai Ouo Kpamy,1 Elhadj Ibrahima Bah,1 M’Mah Bangoura,1 Marc Poncin,5 Sakoba Keita,6 Thierno Mamadou Tounkara,2 Mohamed Cisse,2 and Philippe Vanhems7 1
MATERIALS AND METHODS Study Setting and Population
In an observational cohort study including 89 Ebola patients, predictive factors of death were analyzed. The crude mortality rate was 43.8%. Myalgia (adjusted odds ratio [OR], 4.04; P = .02), hemorrrhage (adjusted OR, 3.5; P = .02), and difficulty breathing (adjusted OR, 5.75; P = .01) were independently associated with death. Keywords.
Ebola virus disease; hemorrhagic fever; mortality.
Ebola virus disease (EVD) is often fatal, with a mortality rate of approximately 65% in African countries [1]. No vaccine or other treatment is currently available. A total of 25 outbreaks, believed to have been caused by zoonotic transmission from wild mammals, have occurred since the first observed cases in humans in 1976 [2]. Outbreaks caused by the genera Ebolavirus and Marburgvirus represent a major public health issue in sub-Saharan Africa. Humans infected with Ebolavirus commonly initially present with symptoms such as fever, vomiting, and severe diarrhea, with visible hemorrhaging occurring in less than half the cases [3, 4]. On 21 March 2014, the World Health Organization was notified of a rapidly evolving outbreak of EVD in the forested regions of southeastern Guinea that subsequently spread to the
Received 12 October 2014; accepted 1 February 2015. Correspondence: Abdoulaye Touré, PharmD, PhD, Faculté de Médecine, Pharmacie OdontoStomatologie, Université de Conakry, Conakry, Guinée ([email protected]). Clinical Infectious Diseases® © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/civ202
This prospective observational study was performed at a center for EVD treatment. This center was implemented by the infectious and tropical diseases department of Donka National Hospital and Médecins Sans Frontières (Doctors Without Borders) at Conakry. The center has been the reference center for Ebola clinical management in Conakry since the beginning of the outbreak. All patients with EVD diagnosed between March and August 2014 were included. Inclusion criteria were a diagnosis of Ebola infection and hospitalization at the Donka center for Ebola treatment. Individuals with suspected Ebolavirus infection were not included in this study. Standardized surveillance was performed in all patients. Patients were followed up from the date of admission in the center until discharge or death. The following data were collected on standardized case-report forms: age, sex, comorbidities, nutritional status, and Ebola symptoms including fever, headache, fatigue, asthenia, myalgia, arthralgia, hiccup, anorexia, nausea, vomiting, stomachache, diarrhea, difficulty breathing, back pain, and hemorrhage. We also recorded time from the beginning of the first symptom to date of hospitalization, and evolution of infection (death or survival). Patient outcomes were analyzed until inpatient death or last point of hospital contact. During their hospitalization in the Ebola treatment center, patients received treatment including rehydration (oral rehydration solution, Ringer lactate), vitamin therapy, antibiotic prophylaxis for the prevention of bacterial infections (ceftriaxone, cefixime, metronidazole), and acetaminophen according to their symptoms. Diagnosis of EVD
All cases of EVD included in this study were confirmed by the diagnostic gold standard, reverse transcription polymerase
BRIEF REPORT
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CID
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1
Downloaded from http://cid.oxfordjournals.org/ at USDSM Wegner Health Science Info. Cntr. on April 9, 2015
Service des Maladies Infectieuses et Tropicales, Hôpital National Donka, 2Chaire de Santé Publique, Département de Pharmacie, 3Chaire de Dermatologie et Maladies Infectieuses, and 4Chaire de Médecine Interne, Université de Conakry, CHU Conakry, 5Médecins Sans Frontières-Belgique, and 6Division Prévention et lutte contre la Maladie, Ministère de la Santé Publique, Guinée; and 7Service d’Hygiène Hospitalière, Epidémiologie et Prévention, Hôpital Edouard Herriot, Hospices Civils de Lyon, et Université Claude Bernard, Université Lyon 1, France
capital city, Conakry, marking the world’s first EVD outbreak in a major metropolitan area [5]. The first results showed that mortality was 71% on the basis of clinical suspicion in areas of Guéckédou, Macenta, and Kissidougou [6, 7]. To the best of our knowledge, the factors associated with death in the current Ebola outbreak were not documented. We undertook a single-center cohort investigation to analyze the factors linked to Ebola symptoms and death in Ebola patients hospitalized in Guinea.
Table 1. Predictors of Mortality in Patients With Ebola Virus Disease Treated Between March and August 2014 at Donka National Hospital Univariate Analysis
Multivariate Analysis
Characteristic
OR
95% CI
P Value
Age, ya Female sex
1.02 1.84
.99–1.05 .75–4.51
.30 .18
Healthcare workerb
0.77
.27–2.23
.64
Malaria Symptoms on admission
0.56
.22–1.45
.23
Fever
1.24
.49–3.18
.65
Headache Fatigue and asthenia
0.67 1.14
.29–1.56 .39–3.34
.36 .81
95% CI
P Value
4.04
1.27–12.88
.01
Myalgia
2.63
.96–7.72
.06
Arthralgia Hiccup
1.97 7.21
.57–6.73 .81–64.46
.28 .08
Anorexia
0.88
.38–2.03
.76
Nausea and vomiting Stomachache
1.07 0.98
.45–2.52 .38–2.56
.88 .97
Diarrhea
2.20
.90–5.38
.08
2.65
.96–7.37
.06
Difficulty breathing Back pain
3.45 2.65
.97–12.22 .23–30.33
.05 .43
5.75
1.42–23.17
.01
Hemorrhage
3.28
.02
3.52
1.20–10.36
.02
1.21–8.87
Abbreviations: CI, confidence interval; OR, odds ratio. a
Age was included as a continuous variable.
b
Medical doctor (n = 11), nurse (n = 5), ambulance worker (n = 1).
chain reaction (RT-PCR), which is able to detect the virus both in patients with primo infection and advanced disease. The diagnosis was performed by highly qualified personnel from France Institute Pasteur and Dakar Institute Pasteur. Diagnostic testing was repeated during the course of the disease in patients. A negative RT-PCR was required to confirm cure and allow patients to be discharged. RT-PCR was performed every 48 hours in clinically recovered patients before they could leave the Ebola treatment center.
factors associated with death. All potential risk factors significant at the 0.2 level in univariate analysis were entered into the model. The goodness-of-fit of the models was assessed by the Hosmer-Lemeshow test. For all tests performed, 2-tailed P values 95% of malaria infections. Paracheck (Orchid Biomedical Systems, Goa, India), which detects a P. falciparum–specific histidine-rich protein (PfHRP-2), was used for each patient for malaria testing. This test requires approximately 5 µL of blood and is readable after 15 minutes. Statistical Analysis
Categorical variables were compared by the χ2 test or Fisher exact test. Continuous variables, expressed as median and interquartile range (IQR), were compared by the Mann–Whitney U-test. A multivariate logistic regression model identified
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RESULTS
Downloaded from http://cid.oxfordjournals.org/ at USDSM Wegner Health Science Info. Cntr. on April 9, 2015
Adjusted OR
death was hypovolemic shock and multiorgan failure in the 39 who died. The results of univariate and multivariate analyses are shown in Table 1. The independent predictive factors of death were hemorrhage (adjusted odds ratio [OR], 3.52; 95% confidence interval [CI], 1.20–10.36), myalgia (adjusted OR, 4.04; 95% CI, 1.27–12.88), and difficulty breathing (adjusted OR, 5.75; 95% CI, 1.42–23.17). DISCUSSION
Notes Acknowledgments. The authors thank Médecins Sans Frontières, the Guinea Red Cross, the World Health Organization in Guinea, and all of the organizations, institutions, professionals, healthcare workers, and political and civic leaders who have made efforts to support the patients. Potential conflicts of interest. All authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References 1. Lefebvre A, Fiet C, Belpois-Duchamp C, Tiv M, Astruc K, Aho Glélé LS. Case fatality rates of Ebola virus diseases: a meta-analysis of World Health Organization data. Med Mal Infect 2014; 44:412–6. 2. House T. Epidemiological dynamics of Ebola outbreaks. eLife 2014; doi:10.7554/eLife.03908. 3. Feldmann H. Ebola—a growing threat? N Engl J Med 2014; doi:10. 1056/NEJMp1405314.. 4. MacNeil A, Farnon EC, Wamala J, et al. Proportion of deaths and clinical features in Bundibugyo Ebola virus infection, Uganda. Emerg Infect Dis 2010; 16:1969–72. 5. Fowler RA, Fletcher T, Fischer WA, et al. Caring for critically ill patients with Ebola virus disease: perspectives from West Africa. Am J Respir Crit Care Med 2014; 190:733–7.
BRIEF REPORT
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Downloaded from http://cid.oxfordjournals.org/ at USDSM Wegner Health Science Info. Cntr. on April 9, 2015
Since Ebolavirus was first identified in 1976, no previous Ebola outbreak has been as large or persistent as the current epidemic, and none has spread beyond East and Central Africa. It is known that EVD is associated with a high mortality rate. In this study, we aimed to analyze the clinical predictive factors of mortality in patients with EVD treated at Conakry center. Data showed that the overall mortality rate was 43.8%. This finding is consistent with results obtained from other studies [2, 8–13]. However, in Guinea, our finding is lower than previous data reported from Gueckedou, Macenta, and Kissidougou, the outbreak epicenter [6]. This could be explained by the fact that, in this country, the first cases of Ebola were reported in these prefectures and that, at that time, Guinean physicians did not have any experience in the management of this disease. This could also be due to the fact that in the prefectures, people are not compliant with the Ebola campaign. Therefore, these patients could have had delayed access to care compared with patients who were admitted to the Conakry center for Ebola treatment. The early symptoms of Ebola include fever, extreme asthenia, diarrhea, nausea and vomiting, anorexia, abdominal pain, headaches, arthralgia, myalgia, and back pain [5, 14]. In our study, univariate analyses showed that the occurrence of these symptoms was not statistically different between the fatal and nonfatal cases. However, the results of the multivariate models showed that myalgia was an independent factor associated with death. This finding could be explained by the fact that Ebola is a very severe disease, and patients tend to have more severe clinical features such as body temperature >39°C. A previous study showed that almost two-thirds of the survivors continued to suffer from myalgia 21 months after their acute illness, and many described their myalgia and arthralgia as major health problems [14]. Moreover, the factors associated with myalgia in EVD patients are not well known. Hemorrhage is one of the main clinical manifestations of EVD, usually in the form of gastrointestinal bleeding. In this study, hemorrhage occurred in 23 patients, corresponding to 38.5% of those who died and 16.0% of those who survived (P = .04). This figure was 30% in Uganda in 2002. Our finding showed that this symptom was independently associated with death (adjusted OR, 3.52; P = .02). This sign usually appeared in the hours preceding death [15]. The occurrence of bleeding
signs indicated a poor prognosis in Ebola patients, except for melena, which was sometimes noted early in the disease and occurred in survivors and nonsurvivors. Difficulty breathing on admission was independently associated with death. Owing to vomiting and diarrhea, which lead to intravascular volume depletion and complications including profound electrolyte disorders, hypoperfusion, and shock, management of Ebola patients includes systematic parenteral rehydration. This could improve the overall prognosis, but could also lead to edema in patients with respiratory disease. Ebolavirus infections are characterized by immunosuppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock [16]. In the current study, in the 39 patients who died, the causes were hypovolemic shock and multiorgan failure. This study has some limitations. First, we did not take into account the length of stay at the center for treatment because the date of discharge was not recorded. This could be useful for survival analysis. Second, the duration of each symptom was not recorded. Finally, treatments such as hydration were administered to patients, but specific data were not recorded. However, to the best of our knowledge, this is the first study that reports the clinical predictors of death in patients with EVD. These results, particularly myalgia, need to be confirmed and complete with biological data or other features related to death.
6. Baize S, Pannetier D, Oestereich L, et al. Emergence of Zaire Ebola virus disease in guinea—preliminary report. N Engl J Med 2014; 371:1418–25. 7. Aylward B, Barboza P, Bawo L, et al. Ebola virus disease in West Africa —the first 9 months of the epidemic and forward projections. N Engl J Med 2014; 371:1481–95. 8. Onyango CO, Opoka ML, Ksiazek TG, et al. Laboratory diagnosis of Ebola virus disease during an outbreak in Yambio, Sudan, 2004. J Infect Dis 2007; 196:S193–8. 9. Bonnet MJ, Akamituna P, Mazaya A. Unrecognized Ebola virus disease at Mosango Hospital during the 1995 epidemic in Kikwit, Democratic Republic of the Congo. Emerg Infect Dis 1998; 4:508–10. 10. Muyembe-Tamfum JJ, Kipasa M, Kiyungu C, Colebunders R. Ebola outbreak in Kikwit, Democratic Republic of the Congo: discovery and control measures. J Infect Dis 1999; 179:S259–62.
11. Mason C. The strains of Ebola. CMAJ 2008; 178:1266–7. 12. Nkoghe D, Kone ML, Yada A, Leroy E. A limited outbreak of Ebola haemorrhagic fever in Etoumbi, Republic of Congo, 2005. Trans R Soc Trop Med Hyg 2011; 105:466–72. 13. Okware SI, Omaswa FG, Zaramba S, et al. An outbreak of Ebola in Uganda. Trop Med Int Health 2002; 7:1068–75. 14. Bwaka MA, Bonnet MJ, Calain P, et al. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis 1999; 179:S1–7. 15. Rowe AK, Bertolli J, Khan AS, et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola virus disease patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis 1999; 179:S28–35. 16. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet 2011; 377:849–62.
Downloaded from http://cid.oxfordjournals.org/ at USDSM Wegner Health Science Info. Cntr. on April 9, 2015
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