Plasmodium Parasitemia Associated with Increased Survival in Ebola Virus-Infected Patients

Kyle Rosenke; Jennifer Adjemian; Vincent J. Munster; Andrea Marzi; Darryl Falzarano; Clayton O. Onyango; Melvin Ochieng; Bonventure Juma; Robert J. Fischer; Joseph B. Prescott; David Safronetz; Victor Omballa; Collins Owuor; Thomas Hoenen; Allison Groseth; Cynthia Martellaro; Neeltje Van Doremalen; Galina Zemtsova; Joshua Self; Trenton Bushmaker; Kristin McNally; Thomas Rowe; Shannon L. Emery; Friederike Feldmann; Brandi N. Williamson; Sonja M. Best; Tolbert G. Nyenswah; Allen Grolla; James E. Strong; Gary Kobinger; Fatorma K. Bolay; Kathryn C. Zoon; Jorgen Stassijns; Ruggero Giuliani; Martin De Smet; Stuart T. Nichol; Barry Fields; Armand Sprecher; Moses Massaquoi; Heinz Feldmann; Emmie De Wit

doi:10.1093/cid/ciw452

Plasmodium Parasitemia Associated with Increased Survival in Ebola Virus-Infected Patients

Kyle Rosenke, Jennifer Adjemian, Vincent J. Munster, Andrea Marzi, Darryl Falzarano, Clayton O. Onyango, Melvin Ochieng, Bonventure Juma, Robert J. Fischer, Joseph B. Prescott, David Safronetz, Victor Omballa, Collins Owuor, Thomas Hoenen, Allison Groseth, Cynthia Martellaro, Neeltje Van Doremalen, Galina Zemtsova, Joshua Self, Trenton BushmakerKristin McNally, Thomas Rowe, Shannon L. Emery, Friederike Feldmann, Brandi N. Williamson, Sonja M. Best, Tolbert G. Nyenswah, Allen Grolla, James E. Strong, Gary Kobinger, Fatorma K. Bolay, Kathryn C. Zoon, Jorgen Stassijns, Ruggero Giuliani, Martin De Smet, Stuart T. Nichol, Barry Fields, Armand Sprecher, Moses Massaquoi, Heinz Feldmann, Emmie De Wit

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Background. The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. Methods. All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. Results. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Conclusions. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.

Original language	English (US)
Pages (from-to)	1026-1033
Number of pages	8
Journal	Clinical Infectious Diseases
Volume	63
Issue number	8
DOIs	https://doi.org/10.1093/cid/ciw452
State	Published - Oct 15 2016
Externally published	Yes

Keywords

Coinfection
Ebolavirus
Plasmodium
Survival

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

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10.1093/cid/ciw452

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Rosenke, K., Adjemian, J., Munster, V. J., Marzi, A., Falzarano, D., Onyango, C. O., Ochieng, M., Juma, B., Fischer, R. J., Prescott, J. B., Safronetz, D., Omballa, V., Owuor, C., Hoenen, T., Groseth, A., Martellaro, C., Van Doremalen, N., Zemtsova, G., Self, J., ... De Wit, E. (2016). Plasmodium Parasitemia Associated with Increased Survival in Ebola Virus-Infected Patients. Clinical Infectious Diseases, 63(8), 1026-1033. https://doi.org/10.1093/cid/ciw452

Rosenke, K, Adjemian, J, Munster, VJ, Marzi, A, Falzarano, D, Onyango, CO, Ochieng, M, Juma, B, Fischer, RJ, Prescott, JB, Safronetz, D, Omballa, V, Owuor, C, Hoenen, T, Groseth, A, Martellaro, C, Van Doremalen, N, Zemtsova, G, Self, J, Bushmaker, T, McNally, K, Rowe, T, Emery, SL, Feldmann, F, Williamson, BN, Best, SM, Nyenswah, TG, Grolla, A, Strong, JE, Kobinger, G, Bolay, FK, Zoon, KC, Stassijns, J, Giuliani, R, De Smet, M, Nichol, ST, Fields, B, Sprecher, A, Massaquoi, M, Feldmann, H & De Wit, E 2016, 'Plasmodium Parasitemia Associated with Increased Survival in Ebola Virus-Infected Patients', Clinical Infectious Diseases, vol. 63, no. 8, pp. 1026-1033. https://doi.org/10.1093/cid/ciw452

@article{bcec889aa6064ca9bf7f14902436c257,

title = "Plasmodium Parasitemia Associated with Increased Survival in Ebola Virus-Infected Patients",

abstract = "Background. The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. Methods. All blood samples from suspected Ebola virus-infected patients admitted to the M{\'e}decins Sans Fronti{\`e}res ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. Results. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Conclusions. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.",

keywords = "Coinfection, Ebolavirus, Plasmodium, Survival",

author = "Kyle Rosenke and Jennifer Adjemian and Munster, {Vincent J.} and Andrea Marzi and Darryl Falzarano and Onyango, {Clayton O.} and Melvin Ochieng and Bonventure Juma and Fischer, {Robert J.} and Prescott, {Joseph B.} and David Safronetz and Victor Omballa and Collins Owuor and Thomas Hoenen and Allison Groseth and Cynthia Martellaro and {Van Doremalen}, Neeltje and Galina Zemtsova and Joshua Self and Trenton Bushmaker and Kristin McNally and Thomas Rowe and Emery, {Shannon L.} and Friederike Feldmann and Williamson, {Brandi N.} and Best, {Sonja M.} and Nyenswah, {Tolbert G.} and Allen Grolla and Strong, {James E.} and Gary Kobinger and Bolay, {Fatorma K.} and Zoon, {Kathryn C.} and Jorgen Stassijns and Ruggero Giuliani and {De Smet}, Martin and Nichol, {Stuart T.} and Barry Fields and Armand Sprecher and Moses Massaquoi and Heinz Feldmann and {De Wit}, Emmie",

note = "Funding Information: Financial support. This work was partially funded by the Intramural Research Program of the NIAID/NIH. Publisher Copyright: {\textcopyright} 2016 Published by Oxford University Press for the Infectious Diseases Society of America 2016.",

year = "2016",

month = oct,

day = "15",

doi = "10.1093/cid/ciw452",

language = "English (US)",

volume = "63",

pages = "1026--1033",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "8",

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TY - JOUR

T1 - Plasmodium Parasitemia Associated with Increased Survival in Ebola Virus-Infected Patients

AU - Rosenke, Kyle

AU - Adjemian, Jennifer

AU - Munster, Vincent J.

AU - Marzi, Andrea

AU - Falzarano, Darryl

AU - Onyango, Clayton O.

AU - Ochieng, Melvin

AU - Juma, Bonventure

AU - Fischer, Robert J.

AU - Prescott, Joseph B.

AU - Safronetz, David

AU - Omballa, Victor

AU - Owuor, Collins

AU - Hoenen, Thomas

AU - Groseth, Allison

AU - Martellaro, Cynthia

AU - Van Doremalen, Neeltje

AU - Zemtsova, Galina

AU - Self, Joshua

AU - Bushmaker, Trenton

AU - McNally, Kristin

AU - Rowe, Thomas

AU - Emery, Shannon L.

AU - Feldmann, Friederike

AU - Williamson, Brandi N.

AU - Best, Sonja M.

AU - Nyenswah, Tolbert G.

AU - Grolla, Allen

AU - Strong, James E.

AU - Kobinger, Gary

AU - Bolay, Fatorma K.

AU - Zoon, Kathryn C.

AU - Stassijns, Jorgen

AU - Giuliani, Ruggero

AU - De Smet, Martin

AU - Nichol, Stuart T.

AU - Fields, Barry

AU - Sprecher, Armand

AU - Massaquoi, Moses

AU - Feldmann, Heinz

AU - De Wit, Emmie

N1 - Funding Information: Financial support. This work was partially funded by the Intramural Research Program of the NIAID/NIH. Publisher Copyright: © 2016 Published by Oxford University Press for the Infectious Diseases Society of America 2016.

PY - 2016/10/15

Y1 - 2016/10/15

N2 - Background. The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. Methods. All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. Results. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Conclusions. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.

AB - Background. The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. Methods. All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. Results. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Conclusions. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.

KW - Coinfection

KW - Ebolavirus

KW - Plasmodium

KW - Survival

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U2 - 10.1093/cid/ciw452

DO - 10.1093/cid/ciw452

M3 - Article

C2 - 27531847

AN - SCOPUS:84991018129

SN - 1058-4838

VL - 63

SP - 1026

EP - 1033

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 8

ER -

Plasmodium Parasitemia Associated with Increased Survival in Ebola Virus-Infected Patients

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Keywords

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