In the JournalsPerspective

New clinical details revealed about first newborn to survive Ebola virus

In a brief report published in The Journal of Infectious Diseases, researchers describe the clinical course and management of Ebola virus disease in the first documented baby to live after being born with congenital infection.

On day 33 of life, the neonate was discharged in good health after receiving treatment with experimental therapies, which included monoclonal antibodies — known as ZMapp (Mapp Biopharmaceutical) — and the novel broad-spectrum antiviral GS-5734 (Gilead Sciences).

“Nearly all pregnancies of [Ebola virus (EBOV)]-infected women end with miscarriage or stillbirth,” Jenny Dörnemann, MSc, from the medical department at Médecins Sans Frontières Belgium, and colleagues wrote. “Since the identification of EBOV, 15 neonates born alive to EBOV-infected mothers have been documented … all died; the longest documented survival duration was 19 days.”

An Ebola viruspositive women admitted to the Nongo Ebola treatment center in Conakry, Guinea, died of hemorrhagic shock after giving birth to a live girl. The doctors isolated the EBOV-infected neonate, then administered ZMapp by IV infusion with incremental infusion rates at a dose of 50 mg/kg on days 1, 5 and 9 of life. They continuously monitored infusions lasting 6 to 10 hours, and recorded no adverse events. The researchers performed a leukocyte transfusion from an Ebola virus disease (EVD) survivor over the course of 2 hours on day 11 of life to support cell-mediated activity by the monoclonal antibodies.

On day 15, the patient developed myoclonic muscle activities in both arms and legs that lasted less than 5 minutes, and a second episode occurred hours later during her sleep, lasting about 1 minute. The doctors administered phenobarbital, first 20 mg/kg, then 10 mg/kg. On day 16, they performed a lumbar puncture and determined that there was no EBOV in her cerebrospinal fluid. Another episode of myoclonic activity occurred on day 18.

On day 19 of life, the doctors began administering a daily dose of 10 mg of the prodrug nucleotide analogue GS-5734, diluted in 50 mL of saline. Episodes of myoclonic activity continued on days 12, 24, 25 and 26; however, GS-5734 was well-tolerated during the whole course of treatment.

Excluding myoclonic episodes, Dörnemann and colleagues observed that liver and kidney function remained normal, no signs of pathology appeared and body weight steadily increased. The patient was discharged on day 33 of life with negative results of EBOV in the blood, urine and skin. After 1 year of weekly follow-up, the patient showed normal growth and neurological development according to age.

“Given the 100% case-fatality rate for congenitally acquired EVD, we found that an increased level of risk was acceptable and chose to administer experimental treatments that had not been given to patients in this age group and had an unproven effect in EVD,” Dörnemann and colleagues wrote. “Further research will be needed to show whether the positive outcome is attributed to one or a combination of the administered treatments.”

In an associated editorial, Frederick G. Hayden, MD, FACP, from the University of Virginia School of Medicine, and colleagues commented on what these experimental therapies have taught outbreak experts about treating EVD. Hayden and colleagues believe that the severity of the Ebola outbreak in West Africa provided the opportunity for testing experimental therapies.

Hayden and colleagues explain, “Ongoing scrutiny of the existing therapeutic landscapes for other high-consequence pathogens, support for clinical research networks to conduct studies in the interevent period, and improved surveillance and diagnostic capacities should help to reduce response times for initiating clinical research in future outbreaks of EVD and other emerging threat pathogens.” by Savannah Demko

Disclosures: Dörnemann reports no relevant financial disclosures. Hayden reports receiving fees from the Wellcome Trust and WHO related to Ebola research outside of the submitted editorial. Hayden also reports that he consults for Medivector and Gilead Sciences

In a brief report published in The Journal of Infectious Diseases, researchers describe the clinical course and management of Ebola virus disease in the first documented baby to live after being born with congenital infection.

On day 33 of life, the neonate was discharged in good health after receiving treatment with experimental therapies, which included monoclonal antibodies — known as ZMapp (Mapp Biopharmaceutical) — and the novel broad-spectrum antiviral GS-5734 (Gilead Sciences).

“Nearly all pregnancies of [Ebola virus (EBOV)]-infected women end with miscarriage or stillbirth,” Jenny Dörnemann, MSc, from the medical department at Médecins Sans Frontières Belgium, and colleagues wrote. “Since the identification of EBOV, 15 neonates born alive to EBOV-infected mothers have been documented … all died; the longest documented survival duration was 19 days.”

An Ebola viruspositive women admitted to the Nongo Ebola treatment center in Conakry, Guinea, died of hemorrhagic shock after giving birth to a live girl. The doctors isolated the EBOV-infected neonate, then administered ZMapp by IV infusion with incremental infusion rates at a dose of 50 mg/kg on days 1, 5 and 9 of life. They continuously monitored infusions lasting 6 to 10 hours, and recorded no adverse events. The researchers performed a leukocyte transfusion from an Ebola virus disease (EVD) survivor over the course of 2 hours on day 11 of life to support cell-mediated activity by the monoclonal antibodies.

On day 15, the patient developed myoclonic muscle activities in both arms and legs that lasted less than 5 minutes, and a second episode occurred hours later during her sleep, lasting about 1 minute. The doctors administered phenobarbital, first 20 mg/kg, then 10 mg/kg. On day 16, they performed a lumbar puncture and determined that there was no EBOV in her cerebrospinal fluid. Another episode of myoclonic activity occurred on day 18.

On day 19 of life, the doctors began administering a daily dose of 10 mg of the prodrug nucleotide analogue GS-5734, diluted in 50 mL of saline. Episodes of myoclonic activity continued on days 12, 24, 25 and 26; however, GS-5734 was well-tolerated during the whole course of treatment.

Excluding myoclonic episodes, Dörnemann and colleagues observed that liver and kidney function remained normal, no signs of pathology appeared and body weight steadily increased. The patient was discharged on day 33 of life with negative results of EBOV in the blood, urine and skin. After 1 year of weekly follow-up, the patient showed normal growth and neurological development according to age.

“Given the 100% case-fatality rate for congenitally acquired EVD, we found that an increased level of risk was acceptable and chose to administer experimental treatments that had not been given to patients in this age group and had an unproven effect in EVD,” Dörnemann and colleagues wrote. “Further research will be needed to show whether the positive outcome is attributed to one or a combination of the administered treatments.”

In an associated editorial, Frederick G. Hayden, MD, FACP, from the University of Virginia School of Medicine, and colleagues commented on what these experimental therapies have taught outbreak experts about treating EVD. Hayden and colleagues believe that the severity of the Ebola outbreak in West Africa provided the opportunity for testing experimental therapies.

Hayden and colleagues explain, “Ongoing scrutiny of the existing therapeutic landscapes for other high-consequence pathogens, support for clinical research networks to conduct studies in the interevent period, and improved surveillance and diagnostic capacities should help to reduce response times for initiating clinical research in future outbreaks of EVD and other emerging threat pathogens.” by Savannah Demko

Disclosures: Dörnemann reports no relevant financial disclosures. Hayden reports receiving fees from the Wellcome Trust and WHO related to Ebola research outside of the submitted editorial. Hayden also reports that he consults for Medivector and Gilead Sciences

    Perspective
    Amesh Adalja

    Amesh A. Adalja

    The remarkable survival of a neonate infected with Ebola by her mother provides proof-of-concept that aggressive supportive care, coupled with the use of innovative experimental treatments, may have the capacity to improve the outcomes of the uniformly fatal congenital Ebola infection. As described in the case report, the neonate herself received 3 novel therapies while the mother received an antiviral prior to delivery; this cocktail approach to anti-Ebola measures merits further study in order to understand which components have the biggest impact. Such studies, as well the 100% efficacious Ebola vaccine, have the potential to change the face of the way future Ebola outbreaks are addressed.

    The accompanying editorial by Hayden and colleagues makes additional points that are important to emphasize. The fact that Ebola was recognized and treated as a potential biological weapon led to strategic national security investments in developing countermeasures against the virus. In 2014, at the height of the West African outbreak, many of these products had progressed through years of development and were able to be used and studied — an important pandemic preparedness lesson to draw for future pandemic potential pathogens.

    • Amesh A. Adalja, MD, FACP
    • Infectious disease physician
      University of Pittsburgh

    Disclosures: Adalja reports no relevant financial disclosures.

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