Derivation and Internal Validation of a Mortality Prognostication Machine Learning Model in Ebola Virus Disease Based on Iterative Point-of-Care Biomarkers.

Background: Although multiple prognostic models exist for Ebola virus disease mortality, few incorporate biomarkers, and none has used longitudinal point-of-care serum testing throughout Ebola treatment center care. Methods: This retrospective study evaluated adult patients with Ebola virus disease during the 10th outbreak in the Democratic Republic of Congo. Ebola virus cycle threshold (Ct; based on reverse transcriptase polymerase chain reaction) and point-of-care serum biomarker values were collected throughout Ebola treatment center care. Four iterative machine learning models were created for prognosis of mortality. The base model used age and admission Ct as predictors. Ct and biomarkers from treatment days 1 and 2, days 3 and 4, and days 5 and 6 associated with mortality were iteratively added to the model to yield mortality risk estimates. Receiver operating characteristic curves for each iteration provided period-specific areas under curve with 95% CIs. Results: Of 310 cases positive for Ebola virus disease, mortality occurred in 46.5%. Biomarkers predictive of mortality were elevated creatinine kinase, aspartate aminotransferase, blood urea nitrogen (BUN), alanine aminotransferase, and potassium; low albumin during days 1 and 2; elevated C-reactive protein, BUN, and potassium during days 3 and 4; and elevated C-reactive protein and BUN during days 5 and 6. The area under curve substantially improved with each iteration: base model, 0.74 (95% CI, .69-.80); days 1 and 2, 0.84 (95% CI, .73-.94); days 3 and 4, 0.94 (95% CI, .88-1.0); and days 5 and 6, 0.96 (95% CI, .90-1.0). Conclusions: This is the first study to utilize iterative point-of-care biomarkers to derive dynamic prognostic mortality models. This novel approach demonstrates that utilizing biomarkers drastically improved prognostication up to 6 days into patient care.

A premature newborn born to an adolescent girl with acute Ebola virus disease and malaria survives in a resource-limited setting in an Ebola treatment unit in DR Congo: "A case report".

Key Clinical Message: In the acute phase of Ebola virus disease (EVD) premature neonatal survival is extremely rare. High mortality is related to prematurity, neonatal complications of Ebola, and precarious conditions of neonatal care in underresourced ETUs. This is a case of preterm neonatal survival in the setting of acute maternal EVD infection. Abstract: This case describes rare preterm newborn survival in the setting of an Ebola treatment unit in Eastern DRC. The neonate was born vaginally to an acutely ill 17-year-old mother who was vaccinated against Ebola virus after being identified as a contact of her father, who was a confirmed case and who did not survive his infection. This woman was admitted to an Ebola treatment unit at 32 weeks of gestation and given monoclonal antibody treatment. She gave birth vaginally, succumbing to postpartum hemorrhage 14 h after delivery. This child survived despite compounding vulnerabilities of preterm birth and maternal Ebola infection. Despite a negative test for EVD, the neonate was given a single dose of monoclonal antibody therapy in the first days of life. We believe maternal vaccination and neonatal monoclonal antibody treatment contributed to the child's survival. The circumstances surrounding neonatal survival in this extremely resource-limited context must be analyzed and disseminated in order to increase rates of neonatal and maternal survival in future outbreaks. Maternal and neonatal health are critical aspects of outbreak response that have been understudied and underreported leaving clinicians severely underresourced to provide life-saving care in outbreak settings. Pregnancy and childbirth do not stop in times of disease outbreak, adequate equipment and trained staff required for quality neonatal care must be considered in future outbreak responses.

Effect of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Vaccination on Ebola Virus Disease Illness and Death, Democratic Republic of the Congo.

We conducted a retrospective cohort study to assess the effect vaccination with the live-attenuated recombinant vesicular stomatitis virus-Zaire Ebola virus vaccine had on deaths among patients who had laboratory-confirmed Ebola virus disease (EVD). We included EVD-positive patients coming to an Ebola Treatment Center in eastern Democratic Republic of the Congo during 2018-2020. Overall, 25% of patients vaccinated before symptom onset died compared with 63% of unvaccinated patients. Vaccinated patients reported fewer EVD-associated symptoms, had reduced time to clearance of viral load, and had reduced length of stay at the Ebola Treatment Center. After controlling for confounders, vaccination was strongly associated with decreased deaths. Reduction in deaths was not affected by timing of vaccination before or after EVD exposure. These findings support use of preexposure and postexposure recombinant vesicular stomatitis virus-Zaire Ebola virus vaccine as an intervention associated with improved death rates, illness, and recovery time among patients with EVD.

Risk Prediction Score for Pediatric Patients with Suspected Ebola Virus Disease.

Rapid diagnostic tools for children with Ebola virus disease (EVD) are needed to expedite isolation and treatment. To evaluate a predictive diagnostic tool, we examined retrospective data (2014-2015) from the International Medical Corps Ebola Treatment Centers in West Africa. We incorporated statistically derived candidate predictors into a 7-point Pediatric Ebola Risk Score. Evidence of bleeding or having known or no known Ebola contacts was positively associated with an EVD diagnosis, whereas abdominal pain was negatively associated. Model discrimination using area under the curve (AUC) was 0.87, which outperforms the World Health Organization criteria (AUC 0.56). External validation, performed by using data from International Medical Corps Ebola Treatment Centers in the Democratic Republic of the Congo during 2018-2019, showed an AUC of 0.70. External validation showed that discrimination achieved by using World Health Organization criteria was similar; however, the Pediatric Ebola Risk Score is simpler to use.

Creating a National Specimen Referral System in Guinea: Lessons From Initial Development and Implementation.

In the wake of the 2014-2016, West Africa Ebola virus disease (EVD) outbreak, the Government of Guinea recognized an opportunity to strengthen its national laboratory system, incorporating capacity and investments developed during the response. The Ministry of Health (MOH) identified creation of a holistic, safe, secure, and timely national specimen referral system as a priority for improved detection and confirmation of priority diseases, in line with national Integrated Disease Surveillance and Response guidelines. The project consisted of two parts, each led by different implementing partners working collaboratively together and with the Ministry of Health: the development and approval of a national specimen referral policy, and pilot implementation of a specimen referral system, modeled on the policy, in three prefectures. This paper describes the successful execution of the project, highlighting the opportunities and challenges of building sustainable health systems capacity during and after public health emergencies, and provides lessons learned for strengthening national capabilities for surveillance and disease diagnosis.