Moses Massaquoi

Nanopore Sequencing as a Rapidly Deployable Ebola Outbreak Tool

Rapid sequencing of RNA/DNA from pathogen samples obtained during disease outbreaks provides critical scientific and public health information. However, challenges exist for exporting samples to laboratories or establishing conventional sequencers in remote outbreak regions. We successfully used a novel, pocket-sized nanopore sequencer at a field diagnostic laboratory in Liberia during the current Ebola virus outbreak.

Effect of Artesunate-Amodiaquine on Mortality Related to Ebola Virus Disease.

BACKGROUND Malaria treatment is recommended for patients with suspected Ebola virus disease (EVD) in West Africa, whether systeomatically or based on confirmed malaria diagnosis. At the Ebola treatment center in Foya, Lofa County, Liberia, the supply of artemether-lumefantrine, a first-line antimalarial combination drug, ran out for a 12-day period in August 2014. During this time, patients received the combination drug artesunate-amodiaquine; amodiaquine is a compound with anti-Ebola virus activity in vitro. No other obvious change in the care of patients occurred during this period. METHODS We fit unadjusted and adjusted regression models to standardized patient-level data to estimate the risk ratio for death among patients with confirmed EVD who were prescribed artesunate-amodiaquine (artesunate-amodiaquine group), as compared with those who were prescribed artemether-lumefantrine (artemether-lumefantrine group) and those who were not prescribed any antimalarial drug (no-antimalarial group). RESULTS Between June 5 and October 24, 2014, a total of 382 patients with confirmed EVD were admitted to the Ebola treatment center in Foya. At admission, 194 patients were prescribed artemether-lumefantrine and 71 were prescribed artesunate-amodiaquine. The characteristics of the patients in the artesunate-amodiaquine group were similar to those in the artemether-lumefantrine group and those in the no-antimalarial group. A total of 125 of the 194 patients in the artemether-lumefantrine group (64.4%) died, as compared with 36 of the 71 patients in the artesunate-amodiaquine group (50.7%). In adjusted analyses, the artesunate-amodiaquine group had a 31% lower risk of death than the artemether-lumefantrine group (risk ratio, 0.69; 95% confidence interval, 0.54 to 0.89), with a stronger effect observed among patients without malaria. CONCLUSIONS Patients who were prescribed artesunate-amodiaquine had a lower risk of death from EVD than did patients who were prescribed artemether-lumefantrine. However, our analyses cannot exclude the possibility that artemether-lumefantrine is associated with an increased risk of death or that the use of artesunate-amodiaquine was associated with unmeasured patient characteristics that directly altered the risk of death.

Reduced evolutionary rate in reemerged Ebola virus transmission chains.

Surveillance of Ebola virus disease flare-ups uncovers a reduced rate of Ebola virus evolution during persistent infections. On 29 June 2015, Liberia’s respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak (“flare-up”) of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over.

Evolution of Ebola Virus Disease from Exotic Infection to Global Health Priority, Liberia, Mid-2014

As the disease spread, the scale of the epidemic required a multi-faceted public health response.

Implementation of an Ebola virus disease vaccine clinical trial during the Ebola epidemic in Liberia: Design, procedures, and challenges

The index case of the Ebola virus disease epidemic in West Africa is believed to have originated in Guinea. By June 2014, Guinea, Liberia, and Sierra Leone were in the midst of a full-blown and complex global health emergency. The devastating effects of this Ebola epidemic in West Africa put the global health response in acute focus for urgent international interventions. Accordingly, in October 2014, a World Health Organization high-level meeting endorsed the concept of a phase 2/3 clinical trial in Liberia to study Ebola vaccines. As a follow-up to the global response, in November 2014, the Government of Liberia and the US Government signed an agreement to form a research partnership to investigate Ebola and to assess intervention strategies for treating, controlling, and preventing the disease in Liberia. This agreement led to the establishment of the Joint Liberia–US Partnership for Research on Ebola Virus in Liberia as the beginning of a long-term collaborative partnership in clinical research between the two countries. In this article, we discuss the methodology and related challenges associated with the implementation of the Ebola vaccines clinical trial, based on a double-blinded randomized controlled trial, in Liberia.

Ebola and Its Control in Liberia, 2014–2015

Several factors explain the successful response to the outbreak in this country.

Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus–Infected Patients

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.

Does this patient have Ebola virus disease

Ebola virus is one of the most virulent human pathogens. Since 1976, Ebola virus disease (EVD) has caused more than 20 outbreaks in Africa, with case fatality rates of 30–90 % in the absence of any approved treatment or vaccination [1]. It is transmitted by direct contact through broken skin or mucous membranes with blood, urine, saliva, faeces, vomit, and other body fluids of symptomatic infected patients or convalescent persons, or through contaminated needle sticks [1, 2]. The current outbreak in West Africa probably began in December 2013 in Guinea [3], and is causing unprecedented concerns for the following reasons: (1) it is due to a strain with 97 % homology with Zaire ebolavirus, the most virulent species, with prior fatality rates as high as 90 %; (2) as of August 22, 2014, four countries have been involved, with 2,615 suspected cases, 1,528 laboratory-confirmed cases, and 1,427 related deaths, which is already many more than the largest epidemic reported to date (425 cases in Uganda, 2000–2001), and the situation is unlikely to be resolved soon [4, 5]; (3) the 2014 West Africa outbreak affects rural as well as urban areas, and recently reached the most populous African country (Nigeria); and (4) experienced governmental and non-governmental organizations, including Médecins Sans Frontières, have been active on the field since March 2014 [3], but have failed to control the epidemic. Many factors contributed to this failure, including population poverty and authorities’ distrust, disease denial in the context of strong religious beliefs, porous borders, weaknesses in public health systems, and inadequate salaries and lack of adequate protection for health care workers. On August 8, 2014, 9 months after the first documented cases, the World Health Organization (WHO) declared this outbreak a public health emergency of international concern and has called for a strong and coordinated international response, stating that ‘‘all nations should be prepared to detect, investigate, and manage Ebola cases’’ [6].

Psychological Distress among Ebola Survivors Discharged from an Ebola Treatment Unit in Monrovia, Liberia - A Qualitative Study

Introduction A consequence of the West Africa Ebola outbreak 2014–2015 was the unprecedented number of Ebola survivors discharged from the Ebola Treatment Units (ETUs). Liberia alone counted over 5,000 survivors. We undertook a qualitative study in Monrovia to better understand the mental distress experienced by survivors during hospitalization and reintegration into their community. Methods Purposively selected Ebola survivors from ELWA3, the largest ETU in Liberia, were invited to join focus group discussions. Verbal-informed consent was sought. Three focus groups with a total of 17 participants were conducted between February and April 2015. Thematic analysis approach was applied to analyze the data. Results The main stressors inside the ETU were the daily exposure to corpses, which often remained several hours among the living; the patients’ isolation from their families and worries about their well-being; and sometimes, the perception of disrespect by ETU staff. However, most survivors reported how staff motivated patients to drink, eat, bathe, and walk. Additionally, employing survivors as staff fostered hope, calling patients by their name increased confidence and familiarity, and organizing prayer and singing activities brought comfort. When Ebola virus disease survivors returned home, the experience of being alive was both a gift and a burden. Flashbacks were common among survivors. Perceived as contagious, many were excluded from their family, professional, and social life. Some survivors faced divorce, were driven out of their houses, or lost their jobs. The subsequent isolation prevented survivors from picking up daily life, and the multiple losses affected their coping mechanisms. However, when available, the support of family, friends, and prayer enabled survivors to cope with their mental distress. For those excluded from society, psychosocial counseling and the survivor’s network were ways to give a meaning to life post-Ebola. Conclusion Exposure to death in the ETU and stigma in the communities induced posttraumatic stress reactions and symptoms of depression among Ebola survivors. Distress in the ETU can be reduced through timely management of corpses. Coping mechanisms can be strengthened through trust relationships, religion, peer/community support, and community-based psychosocial care. Mental health disorders need to be addressed with appropriate specialized care and follow-up.

The Merits of Malaria Diagnostics during an Ebola Virus Disease Outbreak

Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection.