Documenting the development, adoption and pre-ebola implementation of Liberia's integrated disease surveillance and response (IDSR) strategy.

BACKGROUND: In the immediate aftermath of a 14-year civil conflict that disrupted the health system, Liberia adopted the internationally recommended integrated disease surveillance and response (IDSR) strategy in 2004. Despite this, Liberia was among the three West African countries ravaged by the worst Ebola epidemic in history from 2014 to 2016. This paper describes successes, failures, strengths, and weaknesses in the development, adoption, and implementation of IDSR following the civil war and up until the outbreak of Ebola, from 2004 to early 2014. METHODS: We reviewed 112 official Government documents and peer-reviewed articles and conducted 29 in-depth interviews with key informants from December 2021 to March 2022 to gain perspectives on IDSR in the post-conflict and pre-Ebola era in Liberia. We assessed the core and supportive functions of IDSR, such as notification of priority diseases, confirmation, reporting, analysis, investigation, response, feedback, monitoring, staff training, supervision, communication, and financial resources. Data were triangulated and presented via emerging themes and in-depth accounts to describe the context of IDSR introduction and implementation, and the barriers surrounding it. RESULTS: Despite the adoption of the IDSR framework, Liberia failed to secure the resources-human, logistical, and financial-to support effective implementation over the 10-year period. Documents and interview reports demonstrate numerous challenges prior to Ebola: the surveillance system lacked key components of IDSR including laboratory testing capacity, disease reporting, risk communication, community engagement, and staff supervision systems. Insufficient financial support and an abundance of vertical programs further impeded progress. In-depth accounts by donors and key governmental informants demonstrate that although the system had a role in detecting Ebola in Liberia, it could not respond effectively to control the disease. CONCLUSION: Our findings suggest that post-war, Liberia's health system intended to prioritize epidemic preparedness and response with the adoption of IDSR. However, insufficient investment and systems development meant IDSR was not well implemented, leaving the country vulnerable to the devastating impact of the Ebola epidemic.

Ebola Virus Infection Associated with Transmission from Survivors.

Ebola virus (EBOV) can persist in immunologically protected body sites in survivors of Ebola virus disease, creating the potential to initiate new chains of transmission. From the outbreak in West Africa during 2014-2016, we identified 13 possible events of viral persistence-derived transmission of EBOV (VPDTe) and applied predefined criteria to classify transmission events based on the strength of evidence for VPDTe and source and route of transmission. For 8 events, a recipient case was identified; possible source cases were identified for 5 of these 8. For 5 events, a recipient case or chain of transmission could not be confidently determined. Five events met our criteria for sexual transmission (male-to-female). One VPDTe event led to at least 4 generations of cases; transmission was limited after the other events. VPDTe has increased the importance of Ebola survivor services and sustained surveillance and response capacity in regions with previously widespread transmission.

Recently Identified Mutations in the Ebola Virus-Makona Genome Do Not Alter Pathogenicity in Animal Models.

Ebola virus (EBOV), isolate Makona, the causative agent of the West African EBOV epidemic, has been the subject of numerous investigations to determine the genetic diversity and its potential implication for virus biology, pathogenicity, and transmissibility. Despite various mutations that have emerged over time through multiple human-to-human transmission chains, their biological relevance remains questionable. Recently, mutations in the glycoprotein GP and polymerase L, which emerged and stabilized early during the outbreak, have been associated with improved viral fitness in cell culture. Here, we infected mice and rhesus macaques with EBOV-Makona isolates carrying or lacking those mutations. Surprisingly, all isolates behaved very similarly independent of the genotype, causing severe or lethal disease in mice and macaques, respectively. Likewise, we could not detect any evidence for differences in virus shedding. Thus, no specific biological phenotype could be associated with these EBOV-Makona mutations in two animal models.

Ebola Response Impact on Public Health Programs, West Africa, 2014-2017.

Events such as the 2014-2015 West Africa epidemic of Ebola virus disease highlight the importance of the capacity to detect and respond to public health threats. We describe capacity-building efforts during and after the Ebola epidemic in Liberia, Sierra Leone, and Guinea and public health progress that was made as a result of the Ebola response in 4 key areas: emergency response, laboratory capacity, surveillance, and workforce development. We further highlight ways in which capacity-building efforts such as those used in West Africa can be accelerated after a public health crisis to improve preparedness for future events.

Ebola virus disease contact tracing activities, lessons learned and best practices during the Duport Road outbreak in Monrovia, Liberia, November 2015.

BACKGROUND: Contact tracing is one of the key response activities necessary for halting Ebola Virus Disease (EVD) transmission. Key elements of contact tracing include identification of persons who have been in contact with confirmed EVD cases and careful monitoring for EVD symptoms, but the details of implementation likely influence their effectiveness. In November 2015, several months after a major Ebola outbreak was controlled in Liberia, three members of a family were confirmed positive for EVD in the Duport Road area of Monrovia. The cluster provided an opportunity to implement and evaluate modified approaches to contact tracing. METHODS: The approaches employed for improved contact tracing included classification and risk-based management of identified contacts (including facility based isolation of some high risk contacts, provision of support to persons being monitored, and school-based surveillance for some persons with potential exposure but not listed as contacts), use of phone records to help locate missing contacts, and modifications to data management tools. We recorded details about the implementation of these approaches, report the overall outcomes of the contact tracing efforts and the challenges encountered, and provide recommendations for management of future outbreaks. RESULTS: 165 contacts were identified (with over 150 identified within 48 hours of confirmation of the EVD cases) and all initially missing contacts were located. Contacts were closely monitored and promptly tested if symptomatic; no contacts developed disease. Encountered challenges related to knowledge gaps among contact tracing staff, data management, and coordination of contact tracing activities with efforts to offer Ebola vaccine. CONCLUSIONS: The Duport Road EVD cluster was promptly controlled. Missing contacts were effectively identified, and identified contacts were effectively monitored and rapidly tested. There is a persistent risk of EVD reemergence in Liberia; the experience controlling each cluster can help inform future Ebola control efforts in Liberia and elsewhere.

Impact of interventions and the incidence of ebola virus disease in Liberia-implications for future epidemics.

To better understand the impact of national and global efforts to contain the Ebola virus disease epidemic of 2014­15 in Liberia, we provide a detailed timeline of the major interventions and relate them to the epidemic curve. In addition to personal experience in the response, we systematically reviewed situation reports from the Liberian government, UN, CDC, WHO, UNICEF, IFRC, USAID, and local and international news reports to create the timeline. We extracted data on the timing and nature of activities and compared them to the timeline of the epidemic curve using the reproduction number­the estimate of the average number of new cases caused by a single case. Interventions were organized around five major strategies, with the majority of resources directed to the creation of treatment beds. We conclude that no single intervention stopped the epidemic; rather, the interventions likely had reinforcing effects, and some were less likely than others to have made a major impact. We find that the epidemic's turning coincided with a reorganization of the response in August­September 2014, the emergence of community leadership in control efforts, and changing beliefs and practices in the population. Ebola Treatment Units were important for Ebola treatment, but the vast majority of these treatment centre beds became available after the epidemic curve began declining. Similarly, the United Nations Mission for Ebola Emergency Response was launched after the epidemic curve had already turned. These findings have significant policy implications for future epidemics and suggest that much of the decline in the epidemic curve was driven by critical behaviour changes within local communities, rather than by international efforts that came after the epidemic had turned. Future global interventions in epidemic response should focus on building community capabilities, strengthening local ownership, and dramatically reducing delays in the response.

Bolstering Community Cooperation in Ebola Resurgence Protocols: Combining Field Blood Draw and Point-of-Care Diagnosis.

Alison Galvani and colleagues describe a community-based protocol to improve cooperation with Ebola testing as well as contact tracing, quarantining, and treatment.

Prevention of sexual transmission of Ebola in Liberia through a national semen testing and counselling programme for survivors: an analysis of Ebola virus RNA results and behavioural data.

BACKGROUND: Ebola virus has been detected in semen of Ebola virus disease survivors after recovery. Liberia's Men's Health Screening Program (MHSP) offers Ebola virus disease survivors semen testing for Ebola virus. We present preliminary results and behavioural outcomes from the first national semen testing programme for Ebola virus. METHODS: The MHSP operates out of three locations in Liberia: Redemption Hospital in Montserrado County, Phebe Hospital in Bong County, and Tellewoyan Hospital in Lofa County. Men aged 15 years and older who had an Ebola treatment unit discharge certificate are eligible for inclusion. Participants' semen samples were tested for Ebola virus RNA by real-time RT-PCR and participants received counselling on safe sexual practices. Participants graduated after receiving two consecutive negative semen tests. Counsellors collected information on sociodemographics and sexual behaviours using questionnaires administered at enrolment, follow up, and graduation visits. Because the programme is ongoing, data analysis was restricted to data obtained from July 7, 2015, to May 6, 2016. FINDINGS: As of May 6, 2016, 466 Ebola virus disease survivors had enrolled in the programme; real-time RT-PCR results were available from 429 participants. 38 participants (9%) produced at least one semen specimen that tested positive for Ebola virus RNA. Of these, 24 (63%) provided semen specimens that tested positive 12 months or longer after Ebola virus disease recovery. The longest interval between discharge from an Ebola treatment unit and collection of a positive semen sample was 565 days. Among participants who enrolled and provided specimens more than 90 days since their Ebola treatment unit discharge, men older than 40 years were more likely to have a semen sample test positive than were men aged 40 years or younger (p=0·0004). 84 (74%) of 113 participants who reported not using a condom at enrolment reported using condoms at their first follow-up visit (p<0·0001). 176 (46%) of 385 participants who reported being sexually active at enrolment reported abstinence at their follow-up visit (p<0·0001). INTERPRETATION: Duration of detection of Ebola virus RNA by real-time RT-PCR varies by individual and might be associated with age. By combining behavioural counselling and laboratory testing, the Men's Health Screening Program helps male Ebola virus disease survivors understand their individual risk and take appropriate measures to protect their sexual partners. FUNDING: World Health Organization and the US Centers for Disease Control and Prevention.

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.

Clinical Chemistry of Patients With Ebola in Monrovia, Liberia.

The development of point-of-care clinical chemistry analyzers has enabled the implementation of these ancillary tests in field laboratories in resource-limited outbreak areas. The Eternal Love Winning Africa (ELWA) outbreak diagnostic laboratory, established in Monrovia, Liberia, to provide Ebola virus and Plasmodium spp. diagnostics during the Ebola epidemic, implemented clinical chemistry analyzers in December 2014. Clinical chemistry testing was performed for 68 patients in triage, including 12 patients infected with Ebola virus and 18 infected with Plasmodium spp. The main distinguishing feature in clinical chemistry of Ebola virus-infected patients was the elevation in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase levels and the decrease in calcium. The implementation of clinical chemistry is probably most helpful when the medical supportive care implemented at the Ebola treatment unit allows for correction of biochemistry derangements and on-site clinical chemistry analyzers can be used to monitor electrolyte balance.

Ebola Laboratory Response at the Eternal Love Winning Africa Campus, Monrovia, Liberia, 2014-2015.

West Africa experienced the first epidemic of Ebola virus infection, with by far the greatest number of cases in Guinea, Sierra Leone, and Liberia. The unprecedented epidemic triggered an unparalleled response, including the deployment of multiple Ebola treatment units and mobile/field diagnostic laboratories. The National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention deployed a joint laboratory to Monrovia, Liberia, in August 2014 to support the newly founded Ebola treatment unit at the Eternal Love Winning Africa (ELWA) campus. The laboratory operated initially out of a tent structure but quickly moved into a fixed-wall building owing to severe weather conditions, the need for increased security, and the high sample volume. Until May 2015, when the laboratory closed, the site handled close to 6000 clinical specimens for Ebola virus diagnosis and supported the medical staff in case patient management. Laboratory operation and safety, as well as Ebola virus diagnostic assays, are described and discussed; in addition, lessons learned for future deployments are reviewed.

Retrospective Analysis of the 2014-2015 Ebola Epidemic in Liberia.

The 2014-2015 Ebola epidemic has been the most protracted and devastating in the history of the disease. To prevent future outbreaks on this scale, it is imperative to understand the reasons that led to eventual disease control. Here, we evaluated the shifts of Ebola dynamics at national and local scales during the epidemic in Liberia. We used a transmission model calibrated to epidemiological data between June 9 and December 31, 2014, to estimate the extent of community and hospital transmission. We found that despite varied local epidemic patterns, community transmission was reduced by 40-80% in all the counties analyzed. Our model suggests that the tapering of the epidemic was achieved through reductions in community transmission, rather than accumulation of immune individuals through asymptomatic infection and unreported cases. Although the times at which this transmission reduction occurred in the majority of the Liberian counties started before any large expansion in hospital capacity and the distribution of home protection kits, it remains difficult to associate the presence of interventions with reductions in Ebola incidence.

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.

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.

The severe epidemic of Ebola virus disease in Liberia started in March 2014. On May 9, 2015, the World Health Organization declared Liberia free of Ebola, 42 days after safe burial of the last known case-patient. However, another 6 cases occurred during June-July; on September 3, 2015, the country was again declared free of Ebola. Liberia had by then reported 10,672 cases of Ebola and 4,808 deaths, 37.0% and 42.6%, respectively, of the 28,103 cases and 11,290 deaths reported from the 3 countries that were heavily affected at that time. Essential components of the response included government leadership and sense of urgency, coordinated international assistance, sound technical work, flexibility guided by epidemiologic data, transparency and effective communication, and efforts by communities themselves. Priorities after the epidemic include surveillance in case of resurgence, restoration of health services, infection control in healthcare settings, and strengthening of basic public health systems.