Implementation of an antimicrobial stewardship programme in three regional hospitals in the south-east of Liberia: lessons learned.

Background: Antimicrobial stewardship (AMS) programmes can improve the use of antimicrobial agents. However, there is limited experience in the implementation of such programmes in low- and middle-income countries (LMICs). Objectives: To assess the effect of AMS measures in south-east Liberia on the quality of antimicrobial use in three regional hospitals. Methods: A bundle of three measures (local treatment guideline, training and regular AMS ward rounds) was implemented and quality indicators of antimicrobial use (i.e. correct compounds, dosage and duration) were assessed in a case series before and after AMS ward rounds. Primary endpoints were (i) adherence to the local treatment guideline; (ii) completeness of the microbiological diagnostics (according to the treatment guideline); and (iii) clinical outcome. The secondary endpoint was reduction in ceftriaxone use. Results: The majority of patients had skin and soft tissue infections (n = 108) followed by surgical site infections (n = 72), pneumonia (n = 64), urinary tract infection (n = 48) and meningitis (n = 18). After the AMS ward rounds, adherence to the local guideline improved for the selection of antimicrobial agents (from 34.5% to 61.0%, P < 0.0005), dosage (from 15.2% to 36.5%, P < 0.0005) and duration (from 13.2% to 31.0%, P < 0.0005). In total, 79.7% of patients (247/310) had samples sent for microbiological analysis. Overall, 92.3% of patients improved on Day 3 (286/310). The proportion of patients receiving ceftriaxone was significantly reduced after the AMS ward rounds from 51.3% to 14.2% (P < 0.0005). Conclusions: AMS measures can improve the quality of antimicrobial use in LMICs. However, long-term engagement is necessary to make AMS programmes in LMICs sustainable.

Strengthening healthcare workforce capacity during and post Ebola outbreaks in Liberia: an innovative and effective approach to epidemic preparedness and response.

INTRODUCTION: The 2014-2016 Ebola virus disease (EVD) outbreak in Liberia highlighted the importance of robust preparedness measures for a well-coordinated response; the initially delayed response contributed to the steep incidence of cases, infections among health care workers, and a collapse of the health care system. To strengthen local capacity and combat disease transmission, various healthcare worker (HCW) trainings, including the Ebola treatment unit (ETU) training, safe & quality services (SQS) training and rapid response team (RRT), were developed and implemented between 2014 and 2017. METHODS: Data from the ETU, SQS and RRT trainings were analyzed to determine knowledge and confidence gained. RESULTS: The ETU, SQS and RRT training were completed by a total of 21,248 participants. There were improvements in knowledge and confidence, an associated reduction in HCWs infection and reduced response time to subsequent public health events. CONCLUSION: No infections were reported by healthcare workers in Liberia since the completion of these training programs. HCW training programmes initiated during and post disease outbreak can boost public trust in the health system while providing an entry point for establishing an Epidemic Preparedness and Response (EPR) framework in resource-limited settings.

Enhancing laboratory capacity during Ebola virus disease (EVD) heightened surveillance in Liberia: lessons learned and recommendations.

INTRODUCTION: Following a declaration by the World Health Organization that Liberia had successfully interrupted Ebola virus transmission on May 9th, 2015; the country entered a period of enhanced surveillance. The number of cases had significantly reduced prior to the declaration, leading to closure of eight out of eleven Ebola testing laboratories. Enhanced surveillance led to an abrupt increase in demand for laboratory services. We report interventions, achievements, lessons learned and recommendations drawn from enhancing laboratory capacity. METHODS: Using archived data, we reported before and after interventions that aimed at increasing laboratory capacity. Laboratory capacity was defined by number of laboratories with Ebola Virus Disease (EVD) testing capacity, number of competent staff, number of specimens tested, specimen backlog, daily and surge testing capacity, and turnaround time. Using Stata 14 (Stata Corporation, College Station, TX, USA), medians and trends were reported for all continuous variables. RESULTS: Between May and December 2015, interventions including recruitment and training of eight staff, establishment of one EVD laboratory facility, implementation of ten Ebola GeneXpert diagnostic platforms, and establishment of working shifts yielded an 8-fold increase in number of specimens tested, a reduction in specimens backlog to zero, and restoration of turn-around time to 24 hours. This enabled a more efficient surveillance system that facilitated timely detection and containment of two EVD clusters observed thereafter. CONCLUSION: Effective enhancement of laboratory services during high demand periods requires a combination of context-specific interventions. Building and ensuring sustainability of local capacity is an integral part of effective surveillance and disease outbreak response efforts.

Evaluation of a Neonatal Resuscitation Curriculum in Liberia.

Neonatal mortality in Africa is among the highest in the world. In Liberia, providers face significant challenges due to lack of resources, and providers in referral centers need to be prepared to appropriately provide neonatal resuscitation. A team of American Heart Association health care providers taught a two-day neonatal resuscitation curriculum designed for low-resource settings at a regional hospital in Liberia. The goal of this study was to evaluate if the curriculum improved knowledge and comfort in participation. The curriculum included simulations and was based on the Neonatal Resuscitation Protocol (NRP). Students learned newborn airway management, quality chest compression skills, and resuscitation interventions through lectures and manikin-based simulation sessions. Seventy-five participants were trained. There was a 63% increase in knowledge scores post training (p < 0.00001). Prior cardiopulmonary resuscitation (CPR) training, age, occupation, and pre-intervention test score did not have a significant effect on post-intervention knowledge test scores. The median provider comfort score improved from a 4 to 5 (p < 0.00001). Factors such as age, sex, prior NRP education, occupation, and post-intervention test scores did not have a significant effect on the post-intervention comfort level score. A modified NRP and manikin simulation-based curriculum may be an effective way of teaching health care providers in resource-limited settings. Training of providers in limited-resource settings could potentially help decrease neonatal mortality in Liberia. Modification of protocols is sometimes necessary and an important part of providing context-specific training. The results of this study have no direct relation to decreasing neonatal mortality until proven. A general resuscitation curriculum with modified NRP training may be effective, and further work should focus on the effect of such interventions on neonatal mortality rates in the region.

Persistence of Ebola virus after the end of widespread transmission in Liberia: an outbreak report.

BACKGROUND: Outbreak response efforts for the 2014-15 Ebola virus disease epidemic in west Africa brought widespread transmission to an end. However, subsequent clusters of infection have occurred in the region. An Ebola virus disease cluster in Liberia in November, 2015, that was identified after a 15-year-old boy tested positive for Ebola virus infection in Monrovia, raised the possibility of transmission from a persistently infected individual. METHODS: Case investigations were done to ascertain previous contact with cases of Ebola virus disease or infection with Ebola virus. Molecular investigations on blood samples explored a potential linkage between Ebola virus isolated from cases in this November, 2015, cluster and epidemiologically linked cases from the 2014-15 west African outbreak, according to the national case database. FINDINGS: The cluster investigated was the family of the index case (mother, father, three siblings). Ebola virus genomes assembled from two cases in the November, 2015, cluster, and an epidemiologically linked Ebola virus disease case in July, 2014, were phylogenetically related within the LB5 sublineage that circulated in Liberia starting around August, 2014. Partial genomes from two additional individuals, one from each cluster, were also consistent with placement in the LB5 sublineage. Sequencing data indicate infection with a lineage of the virus from a former transmission chain in the country. Based on serology and epidemiological and genomic data, the most plausible scenario is that a female case in the November, 2015, cluster survived Ebola virus disease in 2014, had viral persistence or recurrent disease, and transmitted the virus to three family members a year later. INTERPRETATION: Investigation of the source of infection for the November, 2015, cluster provides evidence of Ebola virus persistence and highlights the risk for outbreaks after interruption of active transmission. These findings underscore the need for focused prevention efforts among survivors and sustained capacity to rapidly detect and respond to new Ebola virus disease cases to prevent recurrence of a widespread outbreak. FUNDING: US Centers for Disease Control and Prevention, Defense Threat Reduction Agency, and WHO.

Implementing infection prevention and control capacity building strategies within the context of Ebola outbreak in a "Hard-to-Reach" area of Liberia.

INTRODUCTION: In August 2014, WHO declared that Ebola outbreak ravaging West Africa including Liberia had become a Public Health Emergency of International Concern (PHEIC). Infection prevention and control (IPC) among healthcare workers was pivotal in reducing healthcare worker infection and containing the recent EVD outbreak. Hard to reach areas (HTRA) presents peculiar challenges in public health emergencies. We present the result of IPC capacity building strategies deployed in Gbarpolu County: an HTRA of Liberia. METHODS: Between April to October 2015, we conducted IPC training and mentorship at the county, district and facility levels in a selected HTRA of Liberia using the keep Safe, Keep Serving manual and the WHO core components of infection control. Serial follow-up assessments and mentoring using the Liberian Minimum standard tool for safe care in Liberian health facilities (MST) were done. RESULTS: 180 (100%) facility based healthcare workers were trained: including 59 clinicians (32%) and 121 (67%) non-clinicians. 100% of the healthcare workers in four selected very HTRAs were trained and underwent facility based-mentorship. Compliance with IPC practice increased: the MST score increased from 75% to 90% and for the MST score for waste management and isolation increased 60% to 87%. CONCLUSION: Strengthening the capacity of healthcare workers for IPC was instrumental for containing the EVD epidemic but also critical for routine safe and quality services. A culture of IPC among healthcare workers in HTRA can be implemented through capacity building and training.

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.

BACKGROUND: The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. METHODS: We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. RESULTS: A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSV∆G-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSV∆G-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSV∆G-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). CONCLUSIONS: A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407 .).

Pediatric Mortality in a Rural Tertiary Care Center in Liberia.

Liberia is a low-income country in West Africa that has faced significant challenges, including a civil war and the recent Ebola epidemic. Little data exists on the more current post-war and pre-Ebola trends of child health in Liberia in the rural setting. This study is a retrospective chart review of pediatric mortality in 2013 at a rural tertiary care center in Liberia, 10 years post-war. From January 2013 to December 2013, there were 50 pediatric deaths, or 5.4% of the 920 total pediatric admissions. The most common cause of neonatal death was sepsis, and the most common cause of death under five years of age was malaria. The majority (82.0%) of the deaths were in children under five. Pediatric mortality at this hospital was similar to other reported mortality six years post-war, and lower than that reported immediately post-war. Neonatal sepsis and malaria are two significant causes of pediatric mortality in this community and, therefore, further efforts to decrease childhood mortality should focus on these causes.

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.

Reduced evolutionary rate in reemerged Ebola virus transmission chains.

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.

Secondary Infections with Ebola Virus in Rural Communities, Liberia and Guinea, 2014-2015.

Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities.

Timing and utilization of antenatal care services in Liberia: Understanding the pre-Ebola epidemic context.

In Liberia, 75% of those who died from 2014 Ebola epidemic were women and the effects of this gruelling epidemic were more severely felt by pregnant women. This immediately raised fears about the long-term impacts of the epidemic on maternal and child health. As part of a larger study, this paper uses Andersen's behavioural model of health care utilization and Goffman's stigma theory to explain the timing and utilization of maternal health services before the outbreak of the Ebola epidemic as a background to the potential long-term effects on maternal health. We conducted survival and multiple regression analysis using the 2007 (N = 3524) and 2013 (N = 5127) Liberia's Demographic and Health Survey (LDHS) data. Our sample consisted of women of reproductive age (15-49 years) that had given birth in the last five years preceding the survey year. The findings show that from 2007 to 2013, there was an overall improvement in the timing of first antenatal care (ANC) visits (TR = 0.92, p < 0.001), number of ANC visits and delivery with skilled birth attendants. The results also show county and regional disparities in the utilization of ANC services with South Eastern A region emerging as a relatively vulnerable place. Also, access to ANC services defined by distance to a health facility strongly predicted utilization. We argue that the Ebola epidemic likely eroded many of the previous gains in maternal health care, and may have left a lingering negative effect on the access and utilization of maternal health services in the long-term. The study makes relevant policy recommendations.

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.

Evaluation of a cardiopulmonary resuscitation curriculum in a low resource environment.

OBJECTIVES: To evaluate whether a 2-day International Liaison Committee on Resuscitation (ILCOR) Universal Algorithm-based curriculum taught in a tertiary care hospital in Liberia increases local health care provider knowledge and skill comfort level. METHODS: A combined basic and advanced cardiopulmonary resuscitation (CPR) curriculum was developed for low-resource settings that included lectures and low-fidelity manikin-based simulations. In March 2014, the curriculum was taught to healthcare providers in a tertiary care hospital in Liberia. In a quality assurance review, participants were evaluated for knowledge and comfort levels with resuscitation before and after the workshop. They were also videotaped during simulation sessions and evaluated on standardized performance metrics. RESULTS: Fifty-two hospital staff completed both pre-and post-curriculum surveys. The median score was 45% pre-curriculum and 82% post-curriculum (p<0.00001). The median provider comfort level score was 4 of 5 pre-curriculum and 5 of 5 post-curriculum (p<0.00001). During simulations, 93.2% of participants performed the pulse check within 10 seconds, and 97.7% performed defibrillation within 180 seconds. CONCLUSIONS: Clinician knowledge of and comfort level with CPR increased significantly after participating in our curriculum. A CPR curriculum based on lectures and low-fidelity manikin simulations may be an effective way to teach resuscitation in this low-resource setting.

Molecular Evidence of Sexual Transmission of Ebola Virus.

A suspected case of sexual transmission from a male survivor of Ebola virus disease (EVD) to his female partner (the patient in this report) occurred in Liberia in March 2015. Ebola virus (EBOV) genomes assembled from blood samples from the patient and a semen sample from the survivor were consistent with direct transmission. The genomes shared three substitutions that were absent from all other Western African EBOV sequences and that were distinct from the last documented transmission chain in Liberia before this case. Combined with epidemiologic data, the genomic analysis provides evidence of sexual transmission of EBOV and evidence of the persistence of infective EBOV in semen for 179 days or more after the onset of EVD. (Funded by the Defense Threat Reduction Agency and others.).

Decreased Ebola Transmission after Rapid Response to Outbreaks in Remote Areas, Liberia, 2014.

We measured the reproduction number before and after interventions were implemented to reduce Ebola transmission in 9 outbreaks in Liberia during 2014. We evaluated risk factors for secondary cases and the association between patient admission to an Ebola treatment unit (ETU) and survival. The reproduction number declined 94% from 1.7 (95% CI 1.1-2.6) to 0.1 (95% CI 0.02-0.6) after interventions began. The risk for secondary infections was 90% lower for patients admitted to an ETU (risk ratio 0.1, 95% CI 0.04-0.3) than for those who died in the community. The case-fatality rate was 68% (95% CI 60-74), and ETU admission was associated with a 50% reduction in death (hazard ratio 0.5, 95% CI 0.4-0.8). Isolation and treatment of Ebola patients had the dual benefit of interrupting community transmission and improving survival.

Elimination of Ebola Virus Transmission in Liberia - September 3, 2015.

Following 42 days since the last Ebola virus disease (Ebola) patient was discharged from a Liberian Ebola treatment unit (ETU), September 3, 2015, marks the second time in a 4-month period that the World Health Organization (WHO) has declared Liberia free of Ebola virus transmission (1). The first confirmed Ebola cases in West Africa were identified in southeastern Guinea on March 23, 2014, and within 1 week, cases were identified and confirmed in Liberia (1). Since then, Liberia has reported 5,036 confirmed and probable Ebola cases and 4,808 Ebola-related deaths. The epidemic in Liberia peaked in late summer and early fall of 2014, when more than 200 confirmed and probable cases were reported each week .

Possible sexual transmission of Ebola virus - Liberia, 2015.

On March 20, 2015, 30 days after the most recent confirmed Ebola Virus Disease (Ebola) patient in Liberia was isolated, Ebola was laboratory confirmed in a woman in Monrovia. The investigation identified only one epidemiologic link to Ebola: unprotected vaginal intercourse with a survivor. Published reports from previous outbreaks have demonstrated Ebola survivors can continue to harbor virus in immunologically privileged sites for a period of time after convalescence. Ebola virus has been isolated from semen as long as 82 days after symptom onset and viral RNA has been detected in semen up to 101 days after symptom onset. One instance of possible sexual transmission of Ebola has been reported, although the accompanying evidence was inconclusive. In addition, possible sexual transmission of Marburg virus, a filovirus related to Ebola, was documented in 1968. This report describes the investigation by the Government of Liberia and international response partners of the source of Liberia's latest Ebola case and discusses the public health implications of possible sexual transmission of Ebola virus. Based on information gathered in this investigation, CDC now recommends that contact with semen from male Ebola survivors be avoided until more information regarding the duration and infectiousness of viral shedding in body fluids is known. If male survivors have sex (oral, vaginal, or anal), a condom should be used correctly and consistently every time.