Grazia Caleo

Ebola outbreak in rural West Africa: epidemiology, clinical features and outcomes

To describe Ebola cases in the district Ebola management centre of in Kailahun, a remote rural district of Sierra Leone, in terms of geographic origin, patient and hospitalisation characteristics, treatment outcomes and time from symptom onset to admission.

Ebola viral load at diagnosis associates with patient outcome and outbreak evolution

BACKGROUND Ebola virus (EBOV) causes periodic outbreaks of life-threatening EBOV disease in Africa. Historically, these outbreaks have been relatively small and geographically contained; however, the magnitude of the EBOV outbreak that began in 2014 in West Africa has been unprecedented. The aim of this study was to describe the viral kinetics of EBOV during this outbreak and identify factors that contribute to outbreak progression. METHODS From July to December 2014, one laboratory in Sierra Leone processed over 2,700 patient samples for EBOV detection by quantitative PCR (qPCR). Viremia was measured following patient admission. Age, sex, and approximate time of symptom onset were also recorded for each patient. The data was analyzed using various mathematical models to find trends of potential interest. RESULTS The analysis revealed a significant difference (P = 2.7 × 10(-77)) between the initial viremia of survivors (4.02 log10 genome equivalents [GEQ]/ml) and nonsurvivors (6.18 log10 GEQ/ml). At the population level, patient viral loads were higher on average in July than in November, even when accounting for outcome and time since onset of symptoms. This decrease in viral loads temporally correlated with an increase in circulating EBOV-specific IgG antibodies among individuals who were suspected of being infected but shown to be negative for the virus by PCR. CONCLUSIONS Our results indicate that initial viremia is associated with outcome of the individual and outbreak duration; therefore, care must be taken in planning clinical trials and interventions. Additional research in virus adaptation and the impacts of host factors on EBOV transmission and pathogenesis is needed.

Exploring the evidence base for national and regional policy interventions to combat resistance

The effectiveness of existing policies to control antimicrobial resistance is not yet fully understood. A strengthened evidence base is needed to inform effective policy interventions across countries with different income levels and the human health and animal sectors. We examine three policy domains-responsible use, surveillance, and infection prevention and control-and consider which will be the most effective at national and regional levels. Many complexities exist in the implementation of such policies across sectors and in varying political and regulatory environments. Therefore, we make recommendations for policy action, calling for comprehensive policy assessments, using standardised frameworks, of cost-effectiveness and generalisability. Such assessments are especially important in low-income and middle-income countries, and in the animal and environmental sectors. We also advocate a One Health approach that will enable the development of sensitive policies, accommodating the needs of each sector involved, and addressing concerns of specific countries and regions.

Prognostic Indicators for Ebola Patient Survival

Odds of survival were greatest when first Ebola virus–positive blood sample collected had low viral load.

Delivery of an Ebola Virus-Positive Stillborn Infant in a Rural Community Health Center, Sierra Leone, 2015.

We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mothers last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women in an Ebola setting.

Strategies for achieving global collective action on antimicrobial resistance

Abstract Global governance and market failures mean that it is not possible to ensure access to antimicrobial medicines of sustainable effectiveness. Many people work to overcome these failures, but their institutions and initiatives are insufficiently coordinated, led and financed. Options for promoting global collective action on antimicrobial access and effectiveness include building institutions, crafting incentives and mobilizing interests. No single option is sufficient to tackle all the challenges associated with antimicrobial resistance. Promising institutional options include monitored milestones and an inter-agency task force. A global pooled fund could be used to craft incentives and a special representative nominated as an interest mobilizer. There are three policy components to the problem of antimicrobials – ensuring access, conservation and innovation. To address all three components, the right mix of options needs to be matched with an effective forum and may need to be supported by an international legal framework.

Inpatient signs and symptoms and factors associated with death in children aged 5 years and younger admitted to two Ebola management centres in Sierra Leone, 2014: a retrospective cohort study

BACKGROUND Médecins Sans Frontières (MSF) opened Ebola management centres (EMCs) in Sierra Leone in Kailahun in June, 2014, and Bo in September, 2014. Case fatality in the west African Ebola virus disease epidemic has been highest in children younger than 5 years. Clinical data on outcomes can provide important evidence to guide future management. However, such data on children are scarce and disaggregated clinical data across all ages in this epidemic have focussed on symptoms reported on arrival at treatment facilities, rather than symptoms and signs observed during admission. We aimed to describe the clinical characteristics of children aged 5 years and younger admitted to the MSF EMCs in Bo and Kailahun, and any associations between these characteristics and mortality. METHODS In a retrospective cohort study, we included data from children aged 5 years and younger with laboratory-confirmed Ebola virus disease admitted to EMCs between June and December, 2014. We described epidemiological, demographic, and clinical characteristics and viral load (measured using Ebola virus cycle thresholds [Ct]), and assessed their association with death using Cox regression modelling. FINDINGS We included 91 children in analysis; 52 died (57·1%). Case fatality was higher in children aged less than 2 years (76·5% [26/34]) than those aged 2-5 years (45·6% [26/57]; adjusted HR 3·5 [95% CI 1·5-8·5]) and in those with high (Ct<25) versus low (Ct≥25) viral load (81·8% [18/22] vs 45·9% [28/61], respectively; adjusted HR 9·2 [95% CI 3·8-22·5]). Symptoms observed during admission included: weakness 74·7% (68); fever 70·8% (63/89); distress 63·7% (58); loss of appetite 60·4% (55); diarrhoea 59·3% (54); and cough 52·7% (48). At admission, 25% (19/76) of children were afebrile. Signs significantly associated with death were fever, vomiting, and diarrhoea. Hiccups, bleeding, and confusion were observed only in children who died. INTERPRETATION This description of the clinical features of Ebola virus disease over the duration of illness in children aged 5 years and younger shows symptoms associated with death and a high prevalence of distress, with implications for clinical management. Collection and analysis of age-specific data on Ebola is very important to ensure that the specific vulnerabilities of children are addressed. FUNDING No specific funding was received for this study. EB is supported by the National Health and Medical Research Council of Australia.

Successful Control of Ebola Virus Disease: Analysis of Service Based Data from Rural Sierra Leone.

Introduction The scale and geographical distribution of the current outbreak in West Africa raised doubts as to the effectiveness of established methods of control. Ebola Virus Disease (EVD) was first detected in Sierra Leone in May 2014 in Kailahun district. Despite high case numbers elsewhere in the country, transmission was eliminated in the district by December 2014. We describe interventions underpinning successful EVD control in Kailahun and implications for EVD control in other areas. Methods Internal service data and published reports from response agencies were analysed to describe the structure and type of response activities, EVD case numbers and epidemic characteristics. This included daily national situation reports and District-level data and reports of the Sierra Leone Ministry of Health and Sanitation, and Médecins Sans Frontières (MSF) patient data and internal epidemiological reports. We used EVD case definitions provided by the World Health Organisation over the course of the outbreak. Characteristics assessed included level of response activities and epidemiological features such as reported exposure (funeral-related or not), time interval between onset of illness and admission to the EVD Management Centre (EMC), work-related exposures (health worker or not) and mortality. We compared these characteristics between two time periods—June to July (the early period of response), and August to December (when coverage and quality of response had improved). A stochastic model was used to predict case numbers per generation with different numbers of beds and a varying percentage of community cases detected. Results There were 652 probable/confirmed EVD cases from June-December 2014 in Kailahun. An EMC providing patient care opened in June. By August 2014 an integrated detection, treatment, and prevention strategy was in place across the district catchment zone. From June-July to August-December 2014 surveillance and contact tracing staff increased from 1.0 to 8.8 per confirmed EVD case, EMC capacity increased from 32 to 100 beds, the number of burial teams doubled, and health promotion activities increased in coverage. These improvements in response were associated with the following changes between the same periods: the proportion of confirmed/probable cases admitted to the EMC increased from 35% to 83% (χ2 p-value<0·001), the proportion of confirmed patients admitted to the EMC <3 days of symptom onset increased from 19% to 37% (χ2 p-value <0·001), and reported funeral contact in those admitted decreased from 33% to 16% (χ2 p-value <0·001). Mathematical modelling confirmed the importance of both patient management capacity and surveillance and contact tracing for EVD control. Discussion Our findings demonstrate that control of EVD can be achieved using established interventions based on identification and appropriate management of those who are at risk of and develop EVD, including in the context of ongoing transmission in surrounding regions. Key attributes in achieving control were sufficient patient care capacity (including admission to specialist facilities of suspect and probable cases for assessment), integrated with adequate staffing and resourcing of community-based case detection and prevention activities. The response structure and coverage targets we present are of value in informing effective control in current and future EVD outbreaks.

Improving mapping for Ebola response through mobilising a local community with self-owned smartphones: Tonkolili District, Sierra Leone, January 2015

Background During the 2014–16 Ebola virus disease (EVD) outbreak, the Magburaka Ebola Management Centre (EMC) operated by Médecins Sans Frontières (MSF) in Tonkolili District, Sierra Leone, identified that available district maps lacked up-to-date village information to facilitate timely implementation of EVD control strategies. In January 2015, we undertook a survey in chiefdoms within the MSF EMC catchment area to collect mapping and village data. We explore the feasibility and cost to mobilise a local community for this survey, describe validation against existing mapping sources and use of the data to prioritise areas for interventions, and lessons learned. Methods We recruited local people with self-owned Android smartphones installed with open-source survey software (OpenDataKit (ODK)) and open-source navigation software (OpenStreetMap Automated Navigation Directions (OsmAnd)). Surveyors were paired with local motorbike drivers to travel to eligible villages. The collected mapping data were validated by checking for duplication and comparing the village names against a pre-existing village name and location list using a geographic distance and text string-matching algorithm. Results The survey teams gained sufficient familiarity with the ODK and OsmAnd software within 1–2 hours. Nine chiefdoms in Tonkolili District and three in Bombali District were surveyed within two weeks. Following de-duplication, the surveyors collected data from 891 villages with an estimated 127,021 households. The overall survey cost was €3,395; €3.80 per village surveyed. The MSF GIS team (MSF-OCG) created improved maps for the MSF Magburaka EMC team which were used to support surveillance, investigation of suspect EVD cases, hygiene-kit distribution and EVD survivor support. We shared the mapping data with OpenStreetMap, the local Ministry of Health and Sanitation and Sierra Leone District and National Ebola Response Centres. Conclusions Involving local community and using accessible technology allowed rapid implementation, at moderate cost, of a survey to collect geographic and essential village information, and creation of updated maps. These methods could be used for future emergencies to facilitate response.

Ebola Management Centre Proximity Associated With Reduced Delays of Healthcare of Ebola Virus Disease (EVD) Patients, Tonkolili, Sierra Leone, 2014-15

Between August-December 2014, Ebola Virus Disease (EVD) patients from Tonkolili District were referred for care to two Médecins Sans Frontières (MSF) Ebola Management Centres (EMCs) outside the district (distant EMCs). In December 2014, MSF opened an EMC in Tonkolili District (district EMC). We examined the effect of opening a district-based EMC on time to admission and number of suspect cases dead on arrival (DOA), and identified factors associated with fatality in EVD patients, residents in Tonkolili District. Residents of Tonkolili district who presented between 12 September 2014 and 23 February 2015 to the district EMC and the two distant EMCs were identified from EMC line-lists. EVD cases were confirmed by a positive Ebola PCR test. We calculated time to admission since the onset of symptoms, case-fatality and adjusted Risk Ratios (aRR) using Binomial regression. Of 249 confirmed Ebola cases, 206 (83%) were admitted to the distant EMCs and 43 (17%) to the district EMC. Of them 110 (45%) have died. Confirmed cases dead on arrival (n = 10) were observed only in the distant EMCs. The median time from symptom onset to admission was 6 days (IQR 4,8) in distant EMCs and 3 days (IQR 2,7) in the district EMC (p<0.001). Cases were 2.0 (95%CI 1.4–2.9) times more likely to have delayed admission (>3 days after symptom onset) in the distant compared with the district EMC, but were less likely (aRR = 0.8; 95%CI 0.6–1.0) to have a high viral load (cycle threshold ≤22). A fatal outcome was associated with a high viral load (aRR 2.6; 95%CI 1.8–3.6) and vomiting at first presentation (aRR 1.4; 95%CI 1.0–2.0). The opening of a district EMC was associated with earlier admission of cases to appropriate care facilities, an essential component of reducing EVD transmission. High viral load and vomiting at admission predicted fatality. Healthcare providers should consider the location of EMCs to ensure equitable access during Ebola outbreaks.