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Background: Ebola virus disease (Ebola) is highly pathogenic, transmissible, and often deadly, with debilitating consequences. Superspreading within a cluster is also possible. In this study, we aim to document Ebola basic reproduction number (R 0 ): the average number of new cases associated with an Ebola case in a completely susceptible population., Methods: We undertook a systematic review and meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published between 1976 and February 27, 2023. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that reported R 0 during Ebola outbreaks in Africa. We excluded studies that reported only the effective reproduction number (R t ). Abstracting data from included studies was performed using a pilot-tested standard form. Two investigators reviewed the studies, extracted the data, and assessed quality. The pooled R 0 was determined by a random-effects meta-analysis. R 0 was stratified by country. We also estimated the theoretically required immunization coverage to reach herd-immunity using the formula of (1-1/R 0 ) × 100 %., Results: The search yielded 2042 studies. We included 53 studies from six African countries in the systematic review providing 97 Ebola mean R 0 estimates. 27 (with 46 data points) studies were included in the meta-analysis. The overall pooled mean Ebola R 0 was 1.95 (95 % CI 1.74-2.15), with high heterogeneity (I 2  = 99.99 %; τ 2  = 0.38; and p < 0.001) and evidence of small-study effects (Egger's statistics: Z = 4.67; p < 0.001). Mean Ebola R 0 values ranged from 1.2 to 10.0 in Nigeria, 1.1 to 7 in Guinea, 1.14 to 8.33 in Sierra Leone, 1.13 to 5 in Liberia, 1.2 to 5.2 in DR Congo, 1.34 to 2.7 in Uganda, and from 1.40 to 2.55 for all West African countries combined. Pooled mean Ebola R 0 was 9.38 (95 % CI 4.16-14.59) in Nigeria, 3.31 (95 % CI 2.30-4.32) in DR Congo, 2.0 (95 % CI 1.25-2.76) in Uganda, 1.83 (95 % CI 1.61-2.05) in Liberia, 1.73 (95 % CI 1.47-2.0) in Sierra Leonne, and 1.44 (95 % CI 1.29-1.60) in Guinea. In theory, 50 % of the population needs to be vaccinated to achieve herd immunity, assuming that Ebola vaccine would be 100 % effective., Conclusions: Ebola R 0 varies widely across countries. Ebola has a much wider R 0 range than is often claimed (1.3-2.0). It is possible for an Ebola index case to infect more than two susceptible individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Whether or not individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease develop clinical sequelae is unknown. We assessed current symptoms and physical examination findings among individuals with pauci-symptomatic or asymptomatic infection and unrecognised Ebola virus disease compared with Ebola virus disease survivors and uninfected contacts., Methods: Between June 17, 2015, and June 30, 2017, we studied a cohort of Ebola virus disease survivors and their contacts in Liberia. Surveys, current symptoms and physical examination findings, and serology were used to characterise disease status of reported Ebola virus disease, unrecognised Ebola virus disease, pauci-symptomatic or asymptomatic Ebola virus infection, or no infection. We pre-specified findings known to be differentially prevalent among Ebola virus disease survivors versus their contacts (urinary frequency, headache, fatigue, muscle pain, memory loss, joint pain, neurological findings, chest findings, muscle findings, joint findings, abdominal findings, and uveitis). We estimated the prevalence and incidence of selected clinical findings by disease status., Findings: Our analytical cohort included 991 reported Ebola virus disease survivors and 2688 close contacts. The median time from acute Ebola virus disease onset to baseline was 317 days (IQR 271-366). Of 222 seropositive contacts, 115 had pauci-symptomatic or asymptomatic Ebola virus infection and 107 had unrecognised Ebola virus disease. At baseline, prevalent findings of joint pain, memory loss, muscle pain, and fatigue were lowest among those with pauci-symptomatic or asymptomatic infection or no infection, higher among contacts with unrecognised Ebola virus disease, and highest in reported survivors of Ebola virus disease. Joint pain was the most prevalent finding, and was reported in 434 (18%) of 2466 individuals with no infection, 14 (12%) of 115 with pauci-symptomatic or asymptomatic infection, 31 (29%) of 107 with unrecognised Ebola virus disease, and 476 (48%) of 991 with reported Ebola virus disease. In adjusted analyses, this pattern remained for joint pain and memory loss. Survivors had an increased odds of joint pain compared with unrecognised Ebola virus disease contacts (adjusted odds ratio [OR] 2·13, 95% CI 1·34-3·39); unrecognised Ebola virus disease contacts had an increased odds of joint pain compared with those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 1·89, 95% CI 1·21-2·97). The adjusted odds of memory loss was more than four-times higher among survivors than among unrecognised Ebola virus disease contacts (adjusted OR 4·47, 95% CI 2·41-8·30) and two-times higher among unrecognised Ebola virus disease contacts than in those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 2·05, 95% CI 1·10-3·84). By 12 months, prevalent findings had decreased in the three infected groups., Interpretation: Our findings provide evidence of post-Ebola virus disease clinical sequelae among contacts with unrecognised Ebola virus disease but not in people with pauci-symptomatic or asymptomatic Ebola virus infection., Funding: National Cancer Institute and National Institute of Allergy and Infectious Diseases of the National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Ebola virus disease case definition is a crucial surveillance tool to detect suspected cases for referral and as a screening tool for clinicians to support admission and laboratory testing decisions at Ebola health facilities. We aimed to assess the performance of the WHO Ebola virus disease case definitions and other screening scores., Methods: In this systematic review and meta-analysis, we searched PubMed, Scopus, Embase, and Web of Science for studies published in English between June 13, 1978, and Jan 14, 2020. We included studies that estimated the sensitivity and specificity of WHO Ebola virus disease case definitions, clinical and epidemiological characteristics (symptoms at admission and contact history), and predictive risk scores against the reference standard (laboratory-confirmed Ebola virus disease). Summary estimates of sensitivity and specificity were calculated using bivariate and hierarchical summary receiver operating characteristic (when four or more studies provided data) or random-effects meta-analysis (fewer than four studies provided data)., Findings: We identified 2493 publications, of which 14 studies from four countries (Sierra Leone, Guinea, Liberia, and Angola) were included in the analysis. 12 021 people with suspected disease were included, of whom 4874 were confirmed as positive for Ebola virus infection. Six studies explored the performance of WHO case definitions in non-paediatric populations, and in all of these studies, suspected and probable cases were combined and could not be disaggregated for analysis. The pooled sensitivity of the WHO Ebola virus disease case definitions from these studies was 81·5% (95% CI 74·1-87·2) and pooled specificity was 35·7% (28·5-43·6). History of contact or epidemiological link was a key predictor for the WHO case definitions (seven studies) and for risk scores (six studies). The most sensitive symptom was intense fatigue (79·0% [95% CI 74·4-83·0]), assessed in seven studies, and the least sensitive symptom was pain behind the eyes (1·0% [0·0-7·0]), assessed in three studies. The performance of fever as a symptom varied depending on the cutoff used to define fever., Interpretation: WHO Ebola virus disease case definitions perform suboptimally to identify cases at both community level and during triage at Ebola health facilities. Inclusion of intense fatigue as a key symptom and contact history could improve the performance of case definitions, but implementation of these changes will require effective collaboration with, and trust of, affected communities., Funding: Médecins sans Frontières., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics., Methods: Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays., Findings: The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300-350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes., Interpretation: The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics., Funding: Defense Biological Product Assurance Office of the US Department of Defense and the Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance and Response Section., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain., Methods: We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage., Findings: 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217., Interpretation: This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt., Funding: US Global Health Security., (Copyright © 2018 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The 2014-2015 Ebola outbreak in West Africa is the largest and longest Ebola Virus Disease (EVD) outbreak in the history, and the virus has escaped across countries and continents via air travel in this outbreak., Method: The interpolated data from WHO Ebola situation reports were used to estimate number of weekly infectious individuals and daily effective reproduction numbers (R t ) in Guinea, Liberia and Sierra Leone. A stochastic dynamic model was performed to estimate the risk of EVD importation into the top 20 final destination countries of air travelers departing from within the three epidemic countries, and the effectiveness of air travel restriction was subsequently evaluated., Results: The daily R t was estimated at 0.72-1.32 in Guinea, 0.62-1.38 in Liberia and 0.81-1.38 in Sierra Leone. The peak of EVD importation probability was observed in early November 2014 and the restriction of air travel may mitigate the risk up to 67.7% (95% CI 66.6-68.7)., Conclusions: Our results suggest that restriction of air travels is effective in reducing the risk of EVD importation but controlling of the virus at the original affected countries is vitally more important for preventing inter-terrestrial dissemination of EVD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: After the detection of an Ebola virus disease outbreak in west Africa in 2014, one of the elements of the response was to contact trace and isolate patients in specialised Ebola treatment units (ETUs) at onset of fever. We aimed to assess the economic feasibility of administering preventive malaria treatment to all contacts of patients with Ebola virus disease, to prevent the onset of febrile malaria and subsequent admission to ETUs., Methods: We used a decision tree model to analyse the costs of preventive malaria treatment (artemisinin-based combination treatment [ACT]) for all contacts of patients with Ebola virus disease (in terms of administration and averted ETU-stay costs) and benefits (in terms of averted ETU admissions) in west Africa, from a health-care provider perspective. The period of analyses was 1 year, which is roughly similar to the duration of the 2014-15 west Africa Ebola outbreak response. We calculated the intervention's cost per ETU admission averted (average cost-effectiveness ratio) by season (wet and dry), country (Liberia, Sierra Leone, and Guinea), and age of contact (<5 years, 5-14 years, and ≥15 years). We did sensitivity analyses to assess how results varied with malaria parasite prevalence (in children aged 2-10 years), daily cost of ETU stay (for Liberian malaria incidence levels), and compliance and effectiveness of preventive malaria treatment., Findings: Administration of ACTs to contacts of patients with Ebola virus disease was cost saving for contacts of all ages in Liberia, Sierra Leone, and Guinea, in both seasons, from a health-care provider perspective. In the wet season, preventive malaria treatment was estimated to reduce the probability of a contact being admitted to an ETU by a maximum of 36% (in Guinea, for contacts aged <5 years), and a minimum of 10% (in Guinea and Sierra Leone, for those aged ≥15 years). Assuming 85% compliance and taking into account the African population pyramid, the intervention is expected to be cost saving in contacts of all age groups in areas with malaria parasite prevalence in children aged 2-10 years as low as 10%. In Liberia during the wet season, malaria preventive treatment was cost saving even when average daily bed-stay costs were as low as US$5 for children younger than 5 years, $9 for those aged 5-14 years, and $22 for those aged 15 years or older., Interpretation: Administration of preventive malaria treatment to contacts of patients with Ebola virus disease should be considered by public health officials when addressing Ebola virus disease outbreaks in countries and seasons where malaria reaches high levels of transmission., Funding: Centers for Disease Control and Prevention., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The ongoing Ebola epidemic in parts of west Africa largely overwhelmed health-care systems in 2014, making adequate care for malaria impossible and threatening the gains in malaria control achieved over the past decade. We quantified this additional indirect burden of Ebola virus disease., Methods: We estimated the number of cases and deaths from malaria in Guinea, Liberia, and Sierra Leone from Demographic and Health Surveys data for malaria prevalence and coverage of malaria interventions before the Ebola outbreak. We then removed the effect of treatment and hospital care to estimate additional cases and deaths from malaria caused by reduced health-care capacity and potential disruption of delivery of insecticide-treated bednets. We modelled the potential effect of emergency mass drug administration in affected areas on malaria cases and health-care demand., Findings: If malaria care ceased as a result of the Ebola epidemic, untreated cases of malaria would have increased by 45% (95% credible interval 43-49) in Guinea, 88% (83-93) in Sierra Leone, and 140% (135-147) in Liberia in 2014. This increase is equivalent to 3·5 million (95% credible interval 2·6 million to 4·9 million) additional untreated cases, with 10,900 (5700-21,400) additional malaria-attributable deaths. Mass drug administration and distribution of insecticide-treated bednets timed to coincide with the 2015 malaria transmission season could largely mitigate the effect of Ebola virus disease on malaria., Interpretation: These findings suggest that untreated malaria cases as a result of reduced health-care capacity probably contributed substantially to the morbidity caused by the Ebola crisis. Mass drug administration can be an effective means to mitigate this burden and reduce the number of non-Ebola fever cases within health systems., Funding: UK Medical Research Council, UK Department for International Development, Bill & Melinda Gates Foundation., (Copyright © 2015 Walker et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: The 2014 epidemic of Ebola virus disease in parts of west Africa defines an unprecedented health threat. We developed a model of Ebola virus transmission that integrates detailed geographical and demographic data from Liberia to overcome the limitations of non-spatial approaches in projecting the disease dynamics and assessing non-pharmaceutical control interventions., Methods: We modelled the movements of individuals, including patients not infected with Ebola virus, seeking assistance in health-care facilities, the movements of individuals taking care of patients infected with Ebola virus not admitted to hospital, and the attendance of funerals. Individuals were grouped into randomly assigned households (size based on Demographic Health Survey data) that were geographically placed to match population density estimates on a grid of 3157 cells covering the country. The spatial agent-based model was calibrated with a Markov chain Monte Carlo approach. The model was used to estimate Ebola virus transmission parameters and investigate the effectiveness of interventions such as availability of Ebola treatment units, safe burials procedures, and household protection kits., Findings: Up to Aug 16, 2014, we estimated that 38·3% of infections (95% CI 17·4-76·4) were acquired in hospitals, 30·7% (14·1-46·4) in households, and 8·6% (3·2-11·8) while participating in funerals. We noted that the movement and mixing, in hospitals at the early stage of the epidemic, of patients infected with Ebola virus and those not infected was a sufficient driver of the reported pattern of spatial spread. The subsequent decrease of incidence at country and county level is attributable to the increasing availability of Ebola treatment units (which in turn contributed to drastically decreased hospital transmission), safe burials, and distribution of household protection kits., Interpretation: The model allows assessment of intervention options and the understanding of their role in the decrease in incidence reported since Sept 7, 2014. High-quality data (eg, to estimate household secondary attack rate, contact patterns within hospitals, and effects of ongoing interventions) are needed to reduce uncertainty in model estimates., Funding: US Defense Threat Reduction Agency, US National Institutes of Health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: A substantial scale-up in public health response is needed to control the unprecedented Ebola virus disease (EVD) epidemic in west Africa. Current international commitments seek to expand intervention capacity in three areas: new EVD treatment centres, case ascertainment through contact tracing, and household protective kit allocation. We aimed to assess how these interventions could be applied individually and in combination to avert future EVD cases and deaths., Methods: We developed a transmission model of Ebola virus that we fitted to reported EVD cases and deaths in Montserrado County, Liberia. We used this model to assess the effectiveness of expanding EVD treatment centres, increasing case ascertainment, and allocating protective kits for controlling the outbreak in Montserrado. We varied the efficacy of protective kits from 10% to 50%. We compared intervention initiation on Oct 15, 2014, Oct 31, 2014, and Nov 15, 2014. The status quo intervention was defined in terms of case ascertainment and capacity of EVD treatment centres on Sept 23, 2014, and all behaviour and contact patterns relevant to transmission as they were occurring at that time. The primary outcome measure was the expected number of cases averted by Dec 15, 2014., Findings: We estimated the basic reproductive number for EVD in Montserrado to be 2·49 (95% CI 2·38-2·60). We expect that allocating 4800 additional beds at EVD treatment centres and increasing case ascertainment five-fold in November, 2014, can avert 77 312 (95% CI 68 400-85 870) cases of EVD relative to the status quo by Dec 15, 2014. Complementing these measures with protective kit allocation raises the expectation as high as 97 940 (90 096-105 606) EVD cases. If deployed by Oct 15, 2014, equivalent interventions would have been expected to avert 137 432 (129 736-145 874) cases of EVD. If delayed to Nov 15, 2014, we expect the interventions will at best avert 53 957 (46 963-60 490) EVD cases., Interpretation: The number of beds at EVD treatment centres needed to effectively control EVD in Montserrado substantially exceeds the 1700 pledged by the USA to west Africa. Accelerated case ascertainment is needed to maximise effectiveness of expanding the capacity of EVD treatment centres. Distributing protective kits can further augment prevention of EVD, but it is not an adequate stand-alone measure for controlling the outbreak. Our findings highlight the rapidly closing window of opportunity for controlling the outbreak and averting a catastrophic toll of EVD cases and deaths., Funding: US National Institutes of Health., (Copyright © 2014 Elsevier Ltd. All rights reserved.)