Global Epidemic of Ebola Virus Disease and the Importation Risk into China: An Assessment Based on the Risk Matrix Method

Objective To analyze the global epidemic status of the Ebola virus disease(EVD) and assess the importation risk into China.Methods Data from World Health Organization reports were used. We described the global epidemic status of EVD from 1976–2021, and assessed and ranked the importation risk of EVD from the diseaseoutbreaking countries into China using the risk matrix and Borda count methods, respectively.Results From 1976–2021, EVD mainly occurred in western and central Africa, with the highest cumulative number of cases(14,124 cases) in Sierra Leone, and the highest cumulative fatality rate(85%) in the Congo. Outbreaks of EVD have occurred in the Democratic Republic of the Congo and Guinea since 2018. The importation risk into China varies across countries with outbreaks of disease.The Democratic Republic of the Congo had an extremely high risk(23 Borda points), followed by Guinea and Liberia. Countries with a moderate importation risk were Nigeria, Uganda, Congo, Sierra Leone,Mali, and Gabon, while countries with a low importation risk included Sudan, Senegal, and Co te d’Ivoire.Conclusion China is under the risk of EVD importation with the globalization and severe epidemic status of EVD. Key attention need to be paid to the Democratic Republic of the Congo, Guinea, and Liberia. Therefore, it is necessary to prevent and prepare in advance for importation risk in China.

Current updates on the epidemiology,pathogenesis and development of small molecule therapeutics for the treatment of Ebola virus infections

Ebola virus disease(EVD)is a rare,highly contagious and a deadly disease with a variable fatality rate ranging from 30%to 90%.Over the past two decades,Ebola pandemic has severely affected the sub-Sahara region including Democratic Republic of the Congo(DRC),and Uganda.The causative agents of the most EVD cases are three distinct species out of six Ebolaviruses namely Zaire Ebolavirus(ZEBOV),Sudan Ebolavirus(SUDV)and Bundibugyo Ebolavirus(BDBV).In recent years,significant strides have been made in therapeutic interventions.Notably,the US Food and Drug Administration has approved two monoclonal antibodies:InmazebTM(REGN-EB3)and Ansuvimab or EbangaTM.Additionally,many small molecules are currently in the developmental stage,promising further progress in medical treatment.Addressing the critical need for preventive measures,this review provides an in-depth analysis of the licensed Ebola vaccines-Ervebo and the combination of Zabdeno(Ad26.ZEBOV)and Mvabea(MVA-BN-Filo)as well as the vaccines which are currently being tested for their efficacy and safety in clinical studies.These vaccines might play an important role in curbing the spread and mitigating the impact of this lethal disease.The current treatment landscape for EVD encompasses both nutritional(supportive)and drug therapies.The review comprehensively details the origin,pathogenesis,and epidemiology of EVD,shedding light on the ongoing efforts to combat this devastating disease.It explores small molecules in various stages of the development,discusses patents filed or granted,and delves into the clinical and supportive therapies that form the cornerstone of EVD management.This review aims to provide the recent developments made in the design and synthesis of small molecules for scientific community to facilitate a deeper understanding of the disease and fostering the development of effective strategies for prevention,treatment,and control of EVD.

Ebola Virus Disease: General Characteristics, Thoughts, and Perspectives

In December 2013, a new round of Ebola virus disease （EVD） first occurred in a remote countryside of Guinea and then spread in Guinea, Liberia, Sierra Leone, and Nigeria of West Africa. EVD, caused by Ebolavirus and previously known as Ebola hemorrhagic fever, is an acute infectious disease with fatality rates up to 90%. As of August 22, 2014, the number of suspected and confirmed cases was 2615, causing 1427 deaths[I]. On August 8, 2014, World Health Organization announced the current outbreak in West Africa as an international public health emergency. The global epidemic tendency remains ambiguous to date. In recent years, China closely collaborates with West Africa in labor, business, overseas education, and also sends aid medical team there. Thus, the risk of importing the disease cannot be ignored. We conduct this literature review of epidemiology, pathogen, prophylaxis, and treatment to provide evidence for controlling the risk and carrying out effective interventions.

Ebola virus disease: past, present and future

Ebola virus disease is one of the most deadly ailments known to mankind due to its high mortality rate(up to 90%) accompanying with the disease. Ebola haemorrhagic fever(EHF) is an infectious disease of animal that can be transmitted to both human and non-human primates. The first epidemic of EHF occurred in 1976 in the Democratic Republic of the Congo. The incubation period of ebola is less than 21 days. Ebola virus infections are depicted by immune suppression and a systemic inflammatory response that leads to damage of the vascular, coagulation and immune systems, causing multi-organ failure and shock. Five genetically distinct members of the Filoviridae family responsible for EHF are as follows: Zaire ebolavirus, Sudan ebolavirus, C?te d'Ivoire ebolavirus, Bundibugyo ebolavirus and Reston ebolavirus. The ongoing 2014 West Africa ebola epidemic has been considered as the most serious panic in the medical field with respect to both the number of human cases and death toll. The natural host for ebola virus is unknown, thus it is not possible to carry out programs to regulate or abolish virus from transmission to people. The ebola virus infection provides little chance to develop acquired immunity causing rapid progression of the disease. It is pertinent to mention that at present, there is no antiviral therapy or vaccine that is helpful against ebola virus infection in humans. The impediment of EHF necessitates much better understanding of the epidemiology of the disease, particularly the role of wildlife, as well as bats, in the spread of ebola virus to humans.

Ebola virus disease: From epidemiology to prophylaxis

The outbreak of Ebola virus disease(EVD) continues to spread through West Africa. Since the first reported EVD in March 2014, the number of cases has increased rapidly, with the fatality rate of >50%. The most prevalent Ebola virus belongs to the species of Zaire ebolavirus, with a mortality rate as high as 90%. Although there were introduced cases in other continents, Africa is the endemic area where fruit bats and apes are suspected to be Ebola virus carriers. The virus might be transmitted from the host animals to humans if humans consume relative raw and contaminated meats; however, human-to-human transmission via close contact is the major route of current outbreaks. EVD happens at any seasons and affected people of any race in any age groups. Direct contact with body fluids of EVD patients and living in the contaminated environment greatly increase the risk of being infected. Transmission viaaerosol is less possible but the transmission via droplet is possible in humans. Thus, health care providers are facing danger of getting Ebola virus infection. So far, there are limited vaccines, drugs and/or therapies to prevent Ebola virus infection or treat EVD. Medical workers should follow the current standard prophylactic procedures. Military forces can orchestrate efficient care to mass EVD casualties. Although it is necessary to speed up the pace of developing effective vaccine and therapeutics for the prevention and treatment of EVD, public health prophylaxis is the most important issue at present to control the spread of this disease cost-effectively.

Social Dynamics of Ebola Virus Disease: A Case of Bundibugyo District, Uganda

Background: Ebola Virus Disease (EVD) presents with a high global mortality and is known to be a highly infectious disease with devastating and gendered effects on the social fabric, yet most of the science has focused on the disease’s biology. However, little has been documented with regard to the gender and social aspects of Ebola Virus Disease (EVD) in two sub counties (Kikyo and Bundibugyo Town Council) in Bundibugyo District in Western Uganda. The study was set to examine the gender differences in the level of knowledge, attitudes and perceptions about EVD. Methods: The study employed a cross-sectional design using both quantitative and qualitative data collection methods. A structured questionnaire was administered to 254 respondents, 50% of whom were women. Simple random sampling was used to select the participants. Questionnaire data were analysed using SPSS at univariate and bivariate levels. Qualitative methods such as key informant interviews (with 6 participants) and Focus Group Discussions (three, one with men alone, another with women alone and the last one with both men and women) were also used to collect additional information from participants. Results: The findings indicated that socio-demographically, the majority (35%) of the respondents were aged between 20 and 29 years, 53% of whom were females. More women (about 56%) compared to men (44%) attained secondary education while more men (about 51% versus 49% of the women) reported that they were married. In terms of religion, the majority of the survey participants were Catholics (59% females and 49% males). With regard to communities’ knowledge about EVD, there was no significant relationship between men and women in terms of prior knowledge about EVD, risk factors and control measures. However, slightly more males (about 51%) than females (49%) had heard about EVD and more males (about 52%) than females (48%) admitted that they were at risk of contracting the disease. On the control measures, slightly more females than males (about 53% vs. 47% respectively) proposed avoiding contact with infected persons. The results further revealed that more males (about 51%) than females (49%) were willing to relate with EVD survivors, and this was due to the latter’s fear of contracting the disease. The major devastating effects of EVD that were reported included loss of lives, disruption of peoples movements, isolation of people, disruption of children’s school activities, stigma and discrimination of survivors. More females (about 52%) than males (about 48%) reported that EVD survivors were discriminated during the EVD outbreak in Bundibugyo District. Conclusions: This study has shown that whereas both men and women demonstrate average knowledge about EVD, there is need for more training and sensitization targeting women who have delusions about the severity of the disease, its risk factors, stigma and the integration of survivors in the affected communities. Communities also need to be sensitized about the gender roles that increase both the burden of EVD and the risk of men and women contracting the disease. This will lead to more culturally sensitive responses to EVD outbreaks in future.

Obstetrical Surgery in the Context of Ebola Virus Disease (Ebola) in Guinea: Lessons Learned from 2 Cases

In this manuscript, the authors have studied obstetrical surgery in the context of Ebola virus disease in Guinea. No protocol recommends childbirth outside of Ebola treatment center, although it has no technical platform and no qualified providers in this area. These were unknown MVE cases in pregnant women/parturient women aged 25 and 40 years, with no education, who were confirmed in the RT-PCR test after surgical management. To fight Ebola virus transmission, traditional protection protocols must be strengthened. Training, supervision and monitoring of providers are key elements for the protection of staff in the event of an EVD outbreak. Improving working conditions and strengthening hand washing, usage of PPE/EPP, decontamination of equipment with 0.5% chlorine solution, hygiene of premises, immunization of personnel involved, are effective measures to combat EVD.

The Ebola virus:a review of progress and development in research

The Ebola virus was identified in the year 1976 and has caused periodic outbreaks in West African countries.The disease has a case fatality rate up to 90%.Ebola has been classified as a biosafety level four pathogen and there is no currently approved vaccine or treatment for the virus.However,remarkable progress has been demonstrated by researchers in understanding the pathogenicity of the Ebola virus.Several animal models have been cultivated to develop diagnostics,vaccines and therapeutic drugs.

Detection and Analysis of Ebola Virus in Sierra Leone-China Friendship Biosafety Laboratory from March 11 to April 20, 2015

Ebola virus disease reemerged in Western Africa in 2014.Chinese Center for Disease Control and Prevention dispatched the first Ebola virus（EBOV）detection team to run newly established Sierra Leone-China Friendship Biological Safety Laboratory.The aims of study were to understand epidemiology,clinical manifestations and survival time of EBOV in patient＇s blood.A total of 913specimens were tested between March 11 and April20, 2015. EBOV positivity occurred in 7.37% of the blood and 0.53% in throat swabs.

Animal models for filovirus infections

The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates （NHPs）, causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.

Indirect costs associated with deaths from the Ebola virus disease in West Africa

Background:By 28 June 2015,there were a total of 11,234 deaths from the Ebola virus disease(EVD)in five West African countries(Guinea,Liberia,Mali,Nigeria and Sierra Leone).The objective of this study was to estimate the future productivity losses associated with EVD deaths in these West African countries,in order to encourage increased investments in national health systems.Methods:A cost-of-illness method was employed to calculate future non-health(NH)gross domestic product(GDP)(NHGDP)losses associated with EVD deaths.The future non-health GDP loss(NHGDPLoss)was discounted at 3%.Separate analyses were done for three different age groups(<=14 years,15–44 years and=>45 years)for the five countries(Guinea,Liberia,Mali,Nigeria,and Sierra Leone)affected by EVD.We also conducted a one-way sensitivity analysis at 5 and 10%discount rates to gauge their impacts on expected NHGDPLoss.Results:The discounted value of future NHGDPLoss due to the 11,234 deaths associated with EVD was estimated to be Int$(international dollars)155,663,244.About 27.86%of the loss would be borne by Guinea,34.84%by Liberia,0.10%by Mali,0.24%by Nigeria and 36.96%by Sierra Leone.About 27.27%of the loss is attributed to those aged under 14 years,66.27%to those aged 15–44 years and 6.46%to those aged over 45 years.The average NHGDPLoss per EVD death was estimated to be Int$17,473 for Guinea,Int$11,283 for Liberia,Int$25,126 for Mali,Int$47,364 for Nigeria and Int$14,633 for Sierra Leone.Conclusion:In spite of alluded limitations,the estimates of human and economic losses reported in this paper,in addition to those projected by the World Bank,show that EVD imposes a significant economic burden on the affected West African countries.That heavy burden,coupled with human rights and global security concerns,underscores the urgent need for increased domestic and external investments to enable Guinea,Liberia and Sierra Leone(and other vulnerable African countries)to develop resilient health systems,including core capacities to detect,assess,notify,verify and report events,and to respond to public health risks and emergencies.

Modeling the role of public health education in Ebola virus disease outbreaks in Sudan

Public involvement in Ebola Virus Disease(EVD)prevention efforts is key to reducing disease outbreaks.Targeted education through practical health information to particular groups and sub-populations is crucial to controlling the disease.In this paper,we study the dynamics of Ebola virus disease in the presence of public health education with the aim of assessing the role of behavior change induced by health education to the dynamics of an outbreak.The power of behavior change is evident in two outbreaks of EVD that took place in Sudan only 3 years apart.The first occurrence was the first documented outbreak of EVD and produced a significant number of infections.The second outbreak produced far fewer cases,presumably because the population in the region learned from the first outbreak.We derive a system of ordinary differential equations to model these two contrasting behaviors.Since the population in Sudan learned from the first outbreak of EVD and changed their behavior prior to the second outbreak,we use data from these two instances of EVD to estimate parameters relevant to two contrasting behaviors.We then simulate a future outbreak of EVD in Sudan using our model that contains two susceptible populations,one being more informed about EVD.Our finding show how a more educated population results in fewer cases of EVD and highlights the importance of ongoing public health education.

Potential for broad-scale transmission of Ebola virus disease during the West Africa crisis:lessons for the Global Health security agenda

Background:The 2014-2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks.The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia,Sierra Leone,and Guinea,hinted at the possibility of broad-scale transmission of Ebola.Main text:Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak,we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission(based on late 2014 air travel patterns).We estimated Ebola cases in three scenarios:a delayed response,a Liberia-like response,and a fast response scenario.Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci,we emphasize the need for improved levels of preparedness and response to public health threats,which is the goal of the Global Health Security Agenda.Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci,had local and international health workers and organizations not committed to a major response effort.Our results underscore the importance of rapid detection and initiation of an effective,organized response,and the challenges faced by countries with limited public health systems.Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel,bolstering primary and critical healthcare facilities,developing public health infrastructure(e.g.laboratory capacity),and improving disease surveillance.With stronger local public health systems infectious disease outbreaks would still occur,but their rapid escalation would be considerably less likely,minimizing the impact of public health threats such as Ebola.Conclusions:The Ebola outbreak could have potentially spread to other countries,where limited public health surveillance and response capabilities may have resulted in additional foci.Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak.

An Ebola virus disease model with fear and environmental transmission dynamics

Recent Ebola virus disease(EVD)outbreaks have been limited not only to the interactions between humans but also to the complex interplay of the environment,human and socio-economic factors.Changes in human behaviour as a result of fear can also affect disease transmission dynamics.In this paper,a compartmental model is used to study the dynamics of EVD incorporating fear and environmental transmission.We formulate a fear dependent contact rate function to measure the rate of person to person,as well as pathogen to person transmissions.The epidemic threshold and the model equilibria are determined and,their stabilities are analysed.The model is validated by fitting it to data from the 2019 and 2020 EVD outbreaks in the Democratic Republic of Congo.Our results suggest that the fear of death from EVD may reduce the transmission and aid the control of the disease,but it is not sufficient to eradicate the disease.Policymakers need to also implement other control measures such as case finding,media campaigns,Quarantine and increase in the number of beds in the Ebola treatment centers,good laboratory services,safe burials and social mobilisation,to eradicate the disease.

Modeling the impact of quarantine during an outbreak of Ebola virus disease

The quarantine of people suspected of being exposed to an infectious agent is one of the most basic public health measure that has historically been used to combat the spread of communicable diseases in human communities.This study presents a new deterministic model for assessing the population-level impact of the quarantine of individuals suspected of being exposed to disease on the spread of the 2014e2015 outbreaks of Ebola viral disease.It is assumed that quarantine is imperfect(i.e.,individuals can acquire infection during quarantine).In the absence of quarantine,the model is shown to exhibit global dynamics with respect to the disease-free and its unique endemic equilibrium when a certain epidemiological threshold(denoted byR 0)is either less than or greater than unity.Thus,unlike the full model with imperfect quarantine(which is known to exhibit the phenomenon of backward bifurcation),the version of the model with no quarantine does not undergo a backward bifurcation.Using data relevant to the 2014e2015 Ebola transmission dynamics in the three West African countries(Guinea,Liberia and Sierra Leone),uncertainty analysis of the model show that,although the current level and effectiveness of quarantine can lead to significant reduction in disease burden,they fail to bring the associated quarantine reproduction number(R Q0)to a value less than unity(which is needed to make effective disease control or elimination feasible).This reduction of R Q0 is,however,very possible with a modest increase in quarantine rate and effectiveness.It is further shown,via sensitivity analysis,that the parameters related to the effectiveness of quarantine(namely the parameter associated with the reduction in infectiousness of infected quarantined individuals and the contact rate during quarantine)are the main drivers of the disease transmission dynamics.Overall,this study shows that the singular implementation of a quarantine intervention strategy can lead to the effective control or elimination of Ebola viral disease in a community if its coverage and effectiveness levels are high enough.

Modeling transmission dynamics of Ebola virus disease

Ebola virus disease （EVD） has emerged as a rapidly spreading potentially fatal disease. Several studies have been performed recently to investigate the dynamics of EVD. In this paper, we study the transmission dynamics of EVD by formulating an SEIR-type transmission model that includes isolated individuals as well as dead individuals that are not yet buried. Dynamical systems analysis of the model is performed, and it is consequently shown that the disease-free steady state is globally asymptotically stable when the basic reproduction number, R0 is less than unity. It is also shown that there exists a unique endemic equilibrium when R0 〉 1. Using optimal control theory, we propose control strategies, which will help to eliminate the Ebola disease. We use data fitting on models, with and without isolation, to estimate the basic reproductive numbers for the 2014 outbreak of EVD in Liberia and Sierra Leone.

Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone

Background:Clinical and laboratory data were collected and analysed from patients with Ebola virus disease(EVD)in Jui Government Hospital in Freetown,Sierra Leone,where patients with EVD were received and/or treated from October 1,2014 to March 21,2015 during the West Africa EVD outbreak.Methods:The study admitted 285 patients with confirmed EVD and followed them up till the endpoint(recovery or death).EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus(EBOV).Results:Among the 285 lab-confirmed EVD cases in Jui Government Hospital,146 recovered and 139 died,with an overall survival rate of 51.23%.Patients under the age of 6 years had a lower survival rate(37.50%).Most non-survivors(79.86%)died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56±6.11 days.More than half survivors(63.69%)turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38±7.58 days.High blood viral load(≥106 copies/ml)was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic(ROC)curve analysis.The probability of patients’survival was less than 15%when blood viral load was greater than 106 copies/ml.Multivariate analyses showed that blood viral load(P=0.005),confusion(P=0.010),abdominal pain(P=0.003),conjunctivitis(P=0.035),and vomiting(P=0.004)were factors independently associated with the outcomes of EVD patients.Conclusions:Most death occurred within 1 week after admission,and patients at the age of 6 or younger had a lower survival rate.Most surviving patients turned blood EBOV negative within 1–4 weeks after admission.Factors such as high blood viral load,confusion,abdominal pain,vomiting and conjunctivitis were associated with poor prognosis for EVD patients.

Sustainable strategies for Ebola virus disease outbreak preparedness in Africa:a case study on lessons learnt in countries neighbouring the Democratic Republic of the Congo

Background: From May 2018 to September 2022, the Democratic Republic of Congo (DRC) experienced seven Ebola virus disease (EVD) outbreaks within its borders. During the 10th EVD outbreak (2018–2020), the largest experienced in the DRC and the second largest and most prolonged EVD outbreak recorded globally, a WHO risk assessment identified nine countries bordering the DRC as moderate to high risk from cross border importation. These countries implemented varying levels of Ebola virus disease preparedness interventions. This case study highlights the gains and shortfalls with the Ebola virus disease preparedness interventions within the various contexts of these countries against the background of a renewed and growing commitment for global epidemic preparedness highlighted during recent World Health Assembly events.Main text: Several positive impacts from preparedness support to countries bordering the affected provinces in the DRC were identified, including development of sustained capacities which were leveraged upon to respond to the subsequent coronavirus disease 2019 (COVID-19) pandemic. Shortfalls such as lost opportunities for operationalizing cross-border regional preparedness collaboration and better integration of multidisciplinary perspectives, vertical approaches to response pillars such as surveillance, over dependence on external support and duplication of efforts especially in areas of capacity building were also identified. A recurrent theme that emerged from this case study is the propensity towards implementing short-term interventions during active Ebola virus disease outbreaks for preparedness rather than sustainable investment into strengthening systems for improved health security in alignment with IHR obligations, the Sustainable Development Goals and advocating global policy for addressing the larger structural determinants underscoring these outbreaks.Conclusions: Despite several international frameworks established at the global level for emergency preparedness, a shortfall exists between global policy and practice in countries at high risk of cross border transmission from persistent Ebola virus disease outbreaks in the Democratic Republic of Congo. With renewed global health commitment for country emergency preparedness resulting from the COVID-19 pandemic and cumulating in a resolution for a pandemic preparedness treaty, the time to review and address these gaps and provide recommendations for more sustainable and integrative approaches to emergency preparedness towards achieving global health security is now.

A review on the Ebola virus,outbreak history and the current research tools to control the disease

The Ebola virus is a zoonotic pathogen causing hemorrhagic fever disease with a high mortality rate.The distribution of this pathogen has been limited to woodlands from Central and West Africa and the forest-savannah ecotone in East Africa.The likely reservoir species are frugivorous bats living in these areas.This pathogen is becoming an increasing threat to human populations since its distribution range is expanding faster than expected.The current Ebola outbreaks in Western Africa and in the Democratic Republic of Congo have rapidly spread infecting high numbers of individuals in five African countries.The disease has reached the United States and Spain.This expansion is due partly to increasing global connectivity.This situation represents a new challenge to control the spread of the disease.Experimental drugs have been used to treat a few infected people with promising results.This gives hope for an effective treatment against Ebola hemorrhagic fever in the near future,though thousands of people remain at risk of infection.The present review aims to give an update of the knowledge on the disease,including features of the Ebola virus,the history of disease outbreaks in Africa and the tools that are being developed in order to control this re-emergent disease.

What did we learn from preparing for cross-border transmission of Ebola virus disease into a complex humanitarian setting-The Republic of South Sudan?

Background:Following the West Africa Ebola virus disease(EVD)outbreak(2013-2016),WHO developed a preparedness checklist for its member states.This checklist is currently being applied for the first time on a large and systematic scale to prepare for the cross border importation of the ongoing EVD outbreak in the Democratic Republic of Congo hence the need to document the lessons learnt from this experience.This is more pertinent considering the complex humanitarian context and weak health system under which some of the countries such as the Republic of South Sudan are implementing their EVD preparedness interventions.Main text:We identified four main lessons from the ongoing EVD preparedness efforts in the Republic South Sudan.First,EVD preparedness is possible in complex humanitarian settings such as the Republic of South Sudan by using a longer-term health system strengthening approach.Second,the Republic of South Sudan is at risk of both domestic and cross border transmission of EVD and several other infectious disease outbreaks hence the need for an integrated and sustainable approach to outbreak preparedness in the country.Third,a phased and well-prioritized approach is required for EVD preparedness in complex humanitarian settings given the costs associated with preparedness and the difficulties in the accurate prediction of outbreaks in such settings.Fourth,EVD preparedness in complex humanitarian settings is a massive undertaking that requires effective and decentralized coordination.Conclusion:Despite a very challenging context,the Republic of South Sudan made significant progress in its EVD preparedness drive demonstrating that it is possible to rapidly scale up preparedness efforts in complex humanitarian contexts if appropriate and context-specific approaches are used.Further research,systematic reviews and evaluation of the ongoing preparedness efforts are required to ensure comprehensive documentation and application of the lessons learnt for future EVD outbreak preparedness and response efforts.