The most devastating Ebola epidemic to date occurred in West Africa between 2013 and 2016. More than 28 000 developed Zaire ebolavirus disease (EVD), and more than 11 000 died.^1,2,3 Around 2500 of these deaths occurred in Guinea, the starting point of this epidemic.^1,2,3

Since 2016, further Ebola outbreaks have occurred in the Democratic Republic of the Congo (DRC) and now Uganda.¹ During this period, substantial advances have been made in introducing Ebola vaccines and improving the level of clinical care for EVD patients.^1,4,5,6,7,8 Treatment provided in Ebola treatment centres (ETCs)⁹ during the Zaire ebolavirus epidemic in the eastern DRC (2018–2020) followed principles of ‘essential emergency and critical care (EECC)’ outlined in the World Health Organization (WHO) guidelines (‘optimized supportive care’).^4,7,8,9,10 Additionally, in a randomised controlled trial (RCT; Pamoja Tulinde Maisha [PALM] trial) conducted in the DRC (2018–2019), administration of Ebola-specific monoclonal antibodies (mAb114, Ebanga; REGN-EB3, Inmazeb) was associated with lower mortality.⁶ Ebola virus disease patients presenting to an ETC early in their disease process with low viral load (VL) benefited from a care package of essential critical care and Ebola-specific treatment.^4,6,7 Survival rates above 80% were reported in these patients.⁶

Optimised design of ETCs allows visibility of patients from the low-risk zone, which enables continuous monitoring and improved communication between clinical teams working in low- and high-risk zones. This configuration facilitates provision of essential critical care and psychological support for patients with confirmed or suspected EVD.^5,9

At the end of the Ebola epidemic in West Africa (2013–2016), vaccinations were introduced as an essential part of a comprehensive outbreak response strategy combining preventive and therapeutic elements.^1,11 All aspects of outbreak management are based on intensive community engagement.¹

In February 2021, Guinea declared a further Zaire ebolavirus outbreak in a region (N’zérékoré) previously affected during the epidemic in 2013–2016.^1,2,12,13 By the end of the outbreak in June 2021, 23 Ebola virus infections were reported (16 confirmed and 7 probable cases). Of these 23 patients, 11 survived and 12 died.^12,13

In this series we describe 13 patients with confirmed EVD and 276 patients with suspected EVD treated in two ETCs, and their clinical outcomes.

The N’zérékoré region has a population of around 480 000 inhabitants, distributed over 11 subprefectures.¹⁴ At the end and after the Ebola epidemic in 2014–2016, centres de traitement épidémiologiques (CT_Epi) were established in several regions in Guinea and were designed to provide care for patients with highly infectious diseases (e.g. Ebola, Lassa, Cholera, COVID-19). As part of the outbreak response, clinical care for patients with confirmed or suspected EVD was provided in two Centres de Traitement Épidémiologique (CT-Epi or ETC), led by the Agence Nationale de Sécurité Sanitaire (ANSS), the outbreak response agency of the Guinean Ministry of Health (MOH).¹⁵ These two ETCs were located in two of the four subprefectures directly affected by the Ebola outbreak. Clinical care in ETCs was supported by the nongovernmental organisation Alliance for International Medical Action (ALIMA) and the WHO.^12,16 Both CT-Epis or ETCs needed some adaptation to allow adequate care for patients with highly infectious diseases (HID; Figure 1).^5,9

In this series, data are reviewed from all patients with suspected or confirmed EVD hospitalised in the ETCs of N’zérékoré and Gouécké during the outbreak period (14 February 2021 – 19 June 2021).

Implementation of comprehensive Ebola outbreak management allowing early identification of EVD patients, contact tracing and preventive measures (e.g. vaccinations) needs strong community engagement.^1,12,16,47 Care of patients with suspected and confirmed EVD is best provided close to affected populations to facilitate early initiation of effective treatment and to improve population confidence in outbreak-response measures.^16,47

During the Ebola outbreak in Guinea (2021), the peripheral ETC in Gouécké could provide essential care. Following prereferral management, critically ill patients with suspected EVD and all confirmed EVD patients were transferred to the ETC in N’zérékoré, where further essential critical care was provided and REGN-EB3 could be administered (Figure 2).^6,10 Patient referral systems are important elements of critical care⁴⁹ and need to be part of outbreak response preparations.

Nine of the 13 described EVD patients survived. All eight patients who received Ebola-specific monoclonal antibodies (REGN-EB3)^6,46 survived. All eight REGN-EB3 recipients had stable vital organ functions at the time of drug administration. In the six REGN-EB3 recipients whose VL results were available, five had low VL (NP-CT > 22). One REGN-EB3 recipient with a relatively high VL (NP-CT:21) also survived. The five EVD patients who did not receive REGN-EB3 were either admitted before the medication was available and/or presented with multi-organ dysfunction on ETC arrival (Online Appendix 1⁴⁸). One patient who did not receive REGN-EB3 survived (EVD patient-2; no VL available).

While this series is too small to draw statistically significant conclusions, outcomes are consistent with results of the PALM trial conducted during the Ebola epidemic in the DRC (2018–2020). This trial reported survival above 80% among EVD patients with low VL (NP-CT > 22) benefiting from essential critical care and administration of Zaire ebolavirus-specific monoclonal antibodies.⁶ Results of a WHO-led guideline development group (published in August 2022) recommend the ‘treatment with either MAB114 or REG-EB3 for patients with confirmed Zaire ebolavirus disease and for neonates of unconfirmed EVD status, 7 days or younger, born to mothers with confirmed EVD’.^17,18 Hence, storage and administration of Ebola-specific monoclonal antibodies need to be part of Ebola outbreak preparedness plans.

Supportive care of EVD patients, outlined in the WHO guidelines, follows general critical care principles aimed at rapid stabilisation of vital organ functions, while considering characteristics of EVD.^{3,4,10,19,20,50}

In this series, at least four of the 13 EVD patients needed O₂ therapy early during ETC admission and may have benefited from noninvasive respiratory support. Over 70% of Ebola patients treated in Europe or the United States required supplemental O₂, noninvasive or invasive respiratory support during their illness.⁴

Different causes of respiratory dysfunction need to be considered in EVD, for example, acute viral or bacterial co-infections, acute respiratory distress syndrome (ARDS) potentially associated with EVD and/or severe co-infections, fluid overload and cardiac dysfunction.^4,51 Additionally, the presence of TB and HIV-associated opportunistic infections needs to be evaluated. Different pathologies may co-exist.⁴

Reliable O₂ supply using O₂ concentrators and an adequate electricity system were established in the ETC in N’zérékoré following WHO recommendations.^52,53

Ebola virus disease patients frequently present with haemodynamic instability associated with serious enteral fluid losses and sepsis-related complications,^3,4 often requiring considerable intravenous fluid replacement. In this context, the use of electrolyte-balanced, isotonic resuscitation fluids may be particularly important.^4,19,20,54

Training sessions integrated in routine practice enabled the ETC team in N’zérékoré to use basic noninvasive respiratory support as well as low-dose vasopressor infusions.¹⁰ Additionally, POCUS was introduced to guide haemodynamic stabilisation.³⁸ Not all patients could benefit from these interventions (Figure 2 and Online Appendix 1⁴⁸), as training in these elements of essential critical care started in March 2021.

Three of the 13 EVD patients may have benefited from red blood cell (RBC) transfusions (Online Appendix 1⁴⁸). These three patients showed signs of haemorrhage associated with haemodynamic instability and died within 48 h of admission. Arranging an urgent RBC transfusion was challenging at the beginning of the Ebola outbreak, as the ETC was situated several km from the blood bank located in the regional hospital.

Five of the 13 EVD patients and 66% of patients with suspected EVD had positive malaria tests. As all Ebola outbreaks so far have occurred in malaria-endemic regions,¹ malaria co-infections need to be anticipated as a cause of anaemia in EVD patients.³⁷ Importantly, around 6% of patients with suspected EVD (16/276) required RBC transfusions in this study (Table 3).

Haemorrhage is an EVD complication that can occur during advanced stages of the disease process.^3,4,55 Causes may include disseminated intravascular coagulation and hepatic injury.^3,4 In this study, clinical signs of coagulopathy associated with haemodynamic instability were seen in three EVD patients. These patients did not survive (Online Appendix 1⁴⁸).

Besides RBC transfusions, options for provision of other blood products should be evaluated in low-resource settings, for example, fresh frozen plasma (FFP) or thrombocyte concentrates.⁴ Fresh dried plasma may be an alternative to provide coagulation factors in settings where production and storage of FFP are challenging.⁵⁶

Developing safe transfusion services was a priority of the ETC laboratory team. Biosecurity measures were established in cooperation with Guinean transfusion services. International and national guidelines for the setup of transfusion services are important elements of outbreak preparedness.

Treatment of neurological emergencies in EVD patients presenting with altered mental status, focal neurological signs or seizures follows essential critical care principles: respiratory and cardiovascular functions need to be stabilised.^4,8,10 Hypoglycaemia occurs frequently in EVD patients, requiring careful surveillance of blood sugar levels.^3,4,10

Potential severe co-infections (e.g. bacterial meningitis, severe malaria) need to be treated.^3,4,10,37 Ebola virus infections can have a direct central nervous system impact, while neurological complications associated with coagulopathies, electrolyte imbalances, renal or hepatic failure need to be considered.^3,4,8

In the management of status epilepticus refractory to first-line antiseizure medication (ASM), injectable levetiracetam can be of particular benefit in the care of EVD patients or other HIDs. Injectable levetiracetam administration is simple and not associated with severe cardiorespiratory side effects.^24,25,26 Even when treating EVD patients in CUBEs,⁵ immediate initiation of emergency interventions can be challenging. Additionally, mechanical ventilation is not a feasible option in many resource-limited contexts. Therefore, it may be beneficial to replace ASM with potential cardiorespiratory side effects (e.g. phenobarbitone and phenytoin) with ASM with a better side effect profile.

Acute kidney injury, electrolyte abnormalities as well as acid–base abnormalities are common complications in EVD.^3,4 Raised creatinine levels are associated with an elevated mortality risk.^4,6,50 Signs of rhabdomyolysis (elevated creatinine kinase), frequently seen in EVD patients, may contribute to renal dysfunction.^3,4 This series emphasises the importance of essential AKI management in contexts without ability to initiate renal replacement therapy (Figure 2).^8,10,30

Elevation of transaminases, amylase and low albumin levels are further biochemistry abnormalities frequently observed in EVD or Lassa virus disease.^3,4,8,10,57

Malaria co-infections are common among EVD patients treated in malaria-endemic regions and need to be managed urgently.^3,37 Early initiation of efficient antibiotic treatment for potential bacterial co-infections is equally important.^3,4,6,8,10

Nutritional support is an essential element in EVD care.²⁹ A proactive approach to enteral nutrition in critically ill EVD patients should follow principles of existing international guidelines.^27,28 Importantly, the WHO has published EVD guidelines for pregnant and breastfeeding women.³⁴

Optimised ETC design facilitates provision of optimised supportive care and prevention of cross-infection.^4,5,9 All patients with suspected or confirmed EVD need to be visible from the low-risk zone, allowing continuous surveillance.^5,9 In this context, the CUBE provides an innovative interface between health workers positioned in the low-risk zone, patients with confirmed or suspected EVD and clinicians working in the high-risk zone.⁵ Additionally, optimised ETC design facilitates psychological support for children and adults as well as provision of palliative care for patients with end-stage critical illness.^5,9 Furthermore, the visibility of ETC care promotes trust among populations affected by Ebola epidemics: ‘Newly designed ETCs are not simple isolation units but are treatment units built around needs of patients, staff, families and communities (WHO)’.^5,9 Experience gained in ETC design can be used in the management of other HID outbreaks.^5,9,57,58,59 In this context, the WHO and the World Food Program (WFP) initiated a design process for a mobile, rapidly deployable ‘infectious disease treatment module’.⁶⁰

Four of the 13 EVD patients treated in N’zérékoré were health workers, which confirms experience from previous Ebola outbreaks indicating a considerable infection risk during patient care in regular health facilities.^1,61 In regions potentially affected by Ebola epidemics, health workers therefore need to be vaccinated and safe working environments need to be established.^1,12,61 Importantly, a recent publication describes postexposure prophylaxis after high-risk contacts using Ebola-specific monoclonal antibodies.⁴²

In agreement with larger studies, this series suggests that initial EVD symptoms are similar to early manifestations of common acute infections (e.g. malaria).^3,55,62 The WHO Ebola case definition therefore has limited specificity, especially in the early phase of a disease outbreak.^{4,45,55,62,63} In this context, screening and triage processes should be strengthened in regular health facilities.^33,59,64 As signs of EVD or other HIDs may not always be identified during the admission process, HID risk assessment needs to continue during routine inpatient care.

Treatment units with limited bed capacity for patients with suspected HID can be integrated in patient circuits of emergency departments of regular health facilities. Efficient laboratory capacities are needed to guarantee rapid exclusion or confirmation of HIDs.^12,65 Rapid outbreak response support for these decentralised treatment units could be triggered by the confirmation of HID and/or increasing numbers of patients with suspected HIDs. Rapidly deployable treatment units for HID can be of value in this context.^60,66

Lassa virus disease was detected in one patient with suspected but nonconfirmed EVD. This patient had clinical and biochemical characteristics similar to EVD patients (Online Appendix 1⁴⁸).^3,4,43 Acute kidney injury was the predominant organ dysfunction in this patient, accompanied by elevated transaminases and signs of rhabdomyolysis, which then progressed to terminal multi-organ failure (MOF).⁴³ It can only be speculated if a COVID-19 co-infection contributed to this patient’s MOF.⁴³

Lassa virus disease is endemic in certain regions in West Africa, including Guinea.^67,68,69 Additionally, in August 2021, the Guinean MOH reported a case of Marburg virus disease (MVD) in the prefecture of the Guéckédou–N’zérékoré region.⁴⁴ These findings emphasise that surveillance and outbreak response systems in West Africa need to prepare for a range of HIDs.^12,65

Among 681 EVD patients recruited in the PALM trial (DRC; 2018–2019), 25% patients were younger than 18 years and almost 13% younger than 5 years.⁶ In this series, the mean age of EVD patients was around 46 years (Figure 2). It can be speculated that during the Ebola outbreak in Guinea (2021), initially adults were infected, while transmission to a wider spectrum of the population could be prevented by control measures (e.g. vaccinations).¹²

Many patients (38%) with suspected EVD reported in this study were 15 years or younger (17% were 5 years or younger), highlighting that ETCs need to prepare for medical and psychological needs of children and adolescents.^32,35

One of the 13 described EVD patients was pregnant. She presented 2 days after onset of symptoms with multi-organ dysfunction (NP-CT:22), and despite initiation of essential critical care, she died around 6 h after ETC admission.

Previous reviews report high mortality rates among pregnant EVD patients.³⁴ Experiences from the Ebola outbreak in the DRC (2018–2020) emphasise that referral pathways and ETCs need to be prepared for rapid initiation of treatment for pregnant women, including essential critical care, early administration of Ebola-specific monoclonal antibodies,^1,34 normal and instrumental deliveries, caesarean sections and obstetric emergencies (e.g. postpartum haemorrhage and eclampsia).³⁴ Additionally, ETCs need to be set up for essential newborn resuscitation and care.^32,33

A family accommodation (‘crèche’) needs to be part of ETC design, offering care for children of EVD patients as well as rehabilitation for surviving mothers and children.^{9,32,34,35,41} Furthermore, the WHO recommends programmes for Ebola survivors designed to address medical and psychosocial challenges and to reduce risk of further Ebola virus transmission (e.g. sexual transmission).^34,41

Health services in Guinea face considerable challenges (e.g. maternal and child health).^70,71 As a result of the Ebola epidemic in West Africa (2014–2016), a substantial impact on general health services was documented.⁷² Therefore, comprehensive outbreak strategies should support efforts to build resilient health systems in epidemic-affected regions.⁷²

Multidisciplinary outbreak response teams can rapidly set up well-designed ETCs close to affected populations. Trained clinical teams can provide optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies, as recommended by the WHO. Pragmatic training in essential critical care integrated in routine ETC activities contributed to capacity building.

The results of this series indicate that initial symptoms of EVD are often nonspecific. One patient with suspected EVD had Lassa virus disease, highlighting the importance of considering differential diagnoses during Ebola outbreaks based on regional epidemiology.