Ebola and Filovirus Disease

Filovirus disease is the acute, systemic, frequently fatal illness caused by enveloped negative sense single stranded RNA viruses of the family Filoviridae, principally the orthoebolaviruses and orthomarburgviruses.

It is characterised by a non-specific febrile prodrome, a dominant gastrointestinal phase with massive fluid and electrolyte loss, and a late phase of shock, acute kidney injury, encephalopathy and, in a minority, overt haemorrhage.

The historical name haemorrhagic fever is misleading: bleeding is a late and inconstant feature, and the illness kills far more often through hypovolaemia, metabolic derangement and multi organ failure than through blood loss.

Taxonomy. Six orthoebolavirus species are described, four of which cause human disease: Orthoebolavirus zairense (Zaire ebolavirus), Orthoebolavirus sudanense (Sudan virus), Orthoebolavirus bundibugyoense (Bundibugyo virus) and Orthoebolavirus taiense (Taï Forest virus).

Reston virus infects non-human primates and swine without documented human illness. Orthomarburgvirus marburgense comprises Marburg and Ravn viruses.

Clinical relevance of species. Species identity determines expected lethality, the validity of a negative test, and which countermeasures are licensed. Zaire ebolavirus carries case fatality of roughly 60 to 90% untreated, Sudan virus roughly 40 to 70%, Bundibugyo virus roughly 25 to 50%, and Marburg virus 24 to 90% across outbreaks.

Licensed vaccines and licensed monoclonal antibodies exist only for Zaire ebolavirus. Species specific assays will miss non-Zaire filoviruses, which has already delayed recognition of Bundibugyo outbreaks.

Epidemiology. Filovirus disease is overwhelmingly an African continental problem, with recognised outbreaks since 1976 in the Democratic Republic of the Congo, Uganda, Sudan and South Sudan, Gabon, the Republic of the Congo, Guinea, Liberia, Sierra Leone, Equatorial Guinea, Tanzania, Rwanda and Côte d'Ivoire.

Overall case fatality across orthoebolavirus outbreaks ranges from 25 to 90%, averaging close to 50%. Outbreaks are amplified by health facilities where infection control is weak, by funeral practices involving contact with the body, and by delayed isolation of the index case.

Bundibugyo virus

This species was first characterised in Bundibugyo District, western Uganda, in 2007, with a second outbreak in the Democratic Republic of the Congo in 2012.

Historical case fatality was lower than for Zaire ebolavirus, in the region of 25 to 40%, but the current epidemic has not reproduced that advantage.

Current outbreak position

An outbreak caused by Bundibugyo virus has been ongoing in the Democratic Republic of the Congo since May 2026, with community transmission continuing and eight provinces affected: Ituri, Nord-Kivu, Sud-Kivu, Tshopo, Haut-Uélé, Bas-Uélé, Sud-Ubangi and Nord-Ubangi.

As of 28 October 2026 the Democratic Republic of the Congo had reported 10 193 confirmed cases and 4 960 deaths, a crude case fatality close to 49%.

This epidemic is expanding faster than previous Ebola outbreaks and is now the second largest on record.

Kenyan situation

Kenya reported its first laboratory confirmed imported Bundibugyo virus case on 6 October 2026. The patient was a Kenyan citizen resident in the Democratic Republic of the Congo. The patient travelled by road to Kampala and flew into Nairobi on 3 October, and died on 5 October.

As of 26 October 2026 Kenya had reported nine confirmed cases and two deaths, all linked to the first case, with the most recent case notified on 20 October 2026. Twenty contacts had completed 21-day follow up and 98 remained under monitoring at that date, from 135 contacts traced in total.

Eight of the nine cases were family members or other relatives of the index case and health workers, which is the classic signature of filovirus amplification: the household and the health facility. All Kenyan cases have been in Nairobi, with no community spread reported.

Nigeria reported a single imported case confirmed on 20 October 2026 in a traveller who developed symptoms on 7 October and sought care in Abuja on 11 October.

Reservoir and spillover

Fruit bats, particularly pteropodid species for orthoebolaviruses and Rousettus aegyptiacus for Marburg virus, are the presumed reservoir.

Human spillover follows contact with bats or bat contaminated material, entry into caves or mines, or handling and butchering of infected non-human primates, duikers and other bushmeat. Marburg virus has a particularly strong association with cave and mine exposure.

Human-to-human transmission

Transmission requires contact of infected blood or body fluid with broken skin or mucous membrane, or percutaneous inoculation. Infectious fluids include blood, vomit, stool, urine, sweat, saliva, tears, breast milk, semen, vaginal secretions, amniotic fluid and the products of conception.

Viral load in fluids rises with illness severity, so the dying patient and the fresh corpse are the most infectious. There is no evidence of airborne spread between humans, although aerosol generating procedures create a genuine occupational hazard.

Incubation and infectious period

The incubation period is 2 to 21 days, most commonly 6 to 12 days. Patients are not considered infectious until symptomatic, which is the biological basis for monitoring rather than isolating asymptomatic contacts.

Infectivity rises steeply through the gastrointestinal phase and persists into early convalescence in blood, and far longer in protected compartments.

Viral persistence

After blood clears, virus may persist in immune privileged sites: semen for 12 months or longer with rare reports beyond 2 years, aqueous humour, cerebrospinal fluid, breast milk, placenta and amniotic fluid.

Sexual transmission from male survivors, breast milk transmission to infants and relapse with meningoencephalitis or uveitis are all documented.

Persistence is the mechanism by which an apparently closed outbreak reignites months later.

Cellular entry. The viral glycoprotein binds attachment factors on the cell surface, the particle is internalised by macropinocytosis, and cathepsins B and L in the endosome cleave the glycoprotein to expose the receptor binding domain.

Fusion requires the endosomal cholesterol transporter Niemann-Pick C1. Monocytes, macrophages and dendritic cells are the earliest and most important targets, followed by hepatocytes, adrenal cortical cells, fibroblasts and endothelium. Lymphocytes are not productively infected.

Immune evasion. Viral protein 35 antagonises interferon regulatory factor 3 and sequesters double stranded RNA, suppressing type I interferon induction. Viral protein 24 blocks nuclear import of phosphorylated STAT1, blunting interferon signalling.

Soluble glycoprotein is secreted in large quantity and acts as an antibody decoy. The net effect is unchecked early replication with a functionally blind innate immune response.

Systemic inflammation. Infected macrophages release tumour necrosis factor alpha, interleukin 1 beta, interleukin 6, interleukin 10 and nitric oxide. This produces fever, vasodilatation, increased vascular permeability and myocardial depression.

Lymphocytes undergo massive bystander apoptosis, so profound lymphopenia coexists with a hyperinflammatory state, and adaptive immunity is delayed at exactly the point it is most needed.

Endothelial and vascular injury. Cytokine driven endothelial activation, glycocalyx shedding and direct infection of endothelium late in illness cause capillary leak, interstitial oedema and intravascular volume depletion that is disproportionate to measured external losses.

Coagulopathy. Infected macrophages express tissue factor, triggering the extrinsic coagulation cascade and disseminated intravascular coagulation.

Consumption of platelets and clotting factors, depletion of protein C, and impaired hepatic synthesis of clotting factors produce a mixed picture of microvascular thrombosis and bleeding. Thrombocytopenia is near universal; prolonged prothrombin time correlates with severity.

Gastrointestinal failure. Mucosal infection and inflammation produce a secretory, cholera like diarrhoea with stool losses that may reach 5 to 10 litres each day in adults, together with high volume vomiting.

This is the dominant cause of death in untreated disease, through hypovolaemic shock, profound hypokalaemia, hypomagnesaemia, hypocalcaemia and metabolic acidosis.

Adrenal and metabolic effects. Infection of the adrenal cortex impairs steroidogenesis, contributing to hypotension poorly responsive to fluid alone. Hepatic injury impairs gluconeogenesis and glycogenolysis, and combined with anorexia produces hypoglycaemia that is frequently silent in a confused patient.

Renal injury. Acute kidney injury is predominantly prerenal from hypovolaemia, compounded by acute tubular necrosis, rhabdomyolysis, nephrotoxic drug exposure and sepsis. It is the single most preventable severity marker, because it is largely a function of how quickly and how adequately fluid is replaced.

Neurological involvement. Encephalopathy arises from metabolic derangement, hypoperfusion, hypoglycaemia and direct central nervous system invasion.

Meningoencephalitis with viral RNA in cerebrospinal fluid has been documented both acutely and in relapse.

Natural history

Illness is conventionally divided into phases:

• an early febrile phase of days 0 to 4
• a gastrointestinal phase of days 3 to 10
• a complications phase of days 7 to 12, in which shock, renal failure, haemorrhage and neurological deterioration cluster
• either death, most often on days 7 to 12 from symptom onset, or convalescence from day 14 onward

Deterioration can be abrupt: a patient walking and drinking in the morning can be in refractory shock by evening.

Prognostic determinants

Poor outcome is associated with:

• high viral load at presentation, the strongest single predictor
• age over 45 years
• age under 5 years
• pregnancy
• markedly raised aspartate transaminase and alanine transaminase
• raised creatinine and urea
• bleeding
• encephalopathy
• delayed presentation after symptom onset
• co-infection

Survival is associated with earlier presentation, lower viral load and, consistently across outbreaks, the quality and intensity of supportive care delivered.

Early phase, days 0 to 4

Abrupt onset fever of 38.0°C or more, profound weakness and prostration out of proportion to the fever, severe headache, myalgia, arthralgia, anorexia, lethargy and intractable hiccups.

Sore throat, odynophagia, non-pruritic maculopapular rash and bilateral conjunctival injection without discharge may be present. This phase is clinically indistinguishable from malaria, typhoid, influenza and bacterial sepsis, which is precisely why exposure history, not symptom pattern, drives early suspicion.

Gastrointestinal phase, days 3 to 10

High volume watery diarrhoea, repeated vomiting, epigastric and diffuse abdominal pain, dysphagia and hiccups dominate. Losses are frequently underestimated because they are not measured.

Clinical dehydration, postural intolerance, tachycardia, oliguria and electrolyte driven weakness and cramps develop rapidly. This is the window in which aggressive fluid and electrolyte replacement changes outcome.

Complications phase, days 7 to 12 and beyond

Circulatory shock, acute kidney injury with oliguria or anuria, encephalopathy, seizures, myocarditis with arrhythmia, respiratory distress, hepatic dysfunction with jaundice and coagulopathy, and secondary bacterial infection.

Bacterial translocation across the damaged gut is a recognised source of bloodstream infection.

Haemorrhagic manifestations

Overt bleeding occurs in fewer than half of confirmed cases and is a late sign. When present it takes the form of petechiae, ecchymoses, oozing from venepuncture and cannula sites, gingival bleeding, epistaxis, subconjunctival haemorrhage, haematemesis, melaena, haematuria, per vaginal bleeding outside menses and, rarely, intra abdominal or intracranial haemorrhage.

Waiting for bleeding before suspecting filovirus disease is the commonest and most lethal diagnostic error.

Children

Children present atypically and deteriorate faster. Fever may be absent in neonates. Poor feeding, lethargy, irritability and vomiting predominate; diarrhoea is common. Dehydration progresses more quickly because of higher surface-area-to-weight ratio and smaller reserves.

Hypoglycaemia is more frequent and more rapidly harmful. Case fatality is highest in those under 5 years. Co-existing severe acute malnutrition changes fluid handling fundamentally and must be screened for on admission.

Pregnancy

Maternal and foetal mortality are both very high. Fever may be absent. Presentation is frequently mistaken for obstetric pathology: hyperemesis, threatened miscarriage, antepartum haemorrhage, chorioamnionitis, preterm labour or postpartum haemorrhage.

Exaggerated nausea and vomiting in a pregnant woman with an exposure history should raise suspicion. Miscarriage, stillbirth and preterm labour are common. Amniotic fluid, placenta and foetal tissue carry extremely high viral loads and remain infectious even when maternal blood has cleared.

Health workers

Health workers often present early because of heightened awareness, and may have atypically mild initial illness, which paradoxically increases the chance of continued work and onward transmission.

Any febrile health worker with contact with a confirmed or suspected case, with or without a recognised breach of protective equipment, should be screened and triaged as a suspect case rather than reassured.

Suspect case. Any person with sudden onset fever, headache, generalised body ache, lethargy, abdominal pain, vomiting, diarrhoea or unexplained bleeding, together with an epidemiological link. The link is travel from or transit through a country with active filovirus transmission in the preceding 21 days, or contact with a confirmed or suspected case.

The same symptom set with an epidemiological link in a person who has died unexplained also meets the definition.

Probable case. A suspect case, living or deceased, without available laboratory results, who has an epidemiological link to a confirmed case or to a recognised transmission chain containing a confirmed case.

Confirmed case. Any person meeting the suspect or probable definition with a positive filovirus reverse transcription polymerase chain reaction result.

Community definition. Illness with hotness of body, diarrhoea or vomiting unresponsive to treatment, with bleeding from body openings, or any sudden unexplained death with a history of bleeding, in a person who has travelled to an area with an active outbreak.

A single epidemiological risk factor combined with at least one compatible sign or symptom is sufficient to triage a patient as a suspect case and isolate them.

Exposure stratification

High risk exposure:

• percutaneous injury or mucous membrane splash with body fluid of a case
• direct care or body fluid contact without adequate protective equipment
• household caregiving without protection
• laboratory processing of specimens without protection or containment
• participation in funeral rites involving contact with human remains in an affected area
• contact with potentially infected bats or non-human primates, alive or dead, including bushmeat handling, cave entry or work near fruit bat roosts
• an infant breastfed by a woman with current or recent infection
• a neonate born to an infected mother
• a sexual partner of a male survivor

Low risk exposure: presence in an affected country within 21 days without identified contact; direct clinical care of a confirmed case with consistent, correct use of protective equipment and no recognised breach.

Screening and triage

Every person entering a health facility should be screened at first contact with a health worker, using a no touch technique at a distance of at least 1 metre. Use hand hygiene at entry and spaced waiting. Use a unidirectional patient flow that separates those screened from those not yet screened.

The screening instrument asks two things: epidemiological exposure in 21 days, and the presence of compatible symptoms. These include:

• fever or history of fever
• headache or body pain
• weakness
• vomiting or diarrhoea
• abdominal pain
• sore throat
• unexplained bleeding including abnormal vaginal bleeding
• rash
• bilateral conjunctivitis
• intractable hiccups

Designated donning, doffing and isolation areas must exist before screening begins, not after the first positive screen.

Molecular confirmation

Reverse transcription polymerase chain reaction on whole blood is the diagnostic method of choice, performed in a containment level 3 facility.

The request must explicitly ask for orthoebolavirus and orthomarburgvirus species identification, because an assay targeting Zaire ebolavirus alone will return a false negative in a Bundibugyo or Sudan virus infection. Results are usually available within 24 hours of arrival at the reference laboratory.

Specimen. Two sterile ethylenediaminetetraacetic acid (purple top) tubes of whole blood: approximately 4 mL into each tube in adults, at least 1 mL into each tube in children.

Serum or plasma are acceptable alternatives for polymerase chain reaction and enzyme immunoassay. In a deceased patient in whom venepuncture is not possible, an oral swab is the specimen of choice; post-mortem examination is not required and should be avoided.

Timing and the repeat rule. Viraemia may be undetectable in the first 72 hours after symptom onset. A negative result on a sample drawn under 72 hours from symptom onset does not exclude disease, and a repeat test must be performed on a fresh sample drawn more than 72 hours after onset, with the patient remaining isolated in the interval.

A negative result on a sample drawn more than 72 hours after symptom onset generally excludes filovirus disease in a patient whose symptoms have an alternative explanation. A repeat test is not required in a patient who has fully recovered from the acute illness.

Cycle threshold. The cycle threshold value is inversely related to viral load and carries prognostic weight: low values, broadly under 20, indicate high viral load and substantially worse prognosis, while values over 30 are associated with better survival.

Cycle threshold is assay dependent and should be interpreted with the issuing laboratory, not compared across platforms.

Other diagnostic methods

Rapid antigen detection assays offer speed at the cost of sensitivity, particularly at low viral loads, and a negative antigen result never excludes disease; their role is triage and surge screening, not exclusion.

Antigen capture enzyme immunoassay, immunoglobulin M and immunoglobulin G serology, immunohistochemistry on post-mortem tissue and virus isolation are reference laboratory techniques. Serology is of limited acute use because antibody appears late, but it is valuable for retrospective case ascertainment and survivor studies.

Supportive laboratory panel

These tests are for clinical management and should be done at the point of care wherever possible, since transporting specimens to a general laboratory creates both delay and risk:

• Full blood count with differential and platelet count

• Sodium, potassium, chloride, bicarbonate, urea, creatinine and glucose

• Liver function tests including transaminases, bilirubin and albumin

• Prothrombin time expressed as international normalised ratio

• Calcium and magnesium where available

• Arterial or venous blood gas with lactate in the unstable patient

• Rapid diagnostic test for malaria in every patient, repeated if initially negative and clinical suspicion persists

• Urinalysis where clinically indicated

• Pregnancy test in women of reproductive age

Expected derangements.

• early leucopenia and lymphopenia followed by neutrophilia with left shift
• thrombocytopenia
• markedly raised aspartate transaminase typically exceeding alanine transaminase, which distinguishes it from most viral hepatitides
• raised urea and creatinine
• hypokalaemia, hypomagnesaemia, hypocalcaemia and hyponatraemia
• metabolic acidosis with raised lactate
• prolonged prothrombin time and activated partial thromboplastin time
• raised amylase in severe disease
• hypoglycaemia
• hypoalbuminaemia

Specimen handling and biosafety

Every specimen from a suspected case is to be treated as highly infectious. Only personnel trained in infection control, safe sampling and correct use of protective equipment should collect specimens.

Specimens are placed in labelled, non-glass, leak proof primary containers and the exterior is disinfected. They are then triple packaged:

• primary leak proof tube
• absorbent material sufficient to take the entire volume
• secondary leak proof container
• rigid outer packaging bearing a biohazard label and the completed case investigation documentation

Refrigerate; do not freeze.

Transport by the fastest available means, with the courier briefed on biohazard handling, and notify the receiving laboratory in advance. Sharps go directly into a puncture resistant container at the bedside and are never recapped, bent or manipulated.

Investigations to defer or avoid

Avoid non-essential invasive procedures, including lumbar puncture, paracentesis and endoscopy, unless the result will change management within hours.

Avoid routine urinary catheterisation, which adds infection risk without adding information that cannot be obtained by weighed or measured output, unless there is urinary obstruction or an unavoidable need for accurate hourly output in shock.

Avoid chest radiography outside the isolation area; use bedside ultrasound where available.

The early phase overlaps almost completely with common tropical and systemic illness, and alternative diagnoses frequently coexist rather than exclude filovirus disease.

• Malaria, including severe and cerebral malaria. Test every patient; a positive malaria test does not exclude filovirus disease and antimalarial treatment must never be delayed while awaiting filovirus results.
• Typhoid and invasive non-typhoidal salmonellosis
• Bacterial sepsis from any source, including meningococcaemia with purpura
• Leptospirosis, with conjunctival suffusion, jaundice and renal failure
• Rickettsial infection, including African tick bite fever and typhus
• Relapsing fever from Borrelia species
• Other viral haemorrhagic fevers: Lassa fever, Crimean-Congo haemorrhagic fever, Rift Valley fever, yellow fever, dengue with severe manifestations. Lassa fever and Crimean-Congo haemorrhagic fever transmit person to person and require the same isolation discipline; Rift Valley fever and yellow fever do not.
• Acute human immunodeficiency virus seroconversion illness
• Viral hepatitis, fulminant
• Acute leukaemia, thrombotic thrombocytopenic purpura and immune thrombocytopenia, which can mimic the bleeding and cytopenias
• Obstetric emergencies in pregnant women: abruption, chorioamnionitis, postpartum haemorrhage, pre-eclampsia with haemolysis, elevated liver enzymes and low platelets

Principles

There is no licensed specific treatment for Bundibugyo virus disease. Survival is determined by the speed and quality of supportive care.

The core interventions are early isolation, aggressive and continuously reassessed fluid and electrolyte replacement, correction of hypoglycaemia, early treatment of co-infection, early vasopressor support when shock persists, meticulous symptom control, and infection prevention that keeps the clinical team intact and working.

Supportive care begins on clinical suspicion and is never delayed for laboratory confirmation.

Immediate actions on meeting the suspect case definition

• Notify the sub-county health office and the national emergency alert line immediately, without waiting for confirmation. The 24-hour national alert line is 719; the national emergency operations centre line is 0716717717.

• Apply full personal protective measures and follow the donning and doffing sequence with a trained observer present.

• Explain to the conscious patient what will happen, why isolation is necessary and what the infection control measures involve.

• Isolate in a designated area, preferably a self-contained single room with its own toilet, adequate ventilation and restricted access.

• Start supportive care at once: intravenous access, fluid resuscitation, glucose correction and antimalarial and antimicrobial treatment where indicated.

• Collect two sterile ethylenediaminetetraacetic acid tubes of whole blood, approximately 4 mL into each tube in adults and at least 1 mL into each tube in children, and complete the case investigation documentation.

• Triple package the specimen and dispatch it by the fastest available means with an explicit request for species identification.

• Restrict the number of staff and relatives entering the isolation area, and log every entry and exit.

• Dispose of all waste as highly infectious waste.

Isolation and unit organisation

Suspect cases must not be cohorted with one another or with confirmed cases, because a suspect case who turns out negative will have been exposed.

Confirmed cases may share wards, bathrooms and toilets. Isolation areas run a unidirectional flow from clean to contaminated, with clear signage, dedicated waste bins and sharps containers, a dedicated toilet, separate donning and doffing spaces, and dedicated hand hygiene and cleaning supplies. Beds are spaced 1 to 2 metres apart.

Each patient has their own basin, bucket, plate, cup, spoon and drinking vessel, which are never shared. Where volumes exceed a single isolation room, a treatment unit with demarcated high risk and low risk zones is required, with the low risk zone housing chlorine preparation, pharmacy, stores, staff meetings, counselling and laundering of reusable items.

Central observation of the patient area from the low risk zone, and two way communication with patients, reduce the number of entries into the high risk zone and therefore the number of exposures.

Vascular access

Obtain intravenous access early in every patient with gastrointestinal symptoms, before shock develops, because cannulation in a shocked, bleeding, agitated patient in full protective equipment is slow and hazardous. Two large bore cannulae are advised in anyone with ongoing losses or bleeding.

Secure the cannula well, use a transparent dressing so the site can be inspected without removing it, and inspect daily for phlebitis or extravasation. Remove any line that is no longer needed. Use safety engineered devices and closed blood collection systems where available.

Fluid resuscitation in adults

Use balanced isotonic crystalloid, with Ringer's lactate preferred over 0.9% sodium chloride for both resuscitation and replacement in sepsis, septic shock and dehydration, including in pregnancy. Sodium chloride 0.9% is preferred where there is traumatic brain injury.

• Able to drink and perfusing. Oral rehydration solution in frequent small sips, with antiemetic cover to improve tolerance. Measure and record stool and vomit volumes and replace them. Escalate to intravenous therapy if intake becomes inadequate, vomiting prevents tolerance or haemodynamics deteriorate.

• Shock or unable to drink. Ringer's lactate 30 mL/kg within the first 3 hours, delivered as repeated aliquots of 250 to 500 mL with full reassessment of perfusion every 30 minutes, rather than as a single large fixed volume bolus. Tailor the volume to comorbidity, cardiac and renal reserve, and pregnancy.

• Ongoing losses. Replace measured gastrointestinal losses volume for volume in addition to maintenance, which in a stable adult is approximately 2 mL/kg/hour.

• Practical measures. Use 1 litre bags with infusion pumps or calibrated giving sets wherever possible, because interrupted flow in an isolation unit is common and consequential. Reassess fluid status at least every 8 hours in a stable patient and far more often in an unstable one.

• Avoid iatrogenic overload. Watch for rising jugular venous pressure, new crepitations, worsening hypoxaemia and peri orbital oedema, particularly where myocarditis or lung injury is evolving. If these appear, slow or stop the infusion and reassess completely. Bedside ultrasound of the inferior vena cava and lung fields, where available, is more reliable than clinical signs alone.

Fluid management in children without severe malnutrition

• Shock, defined as cold hands with weak or absent pulse plus either capillary refill over 3 seconds or conscious level less than alert: Ringer's lactate 20 mL/kg intravenously or intraosseously over 15 minutes. A second 20 mL/kg bolus may be given if shock persists.

  Treat hypoglycaemia at the same time. If haemoglobin is under 5 g/dL or there is severe pallor, transfuse urgently and do not give the crystalloid bolus.

• Severe dehydration without shock, step 1: Ringer's lactate 30 mL/kg over 30 minutes if aged 12 months or more, or over 60 minutes if under 12 months.

• Severe dehydration, step 2: Ringer's lactate 70 mL/kg over 2.5 hours if aged 12 months or more, or over 5 hours if under 12 months, with oral rehydration solution 5 mL/kg/hour by nasogastric tube alongside, if tolerated.

• If intravenous access cannot be obtained: oral rehydration solution 120 mL/kg over 6 hours by nasogastric tube.

• Some dehydration: oral rehydration solution 75 mL/kg over 4 hours, continuing breastfeeding, then reclassify.

• No dehydration: oral rehydration solution 10 mL/kg after each loose stool, continuing feeding.

Reassess at least hourly and reclassify at 3 to 6 hours. Do not repeat boluses mechanically without reassessment; if severe dehydration persists after step 2, obtain paediatric or senior review. Maintenance in children follows the 4-2-1 rule: 4 mL/kg/hour for the first 10 kg, 2 mL/kg/hour for the next 10 kg and 1 mL/kg/hour for each kilogram over 20 kg.

Fluid management in severe acute malnutrition with diarrhoea

Fluid handling is different and the usual volumes are dangerous. In shock, give Ringer's lactate with 5% dextrose at 20 mL/kg over 2 hours; this solution is made by adding 50 mL of 50% dextrose to 450 mL of Ringer's lactate.

If there is severe anaemia, transfuse urgently rather than giving crystalloid.

Once shock is corrected, or in the child who is not shocked, give RESOMAL for malnutrition at 10 mL/kg/hour for 2 hours, then 7.5 mL/kg/hour for 1 hour. Then alternate with F75 for 10 hours, titrating between 5 and 10 mL/kg/hour by tolerance. Switch to 3-hourly feeds at 12 hours.

Where oral or nasogastric fluid cannot be given, use intravenous maintenance at 4 mL/kg/hour. Watch continuously for overload: fast breathing, chest indrawing and peri orbital oedema are early signs; pulmonary oedema and cyanosis are late.

Electrolyte correction

Hypokalaemia is the rule in high output diarrhoea and is a common cause of arrhythmia, ileus and profound weakness. Correct magnesium first, because hypokalaemia is refractory while magnesium is low. Replace potassium chloride orally where tolerated, or intravenously at a maximum of 10 mmol/hour through a peripheral line at a concentration not exceeding 40 mmol/L, or up to 20 mmol/hour through a central line with cardiac monitoring. Recheck 2 to 4 hours after correction.

Hypomagnesaemia: magnesium sulphate 2 g, equivalent to 8 mmol, intravenously over 15 to 30 minutes in adults; 25 to 50 mg/kg to a maximum of 2 g in children. Reduce and monitor closely in renal impairment.

Hyperkalaemia occurs with acute kidney injury and haemolysis, is often clinically silent and is rapidly lethal. Treat potassium over 6.5 mmol/L, or any level with electrocardiographic change, with:

• Calcium gluconate 10%, 10 to 30 mL intravenously over 5 to 10 minutes in adults, or 0.5 mL/kg to a maximum of 20 mL in children, repeated if electrocardiographic changes persist; this stabilises the myocardium and does not lower potassium

• Soluble insulin 10 units with 25 g of glucose, as 50 mL of 50% dextrose or 250 mL of 10% dextrose, intravenously over 15 to 30 minutes, with hourly glucose monitoring for 6 hours

• Nebulised salbutamol 10 to 20 mg in adults, 2.5 to 5 mg in children

• Treatment of the underlying cause, withdrawal of potassium containing fluids and potassium sparing drugs, and renal replacement where available

Hypocalcaemia and hyponatraemia should be corrected in parallel; correct sodium no faster than 8 to 10 mmol/L in 24 hours in chronic or uncertain duration hyponatraemia.

Glycaemic management

Check capillary glucose on admission and at every monitoring round, and in every patient with altered consciousness, seizure or unexplained deterioration. Hypoglycaemia, defined as glucose under 3.0 mmol/L (54 mg/dL), is a medical emergency.

• Adults: 50 mL of 50% dextrose intravenously, equivalent to 25 g, or 100 to 150 mL of 10% dextrose through a smaller vein

• Children: 5 mL/kg of 10% dextrose

• Neonates: 2.5 mL/kg of 10% dextrose

Recheck glucose at 15 minutes and repeat if still low. Follow with a 10% dextrose infusion in the patient who cannot eat, and begin early oral or enteral feeding in the patient who can.

Fever. Paracetamol 1 g 6 to 8 hourly orally or intravenously in adults, maximum 4 g in 24 hours, reduced to a maximum of 3 g in 24 hours in patients under 50 kg, in significant hepatic impairment or in chronic alcohol use. Children 15 mg/kg 6 hourly, maximum 60 mg/kg in 24 hours.

Given that transaminitis is near universal in filovirus disease, review the daily total each day and reduce it in marked hepatic dysfunction. Avoid non-steroidal anti-inflammatory drugs and aspirin entirely because of bleeding and renal risk.

Pain. Paracetamol as first line. For moderate to severe pain add tramadol 50 to 100 mg 8 hourly orally or intravenously, maximum 400 mg in 24 hours. Reduce to 50 to 100 mg 12 hourly with a maximum of 200 mg in 24 hours when estimated glomerular filtration rate is under 30 mL/min. Avoid in seizure risk and in combination with serotonergic drugs.

For severe pain, morphine 2.5 to 5 mg intravenously titrated every 10 minutes to effect in adults, 0.05 to 0.1 mg/kg in children, with close observation for respiratory depression and reduced doses in renal impairment. Avoid non-steroidal anti-inflammatory drugs.

Nausea and vomiting. Ondansetron 4 to 8 mg 8 hourly orally or intravenously in adults, maximum 24 mg in 24 hours; children 0.15 mg/kg to a maximum of 8 mg each dose. Correct potassium and magnesium before and during use because of additive QT prolongation. Metoclopramide 10 mg 8 hourly orally or intravenously in adults for a maximum of 5 days; in those under 18 years use 0.1 to 0.15 mg/kg to a maximum of 10 mg, second line only, with counselling on extrapyramidal reactions.

Diarrhoea. Oral rehydration solution is the priority. Loperamide may be used in adults to reduce stool volume: 4 mg initially then 2 mg after each loose stool, maximum 16 mg in 24 hours. Do not use it in children under 12 years, in suspected invasive bacterial colitis, in bloody diarrhoea or where there is abdominal distension suggesting ileus.

Dyspepsia and gastric protection. Omeprazole 40 mg orally or intravenously once daily in adults; children 5 mg once daily at 5 to 10 kg, 10 mg once daily at 10 to under 20 kg and 20 mg once daily at 20 kg or more. Double the adult dose where there is haemorrhage. For active upper gastrointestinal bleeding, pantoprazole 80 mg intravenously then 8 mg/hour by infusion for 72 hours is the preferred regimen where available.

Hiccups. Intractable hiccups are characteristic and distressing. Treat with chlorpromazine 25 mg 8 hourly orally or 12.5 to 25 mg intramuscularly, watching for hypotension and sedation, or metoclopramide. Exclude gastric distension, electrolyte derangement and uraemia as drivers.

Seizures. Exclude and correct hypoglycaemia and electrolyte derangement first; they are the commonest reversible cause in this setting.

• Adults: diazepam 5 to 10 mg intravenously over 2 to 5 minutes, repeated once after 10 minutes if seizing continues.

  If seizures persist, phenytoin 20 mg/kg intravenously to a maximum of 2 g, infused no faster than 50 mg/min with continuous cardiac monitoring, then maintenance 100 mg 8 hourly.

  Where available, levetiracetam is preferred because it requires no cardiac monitoring and has fewer interactions. Load 40 to 60 mg/kg intravenously to a maximum of 4.5 g, then 500 to 1500 mg 12 hourly, with dose reduction when estimated glomerular filtration rate is under 50 mL/min.

• Children: diazepam 0.3 mg/kg intravenously over 1 minute, or 0.5 mg/kg rectally, repeated once after 5 minutes if seizing continues.

  Buccal midazolam 0.3 mg/kg to a maximum of 10 mg, or intravenous lorazepam 0.1 mg/kg to a maximum of 4 mg, are acceptable alternatives.

  If seizures continue 5 minutes after the second benzodiazepine dose, give phenobarbital 15 to 20 mg/kg intravenously as a load, then maintenance 3 to 5 mg/kg once daily. Have airway support available because of the risk of respiratory depression.

Anxiety, confusion and agitation. Psychological support, calm reassurance, orientation and explanation come first. Confusion in this illness is usually metabolic and demands a metabolic workup rather than sedation.

Where sedation is genuinely necessary for the safety of the patient and staff, use the smallest effective dose of a short acting agent, with one-to-one observation. An agitated patient in a high risk zone is a major source of protective equipment breaches and sharps injuries. Plan additional staffing rather than relying on chemical restraint.

Nutrition

Early and adequate oral or enteral nutrition supports recovery and limits the catabolism that drives respiratory muscle fatigue. Offer small, frequent, high energy, high protein meals as tolerated, with locally acceptable foods. Treat anorexia and nausea actively rather than accepting prolonged poor intake.

Use nasogastric feeding where swallowing is unsafe or intake is persistently inadequate, weighing the aspiration risk. Screen children for severe acute malnutrition on admission and manage with therapeutic feeds. Provide micronutrient supplementation including zinc in children with diarrhoea at 20 mg daily for 10 to 14 days, or 10 mg daily in infants under 6 months.

Empirical antimicrobial treatment

Bacterial co-infection and bacterial translocation are common in severe disease, but reflexive antibiotic use in every patient is harmful. Treat where sepsis or bacterial infection is clinically suspected. Take blood cultures, two sets, before the first dose where this does not delay treatment, and give intravenous antibiotics within 1 hour of recognising septic shock. Review the indication every day and stop what is not needed.

Bloodstream infection with no clear focus, community onset. Amoxicillin with clavulanic acid 1.2 g intravenously 8 hourly; children 30 mg/kg of the amoxicillin component 8 hourly, commonly expressed as 45 mg/kg of the combination 12 hourly. Reduce the frequency when estimated glomerular filtration rate is under 30 mL/min.

Bloodstream infection, hospital onset or after 48 hours of admission. Piperacillin with tazobactam 4.5 g intravenously 6 hourly, with or without an aminoglycoside; children 100 mg/kg of the piperacillin component 6 hourly to a maximum of 4 g each dose. Reduce to 4.5 g 8 hourly when creatinine clearance is 20 to 40 mL/min and to 4.5 g 12 hourly when under 20 mL/min. A carbapenem is reserved for documented or strongly suspected extended spectrum beta lactamase producing organisms, directed by local resistance data.

Suspected typhoid. Ceftriaxone 2 g intravenously once daily in adults; 80 mg/kg once daily in children to a maximum of 2 g. Azithromycin 1 g once daily in adults, 10 to 20 mg/kg once daily in children, is an oral alternative where cannulation is difficult.

Pneumonia, community onset. Mild disease: amoxicillin 1 g orally 8 hourly in adults; high dose amoxicillin 40 to 45 mg/kg each dose 12 hourly in children. Moderate to severe disease: amoxicillin with clavulanic acid 1.2 g intravenously 8 hourly plus azithromycin 500 mg once daily for atypical cover; in children benzylpenicillin with gentamicin, or ceftriaxone, substituting a non-aminoglycoside agent where there is kidney injury.

Pneumonia, hospital onset. Amoxicillin with clavulanic acid 1.2 g intravenously 8 hourly for mild disease; piperacillin with tazobactam 4.5 g intravenously 6 hourly with or without an aminoglycoside for moderate to severe disease.

Urinary tract infection. Lower tract: nitrofurantoin 100 mg orally 12 hourly for 5 days, avoided when estimated glomerular filtration rate is under 45 mL/min. Upper tract, community onset: amoxicillin with clavulanic acid 1 g orally 12 hourly, or 1.2 g intravenously 8 hourly. Upper tract, hospital onset: amikacin 15 mg/kg once daily with trough monitoring, replaced by renally dosed piperacillin with tazobactam where there is kidney injury, which in this illness is most patients.

Skin and soft tissue infection. Flucloxacillin 500 mg to 1 g orally 6 hourly, or 2 g intravenously 6 hourly in adults; 12.5 to 25 mg/kg 6 hourly in children. Clindamycin 600 mg orally 8 hourly, or 900 mg intravenously 8 hourly in adults, and 20 to 40 mg/kg each day in three or four divided doses in children, is the alternative. Where methicillin resistant Staphylococcus aureus prevalence is high, use vancomycin 15 to 20 mg/kg 12 hourly with trough concentrations of 15 to 20 mg/L.

Persistent cough of 2 weeks or more. Send sputum for nucleic acid amplification testing for Mycobacterium tuberculosis, handled with the same containment precautions as all other specimens.

Antimalarial treatment

Malaria co-infection is common, worsens outcome and is readily treatable. Test every patient. Antimalarial treatment must not be delayed while awaiting filovirus results.

• Severe malaria: artesunate 2.4 mg/kg intravenously at 0, 12 and 24 hours, then once daily until oral therapy is tolerated; children under 20 kg receive 3 mg/kg at the same intervals. Give at least three parenteral doses before switching to a full oral course. Monitor for delayed post-artesunate haemolysis between day 7 and day 28, which is easily mistaken for filovirus related anaemia.
• Uncomplicated malaria: artemether with lumefantrine twice daily for 3 days, six doses in total, with the second dose 8 hours after the first. Dose by weight at each administration:
  • adults and those 35 kg or more: four tablets of the 20/120 mg formulation
  • 25 to under 35 kg: three tablets
  • 15 to under 25 kg: two tablets
  • 5 to under 15 kg: one tablet
  Give with fatty food or milk to ensure absorption. This is a real problem in the anorexic, vomiting patient, in whom parenteral artesunate is the safer choice.

Stop antimalarial treatment only when the malaria test is negative and an alternative explanation for fever is established.

Septic shock and vasopressor support

Shock in filovirus disease may be hypovolaemic, septic, cardiogenic from myocarditis, or haemorrhagic, and frequently more than one at once. Call for the most experienced clinician available as soon as shock develops; this is a time critical event and outcome depends on the first 2 hours. Manage in a critical care area where this is possible within the isolation envelope. Severe lactic acidaemia carries a poor prognosis and responds poorly to most interventions other than restoration of perfusion.

Septic shock is diagnosed clinically as suspected infection with systolic blood pressure under 90 mmHg plus one or more of pulse over 100 beats/min, respiratory rate over 24 breaths/min, or temperature under 36°C or over 38°C.

First 2 hours. Oxygen titrated to saturation of 94% or more. Balanced crystalloid 30 mL/kg within 3 hours, delivered in small frequent aliquots with reassessment every 30 minutes. Empirical antibiotics and antimalarials within 1 hour. Start norepinephrine early if shock persists after initial fluid rather than waiting for a fixed volume to be completed, because this reduces pulmonary oedema and improves perfusion sooner.

Search for and treat an additional source of infection. Monitor systolic blood pressure, pulse, respiratory rate, oxygen saturation, conscious level, capillary refill and lactate every 30 minutes. Transfuse if haemoglobin is under 7 g/dL, give dextrose if glucose is under 3.0 mmol/L, and escalate to a senior clinician if there is no improvement.

2 to 6 hours. If perfusion is not improving despite fluid and vasopressor, reconsider the diagnosis: occult internal haemorrhage, undrained infection, myocarditis, tension physiology, adrenal insufficiency. Obtain a second opinion. If perfusion is improving, reduce the fluid rate and watch for overload. Titrate vasopressor to the lowest dose achieving adequate perfusion. Monitor every 30 to 60 minutes with hourly urine output.

6 to 24 hours and beyond. Full clinical reassessment, review of all results, and treatment of the underlying diagnosis. Reduce fluids to maintenance of approximately 2 mL/kg/hour in adults, or the 4-2-1 regimen in children, and switch to oral or enteral intake as tolerated. Convert antibiotics to the oral route once the patient is stable and swallowing safely, and review the regimen at 48 to 72 hours against culture results. Introduce feeding once safe. Monitor every 2 to 8 hours depending on stability.

Vasopressor preparation and dosing. Norepinephrine is first line, with lower mortality and fewer arrhythmias than dopamine. Epinephrine is an acceptable alternative where norepinephrine is unavailable and is preferable where there is cardiac systolic dysfunction.

• Adults with central access: add 4 mL of 1 mg/mL (1:1000) solution to 46 mL of 5% dextrose, giving 50 mL at 80 micrograms/mL.

• Children, and adults through a peripheral line: add 1 mL of 1 mg/mL solution to 49 mL of 5% dextrose, giving 50 mL at 20 micrograms/mL. The more dilute preparation reduces the severity of extravasation injury.

• Start at 0.05 micrograms/kg/min, increase in increments of 0.1 micrograms/kg/min, with a usual maximum of 0.5 to 0.75 micrograms/kg/min.

• Target systolic blood pressure of 90 mmHg or more, or mean arterial pressure of 65 mmHg or more, with resolving signs of poor perfusion. Reassess every 15 to 30 minutes during titration, monitoring pulse every minute and blood pressure every 2 to 5 minutes during initial administration, and wean as soon as perfusion improves.

• A large bore peripheral line is acceptable for initiation rather than delaying treatment for central access, provided the site is inspected every 30 minutes for extravasation. Arrange central access for continuing therapy, using ultrasound rather than landmark technique.

• Stop the infusion immediately for extravasation, indicated by severe site pain or swelling, or for a dangerous arrhythmia. Treat extravasation with phentolamine 0.1 to 0.2 mg/kg to a maximum of 10 mg, diluted and infiltrated around the site.

Haemorrhage and transfusion

Assess for bleeding at every monitoring round, including puncture sites, gums, conjunctivae, stool, urine and the vagina. Bleeding reflects disseminated intravascular coagulation, thrombocytopenia, endothelial injury and impaired hepatic synthesis of clotting factors acting together.

Immediate measures. Airway, breathing, circulation, disability and exposure assessment; two large bore cannulae; balanced crystalloid; early vasopressor if shock persists; direct pressure to accessible bleeding points; active warming, because hypothermia worsens coagulopathy; and minimisation of all non-essential invasive procedures and injections.

Transfusion. Arrange an emergency supply route with transfusion services in advance of need, not at the moment of crisis. Screen all blood to national blood safety requirements even under emergency release. Use group O negative or group specific blood where cross matching would delay life saving transfusion. Document the indication, the volume and the response for every unit.

• Red cells when haemoglobin is under 7 g/dL, or under 9 g/dL with active bleeding or myocardial ischaemia. In children, transfuse urgently when haemoglobin is under 5 g/dL or there is severe pallor, at 20 mL/kg of whole blood or 10 mL/kg of packed cells.

• Platelets when the count is under 50 x 109/L with active bleeding, or under 20 x 109/L without bleeding.

• Fresh frozen plasma 15 mL/kg when the international normalised ratio is over 1.5 with active bleeding.

• Cryoprecipitate when fibrinogen is under 1.5 g/L, or under 2 g/L in postpartum haemorrhage.

• Vitamin K 10 mg intravenously slowly in adults, 250 micrograms/kg in children, where prothrombin time is prolonged.

Tranexamic acid. Not advised for general filovirus associated bleeding, including cannula site, mucosal and gastrointestinal bleeding, because stabilising inappropriate clot in disseminated intravascular coagulation may worsen microvascular thrombosis and organ injury.

It is advised for postpartum haemorrhage in a filovirus disease patient: 1 g intravenously over 10 minutes within 3 hours of birth, repeated once after 30 minutes if bleeding continues, alongside uterotonics, uterine massage, fluid resuscitation, examination of the genital tract and escalation of care.

Acute kidney injury

Monitor urine output in every patient; oliguria of under 0.5 mL/kg/hour in adults or under 1 mL/kg/hour in children is an early warning. Avoid urinary catheterisation unless there is obstruction or an unavoidable need for accurate hourly measurement, because of infection and exposure risk.

Correct hypovolaemia and hypotension promptly; inadequate and delayed fluid resuscitation is the most common preventable driver of kidney injury in this illness. Withdraw nephrotoxic drugs: aminoglycosides, non-steroidal anti-inflammatory drugs, contrast and high dose colistin. Dose adjust every renally cleared drug. Correct hyperkalaemia, acidosis and fluid overload actively.

Renal replacement therapy should be provided where it can be delivered safely, directed by a nephrologist, with full infection control and with attention to circuit disconnection risk. Continuous renal replacement is preferred over intermittent haemodialysis in the haemodynamically unstable patient. The decision balances benefit against the exposure risk to staff and the availability of trained personnel.

Respiratory failure

Respiratory distress is seldom a primary pulmonary manifestation of the virus. It is usually secondary to fluid overload, respiratory muscle fatigue from profound metabolic acidosis and catabolism, aspiration, secondary bacterial pneumonia, tuberculosis, severe malaria or anaemia. Identify and treat the reversible cause.

Monitor oxygen saturation as part of routine observations. Start oxygen at 15 L/min through a non-rebreather mask with reservoir in the hypoxaemic patient and titrate down to the lowest inspired fraction maintaining saturation over 94%. Use positioning, including sitting upright and prone positioning in the cooperative patient, and treat the underlying cause.

Avoid non-invasive ventilation and high flow nasal oxygen. They generate infectious aerosol, carry a high risk of vomiting and aspiration in this patient group, and endanger staff.

Invasive ventilation is reserved for settings with trained, experienced personnel and adequate protective equipment. Clinical triggers mirror those in any multi organ failure and usually arise in the late complications phase:

• Progressive hypoxaemic respiratory failure despite maximal non-invasive oxygen delivery, typically acute respiratory distress syndrome from systemic inflammation or fluid overload

• Hypercapnic failure with respiratory muscle exhaustion driven by the metabolic demands of profound diarrhoea, vomiting and acidosis

• Loss of airway protection from encephalopathy or uraemic deterioration

Institutional conditions must also be met before proceeding:

• a dedicated single patient isolation room
• full high level protective equipment for the intubating team, including a fitted particulate respirator or powered air purifying respirator, face shield and fluid impermeable body covering
• high efficiency particulate air filtration on the expiratory limb of the ventilator
• sufficient trained personnel, including a dedicated observer supervising donning and doffing

Use the most experienced intubator, a rapid sequence technique, a videolaryngoscope where available, and a closed suction system.

A utility and risk assessment is required before the procedure. Where decline is driven primarily by fluid overload from aggressive rehydration, manage fluids and oxygen rather than intubating. Where there is end stage, irreversible multi organ failure, invasive ventilation may be withheld as medically futile and disproportionately hazardous to the clinical team, with the decision made by senior clinicians, documented, and communicated to the family with psychosocial support.

There is no licensed therapeutic and no licensed vaccine for Bundibugyo virus. Products licensed for Zaire ebolavirus, including the recombinant vesicular stomatitis virus vectored vaccine expressing the Zaire glycoprotein and the Zaire specific monoclonal antibodies ansuvimab and the atoltivimab, maftivimab and odesivimab combination, are species specific and are not expected to protect against Bundibugyo virus.

Any use of an unlicensed product should occur under the national framework for monitored emergency use of unregistered and investigational interventions, with documented consent, defined monitoring and mandatory reporting of adverse reactions.

Agents currently under evaluation and potentially available under emergency authorisation include:

• MBP134, a pan ebolavirus two antibody cocktail with activity across Zaire, Sudan and Bundibugyo species in animal models, dosed at 50 mg/kg by intravenous infusion over 1 hour in both adults and children.

• Remdesivir, a nucleotide analogue inhibitor of the viral RNA-dependent RNA polymerase.

  • Adults: 200 mg intravenously on day 1, then 100 mg once daily for 9 further days, 10 days in total.
  • Children 40 kg or more: as for adults.
  • Children aged 28 days or more weighing 3 kg to under 40 kg: 5 mg/kg on day 1, then 2.5 mg/kg once daily.
  • Children aged 28 days or more weighing 1.5 kg to under 3 kg, and neonates under 28 days weighing 1.5 kg or more: 2.5 mg/kg on day 1, then 1.25 mg/kg once daily.

  Monitor transaminases and prothrombin time. Stop for alanine transaminase over 10 times the upper limit of normal or any rise with signs of liver injury. Infusion reactions including hypotension and bradycardia occur; infuse over 30 to 120 minutes.

• Obeldesivir, an orally bioavailable prodrug of the same active nucleoside, attractive in outbreak settings because it removes the need for intravenous infusion in an isolation unit. Dosing follows the authorisation documents in force.

• Maftivimab, a single monoclonal antibody component with broader reported in vitro activity than the full Zaire specific combination.

Post-exposure prophylaxis with an antiviral should be considered for individuals with high risk exposure. Both post-exposure prophylaxis and treatment should be given as early as possible, ideally within 72 hours of exposure or symptom onset, because efficacy in animal models falls sharply with delay.

The recombinant vesicular stomatitis virus vaccine is under evaluation for cross protection against Bundibugyo virus and, where it becomes available for this indication, should be offered to front line responders and health workers under the national framework. Evidence in this area is changing quickly and this section should be reviewed before each publication cycle.

Pregnancy. Maternal and foetal mortality are both high, with miscarriage, stillbirth, preterm labour and maternal haemorrhage. Involve the obstetric team early but never delay isolation or supportive care for obstetric review. Delivery generates very large volumes of highly infectious fluid: the delivery team wears complete protective equipment in a dedicated isolation delivery space with the minimum essential staff. Mode of delivery is determined by obstetric indication and the capability of the unit.

Delay all elective deliveries. Where caesarean section is indicated, use a dedicated theatre and a team trained for this scenario. Basic delivery facilities and a private area for managing miscarriage and vaginal bleeding should exist within the treatment unit.

Give tranexamic acid for postpartum haemorrhage as described, and manage incomplete or spontaneous abortion with full post-abortion care. Instruct women on handling potentially infectious material including products of conception, with the same precautions used in the unit.

Convalescing pregnant women remain in isolation until two negative polymerase chain reaction results 72 hours apart. All recovered women, and women who conceive within 9 months of discharge, should be delivered under full filovirus infection control precautions.

Neonates of infected mothers. Exposed neonates in the first 7 days of life should receive a monoclonal antibody such as MBP134 under the national emergency use framework. Nurse with full protective equipment until two negative polymerase chain reaction results 48 hours apart.

Do not breastfeed until breast milk tests negative twice at least 24 hours apart. Maintain thermal care, early glucose monitoring and early feeding with a safe substitute.

Breastfeeding. Viral RNA is detectable in breast milk. An infant breastfed by a suspected or confirmed case is managed as a suspect case and isolated; never send a potentially infected breastfeeding infant home. Ideally the infected mother stops breastfeeding, decided by individual risk assessment and the availability of acceptable, feasible, affordable, sustainable and safe replacement feeding.

Support the conscious mother to express and discard milk to maintain supply; a health worker in full protective equipment may assist the unconscious mother. Three situations arise. Where mother and child are both asymptomatic contacts, quarantine them together with the mother as primary carer. Where the mother is confirmed and the child is an asymptomatic contact, isolate the mother and quarantine the child with a carer using protective equipment, stopping breastfeeding and providing a substitute.

Where both are confirmed, care for both together, and where no milk substitute is available, breastfeeding may continue. Infants under 6 months need a ready-to-use infant formula; infants and children of 6 to 23 months need formula or ultra-high-temperature whole cow's milk with complementary feeding, supplemented with micronutrient powders where intake is inadequate.

Prioritise breast milk testing for recovered women who wish to resume feeding, and respect and support the woman's informed choice.

Children. Use weight based dosing for every drug and every fluid. Screen for severe acute malnutrition on admission. Treat recognised syndromes, pneumonia, meningitis and shock, with established paediatric regimens. A single trained carer in protective equipment may remain with an unaccompanied or young child in isolation, and requires the same training, supervision and health monitoring as facility staff. Review and catch up routine immunisation once the child is medically stable or at follow up.

Older adults. Age over 45 years is an independent adverse prognostic factor. Cardiac and renal reserve are lower, so fluid resuscitation requires more frequent reassessment and earlier vasopressor support rather than larger boluses. Polypharmacy and baseline renal impairment demand careful dose adjustment. Delirium is more common and should prompt a metabolic workup rather than sedation.

Kidney impairment. Reduce or avoid aminoglycosides, nitrofurantoin when estimated glomerular filtration rate is under 45 mL/min, and non-steroidal anti-inflammatory drugs entirely. Adjust piperacillin with tazobactam, amoxicillin with clavulanic acid, levetiracetam, tramadol, morphine and remdesivir. Recalculate doses as function changes rather than once on admission.

Liver impairment. Transaminitis is near universal and does not itself require dose change, but synthetic failure does. Reduce the daily paracetamol maximum, avoid or reduce tramadol, monitor remdesivir closely, and expect prolonged prothrombin time that reflects synthesis rather than anticoagulation.

Monitoring

Reassess stable suspected and confirmed cases at least every 8 hours, and unstable patients far more frequently, up to every 30 minutes in shock. The daily assessment should cover, at minimum:

• Presence of any red flag feature

• Fluid status: ability to drink, adequacy of intake, measured stool and vomit volumes, urine output, signs of sepsis or shock, signs of overload

• Laboratory review: potassium and magnesium replacement needs, renal function, adequacy of prior resuscitation

• Capillary glucose, with symptomatic hypoglycaemia treated with concentrated dextrose and asymptomatic hypoglycaemia with 10% dextrose and feeding

• Need for continued antibiotics, with daily review and discontinuation of what is unnecessary

• Need for continued antimalarial treatment, stopped on a negative test with an alternative explanation

• Ability to eat and drink, and whether maintenance fluids can be stopped

• Device review: is the cannula site clean, can the cannula be removed, can the urinary catheter be removed, does the patient need help to walk

• In pregnant women: vaginal bleeding, rupture of membranes, foetal movements, lower abdominal pain or other signs of labour, with last menstrual period and expected delivery date recorded

Referral and escalation

Escalate immediately to the most experienced clinician available for shock, any red flag feature, failure of perfusion to improve after initial fluid and vasopressor, significant haemorrhage, encephalopathy or seizure, oliguria persisting after adequate resuscitation, respiratory deterioration, and any obstetric emergency.

Transfer of suspected and confirmed cases to a designated treatment unit should use a dedicated vehicle with a trained crew in full protective equipment, with the receiving unit notified in advance, and with decontamination of the vehicle on return.

Transfer the stabilised patient; resuscitate before moving rather than during movement, because clinical care inside a moving ambulance in full protective equipment is extremely limited.

A contact is an asymptomatic person with physical exposure to a confirmed, probable or suspected case or their body fluids in the preceding 21 days.

This includes anyone who:

• has slept in the same household as a case
• had direct physical contact with a case alive or dead
• had contact with the body at a funeral or during burial preparation
• touched the blood or body fluids of a case
• touched items contaminated with those fluids, such as clothing and linen
• has been breastfed by a case

Health workers, cleaners, waste handlers, laboratory staff, drivers and mortuary staff are all contacts when exposed.

Immediate action after a recognised exposure. Wash exposed skin immediately with soap and water. Irrigate exposed mucous membranes, including conjunctivae, with copious clean water. Report the incident at once, complete an exposure record and undergo risk assessment.

Follow up of contacts. Quarantine high risk contacts in a designated area for 21 days, ideally a single room with a private bathroom, with no interaction between quarantined individuals, because a single positive case among them would otherwise restart the clock for everyone. If interaction occurs and a case arises, all contacts of that case require a further 21 days.

Medically evaluate every contact, record temperature twice daily for 21 days and whenever the contact reports feeling hot, and provide each contact with their own digital thermometer where possible. Conduct contact tracing in person rather than remotely.

Perform polymerase chain reaction testing on days 0, 7, 14 and 21 of quarantine. Any contact who develops fever or other compatible symptoms becomes a suspect case and is hospitalised in strict isolation immediately. An asymptomatic contact who tests positive is managed as a confirmed case.

Discharge from quarantine. Discharge after the full 21-day period if no compatible signs or symptoms have developed and the polymerase chain reaction on a sample collected on day 21 is negative.

Discharge of patients

Contact in quarantine. Asymptomatic throughout, no positive test during quarantine, and a negative polymerase chain reaction on day 21.

Suspect case. Afebrile without antipyretics for 24 hours, or an alternative explanation for fever established; all compatible symptoms resolved or attributed to an alternative diagnosis; and a negative polymerase chain reaction on a sample taken on day 3 or later after symptom onset.

Confirmed case. Discharge criteria:

• completion of any treatment course, for example 10 days of remdesivir
• at least 3 days without fever or significant symptoms
• full resolution of symptoms suggesting ongoing shedding, specifically diarrhoea, cough and bleeding
• substantial clinical improvement with reasonable general condition, meaning the patient can feed, wash and walk independently allowing for baseline disability
• two consecutive negative polymerase chain reaction results on whole blood taken 72 hours apart

A positive result at either point restarts the cycle with isolation and repeat testing after 72 hours.

Discharge procedure. Carry out discharge in a dedicated area at the interface between the high risk and low risk zones, with a one way patient exit, to prevent recontamination.

• The patient bathes with soap and water. Never bathe or spray a patient with chlorine solution; it is harmful and unnecessary.

• Provide fresh clothing. Destroy clothing brought into the unit.

• Decontaminate the mobile phone and charger with alcohol based wipes of at least 70% strength. Wipe every surface continuously for at least 1 minute with the device switched off and unplugged, then place it in a clean bag.

  Destroy any phone that is visibly soiled with body fluid, or whose screen is cracked or damaged, since thorough disinfection is impossible. Instruct the patient not to share the phone.

• Incinerate all other personal belongings that cannot be decontaminated.

• Provide an infection control kit for home use containing handwashing, cleaning and disinfection materials.

• Counsel sexually active male patients on semen persistence, supply condoms, and advise condom use for 12 months, or until two semen polymerase chain reaction tests at least 1 week apart are negative where testing is available.

• Counsel breastfeeding women not to resume feeding until two breast milk polymerase chain reaction tests at least 24 hours apart are negative, and provide a substitute and infant feeding support.

• Clean and disinfect the patient care environment and reusable linen, or incinerate heavily contaminated items.

• Provide nutritional advice using locally available, high energy, easily digestible foods.

• Anticipate rejection and stigma. Counsel the patient, the family and any receiving health facility, and issue a certificate confirming the patient poses no danger to others, together with a discharge summary and sick leave where needed.

• Arrange psychological support, follow up appointments, and advocacy with community leaders where necessary.

Convalescence and post-filovirus syndrome

Survivors commonly experience prolonged fatigue, arthralgia often affecting large joints, myalgia, headache, abdominal pain, anorexia and poor concentration. Specific and important sequelae include uveitis and other ocular inflammation that can progress to cataract and blindness if untreated, sensorineural hearing loss and tinnitus, peripheral neuropathy, cognitive impairment, depression, anxiety and post-traumatic stress. Stigma and loss of livelihood are near universal and materially affect recovery.

Survivor follow up

Offer structured follow up to every survivor, adult and child, at 2 to 4 weeks, 3 months and 6 months, with more frequent review where clinically indicated. Each visit should address:

• Viral persistence: semen and breast milk testing with safe sex and safe feeding counselling until clearance

• Ophthalmology: screening for uveitis and visual impairment, with urgent referral because untreated uveitis causes preventable blindness

• Neurology: screening for hearing loss, headache, neuropathy and cognitive impairment

• Mental health: screening for depression and anxiety using brief validated instruments, with direct enquiry about self-harm rather than reliance on a questionnaire score, and referral where positive

• Nutrition: assessment and support, especially in children

• Immunisation: review and catch up of the routine childhood schedule

• Obstetric planning: women who conceive within 9 months of discharge are delivered under full infection control precautions

• Socioeconomic and stigma: assessment of impact and linkage to available support

Suspect cases discharged with a negative result also need follow up, because both health services and communities may be reluctant to accept them without reassurance.

Mental health and psychosocial support

Begin at first screening or triage, not after a positive result, and extend support to patients, contacts, families, survivors, the bereaved, responders and health workers.

At first contact explain what will happen, offer psychological first aid, check immediate safety, distress, practical needs, pre-existing mental illness and current medicines, obtain consent and a safe contact method, and identify children and others needing additional support.

Address urgent medical needs before questionnaires, and never delay support in order to complete an instrument.

Provide continuity of psychotropic medication; abrupt withdrawal in isolation causes avoidable crises. Deliver results privately and compassionately with the treating team present. Reassess distress, functioning, suicide risk and family needs after a positive result, after deterioration and after bereavement. Maintain safe family contact, including telephone or secure video, and a controlled viewing area separated by a transparent barrier for visitors.

Offer voluntary coping and psychoeducation groups, supervised peer support and structured group therapy where assessed as appropriate, observing infection control and cohorting rules. Escalate to specialist psychiatric assessment for psychosis, severe depression, suicide risk and poor response to initial support. One negative test does not automatically end isolation or contact monitoring, and this should be explained clearly to avoid a damaging cycle of hope and disappointment.

Hand hygiene. Alcohol based hand rub at every point of care is the usual method; wash with soap and water when hands are visibly soiled. Perform hand hygiene before gloving, immediately after glove removal, before handling invasive devices, after contact with blood or body fluids and after contact with items in the patient's immediate environment.

Keep nails short and natural, remove rings, watches and bracelets, and ensure hands are dry before starting any activity. Chlorine at 0.05% is an interim measure for hand hygiene only where alcohol based rub and soap and water are genuinely unavailable.

Protective equipment. Requirements rise with proximity and contact. Screening at 1 metre or more with a no touch technique requires scrubs and closed toe shoes. Screening where distance cannot be maintained adds a fluid resistant gown, a fluid resistant non-collapsible medical mask and one pair of nitrile gloves. Triage with likely patient contact requires scrubs, a fluid resistant coverall, eye protection and two pairs of nitrile gloves, usually with rubber boots.

Direct patient care requires scrubs, a fluid resistant coverall, a gown with head and neck covering, an apron, eye protection, two pairs of gloves and waterproof rubber boots. Environmental services and burial teams require scrubs, a fluid resistant coverall, a heavy duty apron, two pairs of gloves with a heavy duty outer glove, waterproof rubber boots and a particulate respirator for any aerosol generating activity.

Donning sequence.

1. Remove all personal items.
2. Put on scrubs in the changing room.
3. Put on closed footwear.
4. Perform hand hygiene.
5. Select and organise correctly sized equipment.
6. Proceed under the supervision of a trained observer.
7. Perform hand hygiene.
8. Put on inner nitrile gloves.
9. Put on coverall or gown and head cover.
10. Put on particulate respirator.
11. Put on eye protection.
12. Put on head and neck covering over the eye protection strap.
13. Put on waterproof apron.
14. Put on outer long cuff gloves over the coverall cuff.

Use a mirror to confirm no skin, hair or mucous membrane is exposed.

The observer performs a buddy check and records name, cadre and time of entry into the high risk zone.

Doffing sequence. Always under the supervision of a trained observer, with waste containers and receptacles for reusable items ready.

1. Decontaminate outer gloves with alcohol based rub and allow to dry.
2. Remove the apron by breaking the ties and folding inside out away from the body.
3. Decontaminate outer gloves.
4. Remove the head and neck covering from the bottom at the back, rolling back to front and inside to outside.
5. Decontaminate outer gloves.
6. Remove the coverall and outer gloves together, rolling from the inside.
7. Decontaminate inner gloves.
8. Remove eye protection by pulling the strap from behind the head while leaning forward.
9. Decontaminate inner gloves.
10. Remove the respirator from behind, bottom strap first.
11. Decontaminate inner gloves.
12. Remove boots or boot covers without touching them with bare hands.
13. Decontaminate inner gloves.
14. Remove inner gloves with correct technique.
15. Perform hand hygiene on bare hands and proceed to the shower.

Mucous membrane protection comes off last. Aprons, boots and eye protection intended for reuse are individually assigned, cleaned of gross contamination and disinfected.

Environmental cleaning. Clean floors and frequently touched surfaces with soap and water at least twice daily, working from clean to dirty, and always clean before disinfecting. Disinfect with 0.5% chlorine solution or 70% alcohol. Never dry sweep or shake out dusty cloths.

Reconstitute chlorine solution daily, label it with concentration, date and time, keep it covered and away from sunlight, and test with high range chlorine strips where available.

To prepare a solution, grams of chlorine powder for each litre of water equals the desired concentration divided by the available concentration, multiplied by 1000; a 0.5% solution from 65% powder therefore requires 7.7 g for each litre. A 0.5% solution corresponds to 5000 ppm and a 0.05% solution to 500 ppm on test strips. Rinse chlorine residue from metal surfaces after the contact time to prevent corrosion.

Spills.

1. Restrict access and cordon the area.
2. Assess the extent.
3. Don full protective equipment under supervision.
4. Cover the spill with absorbent material.
5. Debulk into a biohazard bag.
6. Clean the surface with soapy water and rinse.
7. Apply 0.5% chlorine for a 15-minute contact time.
8. Rinse off residue.
9. Dispose of contaminated materials as infectious waste.
10. Clean and disinfect the cleaning tools.
11. Doff carefully and perform hand hygiene.
12. Document the incident and report any exposure immediately.
13. Reopen the area only once dry.

Reusable devices. Never reprocess single use items. Do not soak devices in chlorine before cleaning, because organic material inactivates the disinfectant, creates a reservoir for biofilm, poses a transport hazard and encourages disinfectant resistance. Clean mechanically with detergent and water first, then rinse, then disinfect by wiping with 0.5% chlorine for a 15-minute contact time keeping surfaces visibly wet, then rinse off residue. Do not spray disinfectant onto equipment, which creates inhalable chlorine mist.

Linen. Handle only in full protective equipment. Bundle contaminated linen directly into labelled leak proof containers at the point of use. Disinfect the container exterior with 0.5% chlorine before removal.

Heavily contaminated linen that cannot be safely disinfected goes for incineration. Otherwise wash in hot soapy water, rinse, soak in 0.05% chlorine for up to 30 minutes, rinse and air or machine dry.

Where a machine is used and bleach cannot be added, do a hot wash over 60°C with detergent, then soak in 0.05% chlorine, then run a cycle to remove residue.

Transport linen in covered dedicated trolleys with strict separation of clean and soiled. Disinfect the trolleys after each use.

Utensils. Wash plates, cups and utensils with detergent and clean water, immerse in 0.05% chlorine for 30 minutes, rinse and air dry.

Waste. Treat all waste from the care of a suspected or confirmed case, including waste from decontamination, as highly infectious. Segregate at the point of generation into sharps and highly infectious waste. Do not store waste in the unit for more than 24 hours. Transfer it directly to the treatment or destruction area. Seal sharps containers when three quarters full and incinerate.

Health worker protection

Limit continuous time in full protective equipment to 1.5 to 2 hours in the high risk zone because of heat stress and dehydration, and ensure rest, hydration and food between rotations. Never enter the high risk zone alone; donning, doffing and clinical checks require a minimum of two people. Monitor all staff with patient contact daily for symptoms, and refer any symptomatic staff member immediately for screening, triage and isolation rather than managing them informally.

Observe every donning and doffing episode. Assess the risk after any breach and institute quarantine with symptom monitoring where indicated, in a comfortable dedicated facility. Conduct pre-shift and post-shift health checks throughout the response and for 21 days after last exposure. Staffing requires a 20 to 30% surge buffer above nominal establishment to absorb mandatory rest, exposure isolations and attrition, and requires continuous retraining because donning and doffing competence decays quickly.

Deceased patients

Bodies are highly infectious and remain so for a prolonged period. Handle the body as little as possible, and only by trained personnel in full protective equipment. Families must not handle the body. Do not wash or embalm. Limit post-mortem examination to essential evaluations by trained personnel in full equipment including a particulate respirator, and prefer alternatives such as needle biopsy.

Place the body in two sealed body bags, label the exterior of each with the name of the deceased using a waterproof marker, and bury or cremate promptly. Engage religious and community leaders early to agree a process that is both safe and respectful, since community acceptance has repeatedly been the decisive factor in outbreak control.

Disinfect the route taken and the transport vehicle afterwards, and doff according to the full procedure on return.

• Waiting for bleeding, or for laboratory confirmation, before isolating and treating

• Under resuscitation: giving 1 to 2 litres in 24 hours to a patient losing 6 litres each day

• Failing to measure stool and vomit volumes, so losses are never replaced

• Not checking glucose in the confused or deteriorating patient

• Delaying vasopressor until a fixed fluid volume has been completed, producing pulmonary oedema without restoring perfusion

• Giving tranexamic acid for non-obstetric filovirus bleeding

• Using non-steroidal anti-inflammatory drugs for fever or pain

• Giving aminoglycosides in established acute kidney injury

• Delaying antimalarial treatment while awaiting filovirus results

• Continuing empirical antibiotics beyond the point of indication

• Siting a urinary catheter for convenience

• Requesting a filovirus assay without specifying species identification, then accepting a false negative

• Accepting a negative result on a sample drawn under 72 hours from symptom onset as exclusion

• Cohorting suspect cases together

• Spraying patients or equipment with chlorine

• Allowing exhausted staff to extend time in the high risk zone, which is when doffing errors occur