Marburg virus infection

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

all patients

1st line – isolation and infection control

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Once the diagnosis is suspected, patient isolation is a critical first step to prevent nosocomial transmission.[21]

Infection control is of immediate concern. As soon as a clinician decides Marburg virus disease is a possible diagnosis for their patient’s illness, high-level precautionary isolation procedures and personal protective equipment (PPE) should be used until the infection is either confirmed or excluded. It is extremely important to minimise the risk of transmission while working up the patient.[20] Although 'wet symptoms' such as vomiting/diarrhoea may increase transmission risk, Marburg virus should be considered highly infectious and high-level precautions should be used regardless of symptoms at presentation.

The Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) produce detailed guidance on PPE when filovirus disease is suspected:

CDC: guidance on personal protective equipment (PPE) to be used by healthcare workers during management of patients with confirmed Ebola or persons under investigation (PUIs) for Ebola Opens in new window

WHO: personal protective equipment for use in a filovirus disease outbreak - rapid advice guideline Opens in new window

The WHO also produces detailed infection control guidance for healthcare workers in viral haemorrhagic fever outbreak settings:

WHO: infection prevention and control (IPC) guidance summary Opens in new window

Once a diagnosis of Marburg virus disease is suspected and isolation is initiated, a provider should wear full PPE and collect 4mL whole blood in a non-heparinised, preservative-coated tube, and refrigerate or freeze immediately for shipment to a reference lab. Outside of North America and Europe, either reverse transcriptase PCR (RT-PCR) blood tests or oral swabs are used to detect Marburg virus RNA.[41] These tests may return within a few hours or days depending on whether a local or reference lab is used. At this time, providers should consider obtaining good intravenous access with careful central catheter placement (where possible) or multiple peripheral intravenous catheters.[31]

Laboratory testing for possible differential diagnoses, malaria testing, FBC, renal function and electrolytes, and blood lactate level should be sent as soon as intravenous access is obtained, where possible.[31][42]

Plus – fluid and electrolyte management

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Treatment recommended for ALL patients in selected patient group

Initial vital signs should guide initial treatment. Fluid resuscitation is the main supportive treatment, and in patients who have significant gastrointestinal volume loss, massive fluid repletion with strict attention to repleting ongoing losses may be required.[4][30][40] Adult patients usually require ≥ 5-10L/day of intravenous or oral fluids to maintain circulating blood volume in the setting of ongoing gastrointestinal loss.[31]

Monitoring and aggressive correction of potassium levels, acid-base disturbances, and other electrolyte abnormalities can help prevent life-threatening arrhythmias and metabolic complications.

General principles of management for children with Marburg or Ebola virus disease are the same as for adults, with a focus on supportive care and volume resuscitation.[50] Care providers in the 2014 to 2016 West Africa Ebola virus outbreak advocate liberal use of oral rehydration solution (ideally flavoured to improve intake), and early, aggressive parenteral fluid resuscitation, even among those who are apparently well-hydrated.[51] Obtaining intravenous access may be easiest at time of admission, before further fluid losses make vascular access difficult, and a second intravenous line should be considered in 'wet' patients with active vomiting or diarrhoea.[51] Intra-osseous and subcutaneous routes of fluid resuscitation may be necessary in children unable to tolerate oral or intravenous rehydration.[51]

Plus – analgesia/antipyretic

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Treatment recommended for ALL patients in selected patient group

Should be treated with paracetamol first line (for pain and fever).[43]

Opioid analgesics (e.g., morphine) are preferable for more severe pain.[43]

Non-steroidal anti-inflammatory drugs (including aspirin) should be avoided due to their associated increased risk of bleeding and potential for nephrotoxicity.

Primary options

paracetamol: children: 10-15 mg/kg orally/rectally every 4-6 hours when required, maximum 75 mg/kg/day; adults: 500-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

morphine sulfate: children: 0.2 to 0.4 mg/kg orally every 4-6 hours when required, or 0.05 to 0.1 mg/kg intravenously every 4-6 hours when required; adults: 2.5 to 10 mg orally/intravenously every 4 hours when required

Plus – antimalarial treatment

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Treatment recommended for ALL patients in selected patient group

Empiric artesunate-based antimalarial treatment is recommended for all patients with suspected filovirus disease due to 31% lower risk of death in Ebola virus disease patients receiving these medications compared with other antimalarials. Increased survival may be due to treatment of malaria co-infection, prophylaxis preventing co-infection (especially in areas of high malaria-burden), or possibly even some of these drugs having a direct effect on filiovirus activity.[23]

Plus – anti-emetic and anti-diarrhoeal therapy

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Treatment recommended for ALL patients in selected patient group

Early administration of an anti-emetic (e.g., metoclopramide, ondansetron) and anti-diarrhoeal therapy (e.g., loperamide) is recommended as long as diarrhoea is not bloody and other enteric pathogens are not suspected.[26][31][42][57]

Primary options

metoclopramide: children: consult specialist for guidance on dose; adults: 10 mg orally/intravenously every 8 hours, maximum 30 mg/day

ondansetron: children: consult specialist for guidance on dose; adults: 4-8 mg orally/intravenously every 8-12 hours when required, maximum 24 mg/day

loperamide: children: consult specialist for guidance on dose; adults: 4 mg orally initially, followed by 2 mg after each loose stool, maximum 16 mg/day

Plus – consider administration of broad-spectrum antibiotics

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Treatment recommended for ALL patients in selected patient group

Empiric broad-spectrum antibiotics (e.g., ceftriaxone, ciprofloxacin, or ampicillin/sulbactam) should be started to treat possible bacterial translocation from the gut.[31][42]

Plus – consider transfusion of blood products

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Treatment recommended for ALL patients in selected patient group

Transfusion of blood products including transfusion of platelets, packed red blood cells, and even plasma from convalescent donors may also be beneficial.[42]

with hypotension

Plus – vasopressor

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Treatment recommended for ALL patients in selected patient group

Patients developing hypotension should receive appropriate vasopressor support therapy as needed.[26][31][42]

with organ dysfunction

Plus – supportive care

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Treatment recommended for ALL patients in selected patient group

Multi-organ dysfunction is a common feature of advanced infection and may include acute kidney injury, pancreatitis, adrenal failure, and liver damage.

Liver damage (e.g., transaminitis) is common; however, jaundice is not a common feature.[12][25][44]

Renal dysfunction is common in the advanced stages, but may be reversible in early stages with aggressive fluid resuscitation.[12][44] One Marburg virus disease patient with anuria not responsive to fluid resuscitation was treated with renal replacement therapy, an intervention which has also been used in patients with severe Ebola virus disease. However, there are no trial data to support the efficacy of this intervention. Of the five critically ill Ebola virus disease patients with multi-organ failure managed with both invasive mechanical ventilation and renal replacement therapy in Europe and North America, three died.[42][45][46][47][48]

Where resources allow, respiratory supportive care may be helpful, including supplemental oxygen, non-invasive ventilation, or invasive mechanical ventilation if non-invasive ventilation fails.[42] Full supportive care should be provided when possible, and can reduce filovirus disease mortality, with a reported survival rate of 82% in Ebola virus disease patients managed outside the West African setting.[42] Historically, Marburg virus disease is often fatal, with death occurring in approximately 70% (range 23% to 100%) of historical cases.[5] High case fatality rates in Marburg and Ebola virus disease patients in sub-Saharan Africa may be related to the lack of full supportive care available in resource-poor, rural settings where outbreaks have occurred.[49]

with haemorrhage or disseminated intravascular coagulation

Plus – vitamin K, platelet transfusion, and cryoprecipitate

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Treatment recommended for ALL patients in selected patient group

Haemorrhage and disseminated intravascular coagulation (DIC) are uncommon and are usually manifestations of late or severe disease. Vitamin K should be considered to improve coagulopathy, and can be given to patients developing haemorrhage.[26][31][42] Platelet transfusion and cryoprecipitate may also be helpful when platelet or fibrinogen levels are low.[26][31][42]

pregnant

Plus – obstetric interventions

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Treatment recommended for ALL patients in selected patient group

For filovirus-infected pregnant women, the value of usual obstetric interventions such as fetal monitoring, caesarean delivery, induction of labour, or pregnancy interruption must be considered on a case-by-case basis.[4]

In addition to careful deliberation about obstetric intervention, appropriate anticipatory guidance should be provided to all pregnant women. Towards this end, urine pregnancy testing should be considered as part of routine triage testing to appropriately counsel pregnant women on pregnancy complications and management options.

Pregnant filovirus patients are at high risk of spontaneous, pre-term labour and healthcare providers should be prepared for delivery at any time. Pregnancy outcomes can include spontaneous abortion, stillbirth, or delivery of a live fetus, and appropriate precautions should be taken. Regardless of the pregnancy outcome, all products of delivery should be considered potentially infectious and handled accordingly.

Neonatal survival from Ebola virus-infected mothers is almost universally poor, and high fetal loss rates underscore the need to focus efforts on treatment of the pregnant mother, caveats which likely also apply to Marburg virus disease.

breastfeeding

Plus – cessation of breastfeeding

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Treatment recommended for ALL patients in selected patient group

Ebola virus has been cultured from breast milk 15 days after symptom onset and Ebola virus RNA has been detected in breast milk by reverse transcriptase PCR (RT-PCR) 26 days after disease onset.[53][54] This evidence suggests that theoretically Ebola virus might be transmitted through breast milk, though frequent intimate contact between mothers and their children leaves open other possible modes of transmission.

One study of Ebola virus survivors in Sierra Leone demonstrated no excess risk of Ebola virus transmission to infants during breast feeding.[55] Despite this, it is recommended that mothers with suspected or confirmed Ebola virus infection avoid close contact with their infants if safe alternatives to breastfeeding exist.[56] This includes cessation of breastfeeding. The US Centers for Disease Control and Prevention has determined there is insufficient evidence on when it is safe to resume breastfeeding.[56] The same caveats likely apply to Marburg virus infection, though there are no studies of breast milk or breastfeeding in Marburg virus disease to provide evidence-based guidelines.

children

Plus – nutrition

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Treatment recommended for ALL patients in selected patient group

Children should be managed by teams of healthcare workers with paediatric expertise, and early involvement of intensivists has been advocated whenever feasible.[50]

Nutrition should be a high priority in children with filovirus disease, using prepared or ready-to-use therapeutic food, and treating malnourished children according to therapeutic feeding protocols for acute malnutrition.[51]

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Marburg virus infection

Treatment algorithm

all patients

Primary options

Secondary options

Primary options

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