Treatment algorithm

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

symptomatic patients

1st line – isolation and infection control

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symptomatic patients
1st line – 

isolation and infection control

All SAHFs are notifiable diseases to the relevant public health authority.

Symptomatic patients identified as being at risk of having SAHF should be admitted to a healthcare facility with appropriate isolation capabilities (including private bathroom facilities) and good supportive care, where possible.

All healthcare workers attending the patient should have full personal protective equipment (PPE) available to them, and be trained in using it.[32]​ PPE should be used in any contact with the patient or items belonging to them. All items (e.g., clothes, bed linen) and waste should be considered contaminated and disposed of accordingly. The World Health Organization (WHO), United Nations International Children's Emergency Fund (UNICEF), US Centers for Disease Control and Prevention (CDC), and NHS England have published guidance on PPE.

WHO: how to put on and how to remove personal protective equipment (PPE) Opens in new window​​​

CDC: guidance on personal protective equipment (PPE) for evaluating patients suspected to have selected viral hemorrhagic fevers who are clinically stable and do not have bleeding, vomiting, or diarrhea Opens in new window

NHS England: addendum on high consequence infectious disease (HCID) personal protective equipment (PPE) Opens in new window

UNICEF: viral haemorrhagic fevers personal protective equipment specifications note Opens in new window​​​​

Specimens for laboratory investigations should be collected and sent to an approved laboratory with suitable facilities for testing samples for potential biosafety level 4 pathogens, in accordance with local and national policies for high-risk samples and with clear labelling of the specimen to protect laboratory workers. Samples being sent for local testing, such as FBC and biochemistry, should also be clearly labelled. WHO has published guidance on handling blood samples containing highly infectious pathogens. WHO: how to safely collect blood samples from persons suspected to be infected with highly infectious blood-borne pathogens (e.g., Ebola) Opens in new window

Minimising invasive investigations and repeated venepuncture may be achieved by siting a central venous line early in the course of the disease.

Nosocomial transmission of SAHFs has mainly been documented in Bolivian haemorrhagic fever, and occasionally in Argentine haemorrhagic fever.[2][5] Laboratory transmission has been described for Brazilian haemorrhagic fever.[9] Although nosocomial transmission appears less common than in the filoviral haemorrhagic fevers (e.g., Ebola and Marburg), there remains a small risk of infection with a pathogen that causes severe disease and high mortality rates. For this reason full PPE is advised.[5]

Plus – oral or intravenous fluids

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symptomatic patients
Plus – 

oral or intravenous fluids

Treatment recommended for ALL patients in selected patient group

The mainstay of care for all symptomatic patients with SAHFs is supportive, which includes fluid replacement (i.e., for dehydration or shock) and symptom management.[32]

Replacement of fluid and electrolytes is essential to management and should be undertaken diligently with close monitoring of input and output and electrolyte status.

Oral rehydration solutions may be adequate for this purpose in patients who only have mild features of dehydration and are able to tolerate oral fluids at an adequate volume.

For those who are more severely dehydrated or not tolerating oral fluids, intravenous fluids such as 0.9% saline or Hartmann’s solution/lactated Ringer’s, are recommended. Consideration should be given to electrolyte replacement in the context of severe or persistent derangement on monitoring.

There is no specific guidance for the management of children or pregnant women; however, due consideration should be given to amending fluid volumes and fluid type accordingly for these populations.

Plus – analgesia/antipyretic

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symptomatic patients
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analgesia/antipyretic

Treatment recommended for ALL patients in selected patient group

There are currently no specific guidelines for the management of SAHFs; therefore, symptom management should be undertaken in accordance with local guidelines.

An analgesic/antipyretic (e.g., paracetamol) may be given for fever and pain.

Non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated due to their propensity to increase bleeding and the risk of nephrotoxicity, particularly in the context of dehydration.

There is no specific guidance for the management of children or pregnant women; however, due consideration should be given to amending treatments accordingly for these populations.

Primary options

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

Plus – antiemetic

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symptomatic patients
Plus – 

antiemetic

Treatment recommended for ALL patients in selected patient group

There are currently no specific guidelines for the management of SAHFs; therefore, symptom management should be undertaken in accordance with local guidelines.

Antiemetics may be considered for nausea and vomiting, in accordance with local protocols and availability.

There is no specific guidance for the management of children or pregnant women; however, due consideration should be given to amending treatments accordingly for these populations.

Plus – consider broad-spectrum antibiotic

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symptomatic patients
Plus – 

consider broad-spectrum antibiotic

Treatment recommended for ALL patients in selected patient group

Identification of sepsis should be made in a timely fashion.

Antibiotics should be administered promptly if sepsis is suspected as a differential diagnosis or concomitant aetiology.

Appropriate antibiotics will be dictated by local protocols, but should be broad-spectrum and include cover for gram-negative organisms (such as a third generation cephalosporin), under the assumption of possible gut translocation.

Plus – consider convalescent plasma

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symptomatic patients
Plus – 

consider convalescent plasma

Treatment recommended for ALL patients in selected patient group

May be considered in Argentine haemorrhagic fever only.

Convalescent plasma (i.e., from the blood of patients immune to the disease) is only available in the endemic areas of Argentina and Bolivia.

It has been used for treating Argentine haemorrhagic fever for several decades. However, it is now in short supply due to a significant reduction of cases following the introduction of the Candid#1 vaccine.[4][5]

Convalescent plasma should be administered within 8 days of the onset of symptoms in Argentine haemorrhagic fever to obtain maximum benefit.[4]

Convalescent plasma has only been studied in Argentine haemorrhagic fever. A randomised, placebo-controlled trial was undertaken from 1974 to 1978 and demonstrated a reduction in mortality from 16.5% in the placebo arm (normal plasma infused) to 1.1% in the treatment arm (immune plasma infused).[4] The original dose administered was one 500 mL infusion of immune plasma given within the first 8 days since symptom onset. However, large variations were found in the concentration of antibodies in immune plasma being collected from Argentine haemorrhagic fever survivors. For this reason attempts were made to standardise the dose of antibody received from immune plasma.[4] Studies assessing outcomes based on antibody concentration in immune plasma have concluded that a dose of 3500 ‘therapeutic units’ of neutralising antibodies per kilogram bodyweight should be administered.[4]

Administration of convalescent plasma in the context of Argentine haemorrhagic fever has been associated with the development of late neurological syndrome (LNS) with features including febrile episodes, cerebellar signs, and cranial nerve palsies in approximately 10% of patients. This syndrome is more likely to develop if immune plasma is administered more than 8 days from onset of symptoms.[4]

In trials involving non-human primates with Bolivian haemorrhagic fever, LNS has been shown to develop following administration of convalescent plasma, similar to that described in human patients receiving convalescent plasma for Argentine haemorrhagic fever. In one study, 3 of 4 primates that developed LNS succumbed to death after clinical signs of Bolivian haemorrhagic fever had subsided. A further study in rhesus monkeys identified a lethal chronic neurological disease, which 6 animals succumbed to following treatment with convalescent plasma.[2]

Convalescent plasma has also been used in clinical cases of Bolivian haemorrhagic fever, but there are no clinical data on safety or efficacy.[2] Furthermore, supply may not be readily available.

Plus – consider ribavirin

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symptomatic patients
Plus – 

consider ribavirin

Treatment recommended for ALL patients in selected patient group

Ribavirin can be considered in the management of Argentine, Bolivian, and Brazilian haemorrhagic fever as a few studies have suggested a beneficial effect; however, the evidence for its use in these diseases is weak.[2][4][9][34]

In one study, ribavirin was given to patients with Argentine haemorrhagic fever who had symptoms for longer than 8 days prior to presentation and who were outside the therapeutic window for convalescent plasma. This study did not reveal a significant improvement in survival, with mortality rates in the treatment arm of 28.6%.[4] While survival was not improved, there was evidence for an antiviral effect, with viral titres falling to undetectable within 4 days of commencing treatment.[4]

Ribavirin has also been administered in Bolivian haemorrhagic fever, but only in a limited number of patients so efficacy has not been established. Early studies do, however, show promise.[2][37]

A case of Brazilian haemorrhagic fever, managed in the US, was treated with ribavirin with apparent good effect; the patient became afebrile and asymptomatic 48 hours into treatment with undetectable virus by blood culture.[9] A study evaluating ribavirin for the treatment of Argentine haemorrhagic fever in a guinea pig model has shown significant reductions in mortality rate.[36]

Earlier treatment (within the first 8 days of symptoms) with ribavirin may prove beneficial for SAHFs, but this has not been fully investigated in trials involving humans.

Ribavirin may be considered in children with SAHF.

Ribavirin is teratogenic and should not be administered to pregnant women. Furthermore, ribavirin should be avoided in women who are lactating and wish to continue breastfeeding, although in this context the potential benefit to the patient must be weighed against the risk to the infant of stopping breastfeeding. Women of childbearing age who receive ribavirin as treatment should be advised not to conceive during, and for at least 4-6 months following, treatment and should be provided with effective contraception during this time. Men who receive ribavirin should be advised to use effective contraception during, and for 6-7 months following, treatment, and also if their partners are pregnant.

Primary options

ribavirin: children and adults: 33 mg/kg intravenously as a loading dose, followed by 16 mg/kg every 6 hours for 4 days, then 8 mg/kg every 8 hours for 6 days

Plus – platelet/plasma transfusion

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symptomatic patients
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with haemorrhagic disease
Plus – 

platelet/plasma transfusion

Treatment recommended for ALL patients in selected patient group

Haemorrhagic disease is found in approximately 30% of patients with SAHF.[2][4][5][6]

Haemorrhagic disease resulting from SAHF is not consistent with disseminated intravascular coagulation (DIC); therefore, management does not follow the standard management of DIC. Haemorrhage is thought to result from thrombocytopenia, abnormal platelet function, alteration of levels of coagulation factors (depletion of factors VIII and IX, increase in factor V and von Willebrand factor), and activation of fibrinogen.[3][4]

Transfusion of platelets is indicated in the context of thrombocytopenia and active haemorrhage, in accordance with local protocols.

Further management with fresh frozen plasma may also be appropriate in the context of active haemorrhage, in accordance with local protocols.

There is no evidence for the benefit or harm of replacement of clotting factors, where these may be available.

Plus – anticonvulsant

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symptomatic patients
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with seizures
Plus – 

anticonvulsant

Treatment recommended for ALL patients in selected patient group

Approximately 20% to 30% of patients progress to severe neurological symptoms, including seizures.[2][4][5][6]

There are currently no specific guidelines for the management of SAHFs; therefore, neurological symptoms such as seizures should be managed in accordance with local guidelines.

An anticonvulsant should be used to control seizures in accordance with local protocols and availability.

Plus – antimalarial therapy

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symptomatic patients
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with malaria co-infection
Plus – 

antimalarial therapy

Treatment recommended for ALL patients in selected patient group

Patients should be tested for malaria if presenting from a malaria-endemic area.

Those with malaria co-infection should be treated with appropriate antimalarial therapy for the region which they have been resident in, taking into account local sensitivities. See Malaria.

Plus – empirical antibiotic therapy + fluid resuscitation + airway management + consideration for intensive care

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symptomatic patients
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with confirmed sepsis
Plus – 

empirical antibiotic therapy + fluid resuscitation + airway management + consideration for intensive care

Treatment recommended for ALL patients in selected patient group

Identification of sepsis should be made in a timely fashion.

Management of sepsis should be in accordance with standard local guidelines with appropriate antibiotic therapy for the offending pathogen, attention to fluid resuscitation, airway management, and maintaining adequate urine output. See Sepsis in adults.

Consideration should be given to intensive care support if required, and if facilities are available.

Plus – consideration for intensive care

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symptomatic patients
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with multi-organ failure
Plus – 

consideration for intensive care

Treatment recommended for ALL patients in selected patient group

While renal and hepatic impairment are less common in the SAHFs when compared with filoviral disease, approximately 20% of patients may progress to advanced disease with multi-organ failure.[2][3][4][5]

Although the evidence for intensive care is lacking in this specific disease context, the benefits where organ support is required are self-explanatory and intensive care management of patients with Ebola has shown significant improvement in survival rates.[31]

Where the facilities are available and it is safe for healthcare workers to do so, intensive care should be given due consideration for SAHFs.

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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

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