Marburg virus infection is a notifiable disease. The case definition for Marburg virus infection is broad and includes a long list of possible differential diagnoses.
The initial assessment of a patient with suspected Marburg virus infection hinges on two main factors:[18]Centers for Disease Control and Prevention. Case definition for Ebola virus disease (EVD). Feb 2023 (internet publication].
https://www.cdc.gov/vhf/ebola/clinicians/evaluating-patients/case-definition.html
[19]World Health Organization. Ebola and Marburg virus disease epidemics: preparedness, alert, control, and evaluation. Aug 2014 [internet publication].
https://apps.who.int/iris/handle/10665/130160
Epidemiological risk (e.g., living or working in, or travel to, an endemic area in previous 21 days; or laboratory exposure); and
Presence or history of a high fever in the past 48 hours.
Isolation and personal protective equipment (PPE)
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 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.[18]Centers for Disease Control and Prevention. Case definition for Ebola virus disease (EVD). Feb 2023 (internet publication].
https://www.cdc.gov/vhf/ebola/clinicians/evaluating-patients/case-definition.html
[20]Fletcher TE, Brooks TJ, Beeching NJ. Ebola and other viral haemorrhagic fevers. BMJ. 2014 Aug 11;349:g5079.
http://www.bmj.com/content/349/bmj.g5079
http://www.ncbi.nlm.nih.gov/pubmed/25113010?tool=bestpractice.com
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:
The WHO also produces detailed infection-control guidance for healthcare workers in viral haemorrhagic fever outbreak settings:
History
A detailed history can clarify the risk for Marburg virus infection and other acute febrile syndromes.
People living or working in endemic areas (Central and Eastern Africa) or working with Marburg virus or virus-carrying monkeys in a laboratory setting are at the highest risk of infection.[21]Centers for Disease Control and Prevention. Marburg (Marburg virus disease). Feb 2023 [internet publication].
https://www.cdc.gov/vhf/marburg
Recent arrival (within 21 days) from endemic areas is also an important risk factor. Visiting caves or mines inhabited by African fruit bat (Rousettus aegyptiacus) colonies increases suspicion of Marburg virus infection in symptomatic patients.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
In developed countries, most patients with suspected infection will be returning travellers, healthcare workers who have cared for patients during outbreaks, or laboratory workers with occupational exposure. Therefore, a comprehensive history of travel, work, and attendance of burials or funerals is extremely important. Knowledge of the geographical locations of active or prior epidemics helps to clarify the patient's epidemiological risk.
High-risk occupations include those where people work with primates or bats from endemic areas or with high-risk clinical samples, and healthcare or laboratory workers in endemic or outbreak settings.
As malaria is still the most common cause of febrile illness in returning travellers from Africa, the presence of risk factors for acquiring malaria should be assessed (e.g., living/working in, or travelling to, endemic area; inadequate or absent chemoprophylaxis; not using insecticides or bed nets).[22]Mendelson M, Han PV, Vincent P, et al. Regional variation in travel-related illness acquired in Africa, March 1997-May 2011. Emerg Infect Dis. 2014 Apr;20(4):532-41.
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24655358
http://www.ncbi.nlm.nih.gov/pubmed/24655358?tool=bestpractice.com
However, co-infection with malaria and viral haemorrhagic fever does occur, and known or suspected diagnosis of malaria does not exclude a possible diagnosis of Marburg virus infection.[23]Gignoux E, Azman AS, de Smet M, et al. Effect of artesunate-amodiaquine on mortality related to Ebola virus disease. N Engl J Med. 2016 Jan 7;374(1):23-32.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504605
http://www.ncbi.nlm.nih.gov/pubmed/26735991?tool=bestpractice.com
Exposure risk
Contacts of infected patients (including healthcare workers and household contacts) are at risk of infection if the person was exposed to body fluids of the infected patient without appropriate protective equipment. The incubation period after infection is typically 5 to 10 days.[1]Centers for Disease Control and Prevention. Marburg haemorrhagic fever fact sheet. Dec 2014 [internet publication].
http://www.cdc.gov/vhf/marburg/pdf/factsheet.pdf
[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
Brief interactions, such as walking by an infected person or through a hospital, do not constitute close contact.
Contact is defined by the WHO as someone who has:[24]World Health Organization. Case definition recommendations for Ebola or Marburg virus disease. Aug 2014 [internet publication].
https://apps.who.int/iris/handle/10665/146397
Slept in the same household as a patient
Had direct physical contact with the patient during the illness or at the funeral
Touched the patient's body fluids or clothes/bed linens during the illness or soon after death, including washing clothes soiled during the illness
Been breast-fed by the patient (babies).
Other infection risks include exposure to dead or sick animals, caves, or mines in endemic areas, and laboratory contacts.[24]World Health Organization. Case definition recommendations for Ebola or Marburg virus disease. Aug 2014 [internet publication].
https://apps.who.int/iris/handle/10665/146397
In endemic areas, viral transmission may occur from animals to humans even without a notable bite or scratch.[25]van Paassen J, Bauer MP, Arbous MS, et al. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012 Aug;12(8):635-42.
http://www.sciencedirect.com/science/article/pii/S147330991270018X
http://www.ncbi.nlm.nih.gov/pubmed/22394985?tool=bestpractice.com
Case definitions for Ebola virus and Marburg virus can be found on the WHO website:
Symptoms
The incubation period after infection is typically 5 to 10 days, although some estimates range from 2 to 26 days.[11]Pavlin BI. Calculation of incubation period and serial interval from multiple outbreaks of Marburg virus disease. BMC Res Notes. 2014 Dec 13;7:906.
http://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-7-906
http://www.ncbi.nlm.nih.gov/pubmed/25495697?tool=bestpractice.com
[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
Patients are not considered infectious until they develop symptoms.
The initial presentation is non-specific, which makes early clinical diagnosis difficult; however, typical symptoms include:[1]Centers for Disease Control and Prevention. Marburg haemorrhagic fever fact sheet. Dec 2014 [internet publication].
http://www.cdc.gov/vhf/marburg/pdf/factsheet.pdf
[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
Three phases of illness are typically recognised, starting with a few days of high fever, headache, myalgia, and malaise, and followed by a gastrointestinal phase where anorexia, diarrhoea, vomiting, abdominal pain, and dehydration are prominent.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
Other symptoms may include conjunctivitis and rash on the mucous membranes.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
In the second phase, the patient may either recover, or deteriorate with a third phase of illness which includes collapse, neurological manifestations, and bleeding and generalised rash in some patients. Fatalities often occur during this phase, approximately day 8 to 16 of illness.[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
[26]Chertow DS, Kleine C, Edwards JK, et al. Ebola virus disease in West Africa - clinical manifestations and management. N Engl J Med. 2014 Nov 27;371(22):2054-7.
http://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
Physical examination
A full physical examination should be undertaken with the aim of excluding a clear alternative diagnosis while looking for signs of viral haemorrhagic fever (e.g., conjunctival injection, purpuric rash, or other signs of bleeding). Note that Marburg virus disease is a multi-phase illness first presenting with fever and non-specific symptoms, and later progressing to include febrile gastrointestinal symptoms. It is important to note that not all patients will have signs or symptoms of bleeding or coagulopathy.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
[26]Chertow DS, Kleine C, Edwards JK, et al. Ebola virus disease in West Africa - clinical manifestations and management. N Engl J Med. 2014 Nov 27;371(22):2054-7.
http://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
Vital signs should be taken:
Fever: the presenting symptom in most patients, its presence is enough to raise concern for infection in the appropriate epidemiological context. Wide variations in body temperature can be observed during the course of illness with normothermia or hypothermia occurring in the later stages of fatal infection. High fever (>40°C [104°F]) is common.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
Blood pressure: hypotension is a feature of dehydration and shock and is present in later-stage disease.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
It is under-documented in field studies owing to a lack of measuring equipment in endemic areas.[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
Pulse rate: bradycardia may be present in the initial stages of illness; however, tachycardia may be seen in the later stages of infection.[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
Respiratory rate: tachypnoea may be present in later stages of illness, resulting from metabolic acidosis.[25]van Paassen J, Bauer MP, Arbous MS, et al. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012 Aug;12(8):635-42.
http://www.sciencedirect.com/science/article/pii/S147330991270018X
http://www.ncbi.nlm.nih.gov/pubmed/22394985?tool=bestpractice.com
Initial investigations
All specimens should be collected according to the same strict protocols as those for Ebola virus. The CDC and WHO have published guidance on this:
The main confirmatory test for Marburg virus infection is a positive reverse transcriptase polymerase chain reaction (RT-PCR) for Marburg virus from blood or oral (buccal membrane) swab.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
This test should be ordered in all patients with suspected Marburg infection while the patient is in isolation. It has the advantage of returning a result 4 to 48 hours before ELISA testing.[27]Grolla A, Jones SM, Fernando L, et al. The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg outbreak in Angola. PLoS Negl Trop Dis. 2011 May;5(5):e1183.
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001183
http://www.ncbi.nlm.nih.gov/pubmed/21629730?tool=bestpractice.com
In high-resource settings, the test may only be available in regional or national laboratories which have biosafety level 4 facilities.[28]Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar 5;377(9768):849-62.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406178
http://www.ncbi.nlm.nih.gov/pubmed/21084112?tool=bestpractice.com
Viral RNA can be detected in the patient's blood by RT-PCR from as early as day 1 up to days 6 to 17 of symptom onset.[27]Grolla A, Jones SM, Fernando L, et al. The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg outbreak in Angola. PLoS Negl Trop Dis. 2011 May;5(5):e1183.
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001183
http://www.ncbi.nlm.nih.gov/pubmed/21629730?tool=bestpractice.com
[29]Roddy P, Thomas SL, Jeffs B, et al. Factors associated with Marburg hemorrhagic fever: analysis of
patient data from Uige, Angola. J Infect Dis. 2010 Jun 15;201(12):1909-18.
http://jid.oxfordjournals.org/content/201/12/1909.long
http://www.ncbi.nlm.nih.gov/pubmed/20441515?tool=bestpractice.com
A positive PCR result implies that the patient is potentially infectious, particularly in the presence of active diarrhoea, vomiting, or bleeding. If negative, the test should be repeated within 48 hours since viral load is low and can be undetectable early in the course of the illness. Negative tests should be repeated at least 72 hours into infection to rule out a diagnosis if it is strongly suspected (or confirm resolution of infection).[27]Grolla A, Jones SM, Fernando L, et al. The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg outbreak in Angola. PLoS Negl Trop Dis. 2011 May;5(5):e1183.
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001183
http://www.ncbi.nlm.nih.gov/pubmed/21629730?tool=bestpractice.com
[29]Roddy P, Thomas SL, Jeffs B, et al. Factors associated with Marburg hemorrhagic fever: analysis of
patient data from Uige, Angola. J Infect Dis. 2010 Jun 15;201(12):1909-18.
http://jid.oxfordjournals.org/content/201/12/1909.long
http://www.ncbi.nlm.nih.gov/pubmed/20441515?tool=bestpractice.com
It is likely that higher viral load correlates with adverse outcomes and increased mortality.[30]Leligdowicz A, Fischer WA 2nd, Uyeki TM, et al. Ebola virus disease and critical illness. Crit Care. 2016 Jul 29;20(1):217.
http://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1325-2
http://www.ncbi.nlm.nih.gov/pubmed/27468829?tool=bestpractice.com
Malaria is still the most common cause of fever in people who live, work, or travel to endemic areas.[22]Mendelson M, Han PV, Vincent P, et al. Regional variation in travel-related illness acquired in Africa, March 1997-May 2011. Emerg Infect Dis. 2014 Apr;20(4):532-41.
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24655358
http://www.ncbi.nlm.nih.gov/pubmed/24655358?tool=bestpractice.com
All people visiting a malarial area within the last one year should be tested for malaria and treated empirically for malaria if filovirus disease is suspected.[23]Gignoux E, Azman AS, de Smet M, et al. Effect of artesunate-amodiaquine on mortality related to Ebola virus disease. N Engl J Med. 2016 Jan 7;374(1):23-32.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504605
http://www.ncbi.nlm.nih.gov/pubmed/26735991?tool=bestpractice.com
In the case of a positive rapid diagnostic test result for malaria, the infection should be treated while continuing to assess the risk for Ebola or Marburg virus infection and noting the possibility of dual infection.
If Ebola or Marburg virus infection is suspected, it is recommended that appropriate confirmatory tests for Ebola and/or Marburg virus infection are performed before, or in tandem with, tests for other suspected conditions.
Other investigations
Traditionally, no other investigations outside of a malaria screen and RT-PCR were recommended due to the fear of putting laboratory workers at risk. However, it is now recognised that other investigations can be done with relative safety when performed according to recommended guidelines, including informing the laboratory in advance and treating all samples as potentially highly infectious. Local protocols should be clear about safe transport of samples to the local and referral laboratories, and safe handling on receipt in the local laboratory.
The following investigations add valuable information to the work-up and help guide further management, and should be ordered if possible. If investigations are limited by geographical location or facilities, the most important tests to order are renal function, serum electrolytes, and blood lactate.
Renal function and serum electrolytes:
Elevated serum creatinine or urea and abnormal electrolytes may indicate acute kidney injury. This may be seen after several days of infection.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
Hypokalaemia, due to vomiting and diarrhoea or acute kidney injury, was seen in approximately 50% of cases in the 1967 outbreak.[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
Hypocalcaemia has been associated with fatal infection. Haematuria and proteinuria may also be seen in severe disease. Oliguria that does not respond to fluid resuscitation is a poor prognostic sign.[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
[25]van Paassen J, Bauer MP, Arbous MS, et al. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012 Aug;12(8):635-42.
http://www.sciencedirect.com/science/article/pii/S147330991270018X
http://www.ncbi.nlm.nih.gov/pubmed/22394985?tool=bestpractice.com
Blood lactate:
Elevated lactate is a marker of tissue hypoperfusion and is an indicator of shock. It is useful in acutely ill patients with signs of sepsis to identify the degree of systemic hypoperfusion and to guide fluid resuscitation. Lactate-guided resuscitation has been documented in the care of patients with Ebola virus disease.[31]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
ABG:
Arterial or venous pH and bicarbonate are useful in acutely ill patients with signs of sepsis to identify the degree of systemic hypoperfusion and guide fluid resuscitation. Their use has been documented in the care of patients with Ebola virus disease.[31]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
FBC:
Decreasing platelet count and marked lymphopenia can be seen in the initial stages of infection; however, this is not diagnostic. This is often followed by neutrophil leukocytosis in the later stages of infection in patients who eventually recover, along with normalisation of thrombocytopenia. Leukocytosis may persist and show immature forms. Patients with severe disease may show a progressive decline in platelet count as a manifestation of disseminated intravascular coagulation (DIC). Decreased haemoglobin levels have been associated with bleeding in previous outbreaks.[12]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
[25]van Paassen J, Bauer MP, Arbous MS, et al. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012 Aug;12(8):635-42.
http://www.sciencedirect.com/science/article/pii/S147330991270018X
http://www.ncbi.nlm.nih.gov/pubmed/22394985?tool=bestpractice.com
Coagulation studies:
Prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT) is associated with more severe infection and bleeding manifestations such as DIC.[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
LFTs:
Both ALT and AST are usually elevated; however, AST may rise out of proportion to ALT, and this is more suggestive of systemic tissue damage rather than hepatocellular injury.[25]van Paassen J, Bauer MP, Arbous MS, et al. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012 Aug;12(8):635-42.
http://www.sciencedirect.com/science/article/pii/S147330991270018X
http://www.ncbi.nlm.nih.gov/pubmed/22394985?tool=bestpractice.com
Higher mean AST and AST:ALT ratio are associated with severe and fatal infection. Bilirubin, GGT, and ALP are often normal or slightly elevated. Highly elevated ALT with severe jaundice suggests an alternative diagnosis (e.g., viral hepatitis) or very late Marburg virus disease.[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
[25]van Paassen J, Bauer MP, Arbous MS, et al. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012 Aug;12(8):635-42.
http://www.sciencedirect.com/science/article/pii/S147330991270018X
http://www.ncbi.nlm.nih.gov/pubmed/22394985?tool=bestpractice.com
Serum amylase:
Elevated levels have been reported and indicate the presence of pancreatitis, an indicator of severe infection.[13]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6.
http://jid.oxfordjournals.org/content/204/suppl_3/S810.long
http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com
Blood cultures:
Negative blood cultures may be helpful in ruling out bacterial sepsis or enteric fever. Blood should be collected for culture at baseline and/or at the time of the onset of gastrointestinal symptoms or other clinical deterioration. Based on experience with Ebola virus disease, is recommended that all filovirus patients be treated with broad-spectrum antibiotics for possible gut bacteria translocation regardless of blood culture results.[32]Schieffelin JS, Shaffer JG, Goba A, et al. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med. 2014 Nov 27;371(22):2092-100.
http://www.nejm.org/doi/full/10.1056/NEJMoa1411680#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25353969?tool=bestpractice.com
Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing:
A useful diagnostic test with high specificity for filovirus IgM or IgG; however, it is not universally available and was rarely used in the 2014 to 2016 West Africa Ebola virus disease outbreak. ELISA for Marburg virus IgM may be positive as early as days 4 to 7 of infection, IgM levels peak 1 to 2 weeks later, and disappear by 1 to 2 months after convalescence.[33]Wulff H, Johnson KM. Immunoglobulin M and G responses measured by immunofluorescence in patients with Lassa or Marburg virus infections. Bull World Health Organ. 1979;57(4):631-5.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395825
http://www.ncbi.nlm.nih.gov/pubmed/118812?tool=bestpractice.com
Positive IgM or RT-PCR result can be used to confirm the diagnosis of acute Marburg virus disease.
IgG and IgM antibodies:
Useful in later stages of infection. An IgG response develops between day 6 and 18 and can persist for several years. A positive IgM or a rising IgG titre is strong evidence for recent Marburg virus infection.[33]Wulff H, Johnson KM. Immunoglobulin M and G responses measured by immunofluorescence in patients with Lassa or Marburg virus infections. Bull World Health Organ. 1979;57(4):631-5.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395825
http://www.ncbi.nlm.nih.gov/pubmed/118812?tool=bestpractice.com
[34]Deen GF, Broutet N, Xu W, et al. Ebola RNA persistence in semen of Ebola virus disease survivors - final report. N Engl J Med. 2017 Oct 12;377(15):1428-37.
http://www.nejm.org/doi/full/10.1056/NEJMoa1511410
http://www.ncbi.nlm.nih.gov/pubmed/26465681?tool=bestpractice.com