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Ebola

Pathogen:RNA viruses →filoviruses →Ebola virus
Transmission:Physical contact with infected animals, sick individuals or contaminated objects
Geographical range:Tropical Africa
Incidence:Periodic epidemics – over 25,000 cases in the 2014/2015 outbreak in West Africa

Case history

A 22-year old woman from Sierra Leone with an acute 39°C fever visited her physician five days after the onset of the fever. Her symptoms were characterised by general influenza-like symptoms: weakness, muscular and joint pain, headache and decreased appetite. Moreover, she complained about abdominal pain and diarrhea. At the time of visiting the physician, she was not bleeding and had no visible petechiae. A complete blood count with extended infection parameters was performed to investigate the possible cause of the infection.

Ebola virus disease pathophysiology and clinical course

The Ebola virus causes an acute, serious illness – Ebola virus disease (EVD). It is thought that fruit bats of the Pteropodidae family are natural Ebola virus hosts. Humans are infected through direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected animals such as chimpanzees, gorillas, fruit bats, and monkeys found ill or dead in the rainforest.

The incubation period is between 2 to 21 days. Humans are not infectious until they develop symptoms. The first symptoms are the sudden onset of fever, fatigue, muscle pain, headache and a sore throat. These early symptoms are followed by vomiting, diarrhoea, bleeding and symptoms of impaired kidney and liver function.

Ebola virus spreads from the initial infection site to the lymph nodes, liver, spleen and adrenal glands. The endothelial cells, liver cells, and several types of immune cells (monocytes, lymphocytes and dendritic cells) are the main targets of viral infection (1). Macrophages are among the first cells infected by the virus, and the infection results in programmed cell death (2). Macrophage infection leads to the production of pro-inflammatory cytokines, which may induce bystander apoptosis in lymphocyte populations, thereby contributing to lymphopenia and immunosuppression. IL-6 and macrophage-derived TNF-α also induces changes in vascular permeability. The production of tissue factor by infected macrophages leads to dysregulation of coagulation. Hepatocyte infection leads to decreased synthesis of liver-derived clotting factors. Infection of adrenal glands results in hypotension and metabolic disorders, which together with immunosuppression and coagulopathy contribute to multiple organ failure and shock (3). Thus the overall systemic body virus spread leads to hypovolemic shock, disseminated intravascular coagulation, and - if untreated - finally can lead to multiple organ dysfunction syndrome and death.

In acute disease, patients are extremely viremic, and there is evidence of messenger ribonucleic acid (mRNA) of multiple cytokine activation. In vitro studies reveal that these cytokines lead to shock and increased vascular permeability, the basic pathophysiological processes most often seen in viral haemorrhagic fever infection. Another prominent pathological feature is pronounced macrophage involvement. Inadequate or delayed immune response to these novel viral antigens may lead to rapid development of overwhelming viremia. Extensive infection and necrosis of affected organs also are described. Haemorrhagic complications are multifactorial and are related to hepatic damage, consumptive coagulopathy.

Phase I can be characterised as the transfer of the Ebola virus from an animal carrying the virus to a human, usually via small cutaneous lesions. Similar principles apply in human-to-human transmission during Ebola outbreaks. Phase II can be characterised as the early symptomatic stage — usually between days four and ten — where symptoms of a viral illness appear and gradually progress toward more advanced manifestations of the disease. Finally, Phase III represents the advanced Ebola virus disease, with haemorrhagic manifestations, impaired immunity, and end-organ failure.

Laboratory results

              

Day 1

Day 4

Blood countELISA IgM anti-Ebola(+)
ELISA IgG anti-Ebola(+)
 

Case interpretation

Blood analysis showed a mild leucopenia with a relatively high count of lymphocytes (LYMPH% = 45.4%),  a relatively low count of neutrophils (NEUT% = 49.7%) and slightly increased neutrophil activation (NEUT-RI = 53.3 ch).

The abnormal cell distribution in the upper area of the lymphocytes in the WDF scattergram triggered the flag ‘Atypical Lympho?’. The percentage of suspected reactive lymphocytes was increased (Re-LYMPH% = 13.6%), without an increased  AS-LYMPH (0%) but with a decreased W1/W2 ratio, indicating that the patient is undergoing a reactive cellular T cell immune response to a viral infection.

A decreased platelet count was found (PLT-F = 53 x 109/L) and together with the increased immature platelet fraction (IPF = 15.3%) and increased mean platelet volume (MPV = 13.5 fL) this is indicative of thrombocytopenia due to the consumption of platelets in the peripheral blood. It is a common phenomenon in severe viral infections. The high IPF also indicates normal bone marrow thrombopoiesis compensation. Haematocrit and haemoglobin were mildly increased (HCT = 0.439 L/L, HGB = 151 g/L). These findings indicate that the patient who shows an early symptomatic stage, could develop a dangerous haemorrhagic fever due to increased endothelial leakage.

Early diagnosis of Ebola is difficult because the early symptoms are nonspecific to Ebola infection; symptoms are also typical for more common African diseases such as malaria or typhoid fever. The classic early signs for Ebola in haematological laboratory findings are low white blood cell counts, low platelet counts and abnormalities in blood clotting. The presence of atypical, reactive lymphocytes, visible in the WDF and WPC scattergrams and an increased value of Re-LYMPH are often observed during early stages of viral infection, although non-specific for Ebola virus infection. Ebola infections have to be confirmed by more specific laboratory tests, detecting viral RNA or proteins. In this case the Ebola virus disease was confirmed three days later by the positive anti-Ebola IgG and IgM ELISA tests. However, these tests are sensitive enough only several days after the onset of symptoms when the rise in circulating virus within the patient's blood occurs. Thus the use of screening assays for early detection of viral infections during pandemics is essential. 

Literature

  1. Funk DJ, Kumar A (2015): Ebola virus disease: an update for anesthesiologists and intensivists. Can J Anaesth. 62(1):80-91
  2. Chippaux JP (2014): Outbreaks of Ebola virus disease in Africa: the beginnings of a tragic saga. J Venom Anim Toxins Incl Trop Dis. 20(1):44
  3. Mehedi M, Groseth A, Feldmann H, Ebihara H (2011): Clinical aspects of Marburg hemorrhagic fever. Future Virol. Sep;6(9):1091-1106.

Advanced clinical parameters

Reference ranges

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