Haemorrhagic fever

Haemorrhagic fever (arenaviruses, filoviruses, bunaviruses, flaviviruses) are a group of diseases of various viral etiology, characterized by high mortality, in the course of which fever, massive bleeding from mucous membranes, edema and lowering blood pressure are observed.

Haemorrhagic fever – epidemiology

The reservoir and source of infection for humans are usually rodents, but they can also be mosquitoes and ticks (tab. 38.16). Haemorrhagic fever is highly infectious, which, with a relatively short incubation period and non-specific initial symptoms, causes the disease to spread rapidly in the form of epidemic outbreaks. Transmission between humans is usually by droplet infection, which has also been confirmed in other primates. The possibility of infection related to blood donation cannot be excluded.

Of all the hemorrhagic fevers, dengue disease is the most common in Southeast Asia. Up to a million people suffer from it annually. In turn, yellow fever, despite the popularization of vaccinations, remains a serious problem in South America and Africa, where it is detected annually in over 200. people.

Lassa fever was first diagnosed in 1969 in Nigeria. Every year, up to 300 people suffer from it. people, mainly in West Africa, and infection usually occurs through contact with the excreta of small rodents that constitute the virus reservoir. Infections with other viruses from the arenavirus family occur in the form of minor epidemics in South America.

Single epidemic outbreaks of Rift Valley fever are reported in Africa, and Crimean Congo fever in Africa, Asia and Southern Europe. In turn, infections with hantaviruses are particularly common in Asia, where up to 200 people suffer from disease syndromes associated with infections with viruses from this family each year. people. The highest mortality rate, reaching even 80%, is characterized by Ebola virus infections, which occur in the form of sporadic outbreaks in the Democratic Republic of Congo and Sudan, and less frequently in Gabon, Côte d’Ivoire and Uganda. Due to its extremely high infectivity, it spreads particularly quickly in hospitals, including personnel.

Haemorrhagic fever is extremely rare in Europe and North America, and if it does occur, it is in people who have recently returned from endemic areas or who have come into contact with sick people or with infectious material. The most frequently detected infection among GK in travelers is Lassa fever. Despite the theoretical risk and repeated suspicions, Ebola virus infections have not yet been confirmed in Europe and the USA. Single infections with the Marburg virus were recorded in 1967 in Germany, when the disease was first identified.

The causes of hemorrhagic fever

Haemorrhagic fever can be caused by viruses belonging to four different families: Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae. The systematics of these families and disease entities caused by individual virus species are presented in Table 38.17.

The mechanism of the development of hemorrhagic fever

Haemorrhagic fever viruses have a special affinity for vascular walls, multiplying in endothelial cells. However, most disease symptoms result from the release of various inflammatory mediators by other infected cells, such as monocytes and macrophages. It causes secondary impairment of vascular function and coagulation disorders. Initially, there is usually slight vascular damage that does not cause extravasation. Later, mucosal bleeding may occur, with first pressure drop, then shock, and finally collapse.

In the acute phase of the disease, viremia is accompanied by the release of biologically active substances, among which cytokines predominate. The resulting increased vascular permeability is the pathogenetic basis of the viral symptomatology of hemorrhagic fever. Due to the very intensive replication of viruses, an inadequate and delayed immune response as well as intense macrophage activity can usually be observed. As a result of damage to blood vessels, coagulation disorders, increased inflammation and stimulation of necrotic processes, multi-organ failure occurs.

Clinical symptoms of hemorrhagic fever

The initial symptoms of the disease are not very specific and usually include:

1. fever,
2. tiredness,
3. headaches,
4. stomach pain,
5. muscle aches.

In some cases, reddening of the skin and mucous membranes, dilation of the conjunctival vessels, ecchymosis and edema appear during this period. Later, bloody vomiting and diarrhea may occur, as well as systemic mucosal bleeding. Additionally, coagulation disorders and symptoms of bone marrow damage may occur. In the final stage of the disease, hepatic, renal, circulatory and respiratory failure as well as impaired consciousness and collapse are observed.

Course of illness

The shortest incubation period is 2-5 days in the Rift Valley GK and the longest 9-35 days in hantavirus infections. The length of the incubation period as well as the clinical course of the disease depend on the virus species and the massiveness and route of infection. Most GK viruses reveal skin changes related to the instability of the vessel walls, such as redness, ecchymosis, ecchymosis, bruising and swelling.

1. In the course of Lassa hemorrhagic fever, edema is particularly intensified, with no symptoms of bleeding. On the other hand, other arenaviruses (responsible for GK occurring in South America) cause less severe edema with the simultaneous occurrence of various hemorrhagic symptoms. Massive bleeding is observed in the course of the Crimean Congo GK.
2. Hantaviruses cause characteristic petechial skin lesions around the neck, as well as around the armpits, arms and torso. In milder cases, erythematous changes, similar to sunburn, may be found on the head, neck and trunk. They may be accompanied by facial swelling. It happens that the skin lesions resemble a measles rash. In severe cases, there is bleeding from the oral mucosa and from the conjunctiva. Hantavirus infection is usually accompanied by the development of one of two clinical syndromes: haemorrhagic fever with renal syndrome (HFRS) or hantavirus cardio-pulmonary syndrome (HCPS).
3. Filoviruses (Marburg and Ebola) cause the most severe course of the disease. Usually, redness of the palate and throat is accompanied by prodromal pseudo-flu symptoms. After 5-7 days, a papular rash appears, located in the center. Patients do not report pruritus, but lesions transform into large, well-delimited and confluent maculopapular lesions, often haemorrhagic in nature, within 24 hours. In severe forms, which constitute the majority of cases of these GK, there is bleeding from the mucous membranes, from needle puncture sites and from natural body orifices. Rashes with characteristic islands of unchanged skin are observed in the course of dengue fever.

Vascular changes appearing on the skin and mucous membranes are usually accompanied by multi-organ failure of the hematopoietic, nervous and respiratory systems. The degree of liver damage depends on the type of hemorrhagic fever virus and is most severe in infections:

1. Ebola viruses,
2. Marburg,
3. valley fever
4. Rift,
5. the Crimean Congo GK,
6. yellow fever.

Renal failure with oliguria is the predominant symptom of haemorrhagic fever with renal syndrome in the course of hantavirus infection, but may occur in other GKs due to profound hypovolemia resulting from blood loss. Bleeding complications are most severe in Ebola and Marburg virus infections, Crimean Congo haemorrhagic fever and arenavirus-induced South American GK.

How to recognize a hemorrhagic fever?

The diagnosis of the first disease in an epidemic is very difficult due to the non-specificity of symptoms. Only the onset of hemorrhagic symptoms, especially when they appear in a greater number of patients in a short time, facilitates the diagnosis. It should be remembered that due to the high infectivity, all laboratory procedures should be limited to the necessary minimum and performed with extreme caution.

Laboratory tests usually show leukopenia and thrombocytopenia. High levels of transaminases are most often found in patients infected with arenaviruses, and in the course of Lassa it is a symptom indicating a serious threat to life.

Characteristic is the prolongation of the prothrombin time and the coagulation time, with the simultaneous symptoms of intravascular coagulation expressed by a decrease in fibrinogen concentration, thrombocytopenia and the appearance of fibrinogen degradation products. Most patients show high levels of viral load during the clinical symptom period, which can be detected by RT-PCR. However, a greater practical application is the detection of specific antibodies by enzyme immunoassay.

Differentiation of hemorrhagic fever from other ailments

Among the disease entities with which GK should be differentiated, it is primarily disseminated intravascular coagulation syndrome (disseminated intravascular coagulation – DIC) of a different etiology. In patients with symptoms of renal failure and hemorrhagic diathesis, the possibility of development should be considered hemolytic uremic syndrome. If a trip to the regions of occurrence is mentioned in the interview dab, it should also be taken into account in the difference proceedings. Moreover, bloody diarrhea in febrile patients requires differentiation from Salmonella or Shigella infections.

Haemorrhagic fever and treatment

It dominates the medical procedure symptomatic treatment, consisting in supplementing water and electrolyte deficiencies, and in cases of bleeding, also blood and blood products. Do not use intramuscular injections and take anticoagulants. Patients should be isolated, preferably in rooms equipped with systems filtering the air flowing outside. Moreover, patients who cough, patients with vomiting, diarrhea or bleeding should be isolated in negative pressure rooms.

To date, no specific treatment for Ebola and Marburg infections is known. In isolated cases of Ebola hemorrhagic fever, attempts have been made to use serum from convalescents. In most cases, this allowed the patients to survive, but so far no controlled studies have been conducted in this field that could clearly confirm the effectiveness and safety of such a procedure. There have also been attempts to treat hantavirus and GK Lassa infections with orally or intravenously administered ribavirin. The observations so far confirm its effectiveness in the early stage of the disease, preferably within the first 6 days after the onset of symptoms.

Can hemorrhagic fever be prevented?

In order to reduce the risk of infection in endemic regions, it is advisable to take educational activities among the population, aiming to reduce contact with animals constituting the reservoir of GK viruses (rodents, mosquitoes). Prevention of GK Ebola and Marburg is hampered by an unknown reservoir.

Introducing isolation and security measures in places where patients stay can effectively reduce the number of new cases. In outbreaks, a significant proportion of the sick and deceased are usually medical personnel. For this reason, medical personnel should follow special strict rules when dealing with patients with hemorrhagic fever:

1. only the necessary number of doctors and nurses should be involved in the care;
2. in rooms for patients, the staff should use special protection in the form of gloves, glasses with side shields, surgical masks, and in the event of exposure to the secretions and excretions of patients, masks with HEPA filters as well as coveralls covering the whole body, including legs and feet should be used ;
3. all these protections should be removed before entering public spaces.

A safe and effective vaccine against yellow fever is widely used. Vaccines against Argentine haemorrhagic fever (also protects against Bolivian GK), Riftu valley GK and hantaviruses have also been developed, although not widely used. Research into an effective and safe vaccine against GK Ebola and dengue in humans is still ongoing.

What’s the prognosis?

Complications of Rift Valley hemorrhagic fever include inflammation of the retina, testes, brain and liver. Deafness was often observed after GK Lassa had undergone surgery. Hantavirus infection is usually associated with kidney failure. The highest mortality rate, exceeding 80% during some epidemics, is recorded in the course of Ebola CG. Mortality in other hemorrhagic fevers is lower, although infection with any of the GK viruses should always be treated as a serious threat to the patient’s life and a serious epidemiological threat to the environment.

Summation

1. Haemorrhagic fever are ailments of various viral etiology and high infectivity. Their common feature in the clinical picture is bleeding.

2. Haemorrhagic fever most often manifests as epidemic outbreaks in Asia, Africa and South America. Single cases of disease can be brought to the USA and Europe.

3. The pathomechanism of infection with haemorrhagic fever viruses is associated with damage to endothelial cells in which viruses multiply, as well as the release of various mediators by monocytes and macrophages, which secondary to vascular dysfunction and coagulation disorders.

4. The disease begins with non-specific symptoms, such as: fever, fatigue, headaches, abdominal pain and muscle aches, accompanied by reddening of the skin and mucous membranes, dilation of the conjunctival vessels, ecchymosis and edema. In severe clinical forms, bleeding and symptoms of multiple organ failure appear after a few days.

5. Cause of death in hemorrhagic fevers is usually massive haemorrhage, circulatory failure, and vascular collapse. Mortality in some of the described epidemics reached 80%. The management taking into account the high infectivity of the disease, justifying isolation, is based on symptomatic treatment and supplementation of water and electrolyte deficiencies and blood. Ribavirin may be effective in some haemorrhagic fevers, but needs to be confirmed in further studies.

6. Yellow fever prophylaxis is based on vaccination, while for other haemorrhagic fever effective vaccines are not yet widespread or are under development.

Literature

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2. Mahanty S., Bray M.: Pathogenesis of filoviral haemorrhagic fevers, Lancet Infect Dis 2004; 4: 487-498.

3. Marty A.M., Jahrling P.B., Geisbert T.W.: Viral hemorrhagic fevers, Clin Lab Med 2006; 26: 345-386.

4. Cleri D.J., Ricketti A.J., Porwancher R.B., Ramos-Bonner L.S., Vernaleo J.R.: Viral hemorrhagic fevers: current sta tus of endemic disease and strategies for control,Infect Dis Clin North Am 2006; 20: 359-393.

5. Tomashek K.M., Margolis H.S.: Dengue: a potential transfusiontransmitted disease, Transfusion 2011; 51: 1654-1660.

Source: J. Cianciara, J. Juszczyk, Infectious and parasitic diseases; Czelej Publishing House