OVERVIEW
Viral hemorrhagic fever is a group of natural epidemic diseases caused by arboviruses, with fever, hemorrhage and shock as the main clinical features. Viral hemorrhagic fever is widely distributed in the world, and more than ten kinds of viral hemorrhagic fever have been found, with different pathogens, hosts and transmission routes, and complicated clinical manifestations, some of which are serious and have high mortality rates. The common ones include Crimean-Congo hemorrhagic fever, Ebola hemorrhagic fever, Marburg hemorrhagic fever, Lassa fever, Rift Valley fever, Dengue hemorrhagic fever, renal syndrome hemorrhagic fever (formerly known as epidemiological hemorrhagic fever) and so on. Different viral hemorrhagic fevers are often prevalent in certain areas, with renal syndrome hemorrhagic fever predominating in China.
Confirmation of the diagnosis of various hemorrhagic fevers relies on pathogenetic and serologic tests. There is no specific treatment for any of these diseases. Symptomatic and supportive therapies are mainly used, with rehydration, correction of water and electrolyte imbalance, blood transfusion and anti-shock treatment when necessary. Renal dialysis is indicated in the presence of renal failure. Eradication of the vector host is an important preventive measure.
Causes
Since the 1960s, more than 10 types of virus-induced hemorrhagic fever have been found around the world, and their pathogens belong to 4 families, i.e., Leptoviridae, Bunyaviridae, Serratoviridae, and Filoviridae; the modes of transmission include mosquito-borne, tick-borne, animal-borne, and the transmission route is not yet known. Among them, Renal Syndrome Hemorrhagic Fever (RSHF) and Xinjiang Hemorrhagic Fever (Crimean-Congo Hemorrhagic Fever (CCHF)) occur widely in China.
Symptoms
Various viral hemorrhagic fevers have the following basic clinical manifestations, although there are differences.
1. Fever
Fever is the most basic symptom, different hemorrhagic fever, fever duration and fever type is not exactly the same. Mosquito as the medium of hemorrhagic fever is mostly bimodal fever, all kinds of symptoms with the second fever and aggravated, renal syndrome hemorrhagic fever is mostly for the retention of fever.
2. Bleeding and rash
All kinds of hemorrhagic fever have bleeding and rash phenomenon, but the site, time and degree of bleeding and rash are different. In mild cases, there are only a few bleeding spots and rash, in severe cases, gastrointestinal, respiratory or genitourinary hemorrhage can occur.
(1) Renal syndrome hemorrhagic fever Fever usually lasts for 5-7 days, with headache, lumbago and orbital pain, congestion and flushing of the face, cheeks and upper chest, and conjunctival congestion. Small hemorrhagic dots are seen on the skin and mucous membranes, often on the palate, conjunctiva, axilla and anterior and posterior axilla, in clustered distribution or stripes, some patients have bruises at the site of puncture and compression, the pharynx is congested, and the conjunctival sacs are markedly edematous, and the fascicular arm test is positive in more than 95% of patients. When the disease enters the hypotensive shock phase, the congestion phenomenon subsides, the bleeding phenomenon worsens, the skin and mucous membrane hemorrhagic spots increase, and can be fused into bruises, and at the same time can be accompanied by gastrointestinal hemorrhage, pulmonary hemorrhage, etc., and the various symptoms are aggravated. When entering the oliguria stage (mostly in the 8th to 12th day after the disease), the bleeding phenomenon is more significant, and large bruises can be seen on the skin of the compressed area, and hemorrhage of the cavity can occur, such as hemoptysis, vomiting blood, blood in the stool, nosebleed and so on. Oliguria is the most serious stage of the disease, and patients may have multi-organ failure.
(2) Dengue hemorrhagic fever Dengue virus can cause dengue fever without hemorrhagic tendency, but in the past 20 years, dengue fever in Southeast Asia is often accompanied by severe hemorrhage and shock of severe epidemics, called “dengue hemorrhagic fever”. Dengue hemorrhagic fever is a clinical syndrome whose main symptoms include high fever, hepatosplenomegaly, shock and hemorrhagic phenomena, and most patients have scattered bruises on the limbs, face, axillae and soft palate, sometimes fusing into bruises. In addition, there may be erythema, maculopapular rash and rash like a wind ball, and some patients may have nosebleed, gum bleed, gastrointestinal bleed and hematuria.
(3) Hemorrhagic fever in Xinjiang Fever is accompanied by congestion and flushing of the skin of the face, neck and upper chest, and there are bruises and bruises on the chest, back, armpits, face, neck and limbs, which are mostly arranged in the form of stripes in the armpits. Hemorrhagic spots are more in the upper body and less in the lower body, and there are also bruises in the eyes, soft palate and gums. Hematoma and bruises can be seen at the injection site, and there is edema in the conjunctiva of the eyeballs.
(4) Far Eastern hemorrhagic fever is caused by arboviruses, and its vector is rodents, mainly in America and Korea. The onset of the disease is sudden, with systemic symptoms such as fever, headache, backache, and bruises on the conjunctiva and skin (especially in the armpits).
(5) Argentine Hemorrhagic Fever is caused by the arbovirus Junin virus, which is transmitted by mites, and is associated with fever, headache, backache, and bleeding from the gums and nose.
(6) Bolivian Hemorrhagic Fever is caused by Machup virus, a vector of rodents. At the beginning, there are fever, headache, arthralgia and muscle pain. Some patients have allergic skin sensation, and exposure to light may cause pain in the skin. There is obvious conjunctivitis, periorbital edema, but there is no petechiae on the skin and mucous membranes, there may be gastrointestinal bleeding, and diffuse alopecia may occur during the recovery period.
3. Hypotensive shock
Shock can occur in all kinds of hemorrhagic fever, but the frequency and degree of occurrence vary greatly. Renal syndrome hemorrhagic fever occurs most frequently and seriously.
4. Renal failure
Renal syndrome hemorrhagic fever is the most serious renal damage, other hemorrhagic fevers can also have different degrees of renal damage, but most of them are mild, only manifested as mild to moderate proteinuria.
Laboratory tests
1. Early peripheral blood leukocyte count is low or normal, and then increases significantly after 3-4 days, with an increase in the number of rod-shaped nucleated cells and the appearance of more heterogeneous lymphocytes; platelets are significantly reduced.
2. Some patients have slightly prolonged bleeding and coagulation time.
3. Early patients can appear different degrees of proteinuria, individual can be seen tube type, blood urea nitrogen and creatinine increased.
4. Mild liver function abnormalities can be seen in the early stage of the disease, with elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and elevated serum bilirubin in some patients.
5. Antibody detection of specific antigens: ELISA double antibody sandwich method and reverse hemagglutination test can be used to detect circulating antigens in serum, and antibody capture ELISA can also be used to detect specific IgM antibodies for early diagnosis. Complement binding test or neutralization test should be applied to confirm the diagnosis for suspicious results or newly infected patients. Serum specific IgG antibody is more than 4 times higher than that in the acute stage, which has diagnostic value.
6. Others: Renal syndrome hemorrhagic fever can be detected from the patient’s blood leukocytes or urine sediment cells to the hantavirus (or EHF) antigen or viral RNA.
Diagnosis
Clinical diagnosis can be based on epidemiological data, clinical manifestations and laboratory findings. And the definitive diagnosis must have serologic or virologic evidence.
Differential diagnosis
Fever stage should be differentiated from upper respiratory tract infection, sepsis, acute gastroenteritis and bacillary dysentery. The shock phase should be differentiated from other infectious shocks. Oliguria should be differentiated from acute nephritis and other causes of acute renal failure. Bleeding should be distinguished from peptic ulcer bleeding, thrombocytopenic purpura and other causes of disseminated intravascular coagulation (DIC). Those with acute respiratory distress syndrome (ARDS) as the main manifestation should be distinguished from those with other etiologies. If abdominal pain is the main sign, it should be distinguished from surgical acute abdomen.
Treatment
There is no specific treatment for all kinds of viral hemorrhagic fever. For most patients with hemorrhagic fever, early treatment with corticosteroids can achieve better results. Symptomatic treatment should be carried out actively and reasonably, and early anticoagulation should be carried out as far as possible for those with diffuse intravascular coagulation. In addition, the prevention and treatment of shock, hemorrhage, renal failure, pulmonary edema and heart failure should be actively pursued.
1. General treatment
In the early stage, patients should rest in bed, reduce moving, and give enough calories and vitamins. In the early stage of the disease, severe patients can apply small doses of dexamethasone to reduce the symptoms of systemic toxicity, improve the body’s stress capacity and supplement the adrenocorticotropic hormone secretion due to adrenal and pituitary hemorrhage, but should not be applied to patients in the late stage.
2. Antiviral treatment
Ribavirin can be applied in the early stage and injected intravenously for 3 to 5 days. At present, some foreign countries have reported that the application of human specific immunoglobulin injection obtains significant therapeutic effect, and some think that the combined application with ribavirin has better therapeutic effect.
Protect the function of vital organs
Attention should be paid to protect the functions of important organs, such as giving hemodialysis treatment for renal failure, cardiac failure and cardiac muscle protection treatment, respiratory failure, oxygen, respiratory stimulant and other treatments, as well as giving proton pump inhibitors to protect the gastric mucosa in order to prevent bleeding and so on.
Symptomatic treatment
For persistent high fever, give physical or drug cooling, but should pay attention to the use of non-steroidal anti-inflammatory drugs (NSAIDs) as little as possible; for bleeding, give phenolsulfonyl ethylamine, vitamin K, plasminogen complex hemostatic treatment; for nausea and vomiting, give metoclopramide or domperidone. Pay attention to the balance of water and electrolytes, and give glucose injection and balanced salt injection intravenously for those with high fever and vomiting who cannot eat.
Prognosis
The prognosis of severe patients is poor, and the main causes of death are hemorrhage and organ failure, with a case fatality rate of 30%~50%. With the development of blood purification technology, the death rate of renal syndrome hemorrhagic fever in China has been greatly reduced in the past 20 years.
Prevention
Comprehensive measures should be taken to prevent viral hemorrhagic fever, regular extermination of rats, and regular in vitro extermination of ticks on domestic animals to reduce tick density. Those who enter deserts, pastures or forested areas should do a good job of personal protection against tick bites, wear gloves when contacting the blood and excreta of sick animals or patients, and not drink raw milk. Vaccination is the main measure to prevent the disease, but not all viral hemorrhagic fevers have vaccines, and some are still under development. A vaccine for renal syndrome hemorrhagic fever has been successfully developed with good protection. Residents of infected areas, especially field workers, should be actively vaccinated. People traveling or working in the infected areas are also advised to get vaccinated and complete it one month in advance. The protection rate of the renal syndrome hemorrhagic fever vaccine can reach more than 90% after the full vaccination.