OVERVIEW
Green monkey disease is also known as Marburg disease, African hemorrhagic fever, and Marburg-Ebola virus disease. There are no cases or serologic evidence of green monkey disease in China, but in view of the danger it poses to human beings and the monkey industry, it should be given high priority.
Etiology
Marburg virus, also known as Green Monkey Disease Virus and Green Monkey Factor, belongs to the same genus of filovirus in the family Filoviridae as Ebola virus. Marburg virus was discovered earlier than Ebola virus. Marburg virus is the causative agent of Marburg hemorrhagic fever, a disease with a very high morbidity and mortality rate. Marburg hemorrhagic fever was first discovered in 1967 after simultaneous outbreaks in Marburg (from which the disease takes its name) and Frankfurt, Germany, and Belgrade, Serbia.
Marburg and Ebola are two members of the filovirus family. Although caused by different viruses, the two diseases are clinically similar. Both are rare diseases and can cause large outbreaks with high lethality.
Initially, human infections result from prolonged contact with mines or caves inhabited by North African fruit bat colonies. Disease transmission occurs primarily from person to person, due to close contact with blood, secretions, organs, and other bodily fluids of infected individuals. Direct contact between mourners and the bodies of the deceased at funerals may play an important role in the spread of Marburg. Transmission through infected semen can occur as early as 7 weeks after clinical recovery.
Transmission to health care workers has been reported when close contact occurs during the treatment of patients with Marburg because proper infection control precautions were not used. Transmission through contaminated injecting equipment or needle stick injuries has been associated with greater severity of disease, rapid progression, and potentially higher mortality rates.
Symptoms
Sudden onset of illness with an incubation period of 3 to 9 days.
1. Influenza-like symptoms
At the beginning, there are generalized fatigue, chills, profuse sweating, severe headache, conjunctivitis, profuse vomiting, watery diarrhea, diffuse abdominal pain, myalgia, and so on. Small red spots may appear on the buccal mucosa, blisters on the soft palate, and enlarged tonsils. Body temperature peaks at 3 to 4 days, up to 40℃ or more, acute fever often lasts for 2 weeks, but can rise again after 12 to 14 days. The lymph nodes are enlarged all over the body, and in severe cases, the liver, heart, pancreas, kidney, hematopoietic organs and central nervous system can be involved. In the early stage of the disease, there may be sore throat, cough, chest pain, and pulmonary edema may occur; proteinuria may appear in the early stage, and renal failure may occur in the late stage; the patient’s conjunctiva is congested, and eyelid or conjunctivitis may occur.
2. Characteristic symptoms
(1) Rash: 5-7 days after the onset of the disease, scattered follicular red papules appear on the buttocks, trunk and limbs, and one day later, the papules merge with each other, and in severe cases, hemorrhagic diffuse erythema is present. The skin is not itchy, usually lasts for 3 to 4 days and then subsides, flaking, palmoplantar, extremity end flaking is heavier.
(2) Bleeding: while the rash appears, the patient presents hemorrhagic tendency, such as nosebleed, gum bleed, blood in urine and vaginal bleeding, etc. Within 1～2 days of the onset of the disease, there is a large amount of blood in the vomit and feces. Severe cases may die due to the occurrence of shock with disseminated intravascular coagulation.
Examination
1. General examination
Patients may have proteinuria early in the course of the disease, with a marked increase in aspartate aminotransferase (AST) and a small increase in alanine aminotransferase (ALT), resulting in the characteristic AST > ALT. There is a decrease in lymphocytes, followed by an increase in neutrophil counts, and a marked decrease in platelets, with paradoxical platelet aggregation. Sometimes blood amylase is also increased.
2. Specific diagnostic methods
Marburg virus belongs to biosafety level 4 pathogens, virus isolation and culture and research work must be carried out in P4 level laboratories. Its specific diagnostic methods are:
(1) serological detection: detection methods include indirect immunofluorescence test (IFA), enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay technology (RID), etc. IFA can measure IgG and IgM antibodies, IgM antibodies can appear 7 days after the onset of disease and reach the peak very quickly, which can be used for early diagnosis of the disease; IgG antibody reaches the peak 30 days after the infection and lasts for a long time. It lasts for a longer period of time. Methods of detecting antigens include: ELISA to detect antigens in blood, serum or tissue homogenate, and IFA to detect viral antigens in liver cells by monoclonal antibodies.
(2) Electron microscopy: In the acute stage, specimens such as blood and urine of patients or monkeys or livers of dead people or monkeys can be taken, and the diagnosis can be made by electron microscopic observation of virus particles.
(3) Virus isolation: for virus isolation, the above specimens can be inoculated with Vero cells, and the viral antigen in the cells can be detected by immunofluorescence technique after 3 days; the above specimens can also be inoculated with guinea pigs, suckling rats or monkeys, and the viral antigens in the blood or tissues and organs can be examined by electron microscopy or immunofluorescence after the animals develop the disease.
Diagnosis
Marburg virus infection can only be definitively diagnosed in the laboratory by several different tests: (1) enzyme-linked immunosorbent assay (ELISA), (2) antigen detection test, (3) serum neutralization test, (4) reverse transcription polymerase chain reaction (RT-PCR), and (5) isolation of the virus by cell culture.
Testing of clinical samples carries extreme biohazard risks and should only be performed under the highest level of biological protection. Diagnosis can be made on the basis of epidemiology and clinical presentation. In acute cases, the diagnosis can be made by taking the patient’s blood and urine and observing the virus particles by electron microscopy. For virus isolation, blood and urine of the patient can be inoculated with Vero cells, and the viral antigens in the cells can be detected by immunofluorescence after 3 days. Indirect immunofluorescence test not only detects antibodies early and at a high level, but also measures immunoglobulin IgG and IgM antibodies, which appear 7 days after the onset of the disease and reach a peak soon, and can be used for early diagnosis of the disease.
Treatment
There is no specific treatment for viral hemorrhagic fever. For most patients with hemorrhagic fever, early treatment with corticosteroid can achieve a better therapeutic effect. Symptoms should be treated actively and reasonably, and when disseminated intravascular coagulation (DIC) is confirmed, anticoagulation should be carried out as early as possible. In addition, shock, hemorrhage, renal failure, pulmonary edema and heart failure should be actively prevented and treated.
Prognosis
Acute fever usually lasts for 2 weeks, and about 1/3 of patients often die on the 8th to 17th day due to myocarditis, renal failure, convulsions, and coma.