Viral haemorrhagic fevers (VHF)

Viral haemorrhagic fevers (VHF) are caused by a diverse group of viruses belong to the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae. All VHFs have a similar clinical picture with mortality rate varies from 15 –30 % but in the case of VHF due to Ebola virus, the rate is as high as 80 %.

Epidemiology: Person-to-person transmission and nosocomial transmission have been demonstrated for VHFs due to Ebola, Marburg, Lassa, Crimean-Congo hemorrhagic fever, Argentine hemorrhagic fever and Bolivian hemorrhagic fever viruses. Transmission of VHF has been associated with reuse of unsterile needles and syringes and with provision of patient care without appropriate barrier precautions to prevent exposure to blood and other body fluids (including vomitus, urine, and stool) containing the virus. Air-borne transmission of VHF has been described in primates. In general, a combination of contact and airborne isolation precautions should be used for patients who are suspected of having VHF.

Viral haemorrhagic fevers due to Hantaviruses: Hantavirus infection in humans can be categorized into two major syndromes: one characterized by hemorrhages and renal failure, and another characterized by respiratory distress. Recent investigations have revealed several New World Hantaviruses that cause infection characterized by respiratory distress, including Andes virus which was identified in Argentina in 1995.Haemorrhagic fever with renal syndrome (HFRS) is a group of clinically similar illnesses caused by Hantaviruses from the family Bunyaviridae. HFRS includes diseases such as Korean haemorrhagic fever, epidemic haemorrhagic fever and nephropathis epidemica. The viruses that cause HFRS include Hantaan, Dobrava-Belgrade, Seoul and Puumala.

Symptoms of HFRS usually develop within 1 to 2 weeks after exposure to infectious material, but in rare cases, they may take up to 8 weeks to develop. Initial symptoms begin suddenly and include intense headaches, back and abdominal pain, fever, chills, nausea, and blurred vision followed with low blood pressure, acute shock, vascular leakage, and acute kidney failure, which can cause severe fluid overload. The severity of the disease varies depending upon the virus causing the infection. Hantaan and Dobrava virus infections usually cause severe symptoms, while Seoul and Puumala virus infections are usually moderate. It takes weeks or even months for complete recovery.Laboratory tests are used to confirm a diagnosis of HFRS in patients with a clinical history compatible with the disease. Such patients are determined to have HFRS if they are serologically positive for Hantavirus infection, have evidence of Hantavirus antigen in tissue by immunohistochemical staining and microscope examination, or evidence of hantavirus RNA sequences in blood or tissue.
Supportive therapy is the mainstay of care for patients with Hantavirus infections.Treatment with antiviral drug has been shown to decrease illness and death associated with HFRS. Rodent control is the primary strategy for preventing Hantavirus infections. Individuals should avoid contact with rodent urine, droppings, saliva, and nesting materials.

Andes virus infection: Hantaviruses include 112 viruses capable of causing human infection. There is no evidence of person-to-person transmission. However, investigation of the outbreak of Andes virus infection in Argentina during 1996–1997 strongly suggested person-to-person and nosocomial transmission. A diagnosis of Andes virus infection should be considered for health care personnel who develop clinical illness compatible with Andes virus infection within 4 weeks of exposure to infected persons.

Marburg and Ebola virus infection: Marburg and Ebola viruses, classified under Filovirus genus of family Filoviridae, are among the most severe and mysterious viral pathogens emerged during 20th century. African green monkeys (Cercopithecus aethiops) imported from Uganda for use in research and vaccine production constituted the source of the first Marburg virus outbreak in 1967.
Ebola virus was first discovered in Sudan in 1976 and since then at least 1,000 people have died. So far, there are four genetic subtypes of Ebola virus, viz. Zaire, Cote d’Ivoire, Sudan and Ebola-Reston. The Zaire, Cote d’Ivoire and Sudan genetic subtypes have been associated with human disease in west and central Africa, while Ebola-Reston was discovered in Macaques imported from the Philippines for medical research. Occupational exposure to Ebola-Reston from non-human primates is infrequent and results in asymptomatic infection. The natural history of Ebola virus is still a mystery. Clinical diagnosis of Ebola virus infection is challenging because the presentation is nonspecific. ELISA, PCR and virus isolation are the methods for diagnosis.

Haemorrhagic fevers due to Arenaviruses: Many haemorrhagic fevers are associated with Arenaviruses, all of which have natural persistent infection in rodents with humans being accidental hosts. Route of transmission to humans is generally thought to be occured through contamination of food, water, or air contaminated with rodent faeces or urine or by inoculation of skin abrasions. Humans are infected primarily through infected rodents invading human habitats. Contact with infected rodent faeces has produced disease in laboratory personnel.

Junin virus infection: Junin virus, an Arenavirus belonging to Arenavirideae causes Argentine haemorrhagic fever and is characterized by an illness of 1-2 weeks with insidious onset of fever, malaise, rigors, fatigue, headache, vomiting, constipation or diarrhea, conjunctival congestion, retro-orbital pain, epistaxis, petechial hemorrhages beneath skin, palate and gums. Oedema of the upper body may be observed. Haematemesis and melena, encephalopathy, bradycardia and hypertension are reported in severe cases. Case fatality rate may range between 5-30%. Several hundred cases reported each year in Argentina. Rodents are the reservoir for maintenance of the Junin virus in nature.

Machupo virus infection: Machupo virus, an Arenavirus belonging to Arenavirideae causes Bolivian Haemorrhagic fever whose signs and case fatality rate is similar to  Argentine haemorrhagic fever. The vector of Machupo virus is Vespr mouse (Calomys callosus) in Bolivia.

Lassa fever: Lassa fever virus, an Arenavirus belonging to the family Arenavirideae is antigenically related to the agent that causes lymphocytic choriomeningitis (LCM). The vector of virus is rat (Mastomys natalensis) in West Africa. The infection is endemic in Guinea, Liberia, Sierra Leone and some areas of Nigeria. Lassa fever was recognized for the first time in 1969 in a missionary nurse in Lassa, Nigeria while taking care of a patient at hospital. The infection can be asymptomatic in man or may cause a mild illness or produce a severe or even a fatal disease. The onset is gradual with fever, asthenia, muscular pain, cephalalgia and it can affect many organ systems. In animals, natural infection caused by Lassa virus is found in common rodent Mastomys natalensis. The virus is transmitted horizontally among these animals. Human beings get infected through aerosols or direct contact with their excreta. Human –to- human transmission has been reported.

Lymphocytic choriomeningitis (LCM): It is caused by an Arenavirus known as LCM virus (LCMV) belonging to Arenavirideae. The vector of the virus is house mouse. The disease is principally confined to the eastern seaboard and northeastern states in the United States. The virus infects wild mice, M. musculus. The infection also occurs in guinea pigs, rabbits, rats, canines, swine, and primates. Human infections are probably from contaminated food and dust, the handling of dead mice, and mouse bites. Bloodsucking arthropod vectors such as ticks, lice, and mosquitoes may transmit the disease. Man-to-man transmission does not occur. The clinical features of LCM in man may include influenza-like illness for up to 2 weeks and some patients may have complication s  like  orchit is ,  arthritis  and  alopecia .On  rareoccasions , meningoencephalitis may occur. Naturally infected animals including the house mouse do not show clinical symptoms.

Diagnosis of haemorrhagic fevers caused by Junin, Machupo, and Lassa fever viruses can be achieved by serology or virus isolation while control is by reducing the opportunity for exposure to the infected rodents. LCM can be diagnosed by complement fixation test, virus isolation and PCR. Prevention and control strategies for LCM include serologic monitoring, eradication of infection, preventing entry of wild mice to facilities, controlling ectoparasites, observing basic hygienic practices.