Bolivian hemorrhagic fever (BHF), also known as black typhus or Ordog Fever, is a hemorrhagic fever and zoonotic infectious disease endemic to Bolivia after infection by Machupo virus (MACV). The virus is spread primarily by the large vesper mouse (Calomys callosus). BHF was first recognized in 1959 during the first reported outbreak near the city of San Joaquin in the Beni district of northeast Bolivia. Symptoms include fever, malaise, bleeding, and in some cases, death. The mortality rate is estimated at about 20% but during early outbreaks has been as high as 41%. The most recent cases of Bolivian hemorrhagic fever occurred in February 2008. Over 200 suspected cases of BHF were reported.
Cause
Discovery
Machupo virus is the etiological agent of Bolivian hemorrhagic fever. The virus was first isolated in 1963 using the spleen of a diseased patient from the 1963–1964 BHF outbreak. The virus was then subsequently named after a river near the location of the outbreak.
Virology Machupo virus is a part of the Arenaviridae family, which includes viruses like Lassa virus and Chapare virus, the latter of which was once thought to be an additional strain of Machupo. Machupo, endemic to Bolivia, is thus classified as a New World arenavirus (as it is endemic to the Americas). Arenaviruses are enveloped, single-stranded, bi-segmented, negative-sense RNA viruses. Under the electron microscope, Machupo virions are spherical and pleomorphic. They often appear 'sandy' due to their internal ribosomes. Due to its pathogenicity and the absence of approved medical countermeasures, Machupo virus must be handled under Biosafety Level Four conditions, the highest level of biocontainment.
Transmission
Reservoirs and vectors
The known primary reservoir and vector for Bolivian hemorrhagic fever is the large vesper mouse (Calomys callosus) a rodent indigenous to northern Bolivia. Infected animals are asymptomatic and shed the virus in excreta and secreta. Transmission is believed to be from contact with aerosolized particles of infected excreta or secreta to the mucosal membrane. This can be through eating contaminated food, breathing in infected particles, or the direct contact of infected particles with the mucosal membrane. While rare, nosocomial transmission is known to occur with BHF. In 1971, three healthcare workers were infected through interhuman transmission after the admission of an infected patient.
Symptoms Bolivian hemorrhagic fever has an incubation period between 3 and 21 days with an average incubation period of 7 to 14 days. Once symptoms appear, similar to many hemorrhagic fevers, the progression of BHF is biphasic followed by a convalescence period for survivors.
Prodromal phase The prodromal phase begins with the onset of symptoms and lasts between 1 and 5 days. The phase starts with nonspecific, flu-like symptoms including but not limited to; fever, malaise, headache, dehydration, dizziness, arthralgia, myalgia, and cough. Symptoms continue to increase in severity over the course of the prodromal phase. Late-stage prodromal phase symptoms can include; vomiting, diarrhea, abdominal pain, skin hypersensitivity, petechiae, and gingival-bleeding.
Hemorrhagic phase One-third of patients progress into the hemorrhagic phase. This phase lasts between 2 and 10 days. The hemorrhagic phase is characterized by systemic hemorrhagic manifestations. This can present as; petechiae, gingival-bleeding, hemorrhage of mucosal membranes, subconjunctival hemorrhage, bradycardia, hypotension, pulmonary edema, tremors, spasms, delirium, and at its extreme, coma and death. Fatality typically occurs between 7 and 12 days post onset of symptoms. The mortality rate for BHF is estimated at 20%.
Convalescence phase Of those who progress to the convalescence phase, it takes weeks to months to recover. During this phase, patients may experience weakness, hair loss, Beau's lines, rapid pulse, and dizziness.
Treatment There are currently no virus-specific FDA approved therapies for Bolivian hemorrhagic fever. Supportive care is the current recommended treatment for BHF.
Experimental treatments Since 1963, there have been multiple experimental treatments for BHF tested on both humans and non-human primates that have been infected with Machupo.
Immunoglobulin Immunoglobulin treatment consists of administering human immunoglobulin from a recent survivor of BHF. This serum contains antibodies to MACV. This treatment plan proves difficult as there are few survivors of BHF and of those, few are strong enough to donate the necessary plasma. In 1975, researchers inoculated infected rhesus monkeys with human immunoglobulin. All but four of the 12 monkeys survived the initial infection. However, those with higher dosages of the immunoglobulin went on to develop a severe neurological condition that resulted in the death of three subsequent monkeys. In 2007, immunoglobulin was administered to three patients presenting with BHF. Despite the immunoglobulin and other supportive therapies, two of the three patients died days later. In 2008, immunoglobulin was administered to two patients presenting with BHF. One of the two patients did not survive.
Antivirals Ribavirin, an antiviral drug, has been effectively used to treat cases of BHF, but more extensive clinical studies are necessary to fully evaluate the potential of this antiviral.
Prevention
Vaccine Currently, there is no FDA approved human vaccine for Bolivian hemorrhagic fever.
Pest reduction Reduction of the vector species, the large vesper mouse, has been found effective at reducing the number of reported BHF cases. Prior to the identification of transmission vector, and therefore any reduction programs, Bolivia faced its largest BHF epidemic from 1963–1964. The magnitude of this epidemic is thought to have been caused by the rapid proliferation of the large vesper mouse due to the use of DDT that significantly harmed the local feline population, inhibiting them from effectively hunting the rodent populations. However, since, the identification of the transmission vector, rodent reduction programs have been put in place by local health agencies. These include the systemic trapping and poisoning of the mice as well as the expansion of the local feline population. These efforts are believed to be responsible for the lack of BHF cases identified between 1976 and 1993.
History
Outbreaks
… excerpt ends here. Continue reading the full article.
