Marburg virus
Encyclopedia
Marburg virus disease is the name for the human disease caused by any of the two marburgviruses
Marburg virus
(MARV) and Ravn virus
(RAVV). MVD is a viral hemorrhagic fever
(VHF), and is clinically indistinguishable from Ebola virus disease (EVD).
's International Statistical Classification of Diseases and Related Health Problems 10 (ICD-10) for the human disease caused by any of the two marburgviruses
Marburg virus
(MARV) and Ravn virus
(RAVV). In the scientific literature, Marburg hemorrhagic fever (MHF) is often used as an unofficial alternative name for the same disease. Both disease names are derived from the German
city Marburg
, where MARV was first discovered.
and symptom
s was performed during the 1998–2000 mixed MARV/RAVV disease outbreak. MVD has an incubation period
of 3–21 days and begins with a sudden onset of an influenza
-like stage characterized by general malaise
, fever
with chills, arthralgia
and myalgia
, and chest pain
. Nausea
is accompanied by abdominal pain
, anorexia
, diarrhea
, and vomiting
. Respiratory tract
involvement is characterized by pharyngitis
with sore throat
, cough
, dyspnea
, and hiccups. The central nervous system
is affected as judged by the development of severe headaches, agitation
, confusion
, fatigue, depression, seizures, and sometimes coma
. The circulatory system
is also frequently involved, with the most prominent signs being edema
and conjunctivitis
. Hemorrhagic symptoms
are infrequent (the reason why Ebola hemorrhagic fever (EHF) is a misnomer
) and include hematemesis
, hemoptysis
, melena
, and bleeding from mucous membranes (gastroinestinal tract, nose
, vagina
and gingiva
). A maculopapular
rash
, petechia
e, purpura
, ecchymoses
, and hematoma
s (especially around needle injection sites) are other typical hemorrhagic manifestations. However, contrary to popular belief, hemorrhage does not lead to hypovolemia
and is not the cause of death
(total blood loss is minimal except during labor
). Instead, death occurs due to multiple organ dysfunction syndrome (MODS)
due to fluid redistribution, hypotension
, disseminated intravascular coagulation
, and focal tissue
necroses
.
MVD is caused by two viruses classified in the genus Marburgvirus
, family Filoviridae
, order Mononegavirales
:Marburg virus (MARV)
and Ravn virus (RAVV)
.
Marburgviruses are endemic in arid
woodland
s of equatorial Africa
. Most marburgvirus infections were repeatedly associated with people visiting natural cave
s or working in mines
. In 2009, the successful isolation of infectious MARV and RAVV was reported from healthy Egyptian rousettes (Rousettus aegyptiacus)
caught in caves. This isolation strongly suggests that Old World
fruit bat
s are involved in the natural maintenance of marburgviruses and that visiting bat-infested caves is a risk factor for acquiring marburgvirus infections. Further studies are necessary to establish whether Egyptian rousettes are the actual hosts of MARV and RAVV or whether they get infected via contact with another animal and therefore serve only as intermediate hosts. Another risk factor is contact with nonhuman primates, although only one outbreak of MVD (in 1967) was due to contact with infected monkeys. Finally, a major risk factor for acquiring marburgvirus infection is occupational exposure, i.e. treating patients with MVD without proper personal protective equipment
.
Contrary to Ebola virus disease (EVD), which has been associated with heavy rain
s after long periods of dry weather, triggering factors for spillover of marburgviruses into the human population have not yet been described.
, marburgvirions contain non-infectious, linear nonsegmented, single-stranded RNA
genome
s of negative polarity that possesses inverse-complementary 3' and 5' termini, do not possess a 5' cap
, are not polyadenylated
, and are not covalently
linked to a protein
. Marburgvirus genomes are approximately 19 kb
long and contain seven gene
s in the order 3'-UTR
-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR
. The genomes of the two different marburgviruses (MARV and RAVV) differ in sequence.
, marburgvirions are filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched. Marburgvirions are generally 80 nm in width, but vary somewhat in length. In general, the median particle length of marburgviruses ranges from 795–828 nm (in contrast to ebolavirions, whose median particle length was measured to be 974–1,086 nm ), but particles as long as 14,000 nm have been detected in tissue culture. Marburgvirions consist of seven structural proteins. At the center is the helical ribonucleocapsid
, which consists of the genomic RNA wrapped around a polymer
of nucleoprotein
s (NP). Associated with the ribonucleoprotein is the RNA-dependent RNA polymerase
(L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein is embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles are surrounded by a lipid membrane
derived from the host cell membrane. The membrane anchors a glycoprotein (GP1,2) that projects 7 to 10 nm spikes away from its surface. While nearly identical to ebolavirions in structure, marburgvirions are antigen
ically distinct.
begins with virion attachment to specific cell-surface receptor
s, followed by fusion
of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol
. The virus RdRp partially uncoats the nucleocapsid and transcribes
the genes
into positive-stranded mRNAs, which are then translated into structural and nonstructural proteins. Marburgvirus L binds to a single promoter located at the 3' end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3' end of the genome are transcribed in the greatest abundance, whereas those toward the 5' end are least likely to be transcribed. The gene order is therefore a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein
, whose concentration
in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-stranded antigenomes that are in turn transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane
. Virions bud
off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.
, such as other viral hemorrhagic fever
s, falciparum malaria
, typhoid fever
, shigellosis
, rickettsial diseases
such as typhus
, cholera
, gram-negative septicemia
, borreliosis such as relapsing fever
or EHEC enteritis
. Other infectious diseases that ought to be included in the differential diagnosis
include leptospirosis
, scrub typhus
, plague, Q fever
, candidiasis
, histoplasmosis
, trypanosomiasis
, visceral leishmaniasis
, hemorrhagic smallpox
, measles
, and fulminant viral hepatitis
. Non-infectious diseases that can be confused with MVD are acute promyelocytic leukemia
, hemolytic uremic syndrome, snake
envenomation
, clotting factor
deficiencies/platelet disorders, thrombotic thrombocytopenic purpura
, hereditary hemorrhagic telangiectasia
, Kawasaki disease
, and even warfarin
intoxication. The most important indicator that may lead to the suspicion of MVD at clinical examination is the medical history
of the patient, in particular the travel and occupational history (which countries and caves were visited?) and the patient's exposure to wildlife (exposure to bats or bat excrements?). MVD can be confirmed by isolation of marburgviruses from or by detection of marburgvirus antigen or genomic or subgenomic RNAs in patient blood
or serum
samples during the acute phase of MVD. Marburgvirus isolation is usually performed by inoculation
of grivet
kidney epithelial Vero E6 or MA-104 cell culture
s or by inoculation of human adrenal carcinoma SW-13 cells, all of which react to infection with characteristic cytopathic effect
s. Filovirions can easily be visualized and identified in cell culture by electron microscopy due to their unique filamentous shapes, but electron microscopy cannot differentiate the various filoviruses alone despite some overall length differences. Immunofluorescence assays
are used to confirm marburgvirus presence in cell cultures. During an outbreak, virus isolation and electron microscopy are most often not feasible options. The most common diagnostic methods are therefore RT-PCR
in conjunction with antigen-capture ELISA
, which can be performed in field or mobile hospitals and laboratories. Indirect immunofluorescence assays (IFAs)
are not used for diagnosis of MVD in the field anymore.
-approved vaccine
s for the prevention of MVD. Many candidate vaccines have been developed and tested in various animal models. Of those, the most promising ones are DNA vaccines
or based on Venezuelan equine encephalitis virus
replicons
, vesicular stomatitis Indiana virus (VSIV)
or filovirus-like particles (VLPs) as all of these candidates could protect nonhuman primates from marburgvirus-induced disease. DNA vaccines have entered clinical trials. Marburgviruses are highly infectious
, but not very contagious
. Importantly, and contrary to popular belief, marburgviruses do not get transmitted by aerosol
during natural MVD outbreaks. Due to the absence of an approved vaccine, prevention of MVD therefore relies predominantly on behavior modification, proper personal protective equipment
, and sterilization
/disinfection
.
s and the association of several MVD outbreaks with bat-infested mines or caves strongly suggests that bats are involved in marburgvirus transmission to humans. Avoidance of contact with bats and abstaining from visits to caves is highly recommended, but may not be possible for those working in mines or people dependent on bats as a food source.
s and body fluids, or possibly contaminated
materials and utensils. Patients ought to be isolated but still have the right to be visited by family members. Medical staff should be trained and apply strict barrier nursing techniques (disposable face mask, gloves, goggles, and a gown at all times). Traditional burial
rituals, especially those requiring embalming
of bodies, ought to be discouraged or modified, ideally with the help of local traditional healers.
Risk Group 4 Pathogens, requiring Biosafety Level 4-equivalent containment
. Laboratory researchers have to be properly trained in BSL-4 practices and wear proper personal protective equipment.
for MVD. Treatment is primarily supportive in nature and includes minimizing invasive procedures, balancing fluids and electrolyte
s to counter dehydration
, administration of anticoagulants early in infection to prevent or control disseminated intravascular coagulation
, administration of procoagulants
late in infection to control hemorrhaging
, maintaining oxygen
levels, pain management
, and administration of antibiotics or antimycotics to treat secondary infections. Experimentally, recombinant vesicular stomatitis Indiana virus
(VSIV) expressing the glycoprotein of MARV has been used successfully in nonhuman primate models as post-exposure prophylaxis. Novel, very promising, experimental therapeutic regimens rely on antisense technology
: phosphorodiamidate morpholino oligomers
(PMOs) targeting the MARV genome could prevent disease in nonhuman primates.
e, such as orchitis
, hepatitis
, uveitis
, parotitis
, desquamation
or alopecia
. Importantly, MARV is known to be able to persist in some survivors and to either reactivate and cause a secondary bout of MVD or to be transmitted via sperm
, causing secondary cases of infection and disease.
Of the 252 people who contracted Marburg during the 2004–2005 outbreak in Angola, 227 died, for a case fatality rate of 90%.
Although all age groups are susceptible to infection, children are more rarely infected. In the 1998–2000 Congo epidemic, only 8% of the cases were children less than 5 years old.
towns of Marburg
and Frankfurt am Main, and in Belgrade
, Yugoslavia
. The outbreak involved 25 primary MARV infections and seven deaths, and six nonlethal secondary cases. The outbreak was traced to infected grivet
s (species Chlorocebus aethiops) imported from an undisclosed location in Uganda
and used in developing poliomyelitis
vaccines. The monkeys were received by Behringwerke, a Marburg company founded by the first winner of the Nobel Prize in Medicine, Emil von Behring. The company, which at the time was owned by Hoechst
, was originally set up to develop sera
against tetanus
and diphtheria
. Primary infections occurred in Behringwerke laboratory
staff while working with grivet tissues or tissue cultures without adequate personal protective equipment
. Secondary cases involved two physician
s, a nurse, a post-mortem attendant, and the wife of a veterinarian
. All secondary cases had direct contact, usually involving blood, with a primary case. Both physicians became infected through accidental skin pricks when drawing blood from patients.
A popular science account of this outbreak can be found in Laurie Garrett
’s book The Coming Plague.
(today Zimbabwe
). He died in a hospital in Johannesburg
, South Africa
. His girlfriend and an attending nurse subsequently came down with MVD, but survived. A popular science account of these cases can be found in Laurie Garrett
’s book The Coming Plague.
. A French man, who worked as an electrical engineer in a sugar factory in Nzoia (close to Bungoma
) at the base of Mount Elgon
(which contains Kitum Cave
), became infected by unknown means and died shortly after admission to Nairobi
Hospital. The attending physician contracted MVD, but survived. A popular science account of these cases can be found in Richard Preston
’s book The Hot Zone
(the French man is referred to under the pseudonym
“Charles Monet”, whereas the physician is identified under his real name Shem Musoke).
, Kenya
. He had visited Kitum Cave
on Mount Elgon
prior to travelling to Mombasa
, where he developed clinical signs of infection. The boy died after tramsfer to Nairobi
Hospital. A popular science account of this case can be found in Richard Preston
’s book The Hot Zone
(the boy is referred to under the pseudonym
“Peter Cardinal”).
s. The accident occurred at the Scientific-Production Association "Vektor" (today the State Research Center of Virology and Biotechnology "Vektor") in Koltsovo
, USSR (today Russia
). Very little information is publicly available about this MVD case because Ustinov’s experiments were classified. A popular science account of this case can be found in Ken Alibek
’s book Biohazard.
, USSR, when a scientist contracted MARV by unknown means.
, Democratic Republic of Congo from 1998 to 2000, when co-circulating MARV and RAVV caused 154 cases of MVD and 128 deaths. The outbreak ended with the flooding of the mine.
(WHO) began investigating an outbreak of viral hemorrhagic fever
in Angola
, which was centered in the northeastern Uíge Province but also affected many other provinces. The Angolan government had to ask for international assistance, pointing out that there were only approximately 1,200 doctors in the entire country, with some provinces having as few as two. Health care workers also complained about a shortage of personal protective equipment
such as gloves, gowns, and masks. Médecins Sans Frontières
(MSF) reported that when their team arrived at the provincial hospital at the center of the outbreak, they found it operating without water
and electricity
. Contact tracing
was complicated by the fact that the country's roads and other infrastructure have been devastated after nearly three decades of civil war
and the countryside remained littered with land mine
s. Americo Boa Vida Hospital in the Angolan capital Luanda
set up a special isolation ward to treat infected people from the countryside. Unfortunately, because MVD often results in death, some people came to view hospitals and medical workers with suspicion and treated helpers with hostility. For instance, a specially-equipped isolation ward at the provincial hospital in Uíge was reported to be empty during much of the epidemic, even though the facility was at the center of the outbreak. WHO was forced to implement what it described as a "harm reduction strategy", which entailed distributing disinfectants to affected families who refused hospital care. Of the 252 people who contracted MVD during outbreak, 227 died.
s became infected with marburgviruses in Kamwenge District
, Uganda
. The first case, a 29-year-old man, became symptomatic on July 4, 2007, was admitted to a hospital on July 7, and died on July 13. Contact tracing revealed that the man had had prolonged close contact with two colleagues (a 22-year-old man and a 23-year-old man), who experienced clinical signs of infection before his disease onset. Both men had been admitted to hospitals in June and survived their infections, which were proven to be due to MARV. A fourth, 25-year-old man, developed MVD clinical signs in September and was shown to be infected with RAVV. He also survived the infection.
reported that a 41-year-old Dutch woman, who had visited Python Cave in Maramagambo Forest during her holiday in Uganda
suffered of MVD due to MARV infection, and had been admitted to a hospital in the Netherlands
. The woman died under treatment in the Leiden University Medical Centre in Leiden on July 11. The Ugandan Ministry of Health closed the cave after this case. On January 9 of that year an infectious diseases physician notified the Colorado Department of Public Health and Education that a 44-year-old American woman who had returned from Uganda
showed signs of an unknown febrile illness that required hospitalisation. At the time, serologic testing was negative for viral hemorrhagic fever
; she was discharged on January 19, 2008. After the death of the Dutch patient and the discovery that the American woman had visited Python Cave, further testing confirmed the patient demonstrated MARV antibodies and RNA
.
Marburgvirus
The genus Marburgvirus is the taxonomic home of one species whose members are two related viruses that form filamentous virions, Marburg virus and Ravn virus...
Marburg virus
Marburg virus
Marburg virus disease is the name for the human disease caused by any of the two marburgviruses Marburg virus and Ravn virus...
(MARV) and Ravn virus
Ravn virus
Ravn virus is a close relative of the much more commonly known Marburg virus . RAVV causes severe disease in humans and in nonhuman primates in the form of viral hemorrhagic fever...
(RAVV). MVD is a viral hemorrhagic fever
Viral hemorrhagic fever
The viral hemorrhagic fevers are a diverse group of animal and human illnesses that are caused by four distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress...
(VHF), and is clinically indistinguishable from Ebola virus disease (EVD).
Classification
Marburg virus disease (MVD) is the official name listed in the World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
's International Statistical Classification of Diseases and Related Health Problems 10 (ICD-10) for the human disease caused by any of the two marburgviruses
Marburgvirus
The genus Marburgvirus is the taxonomic home of one species whose members are two related viruses that form filamentous virions, Marburg virus and Ravn virus...
Marburg virus
Marburg virus
Marburg virus disease is the name for the human disease caused by any of the two marburgviruses Marburg virus and Ravn virus...
(MARV) and Ravn virus
Ravn virus
Ravn virus is a close relative of the much more commonly known Marburg virus . RAVV causes severe disease in humans and in nonhuman primates in the form of viral hemorrhagic fever...
(RAVV). In the scientific literature, Marburg hemorrhagic fever (MHF) is often used as an unofficial alternative name for the same disease. Both disease names are derived from the German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
city Marburg
Marburg
Marburg is a city in the state of Hesse, Germany, on the River Lahn. It is the main town of the Marburg-Biedenkopf district and its population, as of March 2010, was 79,911.- Founding and early history :...
, where MARV was first discovered.
Signs and symptoms
The most detailed study on the frequency, onset, and duration of MVD clinical signsMedical sign
A medical sign is an objective indication of some medical fact or characteristic that may be detected by a physician during a physical examination of a patient....
and symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s was performed during the 1998–2000 mixed MARV/RAVV disease outbreak. MVD has an incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
of 3–21 days and begins with a sudden onset of an influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
-like stage characterized by general malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
with chills, arthralgia
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
and myalgia
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, and chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...
. Nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
is accompanied by abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
, anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
. Respiratory tract
Respiratory tract
In humans the respiratory tract is the part of the anatomy involved with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...
involvement is characterized by pharyngitis
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....
with sore throat
Sore throat
A sore throat or throat pain is a common physical symptom usually caused by acute pharyngitis, or throat inflammation, though it also occurs in a number of other situations, such as post trauma and in diphtheria. It can cause mild to extreme pain....
, cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
, and hiccups. The central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
is affected as judged by the development of severe headaches, agitation
Agitation
Agitation may refer to:* Agitation , putting into motion by shaking or stirring* Emotional state of excitement or restlessness** Psychomotor agitation, an extreme form of the above, which can be a side effect of antipsychotic medication...
, confusion
ConFusion
ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...
, fatigue, depression, seizures, and sometimes coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
. The circulatory system
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
is also frequently involved, with the most prominent signs being edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
and conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
. Hemorrhagic symptoms
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
are infrequent (the reason why Ebola hemorrhagic fever (EHF) is a misnomer
Misnomer
A misnomer is a term which suggests an interpretation that is known to be untrue. Such incorrect terms sometimes derive their names because of the form, action, or origin of the subject becoming named popularly or widely referenced—long before their true natures were known.- Sources of misnomers...
) and include hematemesis
Hematemesis
Hematemesis or haematemesis is the vomiting of blood. The source is generally the upper gastrointestinal tract. Patients can easily confuse it with hemoptysis , although the latter is more common.-Signs:...
, hemoptysis
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...
, melena
Melena
In medicine, melena or melaena refers to the black, "tarry" feces that are associated with gastrointestinal hemorrhage. The black color is caused by oxidation of the iron in hemoglobin during its passage through the ileum and colon.-Melena vs...
, and bleeding from mucous membranes (gastroinestinal tract, nose
Nose
Anatomically, a nose is a protuberance in vertebrates that houses the nostrils, or nares, which admit and expel air for respiration in conjunction with the mouth. Behind the nose are the olfactory mucosa and the sinuses. Behind the nasal cavity, air next passes through the pharynx, shared with the...
, vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
and gingiva
Gingiva
The gingiva , or gums, consists of the mucosal tissue that lies over the mandible and maxilla inside the mouth.-General description:...
). A maculopapular
Cutaneous conditions
There are many conditions of or affecting the human integumentary system—the organ system that comprises the entire surface of the body and includes skin, hair, nails, and related muscle and glands.- Diseases :...
rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, petechia
Petechia
A petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...
e, purpura
Purpura
Purpura is the appearance of red or purple discolorations on the skin that do not blanch on applying pressure. They are caused by bleeding underneath the skin...
, ecchymoses
Ecchymosis
An ecchymosis is the medical term for a subcutaneous purpura larger than 1 centimeter or a hematoma, commonly called a bruise. It can be located in the skin or in a mucous membrane.-Presentation:...
, and hematoma
Hematoma
A hematoma, or haematoma, is a localized collection of blood outside the blood vessels, usually in liquid form within the tissue. This distinguishes it from an ecchymosis, which is the spread of blood under the skin in a thin layer, commonly called a bruise...
s (especially around needle injection sites) are other typical hemorrhagic manifestations. However, contrary to popular belief, hemorrhage does not lead to hypovolemia
Hypovolemia
In physiology and medicine, hypovolemia is a state of decreased blood volume; more specifically, decrease in volume of blood plasma...
and is not the cause of death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
(total blood loss is minimal except during labor
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...
). Instead, death occurs due to multiple organ dysfunction syndrome (MODS)
Multiple organ dysfunction syndrome
Multiple organ dysfunction syndrome ', previously known as multiple organ failure or multisystem organ failure , is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis...
due to fluid redistribution, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
, and focal tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
necroses
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
.
Causes
| Species name International Committee on Taxonomy of Viruses The International Committee on Taxonomy of Viruses is a committee which authorizes and organizes the taxonomic classification of viruses. They have developed a universal taxonomic scheme for viruses and aim to describe all the viruses of living organisms. Members of the committee are considered to... |
Virus name (Abbreviation) International Committee on Taxonomy of Viruses The International Committee on Taxonomy of Viruses is a committee which authorizes and organizes the taxonomic classification of viruses. They have developed a universal taxonomic scheme for viruses and aim to describe all the viruses of living organisms. Members of the committee are considered to... |
| Marburg marburgvirus Marburg marburgvirus The species Marburg marburgvirus is the taxonomic home of two related viruses that form filamentous virions, Marburg virus and Ravn virus... * (accepted) |
Marburg virus Marburg virus Marburg virus disease is the name for the human disease caused by any of the two marburgviruses Marburg virus and Ravn virus... (MARV; previously MBGV) |
| Ravn virus Ravn virus Ravn virus is a close relative of the much more commonly known Marburg virus . RAVV causes severe disease in humans and in nonhuman primates in the form of viral hemorrhagic fever... (RAVV; previously MARV-Ravn) |
|
| "*" denotes the type species and "accepted" refers to a taxon accepted but not yet ratified by the ICTV. | |
MVD is caused by two viruses classified in the genus Marburgvirus
Marburgvirus
The genus Marburgvirus is the taxonomic home of one species whose members are two related viruses that form filamentous virions, Marburg virus and Ravn virus...
, family Filoviridae
Filoviridae
The family Filoviridae is the taxonomic home of several related viruses that form filamentous virions. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in...
, order Mononegavirales
Mononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
:Marburg virus (MARV)
Marburg virus
Marburg virus disease is the name for the human disease caused by any of the two marburgviruses Marburg virus and Ravn virus...
and Ravn virus (RAVV)
Ravn virus
Ravn virus is a close relative of the much more commonly known Marburg virus . RAVV causes severe disease in humans and in nonhuman primates in the form of viral hemorrhagic fever...
.
Marburgviruses are endemic in arid
Arid
A region is said to be arid when it is characterized by a severe lack of available water, to the extent of hindering or even preventing the growth and development of plant and animal life...
woodland
Woodland
Ecologically, a woodland is a low-density forest forming open habitats with plenty of sunlight and limited shade. Woodlands may support an understory of shrubs and herbaceous plants including grasses. Woodland may form a transition to shrubland under drier conditions or during early stages of...
s of equatorial Africa
Equatorial Africa
Equatorial Africa is an ambiguous term that is sometimes used to refer to tropical Africa, or the region of Sub-Saharan Africa traversed by the equator....
. Most marburgvirus infections were repeatedly associated with people visiting natural cave
Cave
A cave or cavern is a natural underground space large enough for a human to enter. The term applies to natural cavities some part of which is in total darkness. The word cave also includes smaller spaces like rock shelters, sea caves, and grottos.Speleology is the science of exploration and study...
s or working in mines
Mining
Mining is the extraction of valuable minerals or other geological materials from the earth, from an ore body, vein or seam. The term also includes the removal of soil. Materials recovered by mining include base metals, precious metals, iron, uranium, coal, diamonds, limestone, oil shale, rock...
. In 2009, the successful isolation of infectious MARV and RAVV was reported from healthy Egyptian rousettes (Rousettus aegyptiacus)
Egyptian fruit bat
The Egyptian Fruit Bat or Egyptian Rousette is a species of Old World fruit bat found throughout Africa, except in the desert regions of the Sahara, and throughout the Middle East, as far east as Pakistan and northern India...
caught in caves. This isolation strongly suggests that Old World
Old World
The Old World consists of those parts of the world known to classical antiquity and the European Middle Ages. It is used in the context of, and contrast with, the "New World" ....
fruit bat
Bat
Bats are mammals of the order Chiroptera "hand" and pteron "wing") whose forelimbs form webbed wings, making them the only mammals naturally capable of true and sustained flight. By contrast, other mammals said to fly, such as flying squirrels, gliding possums, and colugos, glide rather than fly,...
s are involved in the natural maintenance of marburgviruses and that visiting bat-infested caves is a risk factor for acquiring marburgvirus infections. Further studies are necessary to establish whether Egyptian rousettes are the actual hosts of MARV and RAVV or whether they get infected via contact with another animal and therefore serve only as intermediate hosts. Another risk factor is contact with nonhuman primates, although only one outbreak of MVD (in 1967) was due to contact with infected monkeys. Finally, a major risk factor for acquiring marburgvirus infection is occupational exposure, i.e. treating patients with MVD without proper personal protective equipment
Personal protective equipment
Personal protective equipment refers to protective clothing, helmets, goggles, or other garment or equipment designed to protect the wearer's body from injury by blunt impacts, electrical hazards, heat, chemicals, and infection, for job-related occupational safety and health purposes, and in...
.
Contrary to Ebola virus disease (EVD), which has been associated with heavy rain
Rain
Rain is liquid precipitation, as opposed to non-liquid kinds of precipitation such as snow, hail and sleet. Rain requires the presence of a thick layer of the atmosphere to have temperatures above the melting point of water near and above the Earth's surface...
s after long periods of dry weather, triggering factors for spillover of marburgviruses into the human population have not yet been described.
Genome
Like all mononegavirusesMononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
, marburgvirions contain non-infectious, linear nonsegmented, single-stranded RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
s of negative polarity that possesses inverse-complementary 3' and 5' termini, do not possess a 5' cap
5' cap
The 5' cap is a specially altered nucleotide on the 5' end of precursor messenger RNA and some other primary RNA transcripts as found in eukaryotes. The process of 5' capping is vital to creating mature messenger RNA, which is then able to undergo translation...
, are not polyadenylated
Polyadenylation
Polyadenylation is the addition of a poly tail to an RNA molecule. The poly tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA for translation...
, and are not covalently
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
linked to a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. Marburgvirus genomes are approximately 19 kb
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
long and contain seven gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s in the order 3'-UTR
Three prime untranslated region
In molecular genetics, the three prime untranslated region is a particular section of messenger RNA . It is preceeded by the coding region....
-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR
Five prime untranslated region
A messenger ribonucleic acid molecule codes for a protein through translation. The mRNA also contains regions that are not translated: in eukaryotes these include the 5' untranslated region, 3' untranslated region, 5' cap and poly-A tail....
. The genomes of the two different marburgviruses (MARV and RAVV) differ in sequence.
Structure
Like all filovirusesFiloviridae
The family Filoviridae is the taxonomic home of several related viruses that form filamentous virions. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in...
, marburgvirions are filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched. Marburgvirions are generally 80 nm in width, but vary somewhat in length. In general, the median particle length of marburgviruses ranges from 795–828 nm (in contrast to ebolavirions, whose median particle length was measured to be 974–1,086 nm ), but particles as long as 14,000 nm have been detected in tissue culture. Marburgvirions consist of seven structural proteins. At the center is the helical ribonucleocapsid
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
, which consists of the genomic RNA wrapped around a polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
of nucleoprotein
Nucleoprotein
A nucleoprotein is any protein that is structurally associated with nucleic acid .Many viruses harness this protein, and they are known for being host-specific...
s (NP). Associated with the ribonucleoprotein is the RNA-dependent RNA polymerase
RNA-dependent RNA polymerase
RNA-dependent RNA polymerase , , or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template...
(L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein is embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles are surrounded by a lipid membrane
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
derived from the host cell membrane. The membrane anchors a glycoprotein (GP1,2) that projects 7 to 10 nm spikes away from its surface. While nearly identical to ebolavirions in structure, marburgvirions are antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
ically distinct.
Replication
The marburgvirus life cycleBiological life cycle
A life cycle is a period involving all different generations of a species succeeding each other through means of reproduction, whether through asexual reproduction or sexual reproduction...
begins with virion attachment to specific cell-surface receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s, followed by fusion
Lipid bilayer fusion
Fusion is the process by which two initially distinct lipid bilayers merge their hydrophobic cores, resulting in one interconnected structure. If this fusion proceeds completely through both leaflets of both bilayers, an aqueous bridge is formed and the internal contents of the two structures can mix...
of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
. The virus RdRp partially uncoats the nucleocapsid and transcribes
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
the genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
into positive-stranded mRNAs, which are then translated into structural and nonstructural proteins. Marburgvirus L binds to a single promoter located at the 3' end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3' end of the genome are transcribed in the greatest abundance, whereas those toward the 5' end are least likely to be transcribed. The gene order is therefore a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein
Nucleoprotein
A nucleoprotein is any protein that is structurally associated with nucleic acid .Many viruses harness this protein, and they are known for being host-specific...
, whose concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-stranded antigenomes that are in turn transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. Virions bud
Budding
Budding is a form of asexual reproduction in which a new organism grows on another one. The new organism remains attached as it grows, separating from the parent organism only when it is mature. Since the reproduction is asexual, the newly created organism is a clone and is genetically identical...
off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.
Diagnosis
MVD is clinically indistinguishable from Ebola virus disease (EVD), and it can also easily be confused with many other diseases prevalent in Equatorial AfricaEquatorial Africa
Equatorial Africa is an ambiguous term that is sometimes used to refer to tropical Africa, or the region of Sub-Saharan Africa traversed by the equator....
, such as other viral hemorrhagic fever
Viral hemorrhagic fever
The viral hemorrhagic fevers are a diverse group of animal and human illnesses that are caused by four distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress...
s, falciparum malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
, typhoid fever
Typhoid fever
Typhoid fever, also known as Typhoid, is a common worldwide bacterial disease, transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enterica, serovar Typhi...
, shigellosis
Shigellosis
Shigellosis, also known as bacillary dysentery or Marlow Syndrome, in its most severe manifestation, is a foodborne illness caused by infection by bacteria of the genus Shigella. Shigellosis rarely occurs in animals other than humans and other primates like monkeys and chimpanzees...
, rickettsial diseases
Rickettsia
Rickettsia is a genus of non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci , rods or thread-like . Being obligate intracellular parasites, the Rickettsia survival depends on entry, growth, and replication within the cytoplasm of eukaryotic host cells...
such as typhus
Typhus
Epidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters...
, cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...
, gram-negative septicemia
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, borreliosis such as relapsing fever
Relapsing fever
Relapsing fever is an infection caused by certain bacteria in the genus Borrelia. It is a vector-borne disease that is transmitted through the bites of lice or soft-bodied ticks.-Louse-borne relapsing fever:...
or EHEC enteritis
Verotoxin-producing Escherichia coli
Verotoxin-producing Escherichia coli comprise strains of the bacterium Escherichia coli that, when infecting humans, have been linked with the severe complication hemolytic-uremic syndrome . They are known by a number of names, including enterohemorrhagic E. coli , Shiga-like toxin-producing E...
. Other infectious diseases that ought to be included in the differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
include leptospirosis
Leptospirosis
Leptospirosis is caused by infection with bacteria of the genus Leptospira, and affects humans as well as other mammals, birds, amphibians, and reptiles.The...
, scrub typhus
Scrub typhus
Scrub typhus or Bush typhus is a form of typhus caused by Orientia tsutsugamushi first isolated and identified in 1930 in Japan., accessdate: 16 October 2011...
, plague, Q fever
Q fever
Q fever is a disease caused by infection with Coxiella burnetii, a bacterium that affects humans and other animals. This organism is uncommon but may be found in cattle, sheep, goats and other domestic mammals, including cats and dogs...
, candidiasis
Candidiasis
Thrush redirects here. For the hoof infection see Thrush .Candidiasis or thrush is a fungal infection of any of the Candida species , of which Candida albicans is the most common...
, histoplasmosis
Histoplasmosis
Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease primarily affects the lungs...
, trypanosomiasis
Trypanosomiasis
Trypanosomiasis or trypanosomosis is the name of several diseases in vertebrates caused by parasitic protozoan trypanosomes of the genus Trypanosoma. Approximately 500,000 men, women and children in 36 countries of sub-Saharan Africa suffer from human African trypanosomiasis which is caused by...
, visceral leishmaniasis
Leishmaniasis
Leishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly...
, hemorrhagic smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
, measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
, and fulminant viral hepatitis
Viral hepatitis
Viral hepatitis is liver inflammation due to a viral infection. It may present in acute or chronic forms. The most common causes of viral hepatitis are the five unrelated hepatotropic viruses Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D, and Hepatitis E...
. Non-infectious diseases that can be confused with MVD are acute promyelocytic leukemia
Acute promyelocytic leukemia
Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia , a cancer of the blood and bone marrow. It is also known as acute progranulocytic leukemia; APL; AML with t, PML-RARA and variants; FAB subtype M3 and M3 variant.In APL, there is an abnormal accumulation of immature...
, hemolytic uremic syndrome, snake
Snake
Snakes are elongate, legless, carnivorous reptiles of the suborder Serpentes that can be distinguished from legless lizards by their lack of eyelids and external ears. Like all squamates, snakes are ectothermic, amniote vertebrates covered in overlapping scales...
envenomation
Envenomation
Envenomation is the process by which venom is injected into some animal by the bite of a venomous animal. Many kinds of animals, including mammals , reptiles , spiders , insects , employ venom for hunting and for self defense...
, clotting factor
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
deficiencies/platelet disorders, thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
, hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia , also known as Osler-Weber-Rendu disease and Osler-Weber-Rendu syndrome, is a genetic disorder that leads to abnormal blood vessel formation in the skin, mucous membranes, and often in organs such as the lungs, liver and brain.It may lead to nosebleeds, acute...
, Kawasaki disease
Kawasaki disease
Kawasaki disease , also known as Kawasaki syndrome, lymph node syndrome and mucocutaneous lymph node syndrome, is an autoimmune disease in which the medium-sized blood vessels throughout the body become inflamed. It is largely seen in children under five years of age...
, and even warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
intoxication. The most important indicator that may lead to the suspicion of MVD at clinical examination is the medical history
Medical history
The medical history or anamnesis of a patient is information gained by a physician by asking specific questions, either of the patient or of other people who know the person and can give suitable information , with the aim of obtaining information useful in formulating a diagnosis and providing...
of the patient, in particular the travel and occupational history (which countries and caves were visited?) and the patient's exposure to wildlife (exposure to bats or bat excrements?). MVD can be confirmed by isolation of marburgviruses from or by detection of marburgvirus antigen or genomic or subgenomic RNAs in patient blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
or serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
samples during the acute phase of MVD. Marburgvirus isolation is usually performed by inoculation
Inoculation
Inoculation is the placement of something that will grow or reproduce, and is most commonly used in respect of the introduction of a serum, vaccine, or antigenic substance into the body of a human or animal, especially to produce or boost immunity to a specific disease...
of grivet
Grivet
The grivet is an Old World monkey with long white tufts of hair along the sides of the face. Some authorities consider this and all of the members of the genus Chlorocebus to be a single species, Cercopithecus aethiops. As here defined, the grivet is restricted to Ethiopia, Sudan, Djibouti and...
kidney epithelial Vero E6 or MA-104 cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
s or by inoculation of human adrenal carcinoma SW-13 cells, all of which react to infection with characteristic cytopathic effect
Cytopathic effect
Cytopathic effect or cytopathogenic effect refers to degenerative changes in cells, especially in tissue culture, and may be associated with the multiplication of certain viruses....
s. Filovirions can easily be visualized and identified in cell culture by electron microscopy due to their unique filamentous shapes, but electron microscopy cannot differentiate the various filoviruses alone despite some overall length differences. Immunofluorescence assays
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
are used to confirm marburgvirus presence in cell cultures. During an outbreak, virus isolation and electron microscopy are most often not feasible options. The most common diagnostic methods are therefore RT-PCR
Reverse transcription polymerase chain reaction
Reverse transcription polymerase chain reaction is a variant of polymerase chain reaction , a laboratory technique commonly used in molecular biology to generate many copies of a DNA sequence, a process termed "amplification"...
in conjunction with antigen-capture ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
, which can be performed in field or mobile hospitals and laboratories. Indirect immunofluorescence assays (IFAs)
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
are not used for diagnosis of MVD in the field anymore.
Prevention
There are currently no Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
-approved vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
s for the prevention of MVD. Many candidate vaccines have been developed and tested in various animal models. Of those, the most promising ones are DNA vaccines
DNA vaccination
DNA vaccination is a technique for protecting an organism against disease by injecting it with genetically engineered DNA to produce an immunological response. Nucleic acid vaccines are still experimental, and have been applied to a number of viral, bacterial and parasitic models of disease, as...
or based on Venezuelan equine encephalitis virus
Venezuelan equine encephalitis virus
Venezuelan equine encephalitis virus is a mosquito-borne viral pathogen that causes Venezuelan equine encephalitis or encephalomyelitis . VEE can affect all equine species, such as horses, donkeys, and zebras. After infection, equines may suddenly die or show progressive central nervous system...
replicons
Replicon (genetics)
A replicon is a DNA molecule or RNA molecule, or a region of DNA or RNA, that replicates from a single origin of replication.For most prokaryotic chromosomes, the replicon is the entire chromosome. One notable exception found comes from archaea, where two Sulfolobus species have been shown to...
, vesicular stomatitis Indiana virus (VSIV)
Vesicular stomatitis virus
Vesicular stomatitis Indiana virus is a virus in the family Rhabdoviridae; the well-known Rabies virus belongs to the same family. VSIV can infect insects, cattle, horses, pigs and humans. It has particular importance to farmers in certain regions of the world where it can infect cattle...
or filovirus-like particles (VLPs) as all of these candidates could protect nonhuman primates from marburgvirus-induced disease. DNA vaccines have entered clinical trials. Marburgviruses are highly infectious
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, but not very contagious
Contagious disease
A contagious disease is a subset category of infectious diseases , which are easily transmitted by physical contact with the person suffering the disease, or by their secretions or objects touched by them....
. Importantly, and contrary to popular belief, marburgviruses do not get transmitted by aerosol
Aerosol
Technically, an aerosol is a suspension of fine solid particles or liquid droplets in a gas. Examples are clouds, and air pollution such as smog and smoke. In general conversation, aerosol usually refers to an aerosol spray can or the output of such a can...
during natural MVD outbreaks. Due to the absence of an approved vaccine, prevention of MVD therefore relies predominantly on behavior modification, proper personal protective equipment
Personal protective equipment
Personal protective equipment refers to protective clothing, helmets, goggles, or other garment or equipment designed to protect the wearer's body from injury by blunt impacts, electrical hazards, heat, chemicals, and infection, for job-related occupational safety and health purposes, and in...
, and sterilization
Sterilization (microbiology)
Sterilization is a term referring to any process that eliminates or kills all forms of microbial life, including transmissible agents present on a surface, contained in a fluid, in medication, or in a compound such as biological culture media...
/disinfection
Disinfection
Disinfectants are substances that are applied to non-living objects to destroy microorganisms that are living on the objects. Disinfection does not necessarily kill all microorganisms, especially nonresistant bacterial spores; it is less effective than sterilisation, which is an extreme physical...
.
In endemic zones
The natural maintenance hosts of marburgviruses remain to be identified unequivocally. However, the isolation of both MARV and RAVV from batBat
Bats are mammals of the order Chiroptera "hand" and pteron "wing") whose forelimbs form webbed wings, making them the only mammals naturally capable of true and sustained flight. By contrast, other mammals said to fly, such as flying squirrels, gliding possums, and colugos, glide rather than fly,...
s and the association of several MVD outbreaks with bat-infested mines or caves strongly suggests that bats are involved in marburgvirus transmission to humans. Avoidance of contact with bats and abstaining from visits to caves is highly recommended, but may not be possible for those working in mines or people dependent on bats as a food source.
During outbreaks
Since marburgviruses are not spreading via aerosol, the most straightforward prevention method during MVD outbreaks is to avoid direct (skin-to-skin) contact with patients, their excretionExcretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
s and body fluids, or possibly contaminated
Contamination
Contamination is the presence of a minor and unwanted constituent in material, physical body, natural environment, at a workplace, etc.-Specifics:"Contamination" also has more specific meanings in science:...
materials and utensils. Patients ought to be isolated but still have the right to be visited by family members. Medical staff should be trained and apply strict barrier nursing techniques (disposable face mask, gloves, goggles, and a gown at all times). Traditional burial
Burial
Burial is the act of placing a person or object into the ground. This is accomplished by excavating a pit or trench, placing an object in it, and covering it over.-History:...
rituals, especially those requiring embalming
Embalming
Embalming, in most modern cultures, is the art and science of temporarily preserving human remains to forestall decomposition and to make them suitable for public display at a funeral. The three goals of embalming are thus sanitization, presentation and preservation of a corpse to achieve this...
of bodies, ought to be discouraged or modified, ideally with the help of local traditional healers.
In the laboratory
Marburgviruses are World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
Risk Group 4 Pathogens, requiring Biosafety Level 4-equivalent containment
Biosafety
Biosafety: prevention of large-scale loss of biological integrity, focusing both on ecology and human health .Biosafety is related to several fields:*In ecology ,...
. Laboratory researchers have to be properly trained in BSL-4 practices and wear proper personal protective equipment.
Treatment
There is currently no effective marburgvirus-specific therapyTherapy
This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...
for MVD. Treatment is primarily supportive in nature and includes minimizing invasive procedures, balancing fluids and electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s to counter dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, administration of anticoagulants early in infection to prevent or control disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
, administration of procoagulants
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
late in infection to control hemorrhaging
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
, maintaining oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
levels, pain management
Pain management
Pain management is a branch of medicine employing an interdisciplinary approach for easing the suffering and improving the quality of life of those living with pain. The typical pain management team includes medical practitioners, clinical psychologists, physiotherapists, occupational therapists,...
, and administration of antibiotics or antimycotics to treat secondary infections. Experimentally, recombinant vesicular stomatitis Indiana virus
Vesicular stomatitis virus
Vesicular stomatitis Indiana virus is a virus in the family Rhabdoviridae; the well-known Rabies virus belongs to the same family. VSIV can infect insects, cattle, horses, pigs and humans. It has particular importance to farmers in certain regions of the world where it can infect cattle...
(VSIV) expressing the glycoprotein of MARV has been used successfully in nonhuman primate models as post-exposure prophylaxis. Novel, very promising, experimental therapeutic regimens rely on antisense technology
Antisense therapy
Antisense therapy is a form of treatment for genetic disorders or infections.When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nuc acid that will bind to the messenger RNA produced by that gene and inactivate...
: phosphorodiamidate morpholino oligomers
Morpholino
In molecular biology, a Morpholino is a molecule in a particular structural family that is used to modify gene expression. Morpholino oligomers are an antisense technology used to block access of other molecules to specific sequences within nucleic acid...
(PMOs) targeting the MARV genome could prevent disease in nonhuman primates.
Prognosis
Prognosis is generally poor (average case-fatality rate of all MVD outbreaks to date = 82%). If a patient survives, recovery may be prompt and complete, or protracted with sequelaSequela
A sequela) is a pathological condition resulting from a disease, injury, or other trauma.Chronic kidney disease, for example, is sometimes a sequela of diabetes, and neck pain is a common sequela of whiplash or other trauma to the cervical vertebrae. Post-traumatic stress disorder may be a...
e, such as orchitis
Orchitis
Orchitis or orchiditis is a condition of the testes involving inflammation. It can also involve swelling and frequent infection.-Symptoms:Symptoms of orchitis are similar to those of testicular torsion...
, hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, parotitis
Parotitis
Parotitis is an inflammation of one or both parotid glands, the major salivary glands located on either side of the face, in humans. The parotid gland is the salivary gland most commonly affected by inflammation.-Infectious parotitis:...
, desquamation
Desquamation
Desquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably...
or alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
. Importantly, MARV is known to be able to persist in some survivors and to either reactivate and cause a secondary bout of MVD or to be transmitted via sperm
Sperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
, causing secondary cases of infection and disease.
Of the 252 people who contracted Marburg during the 2004–2005 outbreak in Angola, 227 died, for a case fatality rate of 90%.
Although all age groups are susceptible to infection, children are more rarely infected. In the 1998–2000 Congo epidemic, only 8% of the cases were children less than 5 years old.
Epidemiology
| Year | Virus | Geographic location | Human cases/deaths (case-fatality rate) |
|---|---|---|---|
| 1967 | MARV | Marburg Marburg Marburg is a city in the state of Hesse, Germany, on the River Lahn. It is the main town of the Marburg-Biedenkopf district and its population, as of March 2010, was 79,911.- Founding and early history :... and Frankfurt Frankfurt Frankfurt am Main , commonly known simply as Frankfurt, is the largest city in the German state of Hesse and the fifth-largest city in Germany, with a 2010 population of 688,249. The urban area had an estimated population of 2,300,000 in 2010... , West Germany Germany Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate... ; and Belgrade Belgrade Belgrade is the capital and largest city of Serbia. It is located at the confluence of the Sava and Danube rivers, where the Pannonian Plain meets the Balkans. According to official results of Census 2011, the city has a population of 1,639,121. It is one of the 15 largest cities in Europe... , Yugoslavia Yugoslavia Yugoslavia refers to three political entities that existed successively on the western part of the Balkans during most of the 20th century.... |
31/7 (23%) |
| 1975 | MARV | Rhodesia Rhodesia Rhodesia , officially the Republic of Rhodesia from 1970, was an unrecognised state located in southern Africa that existed between 1965 and 1979 following its Unilateral Declaration of Independence from the United Kingdom on 11 November 1965... and Johannesburg Johannesburg Johannesburg also known as Jozi, Jo'burg or Egoli, is the largest city in South Africa, by population. Johannesburg is the provincial capital of Gauteng, the wealthiest province in South Africa, having the largest economy of any metropolitan region in Sub-Saharan Africa... , South Africa South Africa The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans... |
3/1 (33%) |
| 1980 | MARV | Kenya Kenya Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east... |
2/1 (50%) |
| 1987 | RAVV | Kenya Kenya Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east... |
1/1 (100%) |
| 1988 | MARV | Koltsovo Koltsovo Koltsovo may refer to:*Koltsovo, Novosibirsk Oblast, an urban-type settlement in Novosibirsk Oblast, Russia*Koltsovo, Yekaterinburg, a former urban-type settlement in Sverdlovsk Oblast, Russia; now a part of the city of Yekaterinburg... , Soviet Union Soviet Union The Soviet Union , officially the Union of Soviet Socialist Republics , was a constitutionally socialist state that existed in Eurasia between 1922 and 1991.... |
1/1 (100%) [laboratory accident] |
| 1990 | MARV | Koltsovo Koltsovo Koltsovo may refer to:*Koltsovo, Novosibirsk Oblast, an urban-type settlement in Novosibirsk Oblast, Russia*Koltsovo, Yekaterinburg, a former urban-type settlement in Sverdlovsk Oblast, Russia; now a part of the city of Yekaterinburg... , Soviet Union Soviet Union The Soviet Union , officially the Union of Soviet Socialist Republics , was a constitutionally socialist state that existed in Eurasia between 1922 and 1991.... |
1/0 (0%) [laboratory accident] |
| 1998–2000 | MARV + RAVV | Durba and Watsa Watsa Watsa is a community in Province Orientale of the Democratic Republic of the Congo, administrative center of the Watsa Territory.Watsa was the location of the VI battalion of the Force Publique in the 1940s and 1950s.... , Democratic Republic of the Congo Democratic Republic of the Congo The Democratic Republic of the Congo is a state located in Central Africa. It is the second largest country in Africa by area and the eleventh largest in the world... |
154/128 (83%) |
| 2004–2005 | MARV | Angola Angola Angola, officially the Republic of Angola , is a country in south-central Africa bordered by Namibia on the south, the Democratic Republic of the Congo on the north, and Zambia on the east; its west coast is on the Atlantic Ocean with Luanda as its capital city... |
252/227 (90%) |
| 2007 | MARV + RAVV | Uganda Uganda Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by... |
4/1 (25%) |
| 2008 | MARV | Uganda Uganda Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by... , Netherlands Netherlands The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders... , Colorado Colorado Colorado is a U.S. state that encompasses much of the Rocky Mountains as well as the northeastern portion of the Colorado Plateau and the western edge of the Great Plains... |
2/1 (50%) |
1967 outbreak
MVD was first documented in 1967, when 31 people became ill in the GermanGermany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
towns of Marburg
Marburg
Marburg is a city in the state of Hesse, Germany, on the River Lahn. It is the main town of the Marburg-Biedenkopf district and its population, as of March 2010, was 79,911.- Founding and early history :...
and Frankfurt am Main, and in Belgrade
Belgrade
Belgrade is the capital and largest city of Serbia. It is located at the confluence of the Sava and Danube rivers, where the Pannonian Plain meets the Balkans. According to official results of Census 2011, the city has a population of 1,639,121. It is one of the 15 largest cities in Europe...
, Yugoslavia
Yugoslavia
Yugoslavia refers to three political entities that existed successively on the western part of the Balkans during most of the 20th century....
. The outbreak involved 25 primary MARV infections and seven deaths, and six nonlethal secondary cases. The outbreak was traced to infected grivet
Grivet
The grivet is an Old World monkey with long white tufts of hair along the sides of the face. Some authorities consider this and all of the members of the genus Chlorocebus to be a single species, Cercopithecus aethiops. As here defined, the grivet is restricted to Ethiopia, Sudan, Djibouti and...
s (species Chlorocebus aethiops) imported from an undisclosed location in Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
and used in developing poliomyelitis
Poliomyelitis
Poliomyelitis, often called polio or infantile paralysis, is an acute viral infectious disease spread from person to person, primarily via the fecal-oral route...
vaccines. The monkeys were received by Behringwerke, a Marburg company founded by the first winner of the Nobel Prize in Medicine, Emil von Behring. The company, which at the time was owned by Hoechst
Hoechst AG
Hoechst AG was a German chemicals then life-sciences company that became Aventis Deutschland after its merger with France's Rhône-Poulenc S.A. in 1999...
, was originally set up to develop sera
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
against tetanus
Tetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...
and diphtheria
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...
. Primary infections occurred in Behringwerke laboratory
Laboratory
A laboratory is a facility that provides controlled conditions in which scientific research, experiments, and measurement may be performed. The title of laboratory is also used for certain other facilities where the processes or equipment used are similar to those in scientific laboratories...
staff while working with grivet tissues or tissue cultures without adequate personal protective equipment
Personal protective equipment
Personal protective equipment refers to protective clothing, helmets, goggles, or other garment or equipment designed to protect the wearer's body from injury by blunt impacts, electrical hazards, heat, chemicals, and infection, for job-related occupational safety and health purposes, and in...
. Secondary cases involved two physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s, a nurse, a post-mortem attendant, and the wife of a veterinarian
Veterinarian
A veterinary physician, colloquially called a vet, shortened from veterinarian or veterinary surgeon , is a professional who treats disease, disorder and injury in animals....
. All secondary cases had direct contact, usually involving blood, with a primary case. Both physicians became infected through accidental skin pricks when drawing blood from patients.
A popular science account of this outbreak can be found in Laurie Garrett
Laurie Garrett
Laurie Garrett is a Pulitzer prize-winning science journalist and writer of two bestselling books. She was awarded the Pulitzer Prize for Explanatory Journalism in 1996 for a series of works published in Newsday, chronicling the Ebola virus outbreak in Zaire.-Biographical information:Garrett...
’s book The Coming Plague.
1975 cases
In 1975, an Australian tourist became infected with MARV in RhodesiaRhodesia
Rhodesia , officially the Republic of Rhodesia from 1970, was an unrecognised state located in southern Africa that existed between 1965 and 1979 following its Unilateral Declaration of Independence from the United Kingdom on 11 November 1965...
(today Zimbabwe
Zimbabwe
Zimbabwe is a landlocked country located in the southern part of the African continent, between the Zambezi and Limpopo rivers. It is bordered by South Africa to the south, Botswana to the southwest, Zambia and a tip of Namibia to the northwest and Mozambique to the east. Zimbabwe has three...
). He died in a hospital in Johannesburg
Johannesburg
Johannesburg also known as Jozi, Jo'burg or Egoli, is the largest city in South Africa, by population. Johannesburg is the provincial capital of Gauteng, the wealthiest province in South Africa, having the largest economy of any metropolitan region in Sub-Saharan Africa...
, South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...
. His girlfriend and an attending nurse subsequently came down with MVD, but survived. A popular science account of these cases can be found in Laurie Garrett
Laurie Garrett
Laurie Garrett is a Pulitzer prize-winning science journalist and writer of two bestselling books. She was awarded the Pulitzer Prize for Explanatory Journalism in 1996 for a series of works published in Newsday, chronicling the Ebola virus outbreak in Zaire.-Biographical information:Garrett...
’s book The Coming Plague.
1980 cases
A case of MARV infection occurred in 1980 in KenyaKenya
Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east...
. A French man, who worked as an electrical engineer in a sugar factory in Nzoia (close to Bungoma
Bungoma
Bungoma is a town in Western Province of Kenya, bordered by Uganda in the west. Bungoma town was established as a trading centre in the early 20th century. The town is the headquarters of Kenya's Bungoma District and it hosts a municipal council...
) at the base of Mount Elgon
Mount Elgon
Mount Elgon is an extinct shield volcano on the border of Uganda and Kenya, north of Kisumu and west of Kitale.- Physical features :It is the oldest and largest solitary volcano in East Africa, covering an area of around 3500 km²....
(which contains Kitum Cave
Kitum Cave
Kitum Cave is a non-solutional cave developed in pyroclastic rocks in Mount Elgon National Park, Kenya. The cave extends about into the side of the mountain. The walls are rich in salt, and animals such as elephants have gone deep into the cave for centuries in search of salt...
), became infected by unknown means and died shortly after admission to Nairobi
Nairobi
Nairobi is the capital and largest city of Kenya. The city and its surrounding area also forms the Nairobi County. The name "Nairobi" comes from the Maasai phrase Enkare Nyirobi, which translates to "the place of cool waters". However, it is popularly known as the "Green City in the Sun" and is...
Hospital. The attending physician contracted MVD, but survived. A popular science account of these cases can be found in Richard Preston
Richard Preston
Richard Preston, born August 5, 1954 in Cambridge, Massachusetts, U.S., is a New Yorker writer and bestselling author perhaps best-known for his books about infectious disease epidemics and bioterrorism, although he has written other non-fiction works...
’s book The Hot Zone
The Hot Zone
The Hot Zone is a best-selling 1994 non-fiction bio-thriller by Richard Preston about the origins and incidents involving viral hemorrhagic fevers, particularly ebolaviruses and marburgviruses...
(the French man is referred to under the pseudonym
Pseudonym
A pseudonym is a name that a person assumes for a particular purpose and that differs from his or her original orthonym...
“Charles Monet”, whereas the physician is identified under his real name Shem Musoke).
1987 case
In 1987, a single lethal case of RAVV infection occurred in a 15-year-old Danish boy, who spent his vacation in KisumuKisumu
Kisumu is a port city in western Kenya at , with a population of 355,024 . It is the third largest city in Kenya, the principal city of western Kenya, the immediate former capital of Nyanza Province and the headquarters of Kisumu County. It has a municipal charter but no city charter...
, Kenya
Kenya
Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east...
. He had visited Kitum Cave
Kitum Cave
Kitum Cave is a non-solutional cave developed in pyroclastic rocks in Mount Elgon National Park, Kenya. The cave extends about into the side of the mountain. The walls are rich in salt, and animals such as elephants have gone deep into the cave for centuries in search of salt...
on Mount Elgon
Mount Elgon
Mount Elgon is an extinct shield volcano on the border of Uganda and Kenya, north of Kisumu and west of Kitale.- Physical features :It is the oldest and largest solitary volcano in East Africa, covering an area of around 3500 km²....
prior to travelling to Mombasa
Mombasa
Mombasa is the second-largest city in Kenya. Lying next to the Indian Ocean, it has a major port and an international airport. The city also serves as the centre of the coastal tourism industry....
, where he developed clinical signs of infection. The boy died after tramsfer to Nairobi
Nairobi
Nairobi is the capital and largest city of Kenya. The city and its surrounding area also forms the Nairobi County. The name "Nairobi" comes from the Maasai phrase Enkare Nyirobi, which translates to "the place of cool waters". However, it is popularly known as the "Green City in the Sun" and is...
Hospital. A popular science account of this case can be found in Richard Preston
Richard Preston
Richard Preston, born August 5, 1954 in Cambridge, Massachusetts, U.S., is a New Yorker writer and bestselling author perhaps best-known for his books about infectious disease epidemics and bioterrorism, although he has written other non-fiction works...
’s book The Hot Zone
The Hot Zone
The Hot Zone is a best-selling 1994 non-fiction bio-thriller by Richard Preston about the origins and incidents involving viral hemorrhagic fevers, particularly ebolaviruses and marburgviruses...
(the boy is referred to under the pseudonym
Pseudonym
A pseudonym is a name that a person assumes for a particular purpose and that differs from his or her original orthonym...
“Peter Cardinal”).
1988 laboratory infection
In 1988, researcher Nikolai Ustinov infected himself lethally with MARV after accidentally pricking himself with a syringe used for inoculation of guinea pigGuinea pig
The guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
s. The accident occurred at the Scientific-Production Association "Vektor" (today the State Research Center of Virology and Biotechnology "Vektor") in Koltsovo
Koltsovo
Koltsovo may refer to:*Koltsovo, Novosibirsk Oblast, an urban-type settlement in Novosibirsk Oblast, Russia*Koltsovo, Yekaterinburg, a former urban-type settlement in Sverdlovsk Oblast, Russia; now a part of the city of Yekaterinburg...
, USSR (today Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
). Very little information is publicly available about this MVD case because Ustinov’s experiments were classified. A popular science account of this case can be found in Ken Alibek
Ken Alibek
Colonel Kanatzhan Alibekov — known as Dr. Kenneth Alibek since 1992 — is a former Soviet physician, scientist and biological warfare expert of Kazakh descent. He is a military physician, has PhD in microbiology and ScD in biotechnology...
’s book Biohazard.
1990 laboratory infection
Another laboratory accident occurred at the Scientific-Production Association "Vektor" (today the State Research Center of Virology and Biotechnology "Vektor") in KoltsovoKoltsovo
Koltsovo may refer to:*Koltsovo, Novosibirsk Oblast, an urban-type settlement in Novosibirsk Oblast, Russia*Koltsovo, Yekaterinburg, a former urban-type settlement in Sverdlovsk Oblast, Russia; now a part of the city of Yekaterinburg...
, USSR, when a scientist contracted MARV by unknown means.
1998–2000 outbreak
A major MVD outbreak occurred among illegal gold miners around Goroumbwa mine in Durba and WatsaWatsa
Watsa is a community in Province Orientale of the Democratic Republic of the Congo, administrative center of the Watsa Territory.Watsa was the location of the VI battalion of the Force Publique in the 1940s and 1950s....
, Democratic Republic of Congo from 1998 to 2000, when co-circulating MARV and RAVV caused 154 cases of MVD and 128 deaths. The outbreak ended with the flooding of the mine.
2004–2005 outbreak
In early 2005, the World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) began investigating an outbreak of viral hemorrhagic fever
Viral hemorrhagic fever
The viral hemorrhagic fevers are a diverse group of animal and human illnesses that are caused by four distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress...
in Angola
Angola
Angola, officially the Republic of Angola , is a country in south-central Africa bordered by Namibia on the south, the Democratic Republic of the Congo on the north, and Zambia on the east; its west coast is on the Atlantic Ocean with Luanda as its capital city...
, which was centered in the northeastern Uíge Province but also affected many other provinces. The Angolan government had to ask for international assistance, pointing out that there were only approximately 1,200 doctors in the entire country, with some provinces having as few as two. Health care workers also complained about a shortage of personal protective equipment
Personal protective equipment
Personal protective equipment refers to protective clothing, helmets, goggles, or other garment or equipment designed to protect the wearer's body from injury by blunt impacts, electrical hazards, heat, chemicals, and infection, for job-related occupational safety and health purposes, and in...
such as gloves, gowns, and masks. Médecins Sans Frontières
Médecins Sans Frontières
' , or Doctors Without Borders, is a secular humanitarian-aid non-governmental organization best known for its projects in war-torn regions and developing countries facing endemic diseases. Its headquarters are in Geneva, Switzerland...
(MSF) reported that when their team arrived at the provincial hospital at the center of the outbreak, they found it operating without water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
and electricity
Electricity
Electricity is a general term encompassing a variety of phenomena resulting from the presence and flow of electric charge. These include many easily recognizable phenomena, such as lightning, static electricity, and the flow of electrical current in an electrical wire...
. Contact tracing
Contact tracing
In epidemiology, contact tracing is the identification and diagnosis of persons who may have come into contact with an infected person. For sexually transmitted diseases, this is generally limited to sexual partners but for highly virulent diseases such as Ebola and tuberculosis, a thorough contact...
was complicated by the fact that the country's roads and other infrastructure have been devastated after nearly three decades of civil war
Angolan War of Independence
The Angolan War of Independence began as an uprising against forced cotton cultivation, and became a multi-faction struggle for control of Portugal's Overseas Province of Angola with three nationalist movements and a separatist movement...
and the countryside remained littered with land mine
Land mine
A land mine is usually a weight-triggered explosive device which is intended to damage a target—either human or inanimate—by means of a blast and/or fragment impact....
s. Americo Boa Vida Hospital in the Angolan capital Luanda
Luanda
Luanda, formerly named São Paulo da Assunção de Loanda, is the capital and largest city of Angola. Located on Angola's coast with the Atlantic Ocean, Luanda is both Angola's chief seaport and its administrative center. It has a population of at least 5 million...
set up a special isolation ward to treat infected people from the countryside. Unfortunately, because MVD often results in death, some people came to view hospitals and medical workers with suspicion and treated helpers with hostility. For instance, a specially-equipped isolation ward at the provincial hospital in Uíge was reported to be empty during much of the epidemic, even though the facility was at the center of the outbreak. WHO was forced to implement what it described as a "harm reduction strategy", which entailed distributing disinfectants to affected families who refused hospital care. Of the 252 people who contracted MVD during outbreak, 227 died.
2007 cases
In 2007, four minerMiner
A miner is a person whose work or business is to extract ore or minerals from the earth. Mining is one of the most dangerous trades in the world. In some countries miners lack social guarantees and in case of injury may be left to cope without assistance....
s became infected with marburgviruses in Kamwenge District
Kamwenge District
Kamwenge District is a district in Western Uganda. Like most other Ugandan districts, it is named after its 'chief town', Kamwenge, where the district headquarters are located. Kamwenge District is part of the Kingdom of Toro, one of the ancient traditional monarchies in Uganda...
, Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
. The first case, a 29-year-old man, became symptomatic on July 4, 2007, was admitted to a hospital on July 7, and died on July 13. Contact tracing revealed that the man had had prolonged close contact with two colleagues (a 22-year-old man and a 23-year-old man), who experienced clinical signs of infection before his disease onset. Both men had been admitted to hospitals in June and survived their infections, which were proven to be due to MARV. A fourth, 25-year-old man, developed MVD clinical signs in September and was shown to be infected with RAVV. He also survived the infection.
2008 cases
On July 10, 2008, the Netherlands National Institute for Public Health and the EnvironmentNetherlands National Institute for Public Health and the Environment
The Netherlands National Institute for Public Health and the Environment , is a Dutch research institute that is an independent agency of the Dutch Ministry of Health, Welfare and Sport....
reported that a 41-year-old Dutch woman, who had visited Python Cave in Maramagambo Forest during her holiday in Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
suffered of MVD due to MARV infection, and had been admitted to a hospital in the Netherlands
Netherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
. The woman died under treatment in the Leiden University Medical Centre in Leiden on July 11. The Ugandan Ministry of Health closed the cave after this case. On January 9 of that year an infectious diseases physician notified the Colorado Department of Public Health and Education that a 44-year-old American woman who had returned from Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
showed signs of an unknown febrile illness that required hospitalisation. At the time, serologic testing was negative for viral hemorrhagic fever
Viral hemorrhagic fever
The viral hemorrhagic fevers are a diverse group of animal and human illnesses that are caused by four distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress...
; she was discharged on January 19, 2008. After the death of the Dutch patient and the discovery that the American woman had visited Python Cave, further testing confirmed the patient demonstrated MARV antibodies and RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
.
External links
- ViralZone: Marburg virus
- Center for Disease Control, Infection Control for Viral Haemorrhagic Fevers In the African Health Care Setting.
- Center for Disease Control, Marburg Haemorrhagic Fever.
- Center for Disease Control, Known Cases and Outbreaks of Marburg Haemorrhagic Fever
- World Health OrganizationWorld Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
, Marburg Haemorrhagic Fever. - Red Cross PDF
- Virus Pathogen Database and Analysis Resource (ViPR): Filoviridae