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Hemorrhagic smallpox, sometimes called bloody pox, fulminant smallpox, and blackpox, is a severe and rare form of smallpox and is usually fatal. Like all forms of smallpox it is caused by the variola virus. It is characterized by an incubation period of 7 to 14 days. It has two stages, the first begins with fever, headache, chills, nausea, vomiting and severe muscle aches. The skin flushes in a deep-purple, uneven pattern across the face. The early stage is often mistaken for measles. The late stage is characterized by the appearance of small blisters resembling a severe form of chickenpox. These small blisters then flatten until they are even with the skin, and change into reddish lesions similar to those seen in measles. The skin then turns a deep purple. Lesions appear inside the mouth and active bleeding from oral and nasal mucous membranes is common. This is followed by active bleeding in the gastrointestinal tract, and blood appears in the stool and urine. Blood studies resemble the clinical values of disseminated intravascular coagulation.
In malignant-type smallpox (also called flat smallpox) the lesions remained almost flush with the skin at the time when raised vesicles form in the ordinary type. It is unknown why some people developed this type. Historically, it accounted for 5–10 percent of cases, and the majority (72 percent) were children. Malignant smallpox was accompanied by a severe prodromal phase that lasted 3–4 days, prolonged high fever, and severe symptoms of toxemia. The rash on the tongue and palate was extensive. Skin lesions matured slowly and by the seventh or eighth day they were flat and appeared to be buried in the skin. Unlike ordinary-type smallpox, the vesicles contained little fluid, were soft and velvety to the touch, and may have contained hemorrhages. Malignant smallpox was nearly always fatal.
Referring to the character of the eruption and the rapidity of its development, modified smallpox occurred mostly in previously vaccinated people. In this form the prodromal illness still occurred but may be less severe than in the ordinary type. There is usually no fever during evolution of the rash. The skin lesions tended to be fewer and evolve more quickly, are more superficial, and may not show the uniform characteristic of more typical smallpox. Modified smallpox was rarely, if ever, fatal. This form of variola major is more easily confused with chickenpox.
The illness in humans is a severe form of hemorrhagic fever. Typically, after a 1–3 day incubation period following a tick bite or 5–6 days after exposure to infected blood or tissues, flu-like symptoms appear, which may resolve after one week. In up to 75% of cases, signs of bleeding can appear within 3–5 days of the onset of illness in case of bad containment of the first symptoms: mood instability, , mental confusion and throat petechiae; and soon after nosebleeds, vomiting, and black stools. The liver becomes swollen and painful. Disseminated intravascular coagulation may occur, as well as acute kidney failure, shock, and sometimes acute respiratory distress syndrome. People usually begin to recover after 9–10 days first symptoms appeared. Up to 30% of infected people die by the end of the second week of illness.
There are a number of symptoms of the virus. In the first 1–8 days the first phase begins. The symptoms in this phase are:
- chills
- headache
- pain in the lower and upper extremities and severe prostration
- a rash on the soft palate
- swollen glands in the neck
- appearance of blood in the eyes (conjunctival suffusion)
- dehydration
- hypotension
- gastrointestinal symptoms (symptoms relating to the stomach and intestines)
- patients may also experience effects on the central nervous system
In 1–2 weeks, some people may recover, although others might not. They might experience a focal hemorrhage in mucosa of gingival, uterus, and lungs, a papulovesicular rash on the soft palate, cervical lymphadenopathy (it occurs in the neck which that enlarges the lymph glandular tissue), and occasional neurological involvement. If the patient still has OHF after 3 weeks, then a second wave of symptoms will occur. It also includes signs of encephalitis. In most cases if the sickness does not fade away after this period, the patient will die. Patients that recover from OHF may experience hearing loss, hair loss, and behavioral or psychological difficulties associated with neurological conditions.
The most detailed study on the frequency, onset, and duration of MVD clinical signs and symptoms was performed during the 1998–2000 mixed MARV/RAVV disease outbreak. A maculopapular rash, petechiae, purpura, ecchymoses, and hematomas (especially around needle injection sites) are 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.
Clinical phases of Marburg Hemorrhagic Fever's presentation are described below. Note that phases overlap due to variability between cases.
1. Incubation: 2–21 days, averaging 5–9 days.
2. Generalization Phase: Day 1 up to Day 5 from onset of clinical symptoms. MHF presents with a high fever (~40˚C) and a sudden, severe headache, with accompanying chills, fatigue, nausea, vomiting, diarrhea, pharyngitis, maculopapular rash, abdominal pain, conjunctivitis, & malaise.
3. Early Organ Phase: Day 5 up to Day 13. Symptoms include prostration, dyspnea, edema, conjunctival injection, viral exanthema, and CNS symptoms, including encephalitis, confusion, delirium, apathy, and aggression. Hemorrhagic symptoms typically occur late and herald the end of the early organ phase, leading either to eventual recovery or worsening & death. Symptoms include bloody stools, ecchymoses, blood leakage from venipuncture sites, mucosal & visceral hemorrhaging, and possibly hematemesis.
4. Late Organ Phase: Day 13 up to Day 21+. Symptoms bifurcate into two constellations for survivors & fatal cases. Survivors will enter a convalescence phase, experiencing myalgia, fibromyalgia, hepatitis, asthenia, ocular symptoms, & psychosis. Fatal cases continue to deteriorate, experiencing continued fever, obtundation, coma, convulsions, diffuse coagulopathy, metabolic disturbances, shock and death, with death typically occurring between Days 8 and 16.
Signs and symptoms of VHFs include (by definition) fever and bleeding. Manifestations of VHF often also include flushing of the face and chest, small red or purple spots (petechiae), bleeding, swelling caused by edema, low blood pressure (hypotension), and shock. Malaise, muscle pain, headache, vomiting, and diarrhea occur frequently. The severity of symptoms varies with the type of virus. The “VHF syndrome” (capillary leak, bleeding diathesis, and circulatory compromise leading to shock) appears in a majority of people with filovirus hemorrhagic fevers (e.g., Ebola and Marburg virus), Crimean–Congo hemorrhagic fever (CCHF), and the South American hemorrhagic fevers caused by arenaviruses, but only in a small minority of patients with dengue, Rift Valley fever, and Lassa fever.
The characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. The alternative name for dengue, "breakbone fever", comes from the associated muscle and joint pains. The course of infection is divided into three phases: febrile, critical, and recovery.
The febrile phase involves high fever, potentially over , and is associated with generalized pain and a headache; this usually lasts two to seven days. Nausea and vomiting may also occur. A rash occurs in 50–80% of those with symptoms in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4–7), as a measles-like rash. A rash described as "islands of white in a sea of red" has also been observed. Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point, as may some mild bleeding from the mucous membranes of the mouth and nose. The fever itself is classically biphasic or saddleback in nature, breaking and then returning for one or two days.
In some people, the disease proceeds to a critical phase as fever resolves. During this period, there is leakage of plasma from the blood vessels, typically lasting one to two days. This may result in fluid accumulation in the chest and abdominal cavity as well as depletion of fluid from the circulation and decreased blood supply to vital organs. There may also be organ dysfunction and severe bleeding, typically from the gastrointestinal tract. Shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue, however those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk. This critical phase, while rare, occurs relatively more commonly in children and young adults.
The recovery phase occurs next, with resorption of the leaked fluid into the bloodstream. This usually lasts two to three days. The improvement is often striking, and can be accompanied with severe itching and a slow heart rate. Another rash may occur with either a maculopapular or a vasculitic appearance, which is followed by peeling of the skin. During this stage, a fluid overload state may occur; if it affects the brain, it may cause a reduced level of consciousness or seizures. A feeling of fatigue may last for weeks in adults.
Crimean–Congo hemorrhagic fever (CCHF) is a viral disease. Symptoms may include fever, muscle pains, headache, vomiting, diarrhea, and bleeding into the skin. Onset of symptoms is less than two weeks following exposure. Complications may include liver failure. In those who survive, recovery generally occurs around two weeks after onset.
The CCHF virus is typically spread by tick bites or contact with livestock carrying the disease. Those affected are often farmers or work in slaughterhouses. It can also spread between people via body fluids. Diagnosis is by detecting antibodies, the virus's RNA, or the virus itself. It is a type of viral hemorrhagic fever.
Prevention involves avoiding tick bites. A vaccine is not commercially available. Treatment is typically with supportive care. The medication ribavirin may also help.
It occurs in Africa, the Balkans, the Middle East, and Asia. Often it occurs in outbreaks. In 2013 Iran, Russia, Turkey, and Uzbekistan documented more than fifty cases. The risk of death among those affected is between 10 and 40%. It was first detected in the 1940s.
Typically, people infected with dengue virus are asymptomatic (80%) or have only mild symptoms such as an uncomplicated fever. Others have more severe illness (5%), and in a small proportion it is life-threatening. The incubation period (time between exposure and onset of symptoms) ranges from 3 to 14 days, but most often it is 4 to 7 days. Therefore, travelers returning from endemic areas are unlikely to have dengue if fever or other symptoms start more than 14 days after arriving home. Children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea) and have a greater risk of severe complications, though initial symptoms are generally mild but include high fever.
Marburg virus disease (MVD) is the official name listed in the World Health Organization'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.
Argentine hemorrhagic fever (AHF) or O'Higgins disease, also known in Argentina as mal de los rastrojos, stubble disease, is a hemorrhagic fever and zoonotic infectious disease occurring in Argentina. It is caused by the "Junín virus" (an arenavirus, closely related to the "Machupo virus", causative agent of Bolivian hemorrhagic fever). Its vector is a species of rodent, the corn mouse.
AHF is a grave acute disease which may progress to recovery or death in 1 to 2 weeks. The incubation time of the disease is between 10 and 12 days, after which the first symptoms appear: fever, headaches, weakness, loss of appetite and will. These intensify less than a week later, forcing the infected to lie down, and producing stronger symptoms such as vascular, renal, hematological and neurological alterations. This stage lasts about 3 weeks.
If untreated, the mortality of AHF reaches 15–30%. The specific treatment includes plasma of recovered patients, which, if started early, is extremely effective and reduces mortality to 1%.
Ribavirin also has shown some promise in treating arenaviral diseases.
The disease was first detected in the 1950s in the Junín Partido in Buenos Aires, after which its agent, the Junín virus, was named upon its identification in 1958. In the early years, about 1,000 cases per year were recorded, with a high mortality rate (more than 30%). The initial introduction of treatment serums in the 1970s reduced this lethality.
The infection has a slow onset with fever, malaise, headache and muscular pains, very similar to Malaria symptoms. Petechiae (blood spots) on the upper body and bleeding from the nose and gums are observed when the disease progresses to the hemorrhagic phase, usually within seven days of onset.
Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses in which fever and hemorrhage are caused by a viral infection. VHFs may be caused by five distinct families of RNA viruses: the families "Arenaviridae", "Filoviridae", "Bunyaviridae", "Flaviviridae", and "Rhabdoviridae". All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian "nephropathia epidemica" (a Hantavirus), while others, such as Ebola virus, can cause severe, life-threatening disease.
Omsk hemorrhagic fever is a viral hemorrhagic fever caused by a Flavivirus.
It is found in Siberia. It is named for an outbreak in Omsk.
Living fish afflicted with VHS may appear listless or limp, hang just
beneath the surface, or swim very abnormally, such as constant flashing
circling due to the tropism of the virus for the brain.
External signs may include darker coloration, exophthalmia ("pop eye"),
pale or red-dotted gills, sunken eyes, and bleeding around orbits (eye sockets) and
at base of fins.
Genetics researchers at the Lake Erie Research Center at the University of Toledo are developing a test that will speed diagnosis from a month to a matter of hours.
Venezuelan hemorrhagic fever (VHF) is a zoonotic human illness first identified in 1989. The disease is most prevalent in several rural areas of central Venezuela and is caused by the Guanarito virus (GTOV) which belongs to the Arenaviridae family. The short-tailed cane mouse ("Zygodontomys brevicauda") is the main host for GTOV which is spread mostly by inhalation of aerosolized droplets of saliva, respiratory secretions, urine, or blood from infected rodents. Person-to-person spread is possible, but uncommon.
VHSV is a hemorrhagic disease, meaning it causes bleeding. Internally,
the virus can cause petechial hemorrhaging (tiny spots of blood) in internal
muscle tissue, and petechial or severe hemorrhaging in internal organs and
other tissues. Internal hemorrhaging can be observed as red spots inside
a dead fish, particularly around the kidney, spleen, and intestines, as
well as the swim bladder, which would normally have a clear membrane.
The liver may be pale, mottled with red hyperemic areas, the kidney
may be swollen and unusually red, the spleen may be swollen, and the digestive
tract may be empty.
External signs are not always present, but if they are, hemorrhaging on the
skin's surface can appear as anywhere from tiny red dots (petechiae) to
large red patches.
A "vaccine-preventable disease" is an infectious disease for which an effective preventive vaccine exists. If a person acquires a vaccine-preventable disease and dies from it, the death is considered a vaccine-preventable death.
The most common and serious vaccine-preventable diseases tracked by the World Health Organization (WHO) are: diphtheria, "Haemophilus influenzae" serotype b infection, hepatitis B, measles, meningitis, mumps, pertussis, poliomyelitis, rubella, tetanus, tuberculosis, and yellow fever. The WHO reports licensed vaccines being available to prevent, or contribute to the prevention and control of, 25 vaccine-preventable infections.
Brazilian hemorrhagic fever (BzHF) is an infectious disease caused by the Sabiá virus, an Arenavirus. The Sabiá virus is one of the arenoviruses from South America to cause hemorrhagic fever. It shares a common progenitor with the Junin virus, Machupo virus, Tacaribe virus, and Guanarito virus. It is an enveloped RNA virus and is highly infectious and lethal. Very little is known about this disease, but it is thought to be transmitted by the excreta of rodents.
There have only been three documented infections of the Sabiá virus, only one of which occurred naturally and the other two cases occurred in the clinical setting. The only naturally occurring case was in 1990, when a female agricultural engineer who was staying in the neighborhood of Jardim Sabiá near São Paulo, Brazil contracted the disease. She presented with hemorrhagic fever and died. Her autopsy showed liver necrosis. A virologist who was studying the woman's disease contracted the virus but survived. Ribavirin was not given in these first two cases. Four years later, in 1994, a researcher was exposed to the virus in a level 3 biohazard facility at Yale University when a centrifuge bottle cracked, leaked, and released aerosolized virus particle. He was successfully treated with ribavirin.
Ribavirin is thought to be effective in treating the illness, similar to other arenaviruses. Compared to the patients who did not receive ribavirin, the patient who was treated with it had a shorter and less severe clinical course. Symptomatic control such as fluids to address dehydration and bleeding may also be required.
The Sabiá virus is a Biosafety Level 4 pathogen.
This virus has also been implicated as a means for bioterrorism, as it can be spread through aerosols.
Eczema vaccinatum is a rare severe adverse reaction to smallpox vaccination.
It is characterized by serious local or disseminated, umbilicated, vesicular, crusting skin rashes in the face, neck, chest, abdomen, upper limbs and hands, caused by widespread infection of the skin in people with previous diagnosed skin conditions such as eczema or atopic dermatitis, even if the conditions are not active at the time. Other signs and symptoms include fever and facial and supraglottic edema. The condition may be fatal if severe and left untreated. Survivors are likely to have some scarring (pockmarks).
Smallpox vaccine should not be given to patients with a history of eczema. Because of the danger of transmission of vaccinia, it also should not be given to people in close contact with anyone who has active eczema and who has not been vaccinated. People with other skin diseases (such as atopic dermatitis, burns, impetigo, or herpes zoster) also have an increased risk of contracting eczema vaccinatum and should not be vaccinated against smallpox.
Eczema is also associated with increased complications related to other vesiculating viruses such as chickenpox; this is called eczema herpeticum.
Symptoms of HFRS usually develop within 1 to 2 weeks after exposure to infectious material, but in rare cases, they may take up to 8 weeks to develop. Initial symptoms begin suddenly and include intense headaches, back and abdominal pain, fever, chills, nausea, and blurred vision. Individuals may have flushing of the face, inflammation or redness of the eyes, or a rash. Later symptoms can include low blood pressure, acute shock, vascular leakage, and acute kidney failure, which can cause severe fluid overload.
The severity of the disease varies depending upon the virus causing the infection. Hantaan and Dobrava virus infections usually cause severe symptoms, while Seoul, Saaremaa, and Puumala virus infections are usually more moderate. Complete recovery can take weeks or months.
The course of the illness can be split into five phases:
- Febrile phase: Symptoms include redness of cheeks and nose, fever, chills, sweaty palms, diarrhea, malaise, headaches, nausea, abdominal and back pain, respiratory problems such as the ones common in the influenza virus, as well as gastro-intestinal problems. These symptoms normally occur for three to seven days and arise about two to three weeks after exposure.
- Hypotensive phase: This occurs when the blood platelet levels drop and symptoms can lead to tachycardia and hypoxemia. This phase can last for 2 days.
- Oliguric phase: This phase lasts for three to seven days and is characterised by the onset of renal failure and proteinuria.
- Diuretic phase: This is characterized by diuresis of three to six litres per day, which can last for a couple of days up to weeks.
- Convalescent phase: This is normally when recovery occurs and symptoms begin to improve.
This syndrome can also be fatal. In some cases, it has been known to cause permanent renal failure.
The disease has a fatality rate of 3-10%, and it affects 400-500 people annually.
Monkeypox is an infectious disease caused by the monkeypox virus. Symptoms begin with fever, headache, muscle pains, swollen lymph nodes, and feeling tired. This is then followed by a rash that forms blisters and crusts over. The time from exposure to onset of symptoms is around 10 days. The duration of symptoms is typically 2 to 5 weeks.
Monkeypox may be spread from handling bush meat, an animal bite or scratch, body fluids, contaminated objects, or close contact with an infected person. The virus is believed to normally circulate among certain rodents in Africa. Diagnosis can be confirmed by testing a lesion for the viruses DNA. The disease can appear similar to chickenpox.
The smallpox vaccine is believed to prevent infection. Cidofovir may be useful as treatment. The risk of death in those infected is up to 10%.
The disease mostly occurs in Central and West Africa. It was first identified in 1958 among laboratory monkeys. The first cases in humans were found in 1970 in the Democratic Republic of the Congo. An outbreak that occurred in the United States in 2003 was traced to a pet store where imported Gambian rodents were sold.