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This week we will discuss the hantaviruses. These viruses are found in three distinct, yet large, regions of the world: Asia, Europe, and the Americas. Moreover, they produce two distinct clinical syndromes delineated by these same regional geographies, hemorrhagic fever with renal syndrome in the Old World, and hantavirus pulmonary syndrome in the New World. These viruses can be highly virulent and result in high mortality.
The Pathogen. Hantaviruses are in the Bunyaviridae family of viruses. These spheroid viruses are approximately 95 to 110 nanometers in diameter. They are enveloped viruses with negative-sense, single-stranded RNA genomes in three segments. The three segments are classified as large (L), medium (M), and small (S). Each segment has an associated RNA polymerase:
The Epidemiology and the Landscape. The mode of transmission for hantaviruses is from infected rodents to humans via the airborne route. The virus is shed in the stool, urine, and saliva of the rodent reservoirs. As the excreta dry out, the virus remains viable in dust. If the the dust is disturbed, particularly by human activity in enclosed areas, the virus particles can be inhaled as they are introduced into the air. Hantaviruses are not transmissible from person to person.
There are approximately 100,000 incident cases of HFRS, with between 1% and 15% mortality associated with these cases. Good estimates for HPS incidence and HPS-associated deaths are not available, though the incidence is very low in North America. Nevertheless, the mortality attributable to HPS is generally much higher than that attributable to HFRS. Between 30% and 50% of admitted HPS cases do not survive the disease.
The approximate distribution of concentrated Old World hantaviruses is depicted below in the map by Ho Wang Lee:
Hantaan virus is represented by the shaded areas in northeastern Asia and southeastern Russia, while the shaded areas in southern Europe represent Dobrava virus. The shaded areas in Scandinavia and northwestern Russia represent Puumala virus, which is a less significant cause of human infection. The map above is quite dated, as is obvious from the "U.S.S.R" label. While these approximate areas of concentration are still relevant for today, they are, nevertheless, only approximations and they do only represent the areas of greatest concentration.
The map below published in the journal Emerging Infectious Diseases, gives a much more accurate distribution of the range and concentration of Hantaan virus in China, as well as the primary rodent reservoir, Apodemus agrarius:
The map below depicts the the distribution of New World hantaviruses, with their associated rodent reservoirs in italics.
At its simplest, the landscape of hantavirus infections, whether they are located in the eastern or western hemispheres, is comprised of rodent and human habitats wherein their points of intersection can create loci of zoonotic transmission from the rodents to humans. However, it is insufficient to claim that the landscape epidemiology of hantaviruses can simply be reduced to the contact between rodents (largely mice) and humans. There are, in fact, important features of both the physical and social landscape that determine the degree of contact between humans and the relevant rodent reservoirs.
For the most part, hantavirus transmission occurs in rural settings regardless of the geographic region or virus species. Nevertheless, the particular rural spaces that facilitate transmission can be different. For example, Hantaan virus infection in humans most commonly occurs in agrarian communities. This is driven in large part by the reservoir host, the Striped Field Mouse (Apodemus agrarius), which can exploit crop fields, and any human structures therein, as a readily available ecologic niche across a large portion of its range. As such, an agricultural landscape facilitates the potential contact between this particular reservoir species and human farmers sharing a common space. In addition, human Hantaan virus infection tends to occur in areas of mid to high precipitation.
While still a rural infection, Sin Nombre virus, on the other hand, is most common in the arid and semi-arid regions of the mountain west in North America, which only encompasses a part of the wider range of the reservoir host, the Deer Mouse (Peromyscus maniculatus). Nevertheless, perturbations in climate that lead to higher than normal precipitation can cause dramatic changes in the landscape epidemiology of Sin Nombre virus. In 1993 following an El Nino Southern Oscillation (ENSO), higher than normal levels of precipitation led to exceptionally high production of pine nuts in the southwestern range of the Deer Mouse. Pine nuts are a preferred food source for this mouse and this abundance of food following the ENSO subsequently led to a population explosion in the reservoir host mouse. As such, the contact rate between humans and mice increased as the expanding population of the mice brought them into greater contact with humans in rural settings. This led to a large (and first documented) Sin Nombre virus outbreak in the Four Corners region of the American Southwest. People of the Navajo Nation in particular were greatly affected by this outbreak. It is important to note that human hantavirus infection almost always occurs at the intersection between places of human habitation/occupation and the range of the mouse. Sporadic human infection in a wilderness setting outside the context of a human constructed space is extremely rare.
Control and Prevention. Rodent control is the primary strategy to control hantavirus infection in humans. While rare in any context, taking precautions to eliminate safe spaces for mice in the home or other structures of human habitation or occupation will eliminate effective human to mouse contact and thus block transmission of hantaviruses. The image below depicts the many areas within household structures that can be exploited by mice:
It is clear from the picture that a mouse has many opportunities for both food and habitation in and around the home. In order to eliminate safe spaces for mice the following steps can be employed:
Remove all food sources: Food and garbage should always be kept in well-sealed containers that cannot be breached by rodents. In addition, as depicted above, pet food and/or garden fruit and vegetables left unattended outside will often attract rodents.
Household maintenance: Good maintenance both inside and outside the home can be very important in eliminating rodent habitat. On the outside, overgrown plants and shrubs, unattended woodpiles or debris, and unattended outdoor structures can all serve as welcome homes for rodents, and should be be regularly maintained. On the inside, poorly sealed foundations, roofing, vents, and other household structures can provide easy access to the interior of the house and thus provide good mouse habitat. As such, it is very important to maintain good structural integrity of the house to keep the rodents out.
Pest control: Directly controlling rodent populations can be accomplished by keeping pets, especially cats, in the home, or by setting bait and traps. However, it is extremely important to maintain barrier control when disposing of rodent carcasses or when cleaning or setting traps. Rubber gloves, protective goggles, and a respirator should always be used.
Special case: Infrequently used or poorly ventilated spaces: Some structures that are infrequently used or are poorly ventilated, such as vacation homes, cabins, workplaces, or even standard basements/cellars, may have rodents and be contaminated with excreta and saliva. When confronted with the need to clean these kinds of spaces, the same barrier protection described above should be used (i.e. rubber gloves, protective goggles, and a respirator). In addition, it may be prudent to spray the floor with a disinfectant that is capable of lysing the envelopes of viral particles before sweeping and cleaning the space.
This week we will discuss the hantaviruses. These viruses are found in three distinct, yet large, regions of the world: Asia, Europe, and the Americas. Moreover, they produce two distinct clinical syndromes delineated by these same regional geographies, hemorrhagic fever with renal syndrome in the Old World, and hantavirus pulmonary syndrome in the New World. These viruses can be highly virulent and result in high mortality.
The Pathogen. Hantaviruses are in the Bunyaviridae family of viruses. These spheroid viruses are approximately 95 to 110 nanometers in diameter. They are enveloped viruses with negative-sense, single-stranded RNA genomes in three segments. The three segments are classified as large (L), medium (M), and small (S). Each segment has an associated RNA polymerase:
Hantavirus structure (Published in JASN December 1, 2005 vol. 16 no. 12 3669-3679)
The viruses invade host cells by endocytosis and replicate via the ER-Golgi intermediate compartment. Endothelial cells are the primary target host cells for hantaviruses. Vascular permeability is increased in both pathogenic forms of the disease, and is a key feature of the pathogenesis of these viruses, though hemorrhage and frank renal failure are limited to hemorrhagic fever with renal syndrome (HFRS), while hantavirus pulmonary syndrome (HPS) is characterized by lung involvement.
Hantavirus Life Cycle (Published in Clin. Microbiol. Rev. April 2010 vol. 23 no. 2 412-441)
There are scores of distinct hantavirus species, but the most relevant for human infection are the Hantaan virus of Asia and eastern Europe and the Dobrava virus of southern Europe, which cause HFRS, and the Sin Nombre virus of North America and the Laguna Negra virus and the Andes virus of the Southern Cone of South America, which cause HPS.
The Reservoir. Rodents serve as the natural reservoir for hantaviruses, though the relevant rodent species differ by geography and virus species.
The primary reservoir for the Hantaan virus is Apodemus agrarius, which is commonly known as the Striped Field Mouse:
Apodemus agrarius
This mouse is found from eastern Europe to Japan and is common in both forested and agricultural landscapes, and is, in fact, a common pest to agricultural communities across this very wide geographic region.
The primary reservoir for the Dobrava virus is Apodemus flavicollis, which is commonly known as the Yellow-necked Mouse:
Apodemus flavicollis
This mouse is found in southern Europe in mountainous, forested landscapes.
The primary reservoir for Sin Nombre virus is Peromyscus maniculatus, which is commonly known as the Deer Mouse:
Peromyscus maniculatus
This mouse is found throughout North America and is particularly common in the Mountain West, in forested, or mixed grassland-forested, landscapes.
The primary reservoir for Andes virus, and the many related viruses, is Oligoryzomys longicaudatus, which is commonly known as the long-tailed pygmy rice rat, or colilargo:
Oligoryzomys longicaudatus
This mouse is common in the mountains regions of Argentina and Chile in forested and shrub landscapes. Several other species in the genus Oligoryzomys can also serve as reservoir species for Andes virus.
The Disease. As mentioned above, hantaviruses cause two distinct clinical disease forms: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS).
HFRS typically presents with high fever, severe lower back or abdominal pain, and bleeding, petechiae, and disseminated intravascular coagulation. Intestinal problems are common with associated with nausea, vomiting, and diarrhea. Respiratory dysfunction can sometimes present if there is sufficient fluid accumulation in the lungs. Renal dysfunction is the hallmark of HFRS. Hypotension is also common, as is increased heart rhythm and decreased partial pressure of oxygen in the blood. Shock can occur and must be managed accordingly. Macroalbuminuria and renal failure usually present one to two weeks after the onset of initial symptoms. Thrombocytopenia and increased serum creatinine are common laboratory findings. The Hantaan virus and Dobrava virus are the primary species causing most HFRS cases.
HPS typically presents with high fever, myalgia, headache, but bleeding is not common. The intestinal problems described for HFRS can also present in HPS, including nausea, vomiting and diarrhea. Respiratory symptoms are the hallmark of HPS, but generally NOT during the early period of the infection. Leakage of the alveolar capillary beds leads to fluid accumulation in the alveoli and the later cardiopulmonary symptoms, which include elevated heart rate, rapid breathing, and hypoxia. Thrombocytopenia is common, as it is for HFRS, but hemorrhage is not. Continued loss of fluid into the lungs leads to pulmonary edema, which can be identified radiographically:
Cough and shortness of breath are late stage respiratory symptoms that are common to most patients. Metabolic acidosis can also occur in the later stages. While some degree of proteinuria is also common, extensive renal damage is rare.
There are approximately 100,000 incident cases of HFRS, with between 1% and 15% mortality associated with these cases. Good estimates for HPS incidence and HPS-associated deaths are not available, though the incidence is very low in North America. Nevertheless, the mortality attributable to HPS is generally much higher than that attributable to HFRS. Between 30% and 50% of admitted HPS cases do not survive the disease.
The approximate distribution of concentrated Old World hantaviruses is depicted below in the map by Ho Wang Lee:
Hantaan virus is represented by the shaded areas in northeastern Asia and southeastern Russia, while the shaded areas in southern Europe represent Dobrava virus. The shaded areas in Scandinavia and northwestern Russia represent Puumala virus, which is a less significant cause of human infection. The map above is quite dated, as is obvious from the "U.S.S.R" label. While these approximate areas of concentration are still relevant for today, they are, nevertheless, only approximations and they do only represent the areas of greatest concentration.
The map below published in the journal Emerging Infectious Diseases, gives a much more accurate distribution of the range and concentration of Hantaan virus in China, as well as the primary rodent reservoir, Apodemus agrarius:
Distribution of Hantaan virus in China (Published in: Emerg Infect Dis. 2007 Sep)
The map below depicts the the distribution of New World hantaviruses, with their associated rodent reservoirs in italics.
Distribution of hantaviruses and their reservoir species in the Americas (Published in: Virus Research, Volume 162, Issues 1–2, December 2011, Pages 138-147)
At its simplest, the landscape of hantavirus infections, whether they are located in the eastern or western hemispheres, is comprised of rodent and human habitats wherein their points of intersection can create loci of zoonotic transmission from the rodents to humans. However, it is insufficient to claim that the landscape epidemiology of hantaviruses can simply be reduced to the contact between rodents (largely mice) and humans. There are, in fact, important features of both the physical and social landscape that determine the degree of contact between humans and the relevant rodent reservoirs.
For the most part, hantavirus transmission occurs in rural settings regardless of the geographic region or virus species. Nevertheless, the particular rural spaces that facilitate transmission can be different. For example, Hantaan virus infection in humans most commonly occurs in agrarian communities. This is driven in large part by the reservoir host, the Striped Field Mouse (Apodemus agrarius), which can exploit crop fields, and any human structures therein, as a readily available ecologic niche across a large portion of its range. As such, an agricultural landscape facilitates the potential contact between this particular reservoir species and human farmers sharing a common space. In addition, human Hantaan virus infection tends to occur in areas of mid to high precipitation.
While still a rural infection, Sin Nombre virus, on the other hand, is most common in the arid and semi-arid regions of the mountain west in North America, which only encompasses a part of the wider range of the reservoir host, the Deer Mouse (Peromyscus maniculatus). Nevertheless, perturbations in climate that lead to higher than normal precipitation can cause dramatic changes in the landscape epidemiology of Sin Nombre virus. In 1993 following an El Nino Southern Oscillation (ENSO), higher than normal levels of precipitation led to exceptionally high production of pine nuts in the southwestern range of the Deer Mouse. Pine nuts are a preferred food source for this mouse and this abundance of food following the ENSO subsequently led to a population explosion in the reservoir host mouse. As such, the contact rate between humans and mice increased as the expanding population of the mice brought them into greater contact with humans in rural settings. This led to a large (and first documented) Sin Nombre virus outbreak in the Four Corners region of the American Southwest. People of the Navajo Nation in particular were greatly affected by this outbreak. It is important to note that human hantavirus infection almost always occurs at the intersection between places of human habitation/occupation and the range of the mouse. Sporadic human infection in a wilderness setting outside the context of a human constructed space is extremely rare.
Control and Prevention. Rodent control is the primary strategy to control hantavirus infection in humans. While rare in any context, taking precautions to eliminate safe spaces for mice in the home or other structures of human habitation or occupation will eliminate effective human to mouse contact and thus block transmission of hantaviruses. The image below depicts the many areas within household structures that can be exploited by mice:
It is clear from the picture that a mouse has many opportunities for both food and habitation in and around the home. In order to eliminate safe spaces for mice the following steps can be employed:
Remove all food sources: Food and garbage should always be kept in well-sealed containers that cannot be breached by rodents. In addition, as depicted above, pet food and/or garden fruit and vegetables left unattended outside will often attract rodents.
Household maintenance: Good maintenance both inside and outside the home can be very important in eliminating rodent habitat. On the outside, overgrown plants and shrubs, unattended woodpiles or debris, and unattended outdoor structures can all serve as welcome homes for rodents, and should be be regularly maintained. On the inside, poorly sealed foundations, roofing, vents, and other household structures can provide easy access to the interior of the house and thus provide good mouse habitat. As such, it is very important to maintain good structural integrity of the house to keep the rodents out.
Pest control: Directly controlling rodent populations can be accomplished by keeping pets, especially cats, in the home, or by setting bait and traps. However, it is extremely important to maintain barrier control when disposing of rodent carcasses or when cleaning or setting traps. Rubber gloves, protective goggles, and a respirator should always be used.
Special case: Infrequently used or poorly ventilated spaces: Some structures that are infrequently used or are poorly ventilated, such as vacation homes, cabins, workplaces, or even standard basements/cellars, may have rodents and be contaminated with excreta and saliva. When confronted with the need to clean these kinds of spaces, the same barrier protection described above should be used (i.e. rubber gloves, protective goggles, and a respirator). In addition, it may be prudent to spray the floor with a disinfectant that is capable of lysing the envelopes of viral particles before sweeping and cleaning the space.