Hantaviruses
Scientific name of the causative organism: The scientific name depends on the species because the hantavirues have been classified into a number of species for instance Hantavirus sin nombre virus
I. Classification
Superkingdom: Not applicable
Kingdom: Not applicable
Phylum: Not applicable
Order: Not applicable
Family: Bunyaviridiae
Genus: Hantavirus
Species: A number of species have been identified so far, these include the Sin Nombre Virus, Andes Virus, Hantaan Virus, Seoul Virus, Puumala Virus and Dobrava Virus.
Strain: Not applicable
II. Structure and morphology
If viral: Attachment to humans, enveloped or not, size, DNA or RNA, single or double stranded, integrates into human genome or not
Hantaviruses like the other viruses of the Bunyaviridiae family are spherical enveloped viruses with a diameter ranging from 100-200nm and a tripartite helical nucleocaspid. Hantaviruses are composed of 3-negative sense single stranded RNA segments. These viruses replicate exclusively in the cytoplasm of host cells and hence their RNA is not integrated into the human genome. The envelope glycoproteins of the hantaviruses attach to endothelial cells via two distinct cellular receptors on the surface of host cells, the decay accelerating factor and the β3 integrin chain (Hjelle & Torres-Perez, 2010).
Reproduction (binary fission, budding, sexual, viral, lysogenic)
Hantaviruses reproduce via viral replication in the cytoplasm of host cells. Once they attach to the β3 integrin chain receptors, they enter the cells via endocytosis. The envelope of the virion fuses with the membrane of the endosome releasing nuclocapsids into the cytoplasm. Transcription of viral genes and subsequent replication of viral RNA genomes is then directed by the viral RNA polymerase which is RNA-dependent (Hjelle & Torres-Perez, 2010).
Physical requirement for growth: The hantaviruses replicate within their host cells hence this section is not applicable.
Disease Dynamics :
Modes of transmission: Direct, indirect, (food, water or other) vector, fomite or other. How is the disease spread and what factors contribute to the spread of the disease in humans or in reservoirs?
The disease is spread directly through rodent bites and from one person to another although the mechanism for the latter mode of transmission is poorly understood. It is also transmitted indirectly via inhalation of aerosols from contaminated rodent urine, faeces and/or saliva. Residing in poorly ventilated rodent infested buildings or living in close proximity to areas inhabited by rodents are amongst the factors that have been identified as contributing to the spread of the disease in humans. The factors that promote the cross-transmission of the hantaviruses between rodents are yet to be fully elucidated upon. However, it is thought that cross-transmission occurs in rodents that inhabit synotopic regions or in those from closely related species (Hjelle & Torres-Perez, 2010).
Reservoir: Humans, animals or environment (soil, water, other)
The natural reservoir of the hantaviruses are specific rodent species although antibodies against these viruses have been found in domestic and wild animals like dogs, cats, pigs, deer and cattle (Zeier et al., 2005). The deer mouse scientifically known as Peromyscus maniculatus is amongst the rodents that act as a natural reservoir for the hantaviruses. In specific it has been identified as a reservoir for the Sin Nombre virus serotype of the hantaviruses. Murid of cricetid rodents belonging to the subfamilies Murinae, Sigmodontinae, Arvicolinae and Neotominae are thought to be the main reservoirs of the hantaviruses although recent research has shown that even insects of the Soricidae, Talpidae families also act as reservoirs for the same (Hjelle & Torres-Perez, 2010).
How does the organism infect humans and what tissues are targeted?
The specific process via which hantaviruses infect humans is yet to be fully elucidated upon but research into this is still ongoing. It is however thought that the viruses arrive at their target tissues either through uptake by regional lymph nodes or with or within a lung histiocyte. Upon arrival, the virus seeds within the local endothelium, infects a few cells and ultimately causes a primary viremia. Local production of inflammatory and chemotactic mediators is thought to precede secondary viremia and to be responsible for the development of systemic symptoms of the two diseases. In humans, hantaviruses target the kidneys and the retroperitoneum in HFRS and the lungs specifically the pulmonary bed and lymphoid organs in HCPC.
What are the symptoms of the disease?
The signs and symptoms of HFRS include fever, chills, headache, nausea and vomiting, lethargy, tachycardia, oliguria, facial and truncal flushing, shortness of breath, pulmonary edema with tachypnea, hemorrhages and shock. Meanwhile, HCPS presents with fever, chills, headache, dyspnea, tachypnea, tachycardia, shortness of breath, nausea and vomiting, noncardiogenic pulmonary edema, petechiaes/hemorrhages and shock.
What is the incubation period, the typical length of illness, recovery time and is there acquired immunity to the infection?
The incubation period for HFRS ranges from 1-5 weeks while the illness lasts for a period ranging from 9-30 days; the prodromal stage lasts for 5-10 days, the hypotensive phase on the other hand lasts for 1-3 days and the oliguric phase basically lasts for 3-5 days and is followed by a period of convalescence. The incubation period for HCPS is similar to that of HFRS that is 1-5 weeks. On the length of illness for HCPS; the prodromal /febrile stage for HCPS lasts from 3-10 days, the cardiorespiratory phase 1-6 days and the diuretic phase 1-3 days after which the patient enters a period of convalescence. The period of convalescence for the disease is highly variable between individuals. Regarding acquired immunity to the infection, a study by Manigold et al. (2010) showed that antibody titers against andes hantavirus increased over time in 10 out of 17 patients for a period ranging from months to years after the acute infection episode. They attributed this to the intrinsic latent antigenic stimulation of T-cells which are Gn-specific. Other studies have arrived at a similar conclusion that patients acquire immunity against the disease following an acute infection.
What treatments and prevention are available?
Ribavirin is the specific treatment used in the management of HFRS, cardioventilatory support and dialysis is on the other hand the supportive treatments used for the management of the same. There is no specific treatment for HCPS. Supportive management for HCPS includes extracorporeal membrane oxygenation and cardioventilatory support. Currently, there are no vaccines against hantaviruses although clinical trials aimed at producing an effective vaccine are ongoing. Prevention measures currently practiced include wearing protective gear like gloves when handling rodents such as field mice and avoiding living in rodent infested poorly ventilated buildings (Manigold, 2010).
What are the virulence factors? What are the susceptible populations (and why) and where (what areas of the world or what populations) is the disease found? Is this an opportunistic infection?
Research aimed at identifying the virulence factors in hantaviruses is still ongoing, however, it is thought that the envelope glycoproteins and the nucleocapsid proteins play a significant role in the pathogenesis of the two diseases. No single ethnic population has been shown to be susceptible to the two diseases because they affect everyone. However, the incidence of the disease is higher amongst males than females. In addition, people with variations in certain HLA-antigens experience more severe forms of the two diseases. HCPS and HFRS are not opportunistic infections (Manigold, 2010).
Epidemiology:
What is the incidence of this disease? How prevalent is it world-wide and in the US? What is the mortality rate? What factors contribute to the distribution of the disease?
Hantaviruses are distributed worldwide with about 150,000 cases of HFRS and HCPS being reported annually. The distribution of the two diseases is influenced by the distribution of rodents. 538 cases of human infection by hantavirus were reported in the US in 2009 only. HCPS infections have also been reported in a number of Southern American countries to include Brazil whereby approximately 1,100 cases of the disease have been identified since 1993 and Argentina where more than 1000 cases have been positively identified since 1995. Other countries in the region where cases have been reported include Bolivia, Venezuela, Chile, Peru amongst others. The disease has also been reported in Europe, Africa and in Asia. Case fatality ratios in the US are estimated at 50%, 30% in Argentina, 36% in Chile and 39% in Brazil. Of further note is that the disease has a higher incidence amongst men than in women. Landscape features that potentially impact on rodent population dynamics such as habitat fragmentation and human distribution strongly influence the distribution of the two diseases. For instance, the disease has been shown to be more prevalent in rural areas than in urban areas (Muranyi et al., 2005; Manigold, 2010; Hjelle & Torres-Perez, 2010).
What would you do to prevent the disease if you had unlimited money for that purpose?
I would explore less costly disease prevention measures like educating the public on the need to avoid rodent infested areas as well as the need to use protective gear like gloves and nasal masks when handling rodents or working in rodent infested areas.
References
Hjelle, B., & Torres-Perez, F. (2010). Hantaviruses in the Americas and their role as emerging
pathogens. Viruses, 2(12), 2559-2589. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed
Manigold, T., Mori, A., Graumann, R., Llop, E., Simon, V., Ferrés, M., Valdivieso, F., Castillo,
C., Hjelle, B., & Vial, P. (2010). Highly differentiated, resting gn-specific memory CD8+
T cells persist years after infection by andes hantavirus. PLoS Pathogens, 6(2), e1000779.
Retrieved from http://www.ncbi.nlm.nih.gov/pubmed
Muranyi, W., Bahr, U., Zeier, M., & Woude, F.J. (2005). Hantavirus infection. Journal of
the American Society of Nephrology, 16, 3669-3679. doi: 10.1681/ASN.2005050561.
Retrieved from http://www.ncbi.nlm.nih.gov/pubmed
Zeier, M., Handermann, M., Bahr, U., Rensch, B., Müller, S., Kehm, R., Muranyi, W., & Darai
G. (2005). New ecological aspects of hantavirus infection: a change of a paradigm and a
challenge of prevention: A review [Abstract]. Virus genes, 30(2), 157-180. Retrieved
from http://www.ncbi.nlm.nih.gov/pubmed
