[CINC] Hantavirus

[whalebear at cs.com]

To:  Channel Islands National Marine Sanctuary Naturalist Corps
 
From:  Chuck Rennie, MD, FACEP
            Medical Director
            Channel Islands National Park
 
As most of you know, the past several weeks have seen a cluster of 8 cases of Hantavirus CardioPulmonary Syndrome in Yosemite National Park.  Three of the cases resulted in death.  This note is intended to be a quick primer/update on the syndrome.  I apologize to those who find the language either too technical or too simplistic; this primer is going out to a group with a broad range of biological and medical knowledge.  If anyone should have questions, pleas don't hesitate to e-mail me.
 
HANTAVIRUS
 
Background 
The genus Hantavirus consists of at least 14 viruses and over 30 strains within the family Bunyaviridae.  Other genuses within the family range from plant pathogens to causative agents of hemorrhagic fevers (febrile illnesses with significant bleeding components).  Transmission of Bunyaviridae viruses is generally via arthropod (mosquito) vector, with the exception of Hantaviruses, which are transmitted by rodents.  Hantaviruses first came to medical attention during the Korean War, when approximately 3200 cases of hemorrhagic fever with renal failure were documented among UN forces.  The causative agent, the first known Hantavirus, was not isolated until 1978.  Genomic sequencing indicates these viruses are of some antiquity; they may be millions of years old.  Each species of Hantavirus appears to have a single rodent species as the dominant natural reservoir and to have coevolved with that species.  It is postulated that Hantaviruses evolved in the Old World and crossed the Bering Strait with their mammalian hosts.  Hantavirus syndromes fall into two groups:  a syndrome of hemorrhagic fever with renal failure (hemorrhagic fever with renal syndrome, or HFRS) seen commonly in the Eastern Hemisphere, and a syndrome of severe pulmonary (lung) and cardiac failure (initially called Hantavirus pulmonary syndrome, or HPS, but now referred to as Hantavirus cardiopulmonary syndrome, or HCPS) seen in the Western Hemisphere.  A few cases of HCPS have recently been described in the Eastern Hemisphere.  HFRS was not medically described until the 1950's and HCPS until 1993, but both syndromes are probably of some antiquity.  Descriptions of a disease present at the time of Richard III of England and diseases seen in early 20th century Russia and  in the trenches of World War I were probably HFRS.  In the Western Hemisphere, a Civil War disease and a disease described by the Navajo in the early twentieth century were probably HCPS (the Navajo even postulated transmission by rodents).  Serological evidence links HCPS to a case of pulmonary failure as early as 1959.  The Eastern Hemisphere form (HFRS) is common, with between 150,000 and 200,000 hospitalizations reported annually (over 50% from China alone), and mortalities ranging from less than 0.1% to approximately 10%.  HCPS is (thus far) less common, with only 602 cases documented in the United States.  It is more common in South America; exactly how common in uncertain, given the variable standards of investigation and reporting.
 
 Hantavirus CardioPulmonary Syndrome
Hantavirus CardioPulmonary Syndrome came to medical attention in 1993 with a cluster of pulmonary-related deaths in the Four Corners area of the southwestern United States.  The investigation quickly isolated and named the Sin Nombre virus as a previously undescribed Hantavirus and the etiologic agent in the deaths (tentative names of Four Corners disease and Navajo disease were rejected as too pejorative).  Genomic  sequencing indicates this particular Hantavirus may have evolved over only the past 37-106 years.  The clinical syndrome was labeled HCPS.  Similar species of Hantaviruses cause HCPS in other parts of the United States, Canada, Central, and South America, Each species of Hantavirus is vectored by a different host species of rodent; in the western and southwestern United States all cases of HCPS are due to the Sin Nombre virus (SNV), and the host/reservoir is the deer mouse (Peromyscus maniculatus).  Infection with Sin Nombre virus has been detected at low levels in species other than Peromyscus, but these are probably incidental infections transmitted from the primary reservoir rather than being part of the primary reservoir.  The infected Peromyscus remains outwardly healthy, although histopathologic changes occur in the lungs and liver.  Transmission is by aerosolization of mouse urine, saliva, blood, or feces.  In rare cases rodent bites can transmit the virus.  Two clusters of cases, both in Argentina,  are the only human-to-human transmissions documented. 
 
Epidemiology of Hantavirus 
 Seroprevalence of antibodies to Hantavirus (indicating infection) among Peromyscus in California was 11.8% overall in a study published in 1997.  The locale with the highest prevalence on the mainland was the Truckee area, with an antibody prevalence of  50%.  Infection rates were highest at altitudes greater than 1200m and around human habitation (which may be an artifact of sampling).  In the same study, antibody prevalence in the Channel Islands was 20.9% overall, ranging from 0% on Anacapa, Santa Barbara, and San Nicholas Islands to 2.9% on San Clemente, 14.3% on Catalina, 17.9% on San Miguel, 58% on Santa Rosa, and 71.4% on Santa Cruz Islands.  Several subsequent studies have looked at antibody prevalence on the Channel Islands; despite some problems with sampling methodology, they remain in broad general agreement with the 1997 study.  This is particularly worrisome because the Channel Islands have extremely high densities of Peromyscus, with Santa Barbara Island having the highest density known.
 
Most cases of Hantavirus in the United States are solitary (cases have been described in 34 states), with only 12% occurring in clusters (with a presumed common source).  Case clusters are more common in South America, reaching 39% of cases in one series.  63% of the cases in the United States are in males.  The mean age is 37, with a range of 6-83. Hispanics account for 20% of cases, American Indians 18%, African Americans 2%, and Asians 1%.  Cases are almost exclusively in rural areas, with a predilection for  individuals of lower socioeconomic status, farm workers, and those working around mouse-infested buildings.  There is a dramatic increase in cases at altitudes of greater than 1200m that has been borne out in multiple studies.  Clusters in California have been seen in the Sierra Nevada, most recently in Yosemite National  Park. 
 
Clinical Features of Hantavirus and Treatment
Hantavirus has an incubation period of between one and six weeks (most institutional fact sheets list incubation periods of up to five weeks, but symptom onset has been documented up to slightly more than six weeks after exposure).  The prodrome is flu-like and non-specific.  Fever, chills, and myalgias (muscle aches) predominate for the first 3-5 days, with headache, non-productive cough, nausea, vomiting, and diarrhea frequent concomitants.  The next phase is cardiopulmonary, with the development of severe respiratory distress (Acute Respiratory Distress Syndrome, or ARDS), hypoxemia (low blood oxygen), cardiac depression (heart failure), and hypotension (low blood pressure).  Patients often require intubation and mechanical ventilation (respirator).  In rare cases, diffuse hemorrhage can occur.  Recovery is as rapid as the clinical deterioration.  Mortality in the United States averages 38%,  although mortality tabulated in the US since 1993 has ranged from 18.52% to 50% annually.  
 
There is no specific treatment for HCPS.  Antiviral medication is ineffective for both prophylaxis and treatment (although Ribavirin is of utility in the Old World HFRS).  The only treatment modalities are supportive, including vasopressors for blood pressure, mechanical ventilation for respiratory failure, and antibiotics for secondary infections (antibiotics have no effect on the Hantavirus infection itself).  There is evidence that early admission to the ICU and aggressive pulmonary management improve survival rates.  A DNA vaccine is being developed (phase I clinical trials are underway), and there is experimental evidence that passive immunization with monoclonal or polyclonal antibodies will ameliorate the disease.
 
Infectivity of Hantavirus 
The lethality of HCPS is not in question, nor is the necessity for precautions.  But there are significant questions about the infectivity of the virus.  Before HCPS was described, Peromyscus scampered freely around the Field Station on Santa Cruz Island, the Vail Ranch on Santa Rosa Island, and all over the rest of the Channel Islands.  Recreation at the Field Station was often watching the Peromyscus running around the main room as we did our work after dinner.  They often got into food (hence the metal cabinets in the kitchen).  If the acoustical ceiling tiles were raised, a centimeters- thick layer of mouse droppings was found above them.  There were no precautions when sweeping or otherwise dealing with mice or mouse droppings.  When a group of island residents and biologists were initially briefed about the danger of Hantavirus by an earnest young CDC investigator, Al Vail (the then owner of Santa Rosa Island) perhaps put it in best perspective when he commented "Son, I've been sleeping out there with mice crawling all over me for almost seventy years.  Do you mean to tell me that I might get sick?"  At the Santa Barbara Museum of Natural History, I  watched a colleague dissect Peromyscus intermittently for almost twenty years without gloves, his hands often covered in blood and mouse excrement.  He has had no HCPS symptoms.  Despite the high prevalence of Peromyscus infection on the Channel Islands, no illness compatible with HCPS is known to have occurred (due to the necessity for clearance/registration with the National Park Service, the Nature Conservancy, or past island owners for work on the Channel Islands, the community of researchers and students on the islands has always been somewhat limited.  Most people are known to each other in this small community, and a case of HCPS would not have gone unnoticed).  No case of HCPS is known to have occurred among campers in the Channel Islands.  The CDC also tested over 300 researchers and workers considered to be at high risk for Hantavirus infection through occupational exposure; no cases compatible with HCPS were found, and the seroprevalence of antibodies was 1.14%.  A number of theories have been advanced regarding the lack of cases in the Channel Islands.  It has been theorized that the UV scatter off the water inactivates the Sin Nombre virus (Hantaviruses are known to be UV labile).  It has also been theorized that the damp marine atmosphere might decrease the tendency for aerosolization of the virus (although this would pertain less to areas like the Central Valley of Santa Cruz Island).  In truth, the reasons are unknown.  It is also unknown why, despite the infection rate among Peromyscus of 11.8% in California and the frequent exposure of persons in rural areas to mice, the cases are so sporadic.  
 
Hantavirus Precautions 
Precautions regarding Hantavirus infections, and all rodent-vectored diseases, are critical in any mouse-infested area.  Homes, garages, and outbuildings should be inspected for all possible gaps and holes where rodents could gain entry and all such areas repaired.  Repair should be undertaken prior to the trapping of rodents; research indicates that removal without rodent-proofing is ineffective, and in some cases yields a new rodent population with a higher infection rate of Sin Nombre virus.  

Gloves should be used to clean up all dead rodents or rodent urine or feces.  These areas should first be sprayed thoroughly with a household disinfectant or a 10% solution of bleach and water and allowed to stand for at least thirty minutes.  Any dead rodent should also be dusted with flea powder (fleas carried by rodents may vector the plague) prior to manipulation.  Any rag or paper towel used to pick up the rodent or rodent droppings should be placed in a plastic bag.  Dead rodents should be double-bagged.  The area should then be sprayed with a disinfectant or 10% bleach solution again.  Gloves should be sprayed with bleach or washed with soap and water, then discarded.  After discarding the gloves, hands should  be washed with soap and water.  Any floor areas where rodents may have been present should either be wet-mopped or sprayed with bleach solution before sweeping to prevent aerosolization of dust.  Dry sweeping should never be undertaken in any areas potentially frequented by mice.
 
Before any unused cabin or outbuilding is used, all windows and doors should be opened and the building allowed to air for at least 1-2 hours.  Procedures listed above should be followed for any rodent products.  All countertops should be cleaned with disinfectant or 10% bleach.  Affected bedding should be washed in hot water.  Affected furniture should be cleaned with detergent, disinfectant, or bleach solution.
 
If rodents are trapped, snap traps or poison bait should be used.  Live traps or glue traps may serve to disseminate the virus from an infected rodent.
 
Food should be kept in rodent-proof containers at all times when not in use.  Countertops should be washed down with 10% bleach before and after use.  Pet food should not be left out.  Garbage cans must be securely covered (other considerations, such as bears of raccoons, may pertain).  All trash outside buildings should be removed.  Grass and shrubbery should be neatly trimmed.  Woodpiles should not be kept near buildings and should be at least one foot off the ground.
 
Standard surgical masks, dust masks, or painters' masks are not effective.  If a mask is used, only HEPA (High Efficiency Particulate Air) masks are effective.
 
Please note that the guidelines above are empirical; none have been rigorously vetted.  Most institutions with potential for mouse infestation and Hantavirus have their own protocols, which should be followed (the advice above is a synthesis of recommendations from the CDC, the California State Department of Public Health, the New Mexico Department of Public Health, and the UC Natural Reserve System).
 
Hantavirus and the Future 
The Sin Nombre virus and Hantavirus Cardiopulmonary Syndrome have been in the literature for less than 20 years.  At present HCPS is seen in humans infrequently, although its mortality rate is high.  No definitive treatment exists, and vaccines are currently an unrealized hope for the future.  There is evidence that viral prevalence in mice is partially dependent on both climate changes and disruption/fragmentation of habitat, which means there is a high potential for this disease to become more common.  Scrupulous avoidance of rodents and rodent products, extreme care in cleaning them up, and behavior to minimize interaction with rodents is critical.  Although these behaviors have never been top priorities in venturing into rural or wilderness areas, our survival and avoidance of this and other zoonoses will depend on them in the future.
 
Anyone who ventures onto the Channel Islands or into a rural area with significant rodent presence and develops pulmonary or flu-like symptoms within six weeks should seek medical attention immediately.  The treating physician should be notified of potential exposure to Hantavirus.  Any questions the physician has can be answered either by logging onto the Hantavirus section of the CDC (national Center for Disease Control, based in Atlanta) or by calling the CDC.  I would also be happy to answer questions; I am on call continually for Channel Islands National Park and can be reached in emergencies by dialing Channel Islands National Park dispatch at 805 658-5700 or by mobile phone at 310 938-8387.
 
Thanks for reading this.....
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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