Monday, May 1, 2017

No One Asks if You Rode in a Car

What have I got to do with this?
When patients present at ER and Urgent Care rooms with respiratory symptoms that resemble the flu – or hantavirus – they are supposed to be asked by healthcare providers if they have had contact with rodents in the previous month or so. If so, hantavirus is to be suspected, even if still highly improbable. If not, the small probability attributed to hantavirus becomes even smaller, and the quest for a diagnosis and treatment plan goes on.

But no one asks if you rode in a car, a truck, or a tractor cab. Virtually everyone does so, frequently, so what would be the point? 

If people are, as I've theorized in previous posts, contracting hantavirus by exposure in vehicle cabin air systems, this first line of hantavirus detection simply misses it. Even after diagnosis, many patients who have hantavirus report that they cannot recall having had any kind of contact with rodents.

Detection of hantavirus does not get much better from there.  

Hantavirus Pulmonary Syndrome is a Zebra

Sin Nombre hantavirus infection is thought to be extremely rare in humans. Only about 700 cases have been documented. That makes hantavirus a zebra disease.

Zebras are also rare compared to horses. Unless you happen to be on the Serengeti plains.

When doctors are diagnosing a difficult illness, they are trained to have a rule-of-thumb in the back of their minds. "When you hear hoof beats, don't look for zebras." The odds that your particular patient will turn out to have an extremely rare, "zebra" of an illness, are very low. So don't even look for them, keep your eyes peeled for horses or you will waste valuable time and delay the patient's diagnosis.

But there can be a problem with that. If you don't look for something, you have a reduced chance of finding it. When a disease is a zebra disease, it tends to be misdiagnosed, or missed entirely.

Dr. Hudzik, Dr. SzkodzinskiProf. Polonski: "During medical training, students and residents are being taught a quintessential maxim of clinical medicine—“When you hear hoofbeats, think of horses, not zebras”. Common diseases are what physicians should expect to encounter. Unfortunately, in a world of horses, the hoofbeats of zebras too often go unrecognized or misdiagnosed."

Could hantavirus pulmonary syndrome (HPS) be being misdiagnosed, because it is a rare, zebra of a disease that few practitioners have ever encountered? What measures are in place to capture HPS cases?

Reportable Disease

Because of its severity and high morbidity, about 40%, hantavirus is classified as a reportable disease, the Centers for Disease Control (CDC) is to be notified when cases are diagnosed by local healthcare practitioners. I have been assured by a CDC scientist that this system catches all of the HPS cases, at least in Western Washington. But what if cases of hantavirus infection are simply missed in the first place? 

The number of cases of hantavirus pulmonary syndrome (HPS) that are reported in the CDC's final statistics comprise only those that made it through the gauntlet of being suspected or spotted in blood work, then tested for, and finally forced through the resistance that some care providers show to diagnosing this rare illness. 

This is not the same as the number of actual HPS cases. 

As I studied hantavirus I grew concerned that that exposure difference, automobile cabin air systems, may be causing HPS cases and also causing them to be misdiagnosed. It even seemed possible that there could be a significant number of them. Of course, if you die, or nearly die, a significant number is 1.

Urgent Care Presentation

From the Centers for Disease Control's page on hantavirus pulmonary syndrome, the primary source of guidance on HPS for Emergency and Urgent Care rooms around the country:


Therefore, if you have been around rodents and have symptoms of fever, deep muscle aches, and severe shortness of breath, see your doctor immediately. Be sure to tell your doctor that you have been around rodents—this will alert your physician to look closely for any rodent-carried disease, such as HPS."

According to this guidance, it is incumbent on the patient, the seriously ill person that may be collapsing into hantavirus pulmonary syndrome, to inform the physician that they have had contact with rodents, probably, some time between seven days and seven weeks previously. 

For this measure to work, there has to be extensive public outreach to inform potential patients, which could include almost anyone. Those people have to recall that outreach warning while they are seriously ill (or be fortunate enough to have a friend or family member know that you swept the garage) and you have to think to tell the doctor about it.  

Hantavirus infection should also be suspected if a particular combination of blood test results is obtained. The combination is called a tetrad of symptoms because there are four changes that, together, suggest hantavirus infection. If that tetrad is spotted in the blood count test tests by someone knowledgeable enough to look for it, hantavirus should be suspected. The patient would then likely be tested for antibodies.

Even in the modern, excellent medical facility where my wife recovered, none of our doctors, nurses, or techs had ever encountered hantavirus before as is likely the case with most Hanta patients. It was almost literally the last thing anyone thought of or discussed during a week of brain-wracking over what was going wrong. They did not know what was wrong, so, they treated for everything they could, and provided supportive care. That was the right treatment, (fortunately!) but it does not hinge on, nor support, the diagnosis of hantavirus.

Diagnosis of hantavirus requires testing for antibodies to it, and that is not a trivial thing.

Hantavirus Antibody Testing

Testing requires that the doctors apply for permission from the CDC, almost the only place in the country that performs such testing. They must apply by going through their county or state health departments. The Protocol for Specimen Submission can be found in the CDC website, here:

It includes information on how to obtain the specimen, and ship it in a refrigerated package, along with links to the two forms that are to be completed, and the phone number to call to notify them when you are ready to transmit the specimens after you've received permission, and the International Air Transit Authority regulations to meet for how you package the specimen, and so forth. 

All very helpful. And a lot of time-consuming paperwork. 

Of course, when the physician receives the test results it will be too late to make any changes to patient care. The HPS patient will be dead or recovering by then. Even if results were quicker, there is no specific treatment for hantavirus, aside from caution in administering fluids, which can trigger refractory pulmonary edema. Those fluids were probably already administered during a life-saving effort to stabilize plunging blood pressure a couple days previously.  

By the time that it is received, a positive detection of hantavirus antibodies does not really change patient care. It is also not practical to test every patient for hantavirus, with its extreme rarity the number of false positives might outnumber the true positives.

Signal to Noise Ratio

Even if you aren't expecting a zebra, if one walks up and presents itself, it would be hard to miss. Right?

What if that zebra was engulfed in teaming throngs of horses, gazelles, and zebu? What if HPS resembled other diseases that were far more common? When something could be lost in a cloud of similar things, you have to think about something called signal to noise ratio, (S/N).
Just one of the gang.

HPS patients present with symptoms that resemble a variety of other diseases, syndromes and categories of illness. Influenza, or flu-like illness, is a common early diagnosis. Community acquired pneumonia (CAP), a category, is the catch-all term for respiratory problems that the hospital didn't transmit. CAP can be caused by numerous pathogens, viral and bacterial. Identification of the particular pathogen in a patient is unusual. 

Community acquired pneumonia becomes a catch-all term that is applied when a patient presents with impaired breathing from what is often an undetermined agent or insult to their system. Community acquired pneumonia strikes somewhere between four and five million people in the U.S. per year. 

HPS is one of many "insults" to the system that can cause what is called Acute Respiratory Distress Syndrome, (ARDS), a relatively new and still controversial classification of sudden respiratory collapse that may result from any of a variety of "insults" to the patient. These collapses follow a general pattern, and have a mortality rate of about 40%, about the same as HPS. Somewhere between 50,000 and 100,000 people per year are struck by ARDS in the U.S.

The huge range in these numbers reflects widely varying estimates of the number of severe illnesses and deaths that fall into this syndrome. A study of post mortem victims of respiratory collapse found that about half of all patients that met the criteria for ARDS were not diagnosed as having had ARDS while they were alive. That's a matter of multiple, somewhat different definitions and criteria.
Zebra herd on the Serengeti plain.
From National Geographic

Differentiating ARDS caused by hantavirus from ARDS caused by requires some means of differentiation. Unfortunately, there are only general reasons for guidance. Hantavirus can be ruled out for cases of ARDS that have a clear source, such as a recent surgery or other illness. But hantavirus is only suggested as a faint possibility in cases with known exposure to rodents, and patients often have no way of knowing that they had that exposure, some weeks previously.

Misdiagnosis of hantavirus was recently reported in a case in Brazil, where the HPS syndrome is a newly identified condition. Hantavirus misdiagnosed as Dengue In places where the medical community is not trained to look for hanta, it tends to get missed. A kind of "latching" effect may appear in the statistics for this reason, with states reporting hantavirus enough to get press coverage tending to find more of it afterward.


I can't be certain that people have been contracting hantavirus through infestations of their cabin air systems, but neither can anyone be assured that they are not.

There are reasons to believe that significant numbers of cases of hantavirus go undiagnosed in both Mexico and the United States.

Effort should be undertaken to better determine the scope of undiagnosed hantavirus from any source, and the particular question of whether vehicle cabin air systems are a mode of infection that has slipped "under the radar" of hantavirus detection.

Some comments on related webpages and excerpts from related references

The CDC webpage on hantavirus transmission makes no mention of vehicles, let alone of vehicle cabin air system infestations. 

The King County Public Health site now has a pretty good update on hantavirus posted here: 

This advisory is mainly directed at health care providers. It now specifically calls out vehicle cabin air systems as suspected transmission mechanisms. These changes probably would have never happened if it were not for this website calling attention to these issues. 

Unfortunately, the general hantavirus information page and the Health Insider article make no mention of checking cabin air filters for deer mouse infestation. It does not mention that this common site of Deer mouse infestation even exists. 

This needs to be changed, and the information for health care providers needs to be disseminated on a national basis. It would also be reasonable to develop some form of instruction that for patients presenting with symptoms resembling hantavirus, someone with proper ventilator mask and gloves should check the cabin air filters of vehicles they have used for signs of rodent infestation.

 “Nucleotide sequence data from 5 antibody-positive rodents indicated that Sin Nombre virus (the major cause of hantavirus pulmonary syndrome [HPS] in the United States) is enzootic in the Mexican states of Nuevo León, San Luis Potosí, Tamaulipas, and Veracruz. However, HPS has not been reported from these states, which suggests that in northeastern Mexico, HPS has been confused with other rapidly progressive, life-threatening respiratory diseases."

"The results of this study indicate that SNV is widely distributed in northeastern Mexico. The geographic distribution of Deer mice (P. maniculatus) in Mexico includes 23 states (28), and ≈20 million persons lived in rural areas in this 23-state region in 2010 (32). Yet, to our knowledge, no cases of HPS have been reported from northeastern Mexico or elsewhere in Mexico."

We hypothesize that HPS caused by SNV in Mexico has been confused with other rapidly progressive, life- threatening respiratory diseases (e.g., plague, tularemia, pneumococcal pneumonia, influenza).”
Hantavirus cases by state of reporting from CDC. Note that many states
have never reported hantavirus, even though they have plenty of mice.
Same with three northernmost states of Mexico, as described above.
"Taken together, our preliminary results suggest that ARDS/ALI are likely under recognized conditions, particularly in critically ill patients requiring prolonged mechanical ventilation. Earlier studies have estimated the mortality due to ARDS/ALI at around 133,500 deaths per year in the United States6. Given the possible under recognition however, ARDS/ALI are conditions likely responsible for even more deaths in the population. Besides mortality, ARDS/ ALI also leads to large amounts of costly and often debilitating morbidity in surviving patients and their caregivers1,3,6. Outcomes studies have consistently found significant functional and neuropsychological derangements at both 1 year and 5 years post illness1,2,3. Perhaps better identification of ARDS/ALI in the first place may help to more efficiently allocate health care resources – in turn potentially preventing some of the typical long-term sequelae currently experienced by survivors and their caregivers.
Before making any firm conclusions however, it should be noted that although the results of our preliminary study are suggestive of under recognition of ARDS/ALI, they are subject to a number of important limitations."
The incidence of ARDS in Maryland is in the range of 10-14 cases per 100,000 people. The ARDS mortality rate is 36% to 52%, similar to that calculated in previous studies.

The aetiology of community-acquired pneumonia (CAP) has been studied in various regions and settings. While these studies differ considerably in patient populations, diagnostic methodology, and presence of confounders, one intriguing constant finding is the failure to detect a pathogen in ∼30–60% of cases 19. Among the factors which may explain this observation, ambulatory antimicrobial pretreatment is the most attractive. Accordingly, there is evidence from the literature that the majority of cases of unknown aetiology may be caused by Streptococcus pneumoniae, a pathogen which is easily missed after one single dose of antimicrobial treatment 1, 10. Conversely, the recognition of Legionella pneumophila and Chlamydia pneumoniae has taught that unrecognised pathogens may represent important causes of CAP.
My interview with Outbreak News and coverage of the cabin air system question.

* Note  These posts will use Hanta to specifically indicate the Sin Nombre strain of hantavirus. 



The cabin air filter deer mouse infestation reminds me of the 2012 Yosemite hantavirus outbreak! The Yosemite tent cabin space heaters probably enhanced the Yosemite hantavirus transmission!

Mark Waterbury said...

This is an excellent point. I've been writing an article on the contraction of hantavirus, and this will certainly go into it. The Yosemite outbreak involved tents with a double-wall structure, that would tend to "breath" with wind changes and suck air in and out of the space between the tent walls.

That has a lot in common with a cabin air filter, moving air over a surface with mouse excreta. But when you add in cabin space heaters... it further ups the ante. I hadn't known about those. They would tend to heat the humid, protected hantavirus, drying it out and making it far easier to aerosolize through the air flowing through small holes between the tent walls... It is made for infection promotion.

Look for this post soon and thank you!

Stefan Forge said...

Saved as a favorite, I really like your site! outlook login