The shifting spectrum of emerging infectious diseases

In 1962 Nobel laureate (Medicine/Virology) Sir Frank Macfarlane Burnet remarkably stated that, “To write about infectious disease is to almost write of something that has passed into history.”¹ Fifty-seven years ago in the United States, we crushed smallpox, polio, measles, diphtheria, typhoid and were armed with powerful antibiotics that had experienced virtually zero resistance from microbes. We held a shining sword of power over disease and death. Vaccines and antibiotics were its two cutting edges.

However, although Burnet had lived through the “Spanish influenza” of WWI that killed more than 50 million people (nearly one in 20 worldwide) he had no way of foreseeing HIV/AIDS, Ebolavirus, Legionnaire’s disease, etc.² The idea of emerging infectious diseases was unknown, as was the concept of the immunocompromised host. We have learned many humbling lessons since those days of audacious innocence at our perceived height of power over the microbe.

We have learned that the unseen microbial world is never to be underestimated. All living things have a vigor to exist and will withstand extreme stressors to the limits of physical tolerance to live and reproduce.

Emerging arthropod-borne outbreak in LA

Who could have imagined flea-borne murine typhus in downtown Los Angeles on Sunset Blvd.? Thus far, there have been over 100 confirmed cases. Six of the downtown LA cases were in homeless people. Trash and debris generated by their make-shift dwellings create the perfect environment to support rat populations. The disease is caused by Rickettsia typhi, which is transmitted by fleas whose feces, bearing the bacteria, enter scratches and skin abrasions in human skin. Symptoms include chills, fever, body aches, muscle pains, loss of appetite, nausea, vomiting, cough, and a rash appearing at about day five. Most recover without treatment (Doxycycline is preferred) but severe organ damage can occur. Test results require weeks so empiric treatment will usually be started upon report of flea bites and report of pathognomonic symptoms. Fleas most often originate from rats, cats, and opossums in the Western U.S. (CA, TX, HI).⁴

Overall, according to the CDC, vector borne diseases are extremely important causes of illness and death on every continent. In the U.S., Rocky Mountain spotted fever and Lyme disease are most commonly transmitted by ticks. West Nile virus and Zika virus are spread by mosquitoes, although the latter has not become indigenous. A recent CDC study showed that the number of annual reports of tick-borne bacterial and protozoan diseases (Babesia microti and Cytauxzoonosis) have more than doubled between 2006 and 2014 from >22,000 to >48,000.⁵

Zoonotic bacteria, prions, and viruses

An emerging zoonotic cause of sepsis, endocarditis, and meningitis is Capnocytophaga canimorsus, a Gram (-) bacterium first named in 1989.⁶ The organism is found in the mouths of most healthy dogs (74 percent) and cats (57 percent), but can cause lethal infections in up to about 30 percent of cases when individuals are asplenic, heavy users of alcohol or otherwise immunocompromised.⁶ A lick on a scratch by his puppy nearly cost a young WI boy his life—he lost his fingers and toes to C. canimorsus sepsis.⁷ A 58-year-old S. Milwaukee woman died only two days after admission to hospital with C. canimorsus pneumonia after having been nipped by her new puppy.⁸ A 48-year-old WI man lost parts of all four appendages, part of his nose, and lower lip—and very nearly his life—because his open scratch was licked by his dog.⁹ Finally, a case report of a 70-year-old woman without immune dysfunction, who presented neither scratch nor bite, but who survived C. canimorsus sepsis suggests that “the lick of death” alone may transmit the infection.^{10, 11} Weakened immunity may well present an invitation to Capnocytophaga whether skin is visibly intact or not.

A prion-associated death is suspected in a NY hunter with a history of squirrel brain consumption¹² (considered a delicacy in some parts of the U.S.). In 2015, a 61-year-old man entered a hospital in Rochester, NY with declining mental abilities, confusion, and inability to walk. His MRI scan was consistent with those seen in patients with variant Creutzfeldt-Jakob disease (vCJD), one of the spongiform encephalopathies caused by prions, which are rogue infectious proteinaceous particles. Variant CJD is a progressive neurological degenerative disorder for which there is no treatment and is always lethal.

In Western KY, definite or probable vCJD was seen in five patients with histories of consuming squirrel brains. Variant CJD is one of a number of inheritable or acquired prion diseases which are progressive, incurable, and fatally affect the brain and central nervous system. In this area and others, squirrel brains are used in preparing “burgoo” which is a traditional vegetable and game stew. The authors note that confirmation of the apparent association will be required with a larger population of subjects, but avoidance of consumption of this dish would be well advised.¹³

Recently, three individuals in the U.K. and an Israeli living in the Port Harcourt area of endemic southern Nigeria have been diagnosed with monkeypox virus which originated in Nigeria. At least one of the U.K. residents contracted the virus in the U.K., and smallpox vaccinations were offered to those present in the physician’s office on the same day on which the affected individual was present.¹⁴ Smallpox (variola) has been extinct as a naturally transmitted infectious disease since 1979, thanks to the success of world-wide application of vaccine.

Fortunately, cross-immunity exists between smallpox virus (variola), cowpox (vaccinia), and monkeypox. The latter is far milder and exhibits symptoms of headache, fever, chills, muscle aches, followed by a rash on the face followed by blisters, pustules, and scabs that eventually cover the entire body. Since September 2017, there have been 115 confirmed cases, and there have been 37 at the time this article was written in 2018.¹⁵ The lesson here is that exotic viruses are as near as the next transcontinental flight. Travel, immigration, climate change, deforestation, war, changing human social habits, and many other societal and environmental factors have both subtle and dramatic impacts upon the changing spectrum of emerging and re-emerging infectious diseases.

Record increase in STIs in CA

Sexually-transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia have reached a never-before recorded high (a 45 percent increase in past five years) in California, particularly in Orange County, LA.¹⁶ Cuba, Thailand, and Belarus are presently doing a better job at controlling syphilis. According to the CA Dept. of Public Health, this has led to an unprecedented surge in cases of congenital syphilis. The crisis has been blamed on the deterioration of the health infrastructure beginning in 2008 and budget slashes that occurred ten years ago that were never restored to their original level.¹⁶

Health officials have also coupled the rise of STIs with homelessness, poverty, substance abuse, and mental health problems. According to Dr. H. Bauer of the CA STD Control Branch, the Affordable Care Act has also funneled patients away from public health services toward primary care physicians, and this is not the most effective plan. Those who depended on public clinics for STI screening, etc. may not feel comfortable talking about it with their physicians or may have no physician at all.¹⁶ Thus, economics and government policy play a significant role in shifting patterns of infectious diseases. The sequelae include stillbirths, ectopic pregnancies, infertility, blindness, hearing loss, dementia and ultimately, vastly increased health costs—to mention a few.

Dangerous emerging mycotic infection

Who can recall the last time a CDC advisory was issued to report the isolation of a nosocomial mycotic infection? Candida auris has been growing in notoriety now for several years with a case count of 463 plus in the Fall of 2018. It is an emerging mycotic threat with grave consequences for three reasons: 1. Multidrug resistance; 2. It is difficult to identify and easy to mis-identify, leading to non-optimal treatment; and 3. It has caused serious outbreaks in healthcare facilities that have been difficult to eradicate.¹⁷ It has been reported to be the cause of invasive infections (candidemia) with a high incidence of mortality (approaching 60 percent).¹⁸

Seventy cases of C. auris infections (seven invasive) occurred in the neurosciences intensive care unit of the Oxford University Hospitals, U.K., and all were associated with use of reusable skin-surface axillary temperature probes.¹⁹

The CDC maintains updates on the diagnosis, treatment, and environmental decontamination procedures for Candida auris at https://www.cdc.gov/fungal/candida-auris/c-auris-treatment.html and continues to update the site due to the insidiousness and potentially deadliness of this emerging mycotic infection.

Conclusion

Although Nobel laureates accomplish amazing breakthroughs in science and medicine, they are not necessarily gifted with foresight, as proven by Sir Frank M. Burnet. He apparently believed that infectious diseases were, in 1962, conquered things of the past. Louis Pasteur (1822-1895) who was possibly the greatest of all microbiologists once said, “Gentlemen, it is the microbes that will have the last word.”²⁰ HIV/AIDS, the Ebola viruses, and other numerous dangerous emerging and re-emerging pathogens have proved Pasteur to be correct and that laboratory managers should best remain at the ready.

REFERENCES

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