A laboratory perspective on emerging and re-emerging infectious diseases in North America

In the world of infectious diseases, recently there have been some new factors and some that are “déjà vu all over again,” as Yogi Berra might have put it. Weather, natural disasters, poverty, crowding, unhygienic conditions, travel, contaminated food and water, proximity to animal vectors, and unknown elements have all given rise to surges in infection and increased the need for laboratory services as part of the response to them. One infectious agent was recently identified in the Western world, and several others are old enemies, but all deserve serious attention—because some will almost certainly present in your laboratory. In this article, we review some infectious agents that have made the news during the past year. Information from the U.S. Centers for Disease Control and Prevention (CDC) on how to report and process them is also included.

Acute flaccid myelitis

One of the most troubling emerging infectious diseases, causing concern to healthcare professionals and parents alike, is acute flaccid myelitis or AFM. This viral illness is strongly reminiscent of pre-vaccine polio, and it stirs memories of “iron lungs,” heavy leg braces, and children on crutches in older “Baby Boomers.” According to the CDC, AFM can be caused by multiple strains of RNA enteroviruses closely related to poliomyelitis, loosely termed EV-D68. Symptoms include fairly severe respiratory illness, muscle aches, and acute flaccid paralysis.¹ Dyda et al² have confirmed 120 cases of AFM emerging from various communities, and EV-D68 remains a frustrating mystery. Although enteroviruses are generally transmitted via a fecal-oral route, no common denominator environmental or other factor(s) have been uncovered to link these cases together epidemiologically.

Laboratory professionals will be crucial in contributing toward essential knowledge about this dangerous agent. Clinicians may be asking you to forward specimens to the CDC for confirmation of suspected cases.

This website contains information on how to properly report, package and ship specimens: https://www.cdc.gov/acute-flaccid-myelitis/hcp/specimens.html

Seoul hantavirus

In January 2017, the first documented transmission of Seoul hantavirus from pet rats to humans in the United States was verified. It was detected in Tennessee, Georgia, Illinois, Missouri, South Carolina, and Utah, as well as in Canada.³ Serologic results showed that 183 persons tested antibody-positive for Seoul virus. Of those, 12.5 percent were hospitalized; there were no fatalities. At the same time, humans were unknowingly fostering the virus in Norway rats (Rattus norvegicus) which were being sold as pets. Seventeen people in the U.S. were hospitalized, treated, and released.⁴

This was significant and alarming, because population health experts and others well recalled how, in 1993, hantaviruses caused an outbreak with numerous fatalities in the Four Corners region of the U.S. among members of the Navajo Nation. The dreadful outbreak, which took a number of young lives, was the subject of a major CDC investigation. The source of contagion turned out to be deer mice that had flourished due to a rich pinion nut harvest brought on by unusually heavy rains.⁵

Hantaviruses cause symptoms ranging from mild flu-like illness to severe respiratory disease, including shock, renal failure, and death, even in young, healthy persons. At this point, it is not known if the Seoul hantavirus is present extensively or at all in the U.S. wild rodent population. It is obvious that it could present a significant potential threat and challenge to public health nationwide, especially where rodent infestation is a serious problem.

Laboratory professionals and clinicians should consider testing for Seoul virus (and other hantaviruses) in patients with febrile illnesses who have had or may have had rodent contact. The CDC offers testing, as do some state and commercial laboratories. Complete information concerning specimen submission may be found at https://www.cdc.gov/hantavirus/health-care-workers/index.html.

Hepatitis A virus (HAV)

Hepatitis A virus (HAV), an old enemy, has re-emerged as a public health crisis in San Diego, California, to the extent that certain streets where the homeless congregate were necessarily pressure-washed with chlorine bleach to remove HAV-contaminated human fecal material.⁶ Nearly 69 percent of San Diego’s 580 patients required hospitalization, which is more than three times higher than normal. The mortality rate was 3.4 percent.⁷

Utah’s index case of HAV was proven by molecular testing to have originated in California, and, since January 2017, the number of infected people has grown to 176 among the homeless population in Utah.⁸

Vaccination drives in both states are aimed at containing the spread. A major concern is that it will amplify into the general population via infected food handlers as it has often done in the past. Laboratories in states including California, Utah, Michigan, Kentucky, and Colorado, and several others with substantial homeless populations without adequate sanitary facilities, will continue to see a surge in HAV testing.

Angiostrongylosis

Parasitology labs, particularly those in Hawaii and on the Pacific Coast, should be on heightened alert for queries concerning the rat lungworm parasite, Angiostrongylus cantonensis. This has become a serious problem because of the recent uptick in the population of this parasite’s intermediate vector, the Southeast Asian semi-slug Parmarion martensi.⁹

This pain-inducing and frightening parasitic agent accesses the human body via raw, unwashed, or undercooked vegetables, fruits, seafood, frogs, or contaminated water. Larvae coughed up from the lungs of rats invade P. martensi (tiny slug-like snails). These slugs containing lung worm larvae are ingested by humans via raw vegetables or one of the aforementioned food items. Symptoms include nausea, vomiting, stiff neck, and headache. Human-to-human transmission is not known to occur. Most cases appear to resolve on their own, as the larvae eventually die because humans are a dead-end host. However, infection can be very painful and there is no specific treatment. Also rat lung worm infection is the world’s leading cause of eosinophilic meningitis, which can leave the patient permanently impaired.¹⁰

Regrettably, there is no specific test for A. cantonensis. A few independent labs have developed serologic and PCR tests, but these are not commercially available. According to the CDC, it should be strongly suspected when symptoms resemble bacterial meningitis but results show eosinophilia in blood at >5 percent or in CSF at >10 percent, or travel to endemic areas has been verified, or dietary history supports this diagnosis. The larvae are rarely seen by microscopy of cerebrospinal fluid as they tend to attach to the meninges.¹¹ Ruling out other causes of meningitis is important, and MRI can be useful in this regard. Stool or biological specimens are of no value, as the parasite does not reproduce in humans.

Best tip to your clinicians: Watch eosinophils and consider the patient’s recent personal history. Submission of specimens to the CDC is discouraged, but clinicians and laboratorians can call the Parasitic Diseases Hotline for advice and updates (404-718-4745).

Leptospirosis (Leptospira spp.)

We are increasingly reminded of the dramatic role that weather can play in emerging and re-emerging infections. The catastrophic winds and waves of Hurricane Maria unleashed a “perfect storm” of dozens of cases of Leptospirosis, and another 74 were being investigated in Puerto Rico as of this writing.¹² The corkscrew-shaped bacterial organism is transmitted by the urine of infected animals (most commonly rats) to humans by an oral route or through non-intact skin, eyes, or mucous membranes. It causes serious liver, kidney, and respiratory tract damage, muscle aches, meningitis and even death. Following a water-
associated outbreak in 2015, the CDC reinstated Leptospirosis as a notifiable zoonotic infectious disease in the U.S. It claims nearly 60,000 lives every year worldwide, and its emergence can virtually be counted upon in endemic areas following flooding events.¹³

Vibriosis

Intensified toxic Vibrio illness (vibriosis) caused by Vibrio vulnificus and Vibrio parahaemolyticus, has also been documented scientifically as being associated with hurricane weather patterns. A study in 2014 of oyster beds in Chesapeake Bay first showed that virulence-associated genes in both Vibrio species intensified during post-Hurricane Irene environmental conditions.¹⁴ Laboratories in Houston post-Hurricane Harvey cultured impressive numbers of both from patients. Vibrio vulnificus is a powerful food poisoning bacterium that is contracted from consuming contaminated raw oysters (primarily) and seafood. Dangerous bullous skin lesions and potentially lethal necrotizing fasciitis can occur as a result of infected cuts or abrasions sustained in brackish flood water.¹⁵

Vibrio parahaemolyticus is also associated with contaminated seafood and can cause dangerous infections in cuts and abrasions. Laboratory professionals should be on heightened alert for “storm surges” of these agents following hurricanes and other coastal flooding events involving brackish water. Both of these agents can prove rapidly lethal, and prompt identification is critical, especially in immunocompromised patients.¹⁶

Expecting the unpredictable

It is clear that emerging and re-emerging infectious diseases need not come from distant locales, as they can just as easily arise in the U.S. Chikungunya, Zika, and many exotic viruses still strike and come home with travelers to the Caribbean and points south and elsewhere. They make blood donor screening an ever more difficult task. It has been suggested that an overall deferral of travelling donors might be more effective than using targeted measures. For example, it might be best to defer all international travelers to known virus endemic zones for four weeks.¹⁷

In the world of infectious diseases, plagues that have lain dormant for decades can be reignited overnight. Examples are the current outbreak of bubonic plague (Y. pestis) in Madagascar, the occurrence of human anthrax (B. anthracis) in Africa,¹⁸ and ongoing eruptions of smallpox-like monkeypox in residents of Nigeria.¹⁹ It is noteworthy that the vast majority of these infectious diseases are zoonotic in origin. We also dealt with a norovirus disruption at the recently concluded Winter Olympics, recording nearly 200 cases with 1,200 staffers quarantined to prevent its spread.²⁰ In addition, a Royal Caribbean Cruise ship recently arrived in San Diego with 24 aboard suffering from norovirus gastrointestinal symptoms.²¹

All of which proves we must be eternally vigilant. Clinicians and laboratory professionals need to remain well-informed, aware, and prepared to meet every challenge presented by emerging and re-emerging infectious diseases. The lab provides our earliest alert, and therein lies one of laboratorians’ most important responsibilities.

REFERENCES

1. U.S. Centers for Disease Control and Prevention. Non-polio enterovirus, Enterovirus D-68 for healthcare professionals. https://www.cdc.gov/non-polio-enterovirus/hcp/ev-d68-hcp.html
2. Dyda A, Stelzer-Braid S, Dillon A, Abrar C, MacIntyre C. The association between acute flaccid myelitis (AFM) and Enterovirus D68 (EV-D68)—what is the evidence for causation? Eurosurveillance. 2018;23(3):1-9.
3. Fill MM, Mullins H, May AS et al. Notes from the field: Multiple cases of Seoul virus in a household with infected pet rats – Tennessee, December 2016 – April 2017, MMWR/ Oct 13, 2017/66(40); 1081-1082. 2018;67:131-134.
4. U.S. Centers for Disease Control and Prevention. Multistate outbreak of Seoul Virus. https://www.cdc.gov/hantavirus/outbreaks/seoul-virus/index.html.
5. U.S. Centers for Disease Control and Prevention. Tracking a mystery disease: the detailed story of hantavirus pulmonary syndrome (HPS). https://www.cdc.gov/hantavirus/outbreaks/history.html.
6. Nelson N. Hepatitis A outbreaks. United States—2016-2017, Vaccines work group advisory committee on immunization practices. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-10/hepatitis-04-nelson.pdf
7. Health and Human Services Agency, Hepatitis A, San Diego Hepatitis A Outbreak, Feb. 13, 2018.https://www.sandiegocounty.gov/content/sdc/hhsa/programs/phs/community_epidemiology/dc/Hepatitis_A.htmlhttps://www.sandiegocounty.gov/content/sdc/hhsa/programs/phs/community_epidemiology/dc/Hepatitis_A.html
8. Utah Department of Public Health, Bureau of Epidemiology, Hepatitis A outbreak, Feb. 2, 2018. http://health.utah.gov/epi/.
9. Jarvi SI, Quarta, S, Jacquier S, et al. High prevalence of Angiostrongylus cantonensis (rat lungworm) on eastern Hawai’i Island: a closer look at life cycle traits and patterns of infection in wild rat (Rattus spp.) 2017; PLOS One. https://doi.org/10.1371/journal.pone.0189458
10. U.S. Centers for Disease Control and Prevention, DPDx- Laboratory Diagnosis of Parasitic Diseases of Public Health Concern – Anylostrongyliasis, Feb. 1, 2018. https://www.cdc.gov/dpdx/angiostrongyliasis/index.html.
11. Murphy GS, Johnson S. Clinical aspects of eosinophilic meningitis and meningoencephalitis caused by Angiostrongylus cantonensis, the rat lungworm. Hawai’i J of Med. & Pub. Health. 2013;72(6 Suppl 2):35-40.
12. Rettner R. What is Leptospirosis? Dozens of cases suspected in Puerto Rico. Live Science website. https://www.livescience.com/60775-leptospirosis-puerto-rico.html
13. CDC. Leptospirosis. Oct. 17, 2017. https://www.cdc.gov/leptospirosis/index.htm
14. Shaw KS, Jacobs KM, Crump BC. Impact of Hurricane Irene of Vibrio vulnificus and Vibrio parahaemolyticus concentrations in surface water, sediment and cultured oysters in the Chesapeake Bay, MD, USA. Front. Microbiol. 2014;7(5):204 doi:10.3389/fmicb.2014.00204. E Collection
15. Astor M, ‘Flesh-Eating ’Bacteria from Harvey’s flood waters kill a woman. New York Times. Sept. 17, 2017. https://www.nytimes.com/2017/09/28/health/necrotizing-fasciitis-houston-texas.html?mtrref=www.google.com&gwh=B59E748369124576F5980F40820FBFA9&gwt=pay
16. U.S. Centers for Disease Control and Prevention., Vibrio species causing vibriosis. https://www.cdc.gov/vibrio/index.html
17. Lieshout RW, Krikke HL, Zaaijer F Prinse J. The yield of temporary exclusion of blood donors exposed to emerging infections abroad. Vox Sanguinis. 2013:1(104)12-18.
18. ProMed Mail, Internat. Soc. Inf. Dis, Archive no. 20180122.5572973, Plague – Madagascar: (Antananarivo) Bubonic, Jan. 18, 2018. http://www.who.int/csr/don/21-december-2017-monkeypox-nigeria/en/
19. World Health Organization, Nigeria, Monkeypox –Dec. 21, 2017. http://www.who.int/csr/don/21-december-2017-monkeypox-nigeria/en/20. Lam K. Winter Olympics staff quarantined for norovirus. Fox News Feb. 13, 2018. http://www.foxnews.com/world/2018/02/13/winter-olympics-staff-quarantined-for-norovirus-blames-organizers-for-outbreak-report-says.html.
20. Lam K. Winter Olympics staff quarantined for norovirus. Fox News Feb. 13, 2018. http://www.foxnews.com/world/2018/02/13/winter-olympics-staff-quarantined-for-norovirus-blames-organizers-for-outbreak-report-says.html
21. Gant M. Royal Caribbean cruise arrives in San Diego after 24 people sickened with gastrointestinal illness. Fox News. Feb. 9, 2018. http://www.foxnews.com/travel/2018/02/09/royal-caribbean-cruise-arrives-in-san-diego-after-24-people-sickened-with-gastrointestinal-virus.html

Linda L. Williford Pifer, PhD, SM(ASCP), GS(ABB), is a Professor, Department of Clinical Laboratory Sciences, at the University of Tennessee Health Science Center, where she established The Diagnostic Virology Lab at LeBonheur Children’s Hospital.

Wyenona Hicks, MS, MT(ASCP), SBB, serves as Laboratory Services Manager at LifeSouth.