By Belinda Williams
Species Jump: Human Ehrlichiosis-
Mutant or Emergence?
Introduction:
Ehrlichiosis was first recognized in 1935 as a canine disease caused by a newly discovered bacterium in the Rickettsiaceae family named Ehrlichia canis. Since this discovery, several other Ehrlichia species have been identified as agents responsible for disease in horses, dogs, and cattle. The first case of human ehrlichiosis was reported in Japan in 1954. Two other Ehrlichia species have since been identified as human pathogens. In an age where science has opened a gateway for microbial discovery, it is not surprising to identify previously unknown microorganisms. The surprise in discovery of human Ehrlichia infection is that the human species are virtually indistinguishable from species which cause illness in canines, horses and cattle. One such strain (yet unnamed) differs from cattle and horse strains by only two and three nucleotides, respectively. Such small genetic variance leads one to wonder exactly how the human strains emerged. Such small genetic variance leads one to wonder exactly how the human strains emerged. Genetic similarities suggest that this variance could be the result of a spontaneous point mutation. Such close relationships also lead to the question of whether they are really different species or if they should be classified as separate strains in a single species. There are no conclusive answers to these questions at present, but one can speculate on the answers which may support a species jump or the ability for broad host range infectibility with equal certainty based on available evidence.
Ehrlichia are gram negative, nonmotile, obligate intracellular coccobacilli belonging to the family Rickettsiaceae with much similarity both in structure and disease to the pathogens responsible for Rocky Mountain Spotted Fever,Q-fever, and Typhus. Ehrlichiosis is a tick borne zoonotic infection which passes into mammalian host blood via tick bites. Three tick species have been identified as vectors of Ehrlichia infection; Ixodes scapularis (deer tick), Amblyomma americanum (Lone Star tick), and Dermacentor variabilis (American Dog tick).
After a tick injects Ehrlichia bacteria into a host the bacteria is taken into white blood cells (immune cells) via phagocytosis. Once inside a phagosome the bacteria initiates replication. Such patterns of replication lead to mass destruction of white blood cells as they become too saturated by bacteria to maintain structural integrity. Ehrlichia has a strong tropism for hemapoetic tissue, and infection leads to a variety of bone marrow abnormalities including marrow hypoplasia, normcellularity, and hypercellularity. Anemia is present in about 50% of infected individuals. Ehrlichia infection also causes plasmacytosis, granulomatous inflammation and erythrophagocytosis (the immune system phagocytizes it's own red blood cells). Such massive descruction of immune cells not only produces clinical symptoms, but leaves the host susceptible to secondary infections, often involving opportunistic pathogens rarely involved in causing disease in individuals whose immune system remains intact. Ehrlichia often is involved with organ dysfunction, particularly those of the immune system including the spleen, liver, lymph nodes and bone marrow. There is a marked increase in blood titers of liver enzymes, particularly asparate aminotransferase. Leukopenia, lymphopenia and thrombocytopenia are apparent in infected individuals as the result of destruction of white blood cells. Occasionally, renal (kidney) abnormalities will be noted as an increase in blood urea, nitrogen and creatinine levels. Proteinurea and hematurea may be present. Renal failure is rare, however, and most individuals have a good prognosis of full recovery, particularly children.
Clinical Signs and Symptoms:
Physical symptoms of ehrlichiosis are initially vague and resemble any number of common, milder illnesses, or then can present headache and fever which is often unresponsive to analgesics and antipyretics. Other typicalsymptoms include chills, malaise, muscle aches, sweating, nausea and vomiting. Respiratory involvement has occurred but is rare. Most infected individuals have some recollection of having been bitten by a tick or visiting tick infested areas within the two weeks prior onset of symptoms. Incubation between exposure and disease has ranged from 1 day to 2 weeks, with six days the average incubation time. Ehrlichiosis can be a very serious infection. In cases where treatment has been delayed, Ehrlichia has been documented as a cause of kidney failure, respiratory failure and meningitis with a case fatality rate as high as 5%. Maculpapular rash resembling Rocky Mountain Spotted fever is present in about half of all cases. Disease tends to be more serious in the elderly and other populations of immunocompromised individuals. Due to the vague nature of symptoms and similarities to other illnesses, differential diagnoses is most often Rocky Mountain Spotted Fever. here have also been reported differential diagnoses including leptospirosis, Kawasaki, tularemia, lyme disease, meningococcemia, leukemia, mononucleosis and collagen vascular disease. Early recognition of Ehrlichia infection is important if one is to reduce the risk of fatality.
Symptoms of ehrlichiosis in cattle, dogs, and horses resemble the human infection, although horses developswollen legs as well, which clues veterinarians to the possibility of Ehrlichia infection. One researcher, Dr. John E. Madigan at university of California Davis school of veterinary medicine has noted correlation between outbreaks of equine ehrlichiosis and human cases. "If horses are getting it (ehrlichiosis) in a certain geographical region, people are getting it also," he said. "Veterinarians are very skilled at identifying ehrlichiosis in horses. The appearance of the disease in horses should serve as a marker for public health officials to the potential of human infections occurring in the same area.
Treatment:
Ehrlichia bacteria are susceptible to a broad spectrum of antibiotics, with tetracycline and doxycycline the drugs of choice. Since these drugs can result in abnormal tooth coloration in children, infected children are usually treated with chloramphenicol as an effective alternative. Severe cases may require hospitalization in order to monitor organ function and leukocyte titers and to administer intraveinous fluid replacement. Additional antibiotics may be necessary if secondary infection occurs. There have been cases of spontaneous recovery in the absence of treatment.
Diagnosis:
Because it is so rare, ehrlichiosis is not considered a reportable disease. There are approximately 50 cases every year, although the accuracy of this figure is questionable due to the fact that few physicians recognize it and instead document another disease such as Rocky Mountain spotted fever. Veterinarians have access to antibody detection assays, and these often can be interchangable to detect similar human strains. The Centers for Disease Control currently offers free testing for antibodies against Ehrlichia, and Ehrlichiosis is defined by a four-fold rise or drop in blood antibodytiter. In addition, PCR amplification assays can be used for direct detection of the bacterium.
Human Ehrlichiosis in the United States:
Three strains of Ehrlichia bacteria have been identified as human pathogens. E. sennetsu was first documented in Japan in 1954 as the causitive agent for a mononucleosis-like syndrome called Sennetsu fever. This strain is closely related to E. risticii, a species responsible for Potomac horse fever and some canine infections. In 1986 a new strain emerged as a human pathogen responsible for a Michigan outbreak of ehrlichiosis. This strain, named E. chaffeensis is antigenically related to E. canis, and E. ewingii, two strains responsible for canine outbreaks of ehrlichiosis.Both E. sennetsu and E. chaffeensis have a predolection for invading monocytes and macrophages, producing what is called human monocytic ehrlichiosis, or HME. These two isolates can also be found occasionally in lymphocytes and neutrophils. The host immune system is quickly compromised due to cell destruction, but prompt antibacterial treatment is usually effective and patients recover without complication. In 1993 a third isolate was discovered as the source of a new disease. Symptoms presented as similar to those of the former isolates but with greater severity and subsequent mortality has been as high as 5%. This new species, which is unnamed to date, exclusively infects granulocytes, particularly neutrophils since basophils and eosinophils are of very low titer in normal individuals. The new disease was named Human Granulocytic ehrlichiosis (HGE) based on this predilection for granulocytes. PCR assay has determined this new species to differ from E. equi (equine ehrlichiosis) by only threeAssays for detection of E. equi are usually used in the detection of HGE. Such similarity suggests that all three may be strains of a single species, where a point mutation has taken place and adapted the bacterium to a new host. These similarities are what lead veterinarians such as Dr. Madigan to suspect a direct correlation between equine and human ehrlichiosis outbreaks in a given area. If this emergence is indeed the result of mutation, it was probably spontaneous and random. There has been no evidence that this bacterial species has the ability to share genetic material via plasmids, phage particles, or other means of genetic transfer.
Prevention:
Prevention of Ehrlichia infection involves taking precautions whenever visiting an area where ticks are known to be endemic. Bug spray is often effective, but it is also recommended that long pants and shirts be worn in such areas. One should always examine themselves and their pets for ticks after a visit to tick infested locals, and any ticks should be removed carefully so that they do not leave portions of their mouth within the bite. Prompt disinfection of tick bites is known to dramatically decrease the likelihood of Ehrlichia infection. If redness or swelling develops around the bite, or if one develops flu symptoms they should seek medical attention immediately. Prompt treatment is essential to ensure full recovery and should be started in any case where ehrlichiosis is suspect without waiting for laboratory conformation.nucleotides and from E. phagocytophila (bovine ehrlichiosis) by only two. The new human species and its bovine and equine counterparts are antigenically identical to each other, so much that assays for detection of the pathogen are interchangeable among the three species.
Conclusion:
In a time of discovery and technological innovation it should be expected that formerly unrecognized pathogens will make their way into the human population. Colonization patterns and transoceanic travel have made previously unpopulated areas more accessible. The result is the emergence of disease causing microorganisms formerly isolated from human contact. Microbes are masters of evolution and adapt faster to changing environments and host reservoirs than any other life form. No being can halt the inevitable. The best that can be hoped for is that we continue to devise new ways of slowing down microbes or form treatments which lessen infection severity to a level where the host immune system is able to prevail.
References:
1. " Ehrlichia: Well-known Horse Disease is Key to New Human Infection," American Society for Microbiology: Public communication, 16 Feb. 1996, http://www.asmusa.org/
2. J, McDade, "Ehrlichiosis: a disease of animals and humans," Journal of Infectious Disease, vol.161, pp. 506-617; 1990.
3. K. Abbott, "Hemophagocytic Syndrome: A cause of pancytopenia in human ehrlichiosis," American Journal of Hematology, vol. 38, pp. 230-234;1991.
4. William Schaffner, M.D., Steven M. Standaert, M.D., "Ehrlichiosis - In Pursuit of an Emerging Infection," The New England Journal of Medicine, vol. 334, number 4, pp. 262-263; 25 Jan. 1996.
5. "Article," report by CDC on Human Granulocytic Ehrlychiosis, 1995
6. JS Dumler, JS Bakken,"Ehrlichial diseases of humans: emerging tick-borne infections," Clinical Infections Diseases, vol. 20, pp. 1102-1110; 1995.
7. DB Fishbein, JE Dawson, LE Robinson, "Human ehrlichiosis in the United States," Annual of internal medicine, vol. 120, pp. 736-743;1994.
8. Y. Rikihisa, "The Tribe Ehrlichieae and Ehrlichial Diseases," Clinical Microbiology, Rev, 4(3), pp. 286-308;1991.
9. Robert Heimer, Amy Van Andel, Gary P. Wormser, Mark L. Wilson, "Propagation of Granulocytic Ehrlichia spp. from Human and Equine Sources in HL-60 Cells induced to Differeniate into Functional Granulocytes," Journal of Clinical Microbiology, vol. 35, No. 4, pp. 923-927; Apr. 1997.
10. B.E. Anderson, J.E. Dawson, D.C. Jones, K.H. Wilson, "Ehrlichia chaffeensis, a new species associated with human ehrlichiosis," Journal of Clinical Microbiology, vol. 29, pp. 2838-2842;1991.
Other reports by Belinda Williams
Borna Virus A basis for Neuropsychiatric Illness- The controversy
Belinda Williams' ResumeBack to contents
"I will never let my schooling interfere with my education!" -Mark Twain
Back home!
