Conferencias Magistrales
Ehrlichiosis y anaplasmosis humanas en América
Human Ehrlichiosis and Anaplasmosis in
J. Stephen Dumler
Se realiza una descripción de los agentes de Ehrlichia y Anaplasma que han sido vinculados con la generación de enfermedad los seres humanos, dando especial énfasis Ehrlichia chaffeensis, Anaplasma phagocytophilum y Ehrlichia canis. Se describe además, el cuadro clínico relacionado con cada agente, su correspondiente diagnóstico y tratamiento.
Descriptores: Ehrlichiosis, anaplasmosis, humanos, América
Abstract
A description of Ehrlichia and Anaplasma agents that have been linked to human disease is presented. A particular emphasis is given to Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Ehrlichia canis. The clinical features associated with each agent, as well as the corresponding diagnosis and treatment are also described.
Keywords: Ehrlichiosis, anaplasmosis, humans,
Since the first descriptions, human infections caused by new species, including Ehrlichia chaffeensis (cause of HME or human monocytic ehrlichiosis),1 Ehrlichia ewingii,2 an Ehrlichia muris-like agent (EMLA),3 the Panola Mountain Ehrlichia (PME) which has similarities to Ehrlichia ruminantium,4 and Anaplasma phagocytophilum (cause of human granulocytic anaplasmosis-HGA) have been identified in the Americas.5,6 The only evidence of human infections by any of these species in Central or South America is limited to the cultivation of E. canis from an asymptomatic person in Venezuela,7 several cases of E. canis infection in symptomatic patients in Venezuela,8 a single case of E. chaffeensis infection in a Venezuelan child,9 or to limited serologic suspicion based on high antibody titers in seroprevalence studies or seroconversions in individual patients. All species in these genera are transmitted to their vertebrate hosts by tick bites, including Amblyomma americanum in the
The median age of those diagnosed with HME and HGA is 47 to 52 years,11 and for EMLA infection, 60 years,3 yet all infection has been reported in all age groups.11 Men are affected more often than women by a ratio of 1.4:1. Infection is often reported in those with HIV infection, where the course can be fulminant.20 Other immune compromising conditions such as cancer, diabetes, arthritis, or organ transplantation are reported in up to 12% of HME patients.11 For HGA, increased incidence or severity of infection with HIV infection has not been well documented, and fewer (6.5%) of patients reported pre-existing immune compromising conditions, including asplenia.11
The clinical features of infection have been best delineated in patients from the
Nearly 50% of HME and 36% of HGA patients require hospitalization.11 Complications of infection can occur, including a septic- or toxic-shock syndrome, acute respiratory distress syndrome, acute abdominal syndromes, cardiac failure, renal failure, cranial nerve palsies, brachial plexopathy, demyelinating polyneuropathy, meningoencephalitis (for HME), and opportunistic infections.23 There is very limited evidence that even with recovery from active infection, patients with HGA do not report feeling entirely well up to one year later.24
Diagnosis is suspected with undifferentiated fever or an influenza-like illness after exposures to ticks or reported tick-bites, especially given thrombocytopenia with leukopenia and mild to moderate increases in serum AST or ALT. The diagnosis can be confirmed rapidly by review of a peripheral blood or buffy coat smear stained by Giemsa, Wright or similar Romanowsky methods that demonstrate inclusions (morulae) in monocytes in up to 10% of HME patients, or in neutrophils in up to 75% of HGA patients.25 A specific diagnosis can be made by identification of Ehrlichia spp. or Anaplasma DNA in blood, CSF or tissues using methods such as PCR. The most frequent method for diagnosis is the demonstration of a seroconversion or four-fold increase in specific antibody titer, which is highly sensitive when comparing acute and convalescent sera, but has not been rigorously tested for specificity. Diagnostic serological tests usually use indirect immunofluorescent methods, where the sensitivity and specificity are highest for IgG antibodies. A role for IgM testing has not been clearly established.
All forms of ehrlichiosis and anaplasmosis appear to respond to tetracycline antibiotics, especially doxycycline, although no randomized clinical trials have been conducted. All isolates so far tested are susceptible to these drugs in vitro at easily achieved MICs.26-29 Chloramphenicol should not be used owing to lack of in vitro susceptibility and frequent empirical clinical failures. Although A. phagocytophilum is sensitive to fluoroquinolones in vitro, treatment failures with levofloxacin that required subsequent retreatment with doxycycline are reported.30 Rifampin has low MICs in vitro and has been successfully used in children in empiric studies.31,32
Other forms of human infections by Anaplasmataceae species are reported outside of the
Acknowledgements: This work was supported in part by funding from the US National Institutes of Allergy and Infectious Diseases including grants R01 AI044102, R21 AI096062, and grant 011DUM2013 from the Fisher Center Discovery Program at The Johns Hopkins University.
Conflict of interest: JSD receives royalty payments for patent on the method to grow Anaplasma phagocytophilum to prepare serological reagents.
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