HARDSCIENCEONLYME:  How Tick-Borne Diseases like Babesia and Anaplasma Persist

5th April 2011

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It is important to understand mechanisms of persistence in tick-borne diseases.  Microbes use different mechanisms to evade the immune system and survive. A study by Anthony Barbet of the University of Florida describes the mechanisms by which babesiosis and anaplasmosis persist in animals.  He notes that many vector-borne diseases remain resistant and states: "Some of the most intransigent of these are infections that induce a 'carrier' state, where the animal remains infected, is still able to transmit organisms to the vector, but may show disease symptoms intermittently or not at all. Indeed, it may be difficult to detect the infection by classical means."  He points to Babesia and Anaplasma as prime examples of this type of persistence and discusses how new and sensitive molecular diagnostic methods have made it possible to demonstrate that "a typical infection course consists of numerous relapsing peaks of organisms separated by time periods when they are not detected."

Typically when an acute (new-onset) infection develops, the human or animal immune system will make antibodies and recruit immune cells that attack and destroy the bacteria or parasite. Tickborne agents like Babesia and Anaplasma, on the other hand, use clever mechanisms to avoid the host immune response and establish chronic (long-lasting) infection.  These mechanisms include antigen variation, cytoadhesion, and cycling gene variation of the organism.  The antibodies and immune cells that fight infection are specifically developed in response to the microbe’s outer surface antigens.  By varying their outer surface antigens, microbes can escape detection by the immune system. Cytoadhesion occurs when parasites like Babesia infect blood cells that adhere to the walls of the capillaries in clumps, so that fewer of them are exposed to the immune system.  Cycling gene variation is used by Anaplasma to cycle the organism levels in chronic infection in order to remain below the radar of the immune system.  Understanding these mechanisms of persistence and  immune evasion will allow us to develop treatments that prevent chronic infection with tickborne agents.

ABSTRACT
BARBET, A.F. 2009. Persistence mechanisms in tick-borne diseases. Onderstepoort Journal of Veterinary Research, 76:53-58

The use of new, highly sensitive diagnostic methods has revealed persistent infections to be a common feature of different tick-borne diseases, such as babesiosis, anaplasmosis and heartwater. Antigenic variation can contribute to disease persistence through the continual elaboration of new surface structures, and we know in several instances how this is achieved. Known or suspected mechanisms of persistence in babesial parasites include cytoadhesion and rapid variation of the adhesive ligand in Babesia bovis and genetic diversity in several merozoite stage proteins of different Babesia spp. In Anaplasma, extensive variation in the pfam01617 gene family accompanies cycling of organism levels in chronic infection. One result from the pioneering research at Onderstepoort is the definition of a related polymorphic gene family that is likely involved in immunity against heartwater disease. We are beginning to understand the sizes of the antigenic repertoires and full definition is close, with the possibility of applying simultaneous high-throughput sequencing to the order of 1 000 small genomes. We also, for the first time, can consider modifying these genomes and looking at effects on persistence and virulence. However, important biological questions remain unanswered; for example, why we are seeing a new emerging Anaplasma infection of humans and is infection of endothelial cells by Anaplasma significant to persistence in vivo.

You can follow additional comments on Lyme policy at www.lymepolicywonk.org.  You can contact Lorraine Johnson, JD, MBA at lbjohnson@lymedisease.org.

Related posts:

  1. Babesia
  2. Other Tick-Borne Diseases
  3. HARD SCIENCE ON LYME: Blood Transfusion Risk of Babesia Unacceptable
  4. TOUCHED BY LYME: Tick-borne mystery in Folsom, CA. Can you say “tularemia”?
  5. NEWS: Tick-borne tularemia found in Sacramento County, CA
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