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Borrelia
Borreliosis is a worldwide infectious disease caused by spiral-shaped bacteria known as Borreliae, carried by ticks and louse. Borrelia is a genus of bacteria of the spirochete phylum.
Borrelia is divided into two main clades, the Borrelia burgdorferi sensu lato group and the relapsing fever group.
The B. burgdorferi sensu lato group contains 20 species (like B. burgdorferi,B. afzelii, B. garinii, B. Spielmanii, B. bavariensis, etc), including the causative agents of Lyme borreliosis, and are solely transmitted by hard-bodied ticks. Lyme disease (LD) is the most common tick-born disease with approximately 476,000 patients in the United States annually during 2010–2018 (Kugeler et al., 2021). The LD-causing bacteria are generally transmitted to humans after they are bitten by ticks of the Ixodes family infected with LD causing Borrelia. However, recent reports have raised concerns over Borrelia transmission through blood transfusion based on observations that Borrelia can survive and circulate in the human bloodstream (Pavia and Plummer, 2018).
Lyme disease exhibits a variety of symptoms that may be confused with immune and inflammatory disorders. Inflammation around the tick bite causes skin lesions. Erythema (chronicum) migrans (ECM), a unique expanding skin lesion with central clearing that has a ring-like appearance, is typically the first stage of the disease. Arthritis, neurological disease, and cardiac disease may be later stage manifestations. For signs and symptoms, refer to https://www.cdc.gov/lyme/signs_symptoms/index.html
The relapsing fever group consists of 25 species that includes Borrelia miyamotoi, B. recurrentis, B. hermsii, B. duttonnii, etc. Most of the relapsing fever species are transmitted by soft-bodied ticks but some species are transmitted by hard-bodied ticks (B. miyamotoi, Borrelia lonestari, Borrelia theileri) or by lice (Borrelia recurrentis). B. miyamotoi shares phenotypic characteristics of the relapsing fever group such as relapsing fever, a high level of spirochetemia in blood, and transovarial transmission; however, it also has some characteristics of the B. burgdorferi sensu lato group, most notably transmission by hard-bodied ticks. In contrast to Lyme disease, the rash was uncommon, with fewer than 1 in 10 patients developing a rash.
RF Borrelia are reported to develop immune evasion strategies. One prominent strategy developed by RFB to evade innate immunity involves inactivation of complement by recruiting distinct complement regulatory proteins. In addition, RFB possess a unique system of antigenic variation, allowing them to change the composition of surface-exposed variable major proteins, thus evading the acquired immune response of the human host ( see https://www.frontiersin.org/articles/10.3389/fimmu.2020.01560/full ).
Other tick-borne infections
Borreliosis is the most known tick-borne infection, but it is not the only one, many other pathogens are transmitted by the ticks with or without Borrelia. Clinically relevant tick-borne infections (previously named "co-infections") are caused by Babesia, Bartonella species, Rickettsia, Anaplasma, Ehrlichia, several viruses (like Heartland virus, Powassan virus, Bourbon virus, Tick-borne encephalitis (TBE) virus, ) etc. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease.
Babesia
Babesiosis is caused by apicomplexan parasites of the genus, Babesia.This makes it similar to malaria. While more than 100 species have been reported, only a few have been identified as causing human infections, including B. microti, B. divergens, B. duncani, and a currently un-named strain designated MO-1.
Manifestations of disease include fever, chills, sweating, myalgias, fatigue, hepatosplenomegaly, and hemolytic anemia. Symptoms typically occur after an incubation period of 1 to 4 weeks, and can last several weeks. The disease is more severe in patients who are immunosuppressed, splenectomized, and/or elderly. Infections caused by B. divergens tend to be more severe (frequently fatal if not appropriately treated) than those due to B. microti, where clinical recovery usually occurs.
Bartonella
Bartonellosis is a group of diseases caused by species of the genus Bartonella and is primarily associated with fleas and lice. However, studies have found that certain Bartonella species are carried by the same ticks that carry Lyme disease, and ticks are likely the chief source of human bartonellosis infection. Bartonella (with over 30 named species and 17 Candidatus spp.) were essentially rediscovered in the 1990’s as a cause of vasoproliferative tumors, endocarditis and fever of unknown origin in immunosuppressed or immunocompromised (HIV) patients. Recent medical findings suggest that, while potentially life-threatening to immunosuppressed patients, bartonellosis is associated with chronic illness in immunocompetent patients.
Several species of Bartonella cause severe diseases in humans, such as Cat scratch disease (CSD), endocarditis, trench fever, and Carrion’s disease. Bartonella henselae is the causative agent for CSD and has also been known to cause bacillary angiomatosis, peliosis hepatis, bacteremia, and endocarditis in immunocompromised individuals. Bartonella quintana causes trench fever, described as such due to outbreaks during the two world wars. Carrion’s disease is caused by B. bacilliformis, and is only known to infect humans. Currently, around half the species of the gram-negative bacterial genus Bartonella are known to cause human disease. Some of these species include B. elizabethae, B. washoensis, B. vinsonii, B. koehlare, and B. alsatica.
Rickettsia
Rickettsia species are infectious bacteria that are closely related to other flea- and tick-borne pathogens like Bartonella and Ehrlichia. Rickettsiosis is a global name for all infections caused by these bacteria. The infections can be further classified into two categories; the spotted fever group rickettsioses (SFGR) and the typhus group rickettsioses.
SFGR are caused by Rickettsia that are transmitted by ticks and typically result in characteristic rashes on the extremities, face, and/or trunk of the body. The best-known and deadliest SFGR in the United States is Rocky Mountain spotted fever (RMSF), which is caused by Rickettsia rickettsii. Spotted fevers can range from mild to life-threatening. Most people who get sick with a spotted fever other than RMSF will have an eschar (dark scab at the site of tick or mite bite), fever, headache, and rash. The typhus group rickettsioses are a smaller group that employs a different mode of transmission than the SFGR: R. typhi is transmitted by fleas and R. prowzekii is transmitted by lice.
Anaplasma
Anaplasmosis is a disease caused by the bacterium Anaplasma phagocytophilum. These bacteria are spread to people by tick bites primarily from the blacklegged tick (Ixodes scapularis) and the western blacklegged tick (Ixodes pacificus). Anaplasma species are bacteria that can evade the antimicrobial defenses of white blood cells, like neutrophil granulocytes, and negatively affect the immune system. One of the methods they use is living inside the cells of the host. People with anaplasmosis will often have fever, headache, chills, and muscle aches. The non-specific and chronic symptoms associated with anaplasmosis often mimic other chronic infections and autoimmune diseases.
Ehrlichia
Ehrlichiosis is a general name used to describe diseases mainly caused by the bacteria Ehrlichia chaffeensis, E. ewingii, or E. muris eauclairensis. Ehrlichia species are bacteria that can evade the immune system and infect host cells. They preferentially infect white blood cells in the bloodstream, such as neutrophils and macrophages, but have also been found in spleen, lymph node, and kidney tissue samples.
These bacteria are spread to people primarily through the bite of infected ticks including the lone star tick (Amblyomma americanum) and the blacklegged tick (Ixodes scapularis). People with ehrlichiosis will often have fever, chills, headache, muscle aches, and sometimes upset stomach. The non-specific and chronic symptoms associated with ehrlichiosis often mimic other chronic infections and autoimmune diseases. Ehrlichiosis infection can also mimic liquid tumors.
Testing ticks (animal)
Testing (human) samples for tick diseases
Tick borne disease-related testing
Summarizing TBI-related testing is a huge enterprise. Many articles, books, websites, blogs, etc are available today and multiple conferences are held each year. The goal of the present contribution was to put some of this information together as a convenient resource for patients in order to promote an understanding of the usefulness but also the limitations of available tests and the underlying reasons of failure.
The final aim was also to further emphasize the need for a global, integrative approach for a better management of TBIs.
Testing (human) samples for tick diseases
Initial integrative chronic lyme panel
In order to offer better management of patients with chronic and/or persistent infections that are very difficult to uncover, it is important to focus both on direct pathogen detection as well as on indirect supportive tests, including tests for gastrointestinal issues.
Following many discussions with specialists in chronic infections management, we at R.E.D. Labs are launching the Initial Integrative Chronic Lyme panel.
