Background

Bartonella is a genus classification of bacteria that may infect humans and cause disease. These gram-negative alpha-proteobacteria are intracellular parasites that traditionally are considered opportunistic pathogens, however Bartonella has gained attention for concern for healthy individuals. Generally Bartonella species are transmitted by injury, as in 'Cat Scratch disease', or by insect vectors that include mites, fleas, mosquitoes, some species of biting flies, and is believed to be transmitted by ticks as well. New species of Bartonella are continually being discovered with at least 8 or 9 species having the capacity to infect humans. Once Bartonella gain access to a host via injury or an insect vector the bacteria colonize the local tissues and ultimately invade the host's erythrocytes (red blood cells). Once inside these cells the Bartonella replicate and wait to be reinjested by an arthropod vector, thus completing its life cycle. The most common species of Bartonella in the continental United States includes B. quintana, results in Trench fever, and B. henselae and B. elizabethae, both of which results in Cat-scratch disease. This list is not exhaustive, there are many more species of Bartonella in the United States that may cause disease and likely many that have yet to be discovered. In general, most Bartonella species may result in endocarditis in cases of chronic infection in addition to their acute manifestation of disease. Symptoms resulting from Bartonella infection vary widely depending on the host's response, immunocompetent status, Bartonella species, and length of infection.

Detection Technology

Detection of a Bartonella spp. infection centers around three main technologies. First, microscopic evidence of infection may be obtained if sufficient levels of infection are reached. The detection of Bartonella via microscopic means are generally considered difficult, however Fry Laboratories has developed a variety of proprietary staining techniques that make it possible to detect epierythrocytic and intraerythrocytic infections more reliably. Next, serologic based assays are aimed at determining wether the patient has generated antibodies against any Bartonella species. These tests require that the patient immune response is sufficiently robust to produce specific anti-Bartonella antibodies. Furthermore, even in cases where antibodies against Bartonella are generated determination of the causative species of Bartonella can be difficult as there is much overlap in seroreactivity between Bartonella species. Lastly, molecular diagnostics has opened new doors for diagnostic testing.

Molecular Diagnostics

A review of diagnostic technologies over the last five years is enriched with the advent of molecular diagnostics, specifically polymerase chain reaction (PCR) based tests. These PCR-based tests have proven to be sensitive, accurate, and useful in the detection and species determination of Bartonella species in clinical settings [1-80]. This method has been applied for use in diagnosis and treatment monitoring in humans [5, 6, 10, 11, 14-17, 21-24, 26, 27, 29-35, 37, 38, 40, 42, 46, 47, 50, 68, 69, 71, 72, 75-79, 81, 82]. The scientific understanding of both epidemiologic [12, 23, 24, 26, 29, 36, 43, 44, 54, 55, 59, 66, 67, 70, 76, 79] and strain variation [12, 83, 84] in human Bartonella infections has been greatly accelerated with the innovative application of PCR-based detection technologies. Finally, this technology has been reiteratively improved, expanded, and compared to other existing methods to monitor human Bartonella infections [18, 20, 22-24, 28, 34, 36, 39-41, 43-45, 48, 51, 52, 56, 72, 74, 76, 80, 85].

Human medicine is not the only discipline that has been rapidly affected by these technologies. In zoologic and veterinary medicine PCR-based assays have been used in the detection [67, 86-161], diagnosis of symptoms [95, 105, 113, 116, 117, 122, 123, 128, 132, 137, 140, 145, 147, 158], and monitoring of treatment [128, 137, 162] in both domesticated and wild animals. PCR-based tests have assisted in our understanding of the distribution, reservoirs, and tropism of Bartonella infections [67, 87, 91-94, 97, 99, 101-104, 107, 111, 112, 114, 115, 121, 122, 126, 127, 131, 133, 136, 137, 141, 142, 144, 146, 147, 149-151, 153, 155-157, 159, 160, 163, 164]. We now appreciate the intricacies and variations of the various Bartonella strains and subspecies [90, 92, 96, 118, 126, 131, 146] and common Bartonella co-infections [95, 103, 111-115, 120, 121, 126, 149, 150, 152, 165, 166] that afflict animals. Since PCR testing is rapid , routine, and non-invasive, studies of wild animals have helped determine geographic locations near heavily infested resevoior populations and have assisted in public health awareness [100-102, 110, 112, 114, 118, 120, 121, 124, 126, 129, 131, 133, 144, 150-152, 155, 156, 159, 160, 163, 164, 166]. Lastly, many improvements and innovations in PCR-based tests for Bartonella have come from the veterinary sciences [108, 134-136, 153, 161].

Bartonella has been detected in a wide variety of vectors using this technology [59, 100, 121, 127, 142, 156, 166-192]. Vector transmission [162, 177, 181], epidemiologic distribution [59, 100, 121, 127, 142, 156, 164, 166, 168-171, 173, 175-180, 182-184, 186, 187, 189-192], strain, and co-infection variation [55, 170, 172, 175, 176, 178-180, 182, 185, 187, 189, 192] have all become fertile areas of study. Finally, PCR has assisted in the study of the cell biology of Bartonella [83, 193-197] in addition to improvements in cell culture of these organisms [174].

Summary

By drawing on this rapidly evolving and improving literature Fry Laboratories has generated a genus wide PCR based test to assist in the detection, diagnosis, and speciation of Bartonella infections. All positive samples are reflex sequenced and strain information determined to assist in treatment. The Bartonella spp. test by PCR in conjunction with our proprietary microscopy and serologies allow our laboratory to rapidly and robustly detect any Bartonella spp., even if it is new and unknown to science and medicine.

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