Persistent brain infection and disease reactivation in relapsing fever borreliosis

Larsson, Christer; Andersson, Marcus; Pelkonen, Jenni; Guo, Betty P.; Nordstrand, Annika; Bergström, Sven

doi:10.1016/j.micinf.2006.04.007

Cited by 35 publications

(37 citation statements)

References 26 publications

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“…Tick DNA was extracted by using ammonium hydroxide (NH 4 OH) as Conventional PCR and sequencing 25 All deer blood DNA samples were examined using nested PCR to detect the Borrelia spp. BflaPCR for nested PCR as previously described (Takano et al, 2010) Analyser (Applied Biosystem), and were compared in GenBank for identification to species.…”

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confidence: 99%

A relapsing fever group Borrelia sp. similar to Borrelia lonestari found among wild sika deer (Cervus nippon yesoensis) and Haemaphysalis spp. ticks in Hokkaido, Japan

Lee

Takano

Taylor

et al. 2014

Ticks and Tick-borne Diseases

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eastern part of Hokkaido, Japan. The total prevalence of this Borrelia sp. in tested deer blood samples 4 was 10.6% using conventional PCR and real-time PCR. The prevalence was significantly higher in 5 deer fawns compared to adults (21.9% and 9.4%, respectively). Additionally, there was significant 6 regional difference between our two sampling areas, Shiretoko and Shibetsu with 17% and 2.8% 7 prevalence, respectively. Regional differences were also found in tick species collected from field and 8 on deer. In the Shiretoko region, Haemaphysalis spp. were more abundant than Ixodes spp., while in

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confidence: 99%

A relapsing fever group Borrelia sp. similar to Borrelia lonestari found among wild sika deer (Cervus nippon yesoensis) and Haemaphysalis spp. ticks in Hokkaido, Japan

Lee

Takano

Taylor

et al. 2014

Ticks and Tick-borne Diseases

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“…Mice were infected with B. duttonii, and 80 days later, when the spirochetes were in their persistent and silent state, the animals were also infected with P. berghei. This subsequent malaria infection reactivated the spirochetes in 6 out of 10 mice (Table 1), which can be compared with reactivation in 3 out of 11 mice induced by cortisone injections (18). Moreover, the first spirochetes were seen in blood samples as early as day 13 after introduction of the malaria parasites, which was 19 days earlier than after cortisone treatment (18).…”

Section: Resultsmentioning

confidence: 92%

“…Therefore, we assessed the outcome of concomitant malaria/RF infection in mice by monitoring growth of the rodent malaria parasite P. berghei and the spirochete B. duttonii daily from day 3 postinfection. In mice, P. berghei infection is lethal (27), whereas infection with B. duttonii is generally not fatal (18). In experiments in which mice were infected only with P. berghei, 49.5% of the erythrocytes were parasitized (here referred to as parasitemia) at day 14 postinfection (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Reactivation of latent residual RF Borrelia. After the febrile episodes, RF can persist in the brain as a silent, residual infection that can be activated by immune suppression (18). Therefore, we performed experiments to determine whether the polarized immune response toward malaria could reactivate residual spirochetes.…”

Section: Resultsmentioning

confidence: 99%

“…This subsequent malaria infection reactivated the spirochetes in 6 out of 10 mice (Table 1), which can be compared with reactivation in 3 out of 11 mice induced by cortisone injections (18). Moreover, the first spirochetes were seen in blood samples as early as day 13 after introduction of the malaria parasites, which was 19 days earlier than after cortisone treatment (18). This suggests that the immune response mounted against a residual B. duttonii infection can be disarmed by a secondary malaria infection, which is the first finding of a biologically and clinically relevant cue to reactivate latent RF Borrelia.…”

Section: Resultsmentioning

confidence: 99%

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Concomitant Infection Decreases the Malaria Burden but Escalates Relapsing Fever Borreliosis

et al. 2010

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About 500 million cases of malaria occur annually. However, a substantial number of patients who actually have relapsing fever (RF) Borrelia infection can be misdiagnosed with malaria due to similar manifestations and geographic distributions of the two diseases. More alarmingly, a high prevalence of concomitant infections with malaria and RF Borrelia has been reported. Therefore, we used a mouse model to study the effects of such mixed infection. We observed a 21-fold increase in spirochete titers, whereas the numbers of parasitized erythrocytes were reduced 15-fold. This may be explained by polarization of the host immune response toward the intracellular malaria parasite, resulting in unaffected extracellular spirochetes and hosts that succumb to sepsis. Mixed infection also resulted in severe malaria anemia with low hemoglobin levels, even though the parasite counts were low. Overall, coinfected animals had a higher fatality rate and shorter time to death than those with either malaria or RF single infection. Furthermore, secondary malaria infection reactivated a quiescent RF brain infection, which is the first evidence of a clinically and biologically relevant cue for reactivation of RF Borrelia infection. Our study highlights the importance of investigating concomitant infections in vivo to elucidate the immune responses that are involved in the clinical outcome.In the developing world, concomitant infections are the rule rather than the exception, and the complete clinical picture involves several microorganisms that influence each other as well as the host (8). Malaria is by far the most devastating acute febrile illness in humans, and it is caused by parasitic protozoa of the genus Plasmodium. The World Health Organization (WHO) has estimated that this disease is responsible for 1.5 to 2.7 million deaths annually, and about 1 million of those cases occur in children under the age of 5 years (24,28). Considering that the most prominent symptom of malaria is fever (4) and that the WHO advises that a presumptive malaria diagnosis be made in areas where malaria is endemic, it is plausible that misdiagnoses can be made in patients who are not suffering from malaria or who have a concomitant infection (14). This assumption is supported by the results of a field study conducted by our research team in Togo, West Africa, in which 8.8% of febrile patients diagnosed as having malaria were subsequently found to have relapsing fever (RF) borreliosis, which is caused by spirochete bacteria of the genus Borrelia (21). This could be simply due to incorrect malaria diagnosis, which is plausible since both Plasmodium and RF Borrelia cause systemic infections with similar manifestations that involve recurrent fever, anemia, and hepatosplenomegaly. It could also be due to malaria/RF coinfection, which makes a correct diagnosis even more complex. Moreover, medical personnel are generally not aware of the existence of RF borreliosis, even though the incidence of that condition in countries such as Senegal is the highest des...

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Spirochaetes

Houston

Taylor

Cameron

2014

Encyclopedia of Life Sciences

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Species in the phylum Spirochaetes (order: Spirochaetales) are thin, spiral‐shaped or wave‐like, highly motile bacteria that are best visualised by darkfield microscopy. Spirochaetes are Gram‐negative‐like, in that they possess inner and outer membranes separated by a peptidoglycan‐containing periplasmic space. Beyond these ultrastructural similarities, few parallels exist with conventional Gram‐negative bacteria. There have been more than 90 spirochaete species identified, including the well‐known pathogenic, disease‐causing species Treponema pallidum (syphilis), Leptospira sp. (leptospirosis) and Borrelia burgdorferi (Lyme disease). The phylogenetic relationship among spirochaetes is evident at the level of gross phenotypic characteristics, which include a distinctive morphology derived from the presence of periplasmic flagella. In this article, the authors describe the genomic, physiologic, structural and functional features that make Spirochaetes unique among the prokaryotes. Key Concepts: Spirochaetes are a genetically and morphologically distinct group of bacteria. Spirochaetes are thin spiral‐shaped or wave‐like bacteria that are highly motile. Endoflagella/periplasmic flagella provide spirochaetes with their characteristic corkscrew‐like motility. Spirochaetes differ from typical Gram‐negative bacteria at the ultrastructural level. Spirochaetes are chemo‐organotrophic, grow in diverse conditions and are comprised of both pathogenic and nonpathogenic members. Complete genome sequencing has allowed for the characterisation and differentiation of spirochaetes at the genetic level. Medically important spirochaetes belong to the three genera Borrelia , Leptospira and Treponema .

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Persistent brain infection and disease reactivation in relapsing fever borreliosis

Cited by 35 publications

References 26 publications

A relapsing fever group Borrelia sp. similar to Borrelia lonestari found among wild sika deer (Cervus nippon yesoensis) and Haemaphysalis spp. ticks in Hokkaido, Japan

A relapsing fever group Borrelia sp. similar to Borrelia lonestari found among wild sika deer (Cervus nippon yesoensis) and Haemaphysalis spp. ticks in Hokkaido, Japan

Concomitant Infection Decreases the Malaria Burden but Escalates Relapsing Fever Borreliosis

Spirochaetes

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