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Like several other spirochetes, relapsing fever Borrelia can cause persistent infection of the central nervous system (CNS). By treating mice harboring residual Borrelia duttonii brain infection with the bacteriocidal, cell wall inhibiting antibiotic ceftriaxone, bacteria were cleared from the brain. This shows that the residual infection is not latent but actively growing.

About 500 million cases of malaria occur annually. However, a substantial number of patients who actually have relapsing fever (RF) Borrelia are misdiagnosed with malaria due to similar manifestation and geographic distribution of the two diseases. More alarmingly, high prevalence of mixed infections with malaria and RF Borrelia has been reported. Therefore, we developed a mouse model to study the effects of such mixed infection. We observed a 21-fold increase in spirochete titers, whereas parasitemia decreased 15-fold. This may be explained by polarization of the host immune response towards the intracellular malaria parasite, resulting in unaffected extracellular spirochetes and hosts succumb to sepsis. Furthermore, secondary malaria infection can reactivate a quiescent RF brain infection, which is the first evidence of a clinically and biologically relevant cue for reactivation of dormant RF Borrelia infection. Mixed infection also resulted in severe anemia even though the parasite counts were low. Our study highlights the importance of investigating mixed infections in vivo to elucidate the immune responses that are involved in the clinical outcome, and it also emphasizes the urgent need for improved diagnostics of malaria and other infectious diseases such as RF Borrelia.

Malaria is one of the most devastating diseases of the developing world responsible for approximately two million deaths annually. The high mortality together with the fact that resistance to available antimalarial drugs has increased, highlights the necessity of finding new chemotherapeutics against the parasite. Polyamines play a critical role in the regulation of cell proliferation and differentiation in most organisms including the malaria parasite. Therefore, targeting enzymes in the polyamine synthesis could be a possible approach to combat malaria. In order to evaluate the curative potential of the polyamine biosynthesis inhibitors S-adenosyl-3-thio-1,8-diaminooctane (AdoDATO) and trans-4-methylcyclohexylamine (4MCHA), which both target spermidine synthase, we took the advantage of an accessible mouse model using the rodent malaria parasite, P. berghei. Despite the promising inhibitory potential of AdoDATO, this drug was inefficient against malaria infection in mice. In contrast, 4MCHA restrained the parasite infection, which subsequently led to clearance within 24 days. This curative effect was not synergistically enhanced by combination treatment with the ornithine decarboxylase inhibitor, α-difluoromethylornithine (DFMO) and neither did a prophylactic treatment of 4MCHA increase the antimalarial effect. Interestingly, mice that received 4MCHA treatment gained a protective immunity towards malaria infection. The nature of this protective immunity is not established.