SUMMARY Increases in tick-borne disease prevalence and transmission are important public health issues. Efforts to control these emerging diseases are frustrated by the struggle to control tick populations and to detect and treat infections caused by the pathogens that they transmit. This review covers tick-borne infectious diseases of nonrickettsial bacterial, parasitic, and viral origins. While tick surveillance and tracking inform our understanding of the importance of the spread and ecology of ticks and help identify areas of risk for disease transmission, the vectors are not the focus of this document. Here, we emphasize the most significant pathogens that infect humans as well as the epidemiology, clinical features, diagnosis, and treatment of diseases that they cause. Although detection via molecular or immunological methods has improved, tick-borne diseases continue to remain underdiagnosed, making the scope of the problem difficult to assess. Our current understanding of the incidence of tick-borne diseases is discussed in this review. An awareness of the diseases that can be transmitted by ticks in specific locations is key to detection and selection of appropriate treatment. As tick-transmitted pathogens are discovered and emerge in new geographic regions, our ability to detect, describe, and understand the growing public health threat must also grow to meet the challenge.

RNA elements within flavivirus genomes are potential targets for antiviral therapy. A panel of phosphorodiamidate morpholino oligomers (PMOs), whose sequences are complementary to RNA elements located in the 5-and 3-termini of the West Nile (WN) virus genome, were designed to anneal to important cis-acting elements and potentially to inhibit WN infection. A novel Arg-rich peptide was conjugated to each PMO for efficient cellular delivery. These PMOs exhibited various degrees of antiviral activity upon incubation with a WN virus luciferase-replicon-containing cell line. Among them, PMOs targeting the 5-terminal 20 nucleotides (5End) or targeting the 3-terminal element involved in a potential genome cyclizing interaction (3CSI) exhibited the greatest potency. When cells infected with an epidemic strain of WN virus were treated with the 5End or 3CSI PMO, virus titers were reduced by approximately 5 to 6 logs at a 5 M concentration without apparent cytotoxicity. The 3CSI PMO also inhibited mosquito-borne flaviviruses other than WN virus, and the antiviral potency correlated with the conservation of the targeted 3CSI sequences of specific viruses. Modeof-action analyses showed that the 5End and 3CSI PMOs suppressed viral infection through two distinct mechanisms. The 5End PMO inhibited viral translation, whereas the 3CSI PMO did not significantly affect viral translation but suppressed RNA replication. The results suggest that antisense PMO-mediated blocking of cis-acting elements of flavivirus genomes can potentially be developed into an anti-flavivirus therapy. In addition, we report that although a full-length WN virus containing a luciferase reporter (engineered at the 3 untranslated region of the genome) is not stable, an early passage of this reporting virus can be used to screen for inhibitors against any step of the virus life cycle.Many members of the Flavivirus genus, a group of arthropod-borne viruses in the family Flaviridae, cause significant human diseases; among these, West Nile (WN), dengue (DEN), Japanese encephalitis (JE), yellow fever (YF), Murray Valley encephalitis, and tick-borne encephalitis (TBE) viruses are emerging and reemerging pathogens (7). Approximately 50 to 100 million human cases of DEN virus infection occur annually (29). The recent epidemics of WN virus have caused significant morbidity and mortality in the United States (9). Vaccines for humans are available only for YF, JE, and TBE viruses (7). No drug therapy is currently available to treat flavivirus infections. It is therefore of great importance to public health to develop an efficacious drug therapy against flaviviruses.Flavivirus virions are spherical in shape, with a diameter of approximately 50 nm (21). The flavivirus genome is a singlestranded, plus-sense RNA of approximately 11 kb in length. The genomic RNA consists of a 5Ј untranslated region (UTR), a single long open reading frame (ORF), and a 3Ј UTR (43). The single ORF encodes a polyprotein that is co-and posttranslationally processed by viral and cellular proteases...

The recent outbreaks of West Nile virus (WNV) in the northeastern