Scrub typhus and the rickettsial diseases represent some of the oldest recognized vector-transmitted diseases, fraught with a rich historical aspect, particularly as applied to military/wartime situations. The vectors of Orientia tsutsugamushi were once thought to be confined to an area designated as the Tsutsugamushi Triangle. However, recent reports of scrub typhus caused by Orientia species other than O. tsutsugamushi well beyond the limits of the Tsutsugamushi Triangle have triggered concerns about the worldwide presence of scrub typhus. It is not known whether the vectors of O. tsutsugamushi will be the same for the new Orientia species, and this should be a consideration during outbreak/surveillance investigations. Additionally, concerns surrounding the antibiotic resistance of O. tsutsugamushi have led to considerations for the amendment of treatment protocols, and the need for enhanced public health awareness in both the civilian and medical professional communities. In this review, we discuss the history, outbreaks, antibiotic resistance, and burgeoning genomic advances associated with one of the world’s oldest recognized vector-borne pathogens, O. tsutsugamushi.

Scrub typhus is the most important rickettsial disease in the world. Its previous endemic region was considered to be in Asia, Australia and islands in the Indian and Pacific Oceans; this area was referred to as the Tsutsugamushi Triangle. Accumulation of serological, molecular, genetic, and culture data have shown that not only is scrub typhus not limited to the Tsutsugamushi Triangle, but can be caused by orientiae other than Orientia tsutsugamushi. This review describes evidence currently available that will be instrumental to researchers, healthcare providers and medical leaders in developing new research projects, performing diagnosis, and preventing scrub typhus in locations not previously thought to be endemic.

Rickettsiae constitute a group of arthropod-borne, Gram-negative, obligate intracellular bacteria that are the causative agents of diseases ranging from mild to life threatening that impact on medical and veterinary health worldwide. A total of 6,484 ticks were collected by tick drag from June-October 2013 in the southwestern provinces of the Republic of Korea (ROK) (Jeollanam, n = 3,995; Jeollabuk, n = 680; Chungcheongnam, n = 1,478; and Chungcheongbuk, n = 331). Ticks were sorted into 311 pools according to species, collection site, and stage of development. DNA preparations of tick pools were assayed for rickettsiae by 17 kDa antigen gene and ompA nested PCR (nPCR) assays and the resulting amplicons sequenced to determine the identity and prevalence of spotted fever group rickettsiae (SFGR). Haemaphysalis longicornis (4,471; 52 adults, 123 nymphs and 4,296 larvae) were the most commonly collected ticks, followed by Haemaphysalis flava (1,582; 28 adults, 263 nymphs and 1,291 larvae), and Ixodes nipponensis (431; 25 adults, 5 nymphs and 401 larvae). The minimum field infection rate/100 ticks (assuming 1 positive tick/pool) was 0.93% for the 17 kDa antigen gene and 0.82% for the ompA nPCR assays. The partial 17 kDa antigen and ompA gene sequences from positive pools of H. longicornis were similar to: Rickettsia sp. HI550 (99.4–100%), Rickettsia sp. FUJ98 (99.3–100%), Rickettsia sp. HIR/D91 (99.3–100%), and R. japonica (99.7%). One sequence of the partial 17 kDa antigen gene for H. flava was similar to Rickettsia sp. 17kd-005 (99.7%), while seven sequences of the 17 kDa antigen gene obtained from I. nipponensis ticks were similar to R. monacensis IrR/Munich (98.7–100%) and Rickettsia sp. IRS3 (98.9%). SFG rickettsiae were detected in three species of ixodid ticks collected in the southwestern provinces of the ROK during 2013. A number of rickettsiae have been recently reported from ticks in Korea, some of which were identified as medically important. Results from this study and previous reports demonstrate the need to conduct longitudinal investigations to identify tick-borne rickettsiae and better understand their geographical distributions and potential impact on medical and veterinary health, in addition to risk communication and development of rickettsial disease prevention strategies.

Presently, few studies have investigated the role of domestic cats (Felis catus) in the recrudescence of flea-borne rickettsioses in California and the southern United States. In this study, we aimed to investigate the presence of Rickettsia typhi or Rickettisa felis in domestic cats (F. catus) and the fleas (primarily Ctenocephalides felis, the cat flea) associated with these cats in Riverside County, California. Thirty cats and 64 pools of fleas collected from these cats were investigated for rickettsial infections. Three cats and 17 flea pools (from 10 cats) tested positive for rickettsial infections. polymerase chain reaction and DNA sequencing indicated that one of the cats was positive for R. felis infections, whereas two were positive for Candidatus Rickettsia senegalensis infection. In addition, 12 of the flea pools were positive for R. felis, whereas five were positive for Ca. R. senegalensis. By contrast, no cats or their associated fleas tested positive for R. typhi. Finally, eight sera from these cats contained spotted fever group Rickettsia (SFGR) antibodies. The detection of R. felis and SFGR antibodies and the lack of R. typhi and TGR antibodies support R. felis as the main rickettsial species infecting cat fleas. The detection of Ca. R. senegalensis in both fleas and cats also provides additional evidence that cats and their associated fleas are infected with other R. felis–like organisms highlighting the potential risk for human infections with R. felis or R. felis–like organisms.

Rickettsia montanensis has long been considered a nonpathogenic member of the spotted fever group rickettsiae. However, the infection potential of R. montanensis is being revisited in light of its recent association with a case of human infection in the United States and the possibility that additional cases may have been misdiagnosed as Rocky Mountain spotted fever. To this end, DNA was extracted from American dog ticks (Dermacentor variabilis) removed from Department of Defense (DoD) personnel and their dependents at DoD medical treatment facilities (MTFs) during 2002–2012 (n = 4792). These 4792 samples were analyzed for the presence of R. montanensis (n = 136; 2.84%) and all vector DNA was confirmed to be of D. variabilis origin using a novel Dermacentor genus-specific quantitative real-time polymerase chain reaction procedure, Derm, and a novel Dermacentor species multilocus sequence typing assay. To assess the risk of R. montanensis infection, the positive and negative samples were geographically mapped utilizing MTF site locations. Tick localities were imported into a geographical information systems (GIS) program, ArcGIS, for mapping and analysis. The ecological niche modeling (ENM) program, Maxent, was used to estimate the probability of tick presence in eastern United States using locations of both R. montanensis-positive and -negative ticks, climate, and elevation data. The ENM for R. montanensis-positive D. variabilis estimated high probabilities of the positive ticks occurring in two main areas, including the northern Midwest and mid-Atlantic portions of the northeastern regions of United States, whereas the R. montanensis-negative D. variabilis tick model showed a wider estimated range. The results suggest that R. montanensis-positive and -negative D. variabilis have different ranges where humans may be at risk and are influenced by similar and different factors.

Rickettsia and Leptospira spp. are under-recognized causes of acute febrile disease worldwide. Rickettsia species are often placed into the spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR). We explored the antibody prevalence among humans for these two groups of rickettsiae in four regions of Peru (Lima, Cusco, Puerto Maldonado, and Tumbes) and for Leptospira spp. in Puerto Maldonado and Tumbes. We also assessed risk factors for seropositivity and collected serum samples and ectoparasites from peri-domestic animals from households in sites with high human seroprevalence. In total, we tested 2,165 human sera for antibodies (IgG) against SFGR and TGR by ELISA and for antibodies against Leptospira by a microscopic agglutination test. Overall, human antibody prevalence across the four sites was 10.6% for SFGR (ranging from 6.2% to 14.0%, highest in Tumbes) and 3.3% for TGR (ranging from 2.6% to 6.4%, highest in Puerto Maldonado). Factors associated with seroreactivity against SFGR were male gender, older age, contact with backyard birds, and working in agriculture or with livestock. However, exposure to any kind of animal within the household decreased the odds ratio by half. Age was the only variable associated with higher TGR seroprevalence. The prevalence of Leptospira was 11.3% in Puerto Maldonado and 5.8% in Tumbes, with a borderline association with keeping animals in the household. We tested animal sera for Leptospira and conducted polymerase chain reaction (PCR) to detect Rickettsia species among ectoparasites collected from domestic animals in 63 households of seropositive participants and controls. We did not find any association between animal infection and human serostatus.