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Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these ill...
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... rickettsial diseases commonly have nonspecific clinical signs and symptoms early in the course of disease. Although the clinical presentations of tickborne rickettsial disease overlap, the frequency of certain associated signs and symptoms (e.g., rash and other cutaneous findings), typical laboratory findings, and case-fatality rates differ by pathogen (Table 1). Familiarity with the clinical signs and symptoms and pathophysiology of tickborne rickettsial diseases, including RMSF and other SFG rickettsioses (Box 3), ehrlichioses (Box 4), and anaplasmosis (Box 5) will assist health care providers in developing a differential diagnosis, prescribing appropriate antibacterial treatment, and ordering appropriate confirmatory diagnostic tests. ...
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Purpose of review:
Ticks are the second most important vectors of infectious diseases after mosquitoes worldwide. The growth of international tourism including in rural and remote places increasingly exposes travelers to tick bite. Our aim was to review the main tick-borne infectious diseases reported in travelers in the past 5 years.
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... Although ≈90% of patients with MIS-C or RMSF manifest fever, a rash is present in up to 90% of RMSF patients (6), compared with ≈50% of children with MIS-C (10,14). Patients with RMSF and MIS-C have similar laboratory test abnormalities that include thrombocytopenia, hyponatremia, and elevated inflammatory markers (i.e., procalcitonin and C-reactive protein) (6,9,10,14), probably because both diseases are characterized by a generalized inflammatory response, endothelial damage, and increased vascular permeability (1,10). ...
... Doxycycline is the recommended antimicrobial drug treatment for all patients who have suspected RMSF and should be empirically initiated to reduce fatal outcomes and severe sequelae (1,3,9), particularly in vulnerable children living with social disadvantages (1,14). Physicians and other health personnel practicing in RMSF-endemic areas should systematically consider RMSF in the differential diagnosis of hospitalized patients who have MIS-C to reduce delays in therapy and prevent death and severe sequelae caused by this rickettsial disease. ...
... Doxycycline is the recommended antimicrobial drug treatment for all patients who have suspected RMSF and should be empirically initiated to reduce fatal outcomes and severe sequelae (1,3,9), particularly in vulnerable children living with social disadvantages (1,14). Physicians and other health personnel practicing in RMSF-endemic areas should systematically consider RMSF in the differential diagnosis of hospitalized patients who have MIS-C to reduce delays in therapy and prevent death and severe sequelae caused by this rickettsial disease. ...
Clinical and epidemiological description of a series of five pediatric patients hospitalized due to the suspicion of multisystem inflammatory syndrome (MIS-C) who finally were confirmed as having Rocky Mountain spotted fever. Both diseases share clinical and laboratory similarities. Health personnel should consider that RMSF may be confounded with MIS-C in rickettsial endemic regions
... Our finding extends the richness of the genus Rickettsia in Mexico from 14 to 15 species and adds one more argasid to the list of ticks associated with rickettsiae worldwide (Sánchez-Montes et al. 2021). Its high prevalence in Av. cooleyi in this study region raises the possibility that it could induce a host immune response that could provide at least partial protection against other rickettsiae such as R. rickettsii, and affect Rocky Mountain spotted fever diagnosis by producing cross-reacting serologic tests (Biggs et al. 2016). We previously showed that these coyote individuals had 75% spotted fever group rickettsiae and 60% typhus group seroprevalence , and there is evidence that crossreactivity among SFG and between SFG and TG rickettsiae may occur (Valbuena et al. 2004;Biggs et al. 2016). ...
... Its high prevalence in Av. cooleyi in this study region raises the possibility that it could induce a host immune response that could provide at least partial protection against other rickettsiae such as R. rickettsii, and affect Rocky Mountain spotted fever diagnosis by producing cross-reacting serologic tests (Biggs et al. 2016). We previously showed that these coyote individuals had 75% spotted fever group rickettsiae and 60% typhus group seroprevalence , and there is evidence that crossreactivity among SFG and between SFG and TG rickettsiae may occur (Valbuena et al. 2004;Biggs et al. 2016). Antibody cross-reaction has also been observed between species belonging to the SFG, including R. rickettsii and R. vini, and species belonging to the ancestral group, such as R. bellii, in guinea pigs and chickens experimentally infected (Pacheco et al. 2011;Novakova et al. 2016). ...
We conducted surveillance of mammals to investigate their associations with argasid ticks and tick-borne pathogens. During 2021, a total of 20 wild carnivores and 57 lagomorphs were sampled, and 39 argasid ticks belonging to two species were collected. All mammals and ticks were tested by molecular assays to detect Borrelia and Rickettsia infections. Nine ticks identified as Otobius megnini were collected from two coyotes (Canis latrans) and 30 Alveonasus cooleyi (McIvor 1941) were collected from six bobcats (Lynx rufus) and one rabbit (Sylvilagus auduboni). We detected Rickettsia spp. DNA in 21 of the 27 (77.8%) tested Av. cooleyi and none of the O. megnini. No ticks were PCR-positive for borreliae and all mammals were PCR-negative for both pathogen genera. Phylogenetic analysis based on gltA, htrA, and 16 S rRNA targets revealed that all rickettsiae from Av. cooleyi clustered with ancestral group rickettsiae, likely representing a novel species of possibly endosymbiotic Rickettsia. The significance of Av. cooleyi and the newly identified Rickettsia sp. to the health of wildlife is unknown, and further work is indicated to determine whether they may be relevant to public health or carnivore conservation.
... Although ≈90% of patients with MIS-C or RMSF manifest fever, a rash is present in up to 90% of RMSF patients (6), compared with ≈50% of children with MIS-C (10,14). Patients with RMSF and MIS-C have similar laboratory test abnormalities that include thrombocytopenia, hyponatremia, and elevated inflammatory markers (i.e., procalcitonin and C-reactive protein) (6,9,10,14), probably because both diseases are characterized by a generalized inflammatory response, endothelial damage, and increased vascular permeability (1,10). ...
... Doxycycline is the recommended antimicrobial drug treatment for all patients who have suspected RMSF and should be empirically initiated to reduce fatal outcomes and severe sequelae (1,3,9), particularly in vulnerable children living with social disadvantages (1,14). Physicians and other health personnel practicing in RMSF-endemic areas should systematically consider RMSF in the differential diagnosis of hospitalized patients who have MIS-C to reduce delays in therapy and prevent death and severe sequelae caused by this rickettsial disease. ...
... Doxycycline is the recommended antimicrobial drug treatment for all patients who have suspected RMSF and should be empirically initiated to reduce fatal outcomes and severe sequelae (1,3,9), particularly in vulnerable children living with social disadvantages (1,14). Physicians and other health personnel practicing in RMSF-endemic areas should systematically consider RMSF in the differential diagnosis of hospitalized patients who have MIS-C to reduce delays in therapy and prevent death and severe sequelae caused by this rickettsial disease. ...
We describe 5 children who had Rocky Mountain spotted fever (RMSF) and manifested clinical symptoms similar to multisystem inflammatory syndrome in Sonora, Mexico, where RMSF is hyperendemic. Physicians should consider RMSF in differential diagnoses of hospitalized patients with multisystem inflammatory syndrome to prevent illness and death caused by rickettsial disease.
... Ixodes ticks are known to harbor pathogens of the genera Anaplasma, Borrelia, Ehrlichia, Coxiella, Babesia, and Rickettsia (Biggs et al. 2016; Rochlin and Toledo 2020; Mor- Table 3. Prevalence and mean intensity of tick (Acari: Ixodidae) infestation in rodents according to habitat seasonality in tropical forests of southern Yucatán, México. The prevalence value, calculated as prevalence = (n/N) * 100, is expressed as a percentage and denoted in parentheses. ...
Rodents serve as reservoirs for up to 85 zoonotic diseases, some of which can be transmitted by ticks. Ticks of the Amblyomma and Ixodes genera have been recognized to be associated with 4 rodent species in the Yucatán Peninsula, México. Here, we present new records of rodents acting as hosts for ticks of these genera in tropical forests of Yucatán. Between June 2021–March 2022, Sherman traps were used for rodent capture in the Biocultural State Reserve of Puuc, Yucatán, México. Twelve quadrants with 50 traps each were established in tropical forest sites with varying levels of anthropogenic intervention. Rodents were inspected for ectoparasites, and ticks were collected using entomological forceps and preserved in 70 % ethanol. We captured 160 individuals of 6 rodent species in 5,400 trap nights. The most captured species were Heteromys gaumeri (n = 60) and Sigmodon toltecus (n = 44), while the least represented were Handleyomys rostratus (n = 1). We retrieved 492 ticks, identifying Amblyomma mixtum, parasitizing H. rostratus, H. gaumeri, and S. toltecus; Ixodes cf. Ixodes affinis parasitizing H. gaumeri and Ixodes sp. parasitizing S. toltecus. We reported, for the first time in México, H. rostratus and S. toltecus as hosts for Amblyomma mixtum. Additionally, we present the first record of Ixodes affinis parasitizing H. gaumeri and Ixodes sp. parasitizing S. toltecus in the Yucatán Peninsula. The presence of tick vectors of zoonotic pathogens among rodent reservoirs reflects a latent risk to humans and domestic animals in the region.
... Serologic tests are simple and the most widely used form of testing, with available tests having cross reactivity with various Rickettsia species, as illustrated by our patient's seroreactivity to Rickettsia serology. Depending on availability, there are current serologic assays based on micro-immunofluorescence or western blotting which can differentiate between the different species of spotted fever infections [1,4]. When ordering serology, it is important to remember that seroconversion occurs 7-15 days following symptom onset and therefore, repeat testing may be warranted if initially negative [1]. ...
... Cell cultures can also be used for diagnosis, but samples should be collected prior to initiation of antibiotics for validity of results [1]. Molecular methods such as polymerase chain reaction (PCR) testing on samples taken from eschar swabs or crust, and from blood or tissue biopsy are the most novel method of diagnosis and can provide species-level diagnosis [1,4]. Tick speciation, if available, may provide information on other diseases potentially transmissible by the vector. ...
... Typically, an immunofluorescence assay (IFA) for R. rickettsii IgG antibodies is applied as evidence for any of the rickettsioses in the spotted fever group, including R. conorii. [1] As in the case outlined here, initial serology may be negative, with seroconversion occurring within 7-15 days and lasting for months to years following infection [1,4]. In our case, biopsy revealing leukocytoclastic vasculitis further supported and confirmed the pathophysiology resulting in endothelial damage. ...
... Molecular detection of rickettsial DNA by polymerase chain reaction (PCR) has become widely used for accurate confirmation of rickettsial infections. However, due to the need for advanced resources, the use of PCR in some endemic environments is limited to reference and research laboratories [23]. Furthermore, test sensitivity will depend on the sample type and the time of infection at which the sample was collected [20]. ...
Rocky Mountain or Brazilian spotted fever, caused by Ricketsia ricketssi, is a fulminant,
seasonal, and neglected disease that occurs in focal points of North America and South America.
Rapid detection are essential for a better prognosis and survival rate of the infected individual.
However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory
tests fluctuates. Therefore, this review aimed to identify methods for antibody or antigen detection,
its gaps, and evolution over time. A search was conducted to find all studies in the Pubmed database
that described antibody or antigen detection for Ricketsia ricketsii infection. Initially, a total of 403
articles were screened. Of these articles, only 19 fulfilled the pre-established inclusion criteria and
were selected. Among the different methods applied, the IFA technique was the one most frequently
found in the studies. However, it presented varied results such as low specificity using the indirect
method. Other techniques, such as ELISA and immunohistochemistry, were also found, although
in smaller numbers and with their own limitations. Although some studies showed promising
results, there is a pressing need to find new techniques to develop a rapid and effective Ricketsia
ricketssi infection diagnosis.
... Regardless, the widespread occurrence of this SNP in Rh. sanguineus s.l. collected in the US is worrying as permethrin, due to its relative safety with regards to nontarget species, is commonly used in dog collars and also to treat clothing and homes to control ticks/prevent tick bites and, thereby, reduce transmission of R. rickettsii to humans (Alvarez-Hernandez et al., 2020;Biggs et al., 2016;Minniear and Buckingham, 2009;Zazueta et al., 2021). Of note, this same SNP has also been associated with Rh. sanguineus s.l. ...
The brown dog tick, Rhipicephalus sanguineus sensu lato (s.l.), is an important vector for Rickettsia rickettsii, causative agent of Rocky Mountain spotted fever. Current public health prevention and control efforts to protect people involve preventing tick infestations on domestic animals and in and around houses. Primary prevention tools rely on acaricides, often synthetic pyrethroids (SPs); resistance to this chemical class is widespread in ticks and other arthropods. Rhipicephalus sanguineus s.l. is a complex that likely contains multiple unique species and although the distribution of this complex is global, there are differences in morphology, ecology, and perhaps vector competence among these major lineages. Two major lineages within Rh. sanguineus s.l., commonly referred to as temperate and tropical, have been documented from multiple locations in North America, but are thought to occupy different ecological niches. To evaluate potential acaricide resistance and better define the distributions of the tropical and temperate lineages throughout the US and in northern Mexico, we employed a highly multiplexed amplicon sequencing approach to characterize sequence diversity at: 1) three loci within the voltage-gated sodium channel (VGSC) gene, which contains numerous genetic mutations associated with resistance to SPs; 2) a region of the gamma-aminobutyric acid-gated chloride channel gene (GABA-Cl) containing several mutations associated with dieldrin/fipronil resistance in other species; and 3) three mitochondrial genes (COI, 12S, and 16S). We utilized a geographically diverse set of Rh sanguineus s.l. collected from domestic pets in the US in 2013 and a smaller set of ticks collected from canines in Baja California, Mexico in 2021. We determined that a single nucleotide polymorphism (T2134C) in domain III segment 6 of the VGSC, which has previously been associated with SP resistance in Rh. sanguineus s.l., was widespread and abundant in tropical lineage ticks (>50 %) but absent from the temperate lineage, suggesting that resistance to SPs may be common in the tropical lineage. We found evidence of multiple copies of GABA-Cl in ticks from both lineages, with some copies containing mutations associated with fipronil resistance in other species, but the effects of these patterns on fipronil resistance in Rh. sanguineus s.l. are currently unknown. The tropical lineage was abundant and geographically widespread, accounting for 79 % of analyzed ticks and present at 13/14 collection sites. The temperate and tropical lineages co-occurred in four US states, and as far north as New York. None of the ticks we examined were positive for Rickettsia rickettsii or Rickettsia massiliae.
... Hemorrhagic diseases can also be caused by various bacteria, including but not limited to rickettsial infections (such as Brazilian spotted fever), shigellosis, hemorrhagic salmonellosis, meningococcemia, and leptospirosis, all of which pose significant challenges in diagnosis. A more meticulous search in the bioinformatic data obtained for bacteria revealed abundant reads of Leptospira interrogans in pool 18, and pools 8 and 13 showed high sequence read numbers for Rickettsia rickettsii, which causes Brazilian spotted fever, a hemorrhagic disease associated with high mortality rates [39]. However, specific confirmation of these infections was beyond the scope of our study. ...
Viral hemorrhagic fever poses a significant public health challenge due to its severe clinical presentation and high mortality rate. The diagnostic process is hindered by similarity of symptoms across different diseases and the broad spectrum of pathogens that can cause hemorrhagic fever. In this study, we applied viral metagenomic analysis to 43 serum samples collected by the Public Health Laboratory (Fundação Ezequiel Dias, FUNED) in Minas Gerais State, Brazil, from patients diagnosed with hemorrhagic fever who had tested negative for the standard local hemorrhagic disease testing panel. This panel includes tests for Dengue virus (DENV) IgM, Zika virus IgM, Chikungunya virus IgM, yellow fever IgM, Hantavirus IgM, Rickettsia rickettsii IgM/IgG, and Leptospira interrogans IgM, in addition to respective molecular tests for these infectious agents. The samples were grouped into 18 pools according to geographic origin and analyzed through next-generation sequencing on the NextSeq 2000 platform. Bioinformatic analysis revealed a prevalent occurrence of commensal viruses across all pools, but, notably, a significant number of reads corresponding to the DENV serotype 2 were identified in one specific pool. Further verification via real-time PCR confirmed the presence of DENV-2 RNA in an index case involving an oncology patient with hemorrhagic fever who had initially tested negative for anti-DENV IgM antibodies, thereby excluding this sample from initial molecular testing. The complete DENV-2 genome isolated from this patient was taxonomically classified within the cosmopolitan genotype that was recently introduced into Brazil. These findings highlight the critical role of considering the patient’s clinical condition when deciding upon the most appropriate testing procedures. Additionally, this study showcases the potential of viral metagenomics in pinpointing the viral agents behind hemorrhagic diseases. Future research is needed to assess the practicality of incorporating metagenomics into standard viral diagnostic protocols.
... From the 1950s onward, however, these epidemics diminished. In contrast, the disease continued sporadically in the United States, especially in the Midwest and eastern portions of the country, transmitted by the American dog tick (Dermacentor variabilis) (Biggs, 2016;Dalton et al., 1995;Treadwell et al., 2000;Alvarez-Hern andez et al., 2017). In 2004, a cluster of RMSF cases was identified in eastern Arizona on American Indian tribal lands, and for the first time in the US, the disease was associated with brown dog ticks (Demma et al., 2005(Demma et al., , 2006. ...
... Shortly thereafter, an epidemic of RMSF erupted in northern Sonora state in Mexico, followed by an epidemic in Mexicali in northern Baja California beginning in 2008 and then Tijuana about a decade later, continuing to extend farther south in Baja California (Zazueta et al., 2021;Alvarez-Hern andez et al., 2017). Cases in Mexico now occur in urban centers, small towns, and rural areas in all states at the US-Mexican border and sporadically further south, with stunningly high case fatality rates, typically ranging from 10% to well over 30% and up to 47% in Sonora in 2022, compared with 5e7% in the US (Alvarez-Hernandez et al., 2015;Biggs, 2016;Secretaría de Salud Pública, Gobierno de Sonora, 2022). There is a disproportionate burden of disease and fatalities in children and people in marginalized neighborhoods (Alvarez-Hernandez et al., 2015;L opez-Castillo et al., 2018;Zavala-Castro et al., 2008). ...
Rocky Mountain spotted fever (RMSF) is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st century. Along the US south-western border and across northern Mexico, the brown dog tick, Rhipicephalus sanguineus, is responsible for spreading the disease between dogs and humans. The widespread nature of the disease and the ongoing epidemics contrast with historically sporadic patterns of the disease. Because dogs are amplifying hosts for the Rickettsia rickettsii bacteria, transmission dynamics between dogs and ticks are critical for understanding the epidemic. In this paper, we developed a compartment metapopulation model and used it to explore the dynamics and drivers of RMSF in dogs and brown dog ticks in a theoretical region in western North America. We discovered that there is an extended lag—as much as two years—between introduction of the pathogen to a naïve population and epidemic-level transmission, suggesting that infected ticks could disseminate extensively before disease is detected. A single large city-size population of dogs was sufficient to maintain the disease over a decade and serve as a source for disease in surrounding smaller towns. This model is a novel tool that can be used to identify high risk areas and key intervention points for epidemic RMSF spread by brown dog ticks.
... Lab values such as thrombocytopenia, leukocytosis, and hyponatremia are also of limited use since they can be negative on presentation. The first-line treatment for RMSF in all age groups is doxycycline [11], and treatment should not be delayed if there is any clinical suspicion of the disease. In this case, the patient was given empiric ceftriaxone pending the results of further labs. ...
