BACKGROUND:Timely and accurate diagnosis of spotted fever rickettsioses (SFR) is difficult due to nonspecific symptoms and testing challenges. We evaluated serum antibodies to the tick salivary proteins AV422 and calreticulin as potential markers of recent tick exposure in febrile patients from northern Tanzania. METHODS:We recruited febrile patients at 2 hospitals in Moshi, Tanzania, from February 2012 through May 2014. Acute and convalescent sera from enrolled participants were tested against Rickettsia africae antigen using indirect immunofluorescence assays (IFAs). Participants with ≥4-fold rise in R africae IFA immunoglobulin G reciprocal titer between sera were classified as cases (n = 70), those with paired sera with reciprocal titer ≥64 but no ≥4-fold rise as exposed (n = 40), and participants with reciprocal titer <32 in either sera as unexposed (n = 38). Acute and convalescent sera were tested for calreticulin and AV422 antibodies using enzyme-linked immunosorbent assay. RESULTS:We found significantly higher calreticulin antibody levels in acute sera of cases compared to exposed, unexposed, and the combined comparator of exposed and unexposed (adjusted mean difference [95% confidence interval {CI}], 17.49 [6.37-28.61]; 17.61 [6.55-28.67]; and 18.11 [9.13-27.10], respectively). Calreticulin distinguished cases from exposed and unexposed among persons 0-15 years old with positive predictive value of 0.77 (95% CI, .61-.88) and sensitivity of 0.94 (95% CI, .81-.99). CONCLUSIONS:In the acute phase of febrile illness, measurement of calreticulin antibody, a proposed marker for tick exposure, was higher in patients with confirmed tick-borne illness and had reasonable diagnostic test characteristics.
Rocky Mountain spotted fever (RMSF) is a deadly tick-borne disease caused by the bacterium Rickettsia rickettsii. An ongoing epidemic of RMSF is affecting tribal communities in Arizona, with nearly 500 cases and 28 deaths since 2003. The San Carlos Apache Tribe has been consistently working to prevent RMSF using tick collars on dogs, pesticide treatments around homes, and increasing education for nearly a decade. Besides monitoring human disease levels and tick burden on dogs, we have little understanding of the long-term impact of prevention practices on tick abundance and infection rates in the peridomestic environment. We evaluated risk factors associated for tick infestation at home sites across the San Carlos Indian Reservation as well as R. rickettsii and Rickettsia massiliae prevalence in off-host ticks. Although the presence of fencing appears protective, the number of nearby structures is the most important risk factor associated with increased adult and nymphal tick abundance, highlighting the impact of a free-roaming dog population.
In the United States, alpha-gal syndrome (AGS) is primarily associated with lone star tick (Amblyomma americanum) bites. We describe AGS onset after an Ixodes scapularis tick bite and present AGS surveillance in Maine, 2014-2023. US health and public health professionals should be aware of AGS outside the established lone star tick range.
The incidence of human tick-borne diseases is rising globally. Birds are ecologically significant hosts, capable of local or widespread dispersal for ticks and their associated pathogens, including agents of babesiosis. Despite its emerging importance, surveillance for zoonotic Babesia spp. ((Starcovici, 1893) Piroplasmida: Babesiidae) remains lacking, particularly in avian hosts. This study investigates the prevalence of Babesia spp. in a population of Carolina Wrens ((Latham, 1790) Passeriformes: Troglodytidae Thryothorus ludovicianus) in Missouri, USA. Due to their ground-foraging behavior and documented high tick burdens, we hypothesized that Carolina Wrens would have Babesia spp. infections. Birds were captured using mist nets, examined for ticks, and phlebotomized for blood samples. We prepared blood smears which were analyzed via microscopy for the presence of Babesia spp. parasites. During June and July 2018, we captured 70 birds from 14 species and collected 156 ticks, of which 152 were Ixodes scapularis ((Say, 1821) Acari: Ixodidae). Carolina Wrens accounted for the highest tick burdens (130 ticks total) with juvenile birds having significantly higher nymphal tick burdens than adults. Despite examining the blood smears of 23 Carolina Wrens and 5 Louisiana Waterthrushes (Parkesia motacilla) for Babesia spp., we found no evidence of infection. Our findings emphasize the notably high tick burdens in Carolina Wrens while underscoring the need for broader and more sensitive surveillance for Babesia spp. in bird populations. Understanding the role of avian hosts in the ecology of tick-borne pathogens is key for anticipating and mitigating public health risks associated with tick-borne disease.
Spotted fever group rickettsioses (SFGR) pose a global threat as emerging zoonotic infectious diseases; however, timely and cost-effective diagnostic tools are currently limited. We used data from 449 patients presenting to 2 hospitals in northern Tanzania between 2007 and 2008, of which 71 (15.8%) met criteria for acute SFGR based on >= 4-fold rise in antibody titers between acute and convalescent serum samples. We fit random forest classifiers incorporating clinical and demographic data from hospitalized febrile participants as well as Earth observation hydrometeorological predictors from the Kilimanjaro Region. In cross-validation, a prediction model with 10 clinical predictors achieved an area under the receiver operating characteristic curve of 0.65 (95% confidence interval, .48-.82). A combined prediction model with clinical, hydrometeorological, and environmental predictors (20 predictors total) did not significantly improve model performance. Novel strategies are needed to improve the diagnosis of acute SFGR, including the identification of diagnostic biomarkers that could enhance clinical prediction models.
Testing for spotted fever group rickettsioses (SFGR) and the criteria for identifying suspected patients are not routinely used in Kazakhstan. In 2019, we performed a cross-sectional study in 6 sentinel hospitals in the Pavlodar region. We tested 105 hospitalized patients with SFGR-like symptoms by using PCR or indirect immunofluorescence antibody assay and identified 62 cases of SFGR. Most (78%) cases of disease were caused by Rickettsia sibirica and R. raoultii. Cutaneous signs (eschar or rash) were found in 87% of SFGR patients; 79% had a rash, 48% had an eschar, and 13% had neither. Testing of suspected rickettsia cases resulted in a 27% increase in laboratory-detected SFGR over the mean of the previous 3 years (62 vs. 49). Broadening the case definition by including fever, headache, or myalgia and expanding routine testing for suspected cases of SFGR could contribute to improved case detection and earlier treatment.
In the United States, the Amblyomma maculatum sensu lato (s.l.) group is represented by two, distinct allopatric clusters of hard ticks identified as morphotype II in the eastern US and morphotype III in the southwestern states. Previous studies have shown that the two entities have evolved very recently from a common ancestor, are morphologically distinguishable in the adult stage, and are reproductively incompatible. Because of the recent divergence of the two morphotypes, gene sequences usually analyzed for a phylogenetic species definition are insufficiently informative to assign them to separate species. Microsatellite loci are predominantly non-coding sequences, selectively neutral, and usually have higher mutation rates than mitochondrial and coding nuclear gene sequences. An estimate of their divergence time based on the analysis of 8 previously developed microsatellite loci confirmed the recent speciation hypothesis, dating the radiation to approx. 230-460 years ago. A strong bottleneck signature suggests the establishment of these populations after a 1000-fold reduction in the population size of origin.
Rocky Mountain spotted fever (RMSF) is a tick-borne infection caused by Rickettsia rickettsii Brumpt, which is included in the spotted fever group (SFG) rickettsioses. In the United States, RMSF is transmitted primarily by ticks in the genus Dermacentor and in parts of Arizona and northern Mexico, by Rhipicephalus sanguineus Latreille. SFG rickettsiosis cases have been reported throughout the United States, but between 2018 and 2022, 5 states (Alabama, Arkansas, Missouri, North Carolina, and Tennessee) accounted for over 50% of SFG rickettsiosis cases. The most virulent of the spotted fever group rickettsia (SFGR), R. rickettsii, is potentially fatal if misdiagnosed or left untreated. Tick surveillance is one tool that public health entomologists utilize in identifying potential hot spots of infected ticks. Although the prevalence of R. rickettsii in tick populations is generally low (∼1% or less), the severity of this disease warrants frequent surveillance for the pathogen. With the inadvertent introduction of the longhorned tick into the United States, and its proven laboratory competence for transmitting R. rickettsii, the New Jersey Department of Health initiated surveillance of this tick for R. rickettsii. Here, we report the first finding of R. rickettsii in field-collected longhorned ticks, Haemaphysalis longicornis Neumann.
In this Opinion, the authors investigated peer-reviewed publications on alpha-gal syndrome (AGS), also known as red meat allergy, since its first description in the literature in 2009 to October 2024 to understand academic discipline and geographic affiliation of associated authors. We raise the issue of disproportionate contribution between medical disciplines and ecology/entomology disciplines and emphasize the positive future impacts of increased collaboration between the fields to address current gaps in our fundamental knowledge of this unique tick-borne disease.
We report a patient in North Carolina, USA, with Heartland virus infection whose diagnosis was complicated by previous Ehrlichia chaffeensis infection. We identified E. ewingii-infected and Bourbon virus-infected tick pools at the patient's residence. Healthcare providers should consider testing for tickborne viruses if ehrlichiosis is suspected.
Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007–April 2009. Among 788 participants, median age was 20 (interquartile range 2–38) years. We performed PCR amplification of V1–V2 variable region 16S rRNA on cell pellet DNA, then metagenomic deep-sequencing and pathogenic taxonomic identification. We detected bacterial zoonotic pathogens in 10 (1.3%) samples: 3 with Rickettsia typhi, 1 R. conorii, 2 Bartonella quintana, 2 pathogenic Leptospira spp., and 1 Coxiella burnetii. One other sample had reads matching a Neoerhlichia spp. previously identified in a patient from South Africa. Our findings indicate that targeted 16S metagenomics can identify bacterial zoonotic pathogens causing severe febrile illness in humans, including potential novel agents.
BACKGROUND:In northern Tanzania, Q fever, spotted fever group (SFG) rickettsioses, and typhus group (TG) rickettsioses are common causes of febrile illness. We sought to describe the prevalence and risk factors for these zoonoses in a pastoralist community. METHODS:Febrile patients ≥2 years old presenting to Endulen Hospital in the Ngorongoro Conservation Area were enrolled from August 2016 through October 2017. Acute and convalescent blood samples were collected, and a questionnaire was administered. Sera were tested by immunofluorescent antibody (IFA) IgG assays using Coxiella burnetii (Phase II), Rickettsia africae, and Rickettsia typhi antigens. Serologic evidence of exposure was defined by an IFA titre ≥1:64; probable cases by an acute IFA titre ≥1:128; and confirmed cases by a ≥4-fold rise in titre between samples. Risk factors for exposure and acute case status were evaluated. RESULTS:Of 228 participants, 99 (43.4%) were male and the median (interquartile range) age was 27 (16-41) years. Among these, 117 (51.3%) had C. burnetii exposure, 74 (32.5%) had probable Q fever, 176 (77.2%) had SFG Rickettsia exposure, 134 (58.8%) had probable SFG rickettsioses, 11 (4.8%) had TG Rickettsia exposure, and 4 (1.8%) had probable TG rickettsioses. Of 146 participants with paired sera, 1 (0.5%) had confirmed Q fever, 8 (5.5%) had confirmed SFG rickettsioses, and none had confirmed TG rickettsioses. Livestock slaughter was associated with acute Q fever (adjusted odds ratio [OR] 2.54, 95% confidence interval [CI] 1.38-4.76) and sheep slaughter with SFG rickettsioses case (OR 4.63, 95% CI 1.08-23.50). DISCUSSION:Acute Q fever and SFG rickettsioses were detected in participants with febrile illness. Exposures to C. burnetii and to SFG Rickettsia were highly prevalent, and interactions with livestock were associated with increased odds of illness with both pathogens. Further characterisation of the burden and risks for these diseases is warranted.
Acute Q fever diagnosis via paired serology is problematic because it requires follow-up for convalescent sample collection; as such, it cannot provide a diagnosis to inform a treatment decision at the time of acute presentation. Real-time polymerase chain reaction (PCR) may be a useful approach for the diagnosis of acute Q fever in endemic settings. Among febrile patients enrolled in a sentinel surveillance study for Q fever at two referral hospitals in Moshi, Tanzania, from 2012 to 2014, we analyzed those with paired sera for IgG to Coxiella burnetii (C. burnetii) phase II antigens using immunofluorescent antibody (IFA) testing, and acute serum was tested for C. burnetii with PCR. Acute Q fever was defined as a fourfold or greater rise from the acute to convalescent sample in IFA reciprocal titer or PCR detection that was confirmed through repeat testing. Test characteristics were tabulated. Among 496 participants tested using both paired IFA and PCR testing, 463 (93.3%) tested negative on both IFA and PCR, five (1.0%) tested positive for Q fever on both IFA and PCR, and 28 (5.6%) tested positive for Q fever on IFA alone. The sensitivity of PCR testing using paired IFA testing as an index was 0.15 (5/33), and the specificity was 1 (463/463). C. burnetii PCR testing provides a clinically specific method that may aid in timely diagnosis in settings in which acute Q fever is a common cause of febrile illness. However, we found a low clinical sensitivity of PCR testing on serum when compared with paired IFA serology.
Amblyomma maculatum Koch, the Gulf Coast tick, is expanding northward from its original range in the southeastern United States. In 2013, its most northern collection was in Delaware. Amblyomma maculatum has since been found in Connecticut, Illinois, and New York. It is the vector of the human pathogen Rickettsia parkeri, the causative agent of R. parkeri rickettsiosis. We report the first finding of an established population of A. maculatum in Salem County, NJ, with a R. parkeri infection prevalence rate of 23.8%. Our finding of A. maculatum is consistent with other recent findings in the northeastern United States in that specimens were found in open areas devoid of tree canopy. This discovery demonstrates the importance of tick surveillance in order to identify expanding tick populations and the pathogens they may transmit.
The recovery of a Haemaphysalis longicornis Neumann (Acari: Ixodidae) tick from a dog in Benton County, Arkansas, in 2018 triggered a significant environmental sampling effort in Hobbs State Park Conservation Area. The objective of the investigation was to assess the tick population density and diversity, as well as identify potential tick-borne pathogens that could pose a risk to public health. During a week-long sampling period in August of 2018, a total of 6,154 ticks were collected, with the majority identified as Amblyomma americanum (L), (Acari: Ixodidae) commonly known as the lone star tick. No H. longicornis ticks were found despite the initial detection of this species in the area. This discrepancy highlights the importance of continued monitoring efforts to understand the dynamics of tick populations and their movements. The investigation also focused on pathogen detection, with ticks being pooled by species, age, and sex before being processed with various bioassays. The results revealed the presence of several tick-borne pathogens, including agents associated with ehrlichiosis (n = 12), tularemia (n = 2), and Bourbon virus (BRBV) disease (n = 1), as well as nonpathogenic rickettsial and anaplasmosis organisms. These findings emphasize the importance of public health messaging to raise awareness of the risks associated with exposure to tick-borne pathogens. Prevention measures, such as wearing protective clothing, using insect repellent, and conducting regular tick checks, should be emphasized to reduce the risk of tick-borne diseases. Continued surveillance efforts and research are also essential to improve our understanding of tick-borne disease epidemiology and develop effective control strategies.
Hard ticks (Acari: Ixodidae) have been historically identified by morphological methods which require highly specialized expertise and more recently by DNA-based molecular assays that involve high costs. Although both approaches provide complementary data for tick identification, each method has limitations which restrict their use on large-scale settings such as regional or national tick surveillance programs. To overcome those obstacles, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been introduced as a cost-efficient method for the identification of various organisms, as it balances performance, speed, and high data output. Here we describe the use of this technology to validate the distinction of two closely related Dermacentor tick species based on the development of the first nationwide MALDI-TOF MS reference database described to date. The dataset obtained from this protein-based approach confirms that tick specimens collected from United States regions west of the Rocky Mountains and identified previously as Dermacentor variabilis are the recently described species, Dermacentor similis. Therefore, we propose that this integrative taxonomic tool can facilitate vector and vector-borne pathogen surveillance programs in the United States and elsewhere.
Rocky Mountain spotted fever (RMSF) is a severe tickborne disease that can reach epidemic proportions in communities with certain social and ecologic risk factors. In some areas, the case-fatality rate of brown dog tick-associated RMSF is up to 50%. Because of the spread of brown dog tick-associated ern Mexico, the disease has the potential to emerge and become endemic in other communities that have large populations of free-roaming dogs, brown dog ticks, limited resources, and low provider awareness of the disease. By using a One Health approach, interdisciplinary teams can identify communities at risk and prevent severe or fatal RMSF in humans before cases occur. We have developed a conceptual frameidentify their RMSF risk level and implement prevention and control strategies.
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.
Background Knowledge gaps exist on risk factors for spotted fever group rickettsioses (SFGR) in sub-Saharan Africa. We sought to identify SFGR risk factors in Kilimanjaro Region, Tanzania. Methods We recruited febrile patients presenting at 2 hospitals in Moshi from February 2012 through May 2014. Standardized clinical and risk factor questionnaires were administered. SFGR exposure was defined as a Rickettsia africae immunofluorescence antibody reciprocal titer >= 64, and acute SFGR as a >= 4-fold rise between paired sera. Logistic regression was used to identify associations. Results Of 1190 participants providing >= 1 serum sample, the median age was 21.8 (range, 0.3-100.2) years, 646 (54.3%) were female, and 650 (54.6%) had SFGR exposure. Of 731 participants with paired sera, 67 (9.2%) had acute SFGR. On multivariable analysis, odds of acute SFGR were higher in the age group 0-2 years (adjusted odds ratios [aORs] for older age groups, <0.36; P < .011), rural residence (aOR, 4.1; P = .007), and areas with maximum daily temperature <26 degrees C (aORs for higher temperature groups, <0.42; P < .035). Odds of SFGR exposure were higher in those working in the garden (aOR, 1.8; P = .010) and seeing a dog (aOR, 1.5; P = .010). Odds of SFGR exposure were lower in the age group 0-2 years (aORs for older age groups, >1.5; P < .026), female sex (aOR, 0.62; P < .001), and being from the Chaga tribe (aOR, 0.68; P = .003). Conclusions Those aged <2 years, rural residents, and persons residing in areas with cooler temperatures had increased odds of SFGR. Our results identify groups for further research on tick exposure and for targeted prevention interventions.
Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007-April 2009. Among 788 participants, median age was 20 (interquartile range 2-38) years. We performed PCR amplification of V1-V2 variable region 16S rRNA on cell pellet DNA, then metagenomic deep-sequencing and pathogenic taxonomic identification. We detected bacterial zoonotic pathogens in 10 (1.3%) samples: 3 with Rickettsia typhi, 1 R. conorii, 2 Bartonella quintana, 2 pathogenic Leptospira spp., and 1 Coxiella burnetii. One other sample had reads matching a Neoerhlichia spp. previously identified in a patient from South Africa. Our findings indicate that targeted 16S metagenomics can identify bacterial zoonotic pathogens causing severe febrile illness in humans, including potential novel agents.