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Tick-Borne Co-Infections: Challenges in Molecular and Serologic Diagnoses
2023
Co-infections are a poorly understood aspect of tick-borne diseases. In the United States alone, nineteen different tick-borne pathogens have been identified. The majority of these agents are transmitted by only two tick species, Ixodes scapularis and Amblyomma americanum. Surveillance studies have demonstrated the presence of multiple pathogens in individual ticks suggesting a risk of polymicrobial transmission to humans. However, relatively few studies have explored this relationship and its impact on human disease. One of the key factors for this deficiency are the intrinsic limitations associated with molecular and serologic assays employed for the diagnosis of tick-borne diseases. Limitations in the sensitivity, specificity and most importantly, the capacity for inclusion of multiple agents within a single assay represent the primary challenges for the accurate detection of polymicrobial tick-borne infections. This review will focus on outlining these limitations and discuss potential solutions for the enhanced diagnosis of tick-borne co-infections.
Journal Article
Polymicrobial Nature of Tick-Borne Diseases
by
Tagliafierro, Teresa
,
Benach, Jorge L.
,
Sanchez-Vicente, Santiago
in
Amblyomma
,
Amblyomma americanum
,
Anaplasma
2019
Tick-borne diseases have increased in prevalence in the United States and abroad. The reasons for these increases are multifactorial, but climate change is likely to be a major factor. One of the main features of the increase is the geographic expansion of tick vectors, notably
Amblyomma americanum
, which has brought new pathogens to new areas. The clinical spectrum of tick-borne diseases can range from asymptomatic to fatal infections, with a disproportionate incidence in children and the elderly. In addition, new pathogens that are cotransmitted by
Ixodes scapularis
have been discovered and have led to difficult diagnoses and to disease severity. Of these,
Borrelia burgdorferi
, the agent of Lyme disease, continues to be the most frequently transmitted pathogen. However,
Babesia microti
,
Borrelia miyamotoi
(another spirochete),
Anaplasma phagocytophilum
, and Powassan virus are frequent cotransmitted agents. Polymicrobial infection has important consequences for the diagnosis and management of tick-borne diseases.
Tick-borne diseases have doubled in the last 12 years, and their geographic distribution has spread as well. The clinical spectrum of tick-borne diseases can range from asymptomatic to fatal infections, with a disproportionate incidence in children and the elderly. In the last few years, new agents have been discovered, and genetic changes have helped in the spread of pathogens and ticks. Polymicrobial infections, mostly in
Ixodes scapularis
, can complicate diagnostics and augment disease severity.
Amblyomma americanum
ticks have expanded their range, resulting in a dynamic and complex situation, possibly fueled by climate change. To document these changes, using molecular biology strategies for pathogen detection, an assessment of 12 microbes (9 pathogens and 3 symbionts) in three species of ticks was done in Suffolk County, New York. At least one agent was detected in 63% of
I. scapularis ticks
.
Borrelia burgdorferi
was the most prevalent pathogen (57% in adults; 27% in nymphs), followed by
Babesia microti
(14% in adults; 15% in nymphs),
Anaplasma phagocytophilum
(14% in adults; 2% in nymphs),
Borrelia miyamotoi
(3% in adults), and Powassan virus (2% in adults). Polymicrobial infections were detected in 22% of
I. scapularis
ticks, with coinfections of
B. burgdorferi
and
B. microti
(9%) and of
B. burgdorferi
and
A. phagocytophilum
(7%). Three
Ehrlichia
species were detected in 4% of
A. americanum
ticks. The rickettsiae constituted the largest prokaryotic biomass of all the ticks tested and included
Rickettsia amblyommatis
,
Rickettsia buchneri
, and
Rickettsia montanensis
. The high rates of polymicrobial infection in ticks present an opportunity to study the biological interrelationships of pathogens and their vectors.
IMPORTANCE
Tick-borne diseases have increased in prevalence in the United States and abroad. The reasons for these increases are multifactorial, but climate change is likely to be a major factor. One of the main features of the increase is the geographic expansion of tick vectors, notably
Amblyomma americanum
, which has brought new pathogens to new areas. The clinical spectrum of tick-borne diseases can range from asymptomatic to fatal infections, with a disproportionate incidence in children and the elderly. In addition, new pathogens that are cotransmitted by
Ixodes scapularis
have been discovered and have led to difficult diagnoses and to disease severity. Of these,
Borrelia burgdorferi
, the agent of Lyme disease, continues to be the most frequently transmitted pathogen. However,
Babesia microti
,
Borrelia miyamotoi
(another spirochete),
Anaplasma phagocytophilum
, and Powassan virus are frequent cotransmitted agents. Polymicrobial infection has important consequences for the diagnosis and management of tick-borne diseases.
Journal Article
Identification of reactive Borrelia burgdorferi peptides associated with Lyme disease
by
Guo, Cheng
,
Eschman, Aleah
,
Tokarz, Rafal
in
Antibiotics
,
Antibodies
,
Antibodies, Bacterial - blood
2024
Serology is the primary method of Lyme disease diagnosis, but this approach has limitations, particularly early in disease. Currently employed antibody detection assays can be improved by the identification of alternative immunodominant epitopes and the selection of optimal diagnostic targets. We employed high-density peptide arrays that enabled precise epitope mapping for a wide range of
B. burgdorferi
antigens. In combination with machine learning, this approach facilitated the selection of serologic targets early in disease and the identification of serological indicators associated with different manifestations of Lyme disease. This study provides insights into differential antibody responses during infection and outlines a new approach for improved serologic diagnosis of Lyme disease.
Journal Article
Development of a capture sequencing assay for enhanced detection and genotyping of tick-borne pathogens
by
Jain, Komal
,
Tagliafierro, Teresa
,
Tokarz, Rafal
in
631/1647/514/2254
,
631/326/2521
,
Arachnids
2021
Inadequate sensitivity has been the primary limitation for implementing high-throughput sequencing for studies of tick-borne agents. Here we describe the development of TBDCapSeq, a sequencing assay that uses hybridization capture probes that cover the complete genomes of the eleven most common tick-borne agents found in the United States. The probes are used for solution-based capture and enrichment of pathogen nucleic acid followed by high-throughput sequencing. We evaluated the performance of TBDCapSeq to surveil samples that included human whole blood, mouse tissues, and field-collected ticks. For
Borrelia burgdorferi
and
Babesia microti
, the sensitivity of TBDCapSeq was comparable and occasionally exceeded the performance of agent-specific quantitative PCR and resulted in 25 to > 10,000-fold increase in pathogen reads when compared to standard unbiased sequencing. TBDCapSeq also enabled genome analyses directly within vertebrate and tick hosts. The implementation of TBDCapSeq could have major impact in studies of tick-borne pathogens by improving detection and facilitating genomic research that was previously unachievable with standard sequencing approaches.
Journal Article
Morphologic and genetic characterization of Pterygodermatites ( Mesopectines ) valladaresi n. sp. (Nematoda, Rictulariidae), a parasite of the mouse Mus musculus (Rodentia, Muridae) from the Canary Islands (Spain)
2022
A new rictulariid nematode
Pterygodermatites
(
Mesopectines
)
valladaresi
n. sp., parasite of the house mouse
Mus musculus
(Rodentia: Muridae) in the Canary Islands (Spain) is described by means of light and scanning electron microscopy. The new species belongs to the subgenus
Mesopectines
characterized by a more or less dorsal orientation of the buccal capsule, the presence of three oesophageal teeth, the morphology of the oral denticles and the Spirurida type of arrangement of caudal papillae in males. The most discriminant characteristics between the new species and the existing species in the subgenus
Mesopectines
are (a) the number of cuticular projection pairs (62–64), (b) the size of right and left spicules (respectively, 62–90 µm and 123–139 µm), (c) the number of midventral fans in males (3–4), (d) the number of prevulvar/total cuticular projection pairs (38–42/63–71), (e) the posterior differentiation of combs into spines in relation to the position of the vulva and (f) the anterior position of the vulva in relation to the oesophagus-intestine junction in females. Parasitized hosts and geographical distribution are also useful criteria to distinguish
P.
(
Me.
)
valladaresi
n. sp. from the remaining species of the subgenus. In addition, the
cox1
sequence of the new species is provided and compared with available data of related species.
Un nouveau nématode rictulaire, P
terygodermatites (Mesopectines) valladaresi
n. sp., parasite de la souris domestique
Mus musculus
(Rodentia, Muridae) aux îles Canaries (Espagne) est décrit par microscopie optique et électronique à balayage. La nouvelle espèce appartient au sous-genre
Mesopectines
caractérisé par une orientation plus ou moins dorsale de la capsule buccale, la présence de trois dents œsophagiennes, la morphologie des denticules buccaux et le type Spirurida d'arrangement des papilles caudales chez les mâles. Les caractéristiques les plus discriminantes entre la nouvelle espèce et les espèces existantes du sous-genre
Mesopectines
sont (a) le nombre de paires de projections cuticulaires (62–64), (b) la taille des spicules droit et gauche (respectivement, 62–90 µm et 123–139 µm), (c) le nombre de bourrelets cuticulaires médio-ventraux chez les mâles (3–4), (d) le nombre de peignes prévulvaires par rapport au nombre total de peignes (38–42/63–71), (e) la transformation en épines des peignes après la vulve et (f) la position antérieure de la vulve par rapport à la jonction œsophage-intestin chez les femelles. Les hôtes parasités et la répartition géographique sont également des critères utiles pour distinguer
P. (Me.) valladaresi
n. sp. des autres espèces du sous-genre. De plus, la séquence du
cox1
de la nouvelle espèce est fournie et comparée aux données disponibles sur les espèces apparentées.
Journal Article
Morphologic and Genetic Characterization of Protospirura canariensis n. sp. (Nematoda, Spiruridae), a Parasite of the Black Rat Rattus rattus (Rodentia, Muridae) from El Hierro Island (Canary Archipelago, Spain)
by
Ribas, Alexis
,
Sánchez-Vicente, Santiago
,
Miquel, Jordi
in
Cytochrome
,
Electron microscopes
,
Ethanol
2023
A new spirurid nematode, Protospirura canariensis n. sp., a parasite of the black rat Rattus rattus Linnaeus, 1758 (Rodentia: Muridae), in El Hierro Island (Canary Archipelago, Spain), was described by means of light (LM) and scanning electron microscopy (SEM). The most discriminating characteristics between the new species and the remaining species of the genus Protospirura were observed to be the following: (a) the number of tooth-like outgrowths in the sub-median and lateral lobes of the pseudolabia, both in males and females (2 and 4, respectively); (b) the size of the right and left spicules in males (643–715 µm and 309–412 µm, respectively); and (c) the numbers and arrangements of the cloacal papillae in males. The new species has a total of 17 cloacal papillae (4 large and pedunculated pairs of precloacal papillae, an unpaired precloacal papilla and 4 pairs of postcloacal papillae). The arrangement of the postcloacal papillae are as follows: the first pair are large, pedunculated and placed near the posterior edge of cloaca; the three remaining postcloacal pairs are grouped and located near the posterior tip. In the latter group, the papillae in the first pair are large and pedunculated. The parasitized hosts and their geographical distributions were also useful criteria in distinguishing P. canariensis n. sp. from the remaining species of the genus Protospirura. In addition, the cytochrome c oxidase subunit I (cox1) sequence of the new species was obtained and compared with the available data of related species.
Journal Article
Presence of Stenoponia tripectinata (Tiraboschi, 1902) (Siphonaptera, Ctenophtalmidae) in murine (Rodentia) from the Canary Islands
by
Gómez López, Maria Soledad
,
Vicente, Santiago Sánchez
in
Animal Systematics/Taxonomy/Biogeography
,
Animals
,
Archipelagoes
2012
This article reports the geographical and host distribution of the flea
Stenoponia tripectinata
on the Canary Islands.
S. tripectinata
is widely distributed throughout the Mediterranean and North Africa as a parasite of Muridae rodents. To date, Gran Canaria is the only island of the archipelago where
S. tripectinata
had been found. In this report,
S. tripectinata
has appeared parasitizing 116 specimens of
Mus musculus
out of a total of 660, and only 2
Rattus rattus
of 215 captured. All the trapped Muridae hosts found to be parasitized by
S. tripectinata
came from humid biotopes. The results showed that
S. tripectinata
is present on all the western Canary Islands and on one of the eastern islands, Gran Canaria, the only island already reported. The detection of
S. tripectinata
on El Hierro, La Palma, La Gomera and Tenerife represents the first records of this flea species on those Canary Islands.
Journal Article
Virulence potential of Rickettsia amblyommatis for spotted fever pathogenesis in mice
2021
ABSTRACT
Rickettsia amblyommatis belongs to the spotted fever group of Rickettsia and infects Amblyomma americanum (Lone Star ticks) for transmission to offspring and mammals. Historically, the geographic range of A. americanum was restricted to the southeastern USA. However, recent tick surveys identified the progressive northward invasion of A. americanum, contributing to the increased number of patients with febrile illnesses of unknown etiology after a tick bite in the northeastern USA. While serological evidence strongly suggests that patients are infected with R. amblyommatis, the virulence potential of R. amblyommatis is not well established. Here, we performed a bioinformatic analysis of three genome sequences of R. amblyommatis and identified the presence of multiple putative virulence genes whose products are implicated for spotted fever pathogenesis. Similar to other pathogenic spotted fever rickettsiae, R. amblyommatis replicated intracellularly within the cytoplasm of tissue culture cells. Interestingly, R. amblyommatis displayed defective attachment to microvascular endothelial cells. The attachment defect and slow growth rate of R. amblyommatis required relatively high intravenous infectious doses to produce dose-dependent morbidity and mortality in C3H mice. In summary, our results corroborate clinical evidence that R. amblyommatis can cause mild disease manifestation in some patients.
Rickettsia amblyommatis, an obligate intracellular pathogen transmitted by Lone Star ticks (Amblyomma americanum), infects endothelial cells and causes spotted fever pathogenesis in mice.
Journal Article
Morphologic and Genetic Characterization of IProtospirura canariensis/I n. sp. sup.†
by
Ribas, Alexis
,
Sánchez-Vicente, Santiago
,
Foronda, Pilar
in
Cytochrome oxidase
,
Ethylenediaminetetraacetic acid
,
Genetic aspects
2023
A new spirurid nematode, Protospirura canariensis n. sp., a parasite of the black rat in El Hierro (Canary Islands, Spain), was described by means of light and scanning electron microscopy. The morphological characteristics of the new species and the existing Protospirura species, as well as their host species and geographical distributions, were useful criteria in distinguishing P. canariensis n. sp. from the remaining species of the genus. Novel molecular phylogenetic data of the new nematode were obtained, and were compared with those from available related Protospirura species. A new spirurid nematode, Protospirura canariensis n. sp., a parasite of the black rat Rattus rattus Linnaeus, 1758 (Rodentia: Muridae), in El Hierro Island (Canary Archipelago, Spain), was described by means of light (LM) and scanning electron microscopy (SEM). The most discriminating characteristics between the new species and the remaining species of the genus Protospirura were observed to be the following: (a) the number of tooth-like outgrowths in the sub-median and lateral lobes of the pseudolabia, both in males and females (2 and 4, respectively); (b) the size of the right and left spicules in males (643-715 µm and 309-412 µm, respectively); and (c) the numbers and arrangements of the cloacal papillae in males. The new species has a total of 17 cloacal papillae (4 large and pedunculated pairs of precloacal papillae, an unpaired precloacal papilla and 4 pairs of postcloacal papillae). The arrangement of the postcloacal papillae are as follows: the first pair are large, pedunculated and placed near the posterior edge of cloaca; the three remaining postcloacal pairs are grouped and located near the posterior tip. In the latter group, the papillae in the first pair are large and pedunculated. The parasitized hosts and their geographical distributions were also useful criteria in distinguishing P. canariensis n. sp. from the remaining species of the genus Protospirura. In addition, the cytochrome c oxidase subunit I (cox1) sequence of the new species was obtained and compared with the available data of related species.
Journal Article
Morphologic and Genetic Characterization of Protospirura canariensis n. sp. (Nematoda, Spiruridae), a Parasite of the Black Rat Rattus rattus (Rodentia, Muridae) from El Hierro Island (Canary Archipelago, Spain) /sup
2023
A new spirurid nematode, Protospirura canariensis n. sp., a parasite of the black rat Rattus rattus Linnaeus, 1758 (Rodentia: Muridae), in El Hierro Island (Canary Archipelago, Spain), was described by means of light (LM) and scanning electron microscopy (SEM). The most discriminating characteristics between the new species and the remaining species of the genus Protospirura were observed to be the following: (a) the number of tooth-like outgrowths in the sub-median and lateral lobes of the pseudolabia, both in males and females (2 and 4, respectively); (b) the size of the right and left spicules in males (643–715 µm and 309–412 µm, respectively); and (c) the numbers and arrangements of the cloacal papillae in males. The new species has a total of 17 cloacal papillae (4 large and pedunculated pairs of precloacal papillae, an unpaired precloacal papilla and 4 pairs of postcloacal papillae). The arrangement of the postcloacal papillae are as follows: the first pair are large, pedunculated and placed near the posterior edge of cloaca; the three remaining postcloacal pairs are grouped and located near the posterior tip. In the latter group, the papillae in the first pair are large and pedunculated. The parasitized hosts and their geographical distributions were also useful criteria in distinguishing P. canariensis n. sp. from the remaining species of the genus Protospirura. In addition, the cytochrome c oxidase subunit I (cox1) sequence of the new species was obtained and compared with the available data of related species.
Journal Article