Search Results (61)

Background: Babesiosis and malaria are infectious diseases caused by the intraerythrocytic parasites Babesia and Plasmodium, respectively. While no human red blood cell (RBC) receptors have been shown to be essential for B. microti (Bm) invasion, Duffy (ACKR1) was reported to be essential for P. knowlesi and P. vivax invasion in 1975 and 1976, respectively. This suggests additional medical progress is needed for babesiosis, warranting a detailed analysis. Methods: Given similarities in the target cell of infection, data about babesiosis and malaria cases in the US were obtained from the Centers for Disease Control and Prevention (CDC). Research funding was quantified using National Institutes of Health (NIH) data, and medical progress was evaluated through a literature review. Results: Over the 5-year span of 2018–22, there were 9799 and 7722 confirmed babesiosis and malaria cases, respectively. Confirmed babesiosis cases exceeded malaria cases in 4 of 5 years. In 2022, babesiosis and malaria data were either not reported or unavailable to the CDC by ten and one US state(s), respectively. Regarding babesiosis, it is likely that the vast majority of cases were due to domestically acquired Bm, in the context of no chemoprophylaxis. Concerning malaria, >90% of US cases were imported from foreign locations, ~95% of cases were linked with not taking chemoprophylaxis, and P. falciparum (Pf) was the most common cause. From 2018–22, babesiosis and malaria were the underlying cause of death for 70 and 32 US residents, respectively. NIH funding estimates suggest ~$4 million in support of babesiosis and ~$169 million for malaria in 2024. There are many malaria-inspired medications, two malaria vaccines, and hundreds of characterized Plasmodium proteins, while these measures of medical progress are far behind for babesiosis. Outside of the US, there are >200 million malaria cases per year, while babesiosis is rare. Conclusions: In the US from 2018–22, there were more babesiosis cases and deaths than malaria. Decades of robust CDC and NIH funding for malaria led to its elimination from the US, improved medical knowledge and interventions, and reduced foreign morbidity and mortality. These data suggest that leveraging similar approaches used for malaria, including increased NIH and CDC funding for babesiosis, would likely lead to progress (e.g., improved treatment). Babesiosis qualifies as both a rare and an orphan disease. Full article

The habitats of shrews substantially overlap with those of rodents, which are well known as reservoirs for many tick-borne diseases. However, the ecological role of shrews (Mammalia: Eulipotyphla: Soricidae) remains poorly understood. We examined 103 Sorex spp. (S. unguiculatus, S. gracillimus, S. caecutiens) from Kushiro, Hokkaido, Japan, to investigate their relationships with ticks and tick-borne microorganisms, including Piroplasmida and Anaplasmataceae. Pathogen screening revealed Babesia microti Hobetsu lineage (9.7%), Neoehrlichia mikurensis (26.2%), Ehrlichia japonica (13.6%), and E. muris (0.97%). These intracellular protozoa and bacteria, typically associated with rodents, are recognized zoonotic agents or have zoonotic potential. Detection rates were highest in S. caecutiens (62.5%, 10/16), followed by S. unguiculatus (45.3%, 24/53) and S. gracillimus (23.5%, 8/34). Co-infections were observed between N. mikurensis and B. microti (n = 3) and between N. mikurensis and E. japonica (n = 4). Immature stages of Ixodes ovatus and I. persulcatus were collected from the body surface of shrews, and transstadial transmission of N. mikurensis was suggested by its detection in a molted I. ovatus nymph. These results indicate that shrews act as feeding hosts for immature ticks and reservoirs for multiple tick-borne pathogens. Shrews should be considered important reservoirs for tick-borne diseases. Full article

Although quilombola individuals and their dogs may be exposed to hemoparasites such as A. phagocytophilum, B. microti, and E. chaffeensis, no study to date has been conducted in these populations. The aim of this study was to investigate the presence of antibodies against Anaplasma phagocytophilum, Babesia microti, and Ehrlichia chaffeensis in humans and dogs from quilombola communities in Brazil. Serum samples from humans and dogs were collected from four rural quilombola communities and analyzed using indirect immunofluorescence assays. The results revealed antibody levels of 8% for A. phagocytophilum, 3% for B. microti, and 1% for E. chaffeensis in humans and 60%, 50%, and 65%, respectively, in dogs. Notably, women were significantly more likely to be seropositive for A. phagocytophilum than men (p = 0.0289). Dogs from the Serra do Apon community more commonly had A. phagocytophilum (p = 0.0477) and B. microti (p = 0.0448) than those from the other areas. To the best of our knowledge, this is the first study to report human exposure to A. phagocytophilum and the ocurrence of B. microti in Brazil. The antibody level of vector-borne diseases in humans is a public health concern, particularly in vulnerable populations and rural areas. The dogs were universally hosted Rhipicephalus sanguineus ticks, suggesting their possible role in transmission. Thus, further epidemiological surveillance studies should be conducted in vulnerable populations to mitigate the impact of such zoonotic diseases. Full article

The microbial communities of Ixodes scapularis, the primary vector of Lyme disease in North America, exhibit regional variations that may affect pathogen transmission and vector competence. We analyzed bacterial communities in I. scapularis ticks collected from Broome County, New York, using 16S rRNA gene sequencing (18 ticks) as well as mass spectrometry-based proteomics (36 ticks). According to the 16S rRNA analysis, the endosymbiont Rickettsia buchneri was the most abundant species, with significantly higher (p = 0.0011) abundance in females (54.76%) compared to males (31.15%). We detected Borreliella burgdorferi in 44.44% of ticks and Anaplasma phagocytophilum in two nymphs but in high relative abundances (12.73% and 46.46%). Male ticks exhibited higher bacterial diversity, although the community composition showed no significant clustering by sex or life stage. Co-occurrence analysis revealed negative associations between R. buchneri and Pseudomonas (p = 0.0245), but no associations with B. burgdorferi. Proteomic analysis identified 12 R. buchneri-specific proteins, additionally detecting the protozoan pathogen Babesia microti in 18.18% of females. These findings provide the first comprehensive characterization of I. scapularis microbiomes in the Southern Tier region of New York and suggest broader distribution of R. buchneri across tick life stages than previously recognized, with potential implications for pathogen transmission dynamics. Full article

This study reinforces the value of a One Health approach to infectious disease outbreak investigations. After the onset of neuropsychiatric symptoms in their son, our investigation focused on a family composed of a mother, father, two daughters, the son, two dogs, and a rabbit, all with exposures to vectors (fleas and ticks), rescued dogs, and other animals. Between 2020 and 2022, all family members experienced illnesses that included neurological symptoms. Prolonged menorrhagia (130d) in the youngest daughter ultimately resolved following antibiotic administration. One dog was diagnosed with a splenic hematoma and months later spinal histiocytic sarcoma. The father, both daughters, and one dog were seroreactive to multiple Bartonella spp. antigens, whereas the mother and son were not seroreactive. Bartonella quintana DNA was amplified from specimens obtained from all family members. Based upon DNA sequencing, infection with B. quintana was confirmed for the mother and both pet dogs. Bartonella henselae DNA was amplified and sequenced from the youngest daughter, the son, and one dog (co-infected with B. quintana), and from Ctenocephalides felis collected from their pet rabbit. All five family members and one dog were infected with Babesia divergens-like MO-1. Both parents were co-infected with Babesia microti. Droplet digital PCR supported potential infection with a Borrelia species in three family members. This study provided additional case-based evidence supporting the role of stealth Babesia, Bartonella, and Borrelia pathogens as a cause or cofactor in neurological and neuropsychiatric symptoms. We conclude that a One Health investigation approach, particularly for stealth vector borne pathogens such as Babesia, Bartonella, and Borrelia spp., will enhance clinical and epidemiological understanding of these organisms for animal and human health. During outbreak investigations it is critical to document travel and vector exposure histories, symptoms, and pathology in pets and human patients, contact with rescued, wild, or feral animals and perform diagnostic testing that includes family members, pets, and vectors. Full article

More than one-hundred Babesia species that affect animals and humans have been described, eight of which have been associated with emerging and underdiagnosed zoonoses. Most diagnostic studies in humans have used serology or molecular assays based on the 18S rRNA gene. Because the 18S rRNA gene is highly conserved, obtaining an accurate diagnosis at the species level is difficult, particularly when the amplified DNA fragment is small. Also, due to its low copy number, sequencing of the product is often unsuccessful. In contrast, because the Babesia internal transcribed regions (ITS), between 18S rRNA and 5.8S rRNA, and between 5.8S rRNA and 28S rRNA, contain highly variable non-coding regions, the sequences in these regions provide a good option for developing molecular assays that facilitate differentiation at the species level. In this study, the complete ITS1 and ITS2 intergenic regions of different Piroplasmida species were sequenced to add to the existing GenBank database. Subsequently, ITS1 and ITS2 sequences were used to develop species-specific PCR assays and specific single-plex and multiplex conventional (c)PCR, quantitative real-time (q)PCR, and digital (d)PCR assays for four zoonotic Babesia species (Babesia divergens, Babesia odocoilei, Babesia duncani, and Babesia microti). The efficacy of the assay protocols was confirmed by testing DNA samples extracted from human blood or enrichment blood cultures. Primers were first designed based on the 18S rRNA-5.8S rRNA and 5.8S rRNA-28S rRNA regions to obtain the ITS1 and ITS2 sequences derived from different Piroplasmida species (B. odocoilei, Babesia vulpes, Babesia canis, Babesia vogeli, Babesia gibsoni, Babesia lengau, Babesia divergens-like, B. duncani, B. microti, Babesia capreoli, Babesia negevi, Babesia conradae, Theileria bicornis, and Cytauxzoon felis). Subsequently, using these sequences, single-plex or multiplex protocols were optimized targeting the ITS1 region of B. divergens, B. microti, and B. odocoilei. Each protocol proved to be sensitive and specific for the four targeted Babesia sp., detecting 10⁻² (for B. microti and B. odocoilei) and 10⁻¹ (for B. divergens and B. duncani) DNA copies per microliter. There was no cross-amplification among the Babesia species tested. Using 226 DNA extractions from blood or enrichment blood cultures obtained from 82 humans, B. divergens (seven individuals), B. odocoilei (seven individuals), and B. microti (two individuals) were detected and identified as a single infection, whereas co-infection with more than one Babesia sp. was documented by DNA sequencing in six (7.3%) additional individuals (representing a 26.8% overall prevalence). These newly developed protocols proved to be effective in detecting DNA of four Babesia species and facilitated documentation of co-infection with more than one Babesia sp. in the same individual. Full article

Babesia microti is a protozoan that infects red blood cells, causing hemolytic anemia and flu-like symptoms in humans. Understanding co-infections is crucial for the better diagnosis, treatment, and management of tick-borne diseases. This study examined the prevalence of Babesia microti co-infection with other prevalent tick-borne pathogens in Pennsylvania. The dataset acquired from the Dr. Jane Huffman Wildlife Genetics Institute included passive surveillance data from Ixodes spp. from 2021 to 2023. Submitted ticks were screened for tick-borne pathogens using species-specific TaqMan qPCR. Of the 793 B. microti-positive ticks pulled for analysis, 65.0% were co-infected with other pathogens (n = 516). Notably, 60.9% of the B. microti-positive ticks were co-infected with Borrelia burgdorferi, 10.2% with Anaplasma phagocytophilum Ap-ha, and 7.5% carried a triple co-infection with B. burgdorferi and A. phagocytophilum Ap-ha. The rates of B. microti infection and its co-infections are on the rise, with patterns observed in Pennsylvania and other regions of the USA. While other studies have collected both nymphal and adult ticks to screen for co-infections in Pennsylvania, our study stood out as a unique contribution to the field by focusing exclusively on B. microti-positive ticks. The continued monitoring of tick-borne co-infections is vital to prevent misdiagnosis and ensure effective treatment regimens. Full article

Background/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome bc1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp. and Babesia microti, without showing toxicity in mammals. The objectives of this study are investigating whether ELQ-316, BPQ, and their combination treatment could be effective against Babesia bovis in an in vitro culture model and comparing with imidocarb (ID), the routinely used drug. Methods: In vitro cultured parasites starting at 2% percentage of parasitemia (PPE) were treated with BPQ, ELQ-316, ID, and the combinations of BPQ + ELQ-316 and ID + ELQ-316 at drug concentrations that ranged from 25 to 1200 nM, during four consecutive days. The IC50% and IC99% were reported. Parasitemia levels were evaluated daily using microscopic examination. Data were compared using the non-parametrical Mann–Whitney and Kruskall–Wallis test. Results: All drugs tested, whether used alone or in combination, significantly decreased the survival (p < 0.05) of B. bovis in in vitro cultures. The combination of BPQ + ELQ-316 had the lowest calculated inhibitory concentration 50% (IC50%) values, 31.21 nM (IC95%: 15.06–68.48); followed by BPQ, 77.06 nM (IC95%: 70.16–86.01); ID + ELQ316, 197 nM (IC95%:129.0–311.2); ID, 635.1 nM (IC95%: 280.9–2119); and ELQ316, 654.9 nM (IC95%: 362.3–1411). Conclusions: The results reinforce the higher efficacy of BPQ at affecting B. bovis survival and the potential synergistic effects of its combination with ELQ-316, providing a promising treatment option against B. bovis. Full article

Babesia microti is an Apicomplexan parasite that infects erythrocytes and causes the tick-transmitted infection, babesiosis. B. microti can cause a wide variety of clinical manifestations ranging from asymptomatic to severe infection and death. Some risk factors for severe disease are well-defined, an immune compromised state, age greater than 50, and asplenia. However, increasing cases of severe disease and hospitalization in otherwise healthy individuals suggests that there are unknown risk factors. The immunopathology of babesiosis is poorly described. CD4+ T cells and the spleen both play a critical role in parasite clearance, but few other factors have been found that significantly impact the course of disease. Here, we evaluated the role of several immune mediators in B. microti infection. Mice lacking TNF receptors 1 and 2, the receptors for TNFα and LTα, had a higher peak parasitemia, reduced parasite killing in infected red blood cells (iRBCs), and delayed parasite clearance compared to control mice. Mice lacking CCR2, a chemokine receptor involved in the recruitment of inflammatory monocytes, and mice lacking NADPH oxidase, which generates superoxide radicals, demonstrated reduced parasite killing but had little effect on the course of parasitemia. These results suggest that TNFR-mediated responses play an important role in limiting parasite growth, the death of parasites in iRBCs, and the clearance of iRBCs, and that the parasite killing in iRBCs is being primarily mediated by ROS and inflammatory monocytes/macrophages. By identifying factors involved in parasite killing and clearance, we can begin to identify additional risk factors for severe infection and newer therapeutic interventions. Full article

The United States of America (US) has the highest annual number of human babesiosis cases caused by Babesia microti (Bm). Babesia, like malaria-causing Plasmodium, are protozoan parasites that live within red blood cells (RBCs). Both infectious diseases can be associated with hemolysis and organ damage, which can be fatal. Since babesiosis was made a nationally notifiable condition by the Centers for Disease Control and Prevention (CDC) in January 2011, human cases have increased, and drug-resistant strains have been identified. Both the Bm ligand(s) and RBC receptor(s) needed for invasion are unknown, partly because of the difficulty of developing a continuous in vitro culture system. Invasion pathways are relevant for therapies (e.g., RBC exchange) and vaccines. We hypothesize that there is at least one RBC surface antigen that is essential for Bm invasion and that all Bm hosts express this. Because most RBC surface antigens that impact Plasmodium invasion are in human blood group (hBG) systems, which are generated by 51 genes, they were the focus of this study. More than 600 animals with at least one hBG system gene ortholog were identified using the National Center for Biotechnology Information (NCBI) command-line tools. Google Scholar searches were performed to determine which of these animals are susceptible to Bm infection. The literature review revealed 28 Bm non-human hosts (NHH). For 5/51 (9.8%) hBG system genes (e.g., RhD), no NHH had orthologs. This means that RhD is unlikely to be an essential receptor for invasion. For 24/51 (47.1%) hBG system genes, NHH had 4–27 orthologs. For the ABO gene, 15/28 NHH had an ortholog, meaning that this gene is also unlikely to generate an RBC antigen, which is essential for Bm invasion. Our prior research showed that persons with blood type A, B, AB, O, RhD+, and RhD- can all be infected with Bm, supporting our current study’s predictions. For 22/51 (43.1%) hBG system genes, orthologs were found in all 28 NHH. Nineteen (37.3%) of these genes encode RBC surface proteins, meaning they are good candidates for generating a receptor needed for Bm invasion. In vitro cultures of Bm, experimental Bm infection of transgenic mice (e.g., a CD44 KO strain), and analyses of Bm patients can reveal further clues as to which RBC antigens may be essential for invasion. Full article

Representatives of the genus Sarcocystis are worldwide distributed apicomplexan parasites characterised by two-host prey-predator relationships. Sarcocystis spp. produce sarcocysts in the muscles and brains of intermediate hosts and develop sporocysts in the intestines of definitive hosts. Two species, Sarcocystis glareoli and Sarcocystis microti, previously assigned to the genus Frenkelia, form cysts in the brains of rodents and are transmitted through the common buzzard (Buteo buteo). In our study, brain samples of 694 small mammals caught in different regions of Lithuania were examined for Sarcocystis spp. Additionally, 10 B. buteo and two rough-legged buzzards (Buteo lagopus) were tested for sporocysts of the analysed parasites. Sarcocystis species were identified based on 28S rRNA sequence comparison. Of the eleven species of small mammals tested, Sarcocystis parasites were observed only in the bank vole (Clethrionomys glareolus). Cysts of S. glareoli were detected in 34 out of 374 C. glareolus (9.1%, 95% CI = 6.4–12.5%). Molecular investigation showed the presence of only S. glareoli in the intestines of 50% of B. buteo. Furthermore, two species, Sarcocystis sp. Rod3 and Sarcocystis sp. Rod4, were confirmed in B. lagopus. Our results demonstrate the need for further studies on Sarcocystis cycling between rodents and birds. Full article

Here, we described the prevalence of Borrelia burgdorferi s.l. and Babesia species found in mono- and double infections among Ixodes ricinus ticks occurring in urban areas of the city of Poznań, Poland. We tested 1029 host-seeking ticks and 1268 engorged ticks removed from pet animals. Borrelia afzelii and B. garinii prevailed both in ticks from vegetation (3.7% and 3.7%, respectively) and from pets (3.7% and 0.6%, respectively). Babesia canis and Ba. microti were the most prevalent in host-seeking (2.6% and 1.4%, respectively) and feeding ticks (2.8% and 2.2%, respectively). Babesia microti sequences proved to be identical to the human pathogenic Ba. microti genotype “Jena/Germany”. Sequences of the rarest piroplasm Ba. venatorum (0.7%) were identical with those isolated from European patients. About 1.0% of tested ticks yielded dual infections; in host-seeking ticks, Ba. canis prevailed in co-infections with B. afzelii and B. garinii, whereas Ba. microti and B. afzelii dominated in double-infected feeding ticks. Dual infections, even with a low prevalence, pose a challenge for differential diagnosis in patients with acute febrile disease after a tick bite. The finding of Ba. canis in both tick groups suggests that I. ricinus could be involved in the circulation of this piroplasm. Full article

Small mammals, such as rodents and shrews, are natural reservoir hosts of zoonotic diseases, including parasitic protozoa. To assess the risk of rodent-borne parasitic protozoa in the Republic of Korea (ROK), this study investigated the status of parasitic protozoa, namely Trypanosoma, Babesia, and Theileria, in small mammals. In total, 331 blood samples from small mammals were analyzed for parasites using PCR and sequenced. Samples were positive for Trypanosoma grosi (23.9%; n = 79) and Babesia microti (10%; n = 33) but not Theileria. Small mammals from Seogwipo-si showed the highest infection rate of T. grosi (48.4%), while the highest B. microti infection rate was observed in those from Gangneung-si (25.6%). Sequence data revealed T. grosi to be of the AKHA strain. Phylogenetic analysis of B. microti revealed the US and Kobe genotypes. B. microti US-type–infected small mammals were detected throughout the country, but the Kobe type was only detected in Seogwipo-si. To our knowledge, this is the first nationwide survey that confirmed T. grosi and B. microti infections at the species level in small mammals in the ROK and identified the Kobe type of B. microti. These results provide valuable information for further molecular epidemiological studies on these parasites. Full article

Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk factors for severe disease include general immune suppression, advanced age (>50) and lack of a spleen. However, severe disease can occur in the absence of any known risk factors. The degree to which tick-transmitted B. microti infection confers protection from subsequent exposure is largely unexplored. This is an important question as both the prevalence and geographic range of tick-transmitted B. microti infection continues to increase and individuals in endemic regions may have multiple exposures over their lifetime. In the current study we used a mouse model to evaluate the degree to which primary infection with B. microti protected against secondary challenge with the same parasite strain. We show that CD4 T cells, and to a lesser extent B cells, contribute to protection. However, mice exhibited significant protection from secondary parasite challenge even in the absence of either CD4 T cells or B cells. The protection mediated by CD4 T cells did not depend on their production of IFN-γ as mice with a targeted gene deletion for the IFN-γ receptor remained fully protected against secondary challenge. Other factors including inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88, important for toll-like receptors, IL-18 and IL-1 signaling, were not important for protection against primary or secondary challenge with B. microti. Thus, our study shows that resolution of primary infection with B. microti results in robust protection against secondary challenge with parasites, at least in the short term. Further studies are needed to evaluate the length of protection and the degree to which protection is impacted by parasite heterogeneity. Although we show an important role for CD4 T cells in protection against secondary challenge, our results suggest that no single aspect of the immune system is solely responsible for adequate protection against secondary challenge with B. microti. Full article

Babesiosis is perceived mainly an animal disease; however, awareness that Babesia spp. parasites that can cause diseases in humans is increasing significantly. Babesiosis is spread by the bite of an infected tick (Ixodes spp.), but it can also be transmitted by transfusion of infected blood and from an infected mother to her child during pregnancy or childbirth. The parasites multiply in the bloodstream and destroy red blood cells. This study aimed to assess the influence of Babesia microti on the histological structure of the placenta. Histopathological material collected from pregnant rats infected with Babesia microti was used in the experiment. Microscopic images of the placentas were assessed by Mallory staining and by using methylene blue-stained semi-thin sections. In addition, FISH was used to detect parasite DNA. The presence of piroplasms in both maternal and fetal vessels was demonstrated. Babesia microti infection caused vacuolization of syncytioblasts and cytotrophoblasts, accumulation of collagen fibers in placental villi, and increased adhesion of erythrocytes to the vascular walls. These results indicate that Babesia may influence the course of pregnancy and invite further research on the mechanism of piroplasm penetration into cells. Full article