Detection of New Pathogens in Oklahoma Ticks

Recent surveillance of Oklahoma ticks has detected, not only spreading populations of Ixodes scapularis (blacklegged ticks) but also pathogens not previously detected including bacteria, protozoans, and viruses that pose a serious risk to human health. A one-step multiplex real-time reverse transcription-PCR has detected tick-borne pathogens from a pool of 117 I. scapularis ticks collected from white-tailed deer. Three pooled samples were positive for Borrelia miyamotoi and five pooled samples of ticks tested positive for Deer Tick Virus (Powassan Virus lineage II). This is the first detection of these two pathogens in Oklahoma.

Blacklegged tick samples tested negative for Anaplasma phagocytophilumBorrelia burgdorferi, and Babesia microti . This study provides the first report of B. miyamotoi and DTV detection in Oklahoma I. scapularis ticks. Authors present  evidence that I. scapularis pathogens are present in Oklahoma and they recommend that further surveillance of I. scapularis in Oklahoma is Important.

Access to the full text article can be found here

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Methodology for Detection of Multiple Tick Pathogens

Deer Tick Questing
Blacklegged Deer Tick (Ixodes scapularis)

In this study published by Analytical and Bioanalytical Chemistry, researchers used mass spectrometry-based proteome profiling and parallel reaction monitoring to detect multiple pathogens in black-legged ticks collected from the Southern Tier New York.  Analysis from five combined ticks showed high confidence for identifying 2,052 tick proteins and 41 pathogen proteins. Results showed high peptide spectral match counts for both Rickettsia (8 out of 10 ticks) and Borrelia (5 out of ten) species; 3 out of 10 carried both of these pathogens. Lower counts were found for other less common pathogens, including Anaplasma phagocytophilum and only 1 tick was found to carry no detectable bacteria.

These methods have proven successful for identification and screening of tick-borne pathogen surveillance as well as providing awareness about tick-borne diseases (TBDs) in geographically specific areas. They might also help in the development of biomarkers to provide direct diagnosis  of TBDs, as well as differentiating between different tick-borne diseases, which could improve treatment courses for patients.

This highly specific testing methodology is efficient at defining the expression of different types of pathogen proteins in infected ticks; insight which may better illuminate interactions of tick-pathogens at the molecular level, especially the expression of pathogen surface proteins in ticks.

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Attention Researchers! CDMRP: Announcement for Lyme Research Proposals 2022

The Department of Defense Congressionally Directed Medical Research Program (CDMRP) published a news release alerting Lyme & other tick-borne diseases researchers of anticipated FY22 monies that may become available through the program so that researchers can plan and develop possible grant submissions. 

The CDMRP-TBDRP states that “Applicants are particularly encouraged to submit applications focused on tick-borne diseases (TBDs) and conditions endemic to the U.S., and/or involving patients with persistent Lyme disease.” 

Update: Fiscal Year 2022 (FY22) funding opportunities announcements have been released by CDMRP. Pre-Application (Preproposal) is required and due May 26, 2022 by 5:00 pm (ET). Application submission is by invitation only with applications due August 25, 2022 11:59 pm (ET).

Details of submission requirements can be found in the full news release and announcement. All questions should be addressed directly to the CDMRP program.

Access the FY22 CDMRP-TBDRP Press Release here

Access the FY22 CDMRP-TBDRP Announcement here

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Anaplasmosis Associated with Human Fatality in Vermont

In this case report, authors describe a human fatality associated with an acute tick-borne infection, human granulocytic anaplasmosis caused by the bacterium Anaplasma phagocytophilum. This case occurred in a resident of Vermont. The person presented with multiple comorbidities. Authors recommend that clinicians be aware of the risk factors for severe presentations of this infection and to treat expeditiously when the disease is suspected.

Co-author, Natalie A. Kwit, DVM, MPH (State Public Health Veterinarian at the Vermont Department of Health) stated in a response to an inquiry from the LDA, “Anaplasmosis is an acute febrile illness caused by the bacterium Anaplasma phagocytophilum primarily transmitted by the bite of infected Ixodes scapularis ticks. The incidence of anaplasmosis is highest in the northeastern and upper midwestern United States. Reported cases have steadily increased over time, and in Vermont, the number of reported cases of anaplasmosis nearly doubled each year during 2012–2017. A recent anaplasmosis-related fatality case report highlights that clinicians in hyperendemic areas should be aware of this emerging disease and its more severe presentations, and presumptively treat with doxycycline upon suspicionPrompt recognition and early treatment, especially in persons at higher risk for severe outcomes such as advanced age and comorbidities, should help reduce the morbidity and mortality associated with this disease.”

Access to the full case report can be found here

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Severe Anaplasmosis Case Presents Atypically

Lyme borreliosis research In this case report,  a 79-year-old male sought care through the ER at a New York City hospital after experiencing acute illness and his wife noticed blood in his urine. The patient had several medical comorbidities including: “hypertension, benign prostate hypertrophy status post transurethral prostatectomy, cerebrovascular accident, and pulmonary hypertension.” He presented additional symptoms with fever, shortness of breath, severe thrombocytopenia, hematuria, elevated liver enzymes, and acute renal failure.

The patient’s condition progressed quickly to acute hypoxic respiratory failure, and he required mechanical ventilation. He was then started on intravenous (IV) ceftriaxone and azithromycin for suspected pneumonia, then switched to broader cover antibiotics, IV vancomycin and piperacillin/tazobactam. However, even with change to antibiotics, the patient remained febrile and experienced worsening anemia and heart failure.  The primary care team “was anchored in the diagnosis of pneumonia and stayed locked in the initial diagnosis without considering further differential.”  It was not until day 6 of hospitalization that infectious disease was consulted that the patient’s wife was asked about possible tick exposure. She stated that “the patient regularly walked in a park in New Jersey, and had had a recent tick bite.”  With the tick exposure knowledge it was recommended that the patient’s treatment be upgraded to meropenem and doxycycline. Direct detection tests for anaplasmosis were conducted, however this method is only successful in detection in about 20% of patients, and were negative for this patient.

Due to the delay in diagnosis, this patient suffered from severe illness and complications from anaplasmosis and required an extended hospital stay.  Tick-borne disease treatment was delayed for six days since these illnesses were not considered in the differential. The primary care team lacked the knowledge of tick-borne diseases that are not often seen in a city hospital. Authors note that empirical treatment of tick-borne illnesses should be considered in the proper clinical setting, and travel history should be relevant in any patient presenting with “fever, thrombocytopenia, leukopenia, and elevated liver enzymes, especially between spring and early fall,” even in city hospitals. They further suggest that the delay of early and appropriate treatment may result in the onset of severe illness. 

Read the full text case report here

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Study Confirms Heartland Virus in Lone Star Ticks in Georgia

Heartland Virus in Lone Star Ticks The report of a human death in Georgia from Heartland virus (HRTV) as well as confirmed white-tailed deer exposure to the tick-borne pathogen prompted researchers to collect samples of questing ticks in 2018–2019. The samples were taken from 26 sites near the areas where seropositive deer were captured, as well as the residence of the human patient.

The researchers processed a total of 9,294 Amblyomma Americanum (lone star) ticks in pools by virus isolation in Vero E6 cells and reverse transcription PCR. The positive pools went through whole-genome sequencing with three pools showing the presence of HRTV (minimum infection rate 0.46/1,000 ticks). Cell cultures found HRTV in two pools while none of the ticks tested positive for Bourbon virus. Among the samples, the genome sequencing for the three HRTV isolates exhibited a high degree of similarity, however, there were significant differences with formerly sequenced HRTV isolates.

HRTV was first detected in 2009 and since then approximately 40 more human cases of the disease have been discovered in Missouri, Kansas, Oklahoma, Arkansas, Iowa, Illinois, Tennessee, Indiana, and South Carolina, and, as this study confirms, Georgia. Most of these cases involved patients who had comorbidities and for many, their diseases were serious or deadly.

Studies showing seroprevalence in wildlife suggest an even wider distribution range of HRTV than those states with reported human disease cases. The researchers advise clinicians and those working in public health to be aware of this tick-borne pathogen as it emerges.

Read the study in the CDC’s Emerging Infectious Diseases journal.

Read more about Heartland virus.

Read more about lone star and other tick vectors.

Tafenoquine as Treatment for Relapsing Babesiosis

This study evaluates the effectiveness of tafenoquine (antimalarial primaquine analog) for treatment in an immunocompromised patient infected by a strain of Babesia microti that was partially resistant to both azithromycin and atovaquone treatment. 

Tafenoquine received USDA approval in 2018 for use in only two indications: prophylaxis of malaria (for up to 6 months total) and prevention of relapse of Plasmodium vivax malaria. This drug has a relatively long half-life (14–17 days in humans), therefore a single dose can be administered once per week as an effective malaria prophylactic.

Tafenoquine has been found to be a highly effective treatment for B. microti infections in animal models. Three previous studies with hamsters/mice, including highly immunocompromised mice, demonstrated that tafenoquine effectively and rapidly cleared B. microti parasites from these hosts.

In this case study, an immunocompromised adult patient with multiple relapses of a B. microti infection was treated with a 6 week course of tafenoquine. This patient had previously failed treatment with both azithromycin and atovaquone, relapsing multiple times with babesiosis as documented through both clinical presentation (fevers, night sweats, chills, myalgias) and laboratory confirmation. Tafenoquine was well tolerated by the patient during treatment and over the course of follow-up, approximately 19 months. Additionally, the patient has remained well since treatment with tafenoquine. 

Because of the success witnessed in both animal models and this human case study, investigators indicate that this drug has a potential role in the treatment of patients with babesiosis, especially in patients who are highly immunocompromised and/or resistant to other therapies. They recommend that systematic clinical studies using tafenoquine be considered in other patients with babesiosis.

Read full text article here.

Read another article on Babesia treatment.

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Overview of Several Difficult to Detect Gram-Negative Tick-Borne Pathogens

In this article published in FEMS Microbiology Reviews, researchers provide an overview of the current and future perspectives for diagnosis of several species of difficult to detect Gram-negative bacteria. Investigators discuss the zoonotic and vector-transmitted bacteria, Anaplasma spp., Bartonella spp., Coxiella burnetii, Orientia spp., and Rickettsia spp. These bacteria are strongly adapted to the infected host which impedes growth of these bacteria outside the host as well as identification of these pathogens. Because these bacterial species multiply slowly once they are removed from their host, it complicates the laboratory diagnosis of the disease. The slow growth of bacteria further hinders detection and characterization of the bacteria, and impacts resistance to antibiotic treatment. 

Authors summarize the existing diagnostic protocols for each of the bacteria investigated. They also identify specific limitations that exist for implementing novel diagnostic approaches and highlight the need for further optimizing or expanding the equipment, methods, and pharmaceuticals used in diagnostics and treatment. They discuss new technologies, including mass spectrometry, next generation nucleic acid sequencing, and in vitro diagnostic tools for potentially improved diagnostics of these difficult to detect and treat pathogens.

Read the full text article here

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Seresto Dog Collar Proves Effective in Preventing TBD Transmission

Parasitology Research has published research findings on the effectiveness of the Seresto® (imidacloprid 10% + flumethrin 4.5%) dog collar in preventing transmission of both Borrelia burgdorferi and Anaplasma phagocytophilum. Effectiveness of the prevention collar was tested on dogs in two studies using naturally infected ticks. Each study consisted of a non-treated control group as well as a group treated with the Seresto® collar. All dogs were serologically tested for the presence of pathogens prior to study implementation.

The treated groups of dogs were fitted with Seresto® collars two months prior to tick infestations. All dogs were exposed to ticks that were naturally infected with B. burgdorferi and A. phagocytophilum. In study 1, two of six non-treated dogs became infected with B. burgdorferi, and four of six tested positive for A. phagocytophilum after being exposed to naturally infected Ixodes ricinus ticks. In study two, 10 of 10 non-treated dogs became infected with B. burgdorferi and A. phagocytophilum after being exposed to naturally infected Ixodes scapularis ticks. None of the treated dogs in either study tested positive for B. burgdorferi or A. phagocytophilum. Transmission of both pathogens was successfully blocked for up to 7 months on dogs wearing Seresto® collars.

Investigators reported that no serious treatment-related events were found with use of the Seresto® collar in the treated groups of dogs. Only mild signs of hair loss and skin irritation were observed, primarily in the group dogs treated for 7 months. The use of the acaricide collar showed 100% efficacy for killing ticks at 48 h for both tick species at time periods of 1, 2 and 7 months after the placement of the collar. 

Authors conclude that due to its long-term efficacy, the Seresto® collar may be a valuable tool in the prevention of tick pathogen transmission to dogs. 

NOTE: This article in presented for informational purposes only. The LDA does not recommend or endorse products. 

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Babesiosis Hospitalizations Increased Over 7-Year Period in the US

A new CDC study shows that in comparison with state reporting data, the number of hospitalized patients with Babesia has increased “modestly” over a 7-year period.  Researchers performed this analysis in the United States during 2010–2016. The National Inpatient Sample database was used to characterize the epidemiology of Babesia–associated admissions, reflecting severe Babesia-related disease. Results showed that over a 7-year period, babesiosis was listed as either a primary or secondary diagnosis in a  total of 7,818 hospitalizations. Authors note that hospitalizations were seasonal with over 70% of cases occurring June-August. These cases were predominately situated  in the Northeast and Midwest regions of the US. Patients were also predominantly older men, and although severe illness was documented in more than 58% of patients, mortality rate was less than 2%.  

Authors state that there is uncertainty about increasing hospitalizations in general and question whether the demographics of those who are likely to require hospitalization for babesiosis is increasing, or whether greater awareness of babesiosis symptoms is contributing to increased hospitalizations and recognition of disease. 

The authors maintain that overall health burden, especially for patients at high risk for severe or fatal disease, remains a concern.

This article provides a Medscape CME Activity: “Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.”

Access to the full text article and CME Activity can be found here

Other LDA articles related to Babesia can be found here