Does Paging Clinicians about Tick-Borne Disease Serological Results Impact Clinical Care? A Retrospective Analysis of 70 Cases in North Carolina.

Delayed treatment of Rocky Mountain spotted fever is associated with increased morbidity and mortality. Because the diagnosis cannot be established from a single serological test, guidelines recommend empirical antibiotic initiation in suspect patients. We evaluated a policy used by UNC Health of paging clinicians when acute testing for Rickettsia returned with a titer ≥1:256. Our objective was to assess the potential effect of paging on routine treatment practices. Notably, we found that a high proportion of cases (N = 28, 40%) were not prescribed antibiotics until the results were available. The vast majority of these cases did not have evidence of compatible symptoms or disease progression. These findings suggest that paging may have prompted unnecessary treatment. Overall, the policy, which has now been discontinued, appears to have had limited benefit. Efforts are urgently needed to improve adherence to testing and treatment guidelines.

Tick-borne infections in children in North America.

PURPOSE OF REVIEW: Because both incidence and awareness of tick-borne infections is increasing, review of major infections and recent advances related to their diagnosis and management is important. RECENT FINDINGS: A new algorithm, termed modified two-tier testing, for testing for antibodies to Borrelia burgdorferi , the cause of Lyme disease, has been approved and may replace traditional two-tier testing. In addition, doxycycline is now acceptable to use for treatment of and/or prophylaxis for Lyme disease for up to 21 days in children of any age. Borrelia miyamotoi , a bacterium in the relapsing fever type of Borrelia, is the first of this type of Borrelia that is transmitted by hard-bodied ticks such as Ixodes scapularis. SUMMARY: Awareness of these infections and advances in their diagnosis and treatment is important to assure the best outcomes for affected patients. Table 1 contains a summary of infections discussed.

Impact of the COVID-19 pandemic on delays in diagnosis and treatment of tick-borne diseases endemic to southeastern USA.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic was marked by an increase in diagnosis and treatment delays for a range of medical conditions. Yet the impact of the pandemic on the management of tick-borne diseases, which frequently manifest as an acute febrile illness similar to COVID-19, has not been well described. METHODS: In this retrospective cohort study of patients with suspected tick-borne disease attending the University of North Carolina Health facilities, we compared the timeliness of diagnosis and treatment in a "pre-COVID" period (March 2019 to February 2020) and a "post-COVID" period (March 2020 to February 2021). Participants included patients with an ICD-10 diagnosis code of spotted fever group rickettsiosis or ehrlichiosis and a positive Rickettsia rickettsii or Ehrlichia indirect immunofluorescence assay immunoglobulin G antibody test result. Of the 897 patients who had an eligible diagnosis, 240 (26.8%) met the inclusion criteria. The main outcome was time from initial presentation to definitive diagnosis and treatment. RESULTS: During the 2-year study period, 126 (52.5%) patients were grouped in the pre-COVID period and 114 (47.5%) were grouped in the post-COVID period; 120 (50.0%) were female; and 139 (57.9%) were aged > 50 years. Comparing the post-COVID to the pre-COVID period, the adjusted odds ratio (aOR) for delay in treatment > 0 days was 1.81 (95% confidence interval [CI] 1.07-3.07, P = 0.03), and for a treatment delay > 7 days, 1.65 (95% CI 0.94-2.90, P = 0.08). The odds of a delay in diagnosis were similar for patients in the post- and pre-COVID periods, with an aOR of 1.61 (95% CI 0.96-2.72, P = 0.07) for delays > 0 days, and aOR of 1.72 (95% CI 0.99-3.00, P = 0.05) for delays > 7 days. CONCLUSIONS: The odds of a delay in treatment > 0 days were significantly higher in the post-COVID period than in the pre-COVID period. However, the odds of a delay in treatment > 7 days, or a delay in diagnosis, were similar between these two periods. Shifts in care-seeking, alternative care delivery models and prioritization of COVID-19 may contribute to diminished timeliness of treatment for patients with tick-borne diseases.

Neoehrlichia mikurensis-An emerging opportunistic tick-borne infection in immunosuppressed patients.

BACKGROUND: Neoehrlichia mikurensis (N. mikurensis) is a newly discovered tick-borne pathogen that can inflict life-threatening illness in immunocompromised patients. N. mikurensis infection is only detectable by polymerase chain reaction (PCR)-based methodologies. We describe three distinct clinical manifestations of N. mikurensis infection (neoehrlichiosis) in Danish patients receiving B-lymphocyte-depleting therapy, rituximab, for underlying hematological, rheumatological, or neurological disorders. All three patients went through a protracted pre-diagnostic period. METHODS: N. mikurensis DNA was detected and confirmed using two methods. Blood was tested by specific real-time PCR targeting the groEL gene and by 16S and 18S profiling followed by sequencing. Bone marrow was analyzed by 16S and 18S profiling. RESULTS: N. mikurensis was detected in blood samples in all three cases and in bone marrow from one of the three. The severity of the symptoms ranged from prolonged fever lasting more than 6 months to life-threatening hyperinflammation in the form of hemophagocytic lymphohistiocytosis (HLH). Interestingly, all patients presented with splenomegaly and two with hepatomegaly. After starting doxycycline therapy, symptoms were relieved within a few days, and biochemistry and organomegaly quickly normalized. CONCLUSION: We present three Danish patients recognized by the same clinician over a period of 6 months, strongly suggesting that many cases are going unrecognized. Second, we describe the first case of N. mikurensis-induced HLH and emphasize the potential severity of undetected neoehrlichiosis.

Clinical presentation, diagnostic investigations, treatment protocols and outcomes of dogs diagnosed with tick-borne diseases living in the United Kingdom: 76 cases (2005-2019).

OBJECTIVES: To report the presence of tick-borne diseases in dogs living in the United Kingdom. MATERIALS AND METHODS: Dogs with a final diagnosis of tick-borne diseases made between January 2005 and August 2019 at seven referral institutions in the United Kingdom were included in the study. RESULTS: Seventy-six dogs were included: 25 were diagnosed with ehrlichiosis, 23 with babesiosis, eight with Lyme borreliosis and six with anaplasmosis. Fourteen dogs had co-infections with two or three pathogens. Except for those dogs with anaplasmosis and Lyme borreliosis, most dogs with tick-borne diseases had a history of travel to or from endemic countries. However, three dogs with ehrlichiosis, and one dog each infected with Babesia canis and Babesia vulpes did not have any history of travel. A variety of non-specific clinical signs and laboratory abnormalities were reported. Targeted treatment was successful at achieving clinical remission in 64 (84%) dogs. CLINICAL SIGNIFICANCE: Even in non-endemic areas, veterinary surgeons should consider tick-borne diseases in dogs with compatible clinical presentation and laboratory findings and especially where there is a history of travel. As autochthonous transmission of tick-borne-pathogens does occur, an absence of travel should not rule out tick-borne diseases. Specific diagnostic testing is required to confirm infection, and this enables prompt targeted treatment and often a positive outcome.

Enfermedad por picaduras, la gran olvidada en el algoritmo diagnóstico / Stinging disease, the great forgotten in the diagnostic algorithm

La fiebre botonosa mediterránea es una enfermedad zoonótica febril aguda causada por Rickettsia conorii y transmitida a los humanos por la garrapata marrón Rhipicephalus sanguineus.Todo el mundo es susceptible a las picaduras de garrapata, diversos estudios demuestran que el porcentaje de seropositividad es más elevado en los residentes del medio rural. La mayoría de las veces, al realizar el diagnóstico diferencial de exantema generalizado pruriginoso (causa alérgica, medicamentosa, infecciones bacterianas, virales, fúngicas, estrés…) dejando a un lado las enfermedades por picaduras. Se debe cambiar esa mentalidad dado que el aumento de este tipo de enfermedades es exponencial. Se ha de tener en cuenta que dentro de los riesgos biológicos se encuentran las picaduras y no todas son vánales, requiriendo en nuestro día a día como médicos del trabajo: correcta anamnesis, seguimiento, diagnóstico y tratamiento. Un diagnóstico y tratamiento tardío lleva a un aumento de sintomatología en fase avanzada. (AU)

Mediterranean spotted fever is an acute febrile zoonotic zoonotic disease caused by Rickettsia conorii and transmitted to humans by the brown tick Rhipicephalus sanguineus.Everyone is susceptible to tick bites, but studies show that the rate of seropositivity is higher in rural residents. Most of the time, when making the differential diagnosis of pruritic generalised exanthema (allergic cause, medication, bacterial, viral, fungal infections, stress, etc.), we leave aside diseases caused by bites. We must change this mentality as the increase in this type of disease is exponential. It must be borne in mind that among the biological risks are stings and not all of them are viral, requiring in our day-to-day work as occupational physicians: correct anamnesis, monitoring, diagnosis and treatment. Late diagnosis and treatment leads to an increase in symptoms at an advanced stage. (AU)

Tick borne relapsing fever - a systematic review and analysis of the literature.

Tick borne relapsing fever (TBRF) is a zoonosis caused by various Borrelia species transmitted to humans by both soft-bodied and (more recently recognized) hard-bodied ticks. In recent years, molecular diagnostic techniques have allowed to extend our knowledge on the global epidemiological picture of this neglected disease. Nevertheless, due to the patchy occurrence of the disease and the lack of large clinical studies, the knowledge on several clinical aspects of the disease remains limited. In order to shed light on some of these aspects, we have systematically reviewed the literature on TBRF and summarized the existing data on epidemiology and clinical aspects of the disease. Publications were identified by using a predefined search strategy on electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of TBRF published in English, French, Italian, German, and Hungarian were included. Maps showing the epidemiogeographic mosaic of the different TBRF Borrelia species were compiled and data on clinical aspects of TBRF were analysed. The epidemiogeographic mosaic of TBRF is complex and still continues to evolve. Ticks harbouring TBRF Borrelia have been reported worldwide, with the exception of Antarctica and Australia. Although only molecular diagnostic methods allow for species identification, microscopy remains the diagnostic gold standard in most clinical settings. The most suggestive symptom in TBRF is the eponymous relapsing fever (present in 100% of the cases). Thrombocytopenia is the most suggestive laboratory finding in TBRF. Neurological complications are frequent in TBRF. Treatment is with beta-lactams, tetracyclines or macrolids. The risk of Jarisch-Herxheimer reaction (JHR) appears to be lower in TBRF (19.3%) compared to louse-borne relapsing fever (LBRF) (55.8%). The overall case fatality rate of TBRF (6.5%) and LBRF (4-10.2%) appears to not differ. Unlike LBRF, where perinatal fatalities are primarily attributable to abortion, TBRF-related perinatal fatalities appear to primarily affect newborns.

Rickettsiosis subcommittee report to the tick-borne disease working group.

Tick-borne rickettsial infections are serious, common, and difficult to diagnose. Among the most important factors leading to failure to diagnose and treat tick-borne rickettsioses effectively is a lack of consideration of the potential diagnosis by primary caregivers and emergency department physicians in patients presenting with undifferentiated acute febrile illness during tick season. This situation exists because of insufficient primary and continuing medical education of medical students, primary care and emergency medicine residents, and practicing physicians regarding tick-borne rickettsioses specific to the region where they practice. Delayed initiation of treatment with an appropriate antibiotic is associated with adverse outcomes including increased rates of hospitalization, admission to an intensive care unit, and mortality. The earliest symptoms are nonspecific, consisting of fever, headache, myalgias, and nausea and/or vomiting. Laboratory abnormalities are typically absent at this time when the therapeutic response to an appropriate antibiotic would be optimal. There is a mistaken idea among a substantial portion of physicians that the best antibiotic available, doxycycline, should not be administered to children 8 years of age or younger or during pregnancy. For all of the above reasons, there is unnecessary morbidity and mortality caused by tick-borne rickettsioses. This report proposes measures to address these critical issues regarding tick-borne rickettsioses.

Clinical and diagnostic manifestations of tickborne mixed infection in combination with COVID-19.

The coexistence of various pathogens inside the patient's body is one of the poorly studied and current issues. The aim of the study is to identify the relationship between the indicators of complex laboratory diagnostics and the clinical manifestations of a mixed disease during subsequent infection with the SARS-CoV-2 virus using the example of a case of chronic encephalitis-borreliosis infection. Seven blood serum samples were collected from the patient over the course of a year. For the etiological verification of the causative agents of TBE, Lyme disease and COVID-19, the methods of ELISA and PCR diagnostics were used. The patient was diagnosed with Lyme disease on the basis of the detection of IgG antibodies to Borrelia 5 months after the onset of the disease, since she denied the tick bite. In the clinical picture, there was an articular syndrome and erythema migrans. Later, IgG antibodies to the TBEV were found in the blood. Throughout the study, IgM antibodies to Borrelia were not detected. The exacerbation of Lyme disease could be judged by the clinical manifestations of this disease and by the growth of specific IgG antibodies. A feature of this case was that during an exacerbation of the Lyme disease, an infection with the SARS-CoV-2 virus occurred. Treatment (umifenovir, hydroxychloroquine, azithromycin, ceftriaxone) was prescribed, which improved the condition of the underlying disease, decreased joint pain, decreased IgG levels to borrelia. However, during this period, serological markers of TBEV appear: antigen, IgM antibodies, and the titer of IgG antibodies increases. Most likely, this was facilitated by the switching of the immune system to the SARS-CoV-2 virus, with the simultaneous suppression of borrelia with antibiotics and the appointment of hydroxychloroquine, which has an immunosuppressive effect. Despite the activation of the virus, clinical manifestations of TBE were not observed in the patient, which is most likely associated with infection with a weakly virulent TBEV strain. The further course of tick-borne infections revealed the dominant influence of B. burgdorferi in relation to TBEV. Laboratory studies have shown that suppression of the activity of the borreliosis process by etiotropic treatment subsequently led to the activation of the persistent TBEV.

Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread, tick-borne pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) with high morbidity and mortality. CCHFV is transmitted to humans through tick bites or direct contact with patients or infected animals with viremia. Currently, climate change and globalization have increased the transmission risk of this biosafety level (BSL)-4 virus. The treatment options of CCHFV infection remain limited and there is no FDA-approved vaccine or specific antivirals, which urges the identification of potential therapeutic targets and the design of CCHF therapies with greater effort. In this article, we discuss the current progress and some future directions in the development of antiviral strategies against CCHFV.

Case report: first symptomatic Candidatus Neoehrlichia mikurensis infection in Slovenia.

BACKGROUND: Candidatus Neoehrlichia mikurensis (CNM) is an emerging tick-born pathogen and usually causes symptomatic infection only in immunocompromised patients. Apart from one described case found in the literature where cultivation was successful, all cases so far were diagnosed by using broad-range 16S rDNA PCR. CASE PRESENTATION: Our patient presented with a prolonged febrile state of unknown origin. Clinical presentation, extensive medical workup and classic microbiologic testing were non-conclusive. Several infectious agents and other causes for the febrile state were excluded. In the end, a broad-range 16S rDNA PCR was to be performed to confirm the diagnosis of CNM infection. Treatment was successful with doxycycline. CONCLUSIONS: Due to the obscurity of the pathogen, diagnostic workup in CNM is prolonged and challenging. More awareness is need about this emerging infectious disease in countries with high prevalence of tick-borne diseases as standard microbiological methods are not successful in confirming the diagnosis.

Translational biotechnology for the control of ticks and tick-borne diseases.

Ticks and tick-borne diseases (TBD) represent a challenge for human and animal health worldwide. Climate change, distribution of tick hosts, and ecological and anthropogenically-induced changes contribute to the geographic expansion of ticks and tick-borne pathogens. Traditional control methods are based on the use of acaricides to reduce tick infestations, but vaccines represent a more effective, sustainable and environmentally sound approach for the control of ticks and TBD. Recent application of omics technologies to the study of the mechanisms involved in tick-host-pathogen interactions have advanced the characterization of molecular mechanisms involved in TBD and the identification of candidate vaccine protective antigens. However, as discussed in this opinion paper, translational biotechnology may translate into novel interventions required to advance in addressing the challenge that ticks and TBD represent for world health and economy.

Scalp eschar and neck lymphadenopathy by Rickettsia slovaca after Dermacentor marginatus tick bite case report: multidisciplinary approach to a tick-borne disease.

BACKGROUND: Scalp Eschar and Neck LymphAdenopathy after Tick bite is a zoonotic non-pathogen-specific disease most commonly due to Rickettsia slovaca and Rickettsia raoultii. Diagnosis is mostly based only on epidemiological and clinical findings, without serological or molecular corroboration. We presented a clinical case in which diagnosis was supported by entomological identification and by R. slovaca DNA amplifications from the tick vector. CASE PRESENTATION: A 6-year-old child presented with asthenia, scalp eschar and supraclavicular and lateral-cervical lymphadenopathy. Scalp Eschar and Neck LymphAdenopathy After Tick bite syndrome following a Dermacentor marginatus bite was diagnosed. Serological test on serum revealed an IgG titer of 1:1024 against spotted fever group rickettsiae, polymerase chain reaction assays on tick identified Rickettsia slovaca. Patient was successfully treated with doxycycline for 10 days. CONCLUSIONS: A multidisciplinary approach including epidemiological information, clinical evaluations, entomological identification and molecular investigations on tick, enabled proper diagnosis and therapy.

Tularemia: a re-emerging tick-borne infectious disease.

Tularemia is a bacterial disease of humans, wild, and domestic animals. Francisella tularensis, which is a Gram-negative coccobacillus-shaped bacterium, is the causative agent of tularemia. Recently, an increase in the number of human tularemia cases has been noticed in several countries around the world. It has been reported mostly from North America, several Scandinavian countries, and certain Asian countries. The disease spreads through vectors such as mosquitoes, horseflies, deer flies, and ticks. Humans can acquire the disease through direct contact of sick animals, consumption of infected animals, drinking or direct contact of contaminated water, and inhalation of bacteria-loaded aerosols. Low infectious dose, aerosol route of infection, and its ability to induce fatal disease make it a potential agent of biological warfare. Tularemia leads to several clinical forms, such as glandular, ulceroglandular, oculoglandular, oropharyngeal, respiratory, and typhoidal forms. The disease is diagnosed through the use of culture, serology, or molecular methods. Quinolones, tetracyclines, or aminoglycosides are frequently used in the treatment of tularemia. No licensed vaccine is available in the prophylaxis of tularemia and this is need of the time and high-priority research area. This review mostly focuses on general features, importance, current status, and preventive measures of this disease.

First identification of Anaplasma phagocytophilum in both a biting tick Ixodes nipponensis and a patient in Korea: a case report.

BACKGROUND: Human granulocytic anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum. To date, there have been no reported cases of A. phagocytophilum infection found in both the biting tick and the patient following a tick bite. CASE PRESENTATION: An 81-year-old woman presented with fever following a tick bite, with the tick still intact on her body. The patient was diagnosed with HGA. The tick was identified as Ixodes nipponensis by morphological and molecular biological detection methods targeting the 16S rRNA gene. The patient's blood was cultured after inoculation into the human promyelocytic leukemia cell line HL-60. A. phagocytophilum growth was confirmed via culture and isolation. A. phagocytophilum was identified in both the tick and the patient's blood by Anaplasma-specific groEL- and ankA-based nested polymerase chain reaction followed by sequencing. Moreover, a four-fold elevation in antibodies was observed in the patient's blood. CONCLUSION: We report a case of a patient diagnosed with HGA following admission for fever due to a tick bite. A. phagocytophilum was identified in both the tick and the patient, and A. phagocytophilum was successfully cultured. The present study suggests the need to investigate the possible incrimination of I. nipponensis as a vector for HGA in Korea.

Tickborne Diseases: Diagnosis and Management.

Tickborne diseases that affect patients in the United States include Lyme disease, Rocky Mountain spotted fever (RMSF), ehrlichiosis, anaplasmosis, babesiosis, tularemia, Colorado tick fever, and tickborne relapsing fever. Tickborne diseases are increasing in incidence and should be suspected in patients presenting with flulike symptoms during the spring and summer months. Prompt diagnosis and treatment can prevent complications and death. Location of exposure, identification of the specific tick vector, and evaluation of rash, if present, help identify the specific disease. Lyme disease presents with an erythema migrans rash in 70% to 80% of patients, and treatment may be initiated based on this finding alone. RMSF presents with a macular rash starting on the wrists, forearms, and ankles that becomes petechial. RMSF has a higher rate of mortality than other tickborne diseases; therefore, empiric treatment with doxycycline is recommended for all patients, including pregnant women and children, when high clinical suspicion is present. Testing patient-retrieved ticks for infections is not recommended. Counseling patients on the use of protective clothing and tick repellents during outdoor activities can help minimize the risk of infection. Prophylactic treatment after tick exposure in patients without symptoms is generally not recommended but may be considered within 72 hours of tick removal in specific patients at high risk of Lyme disease.

Management strategies for human babesiosis.

INTRODUCTION: Human babesiosis is reported throughout the world and is endemic in the northeastern and northern Midwestern United States and northeastern China. Transmission is primarily through hard bodied ticks. Most cases of severe disease occur in immunocompromised individuals and may result in prolonged relapsing disease or death. AREAS COVERED: We provide a summary of evidence supporting current treatment recommendations for immunocompetent and immunocompromised individuals experiencing babesiosis. EXPERT OPINION: Most cases of human babesiosis are successfully treated with atovaquone and azithromycin or clindamycin and quinine. Severe disease may require prolonged treatment.