A New Segmented Virus Associated with Human Febrile Illness in China.

BACKGROUND: In 2017, surveillance for tickborne diseases in China led to the identification of a patient who presented to a hospital in Inner Mongolia with a febrile illness that had an unknown cause. The clinical manifestation of the illness was similar to that of tickborne encephalitis virus (TBEV) infection, but neither TBEV RNA nor antibodies against the virus were detected. METHODS: We obtained a blood specimen from the index patient and attempted to isolate and identify a causative pathogen, using genome sequence analysis and electron microscopy. We also initiated a heightened surveillance program in the same hospital to screen for other patients who presented with fever, headache, and a history of tick bites. We used reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and cell-culture assays to detect the pathogen and immunofluorescence and neutralization assays to determine the levels of virus-specific antibodies in serum specimens from the patients. RESULTS: We found that the index patient was infected with a previously unknown segmented RNA virus, which we designated Alongshan virus (ALSV) and which belongs to the jingmenvirus group of the family Flaviviridae. ALSV infection was confirmed by RT-PCR assay in 86 patients from Inner Mongolia and Heilongjiang who presented with fever, headache, and a history of tick bites. Serologic assays showed that seroconversion had occurred in all 19 patients for whom specimens were available from the acute phase and the convalescent phase of the illness. CONCLUSIONS: A newly discovered segmented virus was found to be associated with a febrile illness in northeastern China. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China.).

Subjective health complaints and exposure to tick-borne infections in southern Norway.

OBJECTIVES: Whether tick-borne infections can cause chronic subjective health complaints is heavily debated. If such a causal connection exists, one would expect to find more health complaints among individuals exposed to tick-borne infections than among non-exposed. In this study, we aimed to assess if exposure to tick-borne infections earlier in life, evaluated by examination of serum for IgG antibodies to tick-borne microbes, was associated with self-reported somatic symptom load. MATERIALS & METHODS: All individuals with residential address in Søgne municipality in southern Norway, aged 18-69 years, were invited to participate in the study. Blood samples were analyzed for IgG antibodies to different tick-borne microbes, and somatic symptom load was charted by the Patient Health Questionnaire-15 (PHQ-15). RESULTS: Out of 7424 invited individuals, 2968 (40.0%) were included in the study. We detected IgG antibodies to Borrelia burgdorferi sensu lato (Bb) in 22.9% (95% CI 21.4-24.4). Bb seropositive individuals reported less frequently moderate to severe somatic symptom load (ie, PHQ-15 sum score ≥ 10) than seronegative individuals (12.5% versus 17.7%, difference 5.2% [95% 2.1-8.0]). However, when adjusting for several other variables in a multivariable linear regression model, presence of serum IgG antibodies to Bb was not associated with somatic symptom load. Presence of IgG antibodies to other tick-borne microbes than Bb, or seropositivity to at least two microbes, was also not associated with somatic symptom load. CONCLUSION: Presence of serum IgG antibodies to tick-borne microbes was not associated with self-reported somatic symptom load.

Presence of Borrelia miyamotoi infection in a highly endemic area of Lyme disease.

A series of cases in the Northeast of the US during 2013-2015 described a new Borrelia species, Borrelia miyamotoi, which is transmitted by the same tick species that transmits Lyme disease and causes a relapsing fever-like illness. The geographic expansion of B. miyamotoi in the US also extends to other Lyme endemic areas such as the Midwestern US. Co-infections with other tick borne diseases (TBD) may contribute to the severity of the disease. On Long Island, NY, 3-5% of ticks are infected by B. miyamotoi, but little is known about the frequency of B. miyamotoi infections in humans in this particular region. The aim of this study was to perform a chart review in all patients diagnosed with B. miyamotoi infection in Stony Brook Medicine (SBM) system to describe the clinical and epidemiological features of B. miyamotoi infection in Suffolk County, NY. In a 5 year time period (2013-2017), a total of 28 cases were positive for either IgG EIA (n = 19) or PCR (n = 9). All 9 PCR-positive cases (median age: 67; range: 22-90 years) had clinical findings suggestive of acute or relapsing infection. All these patients were thought to have a TBD, prompting the healthcare provider to order the TBD panel which includes a B. miyamotoi PCR test. In conclusion, B. miyamotoi infection should be considered in the differential diagnosis for flu-like syndromes during the summer after a deer tick bite and to prevent labeling a case with Lyme disease.

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.

What Is Alpha-Gal Syndrome?

This JAMA Patient Page describes alpha-gal syndrome, a type of food allergy to red meat products, and its symptoms, diagnosis, and treatment.

Molecular identification of tick-borne pathogens in asymptomatic individuals with human immunodeficiency virus type 1 (HIV-1) infection: a retrospective study.

BACKGROUND: The studies on the occurrence and diversity of tick-borne infections in HIV-infected individuals have been few, and the subject has been relatively neglected when compared with other common infections associated with HIV. In HIV-positive patients in whom a serological diagnostics is complicated due to reduced positive predictive value, a method where the microorganism is detected directly is of great value. Therefore, we performed a molecular study to ascertain the prevalence and incidence of tick-borne infections in HIV-infected persons in Poland, an endemic area for Ixodes ricinus ticks. METHODS: Genomic DNA was isolated from whole blood of tested patients. Detection of tick-borne pathogens was performed by amplification and sequencing of different loci. Molecular and phylogenetic analyses of obtained nucleotide sequences were performed. Serum samples were analyzed for antibodies against tick-borne pathogens by using commercial tests in all patients. RESULTS: Among 148 studied blood samples from HIV-infected patients, two cases (1.4%) of infection with tick-borne pathogen were reported. No symptoms of tick-borne infection were observed in these cases. In one case a patient was infected with Anaplasma phagocytophilum - the agent of human granulocytic anaplasmosis (HGA) and in the other with Borrelia garinii. CONCLUSIONS: Our study revealed the first case of HIV positive patient infected with A. phagocytophilum. Asymptomatic tick-borne infection can occur in HIV-positive patients. The detailed history of tick bites, especially in endemic tick areas, should be considered as part of anamnesis in routine clinical care of HIV-positive patients.

Tularemia-induced erythema multiforme minor in an 11-year-old girl.

Tularemia is a rare and potentially life-threatening infection caused by the highly infectious gram-negative coccobacillus Francisella tularensis. We present the case of an 11-year old girl who presented with erythema multiforme minor in the setting of an indolent but progressive soft tissue infection and was found to have tularemia. We review the role of dermatologists in identifying the features of and complications associated with this rare zoonosis and discuss the potential effect of climate change on its incidence.

Plasmodium falciparum malaria co-infection with tick-borne relapsing fever in Dakar.

BACKGROUND: West African tick-borne relapsing fever (TBRF) due to Borrelia crocidurae and malaria are co-endemics in Senegal. Although expected to be high, co-infections are rarely reported. A case of falciparum malaria and B. crocidurae co-infection in a patient from Velingara (South of Senegal) is discussed. CASE: A 28 year-old-male patient presented to Aristide Le Dantec Hospital for recurrent fever. He initially presented to a local post health of Pikine (sub-urban of Dakar) and was diagnosed for malaria on the basis of positive malaria rapid diagnostic test (RDT) specific to Plamodium falciparum. The patient was treated as uncomplicated falciparum malaria. Four days after admission the patient was referred to Le Dantec Hospital. He presented with fever (39 °C), soreness, headache and vomiting. The blood pressure was 120/80 mmHg. The rest of the examination was normal. A thick film from peripheral blood was performed and addressed to the parasitology laboratory of the hospital. Thick film was stained with 10% Giemsa. Trophozoite of P. falciparum was identified at parasite density of 47 parasites per microlitre. The presence of Borrelia was also observed, concluding to malaria co-infection with borreliosis. CONCLUSIONS: Signs of malaria can overlap with signs of borreliosis leading to the misdiagnosis of the latter. Thick and thin smear or QBC test or molecular method may be helpful to detect both Plamodium species and Borrelia. In addition, there is a real need to consider co-infections with other endemics pathogens when diagnosing malaria.

The eye and tick-borne disease in the United States.

PURPOSE OF REVIEW: Tick-borne diseases are increasing in incidence and geographic distribution. Several diseases endemic to the United States have ophthalmic manifestations, including the most common tick-borne disease, Lyme borreliosis. As ocular complaints may lead a patient to seek medical evaluation, it is important to be aware of the systemic and ophthalmic manifestations of tick-borne diseases in order to make the correct diagnosis. RECENT FINDINGS: Vision-threatening ophthalmic manifestations are relatively common in Lyme disease and Rocky Mountain spotted fever. Ocular involvement is rare in babesiosis, tick-borne relapsing fever, Powassan encephalitis, ehrlichiosis, anaplasmosis, and Colorado tick fever.There are clear guidelines for diagnosis and treatment of Lyme disease; however, confusion and misinformation among the general public as well as controversy about chronic or late-stage Lyme disease can impact the evaluation of ophthalmic disease. Furthermore, there are many gaps in our knowledge regarding the pathophysiology of ocular borreliosis although it seems likely that Lyme uveitis is rare in the United States. SUMMARY: Knowledge of systemic and ophthalmic manifestations combined with an understanding of the epidemiology of disease vectors is crucial for the diagnosis of tick-borne diseases.

Tickborne Coinfections in the United States.

Unlike mosquitoes, ticks transmit the broadest range of pathogens, including bacteria, viruses, and parasites. Ticks have capitalized on many competitive advantages offered to them by changes in climate and human lifestyle and a greater abundance of wild animal reservoir hosts no longer effectively controlled. As a result, tick-transmitted coinfections are increasing today with both recognized and newly discovered pathogens that complicate differential diagnosis and antimicrobial treatment. Without the support of immunological and molecular diagnostic techniques, usually only available at federal and some state laboratories, the initial differential diagnosis of tickborne coinfections is complicated and antimicrobial therapy may not cover coinfections. Therefore, the objectives of this review were to identify the newly emerging tickborne pathogens in the United States, to describe the evolving epidemiology of tick-transmitted coinfections, to design a decision tree analysis approach to the clinical diagnosis and management of tickborne coinfections, and to recommend effective strategies for the control and personal prevention of tickborne diseases. Clinicians should suspect tickborne coinfections in returning travelers and vacationers with clinical and immunological evidence of multiple infecting agents, especially in cases of unusual presentation or severity, prolonged duration, or nonresponse to single antibiotic therapy, typically with doxycycline. Decision tree models based on pathogen prevalence rates in ticks and their zoonotic reservoirs may assist clinicians in diagnosing tickborne coinfections and guiding initial antimicrobial therapy.

Infections with the tick-borne bacterium "Candidatus Neoehrlichia mikurensis" mimic noninfectious conditions in patients with B cell malignancies or autoimmune diseases.

BACKGROUND: Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. METHODS: We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. RESULTS: The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. CONCLUSIONS: Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.

Bacterial tick-borne diseases caused by Bartonella spp., Borrelia burgdorferi sensu lato, Coxiella burnetii, and Rickettsia spp. among patients with cataract surgery.

BACKGROUND: Clinical data have shown that tick-borne diseases caused by Borrelia burgdorferi sensu lato, Bartonella spp., Coxiella burnetii, and Rickettsia spp. can affect the central nervous system, including the eye. The aim of this study was to establish a relationship between the incidence of cataract and evidence of bacterial infections transmitted by ticks. MATERIAL AND METHODS: Fluid with lenticular masses from inside of the eye and blood from 109 patients were tested by PCR and sequencing. Sera from patients and the control group were subjected to serological tests to search specific antibodies to the bacteria. RESULTS: Microbiological analysis revealed the presence of Bartonella sp. DNA in intraoperative specimens from the eye in 1.8% of patients. Serological studies have shown that infections caused by B. burgdorferi sensu lato and Bartonella sp. were detected in 34.8% and 4.6% of patients with cataract surgery, respectively. CONCLUSIONS: Presence of DNA of yet uncultured and undescribed species of Bartonella in eye liquid indicates past infection with this pathogen. Specific antibodies to B. burgdorferi sensu lato and Bartonella sp. are detected more frequently in patients with cataract compared to the control group. This could indicate a possible role of these organisms in the pathological processes within the eyeball, leading to changes in the lens. Further studies are needed to identify Bartonella species, as well as to recognize the infectious mechanisms involved in cataract development.

Exploring the relationship of supernumerary recurrent renal calculi formation and tick-borne infections: a case report.

A 51-year-old male with a history of Cacchi-Ricci disease and long-standing infection with various species of Borrelia, Babesia, and Bartonella presented with recurrent symptoms of right-sided flank pain. Numerous renal calculi were identified on imaging. The etiology of the calculi had not been previously elucidated. Symptoms intermittently date back to 2002 when uric acid stones were identified. Subsequent calculi analysis revealed calcium oxalate stones. Despite the commonality of nephrolithiasis in patients with Cacchi-Ricci disease, the extreme number of calculi and recurrent presentation of symptoms persisted despite a plethora of medical evaluations, dietary changes, and hereditary testing. This case raises questions of etiology including possible immune deficiency and whether his uncommon microbial history contributes to recurrent stone formation.

Non-lyme tick-borne diseases: a neurological perspective.

Tick-borne diseases are prevalent throughout the world and present a diagnostic challenge owing to their nonspecific clinical symptoms. Many tick-borne diseases involve the central and peripheral nervous systems. Early diagnosis or at least suspicion of a tick-borne cause is necessary to institute early empiric treatment. After a brief review of tick biology, we present the most common tick-borne diseases. A brief discussion of epidemiology, the transmission route, and pathogenesis is followed by a discussion of the clinical manifestations, diagnosis and treatment options when available. The review emphasizes the infectious causes with a significant neurological manifestation.

Lipid mediators of cerebrospinal fluid in response to TBE and bacterial co-infections.

Tick-borne diseases are caused by monoinfection or co-infection with different pathogens, including viruses, bacteria and protozoa. Tick-borne diseases are usually accompanied by oxidative stress which promotes the modifications of the host's lipid metabolism. The aim of the study was to compare total antioxidant status and the level of lipid mediators in the cerebrospinal fluid in response to tick-borne encephalitis (TBE) and bacterial co-infections that cause diseases such as that is Lyme borreliosis (LB) and human granulocytic anaplasmosis (HGA). In our study cerebrospinal fluid samples were obtained from 15 patients with TBE and 6 patients with TBE co-infection with LB and/or HGA at admission and after treatment. Control group consisted of 14 patients in whom meningitis was excluded. Total antioxidant status, levels of lipid peroxidation products, endocannabinoids and eicosanoids (determined by liquid and gas chromatography-mass spectrometry) were compared between the groups. It was found that in TBE patients, total antioxidant status was decreased and accompanied by increased levels of lipid peroxidation products (4-HNE, MDA, isoprostanes and neuroprostanes), major endocannabinoids (AEA and 2AG), and eicosanoids (both anti-inflammatory and pro-inflammatory), which generally declined after treatment. On the other hand, in co-infections, significant changes in the levels of some lipid mediators were observed even after the treatment. TBE alone or along with bacterial co-infections promote redox balance disturbances in the cerebrospinal fluid leading to oxidative stress and increased metabolism of phospholipids in the brain tissue reflected in the level of lipid peroxidation products and lipid mediators. Changes in the level of lipid mediators in patients with co-infections after treatment suggest further intensification of metabolic disturbances rather than their resolution.

Tick-borne infections as a cause of heart transplantation.

Many bacterial species can be a cause of various heart diseases, such as: Borrelia burgdorferi sensu lato, Coxiella burnetii and Bartonella spp. The aim of the present studies was to establish if any tick-borne infections can contribute to serious heart disorders resulting in the need for heart transplantation. Myocardium, aortic and mitral valve samples from hearts removed from patients undergoing heart transplantation were tested. The presence of Bartonella spp., Borrelia afzeli and C. burnetii bacteria in malfunctioning human hearts has been shown. DNA of Bartonella spp., B. burgdorferi and C. burnetii were detected in various parts of tested hearts. DNA of B. afzelii and Bartonella spp. were found in the aortic valves. DNA of C. burnetii was detected in the myocardium. Mixed infections with Bartonella spp. and C. burnetii were also observed. Obtained results indicate that diagnosis of Bartonella spp., B. burgdorferi C. burnetii and Rickettsia spp. infections should be considered in cases of infectious endocarditis with negative blood cultures.

Identification of a new orthonairovirus associated with human febrile illness in China.

The genus Orthonairovirus, which is part of the family Nairoviridae, includes the important tick-transmitted pathogens Crimean-Congo hemorrhagic fever virus and Nairobi sheep disease virus, as well as many other poorly characterized viruses found in ticks, birds and mammals1,2. In this study, we identified a new orthonairovirus, Songling virus (SGLV), from patients who reported being bitten by ticks in Heilongjiang Province in northeastern China. SGLV shared similar genomic and morphological features with orthonairoviruses and phylogenetically formed a unique clade in Tamdy orthonairovirus of the Nairoviridae family. The isolated SGLV induced cytopathic effects in human hepatoma cells in vitro. SGLV infection was confirmed in 42 hospitalized patients analyzed between 2017 and 2018, with the main clinical manifestations being headache, fever, depression, fatigue and dizziness. More than two-thirds (69%) of patients generated virus-specific antibody responses in the acute phase. Taken together, these results suggest that this newly discovered orthonairovirus is associated with human febrile illness in China.