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.

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.

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.

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.

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.

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.

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.

Scrotal tick damage as a cause of infertility in communal bulls in Moretele, South Africa.

Calving rate in communal cattle influences both food security and socio-economics in rural households. A previous study indicated that scrotal damage caused by ticks could affect the fertility of communal bulls and reduce the annual calving rate. The objectives of the study were to investigate the annual calving rate in communal herds by counting calves during herd visits, perform breeding soundness examinations on bulls and identify adult ticks attached to their genitalia. This prospective longitudinal survey was based on participatory rural appraisal. Calving rates were estimated in cows (n = 2398) from 100 randomly selected communal herds in Moretele over 12 months in 2013, during routine visits by animal health technicians. Randomly selected bulls (n = 50) from these herds were tested for Brucella abortus, Trichomonas foetus and Campylobacter fetus subspecies venerealis. The calving rate was 35.86% (0.359). The mean scrotal circumference was 37.63 ± 3.42 cm. Total sperm motility was 78.73 ± 35.73%; progressive sperm motility was 27.39 ± 15.81% and non-progressive sperm motility was 51.34 ± 19.92%. Thirty-five of the 38 bulls examined for breeding soundness exhibited severe scrotal and preputial lesions caused by the adult ticks Amblyomma hebraeum and Hyalomma rufipes. Tick control methods used included spraying (n = 20), pour-on (n = 11), no control (n = 1) and various (n = 18). It was concluded that in Moretele genital tick damage had a more serious impact on the fertility of communal bulls than contagious diseases. Targeted acaricidal spot treatment of the genitalia of communal bulls to prevent infestation is recommended, as tick control strategies used by farmers appeared to be inadequate.

Case report: A patient coinfected by Borrelia burgdorferi sensu lato and spotted fever group Rickettsiae in Urumqi, China.

RATIONALE: Both Borrelia burgdorferi sensu lato and spotted fever group Rickettsiae (SFGR) are pathogens carried by ticks. There is a possibility of co-infection with these tick-borne diseases. PATIENT CONCERNS: Male patient, 63 years-of-age, admitted to hospital with skin rash presenting for 1 week and fever with cough and expectoration for 3 days before admission. DIAGNOSES: We diagnosed that the patient was co-infected by B burgdorferi sl and SFGR using laboratory test results and the patient's clinical manifestations. INTERVENTIONS: The patient started therapy with oral minocycline, then levofloxacin by intravenous injection for SFGR. Meanwhile, he was treated with penicillin G sodium, cefoperazone sulbactam sodium and ceftriaxone by intravenous injection for B burgdorferi sl. OUTCOMES: After the patient was in stable condition, he was discharged from hospital. LESSONS: This case report highlights the possibility of co-infection by 2 tick-borne diseases in Urumqi, Xinjiang Uygur Autonomous Region, China. The antibiotic therapy should be based on the detection of pathogenic bacteria, and the different susceptibilities of co-infecting bacteria should be considered.

Tick-borne pathogens Bartonella spp., Borrelia burgdorferi sensu lato, Coxiella burnetii and Rickettsia spp. may trigger endocarditis.

BACKGROUND: Infections caused by tick-borne pathogens such as Bartonella spp., Borrelia burgdorferi s.l., Coxiella burnetii, and Rickettsia spp. are capable of causing serious lesions of the mitral and aortic valves, leading to a need for valve replacement. OBJECTIVES: The aim of the study was to determine whether such cases are sporadic or frequent. An additional goal was to establish effective diagnostic methods to detect these infections. MATERIAL AND METHODS: The study involved 148 patients undergoing valve replacement. Blood samples were drawn for serological testing. Samples of the removed mitral and aortic valves were tested with polymerase chain reaction and immunohistochemical staining. RESULTS: Specific antibodies to Bartonella spp. were detected in 47 patients (31.7%) and in 1 of the healthy controls (1%) (p < 0.05). Antibodies to B. burgdorferi spirochetes were found in 18 of the patients (12.2%) and in 6 blood donors from the control group (5.8%) (p < 0.1). Antibodies to Rickettsia spp. were detected in 12 (8.1%) and to C. burnetii phase I and II antigens in the serum of 1 patient. All the participants in the control group were seronegative to C. burnetii and Rickettsia spp. antigens. Polymerase chain reaction (PCR) tests for detection of Bartonella spp., B. burgdorferi s.l., C. burnetii and Rickettsia spp. DNA in the valve samples were all negative. Inflammation foci with mononuclear lymphoid cells in the aortic and mitral valves were seen in sections stained with hematoxiline and eozine. In sections dyed using the indirect immunofluorescence method with hyperimmune sera, Bartonella spp. and Rickettsia spp. were found. CONCLUSIONS: The results obtained indicate that laboratory diagnostics for patients with heart disorders should be expanded to include tests detecting tick-borne zoonoses such as bartonelloses, Lyme borreliosis, rickettsioses and Q fever.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis.

The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline, ceftriaxone, or amoxicillin for 28 days. Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them.

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.).

Investigation into the α-Gal Syndrome: Characteristics of 261 Children and Adults Reporting Red Meat Allergy.

BACKGROUND: Red meat allergy has historically been understood as a rare disease of atopic children, but the discovery of the "α-Gal syndrome," which relates to IgE to the oligosaccharide galactose-α-1,3-galactose (α-Gal), has challenged that notion. OBJECTIVE: To describe the clinical and immunologic characteristics of a large group of subjects with self-reported allergy to mammalian meat. METHODS: This was an observational study of 261 children and adults (range, 5-82 years) who presented for evaluation for allergic reactions to mammalian meat. Results were based on serum assays and a detailed questionnaire. RESULTS: α-Gal specific IgE ≥ 0.35 IU/mL was detected in 245 subjects and symptom onset occurred ≥2 hours after eating mammalian meat in 211 (81%). Component testing supported a diagnosis of α-Gal syndrome in 95%, pork-cat syndrome in 1.9%, and primary beef allergy in 1.1%. Urticaria was reported by 93%, anaphylaxis by 60%, and gastrointestinal symptoms by 64%. Levels of IgE and IgG specific to α-Gal were similar in subjects who reported early- or delayed-onset symptoms, and in those with and without anaphylaxis. Levels of α-Gal specific IgE and severity of reactions were similar among those with and without traditional atopy, and among children (n = 35) and adults (n = 226). Blood group B trended toward being under-represented among α-Gal-sensitized subjects; however, α-Gal specific IgE titers were high in symptomatic cases with B-antigen. CONCLUSIONS: The α-Gal syndrome is a regionally common form of food allergy that has a characteristic but not universal delay in symptom onset, includes gastrointestinal symptoms, can develop at any time in life, and is equally common in otherwise nonatopic individuals.

Severe fever with thrombocytopenia syndrome can masquerade as hemorrhagic fever with renal syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with a high fatality rate and high frequency of person-to-person transmission and is caused by SFTSV, a tick-borne Phlebovirus. Because SFTS has similar clinical manifestations and epidemic characters (such as spatial and temporal distributions) with hemorrhagic fever with renal syndrome (HFRS) in China, we reason that SFTS patients might be misdiagnosed as HFRS. METHODOLOGY/PRINCIPAL FINDINGS: Acute-phase sera of 128 clinically diagnosed HFRS patients were retrospectively analyzed for Hantavirus IgM antibodies with ELISA. Hantavirus-negative patients' sera were further analyzed for SFTSV IgM antibodies with ELISA. ELISA showed that 73 of 128 (57.0%) of clinically diagnosed HFRS patients were IgM antibody positive to Hantaviruses. Among the 55 Hantavirus-IgM negative patients, four (7.3%) were IgM antibody positive to SFTSV. The results indicated that the four SFTS patients were misdiagnosed as HFRS. The misdiagnosed SFTS patients had clinical manifestations common to HFRS and were unable to be differentiated from HFRS clinically. CONCLUSIONS: Our study showed that SFTS patients could be clinically misdiagnosed as HFRS. The misdiagnosis of SFTS as HFRS causes particular concern because it may increase the risk of death of SFTS patients and person-to-person transmission of SFTSV without proper care for and isolation of SFTS patients.

Combining primary care surveillance and a meta-analysis to estimate the incidence of the clinical manifestations of Lyme borreliosis in Belgium, 2015-2017.

Lyme borreliosis (LB) is an important tick-borne disease which can cause a broad range of symptoms mainly affecting the skin, the nervous system and the joints. This study aims to estimate the incidence of the different clinical manifestations of LB in Belgium. The incidence of erythema migrans (EM) was estimated through the network of sentinel general practices at 97.6/100,000 inhabitants (uncertainty interval [UI] 82.0-113.0) for the period 2015-2017. This result was used to estimate the incidence of other LB manifestations based on their proportional distribution (ratios) to EM reported in the neighboring countries of Belgium. To estimate these ratios, we performed a systematic review of studies published between February 1, 2008 and January 31, 2018 and pooled the results using a random effects meta-analysis. Six studies were retained in the systematic review, and the meta-analysis estimated the occurrence ratios for Lyme neuroborreliosis/EM, Lyme arthritis/EM and other manifestations/EM at 0.024 (95% confidence interval [CI] 0.016-0.037), 0.022 (95% CI 0.020-0.024) and 0.014 (95% CI 0.012-0.016) respectively. Applying these ratios to the EM incidence in Belgium resulted in an incidence estimation of 2.4/100,000 inhabitants (95% UI 1.5-3.7) for Lyme neuroborreliosis, 2.1/100,000 (95% UI 1.7-2.6) for Lyme arthritis and 1.4/100,000 (95% UI 1.1-1.7) for other less frequent manifestations. Some of these LB manifestations, other than EM, are more severe, hence these estimates are essential to assess the health burden and economic cost of LB which would be highly relevant for patients, healthcare providers and policymakers. As both over- and underestimation of different clinical LB manifestations remain possible due to characteristics of the primary surveillance systems and the disease itself, future studies to validate these estimates would be of great value.

Comorbid infections induce progression of visceral leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL) is a vector borne zoonotic disease endemic in humans and dogs in Brazil. Due to the increased risk of human infection secondary to the presence of infected dogs, public health measures in Brazil mandate testing and culling of infected dogs. Despite this important relationship between human and canine infection, little is known about what makes the dog reservoir progress to clinical illness, significantly tied to infectiousness to sand flies. Dogs in endemic areas of Brazil are exposed to many tick-borne pathogens, which are likely to alter the immune environment and thus control of L. infantum. RESULTS: A cross-sectional study of 223 dogs from an area of Natal, in the Rio Grande do Norte, Brazil, were studied to determine the association between comorbid tick-borne disease and Leishmania infection in this endemic area. The risk of Leishmania seropositivity was 1.68× greater in dogs with tick-borne disease seropositivity compared to those without (Adjusted RR: 1.68, 95% CI: 1.09-2.61, P = 0.019). A longitudinal study of 214 hunting dogs in the USA was conducted to determine the causal relationship between infection with tick-borne diseases and progression of VL. Hunting dogs were evaluated three times across a full tick season to detect incident infection with tick-borne diseases. A logistic regression model with generalized estimating equations to estimate the parameters was used to determine how exposure to tick-borne disease altered VL progression over these three time points when controlling for other variables. Dogs infected with three or more tick-borne diseases were 11× more likely to be associated with progression to clinical VL than dogs with no tick-borne disease (Adjusted RR: 11.64, 95% CI: 1.22-110.99, P = 0.03). Dogs with exposure to both Leishmania spp. and tick-borne diseases were five times more likely to die during the study period (RR: 4.85, 95% CI: 1.65-14.24, P = 0.0051). CONCLUSIONS: Comorbid tick-borne diseases dramatically increased the likelihood that a dog had clinical L. infantum infection, making them more likely to transmit infection to sand flies and people. As an important consequence, reduction of tick-borne disease exposure through topical or oral insecticides may be an important way to reduce progression and transmissibility of Leishmania infection from the canine reservoir to people.

Somatic symptoms and fatigue in a Norwegian population with high exposure to ticks.

BACKGROUND: It is heavily debated whether tick-borne infections cause chronic subjective health complaints. If the hypothesis of a major causal connection is true, one would expect to find more subjective health complaints in a population with high exposure to ticks than in a population with less exposure. In the current study we aimed to assess somatic symptoms and fatigue in a Norwegian population with high exposure to ticks, compare our findings to normative data, and assess predictors of somatic symptom load. MATERIAL AND METHODS: All individuals aged 18-69 years with residential address in Søgne municipality in southern Norway were in the period June 2015 to June 2016 invited to participate in the study. Somatic symptoms were assessed by the Patient Health Questionnaire-15 (PHQ-15) and fatigue by the Fatigue Severity Scale (FSS). A multivariable regression analysis was performed to assess predictors of somatic symptom load. RESULTS: Out of 7424 invited individuals, 2971 (40.0%) returned the questionnaire. 85.1% of 2950 responders reported exposure to tick-bite. PHQ-15 mean sum score was 5.3, and 16.5% reported moderate to severe somatic symptom load (i.e. ≥ 10). FSS mean score was 3.2, and 29.8% scored above the cut-off value for fatigue (i.e. ≥ 4.0). All gender and age groups in our study population had equal or lower mean sum score on PHQ-15 than reported in Swedish normative data, and lower mean score on FSS than reported in Norwegian normative data. In multivariable regression the following factors were associated with higher somatic symptom load (listed in order of descending beta coefficient): Anxiety and depression, number of other diseases, female gender, younger age, recruitment when visiting general practitioner's office, ≤ 6 years education after primary school, tick-bite earlier in life, erythema migrans earlier in life, less physical activity, and modern health worries. CONCLUSION: The study population reported high exposure to tick-bites, but less or equal level of somatic symptoms and less fatigue than found in normative data. There was a weak association between somatic symptom load and exposure to tick-bite and erythema migrans, possibly related to selection bias. Our findings do not support the hypothesis of a major causal connection between tick-borne infections and subjective health complaints.