Rickettsial infections are an unlikely cause of peripheral facial palsy in Southern Jutland, Denmark.

INTRODUCTION: Several infectious aetiologies have been associated with peripheral facial palsy, among others Herpes viridae and Borrelia burgdorferi and, rarely, cases of rickettsiosis. In this study, we prospectively included 19 patients with peripheral facial palsy from the Department of Neurology, University Hospital of Southern Denmark, and 29 healthy controls to examine infectious causes and risk factors of peripheral facial palsy. METHODS: Patients and controls completed a questionnaire regarding exposures, and the patients' medical files were examined. Serum from patients and controls were tested for antibodies against B. burgdorferi, Rickettsia felis and Rickettsia helvetica. Cerebrospinal fluids were tested using polymerase chain reaction for the presence of herpes simplex virus 1 and 2, herpes zoster virus and spotted fever group rickettsial DNA and for intrathecal production of antibodies against B. burgdorferi with an antibody index test. RESULTS: One patient was diagnosed with peripheral facial palsy associated with neuroborreliosis with a positive antibody index test but had a negative serological analysis. No patients had evidence of herpes or rickettsial infection. Fourteen out of the 19 patients had symptom onset in the winter months. Preceding myalgia was the only significant difference in symptoms between patients and controls (p = 0.011). CONCLUSION: Rickettsiosis is unlikely as a common cause of facial palsy in Southern Jutland, Denmark. FUNDING: The study was supported financially by the Knud and Edith Eriksen Mindefond and the Region of Southern Denmark. TRIAL REGISTRATION: The study population and the control group were approved by the Regional Committees on Health Research Ethics for Southern Denmark (S-20170136 and S-20170049) and by the Danish Data Protection Agency (17/31901 and 18/28928). All participants provided informed consent before their enrollment in the study.

Profile of Neurological Manifestations in Children Presenting with Rickettsial Disease.

OBJECTIVE: To study the profile of neurological manifestation of rickettsial disease in children. METHODS: Review of hospital records was done in a tertiary care hospital for the period from January to December, 2020. Data of all the children fulfilling the inclusion criteria i.e., clinical criteria and serology were retrieved from the hospital records. RESULTS: Of the total 7974 children admitted over this period, 178 were diagnosed with rickettsial disease wherein 54 (33.3%) had neurological involvement. Convulsions (59%), altered sensorium (56%), headache (44%), meningeal signs (37%), ataxia, (11%), lateral rectus palsy (7.5%) and stroke (7.5%) were the major neurological manifestations. Cerebrospinal fluid (CSF) analysis done in 30 (55%) children showed pleocytosis [median (IQR) cells 15 (3.75, 50)] with lymphocyte predominance [median (IQR) lymphocytes 11.5 (3, 38.75)] and elevated proteins [median IQR 41.5 (29.75,61)]. Neuroimaging abnormalities noticed were cerebral edema (n=7), cerebellar hyperintensities (n=5), basal ganglia infarcts (n=2) and hippocampal hyperintensities (n=1). CONCLUSION: Early recognition of rickettsial infection as a cause of neurological manifestation would facilitate early specific management.

A tick bite patient with fever and meningitis co-infected with Rickettsia raoultii and Tacheng tick virus 1: a case report.

BACKGROUND: Increasing numbers of tick-borne pathogens are being discovered, including those that infect humans. However, reports on co-infections caused by two or more tick-borne pathogens are scarce. CASE PRESENTATION: A 38-year-old male farmer was bitten by a hard tick, presented with fever (37.7 °C), severe headache and ejection vomiting. Lumbar puncture was performed in the lateral decubitus. The cerebrospinal fluid (CSF) was clear, and analysis showed severe increased pressure (320 mm H2O), mild leukocytosis (126.0 × 106/L, mononuclear cells accounting for 73%) and elevated total protein concentration (0.92 g/L). Bacterial cultures of CSF and blood were negative. The diagnosis of Rickettsia raoultii and Tacheng tick virus 1 (TcTV-1) co-infection was confirmed by amplifying four rickettsial genetic markers and the partial small (S) RNA segment of TcTV-1 from the patient's blood. The patient gradually recovered after treatment with levofloxacin and ribavirin. CONCLUSIONS: This is the first reported co-infection case with fever and meningitis caused by R. raoultii and TcTV-1. It is vital to screen for multiple pathogens in tick-bitten patients, especially in those with severe complex symptoms.

Rickettsia burneti and Brucella melitensis co-infection: a case report and literature review.

Rickettsia is the pathogen of Q fever, Brucella ovis is the pathogen of brucellosis, and both of them are Gram-negative bacteria which are parasitic in cells. The mixed infection of rickettsia and Brucella ovis is rarely reported in clinic. Early diagnosis and treatment are of great significance to the treatment and prognosis of brucellosis and Q fever. Here, we report a case of co-infection Rickettsia burneti and Brucella melitensis. The patient is a 49-year-old sheepherder, who was hospitalized with left forearm trauma. Three days after admission, the patient developed fever of 39.0°C, accompanied by sweating, fatigue, poor appetite and headache. Indirect immunofluorescence (IFA) was used to detect Rickettsia burneti IgM. After 72 hours of blood culture incubation, bacterial growth was detected in aerobic bottles, Gram-negative bacilli were found in culture medium smear, the colony was identified as Brucella melitensis by mass spectrometry. Patients were treated with doxycycline (100 mg bid, po) and rifampicin (600 mg qd, po) for 4 weeks. After treatment, the symptoms disappeared quickly, and there was no sign of recurrence or chronic infection. Q fever and Brucella may exist in high-risk practitioners, so we should routinely detect these two pathogens to prevent missed diagnosis.

Granulomatous mastitis caused by Rickettsia species.

Granulomatous mastitis is a rare inflammatory disease of varying etiology. Tuberculosis and cystic neutrophilic granulomatous mastitis caused by Corynebacterium are the best-established infectious examples. Despite the increasing incidence of Rickettsia-related diseases worldwide, granulomatous inflammation of breast parenchyma caused by Rickettsia has not yet been reported. We present a unique case of bilateral granulomatous mastitis documented with mammography, magnetic resonance imaging and core-needle biopsy. The rickettsial etiology of the disease was proved with specific immunohistochemistry and confirmed with DNA extraction, PCR and serology. The lesions completely resolved after a full-course tetracycline treatment. This case report widens the knowledge about the possible clinical manifestations of Rickettsia infection and adds a new bacterium to the list of etiological factors causing granulomatous mastitis.

Follow-up of a Rickettsia felis encephalitis: Some new insights into clinical and imaging features.

Rickettsia felis (R. felis) infection is a cause of unspecified encephalitis. However, the incidence has been underestimated due to the intracellular features of the pathogen and insufficient understanding of its clinical picture. This study reported a case of R. felis infection in a 26-year-old female who only manifested with certain neurological symptoms. With a lack of specific systemic inflammatory symptoms, the diagnosis was initially misdiagnosed as a brain glioma. However, a brain tissue biopsy showed prominent perivascular inflammatory infiltrations, which indicated inflammatory disease. Spinal fluid metagenomic next-generation sequencing (mNGS) was taken after ruling out other common infectious and autoimmune diseases. The results suggested R. felis infection, which was also supported by Weil-Felix reaction in the serum. After the diagnosis was corrected as R. felis encephalitis, the patient was successfully treated with doxycycline and had a good prognosis at the 1-year follow-up.

Quantitative Proteomics of the Endothelial Secretome Identifies RC0497 as Diagnostic of Acute Rickettsial Spotted Fever Infections.

Mediterranean spotted fever is a reemerging acute tick-borne infection produced by the α-proteobacterium, Rickettsia conorii. Rickettsia conorii infects vascular endothelial cells producing disseminated plasma leakage, manifesting as nonspecific fever, headache, and maculopapular rash. Because there are no available tests of early infection, Mediterranean spotted fever is often undiagnosed and untreated, resulting in significant mortality. To address this critical need, we have applied a quantitative proteomics pipeline for analyzing the secretome of primary human umbilical vein endothelial cells. Of the 104 proteins whose abundance changed significantly in the R. conorii-infected human umbilical vein endothelial cells' secretome, 46 proteins were up-regulated: 45 were host secreted proteins (including cytokines), and 1 was a rickettsial protein, the putative N-acetylmuramoyl-l-alanine amidase RC0497. Proteins with sequence highly homologous to RC0497 were found to be shared by many species of the spotted fever group rickettsiae, but not typhus group rickettsiae. Quantitative targeted proteomics studies of plasma from a mouse model of sublethal and lethal R. conorii identified RC0497 in the blood, and its circulating levels were proportionally associated with infection outcome. Finally, the presence of RC0497 in the serum samples from a cohort of humans presenting with acute rickettsioses was confirmed. The detection of RC0497 has the potential to be a sensitive and specific marker for acute rickettsial spotted rickettsioses.

Hospital based serological evidence of rickettsial diseases and assessment diagnostic tests of pyrexia of unknown origin.

The present study examined hospital-based serological tests of rickettsial infections and assessment for diagnosis of pyrexia of unknown origin (PUO). Blood samples were tested for Weil Felix antigens, ELISA for scrub typhus group and polymerase chain reaction (PCR) to detect the presence of DNA of spotted and scrub typhus group with the help of specific oligonucleotide. We tested 450 patient samples and found 101 Weil Felix-positive with 15 having ≥320 titres. IgM ELISA identified 32 (7.1%) positive cases. Positive PCR was seen in 13 (2.9%) samples, being only 40.1% of those testing positive for ELISA. Rickettsial infection is predominantly diagnosed through serological evidence in combination with molecular techniques. The Weil Felix test has a number of disadvantages and tends to provide false-positive results in a number of scenarios, especially where scrub typhus and spotted fever are widely distributed.

A case with neurological abnormalities caused by Rickettsia raoultii in northwestern China.

BACKGROUND: The number of new rickettsial species are rapidly increasing, and increasing numbers of Rickettsia raoultii (R. raoultii) infection cases have been detected in humans. However, neurological abnormalities caused by R. raoultii are rarely reported, especially in northwestern China. CASE PRESENTATION: A 36-year-old Kazakh shepherd with an attached tick on part temporalis, presented with right eyelid droop, lethargy, fever, headache, fever (38.0-41.0 °C) and erythematous rash. The examination of cerebrospinal fluid (CSF) showed cerebrospinal pressure of 200 mm H2O, leukocyte count of 300.0 × 106/L, adenosine deaminase of 2.15 U/L, and total protein concentration of 0.93 g/L. The diagnosis of R. raoultii infection was confirmed by six genetic markers, and semi-quantified by enzyme-linked immunosorbent assay for rickettsial antigen. The patient gradually recovered after treatment with doxycycline and ceftriaxone. R. raoultii DNA was found both in a tick detached from this patient and in 0.18% (2/1107) of blood samples collected from local shepherds. CONCLUSIONS: This is the first reported case with neurological abnormalities caused by R. raoultii in northwestern China. It is vital to detect rickettsial agents both in blood and CSF for tick bite patients with neurological abnormalities. Public health workers and physicians should pay attention to neurological abnormalities caused by Rickettsia.

When to Think of Rickettsia.

Rickettsiae are globally encountered pathogens with foci of endemicity and epidemic exacerbations under circumstances of crowding and decline of sanitation. Diagnosis is often missed due to misconceptions about epidemiology, confusing terminology and nonspecific clinical presentation. Rickettsioses should be considered in children with febrile illnesses exceeding the usual duration of a viral infection, in particular in children with rash, lymphadenopathy and nearly normal first-line laboratory tests, who reside in or return from endemic areas, recall a compatible contact history, have a constellation of symptoms starting after an arthropod bite, live under troubled social circumstances, or are part of a cluster of similar cases.

[Clinical features and etiologies of acute neuroretinitis in southern Tunisia]. / Profil clinique et étiologique des neurorétinites aiguës dans le sud tunisien.

INTRODUCTION: The diagnosis of neuroretinitis is clinical, with optic nerve involvement and a macular star. The most common etiology is cat scratch disease. MATERIALS AND METHODS: Study of 7 patients (7 eyes) with neuroretinitis. A complete ophthalmic examination, fluorescein angiography and optical coherence tomography were performed for all patients. A focused etiological work-up was conducted. RESULTS: The mean age of the patients was 41.6 years [27-51 years]. Decreased visual acuity was the most common reason for consultation. The neuroretinitis was unilateral in all cases. Subclinical serous retinal detachment was noted in 5 patients. The common etiologies were rickettsiosis (4 cases) and tuberculosis (1 case). Leber's idiopathic stellate neuroretinitis was concluded by the negativity of the etiological investigation. Doxycycline was the treatment of choice for rickettsiosis. CONCLUSION: Rickettsiosis appears to be more common than cat scratch disease as an etiology of neuroretinitis in the present study in southern Tunisia. Moreover, the clinical association of a serous retinal detachment, rarely reported in the literature, seems to be more frequent in our series.

Optical coherence tomography angiography features of retinitis post-rickettsial fever.

The intraocular manifestations of rickettisial retinitis include retinal vasculitis, maculopathy, optic neuritis, and neurosensory detachment. Extensive leakage of dye on the fundus fluorescein angiography may obscure visualization in eyes with retinitis. We report the vascular changes in eyes with rickettsial retinitis and its response to treatment using optical coherence tomography angiography. The microvascular abnormalities we noted were, capillary drop out areas corresponding to retinitis patches, vascular loops, and pruning of vessels. The choriocapillary slabs showed signal void areas. Post-treatment there was vascular remodeling with decrease in non-perfused area, appearance of new vascular lateral branching, and appearance of collaterals.

Severe leptospirosis in a patient with positive serological test for spotted fever rickettsiosis.

Here, we report a case of a 64-year-old man with severe leptospirosis infected in an area in Japan that is non-endemic to leptospirosis. Initially, findings of high-grade fever, mild generalised arthralgia, rashes on the trunk, mild thrombocytopenia, elevated liver enzymes and renal dysfunction led to the suspicion of rickettsiosis, which was an endemic infectious disease in the area. Subsequently, leptospirosis was also considered after carefully reviewing patient history, which revealed that he may have been exposed to mice urine. Finally, leptospirosis was diagnosed after the serum indicated a positive PCR for leptospirosis. Furthermore, due to serum antibody positivity for Rickettsia japonica, false-positivity or coinfection of spotted fever rickettsiosis was suspected. Despite the delayed diagnosis, the patient recovered with antibiotic treatment. Thus, to prevent diagnostic errors, leptospirosis should be potentially considered with high suspicion in patients with acute undifferentiated fever, even in non-endemic areas of leptospirosis.

Intra-aural tick bite causing unilateral facial nerve palsy in 29 cases over 16 years in Kandy, Sri Lanka: is rickettsial aetiology possible?

BACKGROUND: Over the last two decades intra-aural tick infestation (otoacariasis) has been a common occurrence in the hilly central region in Sri Lanka. Very occasional detection of isolated unilateral facial nerve palsy associated with otoacariasis attributed to toxin damage of the nerve prompted us to study the clinico-epidemiology and aetio-pathology of the problem. METHODS: All cases having isolated unilateral facial nerve palsy associated with otoacariasis presented to, Ear Nose and Throat clinic at General Hospital Kandy, Sri Lanka from 2001 to 2016 were included in the study. The facial palsies were assessed with nerve conduction studies and, harvested ticks were identified. RESULTS: There were 29 patients with mean age of 46 years (range 22-76 years) with male to female ratio of 1:1.9. First 12 patients without specific treatment took 1-55 months for recovery and 4 had axonal degeneration. Last 5 patients were treated with doxycycline and recovered in 4 weeks. They had strong sero-conversion of immunofluorescence antibodies against spotted fever rickettsioses and the tick harvested from the last patient was PCR positive for rickettsial DNA. Identified ticks belonged to Dermacentor, Amblyomma, Rhipicephalus and Hyalomma species. CONCLUSIONS: On contrary to popular toxin theory, we were able to demonstrate treatable rickettsial aetio-pathology as the cause of otoacariasis associated lower motor facial palsy in Sri Lanka.

Infections and the kidney: a tale from the tropics.

Tropical infections are caused by a variety of bacteria, viruses and parasitic organisms across varying geographical regions and are more often reported in adults than in children. Most of the infections are acute, presenting as a febrile illness with involvement of multiple organ systems, including the kidney. The gamut of renal manifestations extends from asymptomatic urinary abnormalities to acute kidney injury and-albeit rarely-chronic kidney disease. Tropical infections can involve the glomerular, tubulointerstitial and vascular compartments of the kidney. Leptospirosis, malaria, dengue, rickettsial fever and schistosomiasis are the most prevalent tropical infections which affect the kidneys of children living in the tropics. In this review we discuss renal involvement in these most prevalent tropical infections.