Rare Infectious Agent Research Articles

Exploring viral diversity and metagenomics in livestock: insights into disease emergence and spillover risks in cattle.

Cattle have a significant impact on human societies in terms of both economics and health. Viral infections pose a relevant problem as they directly or indirectly disrupt the balance within cattle populations. This has negative consequences at the economic level for producers and territories, and also jeopardizes human health through the transmission of zoonotic diseases that can escalate into outbreaks or pandemics. To establish prevention strategies and control measures at various levels (animal, farm, region, or global), it is crucial to identify the viral agents present in animals. Various techniques, including virus isolation, serological tests, and molecular techniques like PCR, are typically employed for this purpose. However, these techniques have two major drawbacks: they are ineffective for non-culturable viruses, and they only detect a small fraction of the viruses present. In contrast, metagenomics offers a promising approach by providing a comprehensive and unbiased analysis for detecting all viruses in a given sample. It has the potential to identify rare or novel infectious agents promptly and establish a baseline of healthy animals. Nevertheless, the routine application of viral metagenomics for epidemiological surveillance and diagnostics faces challenges related to socioeconomic variables, such as resource availability and space dedicated to metagenomics, as well as the lack of standardized protocols and resulting heterogeneity in presenting results. This review aims to provide an overview of the current knowledge and prospects for using viral metagenomics to detect and identify viruses in cattle raised for livestock, while discussing the epidemiological and clinical implications.

Clinical applications of metagenomic next-generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study

BackgroundThis study aimed to evaluate the application of metagenomic next-generation sequencing (mNGS) technology to identify pathogens in periprosthetic joint infection (PJI).MethodsA retrospective analysis was conducted on 65 patients suspected of having PJI between April 2020 and July 2023. The patients were categorized into PJI (46 patients) and non-PJI (19 patients) groups based on the 2018 International Consensus Meeting criteria. Clinical data were collected, and both conventional bacterial culture and mNGS were performed. The diagnostic performance of the two methods was compared and analyzed.ResultsmNGS exhibited a sensitivity of 89.13%, a specificity of 94.74%, a positive predictive value of 97.62%, a negative predictive value of 78.26%, and an overall diagnostic accuracy of 90.77%. Compared to microbial culture, mNGS demonstrated superior diagnostic sensitivity while maintaining similar specificity. A total of 48 pathogens were successfully identified using mNGS, with Coagulase-negative staphylococci, Streptococci, Staphylococcus aureus, and Cutibacterium acnes being the most common infectious agents. Notably, mNGS was used to identify 17 potential pathogens in 14 culture-negative PJI samples, highlighting its ability to detect rare infectious agents, including Cutibacterium acnes (n = 5), Granulicatella adiacens (n = 1), Mycobacterium tuberculosis complex (n = 1), and Coxiella burnetii (n = 1), among others, which are not detectable by routine culture methods. However, mNGS failed to detect the pathogen in 4 culture-positive PJI patients, indicating its limitations. Among the 46 PJI patients, 27 had positive culture and mNGS results. The results of mNGS were concordant with those of culture at the genus level in 6 patients with PJI and at the species level in 18 patients. Furthermore, the present study revealed a significantly greater proportion of Staphylococcus aureus in the sinus tract group (45.45%) than in the non-sinus tract group (14.29%), indicating the association of this pathogen with sinus formation in PJI (P = 0.03). Additionally, there was no significant difference in the occurrence of polymicrobial infections between the sinus tract group (27.27%) and the non-sinus tract group (33.33%) (P = 0.37).ConclusionsMetagenomic next-generation sequencing can serve as a valuable screening tool in addition to traditional culture methods to improve diagnostic accuracy through optimized culture strategies.

A Rare Agent in Wound Infection: Leclercia adecarboxylata

As a rare infectious agent, Leclercia adecarboxylata is a gram-negative bacillus belonging to the Enterobacteriaceae family. It can be isolated from human blood, sterile body fluids, sputum, urine, fecal, and wound samples. In this case report, the isolation of L. adecarboxylata as a causative agent in the wound and tissue sample cultures of a soft tissue infection that developed after arthrodesis surgery on the right foot of a 47-year-old female patient who was followed up with Charcot foot treatment due to diabetes in our hospital is presented. The patient's general condition was good, his leukocyte count was 6000/ml, leukocyte distribution was 58% neutrophil predominance, erythrocyte sedimentation rate was 105 mm/hour, and C-reactive protein level was 90 mg/L. Wound and tissue samples from the area considered to be the focus of infection were sent to our laboratory for culture examination. In the samples inoculated into routine identification media and subjected to standard incubation and identification procedures, a growth consisting of pure colonies (monomicrobial) was detected on the culture media. The isolate was identified as L. adecarboxylata by colony morphology, microscopic examinations (gram-negative bacilli), other basic identification procedures, and mass spectrometry (MALDI-TOF MS). Since it is a rare infectious agent, additional biochemical tests were performed; glucose-sucrose-lactose utilization, motility, indole production, and esculin hydrolysis tests were found to be positive, while oxidase, ornithine decarboxylase, hydrogen-sulfide production, citrate utilization, and urease tests were found to be negative. Antibiotic susceptibility tests were performed with the VITEK 2® automated system (Biomérieux, France), and the results were evaluated according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) v13.0 criteria. The isolate, which has a generally sensitive antibiotic profile, was evaluated as the infectious agent and the patient was treated with intravenous ampicillin/sulbactam for five days. The patient, whose laboratory values tended to improve (leukocyte count 4400/ml, neutrophil rate 52.9%), was discharged with peroral amoxicillin/clavulanic acid treatment.

16s rRNA-based phylogenetic analyses of Elizabethkingia anophelis: Detection of Elizabethkingia anophelis, a rare infectious agent from blood and determination of antibiotic susceptibility in Turkey

PurposeElizabethkingia anophelis was firstly isolated from the midgut of the Anopheles gambiae mosquito in 2011. After this year, it was isolated in some intensive care cases in Africa and Asia. This study, it was aimed to confirm the identification of E. anophelis in the blood of a pediatric patient. MethodsAfter the suspicious bacteria were grown on blood agar, MALDI-TOF MS and 16s rRNA gene sequencing methods were used to identify and an antibiotic susceptibility test was carried out by Vitek 2 Compact system according to the EUCAST. Finally, a phylogenetic tree was created based on the 16s rRNA gene region. ResultsThe isolate was identified as E. anophelis by both methods. It was found to be resistant to all beta-lactam antibiotics and also susceptible to ciprofloxacin and levofloxacin. According to the 16S rRNA-based phylogenetic tree, our isolate clustered within a branch containing other E. anophelis. ConclusionThese findings will guide clinicians in choosing which antibiotic to choose if they encounter this agent. Also, the clinicians should be vigilant against this agent, as it is a newly emerging infectious agent in Turkey.

A case report of isolated primary herpes-simplex virus neuroretinitis in an immunocompetent adult

BackgroundHerpes simplex virus (specifically HSV-1 and HSV-2) are greatly prevalent viruses that can cause conjunctivitis, keratitis and other rarer ocular disorders such as acute retinal necrosis syndrome or neuroretinitis. We report a case of an isolated unilateral neuroretinitis with primary HSV infection in an immunocompetent adult without other related clinical features.Case presentationA 60-year-old immunocompetent woman presented with sudden painless central vision loss in her left eye (best corrected visual acuity was 20/200) showing optic disc edema, submacular fluid and a delayed development of a macular star. The macular optical coherence tomography (OCT) showed a serous retinal detachment. Arterial hypertension or exposure to ionizing radiation were ruled out and the microbiological blood test battery was only positive for immunoglobulin M (IgM) for HSV-1 which allowed etiological treatment with oral valacyclovir. Complete resolution and good visual results were found within 3 months.ConclusionsThe present case of isolated neuroretinitis as a primary HSV infection in an immunocompetent patient was resolved with good functional results after valacyclovir treatment. Presence of HSV IgM in absence of other laboratory results could be enough evidence to start HSV treatment in immunocompetent patients with a macular star, as an isolated lesion, after ruling out other non-infectious causes, such as arterial hypertension or exposure to ionizing radiation. Rare infectious agents in immunocompetent patients must be considered in the differential diagnosis of neuroretinitis, even if there are no other typical symptoms or signs that could suggest the disease.

A Rare Cause of Meningitis : Pseudomonas stutzeri

Pseudomonas stutzeri (P. stutzeri) is a gram-negative, aerobic and saprophytic microorganism which found in soil, water and hospital environments. Isolation of bacteria from clinical samples usually refers to colonization rather than infection. However, it rarely causes serious infections. This report presents a 33-year-old male immunocompetent patient who developed P. stutzeri meningitis after cerebrospinal fluid (CSF) fistula operation. Although our case was considered mainly a hospital-acquired infection, the fact that the patient was a recycling employee raises suspicion about the source of the infectious agent. In the literature, four cases of meningitis caused by this microorganism have been identified. When these cases were examined, it was seen that three of them had underlying diseases and the other one had no comorbid disease, but he was older than 65 years. Although our patient is young and has no underlying disease or immunosuppression, the development of meningitis with P. stutzeri, a rare infectious agent, is remarkable. In conclusion, it should be kept in mind that rare agents such as P. stutzeri may be the cause of hospital-acquired meningitis.

Characteristics of Immune Memory and Effector Activity to Cancer-Expressed MHC Class I Phosphopeptides Differ in Healthy Donors and Ovarian Cancer Patients.

Elevated immunity to cancer-expressed antigens can be detected in people with no history of cancer and may contribute to cancer prevention. We have previously reported that MHC-restricted phosphopeptides are cancer-expressed antigens and targets of immune recognition. However, the extent to which this immunity reflects prior or ongoing phosphopeptide exposures was not investigated. In this study, we found that preexisting immune memory to cancer-expressed phosphopeptides was evident in most healthy donors, but the breadth among donors was highly variable. Although three phosphopeptides were recognized by most donors, suggesting exposures to common microbial/infectious agents, most of the 205 tested phosphopeptides were not recognized by peripheral blood mononuclear cells (PBMC) from any donor and the remainder were recognized by only 1 to 3 donors. In longitudinal analyses of 2 donors, effector immune response profiles suggested active reexposures to a subset of phosphopeptides. These findings suggest that the immunogens generating most phosphopeptide-specific immune memory are rare infectious agents or incipient cancer cells with distinct phosphoproteome dysregulations, and that repetitive immunogenic exposures occur in individual donors. Phosphopeptide-specific immunity in PBMCs and tumor-infiltrating lymphocytes from ovarian cancer patients was limited, regardless of whether the phosphopeptide was expressed on the tumor. However, 4 of 10 patients responded to 1 to 2 immunodominant phosphopeptides, and 1 showed an elevated effector response to a tumor-expressed phosphopeptide. As the tumors from these patients displayed many phosphopeptides, these data are consistent with lack of prior exposure or impaired ability to respond to some phosphopeptides and suggest that enhancing phosphopeptide-specific T-cell responses could be a useful approach to improve tumor immunotherapy.

Madura Foot that Presented like Soft Tissue Sarcoma

79 years old female agricultural worker in a farm gardening and taking care of farm animals from Al- Baha western region in Saudi Arabia presented with a 7-year history of left plantar foot soft tissue mass. According to the patient, the swelling had gradually increased in size over a few years, but it was painless and thus had not restricted him from continuing to farm until the lesion started to affect mobility. An X-ray, MRI, and histopathology reported a rare infectious agent Antinomies spp, otherwise referred to as Madura foot. Three-dimensional CT aided in a preoperative surgical plan which included mass excision/ debunking for this challenging lesion. Patient required prolonged anti-infective therapy (> 4 months) after follow the patient improved and not has any pain or recurrence of lesion or infection.

Reactive Arthritis Update: Spotlight on New and Rare Infectious Agents Implicated as Pathogens.

Purpose of ReviewThis article presents a comprehensive narrative review of reactive arthritis (ReA) with focus on articles published between 2018 and 2020. We discuss the entire spectrum of microbial agents known to be the main causative agents of ReA, those reported to be rare infective agents, and those reported to be new candidates causing the disease. The discussion is set within the context of changing disease terminology, definition, and classification over time. Further, we include reports that present at least a hint of effective antimicrobial therapy for ReA as documented in case reports or in double-blind controlled studies. Additional information is included on microbial products detected in the joint, as well as on the positivity of HLA-B27.Recent FindingsRecent reports of ReA cover several rare causative microorganism such as Neisseria meningitides, Clostridium difficile, Escherichia coli, Hafnia alvei, Blastocytosis, Giardia lamblia, Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica/dispar, Strongyloides stercoralis, β-haemolytic Streptococci, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Mycobacterium bovis bacillus Calmette-Guerin, and Rickettsia rickettsii. The most prominent new infectious agents implicated as causative in ReA are Staphylococcus lugdunensis, placenta- and umbilical cord–derived Wharton’s jelly, Rothia mucilaginosa, and most importantly the SARS-CoV-2 virus.SummaryIn view of the increasingly large spectrum of causative agents, diagnostic consideration for the disease must include the entire panel of post-infectious arthritides termed ReA. Diagnostic procedures cannot be restricted to the well-known HLA-B27-associated group of ReA, but must also cover the large number of rare forms of arthritis following infections and vaccinations, as well as those elicited by the newly identified members of the ReA group summarized herein. Inclusion of these newly identified etiologic agents must necessitate increased research into the pathogenic mechanisms variously involved, which will engender important insights for treatment and management of ReA.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11926-021-01018-6.

Distribution of Underlying Causative Organisms, Patient Age, and Survival in Spontaneous spondylodiscitis with Special Focus on Elderly Patients.

spondylodiscitis is becoming a more frequently encountered diagnosis in our clinical practice. Multimorbid and especially older patients build up a relevant portion of cases. The goal of our study was to evaluate our clinical data and to reveal specifics concerning elderly patients with spontaneous spondylodiscitis. We retrospectively analyzed clinical data for the years from 2012 to 2014. The search was conducted on the basis of the International Classification of Diseases, 10th Revision (ICD-10) diagnoses for spondylodiscitis. Postoperative infections were not included in this study. All cases were evaluated in terms of infectious agents (in blood culture and/or computerized tomography [CT]-guided or surgical biopsy), age, and overall survival. Fifty-one patients with spontaneous spondylodiscitis were identified. The most frequent pathogen was methicillin-sensitive Staphylococcus aureus (MSSA; n = 21; 41.17%). Escherichia coli and S. epidermidis were each found in four patients each (7.84%). Methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, and S. hominis were found in three cases (5.88%). Other bacteria were found in one case (each 1.96 %). In 12 cases, there was no bacteria growth (23.53%). One of these patients revealed to have a tuberculosis infection, diagnosed after the study period (in 2015). Two-thirds of the patients were ≥65 years old (n = 34). All three patients with MRSA were >65 years old. Three of seven patients <50 years had IV drug abuse (42.86%). In these patients, rather rare infectious agents for spondylodiscitis were found (P. aeruginosa, S. hominis, Citrobacter). Mortality was 7.84% (n = 4). All of these patients were ≥67 years old, three of four (75%) were ≥75 years old. Our study of spontaneous spondylodiscitis showed a stronger representation of older patients (>65 years). Lethal outcome exclusively concerned the older age group. S. aureus was the most frequent pathogen as shown previously. MRSA infections might be more common in the older age group. Rare causative organisms mainly occurred in patients with iv drug abuse. Further evaluation through randomized multicenter studies focusing on the different subgroups and comorbidities in larger populations and correlation with appropriate treatment options is necessary.

Rare infectious agents in children with hematological disease

Rare infectious agents in children with hematological disease

Aortic valve endocarditis by a rare infectious agent in a patient with a rare congenital mitral valve abnormality.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Rare fungal infectious agents: a lurking enemy.

In the expanding population of immunocompromised patients and those treated in intensive care units, rare fungal infectious agents have emerged as important pathogens, causing invasive infections associated with high morbidity and mortality. These infections may present either as de novo or as breakthrough invasive infections in high-risk patients with hematologic malignancies receiving prophylactic or empirical antifungal therapy or in patients with central venous catheters. Diagnosis and treatment are challenging. Physicians should have a high index of suspicion because early diagnosis is of paramount importance. Conventional diagnostic methods such as cultures and histopathology are still essential, but rapid and more specific molecular techniques for both detection and identification of the infecting pathogens are being developed and hopefully will lead to early targeted treatment. The management of invasive fungal infections is multimodal. Reversal of risk factors, if feasible, should be attempted. Surgical debridement is recommended in localized mold infections. The efficacy of various antifungal drugs is not uniform. Amphotericin B is active against most yeasts, except Trichosporon, as well as against Mucorales, Fusarium, and some species of Paecilomyces and dimorphic fungi. The use of voriconazole is suggested for the treatment of trichosporonosis and scedosporiosis. Combination treatment, though recommended as salvage therapy in some infections, is controversial in most cases. Despite the use of available antifungals, mortality remains high. The optimization of molecular-based techniques, with expansion of reference libraries and the possibility for direct detection of resistance mechanisms, is awaited with great interest in the near future. Further research is necessary, however, in order to find the best ways to confront and destroy these lurking enemies.

A Case of Erythema Nodosum Associated withMycoplasma pneumoniaeInfection: Pathologic Findings and a Presumed Pathogenesis

결절성 홍반은 소아에서 가장 흔한 피하지방층의 염증으로 하지의 압통을 동반한 결절을 특징으로 한다. 이 질환은 다양한 원인에 의해 발생되지만 공통된 조직소견을 보여준다. 저자들은 임상적 소견 및혈청학적 방법으로 마이코플라즈마 폐렴균에 의한 결절성 홍반을 진단하였고 조직병리적인 접근을 통해 결절성 홍반의 면역병인에 대해 고찰해 보았다. 조직병리소견은 제 4형 면역반응 염증을 보였으며 이는 다양한 원인에 의한 결절성 홍반의 발생 기전을 이해하는데 도움을 줄 것이다.

Endocarditis and myocardial abscess caused by group B Streptococcus

Introduction: Group B Streptococcus (GBS) is a rare infectious endocarditis. Patients with GBS infective endocarditis have a high rate of local and systemic complications. Case presentation: A 30-year-old male presented to the Emergency Department with fever, chills, fatigue and a recent onset of symptoms suggestive of stroke following a bout of pyelonephritis. Echocardiography confirmed a diagnosis of endocarditis and blood cultures grew GBS. Antibiotic therapy was initiated with penicillin G and gentamicin. Urological evaluation revealed a urethral stricture. He was taken to the operating room on hospital day 10 for the debridement of his aortic annulus, reconstruction of his aortic root and replacement of his aortic valve. On post-operative day 7, he died of sudden cardiac arrest. A large myocardial abscess located within the interventricular septum was identified post-mortem. Conclusion: Recurrent or complicated urinary tract infections are rare among the young male population. Without evaluation and treatment for the underlying pathology, patients are at risk of developing antimicrobial-resistant infections, which may disseminate rapidly. Although a common pathogen of the urinary tract, GBS is a rare infectious agent for endocarditis. We propose urethral stricture as a risk factor for developing GBS endocarditis. Operative timing for these infections can be challenging; however, urgent and radical surgical debridement appears to yield favourable results.

Left thigh phlegmon caused by Nocardia farcinica identified by 16S rRNA sequencing in a patient with Leprosy: a case report

BackgroundIn recent years, Nocardia farcinica has been reported to be an increasingly frequent cause of localized and disseminated infections in the immunocompromised patient. However, recent literature is limited. We report a case of left thigh phlegmon caused by N. farcinica that occurred in a patient with Leprosy undergoing treatment with prednisone for leprosy reaction.Case presentationWe describe the case of left thigh phlegmon caused by Nocardia farcinica in a 54-year-old Italian man affected by multi-bacillary leprosy. The patient had worked in South America for 11 years. Seven months after his return to Italy, he was diagnosed with Leprosy and started multi-drug antibiotic therapy plus thalidomide and steroids. Then, during therapy with rifampicin monthly, minocycline 100 mg daily, moxifloxacin 400 mg daily, and prednisone (the latter to treat type 2 leprosy reaction), the patient complained of high fever associated with erythema, swelling, and pain in the left thigh. Therefore, he was admitted to our hospital with the clinical suspicion of cellulitis. Ultrasound examination and Magnetic Resonance Imaging showed left thigh phlegmon. He was treated with drainage and antibiotic therapy (meropenem and vancomycin replaced by daptomycin). The responsible organism, Nocardia farcinica, was identified by 16S rRNA sequencing in the purulent fluid taken out by aspiration. The patient continued treatment with intravenous trimethoprim/sulfamethoxazole and imipenem followed by oral trimethoprim/sulfamethoxazole and moxifloxacin. A whole-body computed tomography did not reveal dissemination to other organs like the lung or brain.The patient was discharged after complete remission. Oral therapy with trimethoprim/sulfamethoxazole, moxifloxacin, rifampicin monthly, clofazimine and thalidomide was prescribed to be taken at home. One month after discharge from the hospital the patient is in good clinical condition with complete resolution of the phlegmon.ConclusionN. farcinica is a rare infectious agent that mainly affects immunocompromised patients. Presentation of phlegmon only without disseminated infection is unusual, even in these kinds of patients. In any case, a higher index of suspicion is needed, as diagnosis can easily be missed due to the absence of characteristic symptoms and the several difficulties usually encountered in identifying the pathogen.

Nosocomial Leuconostoc Pseudomesenteroides Meningitis: A Case Report And Review Of The Literature

Leuconostoc spp, a member of the Streptococci family, was found to cause infection in humans in 1985. These infections have been reported in patients who had received vancomycin to treat their underlying diseases. Nosocomial meningitis caused by Leuconostoc spp. was diagnosed in our patient. An extraventricular drainage system catheter was used due to the presence of a thalamic hematoma with ventricular extension. Central nervous system infections due to Leuconostoc spp. are rare. To our knowledge, our case is the sixth case worldwide and the second case reported from Turkey. This case is reported here to draw attention to a rare infectious agent with a high mortality risk.

Therapie von Infektionen durch Schwärzepilze

Since dematiaceous fungi belong to the group of rare infectious agents causing mycoses, therapeutic recommendations are mainly deduced from observations of single cases. In cases of eumycetoma or focal phaeohyphomycoses of the central nervous system (e.g. caused by Cladophialophora bantiana or Exophiala dermatitidis) and in certain cases of chromoblastomycoses, the resection in toto is the therapy of choice, which may be accompanied by antimycotic medication. As antimycotic therapy ex juvantibus in case of phaeohy-phomycoses, a simultaneous application of itraconazole and 5-fluorocytosine is presently most promising. The success depends on an adequate duration of therapy.

Journal Not Un-Notted Up

To the Editor.— The title page of the article by Feman and Tilford 1 on ocular histoplasmosis exhibits two uses of double negative construction (not an uncommon cause and a rare infectious agent). Double negative terminology is gramatically annoying and semantically misleading. For example, the declaration that Tennessee Histoplasma capsulatum is not a rare infectious agent 1 is a gross understatement, since positive histoplasmin skin tests can be obtained in up to 90% of Tennessee residents. 2,3 Double negatives are commonly used as a dodge to avoid more accurate designations of probability or prevalence and should be avoided.