The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification.

PURPOSE: To analyse the demography, etiology, and classification of uveitis at a tertiary academic referral center. METHODS: An observational study was conducted on the archives of uveitic patients at the Ocular Inflammation Service of the Department of Ophthalmology at the University Hospital of Ioannina (Greece) from 1991 to 2020. This study aimed to investigate the epidemiological profile of patients, including their demographics and the main etiologic factors of uveitis. RESULTS: Out of 6191 cases with uveitis, 1925 were infectious, 4125 were non-infectious, and an overall of 141 masquerade syndromes were recorded. Among these cases, 5950 patients were adults, with a slight female predominance, while 241 were children (< 18 years old). Interestingly, 24.2% of cases (1500 patients) were associated with 4 specific microorganisms. Herpetic uveitis (HSV-1 and VZV/HZV) was the most common cause of infectious uveitis (14.87%), followed by toxoplasmosis (6.6%) and tuberculosis (2.74%). In 49.2% of non-infectious uveitis cases, no systematic correlation was found. The most frequent causes of non-infectious uveitis included sarcoidosis, white dot syndromes, ankylosing spondylitis, lens-induced uveitis, Adamantiades-Behçet disease, and idiopathic juvenile arthritis. Infectious uveitis was more common in the rural population, whereas non-infectious uveitis was more frequently recorded in the urban population CONCLUSIONS: Although our study was conducted on a predominantly white Caucasian population, it also reflects the effect of increasing immigration, improvements of diagnostic techniques, changes in referral patterns, and various actual changes in disease incidence.

The Large Hellenic Study of Uveitis: Diagnostic and Therapeutic Algorithms, Complications, and Final Outcome.

PURPOSE: The purpose of this study is to present the diagnostic and therapeutic algorithms, complications, and final outcome in the management of uveitic patients at a tertiary academic referral center. DESIGN: Observational study. METHODS: Analysis of the archives of 6191 uveitic patients at the Ocular Inflammation Service of the Department of Ophthalmology of the University Hospital of Ioannina in Greece from 1991 to 2020. RESULTS: During the 30 years of the study, the diagnostic ability climbed from 45.43% (1991-1995) to 73.4% (2016-2020). This improvement was linked to several factors including the increase in the number of diagnostic paracenteses for the analysis of intraocular fluids, the range and quality of laboratory blood tests, the multimodal ophthalmic imaging, the proper use of nonophthalmic imaging, and the multidisciplinary approach. The degree of uveitis-related complications was related to the severity and cause of inflammation, the recurrence rate, inappropriate treatment, and the prolonged or initially inactive inflammation. The 3 most common complications included cataract, macular edema, and glaucoma. Apart from the modern treatments and surgical techniques, the 3-month preoperative control of inflammation played a critical role in the surgical outcomes. The percentage of patients with a successful outcome increased from 72% (2001-2005) to 90.50% (2016-2020). The center's experience, prompt referral, patient's compliance, and regular follow-ups are associated with a better outcome. The analysis of the results allowed the development of diagnostic and therapeutic algorithms. CONCLUSIONS: Developing diagnostic and therapeutic algorithms allows for the efficient management of uveitis, leading to better visual outcome and therefore a better quality of life.

Spirochetal uveitis: Spectrum of clinical manifestations, diagnostic and therapeutic approach, final outcome and epidemiological data.

PURPOSE: Analysis of cases with spirochetal uveitis related to spirochetes in a tertiary referral academic center. METHODS: Retrospective study of patients diagnosed with uveitis attributed to Treponema pallidum, Leptospira spp. and Borrelia burgdorferi from June 1991 until December 2019. RESULTS: A total of 57 cases of spirochetal uveitis (22 patients with T. pallidum, 26 with Leptospira spp., and 9 with B. burgdorferi) that consisted 1% of the overall number of uveitics were recorded. All these cases presented with a wide spectrum of clinical presentations (anterior uveitis, posterior uveitis, panuveitis, vasculitis, papillitis, and in some rare cases concomitant posterior scleritis). The treatment included mainly penicillin or doxycycline, while corticosteroids were administered systematically in some cases with Borrelia or Leptospira infection. The final visual outcome was favorable (> 6/10 in Snellen visual acuity) in approximately 76% of our patients. CONCLUSION: Despite being rare, spirochetal uveitis can be detrimental for the vision and must always be included in the differential diagnosis.

Evaluating Infectious, Neoplastic, Immunological, and Degenerative Diseases of the Central Nervous System with Cerebrospinal Fluid-Based Next-Generation Sequencing.

Cerebrospinal fluid (CSF) is a clear and paucicellular fluid that circulates within the ventricular system and the subarachnoid space of the central nervous system (CNS), and diverse CNS disorders can impact its composition, volume, and flow. As conventional CSF testing suffers from suboptimal sensitivity, this review aimed to evaluate the role of next-generation sequencing (NGS) in the work-up of infectious, neoplastic, neuroimmunological, and neurodegenerative CNS diseases. Metagenomic NGS showed improved sensitivity-compared to traditional methods-to detect bacterial, viral, parasitic, and fungal infections, while the overall performance was maximized in some studies when all diagnostic modalities were used. In patients with primary CNS cancer, NGS findings in the CSF were largely concordant with the molecular signatures derived from tissue-based molecular analysis; of interest, additional mutations were identified in the CSF in some glioma studies, reflecting intratumoral heterogeneity. In patients with metastasis to the CNS, NGS facilitated diagnosis, prognosis, therapeutic management, and monitoring, exhibiting higher sensitivity than neuroimaging, cytology, and plasma-based molecular analysis. Although evidence is still rudimentary, NGS could enhance the diagnosis and pathogenetic understanding of multiple sclerosis in addition to Alzheimer and Parkinson disease. To conclude, NGS has shown potential to aid the research, facilitate the diagnostic approach, and improve the management outcomes of all the aforementioned CNS diseases. However, to establish its role in clinical practice, the clinical validity and utility of each NGS protocol should be determined. Lastly, as most evidence has been derived from small and retrospective studies, results from randomized control trials could be of significant value.

Aeromonas hydrophila Survives the Treatment of Posttraumatic Cellulitis in the Shelter of an Obscured Fish-Bone Fragment.

Fish bone and/or spine puncture injuries can result in infection of the upper extremities with aquatic bacterial pathogens. Additionally, in such injuries, the inoculation of foreign organic material is frequent and may further complicate the clinical presentation and course of the resulting infection. We describe the case of a 45-year-old female patient with a minimal fish rostrum puncture trauma acquired during preparation of fresh fish meal, which resulted in a galloping hand cellulitis. The alarming clinical presentation and the prompt response of the skin infection to clindamycin obscured the presence of inoculated fish rostrum remnants in the tissue that, three weeks later, gave rise to a foreign body granuloma, from which Aeromonas hydrophila was isolated. Final resolution was achieved with an additional two-week doxycycline treatment. In conclusion, the reported case highlights the potential of the accidentally implanted organic material, as are fish bones, not only to transfer uncommon pathogens but also to offer a sanctuary that favors microbial survival despite antibiotic therapy thus enabling latent or recurrent infections.

Nutritional Status and the Influence of the Vegan Diet on the Gut Microbiota and Human Health.

The human gut microbiota is considered a well-known complex ecosystem composed of distinct microbial populations, playing a significant role in most aspects of human health and wellness. Several factors such as infant transitions, dietary habits, age, consumption of probiotics and prebiotics, use of antibiotics, intestinal comorbidities, and even metabolic diseases may continously alter microbiota diversity and function. The study of vegan diet-microbiota interactions is a rapidly evolving field, since plenty of research has been focused on the potential effects of plant-based dietary patterns on the human gut microbiota. It has been reported that well-planned vegan diets and their associated components affect both the bacterial composition and metabolic pathways of gut microbiota. Certain benefits associated with medical disorders but also limitations (including nutritional deficiencies) have been documented. Although the vegan diet may be inadequate in calorific value, it is rich in dietary fiber, polyphenols, and antioxidant vitamins. The aim of the present study was to provide an update of the existing knowledge on nutritional status of vegan diets and the influence of their food components on the human gut microbiota and health.

Extent of coronary artery disease in patients undergoing angiography for stable or acute coronary syndromes.

BACKGROUND: We aimed to investigate whether the angiographic extent of coronary artery disease (CAD) differs in patients undergoing coronary angiography for stable CAD or acute coronary syndrome (ACS) and identify predictors of CAD extent in these patients. METHODS: We enrolled 584 consecutive patients (463 with stable CAD, 121 with ACS) with angiographically established CAD (≥1 stenosis >25%). The Gensini score was used to assess the extent of coronary atherosclerosis. RESULTS: Stable CAD patients had greater Framingham risk score and greater prevalence of hypertension, hypercholesterolemia, and diabetes (p<0.05 for all). Fasting glucose and systolic and diastolic blood pressure were higher, while high-sensitivity C-reactive protein (hsCRP) levels were lower in patients with stable CAD than in those with ACS (p<0.05 for all). No difference in Gensini score was observed between the two groups (p=0.118), but patients with ACS were more likely to have at least one significant epicardial angiographic lesion (>50% stenosis) (OR 2.0, p=0.022). Higher Gensini score was independently associated with (i) higher hsCRP and glucose levels, hypercholesterolemia, and increased age in stable CAD patients (R2 0.15, p<0001) and (ii) increased age and higher glucose and hsCRP levels in patients with ACS (R2 0.17, p<0001). CONCLUSIONS: Patients undergoing coronary angiography for ACS or stable CAD presented with a similar extent of angiographic CAD, although patients with ACS had a higher prevalence of significant lesions in the presence of a better cardiovascular risk profile and higher inflammation levels. The extent of angiographic CAD in both the groups shared common determinants such as hsCRP, age, and hyperglycemia, but these appeared to explain only a small part of the variation of coronary atherosclerosis.

Tuberculous Posterior Sclero-Uveitis with Features of Vogt-Koyanagi-Harada Uveitis: An Unusual Case.

BACKGROUND Ocular tuberculosis (TB) is a clinical entity that presents with a wide range of clinical manifestations. It is regarded as an extremely challenging condition from the point of view of diagnostic approach and calls for early diagnosis and prompt treatment, as it can potentially lead to blindness. CASE REPORT This is a case report of a 32-year-old male from southern India who has been living and working in Greece over the last 10 years and presented with 2-week history of pain and progressive visual impairment of his left eye. He underwent a thorough clinical ophthalmological examination and imaging of the fundus, and the findings were consistent with uveitis. However, the manifestations of the inflammation were complicated as they included features that could be attributed mainly to Vogt-Koyanagi-Harada (VKH) disease and tuberculous serpiginous-like uveitis. Therefore, a systemic evaluation, together with specific laboratory and paraclinical investigations, were carried out to define the etiology of the inflammation and develop an optimal therapeutic plan. Taking into account specific findings from the chest imaging, a positive purified protein derivative (PPD) skin test, and sputum cultures positive for Mycobacterium tuberculosis (MTB), we set a diagnosis of posterior sclero-uveitis and started our patient on anti-tuberculous treatment. CONCLUSIONS This case reveals an atypical manifestation of tuberculous sclero-uveitis imitating Vogt-Koyanagi-Harada disease together with a few characteristics of serpiginous-like tuberculous uveitis, emphasizing the fact that tuberculosis should always be included in the differential diagnosis of uveitis when there is no obvious underlying disease.

Serum Neutralization Assay for the Determination of Antibody Levels Against Non-Polio Enterovirus Strains in Central and Western Greece.

Mutations and recombination events have been identified in enteroviruses. Point mutations accumulate with a frequency of 6.3 × 10(-4) per base pair per replication cycle affecting the fitness, the circulation, and the infectivity of enteroviral strains. In the present report, the serological status of the Central and Western Greek population (Larissa and Ioannina, respectively) in the 1-10-year, 11-20-year, 21-30-year, and 31-40-year age groups against six non-polio enterovirus strains, their respective echovirus prototypes, and Sabin 1, 2, and 3 vaccine strains was evaluated, through serum-neutralization assay. In the Western Greek population, antibody levels were detected only for clinical isolates of E30 serotype in all age groups, and for environmental isolate LR61G3 (E6 serotype) only in the 31-40 age group, whereas an immunity level was observed in the Central Greek population, against all strains, except for EIS6B (E3 serotype). Amino acid substitutions were encountered across the structural region of the capsid, between the prototypes and the respective isolates. These substitutions may alter the antigenicity of each strain and may explain the variations observed in the neutralization titers of the different strains. As a consequence, these substitutions severely affect antibody binding and increase the ability of the virus to escape the immune response. It is tempting to assume that changes in the antigenic properties observed in circulating echoviruses represent a selection of viral variants that are less prone to be neutralized by human antibodies. These facts argue for the need of immunological studies to the population to avoid epidemics due to the circulation of highly evolved derivatives.

Laboratory diagnosis of human visceral leishmaniasis.

Visceral leishmaniasis (VL), caused by the Leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. VL patients may be asymptomatic or they may present symptoms and findings of a systemic infection. The positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic diseases. The fact that HIV co-infections often produce atypical presentations and the heterogeneity of Leishmania species, which is common in many endemic regions, also complicate the diagnosis. Despite that, some of the parasitological methods are still considered to be the reference standard for VL diagnosis due to their specificity. The development of serological and molecular tests has further enhanced the diagnostic approach of VL. Recombinant antigens have improved the performance of serodiagnostic tests, with DAT and the rK39 antigen based immunochromatographic test being the most appropriate methods for the serological diagnosis of VL. Molecular techniques, despite the fact that their implementation is often difficult and infeasible, have become increasingly relevant due to remarkable sensitivity and specificity, and to the variability of tested samples. Quantitative polymerase chain reaction (qPCR) has been shown to be superior than conventional PCR for the differentiation between active VL and asymptomatic infections, such as for the detection of VL-HIV coinfection. This review summarizes the available methods with their applications in the diagnosis of VL, and focuses on the recent developments in VL diagnostics.

Molecular epidemiology and evolutionary dynamics of Echovirus 3 serotype.

Echovirus 3 (E3) serotype has been related with several neurologic diseases, although it constitutes one of the rarely isolated serotypes, with no report of epidemics in Europe. The aim of the present study was to provide insights into the molecular epidemiology and evolution of this enterovirus serotype, while an E3 strain was isolated from sewage in Greece, four years after the initial isolation of the only reported E3 strain in the same geographical region. Phylogenetic analysis of the complete VP1 genomic region of that E3 strain and of those available in GenBank suggested three main genogroups that were further subdivided into seven subgenogroups. Further evolutionary analysis suggested that VP1 genomic region of E3 was dominated by purifying selection, as the vast majority of genetic diversity presumably occurred through synonymous nucleotide substitutions and the substitution rate for complete and partial VP1 sequences was calculated to be 8.13×10(-3) and 7.72×10(-3) substitutions/site/year respectively. The partial VP1 sequence analysis revealed the composite epidemiology of this serotype, as the strains of the three genogroups presented different epidemiological characteristics.

The Balkan region: NDM-1-producing Klebsiella pneumoniae ST11 clonal strain causing outbreaks in Greece.

OBJECTIVES: Despite the fact that the NDM-1 carbapenemase has successfully disseminated worldwide, outbreaks remain uncommon in the European region. We describe the characteristics of the first outbreaks caused by NDM-1-producing Klebsiella pneumoniae clonal isolates in Greece. METHODS: Between January 2010 and June 2013, 132 non-repetitive carbapenem-resistant Enterobacteriaceae isolates, which gave a positive modified Hodge test and were phenotypically suspected of metallo-ß-lactamase production, were recovered from patients hospitalized at Ioannina University Hospital. Resistance genes were identified by PCR and sequencing. Plasmid profiling, conjugation experiments, enterobacterial repetitive intergenic consensus PCR, PFGE and multilocus sequence typing (MLST) were performed. Patient records were retrieved to access patterns of acquisition. RESULTS: Molecular testing verified the presence in 78 K. pneumoniae isolates, collected from 71 patients, of the blaNDM-1 gene. The blaCTX-M-15, blaOXA-1 and blaTEM-1 genes were also present in most isolates. The blaNDM-1 gene was located on a narrow host range IncFII-type plasmid, of ∼95 kb, flanked upstream by a non-truncated ISAba125 element and downstream by the bleMBL gene. Genotyping clustered all K. pneumoniae isolates into a single clonal type with one subtype and MLST assigned them to sequence type 11. Two outbreaks were noted, the first between November and December 2011 involving four patients and the second initiated in May 2012 and ongoing, involving the remaining patients. All but two cases were characterized as hospital acquired. No links to immigration or travel history to endemic areas were established. CONCLUSIONS: This survey highlights the successful undetected dissemination of yet another carbapenemase in Greece and strengthens the hypothesis of a latent NDM-1 cluster in the Balkan region.

Combined 5' UTR RFLP analysis and VP1 sequencing for epidemic investigation of enteroviruses.

Enteroviruses, the main cause of aseptic meningitis, consist of 100 serotypes, and many of them have been associated with large outbreaks. In the present study, a comparison of RFLP analysis of the 5' untranslated region (5'UTR) and sequencing of both the 5'UTR and VP1 regions was conducted for epidemiological linkage of 27 clinical enterovirus strains. The clinical enterovirus strains were clustered into five restriction profile groups. Even though the restriction profile clusters of clinical isolates were not related to those of the respective prototype strains, epidemiological relationships between the members of each cluster were observed. The restriction profile clusters in the 5'UTR corresponded to the phylogenetic clusters in the VP1 genomic region. The incongruence between the topology of Gior strain in 5'UTR and VP1 phylogenetic trees indicates a recombination event. The proposed RFLP assay in combination with VP1 sequencing can offer crucial epidemiological information about the circulating enteroviruses.

Effects of rosuvastatin with or without ezetimibe on clinical outcomes in patients undergoing elective vascular surgery: results of a pilot study.

OBJECTIVE: Cardiovascular complications represent a major cause of morbidity and mortality in patients undergoing vascular surgery. This was a prospective randomized, open-label study to investigate the effect of lipid-lowering treatment by statin monotherapy or intensified by combining statin with ezetimibe on a  12-month  prognosis after vascular surgery. METHODS: Patients were randomly assigned to receive rosuvastatin (RSV) 10 mg/d or rosuvastatin 10 mg/d plus ezetemibe (RSV/EZT) 10 mg/d, starting prior to scheduled surgical procedure. The primary end point was the first major cardiovascular event, including death from cardiac causes, nonfatal myocardial infarction, ischemic stroke, and unstable angina. RESULTS: A total of 136 patients assigned to RSV and 126 to RSV/EZT completed the study protocol. As many as 6.6% of patients in the RSV group experience a major cardiovascular event within 30 days after surgery versus 5.6% in the RSV/EZT group (P = .72). From month 1 to 12 of the follow-up period, primary end point was observed (9 taking RSV vs 2 in the RSV/EZT group [P = .04]). Intensified lipid-lowering therapy with RSV/EZT was associated with a greater decrease in low-density lipoprotein cholesterol levels compared with RSV (75.87 ± 31.64 vs 87.19 ± 31.7, P = .004), while no differential effect on triglyceride, high-density lipoprotein cholesterol or high-sensitivity C-reactive protein levels was noted between groups. CONCLUSION: Our findings indicate that statin therapy intensified by ezetimibe may reduce the incidence of cardiovascular events within the first 12 months after vascular surgery. Nonetheless, whether the use of ezetimibe as an add-on therapy to reduce cardiovascular risk in these patients needs to be tested in larger future studies.

Genome analysis of two type 6 echovirus (E6) strains recovered from sewage specimens in Greece in 2006.

Echovirus 6 (E6) is one of the main enteroviral serotypes that was isolated from cases of aseptic meningitis and encephalitis during the last years in Greece. Two E6 (LR51A5 and LR61G3) were isolated from the sewage treatment plant unit in Larissa, Greece, in May 2006, 1 year before their characterization from aseptic meningitis cases. The two isolates were initially found to be intra-serotypic recombinants in the genomic region VP1, a finding that initiated a full genome sequence analysis. In the present study, nucleotide, amino acid, and phylogenetic analyses for all genomic regions were conducted. For the detection of recombination events, Simplot and bootscan analyses were carried out. The continuous phylogenetic relationship in 2C-3D genomic region of strains LR51A5 and LR61G3 with E30 isolated in France in 2002-2005 indicated that the two strains were recombinants. SimPlot and Bootscan analyses confirmed that LR51A5 and LR61G3 carry an inter-serotypic recombination in the 2C genomic region. The present study provide evidence that recombination events occurred in the regions VP1 (intraserotypic) and non-capsid (interserotypic) during the evolution of LR51A5 and LR61G3, supporting the statement that the genomes of circulating enteroviruses are a mosaic of genomic regions of viral strains of the same or different serotypes. In conclusion, full genome sequence analysis of circulating enteroviral strains is a prerequisite to understand the complexity of enterovirus evolution.

Postoperative levels of cardiac troponin versus CK-MB and high-sensitivity C-reactive protein for the prediction of 1-year cardiovascular outcome in patients undergoing vascular surgery.

OBJECTIVE: This study evaluated comparatively the predictive value of postoperative cardiac troponin I (cTnI), creatinine kinase (CK)-MB, and high-sensitivity C-reactive protein (hs-CRP) in 1-year cardiovascular mortality and morbidity in patients undergoing elective vascular surgery. METHODS: A total of 295 consecutive patients undergoing elective noncardiac vascular surgery were prospectively followed-up over a period of 12 months. The levels of cTnI, CK-MB, and hs-CRP were measured preoperatively and 24 h after operation. The primary endpoint was the composite of cardiovascular death, nonfatal acute myocardial infarction, ischemic stroke, and unstable angina. RESULTS: The primary endpoints occurred in 11 patients (3.8%). Receiver operating characteristic curve analysis showed that postoperative cTnI was a strong predictor of a cardiovascular event during 1-year follow-up (area under the curve, 0.852; P<0.001). Areas under the curve for hs-CRP and for CK-MB were 0.734 (P=0.008) and 0.494 (P=0.947). A threshold cTnI value of 0.4 ng/ml was highly associated with the occurrence of a cardiovascular event, with a sensitivity of 80% and specificity of 81%. Furthermore, cTnI levels provided a significantly better prediction than CK-MB levels (P=0.009) and tended to be superior to hs-CRP (P=0.2). CONCLUSION: Postoperative cTnI levels seem to be superior to CK-MB and hs-CRP levels for the prediction of 1-year cardiovascular mortality and morbidity in patients undergoing elective vascular surgery.

Use of interferon-gamma release assay for latent tuberculosis infection screening in older adults exposed to tuberculosis in a nursing home.

OBJECTIVES: To assess the additive value of a newly marketed interferon-gamma release assay, QuantiFERON-TB Gold In-Tube (QFT-GIT), to a single tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) in older adults who have been exposed to TB in a nursing home. DESIGN: Contact tracing included clinical examination, chest radiography, TST, and QFT-GIT in TST-negative people (TST< 5 mm). SETTING: A private nursing home. PARTICIPANTS: Seventy-seven individuals (63 elderly residents, 14 young employees) who had been exposed to an active TB case in a private nursing home. MEASUREMENTS: Comparison of TST and QFT-GIT in older adults who have been exposed to TB. RESULTS: For the TST, the positive response rate was 31.7% (n=20) of elderly residents and 43% (n=6) of staff. Positive QFT-GIT results were obtained in seven (16.3%) elderly residents with negative TST, six of whom were aged 80 and older. QFT-GIT increased the percentage of possible LTBI in this group from 31.7% to 42.9%. CONCLUSION: QFT-GIT has a significant additive value to single TST for detecting LTBI in institutionalized older adults, identifying infected subjects anergic to the TST.

An eternal microbe: Brucella DNA load persists for years after clinical cure.

BACKGROUND: Despite the continuing high incidence of brucellosis, vague aspects of pathophysiology, diagnosis, and treatment continue to exist, particularly with regard to the ability of Brucella species to survive inside the host. METHODS: A quantitative real-time polymerase chain reaction assay was used for monitoring bacterial DNA load in brucellosis-affected patients throughout different disease stages. Three or more specimens per patient were obtained (1 at diagnosis, 1 at the end of treatment, and at least 1 during the follow-up period) from 39 patients with acute brucellosis. RESULTS: The majority of patients (87% at the end of treatment, 77% at 6 months after treatment completion, and 70% at >2 years after treatment) exhibited persistent detectable microbiological load despite being asymptomatic. The 3 patients who experienced relapse did not exhibit any statistically significant difference in their bacterial load at any stage of disease or during follow-up. CONCLUSION: Brucella melitensis DNA persists despite appropriate treatment and apparent recovery. This finding offers a new insight into the pathophysiology of the disease: B. melitensis is a noneradicable, persisting pathogen.