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1.
Cell ; 173(5): 1083-1097.e22, 2018 05 17.
Article in English | MEDLINE | ID: mdl-29754819

ABSTRACT

The nervous system, the immune system, and microbial pathogens interact closely at barrier tissues. Here, we find that a bacterial pathogen, Streptococcus pyogenes, hijacks pain and neuronal regulation of the immune response to promote bacterial survival. Necrotizing fasciitis is a life-threatening soft tissue infection in which "pain is out of proportion" to early physical manifestations. We find that S. pyogenes, the leading cause of necrotizing fasciitis, secretes streptolysin S (SLS) to directly activate nociceptor neurons and produce pain during infection. Nociceptors, in turn, release the neuropeptide calcitonin gene-related peptide (CGRP) into infected tissues, which inhibits the recruitment of neutrophils and opsonophagocytic killing of S. pyogenes. Botulinum neurotoxin A and CGRP antagonism block neuron-mediated suppression of host defense, thereby preventing and treating S. pyogenes necrotizing infection. We conclude that targeting the peripheral nervous system and blocking neuro-immune communication is a promising strategy to treat highly invasive bacterial infections. VIDEO ABSTRACT.


Subject(s)
Neurons/metabolism , Neutrophils/metabolism , Streptococcal Infections/pathology , Streptococcus pyogenes/pathogenicity , Animals , Bacterial Proteins/immunology , Bacterial Proteins/metabolism , Botulinum Toxins, Type A/administration & dosage , Calcitonin Gene-Related Peptide/metabolism , Caspase 1/deficiency , Caspase 1/genetics , Diterpenes/pharmacology , Fasciitis, Necrotizing/etiology , Fasciitis, Necrotizing/pathology , Fasciitis, Necrotizing/veterinary , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurons/cytology , Neurons/drug effects , Neutrophils/immunology , Pain/etiology , Signal Transduction , Skin/metabolism , Skin/pathology , Streptococcal Infections/complications , Streptococcal Infections/veterinary , Streptococcus pyogenes/metabolism , Streptolysins/immunology , Streptolysins/metabolism , TRPV Cation Channels/deficiency , TRPV Cation Channels/genetics
2.
Brain Behav Immun ; 115: 319-332, 2024 01.
Article in English | MEDLINE | ID: mdl-37748568

ABSTRACT

BACKGROUND: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are related mental disorders that share genetic, neurobiological, and phenomenological features. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is a neuropsychiatric autoimmune disorder with symptoms of OCD and/or TS associated with streptococcal infections. Therefore, PANDAS represents a strong link between OCD, TS, and autoimmunity. Notably, cerebrospinal fluid (CSF) analyses can provide insight into the central nervous processes in OCD, TS, and PANDAS. METHODS: A systematic literature search according to the PRISMA criteria was conducted to collect all CSF studies in patients with OCD, TS, and PANDAS. The total number of cases and the heterogeneity of the low number of studies were not sufficient for a meta-analysis to provide a high level of evidence. Nevertheless, meta-analytical statistics could be performed for glutamate, 5-hydroxyindoleacetic acid (degradation product of serotonin), homovanillic acid (degradation product of dopamine), 3-methoxy-4-hydroxyphenylglycol (major metabolite of noradrenaline), and corticotropin-releasing hormone (CRH) in OCD. A risk-of-bias assessment was implemented using the Cochrane ROBINS-E tool. RESULTS: Meta-analytical testing identified elevated glutamate levels in the CSF of OCD patients compared with healthy controls, while no significant differences were found in other neurotransmitters or CRH. Single studies detected novel neuronal antibodies in OCD patients and elevated oligoclonal bands in TS patients. For TS and PANDAS groups, there was a dearth of data. Risk of bias assessment indicated a substantial risk of bias in most of the included studies. CONCLUSIONS: This systematic review of available CSF data shows that too few studies are currently available for conclusions with good evidence. The existing data indicates glutamate alterations in OCD and possible immunological abnormalities in OCD and TS. More CSF studies avoiding sources of bias are needed.


Subject(s)
Obsessive-Compulsive Disorder , Streptococcal Infections , Tourette Syndrome , Humans , Child , Norepinephrine , Streptococcal Infections/complications , Corticotropin-Releasing Hormone , Glutamates
3.
BMC Infect Dis ; 24(1): 447, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671388

ABSTRACT

Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus suis infection have been reported worldwide, and most of those cases occurred in Asia. Hearing loss is the most common sequela of Streptococcus suis meningitis. Streptococcus suis infection complicated with acute cerebral infarction has rarely been reported. Therefore, to provide a reference for this disease, we reported a case of acute multiple brain infarctions associated with Streptococcus suis infection. In our report, a 69yearold male patient had Streptococcus suis meningitis and sepsis, which were associated with multiple acute cerebral infarctions in the pons and bilateral frontotemporal parietal occipital lobes. After treatment, the patient exhibited cognitive impairment, dyspraxia and irritability. There are limited case reports of cerebral infarction associated with Streptococcus suis infection, and further research is needed to determine the best treatment method.


Subject(s)
Brain Infarction , Streptococcal Infections , Streptococcus suis , Humans , Streptococcus suis/isolation & purification , Male , Streptococcal Infections/microbiology , Streptococcal Infections/complications , Aged , Brain Infarction/microbiology , Brain Infarction/diagnostic imaging , Brain Infarction/complications , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/complications , Meningitis, Bacterial/drug therapy , Sepsis/microbiology , Sepsis/complications , Anti-Bacterial Agents/therapeutic use
4.
Pediatr Nephrol ; 39(6): 1809-1816, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38170231

ABSTRACT

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is the most common cause of acute nephritis in children globally and, in some cases, may be associated with progressive kidney injury and failure, cumulating in the need for long-term dialysis and/or kidney transplantation. METHODS: Our retrospective study describes the occurrence of APSGN among children (< 14 years) admitted to a tertiary children's hospital in Cape Town, South Africa, from January 2015 to December 2020. RESULTS: Of 161 children who presented with acute nephritis (haematuria, oedema, oliguria, and hypertension), 100 met the inclusion criteria. Demographic, clinical features, laboratory findings, management, and outcome data were collected. APSGN was defined by the clinical presentation of at least two clinical signs of acute nephritis, and low serum complement 3 (C3) level or evidence of a recent streptococcal infection. Most cases of APSGN were associated with streptococcal skin infections: 55/100 (55%); 10/100 (10%) children presented with hypertensive seizures; C3 levels were low in 86/92 (93.5%) children; 94/94 (100%) children had elevated anti-deoxyribonuclease-B (anti-DNase-B) levels; and 80/94 (85%) also had elevated anti-streptolysin O titre (ASOT) at presentation. Eleven (11%) children had a percutaneous kidney biopsy; 4/11 (36%) showed histological features of post-infectious nephritis, and 7/11(64%) also had crescentic glomerulonephritis with immune complex deposits. Sixty-two (62%) children confirmed recovered, and five (5%) progressed to kidney failure, but 29 presumed recovered as they did not return for follow-up to our institution. CONCLUSIONS: Childhood APSGN remains an important health problem in South Africa (SA) with favourable outcomes in most, apart from those with crescentic glomerulonephritis who progressed to kidney failure.


Subject(s)
Glomerulonephritis , Hypertension , Renal Insufficiency , Streptococcal Infections , Child , Humans , Retrospective Studies , South Africa , Renal Dialysis , Glomerulonephritis/diagnosis , Streptococcal Infections/complications , Acute Disease , Hypertension/complications , Renal Insufficiency/complications , Hospitals
5.
Eur J Pediatr ; 183(1): 503-507, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37889290

ABSTRACT

This study describes 5 mediastinitis cases secondary to invasive group A Streptococcus (iGAS) disease in a recent outbreak in Spain. Among 398 iGAS cases between January 2019-March 2023, 5 (1.3%) were mediastinitis, 4 occurring in December 2022, all secondary to pneumonia or deep neck infection. We outline the clinical outcome with a review of the scarce pediatric literature.  Conclusion: mediastinistis is a rare but severe complication of iGAS and a high level of suspicion is required to diagnose it. What is Known: • Group A Streptococcus can cause invasive and severe infections in children. • Mediastinitis is a severe complication from some bacterial infections, mainly secondary due to deep-neck abscesses. What is New: • Mediastinitis is an unrecognized complication due to an invasive group A Streptococcus (iGAS) infection. • In cases of a deep-neck abscess or complicated pneumonia a high clinical suspicion of iGAS mediastinitis is required, especially when the clinical course is not favorable.


Subject(s)
Mediastinitis , Pneumonia , Streptococcal Infections , Humans , Child , Mediastinitis/etiology , Mediastinitis/complications , Spain/epidemiology , Abscess/etiology , Abscess/microbiology , Streptococcus pyogenes , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Streptococcal Infections/epidemiology
6.
Eur J Pediatr ; 183(2): 835-842, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38038770

ABSTRACT

The burden of group A streptococcus (GAS) infection and its rheumatic sequelae remains dramatically high, especially in low-income countries. Recently, an increased number of Acute Rheumatic Fever (ARF) cases was documented in many regions of Italy. The diagnosis of rheumatic sequelae relies on clinical signs and on the evaluation of the Antistreptolysin O titre (ASO), whose variations are globally reported. To re-examine the standard reference value of ASO titre, by measuring either its upper limit of normal (ULN) in a population of healthy children (HC) or comparing these values with streptococcal antibodies registered in a cohort of patients affected by the rheumatic sequelae of GAS infection. We performed a multicenter retrospective study. We enrolled 125 HC, aged 2-17 years, and a total of 181 patients affected by ARF, acute streptococcal pharyngitis, post-streptococcal arthritis, Henoch-Schönlein purpura and erythema nodosum, divided into four groups. The levels of ASO and anti-deoxyribonuclease B (anti-DNase B) titres were analyzed and compared among the various groups. Moreover, the 80th percentile value was calculated and established as the ULN for ASO titre in HC group. The ULN for ASO titre in overall HC group was 515 IU/mL, resulting in higher than used in the routine investigation. The ASO titre was significantly higher in patients with rheumatic sequelae compared with HC group, with a peak in the age between 5 and 15 years.    Conclusion: Our study established a new ULN normal value of streptococcal serology in a childhood and adolescent population of Italy, suggesting the need to extend this revaluation to the critical areas, in order to avoid underestimating ARF diagnosis. The correct interpretation of ASO and anti-DNase B values in the context of rheumatic diseases has been discussed. What is Known: • The global burden of disease caused by group A streptococcus is not known and remains an important cause of morbidity and mortality. Acute rheumatic fever continues to be a serious worldwide public health problem and a recent recurrence of group A streptococcus infection cases is observed. • The streptococcal sequelae requires evidence of preceding streptococcal infection, commonly elevated streptococcal antibody titre, but the upper limit for these titres varies considerably based on age group, region, and origin. What is New: • This study provides population-specific values for streptococcal antibody titres in Italy. • Interpret the results of group A streptococcal antibody tests within the clinical context.


Subject(s)
Rheumatic Diseases , Rheumatic Fever , Streptococcal Infections , Child , Adolescent , Humans , Child, Preschool , Rheumatic Fever/diagnosis , Rheumatic Fever/epidemiology , Antistreptolysin , Retrospective Studies , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Streptococcal Infections/epidemiology , Streptococcus pyogenes , Antibodies, Bacterial , Disease Progression
7.
Clin Exp Nephrol ; 28(5): 359-374, 2024 May.
Article in English | MEDLINE | ID: mdl-38170299

ABSTRACT

BACKGROUND: Post-streptococcal glomerulonephritis (PSGN) is a consequence of the infection by group A beta-hemolytic streptococcus. During this infection, various immunological processes generated by streptococcal antigens are triggered, such as the induction of antibodies and immune complexes. This activation of the immune system involves both innate and acquired immunity. The immunological events that occur at the renal level lead to kidney damage with chronic renal failure as well as resolution of the pathological process (in most cases). Angiotensin II (Ang II) is a molecule with vasopressor and pro-inflammatory capacities, being an important factor in various inflammatory processes. During PSGN some events are defined that make Ang II conceivable as a molecule involved in the inflammatory processes during the disease. CONCLUSION: This review is focused on defining which reported events would be related to the presence of this hormone in PSGN.


Subject(s)
Angiotensin II , Glomerulonephritis , Streptococcal Infections , Streptococcus pyogenes , Humans , Glomerulonephritis/immunology , Glomerulonephritis/microbiology , Glomerulonephritis/etiology , Streptococcal Infections/immunology , Streptococcal Infections/complications , Streptococcal Infections/microbiology , Streptococcus pyogenes/immunology , Animals , Kidney/immunology , Kidney/pathology
8.
J Infect Chemother ; 30(8): 785-788, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38185364

ABSTRACT

Oxazolidinones, such as tedizolid and linezolid, are bacteriostatic antibiotics that inhibit protein synthesis. Based on the findings from animal studies and their mechanism of action, these antibiotics are considered for managing toxic shock caused by clindamycin-resistant Group A Streptococcus (GAS; Streptococcus pyogenes). However, clinical reports on their usage in such cases are limited. Herein, we report a case of a 67-year-old woman with chronic myeloid leukemia who presented with fever, facial swelling, and myalgia. She was diagnosed with cellulitis and empirically treated with meropenem. Blood culture later revealed GAS, and she was diagnosed with streptococcal toxic shock syndrome. The antibiotic regimen was adjusted based on sensitivity results, with clindamycin initially replaced by linezolid and later switched to tedizolid owing to concerns about potential bone marrow suppression. Her condition improved, and she was discharged 15 days after admission. Therefore, tedizolid may be a safer option for managing toxic shock syndrome in patients with comorbidities that include thrombocytopenia.


Subject(s)
Anti-Bacterial Agents , Clindamycin , Shock, Septic , Streptococcal Infections , Streptococcus pyogenes , Humans , Female , Aged , Shock, Septic/drug therapy , Shock, Septic/microbiology , Anti-Bacterial Agents/therapeutic use , Streptococcus pyogenes/drug effects , Streptococcus pyogenes/isolation & purification , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Streptococcal Infections/complications , Clindamycin/therapeutic use , Drug Resistance, Bacterial , Treatment Outcome , Oxazolidinones/therapeutic use , Oxazolidinones/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Cellulitis/drug therapy , Cellulitis/microbiology , Microbial Sensitivity Tests , Tetrazoles
9.
Am J Emerg Med ; 76: 271.e1-271.e3, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38123421

ABSTRACT

Many complications are emerging from Coronavirus Disease 2019 (COVID-19), likely secondary to immune dysfunction and autoimmunity. While dermatologic changes have been reported, de novo guttate psoriasis, typically associated with streptococcal and other viral infections, secondary to COVID-19 infection has been minimally described. The authors report a case of a 34-year-old man who developed a diffuse rash 3 weeks following a COVID-19 infection found to have new onset guttate psoriasis who was responsive to topical corticosteroids and a vitamin D analog.


Subject(s)
COVID-19 , Exanthema , Psoriasis , Streptococcal Infections , Male , Humans , Adult , Streptococcal Infections/complications , COVID-19/complications , Glucocorticoids , Exanthema/etiology
10.
Matern Child Health J ; 28(7): 1258-1263, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38461475

ABSTRACT

OBJECTIVE: To elucidate the association between GBS infection and maternal risk for obstetric hemorrhage (OBH) and OBH-related morbidities (OBH-M). METHODS: This was a retrospective cohort study of all deliveries with a documented GBS status at a single large academic medical center from 2018 to 2019. GBS status was determined by either urine culture or rectovaginal culture collected during the antepartum period. The primary outcomes were quantitative blood loss (QBL), OBH, and a composite of OBH-M. Secondary outcomes were individual components of the OBH-M composite and frequency of hemorrhage-related interventions utilized intrapartum and postpartum. A stratified analysis was conducted examining only patients who were diagnosed intrapartum with an intrapartum intraamniotic infection (III). RESULTS: Of 4679 pregnant individuals who delivered a live infant between January 1, 2018 and January 1,2019 with a documented GBS status, 1,487 were identified as GBS positive (+) and 3192 were identified as GBS negative (-). The GBS + group did not have significantly higher QBL (p = 0.29) or rate of OBH (p = 0.35). There were no significant differences by GBS status in OBH morbidity (p = 0.79) or its individual components or frequency of individual pharmacologic or non-pharmacologic OBHrelated interventions. There were also no significant differences by GBS status among patients with an III. CONCLUSIONS FOR PRACTICE: GBS infection at the time of delivery was not associated with increased risk for OBH or OBH-M. Further research is needed to further explore the relationship between peripartum infections and OBH risk.


Subject(s)
Postpartum Hemorrhage , Streptococcal Infections , Streptococcus agalactiae , Humans , Female , Pregnancy , Streptococcal Infections/epidemiology , Streptococcal Infections/complications , Retrospective Studies , Adult , Streptococcus agalactiae/isolation & purification , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/etiology , Pregnancy Complications, Infectious/epidemiology , Risk Factors , Cohort Studies
11.
Int J Mol Sci ; 25(3)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38339075

ABSTRACT

Recent research suggests that T-cell receptor (TCR) sequences expanded during human immunodeficiency virus and SARS-CoV-2 infections unexpectedly mimic these viruses. The hypothesis tested here is that TCR sequences expanded in patients with type 1 diabetes mellitus (T1DM) and autoimmune myocarditis (AM) mimic the infectious triggers of these diseases. Indeed, TCR sequences mimicking coxsackieviruses, which are implicated as triggers of both diseases, are statistically significantly increased in both T1DM and AM patients. However, TCRs mimicking Clostridia antigens are significantly expanded in T1DM, whereas TCRs mimicking Streptococcal antigens are expanded in AM. Notably, Clostridia antigens mimic T1DM autoantigens, such as insulin and glutamic acid decarboxylase, whereas Streptococcal antigens mimic cardiac autoantigens, such as myosin and laminins. Thus, T1DM may be triggered by combined infections of coxsackieviruses with Clostridia bacteria, while AM may be triggered by coxsackieviruses with Streptococci. These TCR results are consistent with both epidemiological and clinical data and recent experimental studies of cross-reactivities of coxsackievirus, Clostridial, and Streptococcal antibodies with T1DM and AM antigens. These data provide the basis for developing novel animal models of AM and T1DM and may provide a generalizable method for revealing the etiologies of other autoimmune diseases. Theories to explain these results are explored.


Subject(s)
Autoimmune Diseases , Coxsackievirus Infections , Diabetes Mellitus, Type 1 , Enterovirus , Myocarditis , Streptococcal Infections , Animals , Humans , Autoimmune Diseases/complications , Coxsackievirus Infections/complications , Autoantigens , Streptococcus , Streptococcal Infections/complications , Antigens, Bacterial , Receptors, Antigen, T-Cell
12.
Pediatr Rev ; 45(3): 143-151, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38425166

ABSTRACT

Group A Streptococcus causes a variety of clinical manifestations, including pharyngitis and skin and soft tissue infections as well as more invasive disease. There are also multiple nonsuppurative complications of group A Streptococcus infection, including acute rheumatic fever and poststreptococcal glomerulonephritis. Pediatricians should be able to diagnose and treat the various presentations of the infection.


Subject(s)
Glomerulonephritis , Pharyngitis , Rheumatic Fever , Streptococcal Infections , Humans , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Streptococcal Infections/therapy , Rheumatic Fever/complications , Rheumatic Fever/diagnosis , Rheumatic Fever/therapy , Streptococcus pyogenes , Glomerulonephritis/complications , Glomerulonephritis/diagnosis , Pharyngitis/diagnosis , Pharyngitis/etiology
13.
Clin Immunol ; 249: 109276, 2023 04.
Article in English | MEDLINE | ID: mdl-36871764

ABSTRACT

OBJECTIVE: Early stages with streptococcal necrotizing soft tissue infections (NSTIs) are often difficult to discern from cellulitis. Increased insight into inflammatory responses in streptococcal disease may guide correct interventions and discovery of novel diagnostic targets. METHODS: Plasma levels of 37 mediators, leucocytes and CRP from 102 patients with ß-hemolytic streptococcal NSTI derived from a prospective Scandinavian multicentre study were compared to those of 23 cases of streptococcal cellulitis. Hierarchical cluster analyses were also performed. RESULTS: Differences in mediator levels between NSTI and cellulitis cases were revealed, in particular for IL-1ß, TNFα and CXCL8 (AUC >0.90). Across streptococcal NSTI etiologies, eight biomarkers separated cases with septic shock from those without, and four mediators predicted a severe outcome. CONCLUSION: Several inflammatory mediators and wider profiles were identified as potential biomarkers of NSTI. Associations of biomarker levels to type of infection and outcomes may be utilized to improve patient care and outcomes.


Subject(s)
Fasciitis, Necrotizing , Soft Tissue Infections , Streptococcal Infections , Humans , Soft Tissue Infections/complications , Fasciitis, Necrotizing/complications , Fasciitis, Necrotizing/diagnosis , Cellulitis/complications , Prospective Studies , Streptococcal Infections/complications , Biomarkers
14.
Dev Neurosci ; 45(6): 335-341, 2023.
Article in English | MEDLINE | ID: mdl-37699369

ABSTRACT

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is an acute onset or exacerbation of neuropsychiatric symptoms following a group A streptococcus infection. It is believed to be a result of autoimmune response to streptococcal infection, but there is insufficient evidence to fully support this theory. Although this disease is primarily thought to be a disease of childhood, it is reported to occur also in adults. PANDAS is a well-defined clinical entity, but the neuropathology of this condition has not been established yet. We describe the clinical course of a 26-year-old female diagnosed with PANDAS. She committed suicide and her brain was biobanked for further studies. We examined the banked tissue and performed special stains, immunohistochemical, and immunofluorescence analyses to characterize the neuropathology of this condition. Histology of the temporal lobes, hippocampus, and basal ganglia shows mild gliosis and Alzheimer's type II astrocytes. Acute hypoxic ischemic changes were noted in hippocampus CA1 and CA2 areas. Immunostaining shows increased parenchymal/perivascular GFAP staining and many vessels with mild increases in CD3-, CD4-, and CD25-stained lymphocytes in the basal ganglia. The findings suggest that CD4- and CD25-positive T cells might have an important role in understanding the neuroinflammation and pathogenesis of this condition. The case represents the first neuropathological evaluation report for PANDAS.


Subject(s)
Autoimmune Diseases , Mental Disorders , Streptococcal Infections , Humans , Child , Young Adult , Female , Adult , Autoimmune Diseases/diagnosis , Autoimmune Diseases/etiology , Streptococcal Infections/diagnosis , Streptococcal Infections/complications , Brain
15.
Dev Neurosci ; 45(6): 325-334, 2023.
Article in English | MEDLINE | ID: mdl-37231875

ABSTRACT

Pediatric acute-onset neuropsychiatric syndrome (PANS), pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections, Sydenham chorea, and other postinfectious psychiatric deteriorations are thought to be caused by inflammatory/autoimmune mechanisms, likely involving the basal ganglia based on imaging studies. Patients have a relapsing-remitting course and some develop severe refractory psychiatric disease. We found that 55/193 (28%) of consecutive patients meeting PANS criteria developed chronic arthritis and 25/121 (21%) of those with related psychiatric deteriorations developed chronic arthritis. Here we describe 7 of these patients in detail and one sibling. Many of our patients often have "dry" arthritis (no effusions found on physical exam) but subtle effusions detected by imaging and features of spondyloarthritis, enthesitis, and synovitis. Joint capsule thickening, not previously reported in children, is a common finding in the presented cases and in psoriatic arthritis in adults. Due to the severity of psychiatric symptoms in some cases, which often overshadow joint symptoms, and concomitant sensory dysregulation (making the physical exam unreliable in the absence of effusions), we rely on imaging to improve sensitivity and specificity of the arthritis classification. We also report the immunomodulatory treatments of these 7 patients (initially nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs with escalation to biologic medications) and note any coincidental changes to their arthritis and psychiatric symptoms while on immunomodulation. Patients with overlapping psychiatric syndromes and arthritis may have a unifying cause and pose unique challenges; a multi-disciplinary team can utilize imaging to tailor and coordinate treatment for this patient population.


Subject(s)
Arthritis , Autoimmune Diseases , Obsessive-Compulsive Disorder , Streptococcal Infections , Humans , Child , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/drug therapy , Obsessive-Compulsive Disorder/psychology , Arthritis/complications , Autoimmune Diseases/complications , Autoimmune Diseases/diagnosis , Autoimmune Diseases/drug therapy , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Streptococcal Infections/drug therapy , Syndrome
16.
Dev Neurosci ; 45(6): 361-374, 2023.
Article in English | MEDLINE | ID: mdl-37742615

ABSTRACT

Postinfectious neuroinflammation has been implicated in multiple models of acute-onset obsessive-compulsive disorder including Sydenham chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.


Subject(s)
Chorea , Obsessive-Compulsive Disorder , Streptococcal Infections , Animals , Child , Humans , Autoimmunity , Chorea/diagnosis , Chorea/complications , Neuroinflammatory Diseases , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Streptococcal Infections/drug therapy , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/psychology , Autoantibodies/therapeutic use , Inflammation
17.
Eur J Clin Microbiol Infect Dis ; 42(2): 177-182, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36502498

ABSTRACT

Viridans group streptococci (VGS) bloodstream infection (BSI) in neutropenic patients can be a severe complication. A higher prevalence of vancomycin use has been reported due to reduced susceptibility to penicillin. We aimed to assess the impact on mortality of both penicillin minimal inhibitory concentration (MIC) and the use of vancomycin. We conducted a retrospective multicenter study including consecutive neutropenic patients with VGS BSI between 2007 and 2019. Univariable and multivariable analyses were conducted to evaluate risk factors for mortality, including penicillin susceptibility as an independent variable. Non-susceptibility to penicillin was defined as MIC ≥ 0.25. We included 125 neutropenic patients with VGS BSI. Mean age was 53 years and ~ 50% were women. Overall, 30-day mortality rate was 25/125 (20%), and 41 patients (33%) had a VGS isolate non-susceptible to penicillin. In univariable analysis, no significant association was demonstrated between penicillin non-susceptibility and mortality (9/25, 26% vs. 32/100, 32%, p = 0.81). Among patients with a non-susceptible strain, the use of vancomycin was not significantly associated with mortality (empirical, p = 0.103, or definitive therapy, p = 0.491). Factors significantly associated with increased mortality in multivariable analysis included functional status (ECOG > 1, adjusted odds ratio [aOR] 12.53, 95% CI 3.64-43.14; p < 0.0001); allogeneic transplantation (aOR 6.33, 95% CI 1.96-20.46; p = 0.002); and co-pathogen in blood cultures (aOR 3.99, 95% CI 1.34-11.89; p = 0.013). Among neutropenic hemato-oncological patients with VGS BSI, penicillin non-susceptibility and the use of vancomycin were not associated with mortality. Thus, vancomycin should not be used routinely as empirical therapy in neutropenic patients with suspected VGS BSI.


Subject(s)
Sepsis , Streptococcal Infections , Humans , Female , Middle Aged , Male , Penicillins/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Streptococcal Infections/complications , Streptococcal Infections/drug therapy , Streptococcal Infections/epidemiology , Vancomycin/pharmacology , Vancomycin/therapeutic use , Viridans Streptococci , Sepsis/drug therapy , Microbial Sensitivity Tests
18.
Eur J Clin Microbiol Infect Dis ; 42(7): 907-912, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37145237

ABSTRACT

Whether cirrhotic patients with Streptococcus bovis bacteremia have an increased risk of colorectal neoplasm is uncertain. A multicentric retrospective cohort study was conducted investigating associations between S. bovis biotype and species, cirrhosis, and colorectal neoplasm. Out of 779 patients with S. bovis bacteremia, 69 (8.7%) had cirrhosis. No differences were found in the prevalence of colorectal neoplasm between cirrhotic and non-cirrhotic patients undergoing colonoscopy. Among cirrhotic patients, prevalence of colorectal neoplasms was higher in S. bovis biotype I (S. gallolyticus) bacteremia (80%) than in S. bovis biotype II (33.3%; p < 0.007). In conclusion, risk of colorectal neoplasm is high among cirrhotic patients with S. gallolyticus bacteremia.


Subject(s)
Bacteremia , Colonic Neoplasms , Colorectal Neoplasms , Streptococcal Infections , Streptococcus bovis , Humans , Retrospective Studies , Colonic Neoplasms/complications , Colonic Neoplasms/epidemiology , Colorectal Neoplasms/microbiology , Liver Cirrhosis/complications , Bacteremia/complications , Bacteremia/epidemiology , Bacteremia/microbiology , Streptococcal Infections/complications , Streptococcal Infections/epidemiology , Streptococcal Infections/microbiology
19.
BMC Infect Dis ; 23(1): 145, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36890459

ABSTRACT

BACKGROUND: Typical Lemierre's syndrome is usually secondary to an oropharyngeal infection. Recently, several cases following a primary infection site other than the oropharynx have been reported as atypical Lemierre's syndrome; although, these primary lesions are limited to the head and neck. This is the first case potentially sequential to infectious foci outside the head and neck. CASE PRESENTATION: We describe an atypical Lemierre's syndrome in a 72-year-old woman with rheumatoid arthritis, which occurred during the treatment of Streptococcus anginosus bacteremia acquired from a sacral ulcer infection related to rheumatoid vasculitis. At first, the symptoms resolved after the initial administration of vancomycin for the bacteremia caused by methicillin-resistant Staphylococcus aureus and Streptococcus anginosus that entered via a sacral ulcer. On the 8th day, the patient developed a fever of 40 °C and unexpectedly required 10 L of oxygen due to rapid deterioration of oxygenation temporarily. Immediately contrast-enhanced computed tomography was performed to investigate systemic thrombosis including pulmonary embolism. Afterward, the newly formed thrombi at the right external jugular vein, bilateral internal jugular veins, and the right small saphenous vein were detected, and apixaban was started. On the 9th day, the patient again had an intermittent fever of 39.7 °C, and continuous Streptococcus anginosus bacteremia was revealed; subsequently, clindamycin was administered. On the 10th day, she developed a left hemothorax; consequently, apixaban was discontinued, and a thoracic drain was inserted. She repeatedly had an intermittent fever of 40.3 °C, and contrast-enhanced computed tomography detected an abscess formation at the left parotid gland, pterygoid muscle group, and masseter muscle. After Lemierre's syndrome was diagnosed in combination with the abovementioned jugular vein thrombus, clindamycin was replaced with meropenem, and vancomycin was increased. Swelling of the lower part of the left ear became prominent with delay and peaked at approximately the 16th day. The subsequent treatment course was favorable, and she was discharged on the 41st day. CONCLUSION: Clinicians should consider Lemierre's syndrome as the differential diagnosis of internal jugular vein thrombosis occurring during sepsis, even though an antibiotic is administered or a primary infection site is anything besides the oropharynx.


Subject(s)
Bacteremia , Lemierre Syndrome , Methicillin-Resistant Staphylococcus aureus , Rheumatoid Vasculitis , Streptococcal Infections , Female , Humans , Aged , Lemierre Syndrome/complications , Lemierre Syndrome/diagnosis , Lemierre Syndrome/drug therapy , Clindamycin , Vancomycin , Rheumatoid Vasculitis/complications , Ulcer , Bacteremia/diagnosis , Streptococcal Infections/complications
20.
Pediatr Nephrol ; 38(9): 3027-3033, 2023 09.
Article in English | MEDLINE | ID: mdl-36929388

ABSTRACT

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is an immune-mediated inflammatory respsonse in the kidneys caused by nephritogenic strains of group A ß-hemolytic streptococcus (GAS). The present study aimed to present a large patient cohort of APSGN patients to determine the factors that can be used for predicting the prognosis and progression to rapidly progressive glomerulonephritis (RPGN). METHODS: The study included 153 children with APSGN that were seen between January 2010 and January 2022. Inclusion criteria were age 1-18 years and follow-up of ≥ 1 years. Patients with a diagnosis that could not be clearly proven clinically or via biopsy and with prior clinical or histological evidence of underlying kidney disease or chronic kidney disease (CKD) were excluded from the study. RESULTS: Mean age was 7.36 ± 2.92 years, and 30.7% of the group was female. Among the 153 patients, 19 (12.4%) progressed to RPGN. The complement factor 3 and albumin levels were significantly low in the patients who had RPGN (P = 0.019). Inflammatory parameters, such as C-reactive protein (CRP), platelet-to-lymphocyte ratio, CRP/albumin ratio, and the erythrocyte sedimentation rate level at presentation were significantly higher in the patients with RPGN (P < 0.05). Additionally, there was a significant correlation between nephrotic range proteinuria and the course of RPGN (P = 0.024). CONCLUSIONS: We suggest the possibility that RPGN can be predicted in APSGN with clinical and laboratory findings. A higher resolution version of the Graphical abstract is available as Supplementary information.


Subject(s)
Glomerulonephritis , Nephritis , Streptococcal Infections , Child , Humans , Female , Child, Preschool , Infant , Adolescent , Streptococcal Infections/complications , Glomerulonephritis/diagnosis , Kidney/pathology , Acute Disease , C-Reactive Protein
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