Acute Rheumatic Fever Patients Research Articles

Tenascin-C: as a diagnostic biomarker for rheumatic heart disease

BackgroundRheumatic fever is a long-term inflammatory disease that can happen if group A beta-hemolytic streptococci bacteria are not treated well enough. Rheumatic fever is recognized globally as the leading cause of heart disease in the pediatric population. This disease destroys the heart muscle, progressively deteriorating its structure and impairing the function of its valves over time.AimThe aim of this study is to determine the role of serum tenascin-C in the diagnosis of acute rheumatic fever and chronic rheumatic heart disease.MethodsThis case–control study involved a group of 60 Egyptian children. Among them, 20 were diagnosed with acute rheumatic fever, identified using the updated Jones criteria from 2015. Another 20 children, who were suffering from chronic rheumatic heart disease, were also act as a part of the study. The remaining 20 participants, healthy children carefully matched in age and sex, served as the control group.ResultsSerum tenascin-C level was significantly increased in acute rheumatic fever (ARF) and highly significantly increased in chronic rheumatic heart disease (CRHD) groups when compared with control group (P = 0.04, 0.01), respectively. There were highly significant difference between and within the studied groups regarding the mean of serum tenascin-C. Serum tenascin-C mean of ARF, CRHD, and control was 4.82 ± 18.7, 5.46 ± 1.6, and 3.78 ± 2.4, respectively, P = 0.02. Level of serum tenascin-C was lower in cases with severe mitral valve insufficiency. No significant link was found between the level of serum tenascin-C and C-reactive protein (CRP), ESR, and ASO titer, with a P-value greater than 0.5. ROC curve for serum tenascin-C in ARF patients was area under the curve = 0.682 (P = 0.05) with optimal serum tenascin-C cut-off point (> 3.76 ng/ml); ROC curve for serum tenascin-C in CRHD patients was AUC = 0.73 (P = 0.01) with cut-off point level (73.76 ng/ml).ConclusionPatients with ARF and CRHD have increased level of serum tenascin-C. Serum tenancin-C is superior in the diagnosis of ARF in comparison to CRP, ESR, and ASOT. Tenascin-C level can be used as a diagnostic marker for ARF and CRHD.

Clinical profile of acute rheumatic fever in children in Pakistan: A study at a tertiary care hospital.

Objective: To determine the clinical profile of children presenting with acute rheumatic fever (ARF) at a tertiary care healthcare facility. Study Design: Cross-sectional study. Setting: Department of Pediatrics, Rai Medical College Teaching Hospital, Sargodha Pakistan. Period: January 2021 to December 2022. Material & Methods: We analyzed children of both genders aged between 1 month to 18 years and presenting with ARF. At the time of enrollment, medical history was obtained and physical as well as clinical examinations were performed. The demographical and clinical information were recorded. ARF was labeled as per “Modified Jones Criteria”. A special proforma was formed to record study data. Results: In a total of 154 children, 96 (62.3%) were female while the mean age was 9.3±4.6 years. Forty four (28.6%) patients were having first episode of ARF while 110 (71.4%) had recurrence of ARF. Fever was noted to be the most common presentation noted in 121 (78.6%) patients of ARF. Arthritis was significantly more common among patients with first episode of ARF when compared to recurrence of ARF (70.5% vs. 29.1%, p<0.0001). Degree of carditis was significantly more severe among patients with recurrence of ARF (p<0.0001). Conclusion: Majority of the acute rheumatic fever patients present with recurrence of acute rheumatic fever. Fever was the commonest clinical presentation while arthritis was significantly more prevalent among patients with first episode of acute rheumatic fever.

Profiling system-wide variations and similarities between Rheumatic Heart Disease and Acute Rheumatic Fever-A pilot analysis.

Rheumatic heart disease (RHD) continues to affect developing countries with low income due to the lack of resources and effective diagnostic techniques. Understanding the genetic basis common to both the diseases and that of progression from its prequel disease state, Acute Rheumatic Fever (ARF), would aid in developing predictive biomarkers and improving patient care. To gain system-wide molecular insights into possible causes for progression, in this pilot study, we collected blood transcriptomes from ARF (5) and RHD (5) patients. Using an integrated transcriptome and network analysis approach, we identified a subnetwork comprising the most significantly differentially expressed genes and most perturbed pathways in RHD compared to ARF. For example, the chemokine signaling pathway was seen to be upregulated, while tryptophan metabolism was found to be downregulated in RHD. The subnetworks of variation between the two conditions provide unbiased molecular-level insights into the host processes that may be linked with the progression of ARF to RHD, which has the potential to inform future diagnostics and therapeutic strategies. We also found a significantly raised neutrophil/lymphocyte ratio in both ARF and RHD cohorts. Activated neutrophils and inhibited Natural Killer cell gene signatures reflected the drivers of the inflammatory process typical to both disease conditions.

Acute rheumatic fever in adult patients.

Acute rheumatic fever (ARF) is considered as a disorder of children, and attacks in adults are usually a recurrence of disease acquired in the child’s life. Although the incidence of ARF in children has a decreasing trend in developed countries, resurgent and sporadic epidemics still occur in adults. The first attacks of ARF in adult patients without a childhood history can lead to a diagnostic dilemma.A medical record review in adults at least 18 years of age with an arthralgia complaint fulfilling 2015 revised Jones criteria was performed from January 1, 2000 to December 31, 2019.Eleven ARF patients were identified, including 8 with initial attacks (6 females aged 26–42 years, 33.9 ± 5.3) and 3 pre-existing valvular heart disease with recurrent attacks (2 females aged 38–52 years, 45.0 ± 7.0). In addition to febrile pharyngitis and migratory polyarthritis in initial attacks, pericarditis was encountered in 1, valvulitis in 2, prolong PR interval in 3 and skin involvement in 2 patients with erythema marginatum and IgA vasculitis. All responded to antibiotics and nonsteroidal anti-inflammatory drugs therapy with normalized clinical and laboratory abnormalities, no new-onset carditis, and no recurrent disease during a long-term follow-up (3.8–19.8 years, 12.7 ± 5.4).A sporadic occurrence of adult ARF is observed in southern Taiwan. This disease should be considered by physicians for the differential diagnosis of febrile pharyngitis with arthritis and/or carditis in adults, even in areas with a low incidence of ARF.

Incidence and clinical characteristics of acute rheumatic fever in Turkey: Results of a nationwide multicentre study.

To evaluate the incidence and clinical features of acute rheumatic fever (ARF) in Turkey, following the revised Jones criteria in 2015. This multicentre study was designed by the Acquired Heart Diseases Working Group of the Turkish Pediatric Cardiology and Pediatric Cardiac Surgery Association in 2016. The data during the first attack of 1103 ARF patients were collected from the paediatric cardiologists between 1 January 2016 and 31 December 2016. Turkey National Institute of Statistics records of 2016 were used for the determination of ARF incidence with regard to various cities and regions separately. The estimated incidence rate of ARF was 8.84/100 000 in Turkey. The ARF incidence varied considerably among different regions. The highest incidence was found in the Eastern Anatolia Region as 14.4/100 000, and the lowest incidence was found in the Black Sea Region as 3.3/100 000 (P < 0.05). Clinical carditis was the most common finding. The incidence of clinical carditis, subclinical carditis, polyarthritis, aseptic monoarthritis, polyarthralgia and Sydenham's Chorea was 53.5%, 29.1%, 52.8%, 10.3%, 18.6% and 7.9%, respectively. The incidences of clinical carditis, subclinical carditis, polyarthritis and polyarthralgia were found to be significantly different among different regions (P < 0.05). The findings of this nationwide screening of ARF suggest that Turkey should be included in the moderate-risk group.

Ethnically Disparate Disease Progression and Outcomes among Acute Rheumatic Fever Patients in New Zealand, 1989-2015.

We investigated outcomes for patients born after 1983 and hospitalized with initial acute rheumatic fever (ARF) in New Zealand during 1989–2012. We linked ARF progression outcome data (recurrent hospitalization for ARF, hospitalization for rheumatic heart disease [RHD], and death from circulatory causes) for 1989–2015. Retrospective analysis identified initial RHD patients <40 years of age who were hospitalized during 2010–2015 and previously hospitalized for ARF. Most (86.4%) of the 2,182 initial ARF patients did not experience disease progression by the end of 2015. Progression probability after 26.8 years of theoretical follow-up was 24.0%; probability of death, 1.0%. Progression was more rapid and ≈2 times more likely for indigenous Māori or Pacific Islander patients. Of 435 initial RHD patients, 82.2% had not been previously hospitalized for ARF. This young cohort demonstrated low mortality rates but considerable illness, especially among underserved populations. A national patient register could help monitor, prevent, and reduce ARF progression.

Antibody responses to collagen peptides and streptococcal collagen-like 1 proteins in acute rheumatic fever patients.

Acute rheumatic fever (ARF) is a serious post-infectious immune sequelae of Group A streptococcus (GAS). Pathogenesis remains poorly understood, including the events associated with collagen autoantibody generation. GAS express streptococcal collagen-like proteins (Scl) that contain a collagenous domain resembling human collagen. Here, the relationship between antibody reactivity to GAS Scl proteins and human collagen in ARF was investigated. Serum IgG specific for a representative Scl protein (Scl1.1) together with collagen-I and collagen-IV mimetic peptides were quantified in ARF patients (n=36) and healthy matched controls (n=36). Reactivity to Scl1.1 was significantly elevated in ARF compared to controls (P < 0.0001) and this was mapped to the collagen-like region of the protein, rather than the N-terminal non-collagenous region. Reactivity to collagen-1 and collagen-IV peptides was also significantly elevated in ARF cases (P < 0.001). However, there was no correlation between Scl1.1 and collagen peptide antibody binding, and hierarchical clustering of ARF cases by IgG reactivity showed two distinct clusters, with Scl1.1 antigens in one and collagen peptides in the other, demonstrating that collagen autoantibodies are not immunologically related to those targeting Scl1.1. Thus, anti-collagen antibodies in ARF appear to be generated as part of the autoreactivity process, independent of any mimicry with GAS collagen-like proteins.

Echocardiography for latent rheumatic heart disease in first degree relatives of children with acute rheumatic fever: Implications for active case finding in family members.

BackgroundIndividuals with Acute Rheumatic Fever (ARF) often report a family history of ARF or Rheumatic Heart Disease (RHD) however the degree of familial susceptibility to RHD is poorly defined. This study aimed to determine RHD prevalence among first degree relatives of ARF patients using echocardiography.MethodsChildren with ARF were recruited from Auckland, New Zealand. Parents and siblings ≥ 4years were offered echocardiography. Echocardiograms were reported according to World Heart Federation 2012 criteria. RHD prevalence in first degree relatives was compared to previously established population rates in the region.FindingsIn total, 70 index cases with ARF were recruited. Echocardiography was performed in 94 parents and 132 siblings. There were 3 siblings with definite RHD and 9 with borderline RHD. There were 4 parents with definite RHD. Overall prevalence of RHD (definite and borderline) in siblings was 90/1,000 (95% CI 45–143/1,000) compared to 36/1,000 (95% CI 30–42/1,000) in New Zealand children from high ARF incidence populations (p 0.001). Prevalence of definite RHD in parents was 42/1,000 (95% CI 7–87/1,000) compared to 22/1,000 (95% CI 9–36/1,000) in adults from a high ARF incidence New Zealand population (p 0.249).InterpretationRHD prevalence in siblings and parents of ARF cases is significantly greater than in comparable background populations. The contribution of hereditary versus environmental risk factors remains uncertain. We recommend targeted echocardiographic case-finding among siblings and parents of ARF/RHD cases in order to detect previously unrecognized latent RHD.

Pentraxin 3 levels and correlation with disease severity in patients with acute rheumatic fever

Objectives This study aims to investigate serum pentraxin 3 (PTX3) levels during acute episode of acute rheumatic fever (ARF) and their relationship with disease severity.Patients and methods The prospective study was conducted between January 2015 and December 2018 and included 52 ARF patients (22 girls, 30 boys, mean age 10.7±2.1 years; range, 5 to 16 years) experiencing an acute episode and 22 healthy children (13 girls, 9 boys, mean age 10.3±3.8 years; range, 5 to 16 years). ARF patients were classified into three groups based on the clinical course: isolated arthritis (n=17), mild carditis (n=19), and moderate/severe carditis (n=16). Blood samples were collected from all patients before treatment and from the healthy children in the control group to measure PTX3 levels. PTX3 was measured using sandwich enzyme-linked immunosorbent assay method.Results Plasma PTX3 levels were significantly higher in ARF group compared to the control group (4.7±5.2 and 1.2±1.7 ng/mL, p<0.001). Subgroup analysis of serum PTX3 levels in ARF patients with isolated arthritis, mild carditis, and moderate/severe carditis (3.2±3.1 ng/mL, 4.3±5 ng/mL, and 6.7±6.6 ng/mL, respectively) showed that serum PTX3 was significantly higher in the moderate/severe carditis group compared to the other groups (p<0.05). Analysis of echocardiographic data showed that serum PTX3 was positively correlated with left ventricular end-diastolic diameter, left atrial diameters, and mitral A velocity and negatively correlated with E/A ratio (p<0.05; r=0.231, 0.402, 0.562, -0.586, respectively).ConclusionHigh PTX3 level during an acute episode of ARF may help predict the clinical course and the severity of accompanying carditis. However, prospective studies with larger sample sizes are needed.

Abstract 13147: Non-invasive Identification of Carditis in Acute Rheumatic Fever and Rheumatic Heart Disease

Background: The pathogenesis of acute rheumatic fever (ARF) and its evolution into rheumatic heart disease (RHD) is poorly understood. We aimed to identify carditis in patients with ARF and RHD using cardiac magnetic resonance (CMR) tissue characterisation with T1 mapping. We hypothesised that prolonged native T1 time on CMR, would be present in ARF and RHD patients. Methods: We prospectively recruited 62 patients. We recruited 16 patients fulfilling the Jones Criteria for the diagnosis of ARF, 15 controls with an inflammatory condition and 10 healthy controls. We also recruited 11 patients with echocardiographic evidence of RHD and 10 matched controls. All patients underwent CMR with assessment of non-contrast myocardial T1 mapping. The myocardial T1 time, as an index of myocardial inflammation from carditis, was compared between the groups. All T1 times were converted to Z-scores, to enable comparison with different CMR systems. Findings: Patients with ARF had evidence of carditis demonstrated by markedly elevated mean myocardial T1 times. The mean Z score was 2.76(95% CI 1.34-4.17) for patients with ARF compared to 0.32(95% CI -0.25-0.88) for those with non-cardiac inflammatory conditions and 0.00(95% CI -0.72-0.72) for healthy controls, P=0.004. A myocardial T1 Z score greater than 1.4 showed excellent diagnostic performance as a single test for the diagnosis of ARF (AUC = 0.85[0.67-0.99], P=0.001, sensitivity = 82 %, specificity = 92%, Youden’s J = 0.74). Patients with RHD also demonstrated significantly elevated native T1 time compared to matched controls. The mean Z score for RHD patients was 2.79(95% CI 1.3-4.3) compared to 0.00(95% CI -0.72-0.72) in controls, P=0.002. Interpretation: Patients with ARF and RHD have markedly elevated myocardial T1 Z-scores on CMR, consistent with carditis. Incorporating CMR T1 mapping into the diagnostic algorithm for ARF may improve diagnostic certainty and lead to more effective delivery of secondary penicillin prophylaxis.

Development and Evaluation of a New Triplex Immunoassay That Detects Group A Streptococcus Antibodies for the Diagnosis of Rheumatic Fever.

Streptococcal serology is a cornerstone in the diagnosis of acute rheumatic fever (ARF), a postinfectious sequela associated with group A Streptococcus infection. Current tests that measure anti-streptolysin O (ASO) and anti-DNaseB (ADB) titers require parallel processing, with their predictive value limited by the low rate of decay in antibody response. Accordingly, our objective was to develop and assess the diagnostic potential of a triplex bead-based assay, which simultaneously quantifies ASO and ADB together with titers for a third antigen, SpnA. Our previous cytometric bead assay was transferred to the clinically appropriate Luminex platform by coupling streptolysin O, DNaseB, and SpnA to spectrally unique magnetic beads. Sera from more than 350 subjects, including 97 ARF patients, were used to validate the assay and explore immunokinetics. Operating parameters demonstrate that the triplex assay produces accurate and reproducible antibody titers which, for ASO and ADB, are highly correlative with existing assay methodology. When ARF patients were stratified by time (days following hospital admission), there was no difference in ASO and ADB between <28 and 28+ day groups. However, for anti-SpnA, there was a significant decrease (P < 0.05) in the 28+ day group, indicative of faster anti-SpnA antibody decay. Anti-SpnA immunokinetics support very recent group A Streptococcus infection and may assist in diagnostic classification of ARF. Further, bead-based assays enable streptococcal serology to be performed efficiently in a high-throughput manner.

Antistreptolysin O titer and C-reactive protein levels in pediatric patients of acute rheumatic fever.

Objectives: To determine serum levels of antistreptolysin O titre (ASOT) and C-reactive protein (CRP) and their association with clinical manifestations of Acute rheumatic fever (ARF). Study Design: Descriptive study. Setting: Department of Diagnostic Immunology and Serology, Children’s Hospital and Institute of Child Health, Lahore. Period: Jan 2015 to Jan 2016. Material &amp; Methods: Fifty clinically confirmed patients of ARF were included in this descriptive study. The samples were taken from Children hospital and Institute of child health Lahore after written informed consent. The sampling technique was convenient sampling. Results: Out of 50 enrolled patients, males were 32(64%) and women 18(36%). Only 5(10%) patients had normal ASOT levels, 20(40%) patients were with borderline ASOT, and 25(50%) patients had titres above 200 IU/ml. There was no significant association of ASOT with gender, age and arthralgia with p-value = 0.060, 0.875 and 0.473, respectively. However, a significant association was found in ASOT with carditis and C-reactive protein (p-value = 0.028 and 0.014, respectively). Only 3 (6%) patients had CRP levels below 6mg/l, whereas 43 (86%) patients were with CRP levels above 6. Only 4(8%) patients had borderline value of CRP titer. There was no significant association between C-reactive protein with gender, age and arthralgia (p-value = 0.148, 0.184 and 0.574, respectively). Moreover, there was a significant association between C-reactive protein with carditis and AOST (p-value = 0.020 and 0.014, respectively). Conclusion: ASOT and CRP are important laboratory parameters reflecting undergoing infection (mainly caused by Streptococcus pyogenes A) and inflammation in patients of ARF. Rising levels of ASOT and CRP in ARF patients might be used as an indicator of involvement of heart tissues and therefore can be used to monitor transition of rheumatic carditis into Rheumatic heart disease.

Environmental Factors Related to Acute Rheumatic Fever and Rheumatic Heart Disease in Aceh Province

Acute rheumatic fever (ARF) is the body’s immune system reacting to an untreated infection with Group A Streptococcus (GAS) that affects skin, joints, brain, and heart. The heart damage that remains after an occurrence of ARF is called rheumatic heart disease (RHD). The objective of this study was to evaluate the ARF and RHD based on the profile of clinical diagnoses and emerging factors. The data were collected through interviews of the subjects, complete blood counts, the anti-streptolysin titer O analysis, the C-reactive protein Assay, and a statistical analysis. This research was a combination of clinical assessments, the CRP kit, anti-titer O kit, and interviews. The data were analyzed by employing Wilcoxon, Chi-square and Friedman test and also included a correlation analyzed using Spearman’s correlation with significance of (p&lt;0.05. There were 63 samples of ARF and RHD patients involved, consisting of male (50.8%:32) and female (49.9%:31) patients (p&lt;0.05). The factors that triggered ARF and RHD (p&lt;0.05; r=0.88) as well as laboratory diagnosis (p&lt;0.05) of these infections were measured. The ARF caused by residence also caused RHD by the interaction of time with the environment (p&lt;0.05). The population consisted of males (32:50.8%) and females (31:49.2%), and it was not significant (p&gt;0.05), while the streptococcal infection of RHD (63.5%) was much larger than in ARF (36.5%). This was based on the clinical diagnosis of RHD and ARF with a significance of (p&lt;0.05). Also, the residence and the period of interaction with the environment were influences on the RHD and ARF.

678 Profile of Paediatric Tertiary Hospital-Referred Acute Rheumatic Fever Patients in Western Australia Over a 30-Year Period

678 Profile of Paediatric Tertiary Hospital-Referred Acute Rheumatic Fever Patients in Western Australia Over a 30-Year Period

The effect of group A streptococcal carrier on the epidemic model of acute rheumatic fever

BackgroundGroup A streptococcus (GAS) is the most frequent cause of bacterial pharyngitis in school-aged children. The postinfection sequel as acute rheumatic fever (ARF) and rheumatic heart disease that cause morbidity and mortality among young people is public health concerns in several developing countries. Asymptomatic carriage state of GAS is not fully understood in terms of host and bacterial factors. Although the ability of transmitting GAS of the asymptomatic carriers is relatively low, they may present the reservoir of the epidemic. A fraction of GAS carriers is difficult to estimate in practice and may greatly vary between populations. Understanding the role of carriage on the transmission dynamic of GAS is important for assessing the public health impact of the ARF.MethodThis study investigates the effect of GAS carriers on both the transmission and dynamic of ARF cases by using a mathematical model.ResultWe derive the sufficient conditions for which the GAS can spread or extinct from the naive population under the variation of the fraction of symptomatic cases over the incidence of GAS. The threshold is possible to occur in general, but the last condition which is rather restrictive and involves parameter uncertainty. The increasing of carriers in the endemic state leads to the reduction in magnitude of the reproduction number and the number of ARF patients. We demonstrate that the adjustment of parameters can be carried out by the use of endemic state and some specific data.ConclusionWe show theoretically that the presence of asymptomatic carriers may induce the epidemic threshold and reduce the virulence of GAS and the prevalence of ARF.

Comparison of antistreptolysin O and anti-deoxyribonucleic B titers in healthy children to those with acute pharyngitis, acute rheumatic fever, and rheumatic heart disease aged 5-15 years.

Background:Acute rheumatic fever (ARF) affects millions of children in the third world countries like India. The diagnosis of rheumatic fever is based on the Jones criteria with serological titers, antistreptolysin O titer (ASO), and anti-deoxyribonucleic B (ADB), taken as evidence of recent streptococci infection. There is a lack of recent data available on ASO and ADB titers in children from the Delhi/NCR and thus adequate geographical area-specific cutoffs for the region are not available.Aims and Objectives:The aim of this study is to determine and compare the ASO and ADB antibody titers in children with acute pharyngitis, ARF, rheumatic heart disease (RHD), and in healthy children of the Delhi/NCR region.Materials and Methods:Twenty-six cases of ARF, 51 cases of RHD, 50 cases of acute pharyngitis, and 84 healthy normal children were included in the study. A single ASO and ADB titer measurement was done in these children.Results:The ASO titers was raised in acute pharyngitis – 303 IU/ml (interquartile range [IQR], 142–520 IU/ml) and ARF – 347.5 IU/ml (IQR, 125–686 IU/ml) children in comparison to healthy controls – 163.5 IU/ml (IQR, 133–246.5 IU/ml) and RHD patients – 163 IU/ml (IQR, 98.250–324.500). The ADB titers were highest in ARF patients – 570.5 IU/ml (IQR, 276–922 IU/ml) followed with RHD – 205 IU/ml (IQR, 113.6–456.5), healthy controls – 78.25 IU/ml (IQR, 53.39–128.15 IU/ml), and acute pharyngitis – 75.12 IU/ml (IQR, 64.5–136 IU/ml). The upper limit of normal (ULN) values of ASO and ADB computed from normal healthy children were 262.4 IU/ml and 134.44 IU/ml, respectively, and these can be used as cutoff values for recent streptococcal infection in this geographical area.Conclusions:The median ASO titers in acute pharyngitis group and ARF were significantly raised compared to that of the control group. The ADB titers were raised in ARF and RHD patients albeit the levels were higher in ARF patients. The derived ULN values can be used as cutoff reference.

Identification of Carditis in Acute Rheumatic Fever with Myocardial T1 Mapping

Background: The pathogenesis of acute rheumatic fever (ARF) is incompletely understood. Valvulitis is used as part of the diagnostic criteria, while pancarditis has only been demonstrated at autopsy. Purpose: To identify carditis in patients with ARF using T1 mapping on cardiac magnetic resonance (CMR) imaging and echocardiographic global longitudinal strain (GLS). We hypothesised that prolonged native T1 time, consistent with myocardial inflammation, would be present in ARF patients compared to controls. Methods: We prospectively recruited 36 patients; 15 fulfilling the Australian modified Jones Criteria for the diagnosis of ARF, 12 controls with an inflammatory condition without major criteria for ARF and 9 healthy controls. All patients underwent CMR with assessment of non-contrast myocardial T1 mapping as well as echocardiography for GLS. The primary outcome was differences in T1 time between the groups. Results: Patients with ARF had evidence of carditis demonstrated by markedly elevated T1 times [976 (± 167 ms)] compared to those with non-cardiac inflammatory conditions [841 (±50 ms)] and healthy controls [811 (±54 ms)], P = 0.002 (Fig. 1). There was no difference in global longitudinal strain between the groups (−19.4% vs −19.5% vs −20.4%, P = 0.66). Conclusions: Patients with ARF have markedly elevated myocardial T1 times on CMR, consistent with active inflammation from carditis. In contrast, GLS was normal in ARF patients. Incorporating CMR T1 mapping into the diagnostic algorithm for ARF may improve diagnostic certainty and lead to more effective delivery of secondary penicillin prophylaxis.

Identifying Carditis in Acute Rheumatic Fever With Myocardial T1 Mapping

Background: The pathogenesis of acute rheumatic fever (ARF) is incompletely understood. Valvulitis is used as part of the diagnostic criteria, while pancarditis has only been demonstrated at autopsy. Purpose: To identify carditis in patients with ARF using T1 mapping on cardiac magnetic resonance (CMR) imaging and echocardiographic global longitudinal strain (GLS). We hypothesised that prolonged native T1 time, consistent with myocardial inflammation, would be present in ARF patients compared to controls. Methods: We prospectively recruited 36 patients; 15 fulfilling the Australian modified Jones Criteria for the diagnosis of ARF, 12 controls with an inflammatory condition without major criteria for ARF and 9 healthy controls. All patients underwent CMR with assessment of non-contrast myocardial T1 mapping as well as echocardiography for GLS. The primary outcome was differences in T1 time between the groups. Results: Patients with ARF had evidence of carditis demonstrated by markedly elevated T1 times [976(±167 ms)] compared to those with non-cardiac inflammatory conditions [841(±50 ms)] and healthy controls [811(±54 ms)], P = 0.002 (Figure 1). There was no difference in global longitudinal strain between the groups (−19.4% vs −19.5% vs −20.4%, P = 0.66). Conclusions: Patients with ARF have markedly elevated myocardial T1 times on CMR, consistent with active inflammation from carditis. In contrast, GLS was normal in ARF patients. Incorporating CMR T1 mapping into the diagnostic algorithm for ARF may improve diagnostic certainty and lead to more effective delivery of secondary penicillin prophylaxis.

Streptococcal Serology in Acute Rheumatic Fever Patients: Findings From 2 High-income, High-burden Settings.

Globally, there is wide variation in streptococcal titer upper limits of normal (ULN) for antistreptolysin O (ASO) and anti-deoxyribonuclease B (ADB) used as an evidence of recent group A streptococcal infection to diagnose acute rheumatic fever (ARF). We audited ASO and ADB titers among individuals with ARF in New Zealand (NZ) and in Australia's Northern Territory. We summarized streptococcal titers by different ARF clinical manifestations, assessed application of locally recommended serology guidelines where NZ uses high ULN cut-offs and calculated the proportion of cases fulfilling alternative serologic diagnostic criteria. From January 2013 to December 2015, group A streptococcal serology results were available for 350 patients diagnosed with ARF in NZ and 182 patients in Northern Territory. Median peak streptococcal titers were similar in both settings. Among NZ cases, 267/350 (76.3%) met NZ serologic diagnostic criteria, whereas 329/350 (94.0%) met Australian criteria. By applying Australian ULN titer cut-off criteria to NZ cases, excluding chorea, ARF definite cases would increase by 17.6% representing 47 cases. ASO and ADB values were similar in these settings. Use of high ULN cut-offs potentially undercounts definite and probable ARF diagnoses. We recommend NZ and other high-burden settings to use globally accepted, age-specific, lower serologic cut-offs to avoid misclassification of ARF.

Using preceding hospital admissions to identify children at risk of developing acute rheumatic fever

New Zealand (NZ) Māori and Pacific children have high rates of acute rheumatic fever (ARF). Around 150 new cases arise each year. As part of the national ARF prevention programme, funding is available to improve housing. To obtain maximum benefit from interventions, an effective tool is needed for targeting high-risk children. This study aimed to assess the effectiveness of using hospitalisations for identifying children at risk of subsequent ARF. Three potentially avoidable hospitalisation (PAH) groups were investigated, including diseases thought to be influenced by housing. All were developed using expert opinion or systematic reviews. These were: (i) the PAH conditions associated with the housing environment (PAHHE) group; (ii) the Crowding group; and (iii) the Ministry of Health (MoH) group. We analysed NZ public hospital discharge data (2000-2014). The prevalence of ARF among patients hospitalised in each group was calculated to estimate sensitivity and potential effectiveness. The number needed to screen (NNS) to identify one ARF case was estimated as a measure of efficiency. Nearly one-third of ARF patients experienced a PAH as children (before developing ARF). Sensitivity for detecting future ARF ranged from <5% (MoH group) to 27% (PAHHE group). NNS ranged from 502.4 (PAHHE) to 707.5 (MoH). Because ARF is relatively rare, observing hospitalisations is not particularly efficient for targeting prevention activities for this condition alone. However, housing interventions are likely to improve multiple outcomes; thus, the hospital setting is still useful for identifying at-risk children who could benefit from such programmes.