Human brucellosis is considered to be an important but typically under-diagnosed cause of febrile illness in many low and middle-income countries. In Kenya, and throughout East Africa, laboratory diagnosis for the disease is based primarily on the febrile antigen Brucella agglutination test (FBAT), yet few studies of the diagnostic accuracy of this test exist. Assessment of the performance of the FBAT is essential for its appropriate clinical use, as well as for evaluating surveillance data reported by public health systems. To assess FBAT performance, we collected sera from people with symptoms compatible with brucellosis attending two health facilities in Busia County, Kenya. Sera were tested using the FBAT and results compared with those from the Rose Bengal Test (RBT), an assay with well-known performance characteristics. Positives on either test were confirmed using the classical serum agglutination test (SAT)-Coombs test combination and a rapid IgM/IgG lateral flow immunochromatography assay (LFA). A questionnaire focussing on known risk factors for exposure to Brucella spp. was also conducted, and relationships with FBAT positivity examined using logistic regression. Out of 825 recruited individuals, 162 (19.6%) were classified as positive using the FBAT. In contrast, only eight (1.0%) were positive using the RBT. Of the 162 FBAT positives, one (0.62%) had an atypical agglutination in SAT and three (1.9%) showed low Coombs titres. Out of 148 FBAT positive individuals tested using the LFA, five (3.4%) were IgM positive and none were IgG positive. Poor or no correlation was observed between FBAT results and most established risk factors for Brucella infection. We observed substantial disagreement between the FBAT and a number of well-known serological tests, with the majority of reactive FBAT results appearing to be false positives. Poor FBAT specificity, combined with a lack of confirmatory testing, strongly suggests overdiagnosis of brucellosis is common in this low prevalence setting. This is expected to have important economic impacts on affected patients subjected to the long and likely unnecessary courses of multiple antibiotics required for treatment of the disease.

ObjectiveLongitudinal clinical registry-infrastructures such as Anti-Rheumatic Therapies in Sweden (ARTIS) allow simultaneous comparison of the safety of individual immunomodulatory drugs used in clinical practice, with consistent definitions of treatment cohorts, follow-up and outcomes. Our objective was to assess and compare incidence rates of key safety outcomes for individual targeted synthetic or biological disease-modifying antirheumatic drugs (b/ts DMARDs) in rheumatoid arthritis (RA), updating previous reports and including newer treatments including Janus Kinase inhibitors (JAKi).MethodsNationwide register-based cohort study including all patients with RA in Sweden registered as starting any b/tsDMARD 1 January 2010 through 31 December 2020, followed until 30 June 2021 (N=20 117). The incidence rates of selected outcomes, identified through national healthcare registers, were compared between individual b/tsDMARDs, adjusted for confounding by demographics, RA disease characteristics and comorbidity.ResultsThere were marked differences in treatment discontinuations due to adverse events (rates per 1000 person-years ranged from 18 on rituximab to 57 on tofacitinib), but few significant differences were observed for the serious adverse events under study. Neither cardiovascular events nor general serious infections were more frequent on baricitinib or tofacitinib versus bDMARDs, but JAKi were associated with higher rates of hospital-treated herpes zoster (HR vs etanercept, 3.82 (95% CI 2.05 to 7.09) and 4.00 (1.59 to 10.06)). Low number of events limited some comparisons, in particular for sarilumab and tofacitinib.ConclusionData from ARTIS supports that the b/tsDMARDs currently used to treat RA have acceptable and largely similar safety profiles, but differences exist in particular concerning tolerability and specific infection risks.

Objectives AS is known to be a highly heritable disease, but previous studies on the magnitude of the familial aggregation and heritability of AS have been small and inconclusive, with familial relative risks ranging from 17 to 94. We aimed to improve estimates of these factors by studying families of all subjects diagnosed with AS in Sweden over a period of 16 years and to investigate if familial risks vary by sex or type of relative. Methods In a nested case–control study, we identified AS index patients from the National Patient Register (NPR) and the Swedish Rheumatology Quality Register (SRQ) between 2001 and 2016. Each index patient was matched on age and sex to up to 50 general population controls. First-degree relatives of index patients and controls were identified through the Multi-Generation Register, with disease status ascertained in the NPR and SRQ. Familial risks were defined as odds ratios (ORs) of having AS when exposed to a first-degree relative with AS, using conditional logistic regression. Results The overall familial OR for AS was 19.4 (95% CI 18.1, 20.8). Estimates were similar for different relative types and by sex, but having more than one affected relative resulted in a higher risk [OR 68.0 (95% CI 51.3, 90.1)]. Heritability, estimated by assuming sibling risks were completely due to genetics, was 77% (95% CI 73, 80). Conclusion Although the familial risk and heritability of AS are higher than for most other diseases, we report estimates that are substantially lower than commonly referenced numbers for AS from other populations.

Legionella pneumophila, a Gram-negative bacillus, is the causative agent of Legionnaire’s disease, a form of severe community-acquired pneumonia. Infection can have high morbidity, with a high proportion of patients requiring ICU admission, and up to 10% mortality, which is exacerbated by the lack of efficacy of typical empirical antibiotic therapy against Legionella spp. The fastidious nature of the entire Legionellaceae family historically required inclusion of activated charcoal in the solid medium to remove growth inhibitors, which inherently interferes with accurate antimicrobial susceptibility determination, an acknowledged methodological shortfall, now rectified by a new solid medium that gives results comparable to those of microbroth dilution. Here, as an international Legionella community (with authors representing various international reference laboratories, countries and clinical stakeholders for diagnosis and treatment of legionellosis), we set out recommendations for the standardization of antimicrobial susceptibility testing methods, guidelines and reference strains to facilitate an improved era of antibiotic resistance determination.

BackgroundAn increased risk of adverse pregnancy and neonatal outcomes has been reported for pregnancies in women with several rheumatic diseases including rheumatoid arthritis and psoriatic arthritis. In spondyloarthritis (SpA), findings have not been uniform, with some studies reporting increased risks of Cesarean delivery, preterm birth, infants born small-for-gestational-age (SGA), and gestational diabetes- and hypertension, while others have failed to identify any significant differences between women with SpA and general population control women. Most studies reporting no differences have either been small or lacked an appropriate comparison group [1].ObjectivesTo assess the risk of adverse maternal and infant pregnancy outcomes in women with SpA compared to the general population.MethodsIn this nationwide register-based study, we included singleton births between April 2007 and December 2019 in women diagnosed with ankylosing spondylitis (AS; ICD-10 codes M45 or M08.1) or undifferentiated SpA (uSpA; ICD-10 codes M46.8 or M46.9). This was performed through linkage between the National Patient Register and the Medical Birth Register. Each birth was matched on birth year, maternal age, and parity to ten comparator births in women free from chronic inflammatory arthritis at time of birth. Relative risks (RR) of adverse outcomes were estimated by Poisson regression, adjusting for maternal country of birth, BMI, smoking in early pregnancy, educational level, and disposable income in the year before pregnancy.ResultsWomen with SpA (n=1394) were found to be at increased risk of several adverse outcomes compared to general population comparators (n=13932), as displayed in the Figure 1. Women with SpA had an increased risk of gestational diabetes (adjusted RR 1.88 [95% CI 1.10; 2.56]), elective and emergency Cesarean delivery (adjusted RR 1.54 [95% CI 1.32; 1.79] and 1.23 [95% CI 1.02; 1.48], respectively), and moderately preterm birth (adjusted RR 1.52 [95% CI 1.18; 1.97]). An association was seen with both spontaneous and medically indicated preterm birth, but the increase was only significant for spontaneous preterm birth. The risk estimate for preeclampsia was also increased, but failed to reach significance (adjusted RR 1.32 [95% CI 0.96; 1.81]). Infants to mothers with SpA were not more likely to be born SGA, but there was a slightly increased risk estimate of infection during their first year of life (adjusted RR 1.23 [95% CI 0.98; 1.53]).Figure 1.Number of events of adverse pregnancy outcomes among a nationwide cohort of births (n=1394) in Swedish women with SpA and comparator births (n=13932, matched 1:10 on birth year, maternal age, and parity). Relative risks from Poisson regression, adjusted for maternal country of birth, BMI, smoking in early pregnancy, educational level, and disposable income in the year before pregnancy.ConclusionWhile most pregnancies in women with SpA are uneventful, there is an increased risk for a number of adverse pregnancy outcomes. The increased risks for both emergency Cesarean delivery and spontaneous preterm birth suggest that these differences are not only driven by a different management of SpA pregnancies.References[1]Mokbel A, Lawson DO, Farrokhyar F. Pregnancy outcomes in women with ankylosing spondylitis: a scoping literature and methodological review. Clinical Rheumatology 2021;40(9):3465-80.Disclosure of InterestsNone declared