| 1. |
- de Glanville, William A., et al.
(författare)
-
Poor performance of the rapid test for human brucellosis in health facilities in Kenya
- 2017
-
Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:4
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 2. |
- Morin, Matilda
(författare)
-
Etiology and prognosis of spondyloarthropathies using family-based epidemiological methods
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The spondyloarthropathies (SpA) are a group of chronic inflammatory diseases that share several disease characteristics such as inflammation of entheses and extramusculoskeletal manifestations like uveitis, psoriasis, and inflammatory bowel disease. These diseases, or symptoms thereof, are also known to run in families. The purpose of this thesis was to expand knowledge concerning the etiology and prognosis of SpA, using family-based epidemiological methods on data from Swedish health and population registers. In study I, we estimated the familial aggregation of a specific SpA subtype, ankylosing spondylitis (AS), in a nested case-control study of AS cases, population controls, and first-degree relatives of both groups. We were able to provide a precise estimate of the familial aggregation, corresponding to a 20-fold increased risk of AS among first-degree relatives of AS cases. We also estimated the heritability of AS to 77%, i.e. the proportion of susceptibility to AS in the population that is due to genetics. Our estimate can be seen as an upper limit for the heritability, as shared environmental effects were not considered. While both estimates are relatively high, they are lower than previous reports for AS, which have been based on small and often selected samples. In study II, a cohort study, we investigated whether family history of SpA, or its specific subtypes, were predictive of response to treatment with tumor necrosis factor inhibitors (TNFi) in patients with SpA. Despite being such a strong risk factor for disease development, we did not find family history to be associated with prognosis in terms of TNFi drug survival or treatment response at three or twelve months. In study III, we studied temporal trends in pregnancy outcomes among women with axial SpA. We found that women with axial SpA, compared to women from the general population, were at increased risk of pre-eclampsia, preterm birth, and serious infection in the infant. The proportion of cesarean deliveries was also significantly higher among women with axial SpA. The risks had, however, diminished over the last decade, to reach similar levels as in the general population, while the use of effective treatment in the form of TNFi increased before and during pregnancy over the same period. In study IV, we searched for environmental risk factors for AS, with a focus on perinatal characteristics and infections in childhood. In this nested case-control study, we found that having older siblings and a history of tonsillectomy in childhood were associated with AS in adulthood, even after adjustment for childhood socio-economic status and other family-shared confounders through a sibling comparison. By using data from national registers, we were able to perform the hitherto largest studies on these topics regarding etiology and prognosis of SpA. While the genetic influence is substantial in AS, there is a larger contribution of environmental risk factors than previously known. These seem partly related to early life, with a possible influence of childhood infections. We have also added to a growing body of evidence supporting the use of effective treatment in women with axial SpA, before and at least in the beginning of pregnancy, to minimize the risks active that SpA disease pose on pregnancy outcomes.
|
|
| 3. |
- Morin, Matilda, et al.
(författare)
-
Temporal trends in adverse pregnancy outcomes in axial spondyloarthritis in Sweden : a cohort study
- 2023
-
Ingår i: The Lancet Rheumatology. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. - 2665-9913.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence on the risks associated with pregnancy and childbirth in women with axial spondyloarthritis is scarce and conflicting, with more research needed to guide policy and clinical practice. We aimed to assess the risks of adverse pregnancy outcomes in a large cohort of women with axial spondyloarthritis, and to investigate how outcomes varied over time and in relation to anti-rheumatic treatment. Methods: In this register-based cohort study, we included births in Sweden between April 1, 2007, and Dec 31, 2020, to women with axial spondyloarthritis and general population comparators, matched 1:10 on year of delivery, maternal age, and parity. Our main data source was the Medical Birth Register (MBR), which includes over 98% of births in Sweden and prospectively collects data on antenatal care, delivery, and foetal outcomes. The information in MBR was linked to other registers, including the National Patient Register, the Prescribed Drug Register, and registers with demographic data. Our main outcomes were the relative risks of adverse pregnancy outcomes, analysed using modified Poisson regression. We also studied how the frequency of certain adverse outcomes, as well as disease-modifying antirheumatic drug (DMARD) and non-steroidal anti-inflammatory drug treatments, changed over the study period by linear regression and loess plots. Findings: Between April 1, 2007, and Dec 31, 2020, 1580 births in women with axial spondyloarthritis recorded in MBR fulfilled the inclusion criteria and were matched with 15 792 comparator births. Among the 1580 births in women with axial spondyloarthritis, we found increased risks of preterm birth (risk ratio 1.43, 95% CI 1.13-1.80), pre-eclampsia (1.44, 1.08-1.92), elective caesarean delivery (1.59, 1.37-1.84), and serious infant infection (1.29, 1.05-1.59) compared with births in general population comparators. The risks of preterm birth, infant infection, and caesarean delivery decreased by around 0.5 percentage points annually during the study period, while the use of tumour necrosis factor inhibitors during pregnancy increased. Interpretation: In view of remaining concerns regarding safety of the use of biological DMARDs during pregnancy, we saw a reassuring trend in which pregnancy outcomes improved over time in the axial spondyloarthritis group, concurrent with increased use of biological DMARDs. If the current rate of improvement is maintained, women with axial spondyloarthritis treated in accordance with clinical guidelines might eventually not be at an increased risk of adverse pregnancy outcomes.
|
|
