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- Andersson, Marie, 1962-
(author)
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Immunopathogenesis of relapsing fever borreliosis
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Relapsing fever (RF) is caused by different species of Borrelia transmitted by soft ticks or by the human body louse. Illness is characterized by reappearing peaks of high concentrations of spirochetes in blood, concordant with fever peaks separated by asymptomatic periods. Neuroborreliosis is one of the most severe manifestations of RF borreliosis. To understand the immune response during early RF, we analyzed immune cells in brain and kidney of mice infected with B. crocidurae during the acute infection. Our results indicate that brain defense is comprised primarily of innate immune cells. Despite the infiltration of innate immune cells, Borrelia was not completely eradicated. A failure of the host brain to clear the bacteria may give the pathogen a niche where it can persist. Using our mouse model, we revealed that Borrelia duttonii could persist in the mouse brain for up to 270 days, without being present in the circulation. The infection was silent with no change in host gene expression, and the spirochetes could re-enter the circulation after immunosuppression. We propose that the brain is used by the pathogen to evade host immunity and serves as a possible natural reservoir for B. duttonii, a spirochete that has rarely been found in any mammalian host other than man. Borrelia-induced complications during pregnancy have been reported, and are especially common in RF. In our established mouse model of gestational RF, we could show that the fetuses suffered from severe pathology and growth retardation, probably as a consequence of placental destruction. We could also show trans-placental transmission of the bacteria leading to neonatal RF. Surprisingly, pregnant dams had a lower bacterial load and less severe disease, showing that pregnancy has a protective effect during RF. We have used the gestational RF model to investigate host factors favoring disease resolution. Because the spleen is the primary organ responsible for trapping and removing blood-borne pathogens, we have compared temporal changes in spleen immune cell populations and cytokine/chemokine induction during the infection. Spleens of pregnant mice had earlier neutrophil infiltration, as well as faster and higher production of pro-inflammatory mediators. This rapid, robust response suggests a more effective host defense. Thus, an enhanced pro-inflammatory response during pregnancy imparts a distinct advantage in controlling the severity of relapsing fever infection.
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- Arokiasamy, Perianayagam, et al.
(author)
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Chronic Noncommunicable Diseases in 6 Low-and Middle-Income Countries : Findings From Wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (SAGE)
- 2017
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 185:6, s. 414-428
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Journal article (peer-reviewed)abstract
- In this paper, we examine patterns of self-reported diagnosis of noncommunicable diseases (NCDs) and prevalences of algorithm/measured test-based, undiagnosed, and untreated NCDs in China, Ghana, India, Mexico, Russia, and South Africa. Nationally representative samples of older adults aged >= 50 years were analyzed from wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (2007-2010; n = 34,149). Analyses focused on 6 conditions: angina, arthritis, asthma, chronic lung disease, depression, and hypertension. Outcomes for these NCDs were: 1) self-reported disease, 2) algorithm/measured test-based disease, 3) undiagnosed disease, and 4) untreated disease. Algorithm/measured test-based prevalence of NCDs was much higher than self-reported prevalence in all 6 countries, indicating underestimation of NCD prevalence in low-and middle-income countries. Undiagnosed prevalence of NCDs was highest for hypertension, ranging from 19.7% (95% confidence interval (CI): 18.1, 21.3) in India to 49.6% (95% CI: 46.2, 53.0) in South Africa. The proportion untreated among all diseases was highest for depression, ranging from 69.5% (95% CI: 57.1, 81.9) in South Africa to 93.2% (95% CI: 90.1, 95.7) in India. Higher levels of education and wealth significantly reduced the odds of an undiagnosed condition and untreated morbidity. A high prevalence of undiagnosed NCDs and an even higher proportion of untreated NCDs highlights the inadequacies in diagnosis and management of NCDs in local health-care systems.
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- Guo, Betty P, et al.
(author)
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Relapsing fever Borrelia binds to neolacto glycans and mediates rosetting of human erythrocytes.
- 2009
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 106:46, s. 19280-5
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Journal article (peer-reviewed)abstract
- A hallmark of acute relapsing fever borreliosis is severe bacteremia. Some Borrelia species, such as B. duttonii and B. crocidurae, associate with erythrocytes and induce aggregation recognized as erythrocyte rosetting. Erythrocyte rosettes contribute to disease severity by increased tissue invasiveness (such as invasion of CNS and encephalitis), hemorrhaging, and reduced blood flow in affected microcapillaries. Here we report that relapsing fever Borrelia binds to neolacto (Galbeta4GlcNAcbeta3Galbeta4Glcbeta1)-carrying glycoconjugates that are present on human erythrocytes. This interaction is of low affinity but is compensated for by the multivalency of neo-lacto-oligosaccharides on the erythrocyte cell surface. Hence, the protein-carbohydrate interaction is dependent on multivalent neolacto-glycans to mediate binding.
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- Larsson, Christer, 1975-, et al.
(author)
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Complications of pregnancy and transplacental transmission of relapsing-fever borreliosis
- 2006
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 194:10, s. 1367-1374
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Journal article (peer-reviewed)abstract
- Relapsing-fever borreliosis caused by Borrelia duttonii is a common cause of complications of pregnancy, miscarriage, and neonatal death in sub-Saharan Africa. We established a murine model of gestational relapsing fever infection for the study of the pathological development of these complications. We demonstrate that B. duttonii infection during pregnancy results in intrauterine growth retardation, as well as placental damage and inflammation, impaired fetal circulation, and decreased maternal hemoglobin levels. We show that spirochetes frequently cross the maternal-fetal barrier, resulting in congenital infection. Furthermore, we compared the severity of infection in pregnant and nonpregnant mice and show that pregnancy has a protective effect. This model closely parallels the consequences of human gestational infection, and our results provide insight into the mechanisms behind the complications of pregnancy that have been reported in human relapsing-fever infection.
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- Larsson, Christer, 1975-, et al.
(author)
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Persistent brain infection and disease reactivation in relapsing fever borreliosis
- 2006
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In: Microbes and infection. - : Elsevier. - 1286-4579 .- 1769-714X. ; 8:8, s. 2213-2219
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Journal article (peer-reviewed)abstract
- Relapsing fever, an infection caused by Borrelia spirochetes, is generally considered a transient, self-limiting disease in humans. The present study reveals that murine infection by Borrelia duttonii can be reactivated after an extended time as a silent infection in the brain, with no bacteria appearing in the blood and spirochete load comparable to the numbers in an infected tick. The host cerebral gene expression pattern is indistinguishable from that of uninfected animals, indicating that persistent bacteria are not recognized by the immune system nor cause noticeable tissue damage. Silent infection can be reactivated by immunosuppression, inducing spirochetemia comparable to that of initial densities. B. duttonii has never been found in any host except man and the tick vector. We therefore propose the brain to be a possible natural reservoir of the spirochete. The view of relapsing fever as an acute disease should be extended to include in some cases prolonged persistence, a feature characteristic of the related spirochetal infections Lyme disease and syphilis.
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- Wu, Fan, et al.
(author)
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Common risk factors for chronic non-communicable diseases among older adults in China, Ghana, Mexico, India, Russia and South Africa : the study on global AGEing and adult health (SAGE) wave 1
- 2015
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In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 15
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Journal article (peer-reviewed)abstract
- Background: Behavioral risk factors such as tobacco use, unhealthy diet, insufficient physical activity and the harmful use of alcohol are known and modifiable contributors to a number of NCDs and health mediators. The purpose of this paper is to describe the distribution of main risk factors for NCDs by socioeconomic status (SES) among adults aged 50 years and older within a country and compare these risk factors across six lower- and upper-middle income countries. Methods: The study population in this paper draw from SAGE Wave 1 and consisted of adults aged 50-plus from China (N=13,157), Ghana (N=4,305), India (N=6,560), Mexico (N=2,318), the Russian Federation (N=3,938) and South Africa (N=3,836). Seven main common risk factors for NCDs were identified: daily tobacco use, frequent heavy drinking, low level physical activity, insufficient vegetable and fruit intake, high risk waist-hip ratio, obesity and hypertension. Multiple risk factors were also calculated by summing all these risk factors. Results: The prevalence of daily tobacco use ranged from 7.7% (Ghana) to 46.9% (India), frequent heavy drinker was the highest in China (6.3%) and lowest in India (0.2%), and the highest prevalence of low physical activity was in South Africa (59.7%). The highest prevalence of respondents with high waist-to-hip ratio risk was 84.5% in Mexico, and the prevalence of self-reported hypertension ranging from 33% (India) to 78% (South Africa). Obesity was more common in South Africa, the Russia Federation and Mexico (45.2%, 36% and 28.6%, respectively) compared with China, India and Ghana (15.3%, 9.7% and 6.4%, respectively). China, Ghana and India had a higher prevalence of respondents with multiple risk factors than Mexico, the Russia Federation and South Africa. The occurrence of three and four risk factors was more prevalent in Mexico, the Russia Federation and South Africa. Conclusion: There were substantial variations across countries and settings, even between upper-middle income countries and lower-middle income countries. The baseline information on the magnitude of the problem of risk factors provided by this study can help countries and health policymakers to set up interventions addressing the global non-communicable disease epidemic.
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