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- Lundqvist, Jenny, 1975-, et al.
(författare)
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Mixed infection decreases malaria burden and escalate relapsing fever
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- About 500 million cases of malaria occur annually. However, a substantial number of patients who actually have relapsing fever (RF) Borrelia are misdiagnosed with malaria due to similar manifestation and geographic distribution of the two diseases. More alarmingly, high prevalence of mixed infections with malaria and RF Borrelia has been reported. Therefore, we developed a mouse model to study the effects of such mixed infection. We observed a 21-fold increase in spirochete titers, whereas parasitemia decreased 15-fold. This may be explained by polarization of the host immune response towards the intracellular malaria parasite, resulting in unaffected extracellular spirochetes and hosts succumb to sepsis. Furthermore, secondary malaria infection can reactivate a quiescent RF brain infection, which is the first evidence of a clinically and biologically relevant cue for reactivation of dormant RF Borrelia infection. Mixed infection also resulted in severe anemia even though the parasite counts were low. Our study highlights the importance of investigating mixed infections in vivo to elucidate the immune responses that are involved in the clinical outcome, and it also emphasizes the urgent need for improved diagnostics of malaria and other infectious diseases such as RF Borrelia.
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| 2. |
- Nelson, Andreas, et al.
(författare)
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Subjective cognitive complaints and its associations to response inhibition and neural activation in patients with stress-related exhaustion disorder
- 2023
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Ingår i: Stress. - : Taylor & Francis. - 1025-3890 .- 1607-8888. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Stress-related exhaustion is associated with cognitive deficits, measured subjectively using questionnaires targeting everyday slips and failures or more objectively as performance on cognitive tests. Yet, only weak associations between subjective and objective cognitive measures in this group has been presented, theorized to reflect recruitment of compensational resources during cognitive testing. This explorative study investigated how subjectively reported symptoms of cognitive functioning and burnout levels relate to performance as well as neural activation during a response inhibition task. To this end, 56 patients diagnosed with stress-related exhaustion disorder (ED; ICD-10 code F43.8A) completed functional magnetic resonance imaging (fMRI) using a Flanker paradigm. In order to investigate associations between neural activity and subjective cognitive complaints (SCCs) and burnout, respectively, scores on the Prospective and Retrospective Memory Questionnaire (PRMQ) and the Shirom-Melamed Burnout Questionnaire (SMBQ) were added as covariates of interest to a general linear model at the whole-brain level. In agreement with previous research, the results showed that SCCs and burnout levels were largely unrelated to task performance. Moreover, we did not see any correlations between these self-report measures and altered neural activity in frontal brain regions. Instead, we observed an association between the PRMQ and increased neural activity in an occipitally situated cluster. We propose that this finding may reflect compensational processes at the level of basic visual attention which could go unnoticed in cognitive testing but still be reflected in the experience of deficits in everyday cognitive functioning.
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| 3. |
- Nelson, Andreas, et al.
(författare)
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Subjective cognitive complaints in patients with stress-related exhaustion disorder : a cross sectional study
- 2021
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Ingår i: BMC Psychology. - : Springer Nature. - 2050-7283. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Stress-related exhaustion is associated with cognitive impairment as measured by both subjective cognitive complaints (SCCs) and objective cognitive test performance. This study aimed to examine how patients diagnosed with exhaustion disorder differ from healthy control participants in regard to levels and type of SCCs, and if SCCs are associated with cognitive test performance and psychological distress.Methods We compared a group of patients with stress-related exhaustion disorder (n = 103, female = 88) with matched healthy controls (n = 58, female = 47) cross-sectionally, concerning the type and magnitude of self-reported SCCs. We furthermore explored the association between SCCs and cognitive test performance as well as with self-reported depression, anxiety and burnout levels, in the patient and the control group, respectively.Results Patients reported considerably more cognitive failures and were more likely than controls to express memory failures in situations providing few external cues and reminders in the environment. In both groups, SCCs were associated with demographic and psychological factors, and not with cognitive test performance.Conclusion Our findings underline the high burden of cognitive problems experienced by patients with exhaustion disorder, particularly in executively demanding tasks without external cognitive support. From a clinical perspective, SCCs and objective cognitive test performance may measure different aspects of cognitive functioning, and external cognitive aids could be of value in stress rehabilitation.
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| 4. |
- Nelson, Maria, 1979-
(författare)
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Host responses to malaria and bacterial co-infections
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The two main causes of child mortality and morbidity in Africa are malaria and invasive bacterial diseases. In addition, co-infections in sub-Saharan Africa are the rule rather than the exception. However, not much is known about the host-pathogen interaction during a concomitant infection or how it affects the outcome of disease.In order to study the immunological responses during malaria and bacterial co-infections, we established a co-infection mouse model. In these studies we used two pathogenic bacteria found in malaria co-infected patients: Streptococcus pneumoniae and Relapsing fever Borrelia duttonii.Hosts co-infected with malaria and Borrelia showed greatly increased spirochetal growth but low parasite densities. In addition, the co-infected hosts presented symptoms of experimental-cerebral malaria, in an otherwise unsusceptible mouse model. This was found to be a consequence of a dysregulated immune response due to loss of timing and control over regulatory mechanisms in antigen presenting cells thus locking the host in an inflammatory response. This results in inflammation, severe anemia, internal organ damage and pathology of experimental cerebral malaria.On the other hand, in the malaria - S. pneumoniae co-infection model we found that co-infected hosts cleared the bacterium much more efficiently than the single infected counterpart. This efficiency of clearance showed to be neutrophil dependent. Furthermore, in vitro studies revealed that neutrophils isolated from malaria-infected hosts present an altered migratory effect together with a significantly increased capacity to kill S. pneumoniae. This suggests that a malaria infection primes neutrophils to kill S. pneumoniae more efficiently.Furthermore, a study was carried out on plasma samples from Rwandan children under the age of five, on which a full metabolomics profile was performed. We showed that these children could be divided in different disease categories based on their metabolomics profile and independent of clinical information. Additionally, the mild malaria group could further be divided in two sub-groups, in which one had a metabolomic profile resembling that of severe malaria infected patients. Based on this, metabolite profiling could be used as a diagnostic tool to determine the distinct phase, or severity of a malaria infection, identify risk patients and provide helpful and correct therapy.
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