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Waltraud, S., Schmuckenschlager, A., Thunberg, T., Wigren, J., Fors Connolly, A.-M., Assinger, A., . . . Forsell, M. N. E. (2024). Direct and indirect effects of Puumala hantavirus on platelet function. Thrombosis Research, 233, 41-54
Open this publication in new window or tab >>Direct and indirect effects of Puumala hantavirus on platelet function
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2024 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 233, p. 41-54Article in journal (Refereed) Published
Abstract [en]

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.

Keywords
Hemorrhagic fever with renal syndrome, Immunothrombosis, Infection, Platelet dysfunction, Puumala hantavirus, Thrombocytopenia
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-217532 (URN)10.1016/j.thromres.2023.11.017 (DOI)2-s2.0-85177814613 (Scopus ID)
Funder
Region Västerbotten, RV-967545Region Västerbotten, RV-734361Umeå UniversitySwedish Heart Lung Foundation, 20170334Swedish Research Council, 2020-06235The Kempe Foundations, SMK-1560
Available from: 2023-12-14 Created: 2023-12-14 Last updated: 2023-12-14Bibliographically approved
Lwande, O. W., Näslund, J., Sjödin, A., Lantto, R., Luande, V. N., Bucht, G., . . . Evander, M. (2024). Novel strains of Culex flavivirus and Hubei chryso-like virus 1 from the Anopheles mosquito in western Kenya. Virus Research, 339, Article ID 199266.
Open this publication in new window or tab >>Novel strains of Culex flavivirus and Hubei chryso-like virus 1 from the Anopheles mosquito in western Kenya
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2024 (English)In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 339, article id 199266Article in journal (Refereed) Published
Abstract [en]

Surveillance of mosquito vectors is critical for early detection, prevention and control of vector borne diseases. In this study we used advanced molecular tools, such as DNA barcoding in combination with novel sequencing technologies to discover new and already known viruses in genetically identified mosquito species. Mosquitoes were captured using BG sentinel traps in Western Kenya during May and July 2019, and homogenized individually before pooled into groups of ten mosquitoes. The pools and individual samples were then used for molecular analysis and to infect cell cultures. Of a total of fifty-four (54) 10-pools, thirteen (13) showed cytopathic effect (CPE) on VeroB4 cells, eighteen (18) showed CPE on C6/36 cells. Eight (8) 10-pools out of the 31 CPE positive pools showed CPE on both VeroB4 and C6/36 cells. When using reverse transcriptase polymerase chain reaction (RT-PCR), Sanger sequencing and Twist Comprehensive Viral Research Panel (CVRP) (Twist Biosciences), all pools were found negative by RT-PCR when using genus specific primers targeting alphaviruses, orthobunyaviruses and virus specific primers towards o'nyong-nyong virus, chikungunya virus and Sindbis virus (previously reported to circulate in the region). Interestingly, five pools were RT-PCR positive for flavivirus. Two of the RT-PCR positive pools showed CPE on both VeroB4 and C6/36 cells, two pools showed CPE on C6/36 cells alone and one pool on VeroB4 cells only. Fifty individual mosquito homogenates from the five RT-PCR positive 10-pools were analyzed further for flavivirus RNA. Of these, 19 out of the 50 individual mosquito homogenates indicated the presence of flavivirus RNA. Barcoding of the flavivirus positive mosquitoes revealed the mosquito species as Aedes aegypti (1), Mansonia uniformis (6), Anopheles spp (3), Culex pipiens (5), Culex spp (1), Coquilletidia metallica (2) and Culex quinquefasciatus (1). Of the 19 flavivirus positive individual mosquitoes, five (5) virus positive homogenates were sequenced. Genome sequences of two viruses were completed. One was identified as the single-stranded RNA Culex flavivirus and the other as the double-stranded RNA Hubei chryso-like virus 1. Both viruses were found in the same Anopheles spp. homogenate extracted from a sample that showed CPE on both VeroB4 and C6/36 cells. The detection of both viruses in a single mosquito homogenate indicated coinfection. Phylogenetic analyses suggested that the Culex flavivirus sequence detected was closely related to a Culex flavivirus isolated from Uganda in 2008. All four Hubei chryso-like virus 1 segments clusters closely to Hubei chryso-like virus 1 strains isolated in Australia, China and USA. Two novel strains of insect-specific viruses in Anopheles mosquitoes were detected and characterized.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Anopheles spp, Culex flavivirus, Hubei chryso-like virus 1, mosquito-borne viruses, Next generation target enrichment protocol, Western Kenya
National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-217457 (URN)10.1016/j.virusres.2023.199266 (DOI)2-s2.0-85176373416 (Scopus ID)
Funder
Swedish Research Council, 2017-05607
Available from: 2023-12-05 Created: 2023-12-05 Last updated: 2023-12-05Bibliographically approved
Wigren, J., Vikström, L., Rosendal, E., Gröning, R., Gwon, Y.-D., Nilsson, E., . . . Forsell, M. N. E. (2023). At-home sampling to meet geographical challenges for serological assessment of SARS-CoV-2 exposure in a rural region of northern Sweden, March to May 2021: a retrospective cohort study. Eurosurveillance, 28(13), Article ID 2200432.
Open this publication in new window or tab >>At-home sampling to meet geographical challenges for serological assessment of SARS-CoV-2 exposure in a rural region of northern Sweden, March to May 2021: a retrospective cohort study
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2023 (English)In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 28, no 13, article id 2200432Article in journal (Refereed) Published
Abstract [en]

Background: The current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture for testing is usually performed by trained staff at healthcare centres. Long travel distances to healthcare centres in rural regions may introduce a bias of testing towards relatively large communities with closer access. Rural regions are therefore often not represented in population-based data.

Aim: The aim of this retrospective cohort study was to develop and implement a strategy for at-home testing in a rural region of Sweden during spring 2021, and to evaluate its role to provide equal health care for its inhabitants.

Methods: We developed a sensitive method to measure antibodies to the S-protein of SARS-CoV-2 and optimised this assay for clinical use together with a strategy of at-home capillary blood sampling.

Results: We demonstrated that our ELISA gave comparable results after analysis of capillary blood or serum from SARS-CoV-2-experienced individuals. We demonstrated stability of the assay under conditions that reflected temperature and humidity during winter or summer. By assessment of capillary blood samples from 4,122 individuals, we could show both feasibility of the strategy and that implementation shifted the geographical spread of testing in favour of rural areas.

Conclusion: Implementation of at-home sampling enabled citizens living in remote rural areas access to centralised and sensitive laboratory antibody tests. The strategy for testing used here could therefore enable disease control authorities to get rapid access to information concerning immunity to infectious diseases, even across vast geographical distance.

Place, publisher, year, edition, pages
European Centre for Disease Control and Prevention (ECDC), 2023
Keywords
coronavirus disease (COVID-19), laboratory, surveillance, Sweden
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-206673 (URN)10.2807/1560-7917.ES.2023.28.13.2200432 (DOI)000971868200003 ()36995373 (PubMedID)2-s2.0-85151573640 (Scopus ID)
Available from: 2023-04-14 Created: 2023-04-14 Last updated: 2023-09-05Bibliographically approved
Mosomtai, G., Kasiiti, J., Murithi, R., Sandström, P., Landmann, T., Lwande, O., . . . Ottavianelli, G. (2023). Characterizing movement patterns of nomadic pastoralists and their exposure to rift valley fever in Kenya. In: O. Altan; F. Sunar; D. Klein (Ed.), The international archives of the photogrammetry, remote sensing and spatial information sciences: . Paper presented at 39th International Symposium on Remote Sensing of Environment, ISRSE 2023, Antalya, Turkey, April 24-28, 2023 (pp. 211-216). Copernicus GmbH, XLVIII-M-1-2023
Open this publication in new window or tab >>Characterizing movement patterns of nomadic pastoralists and their exposure to rift valley fever in Kenya
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2023 (English)In: The international archives of the photogrammetry, remote sensing and spatial information sciences / [ed] O. Altan; F. Sunar; D. Klein, Copernicus GmbH , 2023, Vol. XLVIII-M-1-2023, p. 211-216Conference paper, Published paper (Refereed)
Abstract [en]

The role of animal movement in spreading infectious diseases is highly recognized by various legislations and institutions such as the World Organisation for Animal Health and the International Animal Health Code. The increased interactions at the nexus of human-animal-ecosystem interface have seen an unprecedented introduction and reintroduction of new zoonotic diseases with high socio-economic impacts such as the COVID-19 pandemic. Rift Valley fever (RVF) is a zoonotic disease that affects both humans and animals and is transmitted by Aedes mosquitoes or through contact with the body fluids of infected animals. This study seeks to characterize movement patterns of pastoralist and how this movement behaviour increases their susceptibility to RVF virus exposure. We levarage on a rapidly growing field of movement ecology to monitor five herds collared from 2013 - 2015 in an RVF endemic semi-arid region in Kenya. The herds were also sampled for RVF antibodies to assess their exposure to RVF virus during the rainy seasons. adehabitatLT package in R was used to analyze the trajectory data whereas the first passage time (FPT) analysis was used to measure the area utilized in grazing. Sedentary herds grazed within 15km radius while migrating herds presented restricted space use patterns during the dry seasons and transient movement during the start and end of the rainy season. Furthermore, RVF virus antibodies were generally low for sedentary herds whereas the migrating herds recorded high levels during their transition periods. This study can be used to identify RVF risk zones for timely and targeted management strategies.

Place, publisher, year, edition, pages
Copernicus GmbH, 2023
Series
The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, ISSN 1682-1750, E-ISSN 2194-9034
Keywords
Mosquito vectors, Movement ecology, Nomadic pastoralism, Rift Valley fever, Seroprevalence
National Category
Pathobiology Infectious Medicine Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-208260 (URN)10.5194/isprs-archives-XLVIII-M-1-2023-211-2023 (DOI)2-s2.0-85156234877 (Scopus ID)
Conference
39th International Symposium on Remote Sensing of Environment, ISRSE 2023, Antalya, Turkey, April 24-28, 2023
Funder
The European Space Agency (ESA)Swedish Research Council, 2013-06257Sida - Swedish International Development Cooperation Agency, SWE-2011-016
Available from: 2023-05-24 Created: 2023-05-24 Last updated: 2023-05-24Bibliographically approved
Vial, P. A., Ferrés, M., Vial, C., Klingström, J., Ahlm, C., López, R., . . . Mertz, G. J. (2023). Hantavirus in humans: a review of clinical aspects and management. The Lancet - Infectious diseases, 23(9), e371-e382
Open this publication in new window or tab >>Hantavirus in humans: a review of clinical aspects and management
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2023 (English)In: The Lancet - Infectious diseases, ISSN 1473-3099, E-ISSN 1474-4457, Vol. 23, no 9, p. e371-e382Article, review/survey (Refereed) Published
Abstract [en]

Hantavirus infections are part of the broad group of viral haemorrhagic fevers. They are also recognised as a distinct model of an emergent zoonotic infection with a global distribution. Many factors influence their epidemiology and transmission, such as climate, environment, social development, ecology of rodent hosts, and human behaviour in endemic regions. Transmission to humans occurs by exposure to infected rodents in endemic areas; however, Andes hantavirus is unique in that it can be transmitted from person to person. As hantaviruses target endothelial cells, they can affect diverse organ systems; increased vascular permeability is central to pathogenesis. The main clinical syndromes associated with hantaviruses are haemorrhagic fever with renal syndrome (HFRS), which is endemic in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS), which is endemic in the Americas. HCPS and HFRS are separate clinical entities, but they share several features and have many overlapping symptoms, signs, and pathogenic alterations. For HCPS in particular, clinical outcomes are highly associated with early clinical suspicion, access to rapid diagnostic testing or algorithms for presumptive diagnosis, and prompt transfer to a facility with critical care units. No specific effective antiviral treatment is available.

Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-211157 (URN)10.1016/S1473-3099(23)00128-7 (DOI)37105214 (PubMedID)2-s2.0-85162136592 (Scopus ID)
Available from: 2023-07-03 Created: 2023-07-03 Last updated: 2024-01-17Bibliographically approved
Ahmad, I., Edin, A., Granvik, C., Kumm Persson, L., Tevell, S., Månsson, E., . . . Normark, J. (2023). High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19. Frontiers In Public Health, 11, Article ID 1104267.
Open this publication in new window or tab >>High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19
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2023 (English)In: Frontiers In Public Health, ISSN 2296-2565, Vol. 11, article id 1104267Article in journal (Refereed) Published
Abstract [en]

Background: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae. Methods: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression. Results: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+. Conclusion: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
COVID-19, EQ-5D, long-COVID, PACS, Post COVID-19 condition (PCC), post-acute COVID syndrome (PACS), SARS-CoV-2
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-205360 (URN)10.3389/fpubh.2023.1104267 (DOI)000937266000001 ()36817925 (PubMedID)2-s2.0-85148359690 (Scopus ID)
Funder
Nyckelfonden, OLL-938628Nyckelfonden, OLL-961416Region Västmanland, 20201009Swedish Research Council, 2020-06235Swedish Heart Lung Foundation, 20200325Swedish Heart Lung Foundation, 20210078Knut and Alice Wallenberg Foundation, VC-2020-0015Umeå UniversityRegion Västerbotten, RV-938855Region Värmland, LIVFOU-939646
Available from: 2023-03-29 Created: 2023-03-29 Last updated: 2023-10-30
Gröning, R., Dernstedt, A., Ahlm, C., Normark, J., Sundström, P. & Forsell, M. N. E. (2023). Immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis patients after rituximab treatment interruption. Frontiers in Immunology, 14, Article ID 1219560.
Open this publication in new window or tab >>Immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis patients after rituximab treatment interruption
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2023 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1219560Article in journal (Refereed) Published
Abstract [en]

Peripheral B cell depletion via anti-CD20 treatment is a highly effective disease-modifying treatment for reducing new relapses in multiple sclerosis (MS) patients. A drawback of rituximab (RTX) and other anti-CD20 antibodies is a poor immune response to vaccination. While this can be mitigated by treatment interruption of at least six months prior to vaccination, the timing to resume treatment while maintaining subsequent vaccine responses remains undetermined. Here, we characterized SARS-CoV-2 S-directed antibody and B cell responses throughout three BNT162b2 mRNA vaccine doses in RTX-treated MS patients, with the first two doses given during treatment interruption. We examined B-cell mediated immune responses in blood samples from patients with RTX-treated MS throughout three BNT162b2 vaccine doses, compared to an age- and sex-matched healthy control group. The first vaccine dose was given 1.3 years (median) after the last RTX infusion, the second dose one month after the first, and the third dose four weeks after treatment re-initiation. We analyzed SARS-CoV-2 S-directed antibody levels using enzyme-linked immunosorbent assay (ELISA), and the neutralization capacity of patient serum against SARS-CoV-2 S-pseudotyped lentivirus using luciferase reporter assay. In addition, we assessed switched memory (CD19+CD20+CD27+IgD-), unswitched memory (CD19+CD20+CD27+IgD+), naïve (CD19+CD20+CD27-IgD+), and double negative (DN, CD19+CD20+CD27-IgD-) B cell frequencies, as well as their SARS-CoV-2 S-specific (CoV+) and Decay Accelerating Factor-negative (DAF-) subpopulations, using flow cytometry. After two vaccine doses, S-binding antibody levels and neutralization capacity in SARS-CoV-2-naïve MS patients were comparable to vaccinated healthy controls, albeit with greater variation. Higher antibody response levels and CoV+-DN B cell frequencies after the second vaccine dose were predictive of a boost effect after the third dose, even after re-initiation of rituximab treatment. MS patients also exhibited lower frequencies of DAF- memory B cells, a suggested proxy for germinal centre activity, than control individuals. S-binding antibody levels in RTX-treated MS patients after two vaccine doses could help determine which individuals would need to move up their next vaccine booster dose or postpone their next RTX infusion. Our findings also offer first indications on the potential importance of antigenic stimulation of DN B cells and long-term impairment of germinal centre activity in rituximab-treated MS patients.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
B cell immunology, COVID-19, multiple sclerosis, rituximab, vaccination
National Category
Infectious Medicine Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-212992 (URN)10.3389/fimmu.2023.1219560 (DOI)37575257 (PubMedID)2-s2.0-85167514064 (Scopus ID)
Funder
Region Västerbotten, RV-969133Swedish Research Council, 2020-0625Swedish Research Council, 2021-04665Knut and Alice Wallenberg Foundation, VA-2021-0018Knut and Alice Wallenberg Foundation, VA-2022-0008Science for Life Laboratory, SciLifeLab
Available from: 2023-08-18 Created: 2023-08-18 Last updated: 2024-01-17Bibliographically approved
Wilkman, L., Ahlm, C., Evander, M. & Lwande, O. W. (2023). Mosquito-borne viruses causing human disease in Fennoscandia - Past, current, and future perspectives. Frontiers in Medicine, 10, Article ID 1152070.
Open this publication in new window or tab >>Mosquito-borne viruses causing human disease in Fennoscandia - Past, current, and future perspectives
2023 (English)In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 10, article id 1152070Article, review/survey (Refereed) Published
Abstract [en]

Five different mosquito-borne viruses (moboviruses) significant to human disease are known to be endemic to Fennoscandia (Sindbis virus, Inkoo virus, Tahyna virus, Chatanga virus, and Batai virus). However, the incidence of mosquito-borne virus infections in Fennoscandia is unknown, largely due to underdiagnosing and lack of surveillance efforts. The Fennoscandian moboviruses are difficult to prevent due to their method of transmission, and often difficult to diagnose due to a lack of clear case definition criteria. Thus, many cases are likely to be mis-diagnosed, or even not diagnosed at all. Significant long-term effects, often in the form of malaise, rashes, and arthralgia have been found for some of these infections. Research into mobovirus disease is ongoing, though mainly focused on a few pathogens, with many others neglected. With moboviruses found as far north as the 69th parallel, studying mosquito-borne disease occurring in the tropics is only a small part of the whole picture. This review is written with the objective of summarizing current medically relevant knowledge of moboviruses occurring in Fennoscandia, while highlighting what is yet unknown and possibly overlooked.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
arbovirus, epidemiology, Fennoscandia, mobovirus, mosquito-borne virus, Sindbis virus
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-206955 (URN)10.3389/fmed.2023.1152070 (DOI)000966309500001 ()2-s2.0-85152536431 (Scopus ID)
Funder
Swedish Research Council Formas, 2020-01056Umeå UniversitySwedish Research Council, 2019-00773
Available from: 2023-04-26 Created: 2023-04-26 Last updated: 2023-09-05Bibliographically approved
Hollowell, T., Sewe, M. O., Rocklöv, J., Obor, D., Odhiambo, F. & Ahlm, C. (2023). Public health determinants of child malaria mortality: a surveillance study within Siaya County, Western Kenya. Malaria Journal, 22(1), Article ID 65.
Open this publication in new window or tab >>Public health determinants of child malaria mortality: a surveillance study within Siaya County, Western Kenya
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2023 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 22, no 1, article id 65Article in journal (Refereed) Published
Abstract [en]

Background: Malaria deaths among children have been declining worldwide during the last two decades. Despite preventive, epidemiologic and therapy-development work, mortality rate decline has stagnated in western Kenya resulting in persistently high child malaria morbidity and mortality. The aim of this study was to identify public health determinants influencing the high burden of malaria deaths among children in this region.

Methods: A total of 221,929 children, 111,488 females and 110,441 males, under the age of 5 years were enrolled in the Kenya Medical Research Institute/Center for Disease Control Health and Demographic Surveillance System (KEMRI/CDC HDSS) study area in Siaya County during the period 2003–2013. Cause of death was determined by use of verbal autopsy. Age-specific mortality rates were computed, and cox proportional hazard regression was used to model time to malaria death controlling for the socio-demographic factors. A variety of demographic, social and epidemiologic factors were examined.

Results: In total 8,696 (3.9%) children died during the study period. Malaria was the most prevalent cause of death and constituted 33.2% of all causes of death, followed by acute respiratory infections (26.7%) and HIV/AIDS related deaths (18.6%). There was a marked decrease in overall mortality rate from 2003 to 2013, except for a spike in the rates in 2008. The hazard of death differed between age groups with the youngest having the highest hazard of death HR 6.07 (95% CI 5.10–7.22). Overall, the risk attenuated with age and mortality risks were limited beyond 4 years of age. Longer distance to healthcare HR of 1.44 (95% CI 1.29–1.60), l ow maternal education HR 3.91 (95% CI 1.86–8.22), and low socioeconomic status HR 1.44 (95% CI 1.26–1.64) were all significantly associated with increased hazard of malaria death among children.

Conclusions: While child mortality due to malaria in the study area in Western Kenya, has been decreasing, a final step toward significant risk reduction is yet to be accomplished. This study highlights residual proximal determinants of risk which can further inform preventive actions.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Child mortality, Children, Demographic surveillance, Epidemiological monitoring, Malaria, Public health
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-205495 (URN)10.1186/s12936-023-04502-9 (DOI)000937711600001 ()36823600 (PubMedID)2-s2.0-85148812992 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 206-1512
Available from: 2023-03-14 Created: 2023-03-14 Last updated: 2023-09-05Bibliographically approved
Björsell, T., Sundh, J., Lange, A., Ahlm, C., Forsell, M. N. E., Tevell, S., . . . Cajander, S. (2023). Risk factors for impaired respiratory function post COVID-19: a prospective cohort study of nonhospitalized and hospitalized patients. Journal of Internal Medicine, 293(5), 600-614
Open this publication in new window or tab >>Risk factors for impaired respiratory function post COVID-19: a prospective cohort study of nonhospitalized and hospitalized patients
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2023 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 293, no 5, p. 600-614Article in journal (Refereed) Published
Abstract [en]

Background: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3–6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness. Methods: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden. Disease severity was defined as mild (nonhospitalized), moderate (hospitalized with or without oxygen treatment), and severe (intensive care). Spirometry, including diffusion capacity (DLCO), was performed 3–6 months after hospital discharge or study enrollment (for nonhospitalized patients). Breathlessness (defined as ≥1 according to the modified Medical Research Council scale) and functional exercise capacity (1-min sit-to-stand test; 1-MSTST) were assessed. Results: Between April 2020 and May 2021, 337 patients were enrolled in the study. Forced vital capacity and DLCO were significantly lower in patients with severe COVID-19. Among hospitalized patients, 20% had reduced DLCO, versus 4% in nonhospitalized. Breathlessness was found in 40.6% of the participants and was associated with impaired DLCO. A pathological desaturation or heart rate response was observed in 17% of participants during the 1-MSTST. However, this response was not associated with reduced DLCO. Conclusion: Reduced DLCO was the major respiratory impairment 3–6 months following COVID-19, with hospitalization as the most important risk factor. The lack of association between impaired DLCO and pathological physiological responses to exertion suggests that these physiological responses are not primarily related to decreased lung function.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
breathlessness, COVID-19, diffusion capacity, post-acute COVID-19 syndrome, spirometry
National Category
Respiratory Medicine and Allergy General Practice
Identifiers
urn:nbn:se:umu:diva-205377 (URN)10.1111/joim.13614 (DOI)000936826900001 ()36815689 (PubMedID)2-s2.0-85148632325 (Scopus ID)
Funder
Nyckelfonden, OLL-938628Nyckelfonden, OLL-961416Swedish Research Council, 2020-06235Swedish Research Council, 2016-06514Swedish Heart Lung Foundation, 20200325Swedish Heart Lung Foundation, 20210078Knut and Alice Wallenberg Foundation, VC-2020-0015Umeå University, RV‐938855Region Västerbotten, RV-938855Region Värmland, LIVFOU-939646
Available from: 2023-03-24 Created: 2023-03-24 Last updated: 2023-07-14Bibliographically approved
Projects
Mosquito-borne zoonosis in animals and humans - MOBOZO [2014-1556_Formas]; Umeå University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2018-8592

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