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Sökning: WFRF:(Mårtensson Andreas 1963 )

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  • Höper, Linnea, et al. (författare)
  • Vasculitis due to Candidatus Neoehrlichia mikurensis : a cohort study of 40 Swedish patients
  • 2021
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 73:7, s. e2372-e2378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Candidatus (Ca.) Neoehrlichia (N.) mikurensis is an emerging tick-borne pathogen of humans that is closely related to Ehrlichia and Anaplasma species. This strict intracellular bacterium escapes detection by routine microbiologic diagnostic methods such as blood culture leading to considerable under-diagnosis of the infectious disease it causes, neoehrlichiosis.METHODS: Here, we describe the vascular and thromboembolic events afflicting a series of 40 patients diagnosed with neoehrlichiosis in Sweden during a 10-year period (2009-2019).RESULTS: The majority of the patients (60%) developed vascular events ranging from repeated thrombophlebitis, deep vein thrombosis, pulmonary embolism, transitory ischemic attacks to arteritis. Younger age was a risk factor for vascular complications. In contrast, there was no difference in the incidence of vascular events between immunosuppressed and immunocompetent patients. However, there were qualitative differences such that deep vein thrombosis exclusively afflicted the immunosuppressed patients whereas arteritis was restricted to the immunocompetent ones. We also present the case histories of two patients who developed vasculitis mimicking polyarteritis nodosa and giant cell arteritis. Both were cured by doxycycline treatment.CONCLUSIONS: Ca. N. mikurensis infection should be considered in patients living in tick-endemic areas of Europe and northern Asia who present with atypical vascular and/or thromboembolic events. Early diagnosis and antibiotics targeting this emerging infectious agent can eradicate the infection and prevent the development of new vascular events.
  • Wass, Linda, et al. (författare)
  • Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients
  • 2018
  • Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 37:9, s. 1673-1678
  • Tidskriftsartikel (refereegranskat)abstract
    • The tick-borne bacterium Candidatus (Ca.) Neoehrlichia (N.) mikurensis is a cause of "fever of unknown origin" because this strict intracellular pathogen escapes detection by routine blood cultures. Case reports suggest that neoehrlichiosis patients may display serological reactivity to Anaplasma (A.) phagocytophilum. Since Anaplasma serology is part of the diagnostic work-up of undetermined fever in European tick-exposed patients, we wanted to investigate (1) the prevalence of A. phagocytophilum seropositivity among neoehrlichiosis patients, (2) the frequency of misdiagnosed neoehrlichiosis patients among A. phagocytophilum seropositive patients, and (3) the frequency of A. phagocytophilum and Ca. N. mikurensis co-infections. Neoehrlichiosis patients (n = 18) were analyzed for A. phagocytophilum IgM and IgG serum antibodies by indirect immunofluorescence assay. Serum samples from suspected anaplasmosis patients (n = 101) were analyzed for bacterial DNA contents by singleplex PCR specific for A. phagocytophilum and Ca. N. mikurensis, respectively. One fifth of the neoehrlichiosis patients (4/18) were seropositive for IgM and/or IgG to A. phagocytophilum at the time of diagnosis. Among the patients with suspected anaplasmosis, 2% (2/101) were positive for Ca. N. mikurensis by PCR whereas none (0/101) had detectable A. phagocytophilum DNA in the serum. To conclude, patients with suspected anaplasmosis may in fact have neoehrlichiosis. We found no evidence of A. phagocytophilum and Ca. N. mikurensis co-infections in humans with suspected anaplasmosis or confirmed neoehrlichiosis.
  • Allwell-Brown, Gbemisola (författare)
  • Antibiotic use among children in low- and middle-income countries : Studies on global trends, and contextual determinants of antibiotic prescribing in Eastern Uganda
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • This thesis aimed to systematically map trends in reported antibiotic use (RAU) among sick under-five children across low- and middle-income countries (LMICs) in 2005-2017, and, to understand the contextual determinants of antibiotic prescribing in Eastern Uganda. Based on 132 national surveys from 73 LMICs, and using Bayesian linear regression models, trends in RAU among sick under-five children (with symptoms of fever, diarrhoea or cough with fast/difficult breathing) across LMICs in 2005-2017 were mapped by WHO region, World Bank country income group, symptom complaint (Study-I), and by the following user characteristics: rural/urban residence, maternal education, household wealth and source of care (Study-II). To provide context, Study-III investigated patterns and contextual determinants of antibiotic prescribing for febrile under-five outpatients (FUO) attending 37 primary and secondary healthcare facilities across Bugisu, a sub-region in Eastern Uganda, based on a healthcare facility survey, and a two-year retrospective review of outpatient registers from January 2019-December 2020. To further strengthen the understanding of contextual determinants of antibiotic prescribing, in Study-IV, 10 focus group discussions and 10 in-depth interviews were conducted with 85 healthcare providers across primary and secondary healthcare facilities in Bugisu, and analysed using thematic analysis.A modest (17%) relative increase in RAU for sick under-five children across LMICs in 2005-2017 was found, with about 43% of the children reportedly receiving antibiotics for their illness in 2017. Low-income, African, and South-East Asian countries consistently recorded the lowest RAU for sick under-five children. Within LMICs, RAU for sick under-five children increased across all user groups in 2005-2017 but remained lowest among the poorest children, those living in rural areas, and having mothers with the lowest education levels. In Bugisu, 62.2% of FUO in surveyed healthcare facilities received antibiotic prescriptions. Amoxicillin and co-trimoxazole accounted for two-thirds of all antibiotic prescriptions. Cotrimoxazole and ampicillin/cloxacillin were prescribed, despite not being indicated in any of the reported conditions in Study-III. Among other interrelated factors across multiple levels of the health system, availability of antibiotics and diagnostics within healthcare facilities, caregiver demands, and governance at national and sub-national levels were important health worker considerations in antibiotic prescribing for febrile under-five patients.These studies suggest that inequitable access to antibiotics remains a challenge between and within LMICs. Yet, misuse and wastage of antibiotics persists in the same populations with the greatest lack of access to antibiotics and formal healthcare services. A health systems strengthening approach is required to improve antibiotic stewardship and overall quality of care in LMICs.
  • Allwell-Brown, Gbemisola, et al. (författare)
  • Determinants of trends in reported antibiotic use among sick children under five years of age across low-income and middle-income countries in 2005–17: A systematic analysis of user characteristics based on 132 national surveys from 73 countries
  • 2021
  • Ingår i: International Journal of Infectious Diseases. - : Elsevier BV. - 1201-9712 .- 1878-3511. ; 108, s. 473-482
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: This study aimed to analyze any reported antibiotic use for children aged <5 years with fever, diarrhea or cough with fast or difficult breathing (outcome) from low-income and middle-income countries (LMICs) during 2005–2017 by user characteristics: rural/urban residence, maternal education, household wealth, and healthcare source visited. Methods: Based on 132 demographic and health surveys and multiple indicator cluster surveys from 73 LMICs, the outcome by user characteristics for all country-years was estimated using a hierarchical Bayesian linear regression model. Results: Across LMICs during 2005–2017, the greatest relative increases in the outcome occurred in rural areas, poorest quintiles and least educated populations, particularly in low-income countries and South-East Asia. In low-income countries, rural areas had a 72% relative increase from 17.8% (Uncertainty Interval (UI): 5.2%–44.9%) in 2005 to 30.6% (11.7%–62.1%) in 2017, compared to a 29% relative increase in urban areas from 27.1% (8.7%–58.2%) in 2005 to 34.9% (13.3%–67.3%) in 2017. Despite these increases, the outcome was consistently highest in urban areas, wealthiest quintiles, and populations with the highest maternal education. Conclusion: These estimates suggest that the increasing reported antibiotic use for sick children aged <5 years in LMICs during 2005–2017 was driven by gains among groups often underserved by formal health services. © 2021 The Author(s)
  • Allwell-Brown, Gbemisola, et al. (författare)
  • Patterns and contextual determinants of antibiotic prescribing for febrile under-five outpatients at primary and secondary healthcare facilities in Bugisu, Eastern Uganda
  • 2022
  • Ingår i: JAC-Antimicrobial Resistance. - : Oxford University Press (OUP). ; 4:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To describe patterns and contextual determinants of antibiotic prescribing for febrile under-five outpatients at primary and secondary healthcare facilities across Bugisu, Eastern Uganda.Methods: We surveyed 37 public and private-not-for-profit healthcare facilities and conducted a retrospective review of antimicrobial prescribing patterns among febrile under-five outpatients (with a focus on antibiotics) in 2019–20, based on outpatient registers. Multilevel logistic regression analysis was used to identify determinants of antibiotic prescribing at patient- and healthcare facility-levels.Results: Antibiotics were prescribed for 62.2% of 3471 febrile under-five outpatients. There were a total of 2478 antibiotic prescriptions of 22 antibiotic types: amoxicillin (52.2%), co-trimoxazole (14.7%), metronidazole (6.9%), gentamicin (5.7%), ceftriaxone (5.3%), ampicillin/cloxacillin (3.6%), penicillin (3.1%), and others (8.6%). Acute upper respiratory tract infection (AURTI) was the commonest single indication for antibiotic prescribing, with 76.3% of children having AURTI as their only documented diagnosis receiving antibiotic prescriptions. Only 9.2% of children aged 2–59 months with non-severe pneumonia received antibiotic prescriptions in line with national guidelines. Higher health centre levels, and private-not-for-profit ownership (adjusted OR, 4.30; 95% CI, 1.91–9.72) were significant contextual determinants of antibiotic prescribing.Conclusions: We demonstrated a high antibiotic prescribing prevalence among febrile under-five outpatients in Bugisu, Eastern Uganda, including prescriptions for co-trimoxazole and ampicillin/cloxacillin (which are not indicated in the management of the common causes of under-five febrile illness in Uganda). Study findings may be linked to limited diagnostic capacity and inadequate antibiotic availability, which require prioritization in interventions aimed at improving rational antibiotic prescribing among febrile under-five outpatients.
  • Allwell-Brown, Gbemisola, et al. (författare)
  • Trends in reported antibiotic use among children under 5 years of age with fever, diarrhoea, or cough with fast or difficult breathing across low-income and middle-income countries in 2005-17: a systematic analysis of 132 national surveys from 73 countries.
  • 2020
  • Ingår i: The Lancet. Global health. - : ELSEVIER SCI LTD. - 2214-109X. ; 8:6, s. e799-e807
  • Tidskriftsartikel (refereegranskat)abstract
    • Global assessments of antibiotic consumption have relied on pharmaceutical sales data that do not measure individual-level use, and are often unreliable or unavailable for low-income and middle-income countries (LMICs). To help fill this evidence gap, we compiled data from national surveys in LMICs in 2005-17 reporting antibiotic use for sick children under the age of 5 years.Based on 132 Demographic and Health Surveys and Multiple Indicator Cluster Surveys from 73 LMICs, we analysed trends in reported antibiotic use among children under 5 years of age with fever, diarrhoea, or cough with fast or difficult breathing by WHO region, World Bank income classification, and symptom complaint. A logit transformation was used to estimate the outcome using a linear Bayesian regression model. The model included country-level socioeconomic, disease incidence, and health system covariates to generate estimates for country-years with missing values.Across LMICs, reported antibiotic use among sick children under 5 years of age increased from 36·8% (uncertainty interval [UI] 28·8-44·7) in 2005 to 43·1% (33·2-50·5) in 2017. Low-income countries had the greatest relative increase; in these countries, reported antibiotic use for sick children under 5 years of age rose 34% during the study period, from 29·6% (21·2-41·1) in 2005 to 39·5% (32·9-47·6) in 2017, although it remained the lowest of any income group throughout the study period.We found a limited but steady increase in reported antibiotic use for sick children under 5 years of age across LMICs in 2005-17, although overlapping UIs complicate interpretation. The increase was largely driven by gains in low-income countries. Our study expands the evidence base from LMICs, where strengthening antibiotic consumption and resistance surveillance is a global health priority.Uppsala Antibiotic Centre, Uppsala University, Uppsala University Hospital, Makerere University, Gothenburg University.
  • Amaratunga, Chanaki, et al. (författare)
  • Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments : a WWARN individual patient data meta-analysis
  • 2019
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 17, s. 1-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Plasmodium falciparum infections with slow parasite clearance following artemisinin-based therapies are widespread in the Greater Mekong Subregion. A molecular marker of the slow clearance phenotype has been identified: single genetic changes within the propeller region of the Kelch13 protein (pfk13; Pf3D7_1343700). Global searches have identified almost 200 different non-synonymous mutant pfk13 genotypes. Most mutations occur at low prevalence and have uncertain functional significance. To characterize the impact of different pfk13 mutations on parasite clearance, we conducted an individual patient data meta-analysis of the associations between parasite clearance half-life (PC1/2) and pfk13 genotype based on a large set of individual patient records from Asia and Africa.Methods: A systematic literature review following the PRISMA protocol was conducted to identify studies published between 2000 and 2017 which included frequent parasite counts and pfk13 genotyping. Four databases (Ovid Medline, PubMed, Ovid Embase, and Web of Science Core Collection) were searched. Eighteen studies (15 from Asia, 2 from Africa, and one multicenter study with sites on both continents) met inclusion criteria and were shared. Associations between the log transformed PC1/2 values and pfk13 genotype were assessed using multivariable regression models with random effects for study site.Results: Both the pfk13 genotypes and the PC1/2 were available from 3250 (95%) patients (n=3012 from Asia (93%), n=238 from Africa (7%)). Among Asian isolates, all pfk13 propeller region mutant alleles observed in five or more specific isolates were associated with a 1.5- to 2.7-fold longer geometric mean PC1/2 compared to the PC1/2 of wild type isolates (all p≤0.002). In addition, mutant allele E252Q located in the P. falciparum region of pfk13 was associated with 1.5-fold (95%CI 1.4-1.6) longer PC1/2. None of the isolates from four countries in Africa showed a significant difference between the PC1/2 of parasites with or without pfk13 propeller region mutations.Previously, the association of six pfk13 propeller mutant alleles with delayed parasite clearance had been confirmed. This analysis demonstrates that 15 additional pfk13 alleles are associated strongly with the slow-clearing phenotype in Southeast Asia.Conclusion: Pooled analysis associated 20 pfk13 propeller region mutant alleles with the slow clearance phenotype, including 15 mutations not confirmed previously.
  • Andersson, Maria, et al. (författare)
  • Coinfection with Enteric Pathogens in East African Children with Acute Gastroenteritis-Associations and Interpretations
  • 2018
  • Ingår i: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 98:6, s. 1566-1570
  • Tidskriftsartikel (refereegranskat)abstract
    • Enteric coinfections among children in low-income countries are very common, but it is not well known if specific pathogen combinations are associated or have clinical importance. In this analysis, feces samples from children in Rwanda and Zanzibar less than 5 years of age, with (N = 994) or without (N = 324) acute diarrhea, were analyzed by realtime polymerase chain reaction targeting a wide range of pathogens. Associations were investigated by comparing codetection and mono-detection frequencies for all pairwise pathogen combinations. More than one pathogen was detected in 840 samples (65%). A negative association (coinfections being less common than expected from probability) was observed for rotavirus in combination with Shigella, Campylobacter, or norovirus genogroup II, but only in patients, which is statistically expected for agents that independently cause diarrhea. A positive correlation was observed, in both patients and controls, between Ct (threshold cycle) values for certain virulence factor genes in enteropathogenic Escherichia coli (EPEC) (eae and bfpA) and toxin genes in enterotoxigenic E. coli (eltB and estA), allowing estimation of how often these genes were present in the same bacteria. A significant positive association in patients only was observed for Shigella andEPEC-eae, suggesting that this coinfection might interact in a manner that enhances symptoms. Although interaction between pathogens that affect symptoms is rare, this work emphasizes the importance and difference in interpretation of coinfections depending on whether they are positively or negatively associated.
  • Andersson, Maria, et al. (författare)
  • Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar
  • 2017
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 65:8, s. 1371-1377
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure. Methods. Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2-59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens. Results. At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34-100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow- up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children. Conclusions. Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.
  • Bagonza, Arthur, et al. (författare)
  • Effectiveness of peer-supervision on pediatric fever illness treatment among registered private drug sellers in East-Central Uganda : An interrupted time series analysis
  • 2021
  • Ingår i: Health Science Reports. - : Wiley. - 2398-8835. ; 4:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale aims and objectives: Appropriate treatment of pediatric fever in rural areas remains a challenge and maybe partly due to inadequate supervision of licensed drug sellers. This study assessed the effectiveness of peer-supervision among drug sellers on the appropriate treatment of pneumonia symptoms, uncomplicated malaria, and non-bloody diarrhea among children less than 5 years of age in the intervention (Luuka) and comparison (Buyende) districts, in East-Central Uganda.Methods: Data on pneumonia symptoms, uncomplicated malaria, and non-bloody diarrhea among children less than 5 years of age was abstracted from drug shop sick child registers over a 12-month period; 6 months before and 6 months after the introduction of peer-supervision. Interrupted time series were applied to determine the effectiveness of the peer-supervision intervention on the appropriate treatment of pneumonia, uncomplicated malaria, and non-bloody diarrhea among children less than 5 years of age attending drug shops in East Central Uganda.Results: The proportion of children treated appropriately for pneumonia symptoms was 10.84% (P < .05, CI = [1.75, 19.9]) higher, for uncomplicated malaria was 1.46% (P = .79, CI = [-10.43, 13.36]) higher, and for non-bloody diarrhea was 4.00% (P < .05, CI = [-7.95, -0.13]) lower in the intervention district than the comparison district, respectively.Post-intervention trend results showed an increase of 1.21% (P = .008, CI = [0.36, 2.05]) in the proportion appropriately treated for pneumonia symptoms, no difference in appropriate treatment for uncomplicated malaria, and a reduction of 1% (P < .06, CI = [-1.95, 0.02]) in the proportion of children appropriately treated for non-bloody diarrhea, respectively.Conclusions: Peer-supervision increased the proportion of children less than 5 years of age that received appropriate treatment for pneumonia symptoms but not for uncomplicated malaria and non-bloody diarrhea. Implementation of community-level interventions to improve pediatric fever management should consider including peer-supervision among drug sellers.
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