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Sökning: WFRF:(Mårtensson Andreas 1963 ) > (2020)

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1.
  • 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.
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2.
  • Bagonza, Arthur, et al. (författare)
  • 'I know those people will be approachable and not mistreat us' : a qualitative study of inspectors and private drug sellers' views on peer supervision in rural Uganda
  • 2020
  • Ingår i: Globalization and Health. - : Springer Nature. - 1744-8603. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Peer supervision improves health care delivery by health workers. However, in rural Uganda, self-supervision is what is prescribed for licensed private drug sellers by statutory guidelines. Evidence shows that self-supervision encourages inappropriate treatment of children less than 5 years of age by private drug sellers. This study constructed a model for an appropriate peer supervisor to augment the self-supervision currently practiced by drug sellers at district level in rural Uganda.METHODS: In this qualitative study, six Key informant interviews were held with inspectors while ten focus group discussions were conducted with 130 drug sellers. Data analysis was informed by the Kathy Charmaz constructive approach to grounded theory. Atlas ti.7 software package was used for data management.RESULTS: A model with four dimensions defining an appropriate peer supervisor was developed. The dimensions included; incentives, clearly defined roles, mediation and role model peer supervisor. While all dimensions were regarded as being important, all participants interviewed agreed that incentives for peer supervisors were the most crucial. Overall, an appropriate peer supervisor was described as being exemplary to other drug sellers, operated within a defined framework, well facilitated to do their role and a good go-between drug sellers and government inspectors.CONCLUSION: Four central contributions advance literature by the model developed by our study. First, the model fills a supervision gap for rural private drug sellers. Second, it highlights the need for terms of reference for peer supervisors. Third, it describes who an appropriate peer supervisor should be. Lastly, it elucidates the kind of resources needed for peer supervision.
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3.
  • Bagonza, Arthur, et al. (författare)
  • Peer supervision experiences of drug sellers in a rural district in East-Central Uganda : a qualitative study
  • 2020
  • Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875 .- 1475-2875. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Support supervision improves performance outcomes among health workers. However, the national professional guidelines for new licenses and renewal for Class C drug shops in Uganda prescribe self-supervision of licensed private drug sellers. Without support supervision, inappropriate treatment of malaria, pneumonia and diarrhoea among children under 5 years of age continues unabated. This study assessed experiences of drug sellers and peer supervisors at the end of a peer supervision intervention in Luuka District in East Central Uganda. Methods Eight in-depth interviews (IDIs) were held with peer supervisors while five focus group discussions (FGDs) were conducted among registered drug sellers at the end of the peer supervision intervention. The study assessed experiences and challenges of peer supervisors and drug sellers regarding peer supervision. Transcripts were imported into Atlas.ti 7 qualitative data management software where they were analysed using thematic content analysis. Results Initially, peer supervisors were disliked and regarded by drug sellers as another extension of drug inspectors. However, with time a good relationship was established between drug sellers and peer supervisors leading to regular, predictable and supportive peer supervision. This increased confidence of drug sellers in using respiratory timers and rapid diagnostic tests in diagnosing pneumonia symptoms and uncomplicated malaria, respectively, among children under 5 years. There was also an improvement in completing the sick child register which was used for self-assessment by drug sellers. The drug shop association was mentioned as a place where peer supervision should be anchored since it was a one-stop centre for sharing experiences and continuous professional development. Drug sellers proposed including community health workers in monthly drug shop association meetings so that they may also gain from the associated benefits. Untimely completion of the sick child registers by drug sellers and inadequate financial resources were the main peer supervision challenges mentioned. Conclusion Drug sellers benefitted from peer supervision by developing a good relationship with peer supervisors. This relationship guaranteed reliable and predictable supervision ultimately leading to improved treatment practices. There is need to explore the minimum resources needed for peer supervision of drug sellers to further inform practice and policy.
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4.
  • Bagonza, Arthur, et al. (författare)
  • Regulatory inspection of registered private drug shops in East-Central Uganda-what it is versus what it should be : a qualitative study
  • 2020
  • Ingår i: Journal of Pharmaceutical Policy and Practice. - : SPRINGERNATURE. - 2052-3211. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Regulatory inspection of private drug shops in Uganda is a mandate of the Ministry of Health carried out by the National Drug Authority. This study evaluated how this mandate is being carried out at national, district, and drug shop levels. Specifically, perspectives on how the inspection is done, who does it, and challenges faced were sought from inspectors and drug sellers. Methods Six key informant interviews (KIIs) were held with inspectors at the national and district level, while eight focus group discussions (FGDs) were conducted among nursing assistants, and two FGDs were held with nurses. The study appraised current methods of inspecting drug sellers against national professional guidelines for licensing and renewal of class C drug shops in Uganda. Transcripts were managed using Atlas ti version 7 (ATLAS.ti GmbH, Berlin) data management software where the thematic content analysis was done. Results Five themes emerged from the study: authoritarian inspection, delegated inspection, licensing, training, and bribes. Under authoritarian inspection, drug sellers decried the high handedness used by inspectors when found with expired or no license at all. For delegated inspection, drug sellers said that sometimes, inspectors send health assistants and sub-county chiefs for inspection visits. This cadre of people is not recognized by law as inspectors. Inspectors trained drug sellers on how to organize their drug shops better and how to use new technologies such as rapid diagnostic tests (RDTs) in diagnosing malaria. Bribes were talked about mostly by nursing assistants who purported that inspectors were not interested in inspection per se but collecting illicit payments from them. Inspectors said that the facilitation they received from the central government were inadequate for a routine inspection. Conclusion The current method of inspecting drug sellers is harsh and instills fear among drug sellers. There is a need to establish a well-recognized structure of inspection as well as establish channels of dialogue between inspectors and drug sellers if meaningful compliance is to be achieved. The government also needs to enhance both human and financial resources if meaningful inspection of drug sellers is to take place.
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5.
  • Brown, Nick, et al. (författare)
  • Efficacy of zinc as adjunctive pneumonia treatment in children aged 2 to 60 months in low-income and middle-income countries : a systematic review and meta-analysis
  • 2020
  • Ingår i: BMJ Paediatrics Open. - : BMJ. - 2399-9772. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Despite advances in vaccination and case management, pneumonia remains the single largest contributor to early child mortality worldwide. Zinc has immune-enhancing properties, but its role in adjunctive treatment of pneumonia in low-income and middle-income countries (LMICs) is controversial and research still active.Methods: Systematic review and meta-analysis of randomised controlled trials of zinc and placebo in pneumonia in children aged 2 to 60 months in LMICs. Databases included MEDLINE, the Cochrane Library, EMBASE, LILACS, SciELO, the WHO portal, Scopus, Google Scholar and ClinicalTrials.gov. Inclusion criteria included accepted signs of pneumonia and clear measure of outcome. Risk of bias was independently assessed by two authors. ORs with 95% CI were used for calculating the pooled estimate of dichotomous outcomes including treatment failure and mortality. Time to recovery was expressed as HRs. Sensitivity analyses considering risk of bias and subgroup analyses for pneumonia severity were performed.Results: We identified 11 trials published between 2004 and 2019 fulfilling the a priori defined criteria, 7 from South Asia and 3 from Africa and 1 from South America. Proportional treatment failure was comparable in both zinc and placebo groups when analysed for all patients (OR 0.95 (95% CI 0.80 to 1.14)) and only for those with severe pneumonia (OR 0.93 (95% CI 0.75 to 1.14)). No difference was seen in mortality between zinc and placebo groups (OR 0.64 (95% CI 0.31 to 1.31)). Time to recovery from severe pneumonia did not differ between the treatment and control groups for patients with severe pneumonia (HR 1.01 (95% CI 0.89 to 1.14)). Removal of four studies with high risk of bias made no difference to the conclusions.Conclusion: There is no evidence that adjunctive zinc treatment improves recovery from pneumonia in children in LMICs.Trial registration number: CRD42019141602.
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6.
  • Gaudenzi, Giulia, et al. (författare)
  • Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda) : Observational Cohort Study Protocol of the "PI-POC" Trial
  • 2020
  • Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 22:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid-based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
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7.
  • Habtemikael, Lidia, et al. (författare)
  • Prevalence of CYP2C8*2 and *3 among Eritreans and its Potential Impact on Artesunate/Amodiaquine Treatment
  • 2020
  • Ingår i: Pharmacogenomics and Personalized Medicine. - 1178-7066. ; 13, s. 571-575
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In Eritrea, artesunate–amodiaquine is the first-line treatment against uncomplicated malaria. Amodiaquine, which is mainly bio-transformed by CYP2C8, is known to be associated with adverse events of different severity. Extrapyramidal events are among the less common but have been reported with non-negligible frequency in Eritrea. This study was conducted to investigate the allele frequencies of CYP2C8*2 and *3, both associated with decreased amodiaquine metabolism, among the Eritrean population.Methods: During September–November 2018, dried blood samples from 380 participants and 17 patients who previously had experienced extrapyramidal symptoms following treatment of artesunate–amodiaquine were collected and PCR-RFLP genotyped for CYP2C8*2 and *3.Results: The allele frequencies of CYP2C8*2 and *3 were determined as 5.9% (95% CI: 4.4– 7.8) and 4.6% (95% CI: 3.2– 6.3), respectively. Four out of the 17 patients with extrapyramidal reactions showed to be carriers of the alleles.Conclusion: CYP2C8*2 and *3 frequencies among Eritreans were found to be intermediate between the documented for Caucasian and African populations. These findings, along with the alleles not being decisive for the occurrence of extrapyramidal events, might be of importance regarding the amodiaquine-containing malaria treatment in Eritrea. Furthermore, it suggests a significant proportion of slow amodiaquine metabolizers in the Sahel region, information of potential interest in the context of amodiaquine-involving seasonal malaria chemoprevention.
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8.
  • Holmström, Oscar, et al. (författare)
  • A novel deep learning-based point-of-care diagnostic method for detecting Plasmodium falciparum with fluorescence digital microscopy.
  • 2020
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Malaria remains a major global health problem with a need for improved field-usable diagnostic tests. We have developed a portable, low-cost digital microscope scanner, capable of both brightfield and fluorescence imaging. Here, we used the instrument to digitize blood smears, and applied deep learning (DL) algorithms to detect Plasmodium falciparum parasites.METHODS: Thin blood smears (n = 125) were collected from patients with microscopy-confirmed P. falciparum infections in rural Tanzania, prior to and after initiation of artemisinin-based combination therapy. The samples were stained using the 4',6-diamidino-2-phenylindole fluorogen and digitized using the prototype microscope scanner. Two DL algorithms were trained to detect malaria parasites in the samples, and results compared to the visual assessment of both the digitized samples, and the Giemsa-stained thick smears.RESULTS: Detection of P. falciparum parasites in the digitized thin blood smears was possible both by visual assessment and by DL-based analysis with a strong correlation in results (r = 0.99, p < 0.01). A moderately strong correlation was observed between the DL-based thin smear analysis and the visual thick smear-analysis (r = 0.74, p < 0.01). Low levels of parasites were detected by DL-based analysis on day three following treatment initiation, but a small number of fluorescent signals were detected also in microscopy-negative samples.CONCLUSION: Quantification of P. falciparum parasites in DAPI-stained thin smears is feasible using DL-supported, point-of-care digital microscopy, with a high correlation to visual assessment of samples. Fluorescent signals from artefacts in samples with low infection levels represented the main challenge for the digital analysis, thus highlighting the importance of minimizing sample contaminations. The proposed method could support malaria diagnostics and monitoring of treatment response through automated quantification of parasitaemia and is likely to be applicable also for diagnostics of other Plasmodium species and other infectious diseases.
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9.
  • Mhamilawa, Lwidiko E, et al. (författare)
  • Electrocardiographic safety evaluation of extended artemether-lumefantrine treatment in patients with uncomplicated Plasmodium falciparum malaria in Bagamoyo District, Tanzania
  • 2020
  • Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875 .- 1475-2875. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundExtended artemisinin-based combination therapy (ACT) for treatment of uncomplicated Plasmodium falciparum malaria with already existing drug regimens, such as artemether-lumefantrine, might be effective in tackling the emerging ACT resistance. However, given the history of cardiotoxicity among anti-malarial drugs structurally similar to lumefantrine, the potential effect of extended artemether-lumefantrine treatment on the electrocardiographic (ECG) QTc interval is of high concern.MethodsMale and non-pregnant females aged 1–65 years, diagnosed with uncomplicated P. falciparum malaria in Bagamoyo district, Tanzania, were randomized into two arms. The intervention arm received an extended, i.e. 6-day, course of artemether-lumefantrine and an additional single low-dose primaquine (0.25 mg/kg) administered together with the last artemether-lumefantrine dose. The control arm received the standard weight-based 3-day course. ECGs were performed at day 0 and 4–5 h after the last dose at day 5. QT intervals were read manually using the tangent method and automatically. Bazett’s (QTcB) and Fridericia’s (QTcF) formulae were used for correction for heart rate. Descriptive statistics were used to calculate baseline characteristics and the number of supra-thresholds QTc intervals (QTc prolongation > 500, change in QTc interval (ΔQTc) > 60 ms). The mean change in QTc interval in and between the two arms was compared using the paired t-test and independent samples t-test, respectively.ResultsA total of 195 patients were enrolled, 103 and 92 in the intervention and control arm, respectively. No patient experienced QTc intervals > 500 ms on day 5 by both formulae. Patients with ΔQTc > 60 ms, for QTcF were 6/103 (5.8%) vs 2/92 (2.2%) and for QTcB 2/103 (1.9%) vs 1/92 (1.1%) in the intervention and control arms, respectively. The mean difference in ΔQTc interval was statistically significant between the two arms with both correction formulae, 11.4 ms (95% CI 2.7–20.0, p = 0.010) and 13.4 ms (95% CI 5.3–21.5, p = 0.001), for QTcB and QTcF, respectively.ConclusionThe extended 6-day course of artemether-lumefantrine did not reveal clinically relevant QTc prolonging effects. However, significant QTcF prolongation and presence of patients with supra-threshold QTc values observed in the intervention arm underscore the importance of further monitoring of QTc parameters in extended artemether-lumefantrine treatment.
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10.
  • Mhamilawa, Lwidiko E, 1988- (författare)
  • New strategies and tools for Plasmodium falciparum case management and surveillance in the era of imminent resistance to artemisinin-based combination therapy in Tanzania.
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Artemether-lumefantrine has been an efficacious first line treatment for uncomplicated Plasmodium falciparum malaria in Tanzania since its introduction in 2006. Interest has developed in understanding the observation of high residual PCR determined positivity rates on day 3 after supervised artemether-lumefantrine treatment in the magnitude of almost 30% in previous assessments from 2015 in Bagamoyo district, Tanzania. Deep sequencing has recently been used to study these Bagamoyo parasites with delayed clearance, and the clearance times by PCR of some P. falciparum sub-populations were similar to artemisinin resistant parasites in Myanmar as assessed by microscopy, albeit lacking the described mutations in the Kelch13 propeller gene associated with artemisinin resistance. Moreover, molecular epidemiological studies from Bagamoyo, have shown temporal selection of lumefantrine associated genetic tolerance/resistance markers (pfmdr1 - N86, 184F, D1246 and pfcrt - K76) in the parasite population following wide scale use of artemether-lumefantrine but without signs of compromised treatment efficacy. On the other hand, traditional epidemiological studies have reported that imported malaria cases in Zanzibar from Tanzania mainland contribute to regressing the malaria elimination efforts in this pre-elimination part of the country.This PhD project explored efficacy and safety of extending the artemether-lumefantrine regimen from standard 3 days to 6 days and adding single low dose primaquine (0.25mg/kg) as a new strategy that can be used in order to protect the therapeutic lifespan of artemether-lumefantrine. Also, whole-genome sequencing was used to study genomic epidemiology of P. falciparum population between Tanzania mainland and Zanzibar.The results revealed that extended artemether-lumefantrine treatment did not have superior efficacy in the current context of artemether-lumefantrine sensitive P. falciparum parasites. However, the safety profile was excellent and similar to standard 3 days treatment. Parasite detection by molecular methods was 84% on day 3 after artemether-lumefantrine treatment. Meanwhile, significant decreases in the effective population sizes were inferred in both Tanzania mainland and Zanzibar parasite populations, that coincide with a period of decreasing malaria transmission in Tanzania. The parasite population from Tanzania mainland and Zanzibar were found to be connected, implying importation of cases from high transmission mainland to pre elimination regions of Zanzibar.Utility of these results is during exploring options of alternative artemisinin-based combination therapy regimens to protect their therapeutic efficacy in an era of imminent artemisinin resistance in sub Saharan Africa. Moreover, the genomic epidemiological findings in this project may be of interest for malaria elimination programs, in the incorporation of molecular tools in future malaria elimination strategies and resistance surveillance, in the context of understanding importation of malaria from high to low transmission regions.
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