ORCID Profile
0000-0002-7010-6340
Current Organisations
University of Queensland
,
University of Melbourne
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Publisher: Research Square Platform LLC
Date: 08-09-2020
DOI: 10.21203/RS.3.RS-65068/V1
Abstract: Identifying febrile children at risk of sepsis in low-resource settings can improve survival, but recognition triage tools are lacking. Here we test the hypothesis that measuring circulating markers of immune and endothelial activation may identify children at risk of sepsis due to all causes. In a prospective cohort study of 2,502 children in Uganda, we show that Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) measured at first clinical presentation, had high predictive accuracy for subsequent in-hospital mortality. sTREM-1 had the best performance, versus 10 other markers, with an AUROC for discriminating children at risk of death of 0.893 in derivation (95% CI 0.843-0.944) and 0.901 in external validation (95% CI 0.856-0.947). sTREM-1 cutoffs corresponding to a negative likelihood ratio (LR) of 0.10 and a positive LR of 10 classified children into low (1306 children, 53.1%), intermediate (942, 38.3%) and high (212, 8.6%) risk zones. The estimated incidence of death was 0.3%, 3.6%, and 31.0%, respectively, suggesting sTREM-1 could be used to risk-stratify febrile children. These findings support sTREM-1 as the basis for rapid triage test for all cause fever syndromes in children in low-resource settings.
Publisher: Cold Spring Harbor Laboratory
Date: 29-03-2021
DOI: 10.1101/2021.03.27.21254483
Abstract: COVID-19 has had considerable global impact, but in sub-Saharan Africa is one of several infectious disease priorities. Prioritization is normally guided by disease burden, but the highly age-dependent nature of COVID-19 and other infectious diseases makes comparisons challenging unless considered through metrics that incorporate life years lost and time lived in adverse health. We therefore compared 2020 mortality and Disability-Adjusted Life Years lost (DALYs lost) estimates for malaria, tuberculosis, and HIV/AIDS in sub-Saharan African populations with 12+ months of COVID-19 burden (up to end March 2021), applying known age-related mortality to United Nations estimates of age structure. We further compared exacerbations of disease burden predicted from the COVID-19 public health response. Data was derived from public sources, predicted exacerbations derived from those published by international agencies. For sub-Saharan African populations north of South Africa, recorded COVID-19 DALYs lost in 2020 was 3.7%, 2.3%, and 2.4% of those estimated for tuberculosis, HIV/AIDS and malaria respectively. Predicted exacerbations of these comparator diseases were greater than the estimated COVID-19 burden. Including South Africa and Lesotho, COVID-19 DALYs lost were % of those for comparator diseases and dominated by them in all age groups below 65 years. The analysis suggests a relatively low impact from COVID-19. While all four epidemics continue, tuberculosis, HIV/AIDS, and malaria remain far greater health priorities based on disease burden. Resource ersion to COVID-19 therefore runs a high risk of increasing the overall disease burden and causing net harm, further increasing global inequities in health and life expectancy.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.IJID.2022.07.018
Abstract: In this study, we aimed to conduct a systematic review to characterize antimicrobial resistance (AMR) patterns for bacterial causes of febrile illness in Africa and Asia. We included published literature from 1980-2015 based on data extracted from two recent systematic reviews of nonmalarial febrile illness from Africa, South Asia, and Southeast Asia. Selection criteria included articles with full bacterial identification and antimicrobial susceptibility testing (AST) results for key normally sterile site pathogen-drug combinations. Pooled proportions of resistant isolates were combined using random effects meta-analysis. Study data quality was graded using the Microbiology Investigation Criteria for Reporting Objectively (MICRO) framework. Of 3475 unique articles included in the previous reviews, 371 included the target pathogen-drug combinations. Salmonella enterica tested against ceftriaxone and ciprofloxacin were the two highest reported combinations (30,509 and 22,056 isolates, respectively). Pooled proportions of resistant isolates were high for third-generation cephalosporins for Klebsiella pneumoniae and Escherichia coli in all regions. The MICRO grading showed an overall lack of standardization. This review highlights a general increase in AMR reporting and in resistance over time. However, there were substantial problems with diagnostic microbiological data quality. Urgent strengthening of laboratory capacity, standardized testing, and reporting of AST results is required to improve AMR surveillance.
Publisher: Public Library of Science (PLoS)
Date: 05-07-2016
Publisher: eLife Sciences Publications, Ltd
Date: 22-06-2021
DOI: 10.7554/ELIFE.67460
Abstract: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD). We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included. On days 1–3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults. Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients. This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.
Publisher: Public Library of Science (PLoS)
Date: 26-07-2021
DOI: 10.1371/JOURNAL.PONE.0254156
Abstract: Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh s les with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA. In a prospective study of 292 patients with suspected pulmonary tuberculosis in Uganda, the clinical sensitivity and specificity was compared against a microbiological reference standard including sputum Xpert MTB/RIF Ultra and solid and liquid culture. TB-LAM LFA had an overall sensitivity of 60% (95%CI 51–69%) and specificity of 80% (95%CI 73–85%). When comparing HIV-positive (N = 86) and HIV-negative (N = 206) patients, there was no significant difference in sensitivity (sensitivity difference 8%, 95%CI -11% to +24%, p = 0.4351) or specificity (specificity difference -9%, 95%CI -24% to +4%, p = 0.2051). Compared to the commercially available Alere Determine TB-LAM Ag test, the TB-LAM LFA prototype had improved sensitivity in both HIV-negative (difference 49%, 95%CI 37% to 59%, p .0001) and HIV-positive patients with CD4+ T-cell counts cells/μL (difference 59%, 95%CI 32% to 75%, p = 0.0009). This report is the first to show improved performance of a urine TB LAM test for HIV-negative patients in a high TB burden setting. We also offer potential assay refinement solutions that may further improve sensitivity and specificity.
Publisher: Public Library of Science (PLoS)
Date: 10-10-2019
Publisher: F1000 Research Ltd
Date: 14-04-2021
DOI: 10.12688/GATESOPENRES.13210.2
Abstract: The race to develop safe and effective SARS-COV-2 vaccines has moved with unprecedented speed. There are now multiple vaccines that have received emergency use authorization from the United States Food and Drug Administration and a host of candidates positioned for approval worldwide. Attention has now turned to allocation, distribution and verification of these vaccines, yet this focus exposes that the underlying infrastructure for global delivery and monitoring is threadbare and unevenly distributed. This presents both a barrier and an opportunity to deploy sustainable infrastructure. Major global stakeholders must convene quickly, collaborate, and collectively invest in global standards, legal models, common vocabularies and interoperable biometric-supported digital health technologies. As the COVID-19 vaccine effort scales, governments, private sector, and NGOs have the chance to place lasting resources needed for equitable and effective delivery that can pay idends into the future.
Publisher: Cold Spring Harbor Laboratory
Date: 20-05-2020
DOI: 10.1101/2020.05.14.20102202
Abstract: COVID-19 transmission and the public health ‘lock-down’ response are now established in sub-Saharan Africa, including Uganda. Population structure and prior morbidities differ markedly between these countries from those where outbreaks were previously established. We predicted the relative impact of COVID-19 and the response in Uganda to understand whether the benefits could be outweighed by the costs. Age-based COVID-19 mortality data from China were applied to the population structures of Uganda and countries with previously established outbreaks, comparing theoretical mortality and disability-adjusted life years (DALYs) lost. Based on recent Ugandan data and theoretical scenarios of programme deterioration, we predicted potential additional disease burden for HIV/AIDS, malaria and maternal mortality. DALYs lost and mortality. Based on population age structure alone Uganda is predicted to have a relatively low COVID-19 burden compared to equivalent transmission in China and Western countries, with mortality and DALYs lost predicted to be 12% and 19% that of Italy. Scenarios of ‘lockdown’ impact predict HIV/AIDS and malaria equivalent to or higher than that of an extensive COVID-19 outbreak. Emerging HIV/AIDS and maternal mortality data indicate that such deterioration could be occurring. The results predict a relatively low COVID-19 impact on Uganda associated with its young population, with a high risk of negative impact on non-COVID-19 disease burden from a prolonged lockdown response. The results are likely to reflect the situation in other sub-Saharan populations, underlining the importance of tailoring COVID-19 responses to population structure and potential disease vulnerabilities. The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported that no important aspects of the study have been omitted and that there are no discrepancies from the study as originally planned.
Publisher: eLife Sciences Publications, Ltd
Date: 14-05-2021
Publisher: Public Library of Science (PLoS)
Date: 22-11-2022
DOI: 10.1371/JOURNAL.PONE.0273872
Abstract: Malaria rapid diagnostic tests (RDTs) have been evaluated in the Peruvian Amazon region and their performance has been variable. This region is known for being the first with documented evidence of wild Plasmodium falciparum parasites lacking pfhrp2 and pfhrp3 genes, leading to false-positive results with HRP2-based RDTs. In our attempt to further characterize the deletion pattern of these genes and their evolutionary relationship, 93 P . falciparum s les, collected in different communities from the Peruvian Amazon region between 2009 and 2010, were analyzed in this study. Genomic DNA was used to lify 18S rRNA, pfmsp2 and pfglurp to confirm the diagnosis and DNA quality, respectively pfhrp2 , pfhrp3 , and their flanking genes were lified by PCR to assess the pattern of the gene deletions. In addition, microsatellite analysis were performed using seven neutral microsatellites (MS) and five microsatellite loci flanking pfhrp2 . The data showed the absence of pfhrp3 gene in 53.76% (50/93) of the s les, reflecting a higher frequency than the proportion of pfhrp2 gene deletions (33.33% 31/93). Among the flanking genes, the highest frequency of deletion was observed in the PF3D7_0831900 gene (78.49% 73/93) for pfhrp2 . MS marker analysis showed the presence of 8 P . falciparum lineages. The lineage Bv1 was the most prevalent among parasites lacking pfhrp2 and pfhrp3 genes. Additionally, using MS flanking pfhrp2 gene, the haplotypes α and δ were found to be the most abundant in this region. This study confirms the presence in this area of field isolates with deletions in either pfhrp2 , pfhrp3 , or both genes, along with their respective flanking regions. Our data suggest that some pfhrp2 fhrp3 deletion haplotypes, in special the lineage Bv1, are widely dispersed within the Peruvian Amazon. The persistence of these haplotypes ensures a proportion of P . falciparum parasites lacking the pfhrp2 fhrp3 genes in this area, which ultimately leads to false-negative results on PfHRP2-detecting malaria RDTs. However, additional studies are needed to not only confirm this hypothesis but also to further delineate the origin and genetic basis for the pfhrp2- and pfhrp3 gene deletions in wild P . falciparum parasites.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1LC00888A
Abstract: Current quantification methods of
Publisher: AOSIS
Date: 21-12-2022
Publisher: BMJ
Date: 07-2021
DOI: 10.1136/BMJGH-2021-006057
Abstract: In low-income and middle-income countries, most patients with febrile illnesses present to peripheral levels of the health system where diagnostic capacity is very limited. In these contexts, accurate risk stratification can be particularly impactful, helping to guide allocation of scarce resources to ensure timely and tailored care. However, reporting of prognostic research is often imprecise and few prognostic tests or algorithms are translated into clinical practice. Here, we review the often-conflated concepts of prognosis and diagnosis, with a focus on patients with febrile illnesses. Drawing on a recent global stakeholder consultation, we apply these concepts to propose three use-cases for prognostic tools in the management of febrile illnesses in resource-limited settings: (1) guiding referrals from the community to higher-level care (2) informing resource allocation for patients admitted to hospital and (3) identifying patients who may benefit from closer follow-up post-hospital discharge. We explore the practical implications for new technologies and reflect on the challenges and knowledge gaps that must be addressed before this approach could be incorporated into routine care settings. Our intention is that these use-cases, alongside other recent initiatives, will help to promote a harmonised yet contextualised approach for prognostic research in febrile illness. We argue that this is especially important given the heterogeneous settings in which care is often provided for patients with febrile illnesses living in low-income and middle-income countries.
Publisher: MDPI AG
Date: 05-06-2023
DOI: 10.3390/TROPICALMED8060309
Abstract: Community awareness and participation in mass screening is critical for schistosomiasis control. This study assessed the impact of sharing anonymized image-based positive test results on the uptake of screening during community mobilization outreach. We conducted an observational study to compare the population response to standard and image-based strategies in 14 communities in Abuja, Nigeria. Six hundred and ninety-one (341 females, 350 males) in iduals participated in this study. We analyzed the response ratio, relative increase, and s le collection time. The potential treatment uptake and change in social behavior were determined based on a semi-structured questionnaire. The mean response ratio of the image-based strategy was 89.7% representing a significantly higher ratio than the 27.8%, which was observed under the standard mobilization approach (p ≤ 0.001). The image-based method was associated with 100% of the participants agreeing to provide urine s les, 94% willing to be treated, 89% claiming to have been invited to participate in the study by a friend, and 91% desiring to change a predisposing behavioral habit. These findings indicate that image-based community awareness c aigns may increase the population’s perception about schistosomiasis transmission and treatment. This raises new possibilities for local resource mobilization to expand services in reaching the last mile in schistosomiasis control.
Publisher: JoGH Ltd
Date: 28-03-2022
DOI: 10.52872/001C.33666
Publisher: Springer Science and Business Media LLC
Date: 25-11-2021
DOI: 10.1038/S41467-021-27215-6
Abstract: Identifying febrile children at risk of sepsis in low-resource settings can improve survival, but recognition triage tools are lacking. Here we test the hypothesis that measuring circulating markers of immune and endothelial activation may identify children with sepsis at risk of all-cause mortality. In a prospective cohort study of 2,502 children in Uganda, we show that Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) measured at first clinical presentation, had high predictive accuracy for subsequent in-hospital mortality. sTREM-1 had the best performance, versus 10 other markers, with an AUROC for discriminating children at risk of death of 0.893 in derivation (95% CI 0.843–0.944) and 0.901 in validation (95% CI 0.856–0.947) cohort. sTREM-1 cutoffs corresponding to a negative likelihood ratio (LR) of 0.10 and a positive LR of 10 classified children into low (1,306 children, 53.1%), intermediate (942, 38.3%) and high (212, 8.6%) risk zones. The estimated incidence of death was 0.5%, 3.9%, and 31.8%, respectively, suggesting sTREM-1 could be used to risk-stratify febrile children. These findings do not attempt to derive a risk prediction model, but rather define sTREM-1 cutoffs as the basis for rapid triage test for all cause fever syndromes in children in low-resource settings.
Location: United States of America
No related grants have been discovered for David Bell.