Point-of-Care Biomarkers to Guide Antibiotic Prescription for Acute Febrile Illness in Sub-Saharan Africa: Promises and Caveats.
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ABSTRACT:
SUBMITTER: van Griensven J
PROVIDER: S-EPMC7423291 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Point-of-Care Biomarkers to Guide Antibiotic Prescription for Acute Febrile Illness in Sub-Saharan Africa: Promises and Caveats.
van Griensven Johan J Cnops Lieselotte L De Weggheleire Anja A Declercq Steven S Bottieau Emmanuel E
Open forum infectious diseases 20200630 8
Empiric malaria treatment in Sub-Saharan Africa has significantly decreased with the scaling-up of malaria rapid diagnostic tests; this coincided with a pronounced increase in empiric antibiotic prescriptions. In high-income countries, guidance for antibiotic prescriptions using biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) has reduced antibiotic use while safe-guarding patient safety. Importantly, several low-cost point-of-care CRP/PCT tests are currently available. Howeve ...[more]
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Project description:BackgroundIn low-resource, malaria-endemic settings, accurate diagnosis of febrile illness in children is challenging. The World Health Organization (WHO) currently recommends laboratory-confirmed diagnosis of malaria prior to starting treatment in stable children. Factors guiding management of children with undifferentiated febrile illness outside of malaria are not well understood.MethodsThis study examined clinical presentation and management of a cohort of febrile Kenyan children at 5 hospital/clinic sites from January 2014 to December 2017. Chi-squared and multivariate regression analyses were used to compare frequencies and correlate demographic, environmental, and clinical factors with patient diagnosis and prescription of antibiotics.ResultsOf 5735 total participants, 68% were prescribed antibiotic treatment (n = 3902), despite only 28% given a diagnosis of bacterial illness (n = 1589). Factors associated with prescription of antibiotic therapy included: negative malaria testing, reporting head, ears, eyes, nose and throat (HEENT) symptoms (ie, cough, runny nose), HEENT findings on exam (ie, nasal discharge, red throat), and having a flush toilet in the home (likely a surrogate for higher socioeconomic status).ConclusionIn a cohort of acutely ill Kenyan children, prescription of antimalarial therapy and malaria test results were well correlated, whereas antibiotic treatment was prescribed empirically to most of those who tested malaria negative. Clinical management of febrile children in these settings is difficult, given the lack of diagnostic testing. Providers may benefit from improved clinical education and implementation of enhanced guidelines in this era of malaria testing, as their management strategies must rely primarily on critical thinking and decision-making skills.
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Project description:Severe-febrile-illness (SFI) is a common cause of morbidity and mortality across sub-Saharan Africa (SSA). The burden of SFI in SSA is currently unknown and its estimation is fraught with challenges. This is due to a lack of diagnostic capacity for SFI in SSA, and thus a dearth of baseline data on the underlying etiology of SFI cases and scant SFI-specific causative-agent prevalence data. To highlight the public health significance of SFI in SSA, we developed a Bayesian model to quantify the incidence of SFI hospital admissions in SSA. Our estimates indicate a mean population-weighted SFI-inpatient-admission incidence rate of 18.4 (6.8-31.1, 68% CrI) per 1000 people for the year 2014, across all ages within areas of SSA with stable Plasmodium falciparum transmission. We further estimated a total of 16,200,337 (5,993,249-27,321,779, 68% CrI) SFI hospital admissions. This analysis reveals the significant burden of SFI in hospitals in SSA, but also highlights the paucity of pathogen-specific prevalence and incidence data for SFI in SSA. Future improvements in pathogen-specific diagnostics for causative agents of SFI will increase the abundance of SFI-specific prevalence and incidence data, aid future estimations of SFI burden, and enable clinicians to identify SFI-specific pathogens, administer appropriate treatment and management, and facilitate appropriate antibiotic use.
| S-EPMC6657909 | biostudies-literature
Project description:BackgroundInappropriate antibiotic use increases selective pressure, contributing to antimicrobial resistance. Point-of-care rapid diagnostic tests (RDTs) would be instrumental to better target antibiotic prescriptions, but widespread implementation of diagnostics for improved management of febrile illnesses is limited.ObjectiveOur study aims to contribute to evidence-based guidance to inform policymakers on investment decisions regarding interventions that foster more appropriate antibiotic prescriptions, as well as to address the evidence gap on the potential clinical and economic impact of RDTs on antibiotic prescription.MethodsA country-based cost-effectiveness model was developed for Burkina Faso, Ghana and Uganda. The decision tree model simulated seven test strategies for patients with febrile illness to assess the effect of different RDT combinations on antibiotic prescription rate (APR), costs and clinical outcomes. The incremental cost-effectiveness ratio (ICER) was expressed as the incremental cost per percentage point (ppt) reduction in APR.ResultsFor Burkina Faso and Uganda, testing all patients with a malaria RDT was dominant compared to standard-of-care (SoC) (which included malaria testing). Expanding the test panel with a C-reactive protein (CRP) test resulted in an ICER of $ 0.03 and $ 0.08 per ppt reduction in APR for Burkina Faso and Uganda, respectively. For Ghana, the pairwise comparison with SoC-including malaria and complete blood count testing-indicates that both testing with malaria RDT only and malaria RDT + CRP are dominant.ConclusionThe use of RDTs for patients with febrile illness could effectively reduce APR at minimal additional costs, provided diagnostic algorithms are adhered to. Complementing SoC with CRP testing may increase clinicians' confidence in prescribing decisions and is a favourable strategy.
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Project description:New and affordable point-of-care testing (POCT) solutions are hoped to guide antibiotic prescription and to help limit antimicrobial resistance (AMR)-especially in low- and middle-income countries where resource constraints often prevent extensive diagnostic testing. Anthropological and sociological research has illuminated the role and impact of rapid point-of-care malaria testing. This paper expands our knowledge about the social implications of non-malarial POCT, using the case study of a C-reactive-protein point-of-care testing (CRP POCT) clinical trial with febrile patients at primary-care-level health centres in Chiang Rai province, northern Thailand. We investigate the social role of CRP POCT through its interactions with (a) the healthcare workers who use it, (b) the patients whose routine care is affected by the test, and (c) the existing patient-health system linkages that might resonate or interfere with CRP POCT. We conduct a thematic analysis of data from 58 purposively sampled pre- and post-intervention patients and healthcare workers in August 2016 and May 2017. We find widespread positive attitudes towards the test among patients and healthcare workers. Patients' views are influenced by an understanding of CRP POCT as a comprehensive blood test that provides specific diagnosis and that corresponds to notions of good care. Healthcare workers use the test to support their negotiations with patients but also to legitimise ethical decisions in an increasingly restrictive antibiotic policy environment. We hypothesise that CRP POCT could entail greater patient adherence to recommended antibiotic treatment, but it could also encourage riskier health behaviour and entail potentially adverse equity implications for patients across generations and socioeconomic strata. Our empirical findings inform the clinical literature on increasingly propagated point-of-care biomarker tests to guide antibiotic prescriptions, and we contribute to the anthropological and sociological literature through a novel conceptualisation of the patient-health system interface as an activity space into which biomarker testing is introduced.
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Project description:BackgroundThe disease burden of Plasmodium falciparum malaria illness is generally estimated using one of two distinct approaches: either by transforming P. falciparum infection prevalence estimates into incidence estimates using conversion formulae; or through adjustment of counts of recorded P. falciparum-positive fever cases from clinics. Whilst both ostensibly seek to evaluate P. falciparum disease burden, there is an implicit and problematic difference in the metric being estimated. The first enumerates only symptomatic malaria cases, while the second enumerates all febrile episodes coincident with a P. falciparum infection, regardless of the fever's underlying cause.MethodsHere, a novel approach was used to triangulate community-based data sources capturing P. falciparum infection, fever, and care-seeking to estimate the fraction of P. falciparum-positive fevers amongst children under 5 years of age presenting at health facilities that are attributable to P. falciparum infection versus other non-malarial causes. A Bayesian hierarchical model was used to assign probabilities of malaria-attributable fever (MAF) and non-malarial febrile illness (NMFI) to children under five from a dataset of 41 surveys from 21 countries in sub-Saharan Africa conducted between 2006 and 2016. Using subsequent treatment-seeking outcomes, the proportion of MAF and NMFI amongst P. falciparum-positive febrile children presenting at public clinics was estimated.ResultsAcross all surveyed malaria-positive febrile children who sought care at public clinics across 41 country-years in sub-Saharan Africa, P. falciparum infection was estimated to be the underlying cause of only 37.7% (31.1-45.4, 95% CrI) of P. falciparum-positive fevers, with significant geographical and temporal heterogeneity between surveys.ConclusionsThese findings highlight the complex nature of the P. falciparum burden amongst children under 5 years of age and indicate that for many children presenting at health clinics, a positive P. falciparum diagnosis and a fever does not necessarily mean P. falciparum is the underlying cause of the child's symptoms, and thus other causes of illness should always be investigated, in addition to prescribing an effective anti-malarial medication. In addition to providing new large-scale estimates of malaria-attributable fever prevalence, the results presented here improve comparability between different methods for calculating P. falciparum disease burden, with significant implications for national and global estimation of malaria burden.
| S-EPMC6560910 | biostudies-literature
Project description:BackgroundIn this work, a platform was developed and tested to allow to detect a variety of candidate viral, bacterial and parasitic pathogens, for acute fever of unknown origin. The platform is based on a centrifugal microfluidic cartridge, the LabDisk ("FeverDisk" for the specific application), which integrates all necessary reagents for sample-to-answer analysis and is processed by a compact, point-of-care compatible device.Methodology/principal findingsA sample volume of 200 μL per FeverDisk was used. In situ extraction with pre-stored reagents was achieved by bind-wash-elute chemistry and magnetic particles. Enzymes for the loop-mediated isothermal amplification (LAMP) were pre-stored in lyopellet form providing stability and independence from the cold chain. The total time to result from sample inlet to read out was 2 h. The proof-of-principle was demonstrated in three small-scale feasibility studies: in Dakar, Senegal and Khartoum, Sudan we tested biobanked samples using 29 and 9 disks, respectively; in Reinfeld, Germany we tested spiked samples and analyzed the limit of detection using three bacteria simultaneously spiked in whole blood using 15 disks. Overall during the three studies, the FeverDisk detected dengue virus (different serotypes), chikungunya virus, Plasmodium falciparum, Salmonella enterica Typhi, Salmonella enterica Paratyphi A and Streptococcus pneumoniae.Conclusions/significanceThe FeverDisk proved to be universally applicable as it successfully detected all different types of pathogens as single or co-infections, while it also managed to define the serotype of un-serotyped dengue samples. Thirty-eight FeverDisks at the two African sites provided 59 assay results, out of which 51 (86.4%) were confirmed with reference assay results. The results provide a promising outlook for future implementation of the platform in larger prospective clinical studies for defining its clinical sensitivity and specificity. The technology aims to provide multi-target diagnosis of the origins of fever, which will help fight lethal diseases and the incessant rise of antimicrobial resistance.
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Project description:We draw upon a framework outlining household recognition and response to child illness proposed by Colvin and colleagues (2013) to examine factors predictive of treatment sought for a recent child illness. In particular, we model whether no treatment, middle layer treatment (traditional healer, pharmacy, community health worker, etc.), or biomedical treatment was sought for recent episodes of diarrhea, fever, or cough. Based on multinomial, multilevel analyses of Demographic and Health Surveys from 19 countries in sub-Saharan Africa, we determine that if women have no say in their own healthcare, they are unlikely to seek treatment in response to child illness. We find that women in sub-Saharan Africa need healthcare knowledge, the ability to make healthcare decisions, as well as resources to negotiate cost and travel, in order to access biomedical treatment. Past experience with medical services such as prenatal care and a skilled birth attendant also increase the odds that biomedical treatment for child illness is sought. We conclude that caregiver decision-making in response to child illness within households is critical to reducing child morbidity and mortality in sub-Saharan Africa.
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Project description:BackgroundAcute infections have been posited as potential precipitants or triggers of the occurrence of stroke among adults with traditional vascular risk factors. We evaluated associations between stroke occurrence and reported febrile illness within 4 weeks (potential antecedent infections) among West Africans.MethodsThe Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with radiologically confirmed strokes. Controls were stroke-free adults matched with cased by age, gender and ethnicity. Detailed evaluations for vascular, lifestyle and psychosocial factors were performed. Participants were asked for evidence of any febrile illness within the past 4 weeks. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval.ResultsAmong 3588 stroke cases recruited in Ghana and Nigeria between August 2014 and July 2018, 363 cases (10.1%) reported having a febrile illness within the 4 weeks prior to stroke occurrence. Having an antecedent infection was associated with stroke occurrence with an unadjusted OR of 1.19 (1.00-1.51) but aOR of 0.83 (0.59-1.17) upon adjusting for traditional vascular risk factors. Stress, aOR of 4.69 (2.59-8.50) and consumption of green vegetables 2.27 (1.35-2.85) were associated with antecedent febrile illness.Conclusion1 in 10 stroke cases reported antecedent history of febrile illness prior to occurrence of stroke but no independent association was observed in this study. Infectious exposures may be important triggers of cardiovascular events requiring further exploratory studies to better understand the role of this emerging risk factor.
| S-EPMC8006213 | biostudies-literature
Project description:BackgroundMalaria incidence is in decline in many parts of SE Asia leading to a decreasing proportion of febrile illness that is attributable to malaria. However in the absence of rapid, affordable and accurate diagnostic tests, the non-malaria causes of these illnesses cannot be reliably identified. Studies on the aetiology of febrile illness have indicated that the causes are likely to vary by geographical location within countries (i.e. be spatially heterogeneous) and that national empirical treatment policies based on the aetiology measured in a single location could lead to inappropriate treatment.MethodsUsing data from Vientiane as a reference for the incidence of major febrile illnesses in the Lao People's Democratic Republic (Laos) and estimated incidences, plausible incidence in other Lao provinces were generated using a mathematical model for a range of national and local scale variations. For a range of treatment protocols, the mean number of appropriate treatments was predicted and the potential impact of a spatially explicit national empirical treatment protocol assessed.FindingsThe model predicted a negative correlation between number of appropriate treatments and the level of spatial heterogeneity. A spatially explicit national treatment protocol was predicted to increase the number of appropriate treatments by 50% for intermediate levels of spatial heterogeneity.ConclusionsThe results suggest that given even only moderate spatial variation, a spatially explicit treatment algorithm will result in a significant improvement in the outcome of undifferentiated fevers in Laos and other similar resource poor settings.
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Project description:INTRODUCTION:Non-malaria febrile illnesses such as bacterial bloodstream infections (BSI) are a leading cause of disease and mortality in the tropics. However, there are no reliable, simple diagnostic tests for identifying BSI or other severe non-malaria febrile illnesses. We hypothesized that different infectious agents responsible for severe febrile illness would impact on the host metabolome in different ways, and investigated the potential of plasma metabolites for diagnosis of non-malaria febrile illness. METHODOLOGY:We conducted a comprehensive mass-spectrometry based metabolomics analysis of the plasma of 61 children with severe febrile illness from a malaria-endemic rural African setting. Metabolite features characteristic for non-malaria febrile illness, BSI, severe anemia and poor clinical outcome were identified by receiver operating curve analysis. PRINCIPAL FINDINGS:The plasma metabolome profile of malaria and non-malaria patients revealed fundamental differences in host response, including a differential activation of the hypothalamic-pituitary-adrenal axis. A simple corticosteroid signature was a good classifier of severe malaria and non-malaria febrile patients (AUC 0.82, 95% CI: 0.70-0.93). Patients with BSI were characterized by upregulated plasma bile metabolites; a signature of two bile metabolites was estimated to have a sensitivity of 98.1% (95% CI: 80.2-100) and a specificity of 82.9% (95% CI: 54.7-99.9) to detect BSI in children younger than 5 years. This BSI signature demonstrates that host metabolites can have a superior diagnostic sensitivity compared to pathogen-detecting tests to identify infections characterized by low pathogen load such as BSI. CONCLUSIONS:This study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings.
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