Understanding Acceptability and Willingness-to-pay for a C-reactive Protein Point-of-care Testing Service to Improve Antibiotic Dispensing for Respiratory Infections in Vietnamese Pharmacies: A Mixed-methods Study

Background: Pharmacies are popular first points of contact for mild infections in the community. Pharmacy services in many countries have expanded to include vaccines and point-of-care tests. In low- and middle-income countries such as Vietnam, poor enforcement of regulations results in substantial volumes of over-the-counter antibiotic sales. Point-of-care tests could provide an economically viable way to reduce antibiotic sales, while still satisfying customer demand for convenient healthcare. C-reactive protein point-of-care testing (CRP-POCT) can reduce antibiotic prescribing for respiratory illness in primary care. Here, we explore the acceptability and feasibility of implementing CRP-POCT in pharmacies in Vietnam. Methods: We conducted a mixed-methods study between April and June 2021. A customer exit survey with 520 participants seeking acute respiratory infection treatment at 25 pharmacies evaluated acceptability and willingness-to-pay (WTP) for CRP-POCT and post-service satisfaction. Factors driving customers” acceptance and WTP were explored through mixed-effects multivariable regression. Three focus group discussions with customers (20 participants) and 12 in-depth interviews with pharmacists and other stakeholders were conducted and analyzed thematically. Results: Antibiotics were sold to 81.4% of patients with CRP levels <10 mg/L (antibiotics not recommended). A total of 96.5% of customers who experienced CRP-POCT supported its future introduction at pharmacies. Patients with antibiotic transactions (adjusted odds ratio [aOR], 2.25; 95% confidence interval [CI], 1.13–4.48) and those suffering acute respiratory infection symptoms for more than 3 days (aOR, 2.10; 95% CI, 1.08–4.08) were more likely to accept CRP-POCT, whereas customers visiting for children (aOR, 0.20; 95% CI, .10–.54) and those with preference for antibiotic treatment (aOR, 0.45; 95% CI, 0.23–0.89) were less likely to accept CRP-POCT. A total of 78.3% (95% CI, 74.8–81.7) of customers were willing to pay for CRP-POCT, with a mean cost of US$2.4 (±1.1). Customer's income and cost of total drug treatment were associated with increased WTP. Enablers for implementing CRP-POCT included customers’ and pharmacists’ perceived benefits of CRP-POCT, and the impact of COVID-19 on perceptions of POCT. Perceived challenges for implementation included the additional burden of service provision, lack of an enabling policy environment, and potential risks for customers. Conclusions: Implementing CRP-POCT at pharmacies is a feasible and well-accepted strategy to tackle the overuse of antibiotics in the community, with appeal for both supply and demand sides. Creating an enabling policy environment for its implementation, and transparent discussion of values and risks would be key for its successful implementation

Modeling of the effect of a thermoelectric magnetic force onto conducting particles immersed in the liquid metal

International audienceSimulation of a thermo-electromagnetic force which acts on a conducting particle immersed into liquid metal is performed using multi-gird multi-physics software AEQUATIO. To verify numerical solutions a model thermoelectric problem is solved using two methods. In the first one a phase function is used to indicate the phase transition whereas in the second the solid particle is described with a real frontier of a simplified shape. Numerical and analytical solutions for a model problem qualitatively agree but strong oscillations are observed in a numerical solution with a phase function. Further AEQUQTIO is applied for calculation of the velocity of a dendrite fragment observed in-situ in experiment of solidification of AlCu alloy. Numerical solution gives a good agreement with the experimental observation

Probing the dynamics of quasicrystal growth using synchrotron live imaging

The dynamics of quasicrystal growth remains an unsolved problem in condensed matter. By means of synchrotron live imaging, facetted growth proceeding by the tangential motion of ledges at the solid-melt interface is clearly evidenced all along the solidification of icosahedral AlPdMn quasicrystals. The effect of interface kinetics is significant so that nucleation and free growth of new facetted grains occur in the melt when the solidification rate is increased. The evolution of these grains is explained in details, which reveals the crucial role of aluminum rejection, both in the poisoning of grain growth and driving fluid flow

Outpatient antibiotic prescribing for acute respiratory infections in Vietnamese primary care settings by the WHO AWaRe (Access, Watch and Reserve) classification: An analysis using routinely collected electronic prescription data

Background: This study aims to investigate patterns of antibiotic prescribing and to determine patient-specific factors associated with the choice of antibiotics by the World Health Organization's Access-Watch-Reserve (WHO AWaRe) class for acute respiratory infections (ARIs) in rural primary care settings in northern Vietnam. Methods: We retrospectively reviewed health records for outpatients who were registered with the Vietnamese Health Insurance Scheme, visited one of 112 commune health centres in 6 rural districts of Nam Dinh province, Vietnam during 2019, and were diagnosed with ARIs. Patient-level prescription data were collected from the electronic patient databases. We used descriptive statistics to investigate patterns of antibiotic prescribing, with the primary outcomes including total antibiotic prescriptions and prescriptions by WHO AWaRe group. We identified patient-specific factors associated with watch-group antibiotic prescribing through multivariable logistic regression analysis. Findings: Among 193,010 outpatient visits for ARIs observed in this study, 187,144 (97.0%) resulted in an antibiotic prescription, of which 172,976 (92.5%) were access-antibiotics, 10,765 (5.6%) were watch-antibiotics, 3366 (1.8%) were not-recommended antibiotics. No patients were treated with reserve-antibiotics. The proportion of watch-antibiotic prescription was highest amongst children under 5-years old (18.1%, compared to 9.5% for 5–17-years, 4.9% for 18–49-years, 4.3% for 50–64-years, and 3.7% for 65-and-above-years). In multivariable logistic regression, children, district, ARI-type, comobid chronic respiratory illness, and follow-up visit were associated with higher likelihood of prescribing watch-group antibiotics. Interpretation: The alarmingly high proportion of antibiotic prescriptions for ARIs in primary care, and the frequent use of watch-antibiotics for children, heighten concerns around antibiotic overuse at the community level. Antimicrobial stewardship interventions and policy attention are needed in primary care settings to tackle the growing threat of antibiotic resistance

Computer-aided prognosis of tuberculous meningitis combining imaging and non-imaging data

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. Clinical features, such as coma, can predict death, but they are insufficient for the accurate prognosis of other outcomes, especially when impacted by co-morbidities such as HIV infection. Brain magnetic resonance imaging (MRI) characterises the extent and severity of disease and may enable more accurate prediction of complications and poor outcomes. We analysed clinical and brain MRI data from a prospective longitudinal study of 216 adults with TBM; 73 (34%) were HIV-positive, a factor highly correlated with mortality. We implemented an end-to-end framework to model clinical and imaging features to predict disease progression. Our model used state-of-the-art machine learning models for automatic imaging feature encoding, and time-series models for forecasting, to predict TBM progression. The proposed approach is designed to be robust to missing data via a novel tailored model optimisation framework. Our model achieved a 60% balanced accuracy in predicting the prognosis of TBM patients over the six different classes. HIV status did not alter the performance of the models. Furthermore, our approach identified brain morphological lesions caused by TBM in both HIV and non-HIV-infected, associating lesions to the disease staging with an overall accuracy of 96%. These results suggest that the lesions caused by TBM are analogous in both populations, regardless of the severity of the disease. Lastly, our models correctly identified changes in disease symptomatology and severity in 80% of the cases. Our approach is the first attempt at predicting the prognosis of TBM by combining imaging and clinical data, via a machine learning model. The approach has the potential to accurately predict disease progression and enable timely clinical intervention

The Drivers of Pathology in Zoonotic Avian Influenza: The Interplay Between Host and Pathogen

The emergence of zoonotic strains of avian influenza (AI) that cause high rates of mortality in people has caused significant global concern, with a looming threat that one of these strains may develop sustained human-to-human transmission and cause a pandemic outbreak. Most notable of these viral strains are the H5N1 highly pathogenic AI and the H7N9 low pathogenicity AI viruses, both of which have mortality rates above 30%. Understanding of their mechanisms of infection and pathobiology is key to our preparation for these and future viral strains of high consequence. AI viruses typically circulate in wild bird populations, commonly infecting waterfowl and also regularly entering commercial poultry flocks. Live poultry markets provide an ideal environment for the spread AI and potentially the selection of mutants with a greater propensity for infecting humans because of the potential for spill over from birds to humans. Pathology from these AI virus infections is associated with a dysregulated immune response, which is characterized by systemic spread of the virus, lymphopenia, and hypercytokinemia. It has been well documented that host/pathogen interactions, particularly molecules of the immune system, play a significant role in both disease susceptibility as well as disease outcome. Here, we review the immune/virus interactions in both avian and mammalian species, and provide an overview or our understanding of how immune dysregulation is driven. Understanding these susceptibility factors is critical for the development of new vaccines and therapeutics to combat the next pandemic influenza

HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8+ T cells

Seasonal influenza virus infections cause 290,000–650,000 deaths annually and severe morbidity in 3–5 million people. CD8+ T-cell responses towards virus-derived peptide/human leukocyte antigen (HLA) complexes provide the broadest cross-reactive immunity against human influenza viruses. Several universally-conserved CD8+ T-cell specificities that elicit prominent responses against human influenza A viruses (IAVs) have been identified. These include HLA-A*02:01-M158-66 (A2/M158), HLA-A*03:01-NP265-273, HLA-B*08:01-NP225-233, HLA-B*18:01-NP219-226, HLA-B*27:05-NP383-391 and HLA-B*57:01-NP199-207. The immunodominance hierarchies across these universal CD8+ T-cell epitopes were however unknown. Here, we probed immunodominance status of influenza-specific universal CD8+ T-cells in HLA-I heterozygote individuals expressing two or more universal HLAs for IAV. We found that while CD8+ T-cell responses directed towards A2/M158 were generally immunodominant, A2/M158+CD8+ T-cells were markedly diminished (subdominant) in HLA-A*02:01/B*27:05-expressing donors following ex vivo and in vitro analyses. A2/M158+CD8+ T-cells in non-HLA-B*27:05 individuals were immunodominant, contained optimal public TRBV19/TRAV27 TCRαβ clonotypes and displayed highly polyfunctional and proliferative capacity, while A2/M158+CD8+ T cells in HLA-B*27:05-expressing donors were subdominant, with largely distinct TCRαβ clonotypes and consequently markedly reduced avidity, proliferative and polyfunctional efficacy. Our data illustrate altered immunodominance patterns and immunodomination within human influenza-specific CD8+ T-cells. Accordingly, our work highlights the importance of understanding immunodominance hierarchies within individual donors across a spectrum of prominent virus-specific CD8+ T-cell specificities prior to designing T cell-directed vaccines and immunotherapies, for influenza and other infectious diseases

Farm-Level Risk Factors for Fish-Borne Zoonotic Trematode Infection in Integrated Small-Scale Fish Farms in Northern Vietnam

BACKGROUND: Northern Vietnam is an endemic region for fish-borne zoonotic trematodes (FZT), including liver and intestinal flukes. Humans acquire the FZT infection by eating raw or inadequately cooked fish. The production of FZT-free fish in aquaculture is a key component in establishing a sustainable program to prevent and control the FZT transmission to humans. Interventions in aquaculture should be based on knowledge of the main risk factors associated with FZT transmission. METHODOLOGY/PRINCIPAL FINDINGS: A longitudinal study was carried out from June 2006 to May 2007 in Nam Dinh province, Red River Delta to investigate the development and risk factors of FZT infections in freshwater cultured fish. A total of 3820 fish were sampled six times at two-month intervals from 96 fish farms. Logistic analysis with repeated measurements was used to evaluate potential risk factors based on information collected through questionnaire interviews with 61 fish farm owners. The results showed that the FZT infections significantly increased from first sampling in June to July 2006 (65%) to sixth sampling in April to May, 2007 (76%). The liver fluke, Clonorchis sinensis and different zoonotic intestinal flukes including Haplochis pumilio, H. taichui, H. yokogawai, Centrocestus formosanus and Procerovum varium were found in sampled fish. Duration of fish cultured (sampling times), mebendazole drug self-medication of household members, presence of snails in the pond, and feeding fish with green vegetation collected outside fish farms all had a significant effect on the development of FZT prevalence in the fish. CONCLUSIONS/SIGNIFICANCE: The FZT prevalence in fish increased by 11 percentage points during a one-year culture period and the risk factors for the development of infection were identified. Results also highlight that the young fish are already highly infected when stocked into the grow-out systems. This knowledge should be incorporated into control programs of FZT transmission in integrated small-scale aquaculture nursery and grow-out systems in Vietnam